RxPG News : Respiratory Medicine

Surgically treating GERD helps preserve lung function before and after transplantation

Mon, 19 Sep 2011 17:34:04 PST

( from http://www.rxpgnews.com ) Surgery to correct gastroesophageal reflux disease, or GERD, can preserve lung function in patients with end-stage pulmonary disease both before and after transplantation, according to a new study from the University of Pittsburgh School of Medicine. The findings, published in the Archives of Surgery, suggest that esophageal testing should be performed more frequently among these patients to determine if anti-reflux surgery is needed.

Many end-stage lung disease patients, particularly those with idiopathic pulmonary fibrosis or cystic fibrosis have GERD, and the reflux problem is very common after lung transplantation, said Blair Jobe, M.D., professor of surgery, Department of Cardiothoracic Surgery, Pitt School of Medicine. Also, GERD has been associated with bronchiolotis obliterans syndrome (BOS), which is a progressive impairment of air flow that is a leading cause of death after lung transplantation. Its cause is not yet known.

"It's possible that reflux, which is due to a weak sphincter between the stomach and esophagus, allows acid and other gastric juices to leak back not only into the esophagus, but also to get aspirated in small amounts into the lungs," Dr. Jobe said. "That micro-aspiration could be setting the stage for the development of BOS."

Lead author Toshitaka Hoppo, M.D., Ph.D., research assistant professor, Department of Cardiothoracic Surgery, Pitt School of Medicine, stressed the importance of esophageal testing for reflux in patients with end-stage pulmonary disease. He noted that "almost one-half of the patients in our series did not have symptoms but were having clinically silent exposure to gastric fluid. Based on this finding, there should be a very low threshold for esophageal testing in this patient population."

For the study, Dr. Jobe's team reviewed medical charts of 43 end-stage lung-disease patients with documented GERD, 19 of whom were being evaluated for lung transplant and 24 who had already undergone transplantation. All the patients were on GERD medications at the time they were evaluated for antireflux surgery (ARS), which prevents fluid from leaking back into the esophagus. Prior to ARS, nearly half of the patients had either no or mild symptoms of GERD and only a fifth had the typical symptoms of heartburn and regurgitation.

The researchers found that nearly all measures of lung function improved after ARS in both the pre- and post-transplant groups. There also were fewer episodes of acute rejection and pneumonia after ARS in the post-transplant group.

"The surgery appeared to benefit even those who hadn't yet had a transplant," Dr. Jobe noted. "Given the shortage of donor organs, ARS might help preserve the patient's own function and buy some more time."

Breast-feeding babies staves off asthma risk

Mon, 25 Jul 2011 18:36:33 PST

( from http://www.rxpgnews.com ) Breast-feeding a baby for six months post birth can stave off their risk of developing asthma-related symptoms in early childhood, says a scientific study.

The study looked at the impact of the duration of breast-feeding and the introduction of alternative liquids or solids in addition to breast milk.

Generation R Study researchers from Erasmus Medical Centre in The Netherlands, used questionnaires to gather data about over 5,000 children, the European Respiratory Journal reports.

They ascertained in the first 12 months after birth whether the children had ever been breast-fed, when breast-feeding was stopped, and whether any other milk or solids were introduced.

Further questionnaires were completed when the children were aged 1, 2, 3 and 4 years to check whether they had any asthma-related symptoms.

The results showed that children who had never been breast-fed had an increased risk of wheezing, shortness of breath, dry cough and persistent phlegm during their first four years, compared to children who were breast-fed for more than six months.

The strongest links were seen with wheezing and persistent phlegm, as children were 1.4 and 1.5 times more likely to develop these symptoms if they had never been breast-fed.

Children who were fed other milk or solids during their first four months in addition to breast milk had an increased risk of wheezing, shortness of breath, dry cough and persistent phlegm during the first four years, compared to children who were exclusively breast-fed for their first four months.

Agnes Sonnenschein-van der Voort, researcher at Generation R, who led the study, said: 'These results support current health policy strategies that promote exclusive breastfeeding for 6 months in industrialised countries.'

--Indo-Asian News service

st/vd/vt

Mannose receptor plays a key role in allergic responses to cat dander

Thu, 10 Mar 2011 06:16:04 PST

( from http://www.rxpgnews.com ) The team of immunologists led by Drs Ghaem-Maghami and Martinez-Pomares in the University's School of Molecular Medical Sciences, and funded by the charity Asthma UK, have identified a cell component which plays a key role in triggering allergic responses to cat dander.

The discovery furthers our understanding of how the body's immune system identifies and reacts to allergens, which could pave the way in developing new ways of treating allergies.

The development is especially good news for the millions of people with asthma whose condition is often worsened by their allergy to airborne allergens from cat dander or house dust mite. Cat dander consists of microscopic pieces of cat skin which easily become airborne.

Dr Amir Ghaem-Maghami said: "There has been a sharp increase in the prevalence of allergies over the past few decades and allergic asthma among children has reached epidemic proportions in many industrialised countries, including the UK.

"Despite improvements in patient care, three people die every day in the UK from asthma, and most therapies target symptoms rather than curing the condition.

"Many people with asthma are highly sensitive to airborne allergens such as cat dander or house dust mite — in fact many studies have shown that up to 40 per cent of children with asthma are allergic to cat allergens.

"A better understanding of how the interaction between allergens and the immune system leads to allergy is vital if we are to develop more effective and efficient treatments for this debilitating condition."

Dr Elaine Vickers, Research Relations Manager at Asthma UK, says: "We are delighted to see the rapid progress that Dr Ghaem-Maghami and his colleagues are making in such a complex area of research.

"This is a great example of where Asthma UK's research funding is leading to a better understanding of asthma which could ultimately benefit thousands of people with both asthma and allergies."

Allergy is a disorder caused by the body's immune system reacting to usually harmless substances found in the environment, known as allergens. Believing itself under attack, the immune system produces a molecule called IgE, which eventually leads to release of further chemicals (including histamine) by certain immune cells which together cause an inflammatory response and the classic symptoms of allergy — itchy eyes, sneezing, runny nose and wheezing.

The Nottingham work, recently published in the Journal of Biological Chemistry, has focused on the role of the mannose receptor (MR), a receptor found on the surface of dendritic cells. These cells are among the first cells in the immune system that come into contact with allergens.

The team recently found that the MR binds to a wide range of allergens and plays an important role in the allergic response to house dust mite allergens. In their latest study they looked at the contribution of MR to allergy caused by a major cat allergen called Fel d 1.

They were able to prove that MR is needed for the body to recognise Fel d 1 as a potential foreign invader and for the production of IgE against Fel d 1. The discovery shows that MR plays a pivotal role not only in recognising allergens but also in provoking the body's allergic response to them.

New genetic variants for COPD discovered in a groundbreaking study by SpiroMeta Consortium

Tue, 15 Dec 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Scientists have discovered five genetic variants that are associated with the health of the human lung. The research by an international consortium of 96 scientists from 63 centres in Europe and Australia sheds new light on the molecular basis of lung diseases.

The research, part-funded by the Medical Research Council (MRC) and Asthma UK, is published today in Nature Genetics. It represents a significant advance because it is the first time that these five common genetic variations have been definitely linked with lung function.

The new findings provide hope for better treatment for lung diseases like Chronic Obstructive Pulmonary Disease (COPD) and asthma. In the past it has been difficult to develop new treatments because the molecular pathways that affect the health of the lung are not completely understood. It's hoped the new pathways discovered could in the future be targeted by drugs.

The ground-breaking research involved a genetic study of 2.5 million sites across the human genome involving samples from 20,000 people across the world. The consortium was led by Dr Martin Tobin from the University of Leicester and Professor Ian Hall from The University of Nottingham.

Lung function is commonly expressed using two measures recorded using a simple device called a spirometer. These measures are termed the FEV1 (or forced expiratory volume in 1 second) which is the volume of air that can be breathed out in 1 second, and the FVC (forced vital capacity) which is the total volume of air that can be breathed out. In chronic obstructive pulmonary disease (COPD), which encompasses chronic bronchitis and emphysema, narrowing of the airways causes a disproportionate reduction in FEV1. Cough, phlegm and shortness of breath are common symptoms of COPD. The simplest way to diagnose COPD is through spirometry, which is usually available in general practitioners' surgeries. Although there is no cure for COPD, stopping smoking and treatments can improve symptoms and reduce the impact of COPD on exercise and daily activities. Drug treatments include bronchodilators and, for exacerbations, may include short-term steroids. Patients with COPD are more susceptible to serious lung infections, so flu vaccination each winter is important.

The genetic determinants of COPD can be studied by investigating the genetic variants that affect the risk of developing COPD itself or by studying lung function itself, on which the diagnosis of COPD is based. Reduced lung function may also occur in patients with other airway diseases such as asthma.

Further research will be needed to study in detail the molecular alterations in the lung that result from the genetic variants identified, and to investigate whether these might be targeted by drugs. At this time there is no case for testing for common genetic variants that might predispose to COPD.

The scientists said: "This work is important because until now we have known very little about the genetic factors that determine an individual's lung function. By identifying the genes important in determining lung function, we can start to unravel the underlying mechanisms which control both lung development and lung damage. This will lead to a better understanding of diseases such as chronic obstructive pulmonary disease (COPD) and asthma. Crucially, it could open up new opportunities to manage and treat patients with lung conditions".

The authors added: "A large reduction in lung function occurs in chronic obstructive pulmonary disease (COPD), which affects around 1 in 10 adults above the age of 40 and is thought to be the fourth most common cause of death worldwide. Smoking is the major risk factor for development of COPD. Lung function and COPD cluster within families, indicating that variations in genes also predispose individuals to reduced lung function.

"The scientists of the SpiroMeta consortium compared genetic variants at each of 2.5 million sites across the human genome in over 20,000 individuals of European ancestry with their lung function measures. In five different locations in the human genome, genetic variants resulted in alterations in lung function. The scientists showed that these were real findings by checking the effects of the same variants in over 33,000 additional individuals. They also compared their results to those of a second consortium, CHARGE, which has published a paper in the same issue of the journal.

The scientists emphasise that they do not expect these findings to lead to immediately to genetic tests to predict who will develop lung disease. What is more important, they say, is that the findings will help understand the underlying causes of lung diseases and thus may indicate new ways of treating the condition.

"The research would not have been possible without the generous support of the participants of the contributing studies from the UK, Europe and Australia, to whom we offer our thanks."

Horse barn workers at high risk of respiratory symptoms

Sun, 22 Nov 2009 09:29:00 PST

( from http://www.rxpgnews.com ) The estimated 4.6 million Americans involved in the equine industry may be at risk of developing respiratory symptoms due to poor air quality in horse barns, according to a questionnaire study undertaken earlier this year by investigators at Tufts University’s Cummings School of Veterinary Medicine.

The study—which polled more than 80 New England horse barn workers—found that 50 percent of individuals working in barns complained of coughing, wheezing, or other ailments in the last year, compared to just 15 percent in the control group of 74 people. Moreover, increased exposure to barns yielded higher rates of self-reported respiratory symptoms, the study reports. The study was published in the journal Occupational Medicine and funded by the National Institutes of Health.

“It has long been known that lower respiratory illness is common in horses, and this is typically attributed to the amount of dust in barns,” said Melissa R. Mazan, DVM, associate professor of clinical sciences at the Cummings School and the study’s lead author. “Our hope was to see whether this poor air quality affects horse owners, and it appears that it might.”

For the study, Mazan and her colleagues at the Cummings School—including Jessica Svatek, Louise Maranda, and Andrew M. Hoffman—collaborated with researchers from the Harvard School of Public Health, the University of Connecticut, and the National Health and Environmental Effects Research Laboratory at the Environmental Protection Agency’s Research Triangle Park.

Although further study is necessary to determine the causes of respiratory distress, Dr. Mazan says, the results are striking—and may be similar among pig, dairy and chicken farmers, who work in environments similarly high in organic dust. A 2001 study of European animal farmers found similar results.

Investigation of exposure to the dust, lung function and horse dander allergies in the barn-exposed group will be necessary to determine how best to protect the health of this group, Dr. Mazan says.

Pulmonology research is one of four NIH-funded basic science divisions at the Cummings School, which also conducts research on infectious diseases, liver and hepatic illness, and reproduction and neurobiology, in addition to robust clinical, international, and sustainability research.

Carbon nanotubes can affect lung lining

Tue, 03 Nov 2009 23:06:00 PST

( from http://www.rxpgnews.com ) Carbon nanotubes which are used in everything from sports equipment to medical applications can affect the lining of the lungs, say researchers.

The long term effects, however, remain unclear.

The study was a collaboration between North Carolina State University -, The Hamner Institutes for Health Sciences, and the National Institute of Environmental Health Sciences.

Using mice in an animal model study, researchers set out to determine what happens when multi-walled carbon nanotubes are inhaled.

Specifically, researchers wanted to determine whether the nanotubes would be able to reach the pleura, which is the tissue that lines the outside of the lungs and is affected by exposure to certain types of asbestos fibres which cause cancer.

Researchers found that inhaled nanotubes do reach the pleura and cause health effects. Short-term studies described in the paper do not allow conclusions about long-term responses such as cancer.

The 'unique reaction' began within one day of inhalation of the nanotubes, when clusters of immune cells - began collecting on the surface of the pleura.

Localised fibrosis, or scarring on parts of the pleural surface that is also found with asbestos exposure, began two weeks after inhalation.

The study showed the immune response and fibrosis disappeared within three months of exposure. However, this study used only a single exposure to the nanotubes, says an NCSU release.

It remains unclear whether the pleura could recover from chronic, or repeated, exposures.

'More work needs to be done in that area and it is completely unknown at this point whether inhaled carbon nanotubes will prove to be carcinogenic in the lungs or in the pleural lining,' an NCSU release said.

These findings were published in Nature Nanotechnology.

Pirfenidone could be new agent for treatment of Idiopathic pulmonary fibrosis.

Sun, 17 May 2009 10:59:07 PST

( from http://www.rxpgnews.com ) A large, well-controlled, multi-national clinical trial program has demonstrated the effectiveness and safety of what may become the first FDA-approved medicine for idiopathic pulmonary fibrosis, or IPF.

In a Phase III clinical study program called "CAPACITY," investigators discovered that the oral anti-fibrotic and anti-inflammatory agent, pirfenidone, could slow the deterioration of lung capacity in patients suffering from IPF.

The researchers presented their findings on Sunday, May 17, at the American Thoracic Society's 105th International Conference in San Diego.

The CAPACITY trial consisted of two multi-national, randomized, double-blind, placebo-controlled Phase III trials (CAPACITY 1 and CAPACITY 2) designed to evaluate the safety and efficacy of pirfenidone in IPF patients with mild to moderate impairment in lung function. The primary endpoint of change in percent predicted forced vital capacity (FVC) at week 72 was met with statistical significance in CAPACITY 2 (p=0.001), along with the secondary endpoints of categorical change in FVC and progression-free survival (PFS), defined as time to either death, a 10-percent decrease in FVC or a 15-percent decrease in DLCO (diffusing capacity of the lung for carbon monoxide). The primary endpoint was not met in CAPACITY 1 (p=0.501), but evidence of a pirfenidone treatment effect on the primary endpoint was observed at several periods in that trial. Importantly, greater than 80 percent of patients in the trials completed treatment and greater than 90 percent completed the study.

An exploratory analysis of pooled data from both trials revealed that treatment with pirfenidone resulted in a 30-percent relative reduction in the percentage of patients who experienced an absolute decline in percent predicted FVC of at least 10 percent. This magnitude of decline is considered clinically meaningful, as a 10-percent decline in percent predicted FVC has been shown in multiple studies to be an independent predictor of mortality in patients with IPF. Exploratory analyses of pooled data from the two CAPACITY studies also demonstrated a statistically significant treatment effect on the primary endpoint of change in percent-predicted FVC at week 72, progression-free survival time and change in six-minute walk test distance.

"While it was disappointing that the primary endpoint was not met in CAPACITY 1, important consistencies between the two CAPACITY studies were observed in the overall treatment effect of pirfenidone," said Paul Noble, M.D., co-chair of the CAPACITY program and professor of medicine and chief of Pulmonary, Allergy and Critical Care Medicine at Duke University Medical Center. "The treatment effect observed in the CAPACITY studies was generally consistent with that observed in the Phase III study in IPF patients conducted by Shionogi in Japan. Collectively, these three studies give us a very good sense of the impact that pirfenidone has on the progression of IPF over at least one year."

According to the National Heart, Lung, and Blood Institute, about 200,000 Americans have idiopathic pulmonary fibrosis, a condition that scars tissue deep in the lungs. Most patients are diagnosed with the disease in their 50s and 60s, and many people live only three to five years after being diagnosed. There are no approved medications in the United States or Europe to treat the disease. Pirfenidone is approved in Japan for the treatment of IPF.

A total of 779 patients were enrolled in the CAPACITY trials at 110 sites in 11 countries. The mean age of participants was 66. To be eligible for the study, patients had to have a definitive diagnosis made by high-resolution CT scan or by biopsy, and a FVC ≥ 50 percent of predicted values and a DLCO ≥ 35 percent of predicted value.

Dr. Roland du Bois, M.D., professor of medicine at National Jewish Health, in Denver, Colo., and CAPACITY co-chair, concurred that these studies were very encouraging for IPF sufferers and added that "the safety and tolerability of pirfenidone was reassuring. The principal side effects experienced by patients in the studies were gastrointestinal discomfort and photo-sensitivity, both of which were manageable in the majority of patients."

The CAPACITY trials follow a Phase III clinical study conducted in Japan that was reported at the American Thoracic Society's 2008 International Conference in Toronto. That trial, which demonstrated the ability of pirfenidone to reduce the decline of lung capacity and improve progression-free survival, served as the basis for the Japanese regulatory authorities' approval of the medicine for the treatment of IPF in Japan.

Dr. du Bois concluded, "When taken in the context of the urgent unmet medical need for new medicines to treat IPF patients, the collective efficacy and safety data from the two CAPACITY studies, corroborated by a similar study in Japan, make a case for the use of pirfenidone in this disease setting."

InterMune, Inc., the developer of the medication, is preparing a New Drug Application (NDA) for pirfenidone for the treatment of IPF, which it expects to submit to the FDA in the summer of 2009, to be followed by a Marketing Authorization Application (MAA), which will be submitted to the European Medicines Agency (EMEA) around the end of 2009. Meanwhile, all patients in the study have been offered pirfenidone as part of an open-label, long-term safety study called RECAP.

MEMS sensor for remote monitoring of asthmatic patients

Sun, 24 Aug 2008 10:26:24 PST

( from http://www.rxpgnews.com ) An inexpensive web-enabled device for measuring lung function in patients with asthma and other disorders is being developed by researchers at Texas Instruments, in Bangalore, India, and co-workers. Writing in the International Journal of Biomedical Engineering and Technology, the team explains how the devise could allow physicians to monitor their patients remotely and quickly instigate medical attention in an emergency.

Spirometers are commonly used to measure lung capacity and the response of breathing during therapy. However, the widespread application of spirometers is limited in the developing world and in remote regions because of the high instrument cost of the instrument and a lack of specialist healthcare workers trained in its use.

Texas Instruments researcher N.C.S. Ramachandran is an expert in high-speed and low-power digital design and is working with professor of electrical engineering Vivek Agarwal of the Indian Institute of Technology, Bombay, India, on the development of an inexpensive and easy to operate spirometer that can be quickly hooked up to an internet connection through built-in web and data encryption software.

Simply monitoring cough and wheezing in asthma sufferers does not always provide an accurate assessment of the severity of their symptoms. Breathing tests carried out using a spirometer, on the other hand, are much more accurate and can provide a clear indication of whether or not medication is being effective.

The team has developed the device as a low-cost, portable spirometer built around a pressure sensor for detecting airflow. The sensor is fabricated using technology similar to that for manufacturing computer chips and is based on microelectromechanical system (MEMS). The MEMS spirometer can measures the flow and volume of air moving in and out of the patient's lungs.

The use of mass production techniques for making the MEMS sensor, means the device can be inexpensive (a few dollars per unit), small, and so portable. Embedding of the necessary electronics and software to allow it to connect to a computer and the Web make it ideal for remote monitoring by a patient's healthcare worker. "Not only can the remotely located patient consult a specialist," the researchers say, "the specialist too can instruct the patient for specific test procedures and treatment."

Obese children have respiratory problems during surgery

Fri, 22 Feb 2008 07:39:25 PST

( from http://www.rxpgnews.com ) Add this to the growing list of health challenges faced by obese children: A new study from the University of Michigan Health System finds that obese children are much more likely than normal-weight children to have problems with airway obstruction and other breathing-related functions during surgery.

Obese children were found to have a higher rate of difficult mask ventilation, airway obstruction, major oxygen desaturation (a decrease in oxygen in the patient’s blood), and other airway problems. The study appears in the March issue of the journal Anesthesiology.

“To our knowledge, this is the first study of its kind,” says lead author Alan R. Tait, Ph.D., professor in the Department of Anesthesiology at the U-M Health System. This large-scale prospective study examines the effect of overweight and obesity on the outcomes of operations in children undergoing elective non-cardiac surgery.

“Based on current trends, it is likely that anesthesiologists will continue to care for an increasing number of children who are overweight or obese,” Tait says, “so it is vital that we are aware of the higher risk they face in the operating room.”

Researchers studied the experiences of 2,025 children who were having elective surgery. Of those, 1,380 were normal weight, 351 were overweight and 294 were obese. Children ranged in age from 2 to 18 years old.

In addition to the problems the obese patients experienced during surgery, they also had a higher rate of illnesses and conditions including asthma, hypertension, sleep apnea and Type II diabetes. These conditions all can contribute to problems during surgery, Tait notes.

By the numbers:

An estimated 15 to 17 percent of children and adolescents in the United States are considered obese.

Major airway obstructions occurred in 19 percent of obese children, compared with 11 percent of normal-weight children.

Nearly 9 percent of obese children experienced difficult mask ventilation, compared with 2 percent of normal-weight children.

17 percent of obese children in the study experienced major oxygen desaturation (decreased oxygen in the blood), compared with 9 percent of normal-weight children.

28 percent of obese children had asthma, compared with 16 percent of normal-weight children.

It should be noted however, that despite the increased risk of adverse events among children who are obese, none resulted in significant illness.

New York Methodist Hospital to study airway bypass treatment for emphysema

Wed, 06 Feb 2008 00:05:00 PST

( from http://www.rxpgnews.com ) Brooklyn, NY, February 4, 2007 -- New York Methodist Hospital today announced the start of the EASE (Exhale Airway Stents for Emphysema) Trial, an international, multi-center clinical trial to explore an investigational treatment that may offer a significant new, minimally-invasive option for those suffering with advanced widespread emphysema. The study focuses on a procedure called airway bypass that involves creating pathways in the lung for trapped air to escape and in turn, relieve emphysema symptoms including shortness of breath.

Emphysema is a chronic, progressive, and irreversible lung disease characterized by the destruction of lung tissue. The loss of the lungs' natural elasticity and the collapse of airways in the lung combine to make exhalation ineffective, leaving the emphysema sufferer with hyperinflation because they can't get air out of their lungs. With hyperinflation, breathing becomes inefficient and the patient is always short of breath. Even the most nominal physical activities become difficult for emphysema patients and many become dependent on oxygen therapy.

We are excited to be part of this study because currently there are limited treatment options for the emphysema patients. Patients are often in poor physical condition, struggling with each breath, states Arthur Sung, MD, Director of Interventional Pulmonology and the principal investigator of the study at NYM's Institute for Asthma and Other Lung Diseases. By creating new pathways for airflow with the airway bypass procedure, we hope to reduce hyperinflation and improve lung function. If patients can breathe easier it is likely to improve their quality of life.

Short sleep times in patients with chronic medical diagnoses associated with obesity

Sun, 16 Dec 2007 10:09:26 PST

( from http://www.rxpgnews.com ) A study published in the December 15 issue of the Journal of Clinical Sleep Medicine (JCSM) demonstrates an association between short sleep times and obesity in patients with chronic medical problems.

The study surveyed 200 patients attending internal medicine clinics to determine their sleep habits, lifestyle characteristics, and medical diagnoses.

According to the results, subjects with short sleep times (less than seven hours) had a significantly increased likelihood of obesity defined by a body mass index greater than 30 kg/meters2 when compared to the reference group of eight to nine hours. There was a U-shaped relationship between obesity and sleep time in women indicating that women who had both short and long sleep times were more likely to be obese. This relationship was not present in men. Other factors predicting obesity in these clinic patients included young age (18 to 49 years), not smoking, drinking alcohol, hypertension, diabetes, and sleep apnea.

“Our study demonstrates that short sleep times have an association with obesity in adults with chronic medical problems and that chronic disease and attendant therapies and/or changes in physical activities do not obscure this relationship,” said Kenneth Nugent, MD, of Texas Tech University, lead author of the study. “This study suggests that adults should sleep eight to nine hours per night to maintain optimal weight. Whether or not manipulating sleep time in adults will prevent additional weight gain or facilitate weight loss is unclear. This question will require therapeutic trials in which sleep hygiene is addressed during weight loss studies.”

A strong relationship exists between weight and obstructive sleep apnea (OSA), in that your neck gets thicker as you gain weight. This increases the level of fat in the back of the throat, narrowing the airway. With more fat in the throat, your airway is more likely to be blocked.

People with OSA are often obese and have a neck size of more than 17 inches. Many people with OSA also have high blood pressure.

It is estimated that four percent of men and two percent of women have OSA, and millions more remain undiagnosed.

First introduced as a treatment option for OSA in 1981, continuous positive airway pressure (CPAP) is the most common and effective treatment for OSA. CPAP provides a steady stream of pressurized air to patients through a mask that they wear during sleep. This airflow keeps the airway open, preventing the pauses in breathing that characterize sleep apnea and restoring normal oxygen levels.

Strong link between air pollution and acute bronchitis diagnoses in preschool-aged children

Thu, 11 Oct 2007 15:06:05 PST

( from http://www.rxpgnews.com ) In one of the first studies to examine air pollution in relation to infant and early childhood health, a UC Davis researcher has discovered a strong link between exposure to components of air pollution and acute bronchitis diagnoses in preschool-aged children. Those components – polycyclic aromatic hydrocarbons, or PAHs – contribute to air pollution from a variety of sources, including coal burning, vehicle exhaust, wood-burning stoves, tobacco smoke and grilling food.

Led by UC Davis environmental epidemiologist Irva Hertz-Picciotto, the Czech Early Childhood Health Study involved 1,133 children from birth to 4.5 years of age born in two districts of the Czech Republic between 1994 and 1998. One of those districts, Teplice (pronounced Tuh-PLEET-zuh), is known for its high levels of air pollution. The other, Prachatice (pronounced prah-kuh-TEET-zuh), has much lower levels of air pollution.

Hertz-Picciotto and colleagues compared information on medical diagnoses of lower respiratory illnesses such as bronchitis, croup, pneumonia and asthma with detailed data on air quality. The findings revealed a significant increase in diagnoses of acute bronchitis when children aged 2 to 4.5 were exposed to medium-to-high levels of PAHs for 30 consecutive days.

“This is the first large-scale, comprehensive study looking at early childhood respiratory infections and the constituents of today’s air pollution,” said Hertz-Picciotto, a UC Davis professor of epidemiology and lead author of the study. “We found that polycyclic aromatic hydrocarbons have a significant effect on the lung health of children in the study, in particular in increases in acute bronchitis diagnoses for toddlers and preschoolers. We saw the biggest impact on children old enough to play outside, while infants were affected but not quite as much.”

Scientists classify the components of air pollution as either particles or a variety of chemical compounds. Whereas a number of studies have examined particles, sulfur dioxide and ozone, very little research in human populations have addressed PAHs, which result from the incomplete combustion of carbon-containing fuels such as wood, coal, diesel or tobacco. Current environmental regulations in both the United States and Europe focus on controlling particulate emissions.

“Our work strongly suggests that regulators consider efforts to curb PAHs as well. Reducing particles may also reduce chemical emissions but the impact will depend on what control measures are taken. When it comes to children’s lung health, we need to take steps to reduce all risk factors,” Hertz-Picciotto said. “Additional precautions particularly pertinent here in California to protect children from the harmful effects of PAHs include not smoking around children and using alternatives to wood for heating homes in the winter.”

Hertz-Picciotto and colleagues collected standardized medical records and information from parent questionnaires about work history, demographics, lifestyle, and reproductive and medical histories. Follow-up information was collected once for each child at the age of 3 for those born between 1994 and 1996 and at age 4.5 for those born in 1997 or 1998.

At the same time, the team collected detailed air quality sampling data on levels of particulate and PAH air pollution in the regions. PAHs are particularly difficult and expensive to measure. Hertz-Picciotto and her researchers had unique access to daily measures of air quality -- both particulate matter and PAHs -- for winter months, while measures were taken at three-day intervals in the fall and spring and six-day intervals in the summer when these air pollutants are at their lowest. As a result, the volume and detail of medical and environmental data used in the analysis is uniquely robust and allowed researchers to control for a whole host of potentially confounding factors.

“It is an impressive amount of very complete data, giving us a rare opportunity to look at the impact of air pollution on the health of young children and the actual components comprising that pollution,” Hertz-Picciotto explained. “We were able to correct for everything from duration of breast feeding to smoking in the home to average daily temperature.”

The PAH levels identified in the Czech Republic are comparable to those found in Western Europe and the United States. Some rural areas of California, for example, see sharp increases of PAHs in the winter due to the burning of wood stoves for heat. Likewise, increases in bronchitis in the Czech children were seen in the winter months when air quality was the poorest.

In addition to comparable air pollution profiles to those in the United States, the Czech Republic was an ideal study site for evaluating physician-diagnosed illnesses because of its open public-health infrastructure. All citizens of the Czech Republic are entitled to free, readily available medical care. Families remain with one pediatrician for all of their children from birth to adulthood. For researchers, this meant access to thousands of standardized medical records and participation rates of more than 95 percent by those asked to fill out follow-up questionnaires.

“There are virtually no barriers to receiving health care in the Czech Republic and virtually all families develop strong, lasting relationships with their pediatricians and nurses,” Hertz-Picciotto said. “This definitely helped keep participation levels high.”

Bronchitis occurs when the inner walls that line the main air passageways of the lungs become infected, inflamed and narrowed. It usually follows a cold or the flu. The result is a persistent, productive cough, shortness of breath and chest tightness and pain. Some cases of bronchitis can be treated by antibiotics but most are due to viruses, for which there are no treatments. Acute bronchitis is among the top 10 conditions for which patients seek medical care. It is a major contributor to missed school for children and workdays for parents who stay home with them. Estimated costs for evaluating and treating this illess are between $200 and $300 million each year.

“Air quality negatively impacts children’s health and has a definite economic impact on health systems and families,” Hertz-Picciotto said.

Scientists have yet to discover the biological mechanism by which air pollution in general and PAHs in particular contribute to lower respiratory illnesses. Hertz-Picciotto theorizes that the chemicals in air pollution may have an impact on the immune system.

“It’s possible that increased inflammation of the airways due to the PAH exposure compromises the immune system and makes it easier for viruses to take hold,” she explained. “We need more basic science to answer this question.”

In the meantime, Hertz-Picciotto and her colleagues will continue to investigate the impact of other air pollution components and their potential connections to childhood illnesses using the Czech data sets. They will also be looking at whether prenatal exposure to air pollution leads to increased susceptibility to illness, such as asthma and hay fever, later in life.

Mediterranean diet halves risk of progressive lung disease

Mon, 14 May 2007 20:09:19 PST

( from http://www.rxpgnews.com ) A Mediterranean diet halves the chances of developing progressive inflammatory lung disease (COPD), reveals a large study, published ahead of print in Thorax.

COPD (chronic obstructive pulmonary disease) is an umbrella term for chronic progressive lung disease, such as emphysema and bronchitis. It is expected to become the third leading cause of death worldwide by 2020, with cigarette smoking the primary factor in its development.

The researchers tracked the health of almost 43,000 men, who were already part of the US Health Professionals Follow up Study. This began in 1986 and involved more than 50,000 US health care professionals aged between 40 and 75, who were surveyed every two years.

They were asked questions about lifestyle, including smoking and exercise, diet and medical history. Dietary intake was assessed in detail every four years.

Eating patterns fell into two distinct categories: those who ate a diet rich in fruit, vegetables, whole grains and fish (Mediterranean diet); and those who ate a diet rich in processed foods, refined sugars, and cured and red meats (Western diet).

Between 1986 and 1998, 111 cases of COPD were newly diagnosed.

The Mediterranean diet was associated with a 50% lower risk of developing COPD than the Western diet, even after adjusting for age, smoking, and other risk factors.

And men who ate a predominantly Western diet were more than four times as likely to develop COPD, even after taking account of other influential factors.

The higher the compliance with a Mediterranean diet, the lower was the risk of developing COPD over the 12 year period.

Conversely, the higher the compliance with the Western diet, the higher was the risk of developing COPD.

Newborns with respiratory distress should be evaluated for primary ciliary dyskinesia

Wed, 21 Feb 2007 06:05:47 PST

( from http://www.rxpgnews.com ) Newborns with respiratory distress should be evaluated for primary ciliary dyskinesia, a rare genetic disease that has features similar to cystic fibrosis, says Thomas Ferkol, M.D., from Washington University School of Medicine in St. Louis. He reports finding that about 80 percent of patients with primary ciliary dyskinesia (PCD) have a history of newborn respiratory distress.

"The diagnosis of PCD requires a high index of suspicion, but PCD must be considered in any term newborn who develops respiratory distress or persistent hypoxemia (low oxygen in the blood), especially those who have reversed internal organs or an affected sibling," says Ferkol, director of the Division of Pediatric Allergy and Pulmonary Medicine at Washington University School of Medicine and St. Louis Children's Hospital.

Reviewing published reports, Ferkol and Margaret Leigh, M.D., professor of pediatrics at the University of North Carolina at Chapel Hill (UNC), found that neonatal respiratory distress was a common clinical symptom of PCD, a chronic airway disease that affects about 1 in 15,000 children. Their findings appeared in the December issue of Seminars in Perinatology.

Also known as immotile cilia syndrome, ciliary aplasia or Kartagener Syndrome, PCD causes persistent wheezing and cough in children and is associated with recurrent or persistent sinus and ear infections. Half of patients with PCD have reversed internal organs, called situs inversus, and males are usually infertile.

In PCD patients, the cilia, tiny hairs that move mucus, bacteria and particulates out of the respiratory tract, including the lungs, middle ear and paranasal sinuses, have abnormal or no motion. As a result, the airways become obstructed and infected, which incites a destructive inflammatory process in those organs. Cilia are also present in the female reproductive system, central nervous system and gut.

"The tricky thing about this disease is that many of the clinical symptoms are very similar to other more common conditions, such as asthma, allergy or cystic fibrosis," Ferkol says. "Physicians often fail to consider PCD, in part because we don't have a great diagnostic test for the disease."

Ferkol indicates that several clinical features of PCD mirror those found in the more-common cystic fibrosis, including chronic sinus and lung disease as well as male infertility. However, chronic ear disease and neonatal respiratory distress are relatively uncommon in cystic fibrosis and should prompt the caregiver to consider PCD.

"Once children with PCD are past the newborn period, the signs and symptoms that typically bring them to medical attention are chronic ear disease, hearing loss and a runny nose that persists despite seasonal changes or the use of antibiotics and antihistamines," Ferkol says. "But as patients age, the lung manifestations become more evident. Also, infertility becomes a greater issue in adulthood."

Because definitive testing is not always readily available, patients with PCD are often diagnosed late. In addition, treatment of PCD in the community is highly variable, largely because the necessary clinical studies have not been performed.

Ferkol, also associate professor of pediatrics and of cell biology and physiology and director of the Cystic Fibrosis Center at Washington University School of Medicine, is leading the Washington University research team that is part of a national consortium investigating the genetic causes of PCD. The Genetic Diseases of Mucociliary Clearance Consortium, based at UNC, is part of the National Institutes of Health Rare Diseases Clinical Research Network.

The consortium aims to improve diagnosis and treatment of PCD as well as to better define its origin and how it progresses.

"We want to identify as many PCD patients as we can to help us understand the genetics, pathophysiology and clinical spectrum of this disease so we can devise better, more effective treatment strategies," Ferkol says.

Ultimately, members of the consortium will invite patients with PCD to enroll in a long-term study where they will be monitored and be eligible to participate in clinical trials of potential treatments, Ferkol says.

Slow-release morphine helps in chronic treatment resistant cough

Thu, 15 Feb 2007 13:50:19 PST

( from http://www.rxpgnews.com ) Slow-release morphine helped a group of patients with long-term, treatment-resistant chronic cough reduce their daily cough score levels by 40 percent.

The research results appear in the second issue for February 2007 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Alyn H. Morice, M.D., of the Department of Academic Medicine at the University of Hull and Castle Hill Hospital in East Yorkshire, United Kingdom, and six associates enrolled 27 patients with intractable cough in an eight-week, randomized, double-blind, placebo-controlled study to test the use of slow-release morphine sulfate versus a placebo on their cough. Each phase lasted four weeks.

Morphine, derived from opium, is used in medicine as an analgesic, light anesthetic or a sedative. Although opiates have been long advocated for the suppression of cough, there are few trial data to support this recommendation. In fact, prior to this research, the use of opiates in intractable chronic cough had never been studied.

"Although acute cough is benign and self-limiting, chronic persistent cough can have a devastating effect on the quality of life of sufferers," said Dr. Morice. "This research provides evidence for the use of opiates in chronic cough."

The investigators found a "rapid and highly significant reduction by 40 percent in daily cough scores was noted by patients on slow-release morphine sulfate."

Patients responded quickly to treatment starting at five milligrams twice daily. The researchers found patients benefited the most by day five of treatment, and that this response was sustained through the remainder of the four-week period. The authors noted that the rapid response to morphine was in contrast to the absence of any effect of placebo.

The 27 participants, 18 of whom were female, were recruited from a hospital cough clinic. All had endured a chronic, persistent cough for more than three months. Their average age was 55.

During each four-week interval, patients made three visits to a clinical trial center, where they filled out a quality-of-life questionnaire on the impact of chronic cough on activities of daily living. A spirometric lung test was performed at the first visit, and lung function was measured on each subsequent visit.

In addition, each participant assessed their cough severity daily, rating it from 0 to 9 on a record card. Participants could not use other cough remedies, including over-the-counter products, during the eight-week study period.

According to the authors, one-third of the participants increased their dose of morphine sulfate from 5 mg to 10 mg twice daily during the first month; 11 percent did so in the second month; and a further 22 percent joined them in the third month. By the end of the study, two-thirds of the patients had increased their dose to 10 milligrams.

"The optimum dose in the suppression of chronic cough lies between 5 and 10 mg twice daily," said Dr. Morice, who added that the most common side effects were constipation (40 percent) and drowsiness (25 percent).

The investigators believe that the risk-benefit ratio makes low-dose morphine sulfate a credible therapeutic option for patients with chronic cough who fail other specific treatments

Inhaled treatments work better for asthmatic kids

Wed, 24 Jan 2007 10:53:36 PST

( from http://www.rxpgnews.com ) New York, Jan 24 - Inhaled treatments work better for children suffering from asthma compared to other methods of treatment, say scientists after comparing the effectiveness and safety of different medicines.

Although several medications are available to help children control asthma, clinical trials directly comparing them have not been conducted, reported health portal News Medical.

For the first time, researchers in the Childhood Asthma Research and Education Network of the National Heart, Lung, and Blood Institute - compared the effectiveness and safety of three different medicines for initial daily therapy for school-aged children with mild to moderate persistent asthma.

The researchers, who studied 285 children aged six to 14 years, found that after 48 weeks, inhaled corticosteroidsm, an asthma drug, were the most effective initial daily therapy for children with mild to moderate persistent asthma.

These results support the current asthma clinical guidelines, which recommend inhaled corticosteroids as the preferred initial therapy for children with mild to moderate asthma.

Dogs may help prevent kids from wheezing

Wed, 06 Dec 2006 18:41:37 PST

( from http://www.rxpgnews.com ) Washington, Dec 6 - Exposure to multiple dogs along with presence of a certain types of bacteria could help prevent kids from wheezing, says a new study.

David Bernstein, professor of immunology at the University of Cincinnati and other researchers, found this after studying about 500 infants, reported online edition of health magazine WebMD.

Wheezing in infants is associated with a higher risk of developing allergies and asthma later in life.

The researchers found that infants who live in a home with two or more dogs and a high level of certain types of a bacterial substance were a third less likely to develop wheezing in the first year of life than those who didn't live with dogs, it said.

'Our bodies are programmed to produce allergic responses early in life,' Bernstein said. 'But there are environmental factors like bacterial endotoxins that may modify the immune system and block development of allergies early in life'.

'We do not yet understand how and why exposure to high levels of bacterial endotoxins and multiple dogs in the home exert a protective effect in these high-risk infants from wheezing early in life,' Bernstein said.

The results of the study were published in the Journal of Allergy and Clinical Immunology.

Acute lung injury is prevented by FoxM1 protein

Fri, 15 Sep 2006 17:56:00 PST

( from http://www.rxpgnews.com ) Researchers at the University of Illinois at Chicago College of Medicine have identified a molecule that plays a critical role in the recovery of lung tissue following severe injury.

The study appeared in the Sept. 1 issue of the Journal of Clinical Investigation.

In acute lung injury -- usually resulting from infection, inflammation or surgical trauma -- cells that line the blood vessels in the lung lose their ability to form a barrier, allowing fluid to seep into the lung's air spaces and resulting in respiratory failure. Such damage is a significant cause of death in critically ill patients.

Very little is known about how the lung repairs this lining layer, called the endothelium, said You-Yang Zhao, research assistant professor of pharmacology.

"We thought it likely that the ability of cells to repair and restore the endothelium might depend on their ability to proliferate and fill in gaps in the endothelial monolayer barrier that allow leaking," said Zhao, who is lead author of the study.

Earlier studies had shown that FoxM1, a protein that controls the expression of genes, plays a critical role in cell proliferation. Working with the late Robert Costa, professor of biochemistry and molecular genetics at UIC, whose research focused on FoxM1, the researchers developed a mouse model that lacked the FoxM1 gene only in endothelial cells.

In the study, lung injury was induced in normal mice and in the gene-deleted mice. Blood vessels in the FoxM1-deficient mice continued to leak fluid, and the mice were significantly less likely to recover, resulting in a seven-times-greater mortality rate.

Although the immune response of each group was similar, there was less endothelial cell proliferation in the gene-deficient mice after the injury, suggesting that inability to fill the gaps in the barrier with new cell growth impaired the ability to recover.

Asrar Malik, professor and head of pharmacology at UIC, says the results suggest that lung injury activates a repair program, mediated by FoxM1, that encourages cell growth and restores the barrier integrity.

"This suggests future therapies for acute lung injury that target this molecule could promote endothelial regeneration and the patient's recovery," said Malik, who is senior author of the paper.

Six-minute walk test predicts mortality rates in patients with pulmonary fibrosis

Fri, 15 Sep 2006 17:46:00 PST

( from http://www.rxpgnews.com ) For idiopathic pulmonary fibrosis (IPF) patients awaiting lung transplantation, a simple walk test can predict mortality rates. A new study found that individuals with IPF who can cover less than 680 feet during the six-minute test are four times more likely to die than those who can walk greater distances.

The research appears in the second issue for September 2006 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

David J. Lederer, M.D., of the Division of Pulmonary, Allergy and Critical Care Medicine at Columbia University College of Physicians and Surgeons in New York City, and five associates examined the records of 454 adult IPF patients on U.S. transplantation waiting lists.

In IPF, lung tissue is damaged by an unknown cause. The walls of the air sacs become inflamed, which leads to scarring or fibrosis. As a result, patients with IPF frequently suffer from progressive respiratory failure. Eventually, the scarring causes permanent loss of the lungs' ability to transport oxygen.

To date, lung transplantation is the only medical therapy that has been shown to improve survival. Twenty-percent of all lung transplant procedures performed worldwide involve patients with IPF.

The investigators call the six-minute walk test a "simple, safe, reliable and inexpensive" way to assess the self-paced exercise capacity of IPF patients. It varies little when repeated on the same person over a short period of time.

"A total of 209 patients had a six-month follow-up without undergoing lung transplantation," said Dr. Lederer. "Forty-nine of these patients, 23 percent, died during that time period. The six-minute walk test's ability to separate those alive at six months from those who died was not only significantly better than chance, but also superior to the forced vital capacity percent (FVC%) predicted test."

The authors noted that a lower six-minute walking distance was associated with more severe lung disease, status as a minority and lower educational attainment in a nationwide cohort of patients with IPF who were listed for lung transplantation.

The test also predicted waitlist mortality independently of age, sex, race, lung function indices, presence of pulmonary hypertension and other potential confounders.

According to the investigators, the six-minute walk test has at least four advantages over other tests: 1) it is less costly than other tools; 2) it can be performed on patients with severe hypoxemia (inadequate amounts of oxygen in the blood) who require continuous high-flow oxygen; 3) it can be performed in any sufficiently long hallway by appropriately trained personnel; and 4) it does not require specialized equipment and expertise found only in established pulmonary function laboratories;

The authors concluded that a test like FVC% predicted might not be valid for gauging survival in patients with IPF who have been listed for lung transplantation because of the serious nature of their illness.

A dog in home may worsen asthma in children

Tue, 29 Aug 2006 21:08:00 PST

( from http://www.rxpgnews.com ) A new study from researchers at the Keck School of Medicine of the University of Southern California (USC) suggests that having a dog in the home may worsen the response to air pollution of a child with asthma. The study was published this week in the online edition of Environmental Health Perspectives, the journal of the National Institute of Environmental Health Sciences.

In "Dog Ownership Enhances Symptomatic Responses to Air Pollution in Children with Asthma," researchers looked at the relationship between chronic cough, phlegm production or bronchitis and dog and cat ownership among 475 southern California children with asthma who participated in the Children's Health Study, a longitudinal study of air pollution and respiratory health.

Children with dogs had significantly increased cough, phlegm production and bronchitis responses to the measured pollutants, including nitrogen dioxide, ozone, particulate matter and acid vapor. There were no increases of these symptoms in children who lived in homes without pets or who lived with only cats.

"Further work is needed to determine what it is about dogs that may increase an asthmatic child's response to air pollution," says Rob McConnell, M.D., professor of preventive medicine at the Keck School of Medicine of USC and lead author of the study.

McConnell and colleagues speculated that the increased response to air pollution from a dog in the home may really be due to increased levels of endotoxin, which is more common in homes where there is a dog.

"Cats are highly allergenic, and children with asthma are often allergic to cats," says McConnell. "Therefore if an allergen were enhancing the lung's response to air pollution, we'd be more likely to see an association with cats. But in this study we see an effect of air pollution in homes with dogs, so we think endotoxin exposure is a more likely explanation for our results than allergen exposure."

Endotoxin is a part of the cell wall of common bacteria in the environment. The authors note that inhaled endotoxin produces a marked inflammatory response in the lungs, and it may cause the airways of people with asthma to constrict. In previous studies, endotoxin has been shown to enhance the inflammatory effect of diesel exhaust particulate, inhaled highway aerosols and ozone in the lungs of experimental animals.

"There's experimental literature that shows both allergens and endotoxin interact with air pollution and increase the effect of each other," says McConnell. "But there's been very little study to see if these experiments have relevance for the general population of children with asthma."

McConnell cautioned that much more study is needed to specify why, exactly, children with asthma living in homes with dogs had an enhanced response to air pollution.

"There are other possible explanations for the findings," he says, "and actual measurements of home allergen and endotoxin, in addition to air pollution, would be important to evaluate further our hypothesis. It could also be that something only indirectly related to dogs could explain these results, for example that kids with dogs exercise outside more so they have more exposure to air pollution."

Cystic fibrosis-related diabetes is due to functional abnormalities in beta cells

Mon, 10 Jul 2006 06:21:00 PST

( from http://www.rxpgnews.com ) A growing number of cystic fibrosis patients are battling a second, often deadly complication: a unique form of diabetes that shares characteristics of the type 1 and type 2 versions that strike many Americans.

Many of these patients are teens who take enzymes to help digest their food and undergo daily physical therapy to loosen the thick, sticky mucus that clogs their lungs. But despite treatments that are helping thousands to live decades longer than ever before, when diabetes strikes, their life expectancy plummets -- on average by two years for men and an astounding 16 for women.

Now a University of Florida study in animals suggests diabetes in cystic fibrosis patients is not caused by the destruction of insulin-producing cells in the pancreas -- as is often the case in patients with the traditional form of type 1 diabetes -- but by differences in how these cells function.

Cystic fibrosis patients with diabetes produce some insulin on their own, but they require daily injections to boost their levels when eating so they can properly use sugar and other food nutrients for energy. At times they also become very resistant to the insulin they do make, similar to people with type 2 diabetes.

"For the longest time, the development of diabetes in cystic fibrosis has been thought to be chronic destruction of pancreas, so eventually you get loss of the insulin-producing beta cells," said Michael Stalvey, M.D., an assistant professor of pediatrics at UF. "Our study provides some early evidence to suggest there is an inherent difference in beta cell function."

Cystic fibrosis patients suffer recurrent episodes of infection and inflammation that slowly destroy the lungs. The pancreas is also affected, interfering with proper digestion. The disease stems from a faulty gene that blocks the normal passage of salt and water through the body's cells. It is this gene deficiency that is proposed to cause insulin-producing cells to malfunction, Stalvey said.

About 30,000 Americans have cystic fibrosis, making it the nation's most common lethal hereditary disorder. On average, they will not live past 35, though some are living through their 40s and even into their 60s. As each year passes, the likelihood they will develop diabetes increases. As many as 16 percent of all patients with cystic fibrosis also have diabetes, a number that is expected to rise as overall life expectancy for cystic fibrosis patients increases. Half will show signs of diabetes by age 30 and will suffer a rapid decline in overall health and lung function, muscle mass and body mass index.

"It's becoming more and more frequent because of the increasing age of patients," Stalvey said. "That's part of the reason why new recommendations call for screening patients 14 years and older yearly with an oral glucose tolerance test. Each year we know their likelihood of developing diabetes gets higher and higher.

"These young people, teenagers or young adults in their early 20s, have been fighting all their lives to stay healthy and keep their nutrition up," he added. "Now they've just been given something that potentially will overwhelm them. It's a huge thing for them, given the consequences that diabetes means to their underlying condition."

In the UF study, researchers developed the first animal model for the study of cystic fibrosis-related diabetes. They used mice that scientists from the University of North Carolina engineered to be missing the gene that makes the protein responsible for transporting salt and water across the cell membrane. People with cystic fibrosis have a mutated form of this protein.

UF scientists administered a low dose of a chemotherapy drug that weakened insulin-producing cells but did not destroy them. They then tested the animals' ability to regulate their blood sugar while fasting and after receiving glucose, simulating the rise in blood sugar that occurs after eating food.

Animals with the protein deficiency were more sensitive to the effects of the chemotherapy drug and had more difficulty regulating blood sugar levels, both while fasting and after receiving glucose. Mice that were still able to produce the crucial protein that prevents cystic fibrosis were able to maintain normal blood sugar levels, even after the drug had damaged some of their insulin-producing cells.

"This goes beyond improving our understanding of patients with cystic fibrosis-related diabetes; it also will help us improve our understanding of other forms of diabetes and help us work on strategies for a future cure," Stalvey said.

"Twenty-five percent of adolescents and 40 percent of adults with cystic fibrosis have diabetes, and diabetes is associated with poorer survival in this population," said Antoinette Moran, M.D., division head of pediatric endocrinology and director of the Pediatric Diabetes Program at the University of Minnesota Medical School. "The cause of cystic fibrosis-related diabetes is not completely understood, but it is clearly different from other forms of diabetes. The study by Stalvey and colleagues is important because it is the first to show that there are intrinsic abnormalities in the insulin-producing cells of the pancreas related to the genetic defect that causes cystic fibrosis."

COPD patients using beta-agonist inhalers are at risk

Mon, 10 Jul 2006 06:15:00 PST

( from http://www.rxpgnews.com ) A new analysis that compares two common inhalers for patients suffering from chronic obstructive pulmonary disease (COPD) finds that one reduces respiratory-related hospitalizations and respiratory deaths, but the other -- which is prescribed in the majority of cases -- increases respiratory deaths.

The Cornell and Stanford universities' statistical analysis of 22 trials with 15,276 participants found that common bronchodilators known as anticholinergics (generically named tiotropium and ipratropium) reduced severe respiratory events by 33 percent and respiratory-related deaths by 73 percent, compared with a placebo.

However, the same meta-analysis (which combines the results of the numerous studies) found that regularly inhaled beta-agonists (metaproterenol [Alupent], formoterol [Foradil], salmeterol [Serevent, Advair] and albuterol [Proventil, Ventolin, Volmax and others]) increased the risk of respiratory death more than twofold, compared with a placebo.

Yet only 5 percent of all prescriptions for COPD are anticholinergics, with beta-agonists dominating what doctors prescribe, the researchers report.

COPD is a progressive lung disease characterized by difficulty breathing, wheezing and a chronic cough. Complications include bronchitis and pneumonia. It is often associated with smoking.

"When patients used the anticholinergics, they experienced fewer severe exacerbations requiring hospitalizations and fewer respiratory deaths than those taking only a placebo," said Edwin Salpeter, the J.G. White Distinguished Professor of Physical Sciences Emeritus at Cornell, who led the statistical analysis in the study. An eminent astrophysicist, Salpeter has more recently focused his attention on medical statistics. "With the beta-agonists, it's the other way around, where the number of respiratory deaths increased when compared with those who took only the placebo."

"These results suggest that anticholinergics should be the bronchodilator of choice in COPD," said Shelley Salpeter, M.D., Edwin Salpeter's daughter and the lead author. She is a clinical professor of medicine at Stanford's School of Medicine and a physician at Santa Clara Valley Medical Center in San Jose, Calif. "The long-term safety of beta-agonists in patients with COPD should be addressed."

A recent meta-analysis by the Salpeters also revealed that beta-agonist inhalers increased both hospitalizations and deaths in asthma sufferers of all ages.

Previous studies have shown that patients with COPD build up tolerance to beta-agonists' bronchodilator and bronchoprotective effects after regular treatment compared with the first dose.

While beta-agonists may reduce symptoms through bronchodilation, the researchers believe they also promote bronchial inflammation and sensitivity by reducing bronchial protection without any warning of increased symptoms, which can then lead to a life-threatening response.

In the trials that were analyzed, only two patients out of 4,036 who took anticholinergics died of respiratory causes, while 12 of 3,845 participants in the placebo group died of respiratory ailments. When patients inhaled beta-agonists, there were 21 respiratory deaths out of 1,320 patients and eight respiratory deaths out of 1,084 participants in the placebo group.

Beta-agonists linked with increased number of respiratory deaths -study shows

Sat, 08 Jul 2006 20:36:00 PST

( from http://www.rxpgnews.com ) A new analysis that compares two common inhalers for patients suffering from chronic obstructive pulmonary disease (COPD) finds that one reduces respiratory-related hospitalizations and respiratory deaths, but the other -- which is prescribed in the majority of cases -- increases respiratory deaths.

The Cornell and Stanford universities' statistical analysis of 22 trials with 15,276 participants found that common bronchodilators known as anticholinergics (generically named tiotropium and ipratropium) reduced severe respiratory events by 33 percent and respiratory-related deaths by 73 percent, compared with a placebo.

However, the same meta-analysis (which combines the results of the numerous studies) found that regularly inhaled beta-agonists (metaproterenol [Alupent], formoterol [Foradil], salmeterol [Serevent, Advair] and albuterol [Proventil, Ventolin, Volmax and others]) increased the risk of respiratory death more than twofold, compared with a placebo.

Yet only 5 percent of all prescriptions for COPD are anticholinergics, with beta-agonists dominating what doctors prescribe, the researchers report.

The study, now online, will be published in an upcoming issue of the Journal of General Internal Medicine.

COPD is a progressive lung disease characterized by difficulty breathing, wheezing and a chronic cough. Complications include bronchitis and pneumonia. It is often associated with smoking.

"When patients used the anticholinergics, they experienced fewer severe exacerbations requiring hospitalizations and fewer respiratory deaths than those taking only a placebo," said Edwin Salpeter, the J.G. White Distinguished Professor of Physical Sciences Emeritus at Cornell, who led the statistical analysis in the study. An eminent astrophysicist, Salpeter has more recently focused his attention on medical statistics. "With the beta-agonists, it's the other way around, where the number of respiratory deaths increased when compared with those who took only the placebo."

"These results suggest that anticholinergics should be the bronchodilator of choice in COPD," said Shelley Salpeter, M.D., Edwin Salpeter's daughter and the lead author. She is a clinical professor of medicine at Stanford's School of Medicine and a physician at Santa Clara Valley Medical Center in San Jose, Calif. "The long-term safety of beta-agonists in patients with COPD should be addressed."

A recent meta-analysis by the Salpeters also revealed that beta-agonist inhalers increased both hospitalizations and deaths in asthma sufferers of all ages.

Previous studies have shown that patients with COPD build up tolerance to beta-agonists' bronchodilator and bronchoprotective effects after regular treatment compared with the first dose.

While beta-agonists may reduce symptoms through bronchodilation, the researchers believe they also promote bronchial inflammation and sensitivity by reducing bronchial protection without any warning of increased symptoms, which can then lead to a life-threatening response.

In the trials that were analyzed, only two patients out of 4,036 who took anticholinergics died of respiratory causes, while 12 of 3,845 participants in the placebo group died of respiratory ailments. When patients inhaled beta-agonists, there were 21 respiratory deaths out of 1,320 patients and eight respiratory deaths out of 1,084 participants in the placebo group.

Beta-agonists more than double death rate in COPD patients

Wed, 05 Jul 2006 15:18:00 PST

No evidence for inhaled corticosteroids efficacy in cystic fibrosis

Thu, 15 Jun 2006 16:57:00 PST

( from http://www.rxpgnews.com ) In comparison to cystic fibrosis (CF) patients who regularly use inhaled corticosteroid, those who did not use these drugs for six months exhibited no positive or negative effects in terms of major disease factors. Such factors include amount of lung function decline, number of antibiotics prescribed, time to onset of acute chest exacerbation or frequency of using a bronchodilator.

Ian M. Balfour-Lynn, M.D., F.R.C.P., of the Department of Pediatric Respiratory Medicine at Royal Brompton Hospital in London, and six associates concluded that it is safe for CF patients to stop using inhaled corticosteroids in order to lower their drug burden, to reduce potential adverse side effects, and to save money.

According to the authors, 52 percent of children and 55 percent of the adults with CF in Great Britain have been prescribed inhaled corticosteroid medication for their illness.

CF, an inherited disorder, is characterized by the production of thick, sticky mucus that frequently obstructs the lungs. The problem can lead to life-threatening lung infections and difficulties with the pancreatic ducts, preventing normal digestion and causing patient malnutrition. Because of improved treatment techniques in recent years, however, patient survival has increased from 25 to 33 years.

"Oral corticosteroids slow the progression of CF lung disease, but long-term use is precluded by unacceptable side effects," said Dr. Balfour-Lynn. "A systematic review of inhaled corticosteroid use in CF revealed 10 randomized controlled trials, with six having been published. The trials studied 293 adults and children. Although there was variable methodological quality among the studies, the conclusion was that there was 'no evidence from existing trials to support the practice of prescribing inhaled steroids in cystic fibrosis.'"

The authors noted that 52 percent of the patients were on high-dose inhaled corticosteroids (1,000 micrograms or more per day). At those levels, the drug can lead to significant symptoms related to adrenal suppression and insufficiency. Also, among pediatric patients, slowing of linear growth has been a problem for individuals taking the drug for a year or more.

Over a 6-month period, the researchers studied 84 CF patients (median age 14.6 years) who were using an inhaled corticosteroid (fluticasone) and 87 CF patients (median age 15.8 years) who were not.

"Replacing the inhaled corticosteroids with a placebo was found to be safe as there was no significant increase in lung-related adverse effects leading to withdrawal from the study, nor an increased need for oral corticosteroids," said Dr. Balfour-Lynn.

The researchers stressed that they were not advocating stopping inhaled corticosteroid use in all CF patients, but urging clinicians to assess the need in each individual.

"If there is objective evidence that a patients benefited when inhaled corticosteroids were first started, then it is likely they should be continued on the drug," said Dr. Balfour-Lynn.

Lung function test underused in patients with COPD

Wed, 14 Jun 2006 20:14:00 PST

( from http://www.rxpgnews.com ) At least two thirds of patients with chronic obstructive pulmonary disease (COPD) do not receive lung function testing that is recommended for the accurate diagnosis and effective management of the disease, suggesting that the majority of patients are diagnosed with COPD based on symptoms alone. New research published in the June issue of CHEST, the peer-reviewed journal of the American College of Chest Physicians (ACCP), finds that only one third of patients recently diagnosed with COPD underwent spirometry, a noninvasive lung function test, to confirm COPD or to manage their condition. Current national guidelines recommend spirometry for the diagnosis and management of COPD.

"Spirometry testing is necessary for the diagnosis and staging of COPD, yet the majority of patients with COPD are being diagnosed based on symptoms and smoking history," Todd A. Lee, PharmD, PhD, Hines VA Hospital, Hines, IL, Northwestern University Feinberg School of Medicine, Chicago, IL. "While these patients may indeed have COPD, spirometry is needed to make a definite diagnosis. As a result, patients who do not have COPD may be receiving unnecessary chronic therapy."

Lee and colleagues examined the use of spirometry among 197,878 patients (98 percent men) from the Veterans Health Administration (VHA) health-care system who were newly diagnosed with COPD. Patient records were reviewed for the general use of spirometry and spirometry related to exacerbation or surgery over a 12-month period. Of the patients, 33.7 percent had at least one spirometry through the VHA over the course of a year. A random sample of 6,000 patients revealed an additional 4.3 percent of patients underwent spirometry in non-VHA settings. Among patients who experienced acute exacerbation of COPD, spirometry was performed only 21.4 percent of the time, despite current guidelines that recommend spirometry four to six weeks after an exacerbation. Spirometry was used most frequently around surgical procedures that required general anesthesia, with 85.5 percent of patients having spirometry performed 30 days or less before their procedure.

A pulmonary clinic visit was the factor that had the highest association with having a spirometry test. Patients seen by a pulmonologist were three times more likely to have a spirometry test than those with no pulmonary visit. Younger age was significantly associated with the likelihood of having spirometry performed. Compared to patients younger than 50 years old, the likelihood of having a spirometry performed was 18 percent lower in those 60-69 years, 32 percent lower in those 70-79 years, and 48 percent lower in those 80 years or older. In addition, mental health and substance abuse diagnosis were also associated with lower likelihood of having spirometry performed.

"Providers may be more reluctant to use spirometry in older patients because of concerns about the validity and acceptability of the test results," said Dr. Lee. "Providers also may be interested in a definitive diagnosis for younger patients that are experiencing symptoms associated with COPD and thus refer these patients for spirometry." Although the role of spirometry in routine clinical practice remains unclear, researchers believe there is a need to increase the training and use of lung function testing in the primary care setting.

"COPD is a highly preventable disease most commonly caused by long-term smoking," said W. Michael Alberts, MD, FCCP, President of the American College of Chest Physicians. "Symptoms of COPD may not be noticeable for several years, making it difficult to diagnose and treat the disease in its early stages. Lung function testing for smokers and other high-risk patients may help with early identification of COPD and more effective disease management."

Wrinkles clue to risk of progressive lung disease (COPD)

Wed, 14 Jun 2006 20:05:00 PST

( from http://www.rxpgnews.com ) Middle aged smokers, who are heavily lined with wrinkles, are five times as likely to have chronic obstructive pulmonary disease, or COPD for short, suggests research published ahead of print in Thorax.

COPD is an umbrella term for a range of progressive chronic lung diseases, such as emphysema and bronchitis, which block the airways and restrict oxygen flow around the body.

In excess of 1 million people are thought to have COPD in the UK, many of whom have not been diagnosed. And the World Health Organization estimates that it will become the third leading cause of death in the world by 2020.

It is well known that smoking causes premature ageing of the skin, and similarly, most cases of COPD are caused by smoking.

But not all smokers go on to develop COPD, and the researchers wanted to know if the extent of facial wrinkling might provide a clue as to a smoker's likelihood of having the disease.

They studied 149 current and former middle aged smokers from 78 families. In all, 68 people had COPD.

More than 80% (124) of the total sample had no or very few facial lines, and 25 had widespread wrinkles.

Forced expiratory volume in 1 second, which measures lung strength, was significantly lower in those with extensive wrinkling than it was in those whose faces were only minimally lined.

And those with lined faces were five times more likely to have COPD than those without, after taking account of age and the number of years as a smoker. Facial wrinkling was also associate with triple the risk of more severe emphysema.

Antibiotics reduce risk of dying from COPD attack by 77 percent

Mon, 12 Jun 2006 20:21:00 PST

( from http://www.rxpgnews.com ) People with chronic obstructive pulmonary disease often experience short term worsening and aggravation of their symptoms. To date, there has been conflicting evidence as to whether these exacerbations should be treated with antibiotic therapy. A new systematic review to be published in The Cochrane Library, Issue 2, 2006 now concludes that they should be used. The researchers found that antibiotics reduce the risk of dying from the attack by 77%, decreases the risk of treatment failure by 53% and decrease the risk of developing pussy sputum by 44%. There is, however, a small increase in the risk of developing diarrhoea.

Many people question whether antibiotics should be used to combat exacerbations of COPD. The uncertainty stems from the growing desire to use antibiotics only when necessary, combined with the recognition that up to one third of exacerbations of COPD have are not caused by infections, and some others are due to viral infections.

A large number of trials have been conducted to try and address this situation, but a simple comparison suggests that the data is contradictory.

To clarify the situation the Cochrane Review Authors performed a systematic review of available data, and identified 11 trials involving 917 patients.

"The review showed clearly that antibiotic therapy, regardless of which antibiotic was used, reduced the risks involved in an exacerbation, and as might be expected, the effects is greatest in patients with more severe disease," says lead Review Author Dr Felix Ram, Senior Lecturer in Respiratory Medicine & Clinical Pharmacology in the School of Health Sciences, at Massey University in Auckland, New Zealand.

"The controversy over whether antibiotics should be prescribed to patients with acute exacerbations of COPD has been very highly debated and unsolved for many years in the respiratory field and this review will help to finally resolve this long outstanding issue in the management of our COPD patients," adds Dr Ram.

Women with chronic obstructive pulmonary disease (COPD) fare worse than men

Mon, 12 Jun 2006 20:02:00 PST

( from http://www.rxpgnews.com ) Women with chronic obstructive pulmonary disease (COPD) fare worse than men both in terms of the severity of their disease and their quality of life. These differences may play a role in the increased death rate seen among female patients with COPD, said researcher Claudia Cote, M.D., Assistant Professor of Medicine at the University of South Florida in Tampa.

The researchers studied 85 women, and compared them with 95 men who had the same levels of COPD severity according to guidelines of the Global Initiative for Chronic Lung Disease (GOLD). They found that female patients were significantly younger than male patients with the same severity of disease. The women had lower lung function, more trouble breathing, and reported a worse quality of life. The women also received a worse score on the BODE index, which looks at lung function, nutritional status, symptoms and exercise capacity in order to measure a COPD patient's disease severity and predicted survival.

COPD is the fourth leading cause of death in America, claiming the lives of 120,000 Americans in 2002. Beginning in 2000, women have exceeded men in the number of deaths attributable to COPD. In 2002, over 61,000 females died compared with 59,000 males.

Reasons that women with COPD do worse than their male counterparts, Dr. Cote said, may be related to underdiagnosis, misdiagnosis and less access to healthcare.

While the study findings may appear discouraging for women with COPD, the way in which the patients were assessed can lead to improvements in treatment for all COPD patients, Dr. Cote said.

"Until recently, doctors have used only lung function as a measurement for COPD severity," Dr. Cote said. "But we've come a long way in understanding this disease, and we now know that while COPD affects the respiratory system, it also has tremendous consequences on the peripheral muscles, cardiovascular system, and overall nutritional status--it's a multi-systemic disease. If we only measure respiratory function we will be overlooking other organ impairment and then will miss an opportunity for intervention."

Understanding that COPD can affect many aspects of a patient's health gives doctors more tools to treat patients, Dr. Cote said. "Traditionally, doctors have just looked at airflow obstruction, which doesn't respond well to drug treatment and has the tendency to deteriorate as a person ages, so the disease has seemed poorly treatable and minimally reversible. But by doing a comprehensive assessment, looking at a patient's nutritional status, exercise capacity and symptoms, it becomes more possible to treat COPD because such impairment is amenable to intervention."

For example, she said, there are now two long-acting bronchodilators that have been shown to improve not only lung function but also exercise capacity, symptoms, health status and lung hyperinflation in COPD patients. Non-drug interventions such as pulmonary rehabilitation can also improve some of these outcomes and improve survival, while surgery such as lung volume reduction and lung transplantation greatly help selected patients while prolonging their lives. "We should see COPD as a treatable disease and be aggressive in the management of our patients. Maybe then we'll be able to impact survival," she said. "COPD no longer has to be seen as a chronic, relentless, and fatal disease--we can help patients live longer with better quality of life."

This message is important for women in particular, Dr. Cote said. "Women's life expectancy is on average seven years longer than men's, so women who are living with a chronic illness like COPD will bear a heavier burden of disease compared with men."

There is a growing awareness that COPD is treatable, and that there are tools to assess how patients are doing on many levels, Dr. Cote said. "Physicians will start treating COPD more aggressively, because they know they can provide important improvements in outcomes for their patients."

Hcp1 plays a critical role in cystic fibrosis infection

Sat, 10 Jun 2006 13:43:00 PST

( from http://www.rxpgnews.com ) Harvard Medical School researchers have discovered one way that a hardy disease-causing bacteria could be surviving in the lungs of chronically infected cystic fibrosis (CF) patients.

"This work is important because pathogenic bacteria such as Pseudomonas aeruginosa (PA) use protein secretion systems to cause disease in their hosts," said Joseph Mougous, lead author of the study published in the June 9 issue of Science. "In the case of Pseudomonas aeruginosa, the host may be a cancer patient with a weakened immune system, a burn patient, or a person with cystic fibrosis (CF)."

Pseudomonas aeruginosa (PA), a pathogen that infects more than 80 percent of cystic fibrosis patients, is a leading cause of these patients' death. PA is difficult to treat because it is resistant to many drugs.

"Since we know so little about what this bacterium is up to while it's engaged in these chronic infections, the discovery of this protein secretion system might lead to finding a new target for treatments," said Mougous, a research fellow in the Harvard Medical School (HMS) Department of Microbiology and Molecular Genetics.

Researchers at Argonne National Laboratory (ANL) provided one of the clues that contributed to the HMS discovery. Working through a number of pathogenic proteins, ANL protein crystallographer Marianne Cuff saw a bagel-shaped pore that might be involved in transferring toxins into cells. She deposited the structure of the protein, called Hcp1, into the Protein Data Bank, a resource used by biologists worldwide to find information about the proteins they are studying.

While exploring the Protein Data Bank, Mougous, who was studying PA in the laboratory of department chair John Mekalanos, recognized that the amino acid sequence of Hcp1 in PA closely resembled that of Hcp1 in Vibrio cholerae. The Mekalanos lab had previously discovered that the Hcp1 protein of V. cholerae is released from the bacterium via a novel secretion pathway. Because Hcp1 proteins from both pathogens belong to the same protein family, Mougous wondered whether the Pseudomonas Hcp1 might also be secreted via this pathway.

The Harvard and Argonne researchers quickly formed a collaboration and confirmed the hypothesis. They then turned their attention to Hcp1 in cystic fibrosis patients to gain more insight in the role of Hcp1 during infection.

Working with cystic fibrosis patients at Children's Hospital Boston, the HMS researchers sought and found Hcp1 in the sputum of patients with P. aeruginosa. They also found Hcp1 antibodies in the patients' blood further evidence that Hcp1 plays a critical role in the infection. The human immune system creates antibodies to pathogens it is exposed to.

"CF patients are particularly susceptible to PA," Mougous said. "The bacterium thrives in the excess mucus that accumulates in their lungs. Once a PA infection in a CF patient's lung has been established, these hardy bacteria are difficult or impossible to clear, which over many years eventually results in the death of the patient. Our paper provides evidence that the protein secretion system we discovered represents at least one way this bacterium could be promoting its own survival in the lungs of CF patients."

"This finding provides a possible drug target to fight the infection in cystic fibrosis patients," added Andzrej Joachimiak, director of Argonne's Structural Biology Center and of the Midwest Center for Structural Genomics based at Argonne.

Infants exposed to cigarette smoke are more likely to develop allergic rhinitis

Thu, 18 May 2006 03:16:00 PST

( from http://www.rxpgnews.com ) University of Cincinnati (UC) epidemiologists say itâs environmental tobacco smokeânot the suspected visible moldâthat drastically increases an infantâs risk for developing allergic rhinitis by age 1.

Commonly known as hay fever, allergic rhinitis occurs when a personâs immune system mistakenly reacts to allergens (aggravating particles) in the air. The body then releases substances to protect itself, causing the allergy sufferer to experience persistent sneezing and a runny, blocked nose.

This is the first study to show a relationship between environmental tobacco smoke exposure and allergic rhinitis in year-old infants, the UC team reports in the June issue of Pediatric Allergy and Immunology and an early online edition May 17.

âPrevious studies have addressed risk factors for allergic rhinitis, but they failed to examine multiple environmental exposures, and some yielded contradictory results,â says Jocelyn Biagini, lead author and an epidemiologist in UCâs environmental health department.

The study evaluated the effects of numerous indoor exposures to such things as environmental tobacco smoke, visible mold, pets, siblings and the day-care environment on 633 infants under age one.

âWe found that infants who were exposed to 20 or more cigarettes a day were three times more likely to develop allergic rhinitis by their first birthday than those who were not exposed,â says Biagini.

These findings, she says, suggest that for the health of their children, itâs important for parents to eliminate tobacco smoke from their homes.

âAn infantâs lungs and immune system are still developing in the first year of life,â says Grace LeMasters, PhD, coauthor and principal investigator of the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). âEnvironmental tobacco smoke puts harmful particulates in the air thatâwhen inhaled regularly at such an early ageâcould lead to serious allergic conditions like asthma.â

CCAAPS, funded by the National Institute of Environmental Health Sciences, is a five-year study examining the effects of environmental particulates on childhood respiratory health and allergy development.

About 43 percent of children, says Dr. LeMasters, are exposed to home environmental tobacco smoke. According to the Centers for Disease Control and Prevention, about 21 percent of all American adults smoke cigarettes. Of them, 12 percent report smoking 25 or more cigarettes daily.

While household mold, long thought to be a major cause, did not contribute to allergic rhinitis development, Biagini says, it did increase the infantâs risk for ear infections.

Infants exposed to a mold patch about the size of a shoebox were five times more likely to contract ear infections requiring antibiotics than those living in mold-free homes, she explains.

The UC study also suggests that infants with older siblings are less likely to have allergic rhinitis.

âResearch has shown that exposure to certain infections early in life may decrease your risk for allergic diseases,â explains James Lockey, MD, professor of environmental health and pulmonary medicine. âWe found a âsibling protective effectâ for allergic rhinitisâthis may mean the more siblings infants have, the more infections they are exposed to. As a result, the infantâs body may be better equipped to fight off allergic diseases later in life.â

PEAK Trial: Inhaled steroids do not prevent chronic asthma

Thu, 11 May 2006 17:36:00 PST

( from http://www.rxpgnews.com ) Daily treatment with inhaled corticosteroids can reduce breathing problems in pre-school-aged children at high risk for asthma but they do not prevent the development of persistent asthma in these children, according to new results from the Childhood Asthma Research and Education (CARE) Network supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health.

Studies in older children and adults show that the most effective long-term control medicine for persistent asthma (symptoms more than two days a week or more than twice a month at night) is inhaled corticosteroids, which reduce airway swelling and help prevent asthma symptoms (e.g., asthma attacks). The Prevention of Early Asthma in Kids (PEAK) multicenter clinical trial, published in the May 11, 2006, issue of the New England Journal of Medicine, answers a question that pediatricians and researchers have been asking for years: Can medicine that treats the inflammation of asthma be used to prevent the disease if given early enough in at-risk patients?

"Asthma is an enormous public health problem, and this study was designed to see if we could stop the development of asthma in its tracks while the lungs are still developing in young children known to be at high risk," said NHLBI Director Elizabeth G. Nabel, MD. "Although this study shows that inhaled corticosteroids do not prevent chronic asthma, it provides clear evidence that inhaled corticosteroids benefit even some of our youngest patients."

A breathing disease in which the airways are inflamed, asthma is the most common chronic childhood illness in the United States. In 2004, nearly 9 million children had been diagnosed with asthma, including 1.5 million under the age of 5 years, according to the Centers for Disease Control and Prevention (CDC). In addition, children 4 years old or younger have the highest rates of hospitalization (59 per 10,000) and emergency room use (162 per 10,000) due to asthma of any age group. Overall, CDC estimates that more than 20 million Americans have been diagnosed with asthma.

Researchers have found that in most cases of chronic asthma, symptoms such as frequent coughing, wheezing (a whistling or squeaky sound during breathing) or shortness of breath begin during the first three years of life. Declines in lung function can occur this early as well. However, few studies have been conducted in children under 4 years of age.

In the PEAK trial, 285 children ages 2 to 3 years at high risk for asthma were randomly selected to receive either daily treatment of inhaled corticosteroid treatment (fluticasone propionate [Flovent] 88 mcg twice daily, using a metered-dose inhaler with a valve spacer and mask) or placebo for two years. All children in the study received additional medication to treat symptoms if they occurred. After two years, daily use of inhaled corticosteroids (or placebo) was stopped, and all participants were observed for an additional year to determine if the earlier treatment had lasting effects. Researchers report no significant differences between the participants in the treatment group and participants in the control (placebo) group during this observation period.

"We found that inhaled corticosteroids did not alter the natural course of disease in children who began daily treatment at 2 or 3 years of age," noted Theresa W. Guilbert, MD, lead author of the paper and assistant professor of pediatrics at the Arizona Respiratory Center of the University of Arizona College of Medicine in Tucson. "After a year without treatment, the children who had received inhaled corticosteroids had roughly the same frequency and severity of asthma-related symptoms and similar levels of lung function as the children who had not been treated."

During the two-year treatment period, however, children treated with the daily inhaled corticosteroids had significantly fewer and less severe asthma symptoms than their peers who were given placebo. For example, children treated with inhaled corticosteroids had on average 2 days of symptoms per month compared to 4 days of symptoms per month in the placebo group. They also had a lower rate of severe asthma exacerbations requiring additional treatment with oral corticosteroids and had less need for leukotriene receptor antagonists or additional inhaled steroid treatments.

The researchers found that the inhaled corticosteroids appeared to slow the growth of the children in the treatment group; however, this effect appeared to be temporary. The difference in growth rate was significant between the two groups during the first year of the study, but not during the second year of treatment. During the third-year observation period, the children who had been regularly treated with inhaled corticosteroids grew more quickly than the children who had not received inhaled corticosteroids. Overall, the children in the placebo group grew an average of 1.1 cm more than the children in the treatment group after two years, but by the end of the three-year study, the difference in average increase in height dropped to 0.7 cm.

"Another helpful outcome of the PEAK study is that it demonstrated that the asthma predictive index used in the study can help identify children who are at high risk for asthma-related problems," noted Lynn M. Taussig, MD, chair of the CARE Network, special advisor to the Provost, University of Denver and past president and chief executive officer of National Jewish Medical and Research Center.

The asthma predictive index showed that children at risk are those with frequent wheezing who also have either

* one of the following: eczema (a chronic skin disease characterized by itchy, inflamed skin), allergic reactions to airborne substances such as dust mites, or a parent with asthma; OR
* two of the following: food allergy, wheezing unrelated to colds, or elevated levels of eosinophils (a type of white blood cell).

"Perhaps the asthma predictive index can be used as a tool to help parents and pediatricians recognize vulnerable children early, in order to begin treatment and help the children have as many symptom-free, active and playful days as possible," said Taussig. The results of PEAK are similar to a large, five-year study of older children (ages 5 to 12 years), which demonstrated that inhaled corticosteroids are generally safe and effective for children with mild-to-moderate asthma. Like PEAK, the NHLBI-supported Childhood Asthma Management Program (CAMP) showed a slight reduction in growth rate among children taking inhaled corticosteroids only during the first year of treatment. Also like PEAK, the benefits of treatment stopped when the treatment was discontinued.

Guidelines from the National Asthma Education and Prevention Program recommend inhaled corticosteroids or another daily long-term control medication in older children and adults with persistent asthma to prevent symptoms and quick-relief medication such as inhaled bronchodilator to treat acute asthma symptoms if they occur. The results of the PEAK study provide strong support for extending the use of inhaled corticosteroids, for the same reasons, to pre-school children at high risk for asthma.

Breathing Heliox 28 significantly improve the exercise performance in COPD

Sat, 15 Apr 2006 18:48:00 PST

( from http://www.rxpgnews.com ) Breathing a special gas mixture may significantly improve the exercise performance of individuals with severe chronic obstructive pulmonary disease (COPD). During an endurance walking test, the patients found that they could improve their walking distance by 64 percent with less shortness of breath.

Elizabeth A. Laude, Ph.D., of the University of Sheffield in the United Kingdom, and seven associates investigated the effects of varying oxygen and helium levels in the air breathed during exercise by 82 patients who had severe, but stable COPD.

The investigators tested four different gas mixtures with the patients: 72 percent helium and 28 percent oxygen (Heliox28); 79 percent helium and 21 percent oxygen (Heliox21); 72 percent nitrogen and 28 percent oxygen (Oxygen28); and 79 percent nitrogen and 21 percent oxygen (medical air).

"Patients walked significantly further while breathing Heliox 28 than with either Heliox 21 or Oxygen 28," said Dr. Laude.

By replacing the nitrogen with normal supplementary oxygen with lower density helium gas, the researchers hoped that they might reduce airway resistance and improve the participants' respiratory gas exchange.

"COPD is associated with impaired exercise capacity, which contributes significantly to a reduced quality of life in these patients," said Dr. Laude.

COPD results from persistent obstruction of the airways associated with either severe emphysema or chronic bronchitis. In emphysema, the tiny air sacs of the lung (alveoli) become enlarged and their walls are destroyed. In chronic bronchitis, the bronchial glands enlarge, causing a chronic cough and excess mucus. Ten to 15 percent of all smokers develop COPD as a result of irritants in tobacco that cause inflammation of the alveoli.

During the exercise test, the gas mixtures were administered through face masks with a special valve for the incoming gas. An investigator carried a gas cylinder with the mixture while walking beside the patient.

Individuals with the worst lung function test results showed the greatest benefit from the special mixtures.

"Although the recent American Thoracic Society/European Respiratory guidelines had recognized COPD is a preventable and treatable condition, it is still regarded by many as one in which significant improvement is not possible," said Dr. Laude. "Our data shows this is not the case. The changes in endurance exercise and reductions in breathlessness we report while breathing increased inspired oxygen or heliox gas mixtures are substantial, being at least comparable to those achieved with current bronchodilator therapy, pulmonary rehabilitation or even lung volume reduction surgery."

In an editorial on the article in the same issue of the journal, Jadwiga A. Wedzicha, M.D., of University College London in the United Kingdom, tried to answer a fundamental question raised by the study. He wrote: "Can these findings be applied in clinical practice? The most promising use of Heliox mixtures would be as an adjunct of pulmonary rehabilitation in patients with severe COPD who are still disabled by dyspnea and are unable to achieve full benefits of training despite pharmacologic treatment and ambulatory oxygen therapy. Use of Heliox with rehabilitation needs to be tested in large controlled studies with appropriate outcome measures. Heliox is also easier for the patient to tolerate during exercise than noninvasive ventilation, but the two treatments will need formal comparisons. However, before any further development in Heliox therapy for COPD, improved methods of delivery of Heliox to the hospital clinic and community would need to be developed. Recent data shows that despite benefits in patients with COPD, compliance with ambulatory oxygen in the community is relatively poor."

Telithromycin antibiotic could help in asthma attack

Sat, 15 Apr 2006 18:08:00 PST

( from http://www.rxpgnews.com ) A relatively new kind of antibiotic has been found to provide faster relief from an asthma attack, but more research is necessary before the drug can be prescribed, says a study.

Asthma, a chronic ailment that afflicts millions around the world, causes inflammation of the airways, or bronchi, and affects the way air enters and leaves the lungs, thereby disrupting breathing.

During an asthmatic attack, the airways of a patient become narrow, making it difficult to breathe. Doctors say steroids can help to treat the underlying lung inflammation associated with the condition, but they say that better drugs are needed to treat asthma attacks.

Sebastian Johnston at Imperial College, London, and colleagues tested telithromycin, an antibiotic by Sanofi-Aventis, on 278 adults with asthma, reported the online edition of New Scientist.

The antibiotic is typically used to treat chronic bronchitis and also appears to have anti-inflammatory properties.

Those who took the antibiotic reported twice as many symptom-free days as their counterparts who received the placebo. During the 10-day treatment period, those on telithromycin had a 40 percent reduction in symptoms as opposed to a 27 percent reduction seen in those on standard treatment alone.

They also showed a speedier recovery - about five days compared with eight days for the control group. Patients were considered to have recovered from their acute attack if they showed a 50 percent reduction in symptoms.

Medical experts however fear that antibiotic resistance would increase if physicians prescribe telithromycin improperly. They say that further trials of the drugs are necessary.

Antibiotics are not formally approved to treat asthma but some physicians prescribe them to asthma sufferers who show respiratory problems that could be due to bacterial infection.

Combined treatment cuts inflammatory cells in chronic obstructive pulmonary disease

Mon, 03 Apr 2006 06:48:00 PST

( from http://www.rxpgnews.com ) The combination of two existing clinical treatments, salmeterol and fluticasone propionate, can significantly reduce inflammatory cells in the airways of current and former smokers being treated for moderate to severe chronic obstructive pulmonary disease (COPD).

Neil Barnes, M.D., Professor of Respiratory Medicine at London Chest Hospital in United Kingdom, and nine colleagues, performed a randomized, double-blind, placebo-controlled, parallel-group, multi-center study on 140 COPD patients. Of this total, 67 patients (average age 65) were treated with salmeterol/fluticasone propionate, while 73 individuals received a placebo medication. Both treatment groups were matched for demographics, smoking history, and baseline lung function.

"This is the first demonstration that a currently available treatment can reduce the exaggerated bronchial inflammation in COPD," said Dr. Barnes. He adds that this therapy decreased inflammation by 36 percent.

After conducting a biopsy examination, the researchers conclude that the combination therapy significantly reduced the absolute numbers of certain inflammatory cells, including leukocytes, CD8+ cells and CD4+ cells, and caused a reduction in cells expressing genes for certain pro-inflammatory mediators in the lung.

"Inflammation in COPD is distinct from that in asthma and is characterized by a predominance of CD8+ cells at all airway levels, including the functional part of the lung, or parenchyma," explained Dr. Barnes.

According to the authors, this broad spectrum of anti-inflammatory effects was also accompanied by a significant improvement in lung function.

"The magnitude of the improvement in the standard lung function test was similar to or greater than that seen in other studies of anti-inflammatory treatments used in COPD," said Dr. Barnes.

Using a bronchoscope, the investigators examined each participant's lung passages one week before the study began and after 12 weeks of treatment. Only four patients experienced adverse reactions to the bronchoscopy, such as nose bleed, cough, sore throat, etc.

The researchers gave six patients in the treatment group and eight in the control cohort an antibiotic to reduce worsening COPD symptoms. One patient from the treatment group also was hospitalized to treat worsening symptoms.

"As designed, our research represents the largest biopsy study ever to be completed in COPD," said Dr. Barnes.

He noted that these findings support the premise that the combination treatment could be applied earlier than currently proposed in existing COPD guidelines.

Study finds in utero arsenic exposure tied to lung disease

Tue, 28 Mar 2006 21:04:00 PST

( from http://www.rxpgnews.com ) Children who are exposed to high levels of arsenic in their drinking water are seven to 12 times more likely to die of lung cancer and other lung diseases in young adulthood, a new study by University of California, Berkeley, and Chilean researchers suggests.

The risk of dying due to bronchiectasis, usually a rare lung disease, is 46 times higher than normal if the child's mother also drank the arsenic-contaminated water while pregnant, according to the study. These findings provide some of the first human evidence that fetal or early childhood exposure to any toxic substance can result in markedly increased disease rates in adults.

"The extraordinary risk we found for in utero and early childhood exposure is a new scientific finding," says the study's lead author, Allan Smith, professor of epidemiology at UC Berkeley's School of Public Health. "I sometimes ponder the improbability that drinking water with concentrations of arsenic less than one-thousandth of a gram per liter could do this, and think that I've got to be wrong. But our years of working with arsenic exposure in India and Chile tie in with this study perfectly."

The paper will appear in the July print issue of Environmental Health Perspectives and will be posted on its Web site today, Monday, March 27.

Classified as a semi-metal, the element arsenic is one of the most potent cancer-causing agents known. Skin, bladder and lung cancer rates are substantially higher in regions where the tasteless, colorless substance occurs in drinking water. A recent study by Smith showed that adults exposed to arsenic can also develop decreased lung function similar to that experienced by cigarette smokers. And, in a paper to be published on April 1 in the American Journal of Epidemiology, Smith and his colleagues provide evidence that women exposed to high concentrations of arsenic during pregnancy experience six-fold increases in stillbirths and other adverse effects.

Arsenic is particularly prevalent in Region II, a province in the north of Chile and one of the driest places on earth. In 1958, the cities there of Antofagasta and neighboring Mejillones tapped into arsenic-laden rivers to supply their growing populations with water. For the next 13 years, until an expensive arsenic removal plant was installed, the water supply for all residents in the cities was laced with an average of 860 micrograms per liter of arsenic. In contrast, the standard for arsenic in drinking water in the United States was recently dropped from 50 micrograms per liter to 10 micrograms per liter, with compliance required in 2006. (A microgram is a millionth of a gram.)

With such clear-cut exposure to arsenic, the unfortunate Chilean cities became a tragic natural experiment for studying the effects of arsenic on humans.

From earlier work he and others conducted in India, Smith knew that arsenic is associated with bronchiectasis, a rare lung disease that causes distortion and dilation of the bronchi, eventually leading to chronic infections. A study involving death certificates for young adults in Antofagasta and Mejillones, Smith realized, would reveal whether lung cancer and bronchiectasis could also occur as a result of childhood exposure to arsenic.

Working with colleagues Guillermo Marshall and Catterina Ferreccio from the Pontificia Universidad Católica de Chile in Santiago, Smith compared the death rates from 1989 to 2000 of young adults in the two cities with the rates in the rest of Chile, outside of Region II. The team focused on two groups: those born between 1951 and 1958, when the water supply to the cities had relatively low arsenic concentrations, and those born during the high-exposure period of 1958 to 1971.

Both groups, they reasoned, would have been exposed to high levels of arsenic throughout some or most of their childhoods, but the second group would also have been exposed in utero, that is, while in the womb. Exposure for both groups would have abruptly declined at the same time, in 1971, when the arsenic removal plant went online.

The researchers' findings were dramatic. For people exposed to arsenic only as children, the death rate from lung cancer was seven times greater than in the rest of Chile, while the death rate from bronchiectasis was 12 times greater. For those with both early childhood and in utero exposure, the death rate from lung cancer was six times greater than that in the rest of Chile, and the death rate from bronchiectasis was an astonishing 46 times greater.

In absolute numbers, there were nine deaths from bronchiectasis, 16 from lung cancer and seven from other lung diseases in adults aged 30 to 49 who were born during the period of high exposure. In the year 2000, there were about 300,000 people living in the two cities where the study was conducted.

"In all my career, these are the most amazing findings I've confronted so far," Smith says. "Their magnitude is unparalleled. Not only are these the highest death rates for lung cancer and bronchiectasis ever discovered among young adults, but they are also the strongest evidence I know of to date that implicates not just arsenic, but any environmental exposure in utero or in early childhood to any adverse health effect in adults."

Putting these results in perspective, studies have found that the rates of early-adult lung cancer among survivors of the atomic bombings at Hiroshima and Nagasaki who were exposed to high levels of radiation before birth or as children are many times lower than those in Antofagasta and Mejillones, as are the rates among young adults exposed to secondhand tobacco smoke as children. Only active smoking itself results in lung cancer rates higher than the seven-fold increase found in his study, Smith says.

Cystic fibrosis research could benefit from multi-functional sensing tool

Mon, 27 Mar 2006 16:17:00 PST

( from http://www.rxpgnews.com ) Researchers are using an innovative, multi-functional sensing tool to investigate adenosine triposphate (ATP) release and its role in cystic fibrosis. The ATP study marks the first application of a novel sensing system developed by a research team led by Christine Kranz at the Georgia Institute of Technology.

This patented technology adds recessed micro- and nano-electrodes to the tip of an atomic force microscope (AFM), creating a single tool that can simultaneously monitor topography along with electrochemical activity at the cell surface.

The new multi-functional imaging technique will advance the study of biological samples, said Boris Mizaikoff, an associate professor at Georgia Tech's School of Chemistry and Biochemistry and director of its Applied Sensors Lab. "Conventional AFM can image surfaces, but usually provides limited chemical information," he explained. "And though scanning electrochemical microscopy (SECM), another probing technique, provides laterally resolved electrochemical data, it has limited spatial resolution. By combining AFM and SECM functionality into a single scanning probe, our tool provides researchers with a more holistic view of activities at the cell surface."

In addition to Mizaikoff and Kranz, the team also includes post-doctoral scholar Jean-Francois Masson and graduate student Justyna Wiedemair.

In the ATP study, which is sponsored by the National Institutes of Health and done in collaboration with Douglas Eaton at Emory University's School of Physiology, the Georgia Tech team used the multi-scanning biosensors to study ATP release at the surface of live epithelial cells (cells that cover most glands and organs in the body). ATP, a chemical involved in energy transport, is of interest to medical researchers because elevated levels have been linked with cystic fibrosis, a disease that affects one out of every 2,500 people in the United States.

Using epithelial cell cultures from Emory, the Georgia Tech researchers have demonstrated that their multi-functional biosensors work at the live-cell surface during in vitro studies.

"Before you can identify what triggers the ATP release, we must be able to quantitatively measure the released species at the cell surface," Mizaikoff said, noting that many pathological events involve the disruption of chemical communication and molecular signaling between cells, especially in the nervous system, lungs and kidneys.

Improved understanding of cellular communication can lead to new strategies for treating diseases, Mizaikoff added: "Being able to operate sensors in an electrochemical imaging mode at the micro- and nanoscale is an exciting opportunity for complementing optical imaging techniques. There are many clinical research problems that these biosensors can help with."

During the same ACS session, the Georgia Tech team will also present findings of a related project.

A collaboration with Estelle Gauda at Johns Hopkins University and also supported by NIH grants, this project monitors ATP release at the carotid body. (The carotid body is a chemoreceptor that, among other functions, monitors oxygen content in the blood and helps control respiration.)

Chronic oxygen stress too much or too little oxygen during early postnatal development can lead to a deficiency in the amount of oxygen reaching body tissues in premature infants and newborn animals. But little is known about how oxygen stress affects regulatory networks and alters chemoreceptors. To gain insights, the Georgia Tech researchers will study ATP, which is among the signaling molecules released by the carotid body.

Researchers incorporate the same technology used for the multi-functional scanning probe. For this study, however, they have tailored the biosensor to work at a larger scale microelectrodes are about 25 micrometers in diameter as opposed to the sub-micrometer dimensions of the combined AFM-SECM approach.

"There are a lot of emerging sensor technologies, but few have been adapted for routine use in medical research, which is one of the development goals at the Applied Sensors Lab," Mizaikoff said. "As analytical chemists, we want to develop quantitative sensing devices that can answer important questions for clinical researchers."

Loss of CFTR-mediated fluid secretion is the culprit in cystic fibrosis

Sun, 19 Mar 2006 20:56:00 PST

( from http://www.rxpgnews.com ) Scientists at Stanford University have determined that the buildup of sticky mucus found in cystic fibrosis is caused by a loss in the epithelial cell's ability to secrete fluid. This research appears as the "Paper of the Week" in the March 17 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.

Cystic fibrosis is the most common, fatal genetic disease in the United States. It causes the body to produce thick, sticky mucus that builds up in the lungs and blocks the airways. This makes it easy for bacteria to grow and leads to repeated serious lung infections. The thick, sticky mucus can also block tubes in the pancreas, preventing digestive enzymes from reaching the small intestine.

The disorder results from mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR), a membrane channel regulator essential for proper salt and water movement across some epithelia. Currently, there are two essentially opposite explanations for the inability of the body to clear mucus from the airways in cystic fibrosis. The first is that the defective CFTR is unable to aid in fluid secretion in cystic fibrosis airway glands. The second explanation is that the glands still secrete fluid via non-CFTR pathways, but the fluid is reabsorbed by other channels. In fact, it has been proposed that one of CFTR's functions is to inhibit the activity of a channel called the epithelial Na+ channel (ENaC).

Nam Soo Joo and colleagues at Stanford University attempted to determine which hypothesis was correct by measuring the secretion from glands from patients with cystic fibrosis and from normal pigs. They added ENaC inhibitors to the glands to determine if the channel plays a role in mucus clearance. The researchers found no evidence that the inhibitors altered secretion rates in either normal or cystic fibrosis glands. This suggested that loss of CFTR-mediated fluid secretion is the culprit in cystic fibrosis.

"We previously showed that cystic fibrosis airway glands have defective gland secretion in response to certain drugs," explains Joo. "The results of our present study provide evidence that the defective cystic fibrosis gland secretion is not due to a potentially excessive fluid reabsorption pathway within glands but is due to most likely to a lack of fluid secretion from cystic fibrosis glands."

Tomatoes, carrots can cut asthma risk

Sun, 19 Mar 2006 20:14:00 PST

( from http://www.rxpgnews.com ) Eating plenty of tomatoes, carrots and leafy green vegetable could help in reducing asthma risk in women, says a study.

Earlier research had found that asthma attacks in women were more than men due to hormonal changes, particularly during their monthly periods.

Researchers at the National Institute of Public Health in Mexico studied about 69,000 women and found lowered asthma risk in those who ate plenty of such vegetables, reported the online edition of medical journal Thorax.

COPD is slated to become world's biggest killer by 2020 - WHO

Mon, 13 Mar 2006 20:31:00 PST

( from http://www.rxpgnews.com ) A smoking-related illness that narrows one's breathing passage is slated to become the world's third biggest killer by 2020, according to the WHO.

Called Chronic Obstructive Pulmonary Disease (COPD), the ailment entails two specific health problems: chronic-obstructive bronchitis and emphysema of the lungs.

Unlike simple bronchitis, the breathing passages narrow due to swelling of the mucous membrane and emphysema decomposes lung tissue. People with this disease find that the obstructions quickly lead to disabilities.

Officials with WHO look at the spread of this disease with concern, especially given the 1.1 billion smokers worldwide.

COPD is especially tricky because it works very slowly and becomes noticeable only after it has attacked the body for years.

"One regular symptom is abnormal bronchial passage sensitivity to outside influences. That outside influence, as a rule, is cigarette smoking," explains Michael Pfeifer of the Regensburg University Clinic.

Said German lung specialist Michael Barczok: "The sooner the disease is recognised, the better the chances to control it. Breathing problems after exertion are an early symptom."

As of now, there are no therapies to rebuild lungs. What is destroyed is destroyed, said Pfeifer.

Inhaled steroid may work better for normal-weight people

Thu, 23 Feb 2006 12:18:00 PST

( from http://www.rxpgnews.com ) As the nation's collective waistline has swelled in recent decades, rates of asthma diagnoses also have accelerated. Indeed, much research has affirmed a link between the two conditions.

But doctors also recognize that asthma may not behave the same way among people who have different body types. With a variety of asthma medications on the market, what kinds work best for lean people and what kinds work best for obese people? The answer may be different for each group.

A new study suggests that people who are overweight or obese may have better results with the prescription pill sold as Singulair than with a type of inhaled steroid, while leaner people may have better luck with an inhaled steroid, called beclomethasone and sold as beclovent, vanceril and other brand names. The findings appear in the new issue of the European Respiratory Journal.

"It is increasingly recognized that obese people are more prone to develop asthma, but there is no information about whether obesity influences people's responses to particular asthma medications," says lead author Marc Peters-Golden, M.D., professor of internal medicine and director of the Fellowship Program in Pulmonary and Critical Care Medicine at the University of Michigan Medical School.

"Our findings are the first to suggest the possibility that obesity might be a factor that influences how well asthmatics respond to particular medications," Peters-Golden says.

Singulair is the brand name of montelukast sodium and is sold by Merck & Co., which funded this study.

Researchers looked at data from four previous multi-center, randomized clinical trials from 3,073 patients with moderate asthma. The data included the patients' responses to Singulair/montelukast, a beclomethasone inhaled steroid and a placebo, and the participants' body mass index numbers, which placed them in the categories of normal, overweight and obese.

In general, the severity of people's asthma was found to be greater among those in the overweight and obese groups, which supports findings from other studies.

In addition, the inhaled steroid was found to be better than Singulair at increasing the number of asthma control days (ACD) among people in the normal weight category. An ACD is defined as a day with no more than two puffs of an inhaler, no night-time awakenings and no asthma attacks.

On the other hand, the inhaled steroid resulted in a reduced effect in the percentage of ACDs among obese people in the study that is, the benefit of the inhaled steroid declined with increasing body mass index.

In contrast, the positive impact of Singulair did not decrease in obese and overweight people when compared to its impact on people of normal weight. The research also suggests that the higher a person's body mass index, the greater his or her response to Singulair compared to a placebo, a pill with no medicinal benefit. This is an indication, Peters-Golden says, that obese and overweight people may in fact respond better to this medication.

Still, he is not inclined to suggest that doctors change the way in which they prescribe medication not yet, anyway.

"Our study looks back at material from previous trials. I'd like to see a prospective study in which lean patients and heavy patients are enrolled at the outset, and you compare both types of medications in both groups," Peters-Golden says. If verified by other studies, this insight may help physicians to better tailor medication regimens to meet individual patient needs.

Peters-Golden also notes that much research about asthma and other conditions is exploring the possibility that genetic factors might explain individual variations in responses to medications. He says it is likely that a variety of factors, including genetic ones and acquired factors such as weight, combine in a complex and intertwined manner to influence a person's reaction to medications.

Information about Singulair/montelukast: This medication, usually taken once a day, is a type of leukotriene antagonist that is, it blocks leukotrienes in the body. Leukotrienes are chemicals in the human body that can affect the breathing passages. Information about the beclomethasone inhaled steroid: Beclomethasone is a steroid that prevents the release of substances in the body that cause inflammation. Inhalation of beclomethasone prevents asthma attacks and other conditions involving inflammations of the lung tissues.

Female foetus could increase expectant woman's asthma

Fri, 03 Feb 2006 15:38:00 PST

( from http://www.rxpgnews.com ) Asthmatic women pregnant with girls are more likely to experience severe asthma symptoms than those carrying a male foetus, says a study.

Michael B. Bracken and other researchers at Yale School of Medicine studied 702 pregnant women throughout southern New England who were trained to assess their lung function for 10-day intervals at selected points in pregnancy.

Lung function and a number of other factors that might influence severity of the mother's asthma were recorded automatically, reported science portal EurekAlert.

Asthma worsened in mothers with either male or female foetuses until about 30 weeks gestation, after which there was an improvement in lung function. However, throughout pregnancy, mothers with a male foetus had 10 percent better lung function.

"However, this difference due to sex is potentially important but needs to be placed in the context of other factors which have a greater impact on the severity of the mother's asthma, including inadequate medical management of asthma symptoms, and whether the mother was a smoker or not," an expert said.

The finding, published in the February issue of American Journal of Epidemiology, is one of the first and largest studies to investigate the effect of foetal sex on the severity of the mother's asthma, and one of the largest to investigate the effect of foetal sex on any disease of the mother, it said.

Asthma is one of the most common diseases associated with pregnancy. An upcoming study by the authors to be published this spring shows that eight to nine percent of pregnant women have a history of asthma.

New Model To Help Physicians Identify Patients With Pulmonary Embolism

Wed, 25 Jan 2006 00:27:00 PST

( from http://www.rxpgnews.com ) Looking at 10 easily obtained risk factors, including age, blood pressure and medical history, could help physicians identify patients with pulmonary embolism who are at low risk of death in the short term and therefore are candidates for outpatient treatment, according to a new study in the January 23 issue of the Archives of Internal Medicine, one of the JAMA/Archives journals.

Pulmonary embolism (PE) generally occurs when a blood clot that develops in the veins of the leg or pelvis becomes dislodged and results in sudden blockage of an artery in the lung. It is a major health problem in the United States, causing more than 100,000 hospitalizations in 2002, according to background information in the article. The condition can be fatal, but evidence suggests that nonmassive PE, which is not accompanied by respiratory failure or other serious complications, could effectively and safely be treated on an outpatient basis, the authors write.

Previous studies have shown that outpatient treatment for PE also could be economically beneficial-the authors estimate that if 20 percent of people with PE were treated as outpatients, up to $91 million per year could be saved in the United States alone. However, "outpatient treatment for nonmassive PE is not widely accepted because no explicit clinical criteria exist to accurately identify patients with PE who are at low risk of adverse outcomes," they write. "Therefore, we sought to develop an objective and easily applied clinical prediction rule to identify patients with PE at low risk of short-term mortality and other adverse medical outcomes who are candidates for outpatient treatment."

Drahomir Aujesky, M.D., M.Sc., University of Lausanne, Switzerland, and colleagues developed this prediction rule or model by evaluating 15,531 admitted patients who received a discharge diagnosis of PE from 186 Pennsylvania hospitals. By concentrating on 10,354 patients, they identified 10 risk factors that indicated a greater risk of short-term death (within 30 days), including an age of 70 years or older; a history of cancer, heart failure, chronic lung disease or chronic kidney disease; cardiovascular disease; altered mental status; a high pulse rate; low systolic blood pressure; and reduced oxygen saturation in arterial blood. Patients without any of these factors are considered low-risk and eligible for outpatient treatment.

The researchers then tested their model on the remaining 5,177 participants in the original study group and by using data from a previous study of 221 Swiss patients with PE. Low numbers of patients in these two groups-1.5 percent and none, respectively-who were low-risk according to the model died within 30 days, and less than 1 percent developed non-fatal complications. "This simple prediction rule accurately identifies patients with pulmonary embolism who are at low risk of short-term mortality and other adverse medical outcomes," the authors write. "Prospective validation of this rule is important before its implementation as a decision aid for outpatient treatment."

Although previous studies have linked certain indicators with prognosis for patients with PE, none have been used to group patients by risk, writes Lisa K. Moores, M.D., Walter Reed Army Medical Center, Washington, D.C., in an accompanying editorial. "The important question may not be who has PE but who is likely to have a recurrent fatal PE?" she writes.

"The study by Aujesky and colleagues is exciting because it is the first to combine several factors into a score that can be used to determine the appropriate treatment setting," Dr. Moores writes. "Perhaps more importantly, the risk score can be calculated quickly and reliably with clinical data easily obtained in the initial history review and physical examination."

CAPRIE study: Moxifloxacin more effective in elders pneumonia

Tue, 24 Jan 2006 23:52:00 PST

( from http://www.rxpgnews.com ) A newer antibiotic medication proved more effective at knocking out community-acquired pneumonia (CAP) in patients 65 and older than the antibiotic that has been the front-line CAP treatment the last decade, according to a national study coordinated at The University of Texas Health Science Center at San Antonio.

CAP is the fifth-leading cause of death in the elderly, is diagnosed in 5.6 million adults annually in the U.S., and is 60 percent more likely to occur in the elderly than in the general population. The Community-Acquired Pneumonia Recovery in the Elderly (CAPRIE) study, led by Antonio Anzueto, M.D., professor of medicine at the Health Science Center, is reported in the current issue of Clinical Infectious Diseases.

"The CAPRIE study is very unique in that it was conducted only in patients 65 and older, such as the median age was 78," Dr. Anzueto said. "Community-acquired pneumonia is a common infectious disease process in the elderly. Pneumonia has been identified as the leading infectious disease associated with the higher mortality (death) in this age group. This is also the first time the two leading antibiotics for CAP have been compared in a well-controlled clinical trial."

Treated with the newer medication, moxifloxacin HCI, 97.9 percent of hospitalized patients recovered within three to five days of therapy onset, compared to 90 percent of patients treated with the standard medication, levofloxacin. Study findings were in 281 patients at 47 centers.

"At the end of the day, another important question was safety," Dr. Anzueto said. "This study involved very sophisticated assessment of cardiac safety. We found both treatments to be safe." San Antonio patients were treated at the South Texas Veterans Health Care System.

Moxifloxacin HCI's greater efficacy earlier in hospital stays should lead to less occurrence of incapacitating long-term effects, Dr. Anzueto said.

Moxifloxacin HCI and levofloxacin are in a group of antibiotics known as fluoroquinolones.

Using microDMx sensor to develop better instruments to treat lung disease

Tue, 24 Jan 2006 15:57:00 PST

( from http://www.rxpgnews.com ) A new technique based on the same technology used to detect chemical warfare agents and explosives is being employed by scientists at The University of Manchester to treat hospital patients with lung disease.

Dr Paul Thomas and a team of researchers are using a sensor, commonly used to detect explosives at airports, to develop a new way of diagnosing lung disease.

The microDMx" sensor, developed by Sionex Corporation, is being used to develop a new technique which is able to detect 'unhealthy' molecules present in the breath of a patient.

The technology is currently being tested at Wythenshawe Hospital's North West Lung Research Centre (NWLRC). The aim is to produce a device which will enable doctors to monitor patients with lung or respiratory conditions by simply asking them to breathe into it.

The microDMx sensor is based on a Differential Mobility Spectrometer (DMS) and is a significant advance over the current Ion Mobility Spectrometer (IMS) systems which are currently deployed in airports to detect minute traces of explosives or drugs. The microDMx sensor is able to identify molecules that may be the cause of lung diseases such as cancer, asthma and chronic obstructive pulmonary disease caused by smoking.

Dr Paul Thomas from the University's School of Chemical Engineering and Analytical Science, who is leading the research, said: "Our vision is that one day we will be able to detect a previously undetectable tumour metabolising inside a human lung simply by asking a patient to breathe into a device like this. For now our aim to use the microDMx sensor to develop better instruments which will improve patient care and treatment.

"The potential is such that we will not only be able to provide more accurate diagnosis, but we will also be able to tailor treatments to the individual. For instance, if a patient is taking steroids for asthma, we would be able determine whether they were being given the right amount of steroids from the molecules in their breath which relate to the severity of the inflammation in their lungs."

NWLRC Consultant Dr Dave Singh, said: "This research could make dramatic improvements to the detection of lung diseases. We are really excited about the future possibilities for diagnosing diseases, and monitoring the response to treatment."

The microDMx sensor can be used to detect and analyse a broad spectrum of molecules associated with different conditions with extreme sensitivity. It can also be configured to block out molecules produced by common ailments such as sore throats or chesty coughs which may interfere with the accuracy of data.

"What is unique about this sensor, and the use of the microDMx technology, is the fact that it can be configured to not just analyse one disease or condition, but it has the potential to be used to analyse a broad spectrum of conditions from asthma, to cancer and metabolic disorders such as diabetes," says Dr Thomas.

The microDMx sensor is a microfabricated chip which operates as a programmable chemical filter allowing specific ion species to be selected and detected by the application of RF and DC electric fields. The older IMS technology which is used by the military and security services for the detection of chemical warfare agents, drugs and explosives has had little use beyond its use by the military and security services despite its ability to separate molecules on the basis of their shape and size. The DMS and microDMx technology however offers significant advantages over conventional IMS in terms of increased sensitivity and selectivity which make it more applicable for much wider range of applications outside the previous narrow focus.

New treatment for cystic fibrosis patients

Thu, 19 Jan 2006 13:10:00 PST

( from http://www.rxpgnews.com ) Scientists have discovered a new therapy for lung problems associated with cystic fibrosis that they say may reduce the use of antibiotics.

Cystic fibrosis is a genetic disorder that causes chronic lung damage due to the build-up of excessive amounts of sticky mucus.

The treatment developed by researchers at the University of North Carolina and the University of Sydney involves inhaling a salt water aerosol solution almost twice as salty as the Atlantic Ocean, reported the online edition of BBC News.

This helps to cut damage by restoring a thin lubricant layer of water that normally coats airway surfaces, it said.

In healthy people, the water layer lining in the airways helps to clear away excess amounts of mucus by sweeping it up into the mouth where it can be swallowed.

But this water layer is missing in people with cystic fibrosis, so they are unable to prevent mucus from clogging up their lungs. Ultimately, this can lead to respiratory failure.

The new therapy works by using salt to suck water from the lung tissues out on to their surface, the researchers said.

The US team used the aerosol to treat a small group of cystic fibrosis patients. They found that it significantly improved mucus clearance, lung function and breathing symptoms.

The Australian team then applied it to another 164 patients for a longer period, almost a year. They found patients needed fewer antibiotics to treat lung infections and were more able to attend work or school.

"It gives us great hope that use of this therapy will reduce how often patients feel ill, will slow the decline of lung function over time and will help these people live longer," researcher Scott Donaldson said.

Osteopontin may be useful in the treatment of Idiopathic Pulmonary Fibrosis

Thu, 12 Jan 2006 05:41:00 PST

( from http://www.rxpgnews.com ) In an article in the Jan. 15 issue of the American Journal of Respiratory Critical Care Medicine, University of Pittsburgh researchers report that a serious, life-threatening form of pulmonary fibrosis, called idiopathic pulmonary fibrosis, lacks all the hallmarks of inflammation and is probably unnecessarily treated with anti-inflammatory drugs. Moreover, in a related study, the investigators identified a protein found in excess amounts in the lung tissue of patients with idiopathic pulmonary fibrosis, which may be a more appropriate target for therapy.

Interstitial lung disease describes a diverse set of chronic lung conditions that often have strikingly similar symptoms but different clinical courses. However, all are characterized by differing degrees of progressive scarring of lung tissue between the air sacs, or the interstitium. With repeated damage, the interstitium becomes thickened and stiff, or fibrotic, making it increasingly difficult for the individual to breathe. Some forms of interstitial lung disease, particularly idiopathic pulmonary fibrosis, which has no known cause, have a very high death rate due to respiratory failure. Effective treatment, however, is complicated by the fact that a definitive diagnosis often requires a lung biopsy.

"Unfortunately, many patients do not receive lung biopsies. As a result, about one-third of patients who come to our clinic have previously been misdiagnosed, and many have been treated with the wrong medications," explained James Dauber, M.D., medical director of the University of Pittsburgh's Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, and professor of medicine, division of pulmonary, allergy and critical care medicine.

To improve the diagnosis and treatment of interstitial lung diseases, Naftali Kaminski, M.D., director of the Simmons Center and associate professor of pathology and human genetics, Dr. Dauber, and their coworkers decided to test the effectiveness of DNA microarray chip technology in distinguishing between the gene expression patterns of several types of interstitial lung diseases. Because it can be difficult to obtain lung biopsy samples for some types of interstitial lung disease, the Simmons Center investigators collaborated with researchers in Mexico to obtain samples for another type of pulmonary fibrosis known as hypersensitivity pneumonitis - a pneumonia-like inflammation of the lungs caused by the body's immune reaction to small air-borne particles that is more prevalent in countries such as Mexico where pet birds are common.

Drs. Dauber, Kaminski and their collaborators obtained lung biopsy samples from15 patients diagnosed with idiopathic pulmonary fibrosis; 12 patients with hypersensitivity pneumonitis; and eight patients with a third, less-understood type, known as nonspecific interstitial pneumonia. The latter is characterized by inflammation and fibrosis that occurs suddenly and progresses rapidly over a relatively short period of time.

When the investigators analyzed the gene expression patterns of the samples using a DNA microarray chip containing sequences for approximately 46,000 known gene clusters--which represent most of the genes in the human genome--the results were startling. Although all of the patients from whom the samples were taken had similar X-ray and laboratory test results, their gene expression patterns were radically different. Indeed, the investigators found that the hypersensitivity pneumonitis samples showed significantly increased expression of genes associated with inflammation, immune cell activation and immune response. In contrast, there was almost no genetic evidence of inflammation in the idiopathic pulmonary fibrosis samples.

"Our results show that interstitial pulmonary fibrosis and hypersensitivity pneumonitis, which clinically often look quite similar, are really two vastly different conditions," said Dr. Kaminski. "Idiopathic pulmonary fibrosis is characterized by the increased expression of genes involved in the re-growth of lung tissue. So, it is not really an inflammatory condition per se. On the other hand, hypersensitivity pneumonitis does exhibit all of the hallmarks of inflammation, with increased expression of genes that control T-cell activation and immune responses."

Another surprising finding came when the investigators compared these gene expression patterns to those exhibited by biopsies from the eight patients diagnosed with nonspecific interstitial pneumonia. Two of the eight cases exhibited interstitial pulmonary fibrosis-like gene expression patterns, one closely resembled the gene expression pattern of hypersensitivity pneumonitis, while the other five expression patterns resembled neither. Thus, the investigators were able to reclassify some of the cases of nonspecific interstitial pneumonia using this technology.

In an accompanying editorial, Victor J. Thannickal, M.D., of the University of Michigan and Athol U. Wells, M.D., of the Royal Brompton Hospital in London wrote that although "further studies with greater numbers of patients are required," these genetic signatures "provide important clues to the observed differences in clinical course, prognosis and responses to therapy in these two disease processes."

If these findings hold up in larger studies--and Dr. Kaminski is strongly convinced that they will--the diagnosis and management of interstitial lung disease may radically change. In particular, patients with idiopathic pulmonary fibrosis, who are commonly prescribed a course of corticosteroids or other anti-inflammatory drugs as the first line of treatment, will not be subjected to such unwarranted and potentially harmful approaches.

"Until now, the treatment of idiopathic pulmonary fibrosis has been primarily focused on its inflammatory component. However, our findings indicate that lung tissue from these patients does not exhibit a typical inflammatory pattern. So, these patients need to be managed in an entirely new way," said Dr. Kaminski.

Although there currently is no effective treatment for idiopathic pulmonary fibrosis, results of another study suggest help may soon be on the way. Dr. Kaminski and his colleagues reported in the Sept. 6 online edition of PLoS Medicine that idiopathic pulmonary fibrosis lung tissue samples display an "over-abundance" of a protein known as osteopontin, which other studies have implicated in the growth and progression of tumors. In further examining the potential role of osteopontin in idiopathic pulmonary fibrosis, Dr. Kaminski's group found that it directly increases the proliferation and movement of fibroblasts, cells centrally involved in lung fibrosis.

"Taken together, these findings are very exciting, because we now have a basis for designing drugs that are specifically directed against osteopontin. By manipulating osteopontin levels, we may be able to slow or stop the course of this deadly disease. In addition, the level of osteopontin may be used as a diagnostic marker for this disease," explained Dr. Kaminski. He added that his group is currently investigating whether measuring the expression patterns of osteopontin and other genes can predict disease progression and outcome.

In addition to Drs. Kaminski and Dauber, other investigators involved in this research include Kevin Gibson, M.D., Thomas Richards, Ph.D., and Samuel Yousem, M.D., from the University of Pittsburgh; Moises Selman, M.D., Lourdes Barrera, Msc., and Andrea Estrada, M.D., of the Instituto Nacional de Enfermedades Respiratorias in Tlalpan, Mexico; Annie Pardo, Ph.D., of the Facultad de Ciencias, Universidad National Autonoma de Mexico, Mexico City.

Idiopathic Interstitial Pneumonia (IIP) Linked to Linked to Genes and Smoking

Wed, 02 Nov 2005 13:03:00 PST

( from http://www.rxpgnews.com ) New research shows that idiopathic interstitial pneumonia (IIP), a group of potentially fatal disorders that affects the lungs, may be caused by an interaction between a specific genetic background and cigarette smoking. In a study of 111 families that had at least two relatives with IIP, people who smoked cigarettes were three times more likely than non-smokers to develop the disease. The research was supported by the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Environmental Health Sciences (NIEHS), both institutes within the National Institutes of Health.

IIPs are often accompanied by scarring and inflammation of the lung known as pulmonary fibrosis. Pulmonary fibrosis makes the delivery of oxygen to the bodys tissues difficult and is often fatal. About one-half of patients die within the first five years of being diagnosed with idiopathic pulmonary fibrosis. The study appearing in the November 1 issue of the American Journal of Respiratory and Critical Care provides new insight into what might cause IIP and new directions for preventing these diseases.

"This study illustrates the important role that a specific environmental exposure, in this case cigarette smoking, can play in the development of this type of lung disease among people who have a specific gene, said David A. Schwartz, M.D., NIEHS Director and a lead researcher on the study. It once again underscores why people should not smoke.

Pulmonary fibrosis currently affects approximately 100,000 people in the United States, with an estimated 30,000 people being diagnosed each year, added Elizabeth G. Nabel, MD, NHLBI Director. This study enhances our understanding of one form of pulmonary fibrosis, which could help lead us to strategies for genetic testing, prevention, and treatment of this devastating and complex disease.

Researchers from three sites enrolled and evaluated 111 families with a diagnosis of IIP in at least two affected relatives. The sample included 309 people affected with an IIP and 360 unaffected relatives. Each participant completed a detailed health and environmental exposure questionnaire, a chest x-ray, and a lung diffusion test, which determines how well oxygen passes from the air sacs of the lungs into the blood.

The researchers evaluated the data in many different ways. They used a family-based case control study to determine if there was a relationship between cigarette smoking and familial interstitial pneumonia (FIP). They also used two methods to determine if there was in fact a genetic component to FIP. FIP is the term used when 2 or more cases of IIP occur in the immediate family.

The researchers found that there is a genetic basis for this disease. In addition to the fact that 111 families had 2 or more relatives with this disease, the researchers also found similar age-at-diagnosis and significant risk among siblings. Older people, males, and those who smoked also showed a greater risk of developing FIP. After controlling for age and gender, having ever smoked cigarettes increased the likelihood of developing this disease 3.6 times.

We now know that a certain genotype places someone at risk for this disease, said Mark Steele, M.D., Associate Professor, Duke University Medical Center, the lead author on the paper. Independent of genes, cigarette smoking also contributes to the development of this disease. The next step is to identify the specific gene or genes that cause the disease.

Steele also noted that because this is the first study to include different types of IIP within the same families, it may be plausible that although a common gene may predispose one to develop FIP, some other factor, such as the environment, may result in a unique type of IIP.

Childhood Asthma Affecting More than Just Breathing

Wed, 26 Oct 2005 23:57:00 PST

( from http://www.rxpgnews.com ) Recent research has shown that kids with asthma may also be at risk for psychological problems such as depression, anxiety, and problems in their social lives including peer interactions. This study, recently published in the Journal of Child and Adolescent Psychiatric Nursing, is one of the first to examine relationships among asthma, anxiety and depression, and several aspects of social functioning in urban children.

Findings suggest that among children with and without asthma from urban environments, social functioning is related to both depression and anxiety. Specifically, children with higher levels of anxiety and/or depression were more likely to have poorer interpersonal relations with others, feeling as though other children do not like them, do not respect them, and/or do not want to play with them. They also may experience more stress associated with social interactions and have fewer friends than children without internalizing problems.

The results of this study reinforce the importance of appropriate mental health training for nurses and other health care providers who come into contact with children in urban community health centers, says the studys lead author, Jennifer Bender Berz.

As many as 9 million children in the United States have been diagnosed with asthma, making it one of the most common chronic illnesses among children.

Genetic variations influence cystic fibrosis' severity

Sat, 08 Oct 2005 05:24:00 PST

( from http://www.rxpgnews.com ) Subtle differences in other genes -- besides the defective gene known to cause the illness cystic fibrosis -- can significantly modify the inherited disease's severity, a large new multi-center national study has concluded.

The study, led by University of North Carolina at Chapel Hill and Case Western Reserve University researchers, for the first time shows that particular versions of the transforming growth factor beta 1 (TGFb1) gene are largely responsible for how badly the illness affects patients' lungs.

A report on the findings appears in the Oct. 6 issue of the New England Journal of Medicine.

"As this gene is one of about 30,000 genes in our bodies, its identification as a modifier of the CF lung disease allows us a specific target to focus on for improving CF therapy," said Dr. Mitchell L. Drumm, associate professor of pediatrics and genetics at Case. "As we better understand its function in lung disease, we hope it will allow us to design better and more specific therapies. Because other researchers have found a similar effect of this gene in asthma, the implications likely extend to other disorders affecting the lungs as well."

More than 50 hospitals and medical centers and scores of physicians across the United States and Canada participated in the investigation, which was actually two closely related studies with separate groups of patients. Findings were essentially the same for both, according to principal investigator Dr. Michael R. Knowles, professor of medicine at the UNC School of Medicine.

"This study is especially important in the field of genetic modifiers, because we had enough patients -- over 1,300 -- and a robust study design to assure that our observation is likely correct," Knowles said. "That is in contrast to much of the previous work in this area where the number of subjects was usually too small to be conclusive.

"The observation has tremendous implications about the future for prognosis and potential new therapies in CF," he said. "We are on the verge in the next two or three years of being able to test for other such genetic variants across the entire human genome. Our hope is to be able to identify most of the important gene modifiers in CF so that they can be used for prognosis, the identification of novel therapeutic targets and perhaps even directing therapy in an individual patients toward different types of adverse gene modifiers."

Initially, the study involved 808 cystic fibrosis patients who had inherited an altered form of a gene known as delta F508 from both parents. The second study involved 498 people with the condition. By measuring the volume of air when patients' exhaled strongly into a machine, researchers determined how severe each subject's lung disease was.

Scientists then correlated patients' level of illness against various genetic mutations and found that variants of a gene known as TGFb1 were associated with worse disease. The findings appear to exonerate certain other previously suspected mutations.

Besides Drumm and Knowles, authors of the report include Drs. Fred A. Wright and Fei Zou, associate professor and assistant professor of biostatistics, respectively, at the UNC School of Public Health, and, at Case, Drs. Mark D. Schluchter and Michael Konstan, professors of pediatrics; and Dr. Katrina Goddard, associate professor of epidemiology and biostatistics. Thirteen other scientists and clinicians also contributed to the work and were listed as co-authors.

In an accompanying editorial, Drs. Christina K. Haston and Thomas J. Hudson of McGill University in Montreal praised the new study.

"There are many lessons about modifier genes to be extrapolated from this study, starting with recognition of the tremendous importance of the study design," Haston and Hudson wrote.

Among its strengths, they said, were its large size -- which is essential for such studies if they are to be useful -- that it focused on a single class of gene variation and that it took into account numerous possible confounders such as sex, other illnesses like asthmas, enrollment sites, associated diseases and infections.

"There are likely a number of gene modifiers in CF and other diseases, and this current paper describes one of the first robust examples," Knowles said. "Some CF patients may do worse because of 'severe inflammation' genes, whereas others may do worse because of differences in mucus genes. Still others might because of their growth and metabolism genes, etc... Thus, therapy might need to be targeted to a particular area or areas in individual patients. This is important not only for CF, but for other lung diseases as well because gene modifiers we discover in CF will be seen in other diseases, and there are already examples of that."

Omalizumab has long-term benefits in severe allergic asthma

Thu, 29 Sep 2005 20:49:00 PST

( from http://www.rxpgnews.com ) New long-term data show that Xolair® (omalizumab), a first-in-class monoclonal antibody for treating severe allergic asthma, helped patients to maintain control of their disease and was safe and well-tolerated in studies lasting more than three years. The data were presented at the European Respiratory Society (ERS) congress in Denmark, along with results from seven clinical studies showing that Xolair significantly improved the lung function of patients.

Long-term control of severe allergic asthma was demonstrated in a study spanning 180 weeks of observation. The design included a 32-week randomised, double-blind, parallel-group, placebo-controlled study, followed by a 96-week open-label extension and a further 52-week extension.

As a result, patients completing the study and both extensions had been treated for more than three years. Disease control was maintained throughout the follow-up period in Xolair patients, who exhibited lower than expected changes in lung function and reduced use of inhaled corticosteroids (ICS).1

"These results confirm that omalizumab potentially provides an important breakthrough in the fight against allergic asthma," said Prof. Marc Humbert of the Service de Pneumologie et Réanimation Respiratoire, Hôpital Antoine Béclère, Clamart, France. "Many people suffering from severe asthma have a substantially impaired quality of life and endure the constant fear that their next attack may prove fatal. By reducing exacerbations and the burden of disease, anti-IgE therapy offers a new approach to the treatment of this intractable condition."

Xolair manages asthma by targeting an underlying cause of allergic disease (up to 90% of asthma being allergic in origin2). It is designed to block the action of IgE, which is responsible for initiating the cascade of inflammatory symptoms such as airway constriction, mucus production, wheezing and shortness of breath. Xolair has been shown to decrease asthma exacerbations in some of the most difficult-to-treat patients whose condition remains inadequately-controlled despite the best conventional therapy, including inhaled corticosteroids, long-acting beta2-agonists and other controller medications.

The Committee for Medicinal Products for Human Use (CHMP) recently gave a positive opinion on initial marketing authorisation for Xolair, opening the way for approval by the European Commission and for the therapy to become available in EU countries.

More about the three-year study demonstrating efficacy and safety
In the 32-week placebo controlled study, 341 patients received Xolair (at least 0.016 mg/kg/IgE [IU/mL] every four weeks) or placebo. A total of 222 patients entered Extension 1 (96 weeks), 178 of whom continued into Extension 2 (52 weeks). Patients in the extensions maintained stable lung function (measured by forced expiratory volume in one second, or FEV1). Mean FEV1 was 2.24 litres at the start of Extension 1 and 2.26 litres at the end of Extension 2, indicating persistency of therapeutic benefit from Xolair. In addition, more than 80% of patients had good/excellent asthma control during the extensions. Patients receiving inhaled corticosteroids at the start of Extension 1 and remaining on the same steroid reduced their ICS use by an average of 11% between the start of Extension 1 and the end of Extension 2.

In this long-term study, the overall incidence of adverse events was similar in the Xolair and placebo groups during the 32-week placebo-controlled study and Extension 1 (i.e. approximately 80% in both groups). During Extension 2, 134 patients (75%) had at least one adverse event, most of which were mild to moderate in severity. Serious adverse events remained infrequent during the second extension (4.5%) and were deemed by the treating physician to be unrelated to Xolair.3

Improvements in lung function and quality of life
Pooled data were also presented from seven trials in which allergic asthma patients (93% of whom had severe persistent disease) received Xolair as an add-on to inhaled corticosteroids, with or without oral corticosteroids and long-acting beta2-agonists. Out of 4,308 patients in the studies, FEV1 data were available for 3,537 patients (Xolair 2,443; control 1,094). Among Xolair recipients, 29.1% increased their FEV1 by ≥200mL while 17.5% showed a ≥200mL decrease. In the control group, 26.4% had a ≥200mL increase in FEV1 and 26.1% had a ≥200mL decrease. This equates to a net benefit of 11.6% for Xolair patients versus 0.3% for control (P<0<0<0<80

CD23 structure revealed by NMR spectroscopy

Wed, 21 Sep 2005 19:22:00 PST

( from http://www.rxpgnews.com ) The structure of a molecule that regulates levels of the key antibody involved in allergic reactions and asthma, IgE, has been revealed by researchers from Oxford University and Kings College London. The study, published in Journal of Experimental Medicine, will help in the discovery of drugs to treat these two conditions.

IgE is thought to make certain cells of the immune system (mast cells) more sensitive to allergens, so lowering circulating levels of active IgE is a possible way of reducing the symptoms of allergies or allergic asthma.

The low-affinity receptor for IgE, called CD23, plays a dual role in the production of IgE. It can either inhibit or stimulate the antibodys production, depending whether it is attached or detached from the cell membrane.

Small molecules that bind to CD23 and prevent it from stimulating IgE production could be potential allergy and asthma treatments.

The researchers at Oxford and Kings used nuclear magnetic resonance (NMR) spectroscopy to discover the structure of CD23. Professor Brian Sutton from Kings, a co-researcher on the study, said: Currently a therapy that blocks IgE functioning is available, but it is expensive. Drugs that prevent the production of IgE might be a much cheaper way of treating allergies. Dr James McDonnell from Oxford University, who led the study, said: This is an important step forward in understanding some of the underlying mechanisms of the allergic response. Asthma UK funded part of the work. Dr Lyn Smurthwaite, their Research Development Manager said: The development of new therapies for people with asthma is an important part of Asthma UKs research programme'.

Bacteria in Household Dust May Trigger Asthma

Fri, 09 Sep 2005 15:30:00 PST

( from http://www.rxpgnews.com ) Researchers at NIEHS and the University of Iowa found a strong association between endotoxin levels and the prevalence of diagnosed asthma, asthma symptoms, asthma medication use, and wheezing. These relationships were strongest for bedroom floor and bedding dust. Households with higher endotoxin concentrations experienced higher prevalence of respiratory symptoms

Endotoxins are found in the cell wall of bacteria and are only released when bacteria ruptures or disintegrates. Because bacteria can be found everywhere in the home, the likelihood of their release is high. Once released, endotoxins can cause inflammation of the airways and lead to asthma symptoms.

Two research assistants visited each household, administered a detailed questionnaire, conducted a home inspection, and used a standardized protocol to collect samples. Dust samples were collected from bedroom, kitchen and living room floors, bedding, and upholstered furniture and assayed for endotoxin. A disease association analysis was performed to correlate endotoxin concentrations to specific health outcomes.

"When we analyzed the dust samples, we found that kitchen and living room floors had the highest concentrations of endotoxin," said Darryl C. Zeldin, M.D., a Senior Investigator at NIEHS. "However, when we looked at where the health impact of the dust was the most significant, we found that the likelihood of having recent asthma symptoms was nearly three times greater among individuals with exposure to high levels of endotoxin in the bedroom."

The researchers found that all dust samples contained detectable levels of endotoxin. The average concentration of endotoxin ranged from 80.5 units per milligram of dust on kitchen floors to 18.7 on bedding. Family room floors had endotoxin concentrations of 63.9 units per milligram of dust; sofas had concentration levels at 44.8; and 35.3 units on bedroom floors.

"Interestingly, endotoxin exposure worsens asthma symptoms in adults, regardless of whether an individual has allergies or not" said Peter S. Thorne, Ph.D., a researcher at the University of Iowa and lead author on the paper. "This suggests that exposure to endotoxin increases asthma risk even in non-allergic individuals."

Since the mid 1960s, researchers knew that house dust contains endotoxin, but it is only within the last five years that they began to understand the impact of household endotoxin on human health. Knowing what triggers asthma, whether it is endotoxins or something else, may help a physician better prevent or treat symptoms.

"This study implies that it is not just the concentration of the endotoxin that matters," added Dr. Schwartz, Director of NIEHS. "Understanding how factors such as duration of exposure, timing of the exposure, and genetic factors, contribute to the development of diseases like asthma will lead to new insights into how to prevent and treat this important disease." NIEHS is implementing new studies to better understand the role that the indoor environment plays in the development and severity of asthma.

Role of Osteopontin in Idiopathic Pulmonary Fibrosis

Thu, 08 Sep 2005 16:22:00 PST

( from http://www.rxpgnews.com ) Idiopathic pulmonary fibrosis is a chronic progressive scarring disease of the lung in which gradually the walls of the air sacs of the lungs become replaced by fibrotic tissue. When scarring forms, there is an irreversible loss of the tissue's ability to transfer oxygen into the bloodstream.

The disease affects more than 5 million people worldwide, of whom 40,000 die every year. Misdiagnosis is common because the origin and development of the disease is not completely understood. There are also no effective treatments; drugs to treat lung scarring are still in the experimental phase, and treatments to suppress inflammation have no beneficial effect in most patients.

Although significant advances have been made in the characterization of the clinical features of this disease, the molecular mechanism in humans is still largely unknown. In general, pulmonary fibrosis might be the result of an autoimmune disorder, the after effects of a viral infection, or a genetic condition. Pulmonary fibrosis also occurs after inhalation of some pollutants, in association with diseases such as scleroderma, rheumatoid arthritis, lupus, and sarcoidosis, and after certain medications and therapeutic radiation. However, the etiology of idiopathic pulmonary fibrosis is presently unknown.

Now Annie Pardo and colleagues examine the role of osteopontin, which has diverse functions as a cell-adhesion and migration molecule, in the pathogenesis of idiopathic pulmonary fibrosis. Osteopontin is a multifunctional cytokine that has been implicated in several physiological and pathological processes including bone resorption, malignant transformation, and metastasis. It is also considered a key molecule for regulating inflammation, cellular immune response, and tissue repair, with a unique effect on T cell function.

Using oligonucleotide microarrays these researchers have previously demonstrated that osteopontin is highly upregulated in bleomycin-induced lung fibrosis in micean animal model of pulmonary fibrosis.

In the current study, they used microarrays to analyze gene expression patterns in lung samples (13 samples from people with idiopathic pulmonary fibrosis and 11 from control individuals). They found that osteopontin was the most upregulated gene in the lungs of patients with idiopathic pulmonary fibrosis, and that it was mainly expressed by alveolar epithelial cells.

To better understand the potential local profibrotic effects of osteopontin they then studied its effects on lung fibroblasts and alveolar epithelial cells and found that osteopontin induced a significant increase in migration and proliferation in both fibroblasts and epithelial cells. However, although the effect on fibroblast migration/proliferation was dependent mainly on integrins, in epithelial cells proliferation was mainly dependent on CD44 and migration was dependent on CD44 and integrin signaling.

Osteopontin also showed profibrotic-relevant effects on molecules involved in extracellular matrix remodeling. For example, in fibroblasts osteopontin increased TIMP-1 and type I collagen and inhibited MMP-1 expression, whereas in alveolar epithelial cells it induced MMP-7.

These findings concur with previous studies in experimental tissue fibrosis that have suggested a possible profibrotic role of osteopontin, said the authors. For example in kidney fibrosis, osteopontin enhances macrophage recruitment and stimulates the development of renal scarring after an acute ischemic insult; most importantly, mice that do not express the gene for osteopontin are protected from lung fibrosis induced by the drug bleomycin.

Altogether the results suggest a mechanism to explain most of the profibrotic effects of osteopontin by direct effects on fibroblasts and epithelial cells in the lungs. The findings also suggest that the interaction between MMP-7 and osteopontin might be involved in the progressive nature of the disease. Osteopontin is a potential target for therapeutic intervention in this relentless, incurable disease.

Early life tobacco exposure more harmful to lungs

Tue, 06 Sep 2005 20:35:00 PST

( from http://www.rxpgnews.com ) A new study finds early life exposure to second-hand smoke can produce life-long respiratory problems. The study of 35,000 adult non-smokers in Singapore found that those who lived with a smoker during childhood had more respiratory problems, including chronic cough. Study participants who reported eating more fruit and soy fiber as adults seemed to be protected against some of the negative health effects often associated with early tobacco exposure.

Individuals 18 or younger, living with one or more smokers, were more than twice as likely to suffer from chronic dry cough as adults, according to a new study published by researchers at the National Institute of Environmental Health Sciences (NIEHS), a part of the National Institutes of Health, the University of Minnesota, and the National University of Singapore. This paper, which appears online in Thorax, is the largest study to date on the effects of childhood exposure to environmental tobacco smoke (ETS) on later respiratory disease, and the first to include data on dietary intake.

"This research adds to a growing body of evidence that exposure to second-hand smoke early in life has health consequences that can last a lifetime," said Dr. David Schwartz, Director of the NIEHS. "In addition to finding ways to reduce the exposure of children to tobacco smoke and other environmental pollutants, we also need to look for ways to reduce the disease burden."

The data for this study were collected from the Singapore Chinese Health Study, a population of men and women of Chinese ethnicity ranging in ages from 45 to 74 at enrollment, who live in Singapore. The 35,000 non-smokers provided information regarding ETS before and after age 18, a medical history including information on respiratory symptoms of chronic cough, phlegm production and asthma diagnosis, as well as information on dietary intake.

Chronic cough was defined as occurring on most days for at least three months of the year and lasting more than two years in a row. More than 45 percent of the study participants reported having fathers who smoked, and 19 percent reported having mothers who smoked. The researchers found that more smokers in the home during childhood, was linked to a greater incidence of chronic cough, and chronic phlegm.

"Because we had previously found in this Singaporean population data suggesting that a diet high in fruit and soy fiber may reduce the incidence of chronic respiratory symptoms, we decided to study the impact of fiber on problems associated with early tobacco exposure," said NIEHS researcher Stephanie London, M.D. "We actually found that people who ate even a small amount of fruit fiber had less chronic cough related to environmental tobacco smoke."

Study participants who ate more than 7.5 grams of fiber each day had fewer health effects associated with ETS. This is equivalent to eating about two apples a day. Dr. London pointed out that the average weight of the Singapore study participants was 127 lbs. She also added that most Singaporeans get their fiber from fruits, vegetables and soy.

"Fiber may have beneficial effects on the lung," said Dr. London. "It seems to have the ability to reduce blood glucose concentrations, reduce inflammation, and enhance antioxidant processes. All of these may help to protect the lung against environmental insults, such as ETS in childhood. However, the possible benefits of fiber should not lessen the importance of reducing exposure to environmental tobacco smoke."

How to design a better drug to treat cystic fibrosis

Sun, 04 Sep 2005 08:30:00 PST

( from http://www.rxpgnews.com ) John Tomich, a Kansas State University professor of biochemistry, spends much of his day thinking about how to design a better drug to treat cystic fibrosis.

A chronic and progressive disease, cystic fibrosis is usually diagnosed in childhood. It causes mucus to become thick, dry and sticky. The mucus builds up and clogs passages in the lungs, pancreas and other organs in the body.

There is no cure for cystic fibrosis. Management of the disease varies from person to person and generally focuses on treating respiratory and digestive problems to prevent infection and other complications. Treatment usually involves a combination of medications and home treatment methods, such as respiratory and nutritional therapies.

Tomich, along with colleagues Takeo Iwamoto, a K-State research assistant professor, and Shawnalea J. Frazier, senior in biochemistry, Haysville, have been working to understand how ions travel across cell membranes, specifically the anion part of sodium chloride.

Tomich presented a paper on the trios' findings, "Assessing The Contributions of H-Bonding Donors to Permeation Rates and Selectivity in Self-Assembling Peptides that Form Chloride Selective Pores," Aug. 28 at the Membrane Active, Synthetic Organic Compounds Symposium of the American Chemical Society's national meeting and exposition in Washington, D.C.

"What's kind of an honor about this is we were one of the few, purely biochemical research groups who are presenting in this symposium," Tomich said. "This is a section organized by organic chemists."

Tomich and his collaborators have used a series of single and double amino acid substitutions to modulate the activity of a channel forming peptide derived from the second transmembrane segment of the alpha subunit of the human spinal cord glycine receptor.

Tomich said chloride ions are hydrogen bond acceptors; consequently, it is hypothesized the hydroxyl function contributes strongly to ion throughput across and/or ion selectivity within the channel structures. Residue replacements in the peptide involving the 13th and 17th positions were designed to correlate hydrogen-bonding strength with selectivity and permeation rates. The hydrogen bonding strengths of the amino acid side-chains correlate directly with anion selectivity and inversely with transport rates for the anion.

According to Tomich, these results will help in optimizing these two counteracting channel properties.

"Your body knows how to separate these things all by itself," Tomich said. "Sodium is usually higher outside the cell, potassium is higher inside the cell and chloride, depending on the cell type, can be the same or different.

"The chemical mechanisms directing chloride binding and transport are poorly understood," he said. "The mechanisms determining how sodium, potassium and calcium get across are much better known. We're trying to find out how chloride actually gets across so we will then be able to manipulate both the transport rates and selectivity."

Tomich began working on this many years ago. Over the past 15 years, his lab has developed more than 200 sequences that showed varied ion transport activity in synthetic membranes, as well as cultured epithelial cells and animals. From all of that they can change virtually the way this ion channel assembles. Some of the compounds that he has designed work at very low concentrations but lack some of the chloride specificity that it once had. Their presentation discussed how the researchers back-designed the channel pore so it can be more specified for chloride.

"Our goal is to make a drug that would work efficiently and effectively at low doses," Tomich said. "We have some early designs that are highly selective for chloride, but you'd have to give them a lot of the compound to see the effect."

Emotion processing centers in brain linked with asthma

Mon, 29 Aug 2005 22:15:00 PST

( from http://www.rxpgnews.com ) The mere mention of a stressful word like "wheeze" can activate two brain regions in asthmatics during an attack, and this brain activity may be associated with more severe asthma symptoms, according to a study by University of Wisconsin-Madison researchers and collaborators.

The study, which appears in the Proceedings of the National Academy of Sciences (Online, August 29, 2005), reveals a functional link between emotion processing centers in the brain and certain physiological processes relevant to disease.

UW-Madison psychology professor Richard Davidson, an expert on emotions; and UW-Madison medicine professor William Busse, an expert on asthma; are senior co-authors on the study. Melissa Rosenkranz, a graduate student at the UW-Madison Laboratory for Affective Neuroscience, is the lead author.

"While this study was small, it shows how important specific brain circuits can be in modulating inflammation," says Davidson, director of the affective neuroscience laboratory and the Waisman Laboratory for Functional Brain Imaging and Behavior. "The data suggest potential future targets for the development of drugs and behavioral interventions to control asthma and other stress-responsive disorders."

Previous studies and clinical evidence have shown that stress and emotional turmoil adversely affect people with inflammatory diseases like asthma. And signs of inflammation have been shown to affect the brain. But until now, nobody knew exactly what brain circuits were involved in these seemingly intertwined emotional and immune events or how the circuits might influence the severity of an acute asthma response.

Researchers used functional magnetic resonance imaging (fMRI) to scan the brains of six mildly asthmatic people who were asked to inhale ragweed or dust-mite extracts.

Subjects were then shown three types of words: asthma-related (such as "wheeze"), non-asthma negative (such as "loneliness") and neutral (such as "curtains"). Shortly after, researchers measured lung function in the subjects as well as molecular signs of inflammation in their sputum.

The fMRI scans revealed that the asthma-related terms stimulated robust responses in two brain regions--the anterior cingulate cortex and the insula--that were strongly correlated with measures of lung function and inflammation. The other types of words were not strongly associated with lung function or inflammation.

The two brain structures are involved in transmitting information about the physiological condition of the body, such as shortness of breath and pain levels, says Davidson, and they have strong connections with other brain structures essential in processing emotional information.

"In asthmatics, the anterior cingulate cortex and the insula may be hyper-responsive to emotional and physiological signals, like inflammation, which may in turn influence the severity of symptoms," says Davidson.

The researchers suspect that other brain regions may also be involved in the asthma-stress interaction.

Study Shows Benefits of Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease

Mon, 15 Aug 2005 18:02:00 PST

( from http://www.rxpgnews.com ) Researchers who designed two different studies to reduce potentially biased results among chronic obstructive pulmonary disease (COPD) patients who used inhaled corticosteroids (ICS) reported a 30 percent reduction in risk for either rehospitalization or death from the disease.

In an effort to avoid "immortal time bias," the authors created 2 matched sets of patients, based on a cohort from the United Kingdom's General Practice Database. All patients had been hospitalized for a COPD-related condition between 1990 and 1999. In the first study, each group of matched patients numbered 393 individuals. One set had been treated with ICS and the other was untreated. In the second study, also free of potential bias, a case-control analysis of 2,222 patients was designed without regard to ICS exposure status. Both resulted in approximately a 30 percent reduction in the risk for either rehospitalization or death for patients who used ICS over a one-year follow-up period.

COPD is a lung disease characterized by airflow obstruction that interferes with normal breathing. The two most frequent disease conditions that underlie COPD are severe emphysema and chronic bronchitis. Years of smoking are the primary cause for these illnesses.

According to the authors, COPD is currently the fourth leading cause of death worldwide, causing more than 2.5 million deaths per year. Also, the illness is the leading cause of hospitalization in the U.S., particularly among older patients.

With different study designs reducing potential bias, the study's results consistently showed an association between ICS use and the reduction of risk of hospitalization and death, the investigators concluded.

Investigators Reveal a Key to Viral-Induced Asthma

Mon, 15 Aug 2005 17:59:00 PST

( from http://www.rxpgnews.com ) Researchers have discovered a new way to distinguish virus-induced asthma from that of allergen-caused disease based on a study of 59 asthma patients who were experiencing an acute exacerbation.

The investigators compared sputum cellular profiles of the 59 acute asthmatics against those of 45 controls. The control groups included 14 patients with stable asthma and no viral infection, 15 subjects without asthma but with a viral infection, and 16 healthy, uninfected persons. To establish infection status along with pulmonary status/history, participants completed common cold and asthma questionnaires, microbiological tests, and lung function and allergy (atopy) tests.

A respiratory virus was detected in 46 subjects, or 78 percent, of those with acute asthma.

In both children and adults, asthma exacerbations are caused by viral respiratory infections. Eighty three percent of the cases were infected with rhinovirus.

Expression of interleuken 10 (IL-10), a potent immunoregulator that functions to suppress immune responses broadly, was significantly increased in acute asthma with viral infections when compared with the control groups. Upon recovery from acute asthma, IL-10 gene expression returned to normal levels.

Consequently, according to the authors, IL-10 gene expression from airway cells appears to be a feature of virus-induced acute asthma. They said that their results reveal different mechanisms at work in virus-induced asthma patients than those described in allergen-induced asthma.

T lymphocytes cause airway thickening in asthma

Sun, 14 Aug 2005 14:30:00 PST

( from http://www.rxpgnews.com ) MUHC scientists have discovered that our body's own defense mechanism causes some of the most serious asthma symptoms. The study by MUHC researchers Dr. David Ramos-Barbón, Dr. Elizabeth Fixman and Dr. James Martin, published in a recent issue of Journal of Clinical Investigation (JCI), reveals that T lymphocytes--our body's defense cells--are responsible for the airway thickening, which increases the chances of a dangerous asthma attack. The discovery provides hope that new treatments might be developed to combat the disease, which currently has no cure.

Asthma symptoms are triggered by two factors: inflammation of the airways in the lungs, and thickening of airway muscle in the bronchi--an irreversible condition that doctors refer to as airway remodeling. Certain allergens--commonly dust and animal hair--can trigger inflammation, but the causes of airway remodeling (and the link between the two) have remained a mystery. MUHC researchers have now discovered that remodeling is actually caused by T lymphocytes--part of our body's own defense mechanism. "T lymphocytes are the traffic cops of the cellular world," says Dr. Ramos-Barbón. Where antigens are present, T lymphocytes can be found directing the body's defense mechanism, which in the case of asthmatics results in airway remodeling. "This is a natural response designed to protect the body from disease," notes Dr. Ramos-Barbón. "But in this case it actually promotes conditions that favour asthma, leading to increased symptoms such as coughing and difficulty breathing.

To make their discovery, researchers at the MUHC removed T lymphocytes from asthmatic rats, made them fluorescent by adding a jellyfish gene, and then transplanted them into non-asthmatic rats. "The fluorescence allowed us to track the movement of the T lymphocytes and determine their effect on the non-asthmatic rats," says Dr. Ramos-Barbón. Researchers were surprised to discover that the T lymphocytes moved directly to--and infiltrated--the airway walls of the non-asthmatic rats, causing extensive remodeling. Moreover, researchers discovered that the T lymphocytes must be in direct contact with the cells of the airway wall in order to cause remodeling.

"The next step is to develop mechanisms to interrupt this process and combat asthma," says Dr. Ramos-Barbón, who was presented the Eldon R. Smith Award for this research at the inaugural National Research Forum for Young Investigators in Circulatory and Respiratory Health, a major training and educational initiative of the CIHR Institute of Circulatory and Respiratory Health.

"This discovery is particularly exciting because it provides insight as to how the body's own CD4 T lymphocytes cause the thickening of the airway muscle, which increases the chances of a dangerous asthma attack. This research opens up new ways to prevent and treat asthma and its complications," said Dr. Bhagirath Singh, Scientific Director of CIHR's Institute of Infection and Immunity. "Continued research is key to advancements and hope for new diagnostic tests and treatments".

Protective effect of statins against pneumonia

Mon, 25 Jul 2005 17:35:00 PST

( from http://www.rxpgnews.com ) Patients hospitalised because of pneumonia are at less risk of dying from the disease if they have been taking the widely used cholesterol-lowering drugs 'statins' before hospital admission. These results, published today in the Open Access journal Respiratory Research, suggest another beneficial use of statins, which are prescribed to an increasing number of patients to prevent and treat high cholesterol, diabetes, heart disease and vascular disease.

Pneumonia is the seventh most common cause of death and the leading cause of death from infection in the USA, where it kills up to 40,000 people every year those most at risk are very young children, elderly people and patients with underlying health problems such as AIDS or chronic obstructive pulmonary disease (CPOD). The disease is caused by viruses or bacteria, which are becoming resistant to the antibiotics used to treat bacterial pneumonia.

Eric Mortensen and colleagues, from the University of Texas Health Centre at San Antonio measured the risk of dying from pneumonia in patients admitted with pneumonia who were taking statins prior to their entry into hospital. They compared it with the risk of dying from the disease in pneumonia patients who were not taking statins. The authors used the Pneumonia Severity Index to rate the risk of dying within 30 days of admission to hospital in the two groups of patients. The results of their statistical analysis show that patients who were on a statin when they entered hospital were 2.8 times less likely to die than patients who were not on statins.

"Prior outpatient statin use was associated with decreased mortality in patients hospitalized with community-acquired pneumonia despite their use being associated with comorbid illnesses likely to contribute to increased mortality", write the authors.

More research is needed to explain the protective effect of statins on patients suffering from pneumonia. Statins act on the cholesterol-regulating enzyme HMG-CoA reductase, but they are also known to affect the immune system and this might explain their effect on pneumonia patients.

M. catarrhalis, a "Harmless" Bacterium Found to Cause 10 Percent of COPD Flare-Ups

Thu, 21 Jul 2005 23:23:00 PST

( from http://www.rxpgnews.com ) A ubiquitous bacterial strain thought to be uninvolved in chronic obstructive pulmonary disease (COPD) in fact is responsible for 2-4 million flare-ups of the condition that occur annually in the United States, researchers from the University at Buffalo have shown.

The bacterium, Moraxella catarrhalis or M. catarrhalis, often is present in sputum of adults with COPD. However, its potential role in the disease was ignored for decades, because studies in the early 1950s had found it to be relatively harmless.

A study published in the July 15 issue of the American Journal of Respiratory and Critical Care Medicine reports that M. catarrhalis was found to be responsible for approximately 10 percent of exacerbations of COPD. Timothy F. Murphy, M.D., professor of medicine and microbiology in the UB School of Medicine and Biomedical Sciences, was lead author on the study.

"This paper is the first to study the involvement of M. catarrhalis in a prospective way in adults with COPD," Murphy said. "Using rigorous methods, our work has shown that acquiring M. catarrhalis is strongly associated with the onset of symptoms of an exacerbation.

"People with COPD, estimated to be about 20 million in the U.S., experience one to two exacerbations per year," said Murphy, chief of the UB medical school's Infectious Diseases Division and a pioneer in vaccine development for respiratory disease. "If 10 percent of all exacerbations are caused by M. catarrhalis, that translates to 2-4 million exacerbations annually."

COPD is the fourth leading cause of death in the U.S. and many of those deaths occur during exacerbations, he said. "Exacerbations also cause enormous morbidity and health-care costs. They lead to physician visits, emergency room visits, hospital admissions and respiratory failure requiring mechanical ventilation."

In addition to showing that M. catarrhalis is involved in exacerbations of COPD, the researchers also found that patients make immune responses to the bacterium when they acquire it.

"Both of these observations provide lines of evidence that M. catarrhalis is a pathogen for these patients and provide a strong rationale for pursuing the development of vaccines to prevent M. catarrhalis infections in people with COPD," Murphy said.

The study involved 104 adults with COPD who were seen at the outpatient clinic at the Buffalo Veterans Affairs Medical Center over 81 months. During this period, patients made 3,009 clinic visits, 560 of which were during exacerbations. Sputum samples were collected at each clinical visit and molecular typing of organisms was conducted, as well as assays to measure immune response.

Researchers identified 120 episodes of M. catarrhalis infections in 50 patients, nearly half of which were associated with flare-ups of COPD. There was no evidence that exacerbations were associated with acquisition of a new strain of another pathogen.

"We know that M. catarrhalis causes ear infections in children," said Murphy. "With these new observations regarding the importance of the bacterium in adults with COPD, we have even more reason to forge ahead with developing a vaccine to prevent M. catarrhalis infections."

Inhale magnesium sulphate along with beta-2-agonists during asthma attacks

Wed, 20 Jul 2005 15:07:00 PST

( from http://www.rxpgnews.com ) Severe asthma attacks can be life threatening and intravenous magnesium sulphate is known to help, but inhaling nebulised magnesium sulphate can also improve lung function.

Asthma is a chronic disease of the lungs where people have periods where their breathing is stable, and other periods where it is restricted. These 'exacerbations' or 'attacks' can be mild or so severe that the person needs hospital treatment.

During most episodes people use inhaled beta-2-agonists, but in more severe cases these alone may not be enough to restore breathing to normal. The Cochrane Review Authors therefore searched the literature to examine the evidence regarding the use of inhaled magnesium sulphate as an additional therapeutic option.

They concluded that there was good evidence that nebulised magnesium sulphate was safe and effective and that it should be considered as an additional therapy along with beta-2-agonists.

"We also found that magnesium sulphate was most useful in situations where the exacerbation was severe," says lead author Maurice Blitz, who works in the Division of General Surgery, at the University of Alberta, Canada

MAC Treatment can cause ocular toxicity

Sat, 16 Jul 2005 00:13:00 PST

( from http://www.rxpgnews.com ) Ethambutol, a vital component of multidrug regimens for Mycobacterium avium complex (MAC) lung disease, can cause ocular toxicity if taken on a daily basis, according to a study in the second issue for July 2005 of the American Thoracic Society's peer-reviewed journal. Writing in the American Journal of Respiratory and Critical Care Medicine, the researchers recommended monthly visual acuity and color discrimination testing for patients taking doses of the drug greater than 15 to 20 milligrams per kilogram of body weight, those who receive the medication for longer than 2 months, and patients with renal insufficiency since the compound is cleared by the kidneys.

According to the investigators, the central fibers of the optic nerve are most commonly affected. The drug can cause blurred vision, decreased visual acuity, central blind or dark spots in the visual field, and often loss of the ability to detect green and sometimes red.

They point out, however, that ethambutol is a critical component of routine therapy for MAC disease which accounts for most mycobacterial infections other than tuberculosis in humans. MAC disease bacteria usually affect the lung, but may involve the lymph nodes, bones, joints, and skin. These bacteria are highly resistant to most antibiotics, but the infections they cause are not contagious. MAC infection in the lung usually develops slowly; the first symptoms generally involve coughing and spitting up mucus.

In this study, 229 patients with MAC lung disease received 16 months of multidrug therapy that included ethambutol. Patients on daily therapy received ethambutol at 25-mg/kg doses for the first 2 months, and then 15 mg/kg doses for the remainder of therapy. Patients on three-day-a-week therapy (Monday, Wednesday, and Friday) received a 25 mg/kg dose each day.

Of the 229 patients, 50 were known to have preexisting ocular disease.

The authors said that while on ethambutol, 97 patients consulted an ophthalmologist and 24, or 10 percent, stopped taking the drug temporarily. Eight of the 139 patients on daily therapy were diagnosed with ocular toxicity caused by the drug.

After they discontinued the drug, all patients with ocular disease caused by ethambutol returned to the same visual status they had prior to the start of the study.

Key to Potential Vaccine to COPD Bacteria

Sat, 16 Jul 2005 00:13:00 PST

( from http://www.rxpgnews.com ) Researchers believe that the acquisition and reasonably quick clearance of a bacterial strain called Moraxella catarrhalis from the lungs of chronic obstructive pulmonary disease (COPD) patients results in long-lasting, strain-specific protection from reacquisition and has important implications for vaccine development. The investigators assessed 104 adults with COPD for 81 months. They said that bacteria cause many of the exacerbations which characterize the disease and that such organisms, through chronic colonization, contribute to the airway inflammation that is the hallmark of the disease.

COPD is a term for lung diseases characterized by airflow obstruction that interferes with normal breathing. The two most frequent disease conditions that underlie COPD are severe emphysema and chronic bronchitis. Years of smoking are the primary cause for the diseases that underlie COPD, which, in 2002, claimed the lives of 120,000 Americans and cost the nation $37.2 billion.

In the study, the authors pointed out that 10.2 percent of the 560 exacerbations were likely caused by M. catarrhalis bacteria.

According to the authors, for the 20 million adults in the U.S. who have COPD, exacerbations occur at a rate of 1 to 2 annually. Based on their estimates, M. catarrhalis bacteria causes 2 to 4 million exacerbations annually in the U.S. Most individuals carried the organism M. catarrhalis for only a single monthly clinic visit. This relatively short duration of infection is in striking contrast to that observed for H. influenzae bacteria which colonized subsets of patients for a much longer time.

According to the researchers, the long-lasting, strain-specific protection offered by the acquisition and clearance of M. catarrhalis supports the concept that humans make protective responses that are capable of clearing the bacteria from the respiratory tract and preventing reacquisition. They said that their future work will focus on developing similar protective responses.

The study appears in the second issue for July 2005 of the American Thoracic Society's peer-reviewed American Journal of Respiratory and Critical Care Medicine.

Vitamin D Repletion Regimen for CF did not work

Sat, 16 Jul 2005 00:13:00 PST

( from http://www.rxpgnews.com ) The recently published vitamin D repletion regimen suggested by the Cystic Fibrosis Foundation's Consensus Panel on Bone Health for replacing the vitamin in cystic fibrosis (CF) patients has been called by researchers who tested it "strikingly ineffective." Out of 66 adults with CF, only 5 patients who had been treated with 50,000 international units of the vitamin per week for eight weeks had their serum levels corrected to the recommended degree.

The study was designed to determine the percentage of adults with CF who required the recommended vitamin D. repletion therapy because of serum levels below 30 nanograms per milliliter (30 ng/ml); to evaluate for the first time the effectiveness of a stepped up repletion protocol for CF patients; and to provide CF-specific data to assist in future optimal dosing.

Cystic fibrosis is a life-shortening inherited disorder that affects 30,000 persons in the U.S. Patients who are born with this problem produce abnormally thick and sticky mucus that often obstructs the lungs, leading to lung infections, as well as to the clogging of the pancreatic ducts which can prevent normal digestion. However, treatment for the disorder has improved greatly and predicted survival rates have increased from an average age of 25 in 1985 to over age 33 in 2005.

Since there has been an increase in survival, researchers have also been considering other health issues unique to the adult CF population. One issue is bone health because studies of bone density have determined that despite a young age, approximately 20 to 25 percent of adults with CF have osteoporosis and another 40 percent have osteopenia.

(Osteopenia is low bone volume due to inadequate replacement of bone loss from normal disintegration. Osteoporosis is abnormal loss of bone tissue, causing fragile bones that fracture easily.)

A adequate supply of vitamin D is needed for the body to absorb calcium from food and incorporate it into bone. A deficiency of vitamin D leads to abnormal bone growth and repair.

Of the 134 adults with CF in this study, 109 (81.3 percent) were found to have vitamin D levels below the recommended 30 ng/ml.

Of the 49 patients who started the second eight-week repletion test comprising a total of 800,000 international units of vitamin D, 33 completed the full course, but none corrected their vitamin D deficiency.

The authors noted that further research is required to determine the optimal level of vitamin D needed in order for CF patients to maximize calcium absorption and maintain bone health.

The research article appears in the second issue for July 2005 of the American Thoracic Society's peer-reviewed American Journal of Respiratory and Critical Care Medicine.

Giving oxygen may do more harm than good - Study

Tue, 12 Jul 2005 13:09:00 PST

( from http://www.rxpgnews.com ) Doctors and paramedics who give their patients oxygen the most commonly administered "drug" in the world may be doing more harm than good, a Queen's University researcher contends.

And although there's a simple solution adding carbon dioxide to the mix it isn't being used by most Canadian hospitals and emergency services networks, says Dr. Steve Iscoe, a respiratory physiologist. This has implications for treating a number of serious health conditions, including heart disease, stroke, diabetes, difficult labour and delivery, and wound healing.

Dr. Iscoe's commentary, based on his own and other researchers' findings, is published in the July issue of CHEST, the Cardiopulmonary and Critical Care Journal. Co-author of the article is Dr. Joseph Fisher, from the Toronto General Hospital's Department of Anesthesia.

"Pure oxygen can reduce blood flow to organs and tissues by increasing ventilation," Dr. Iscoe explains. "The increase in ventilation, which is almost never considered, 'blows off' carbon dioxide, and this fall constricts blood vessels. When carbon dioxide is added, however, the blood vessels dilate, increasing blood flow and causing more oxygen to reach tissues in key areas like the brain and heart."

Researchers in the early 1900s observed that breathing pure oxygen increased ventilation and lowered carbon dioxide levels. Based on their observations, several tried adding carbon dioxide and claimed success in resuscitating people and infants and treating carbon monoxide poisoning.

But the practice of using expired air even before it was known to contain carbon dioxide dates back much further. The use of mouth-to-mouth resuscitation on infants was recorded in a 1754 book by Benjamin Pugh, A Treatise of Midwifery, and there are biblical references to the custom. Yet modern medical texts do not mention that inhalation of oxygen decreases carbon dioxide levels and the effects on blood flow; consequently it is not part of standard practice.

"It's puzzling that a simple idea like this has received so little attention from clinicians," says Dr. Iscoe. Although there has been some concern about the possibility of patients receiving too much carbon dioxide (which can cause discomfort), he points out that new designs for oxygen masks allow precise monitoring of levels delivered or, in fail-safe mode, prevent inhalation of carbon dioxide. One can even use the patient's own expired carbon dioxide, the researcher adds.

"The reduction in oxygen delivery to the fetus, the brain, the heart, and other body tissues that might be induced by oxygen administration is, as this paper points out, largely unrecognized even by respirologists such as myself," says Dr. Peter Macklem, professor emeritus of medicine at McGill University and 1999 recipient of the prestigious Gairdner Foundation Wightman Award for outstanding leadership in medicine and medical science.

"If we respirologists are unaware, then internists, surgeons, obstetricians, pediatricians and family physicians who are at the front line of treatment for most of the clinical conditions they describe are unlikely to be better informed," Dr. Macklem continues. "The magnitude of the risk now needs to be quantified by appropriate clinical trials. While it will take a few years before we will know for sure, the wisest course of action in the interim is to administer low concentrations of carbon dioxide along with oxygen therapy."

Among the areas where Drs. Iscoe and Fisher see particular benefits for patients from improved oxygen delivery are:

# heart attack;
# stroke;
# carbon monoxide poisoning;
# wound healing in hospitals, where drug-resistant infections are on the rise;
# cerebral blood flow to fetuses during difficult birth procedures; and
# treating foot ulcers and gangrene in people with type 2 diabetes.

Dr. Iscoe hopes to evaluate the promise of the new technique in a study of diabetic patients. As the incidence of obesity rises, diabetes is expected to affect a growing number of people and exert increasing demands on the health care system.

"I think it's incumbent on health professionals to consider carbon dioxide when administering oxygen, since we know that carbon dioxide levels control blood flow to so many parts of the body," Dr. Iscoe says. "We should look at carbon dioxide not as an enemy, but as an ally."

Findings offer therapeutic potential for human asthma treatment

Wed, 06 Jul 2005 13:24:00 PST

( from http://www.rxpgnews.com ) Disruption of a single gene, Nrf2, plays a critical role in determining the susceptibility to asthma. A research team led by Shyam Biswal, PhD, at the Johns Hopkins Bloomberg School of Public Health found the absence of Nrf2 exacerbated allergen-mediated asthma in mice models. The studys findings, published in the July 4, 2005, edition of the Journal of Experimental Medicine, may hold therapeutic potential for the treatment of human asthma.

Asthma is a complex inflammatory disease of the airway characterized by airway inflammation and hyperreactivity. The incidence of asthma has doubled in the past two decades in the United States, affecting 20 million Americans. Controlling inflammation is a focus of asthma therapy. Inflammation occurs when certain cells migrate into the airways. These inflammatory cells release reactive oxygen species (ROS), causing the airway lining to swell and restrict. ROS is thought to cause lung tissue damage as well. ROS levels are normally offset by antioxidants in non-asthmatics. Recently, researchers have been hunting for novel genes that regulate inflammation with the hope of developing them as targets for the next generation of asthma drugs.

Suspecting that a defect in antioxidant response exacerbates asthma severity, the team of researchers began looking into the genetic factors that might contribute to this deficiency. In 2002, Biswals lab discovered Nrf2 acts as a master regulator of the majority of antioxidant pathways and detoxifying enzymes for environmental pollutants. This led researchers to consider the role of Nrf2 in lung inflammatory diseases caused by exposure to allergens. They found that the absence of the Nrf2 gene increased migration of inflammatory cells into the airways and caused an enhanced asthmatic response in mice. Nrf2 is critical for proper response to allergens in lungs and maintenance of a balance between ROS production. Antioxidant capability regulated by Nrf2 may be a major determinant of susceptibility to allergen-mediated asthma, says Biswal. Nrf2 regulated pathways seem to intervene inflammation at several points.

The findings provide a better understanding of the human bodys defense mechanisms to stress, which may hold clues to better control the inflammation process and improve control over asthma and its symptoms. Study coauthor Tirumalai Rangasamy, PhD said that the next step for researchers will be to look for molecular mechanism of regulation of asthmatic inflammation by Nrf2 and determine if there are alterations in the response of Nrf2 gene in asthma-prone humans. Future studies will determine the therapeutic potential of targeting Nrf2 for treatment of asthma.

Little benefit of antibiotics for uncomplicated lower respiratory tract infections

Wed, 22 Jun 2005 13:16:00 PST

( from http://www.rxpgnews.com ) Patients with uncomplicated lower respiratory tract infections, such as bronchitis, who were given antibiotics had little difference in symptom relief compared to patients who did not receive antibiotics, according to a study in the June 22/29 issue of JAMA.

Acute lower respiratory tract illness is the most common condition treated in primary care, according to background information in the article. In the United States, excess antibiotic prescribing is mainly for pharyngitis and acute bronchitis, amounting to 55 percent of prescriptions and costing $726 million per year. A consensus has been made for limiting antibiotic use in acute lower respiratory tract infection. However, recent reviews have come to diverse conclusions about the likely effectiveness of antibiotics and a recent review confirms a moderate effect of antibiotics on illness course; the debate continues unabated about the role of antibiotics because these reviews are relatively small. There are also concerns about complications if antibiotics are not prescribed and debate about which clinical characteristics identify those patients at higher risk.

The relative importance of prescribing strategies and information about natural history is also unclear. Preliminary evidence suggests that provision of an information leaflet can affect return rate and antibiotic use in lower respiratory tract infection, although the effect on symptomatic management of such a simple leaflet and whether a leaflet provides additional benefit to simple verbal information remains unclear.

Paul Little, M.D., of the University of Southampton, Highfield, England, and colleagues conducted a study to assess the effectiveness of three different antibiotic prescribing strategies on symptoms, beliefs, and behavior and to assess the effectiveness of an information leaflet compared with brief verbal information alone. The randomized controlled trial, conducted from August 1998 to July 2003, included 807 patients who presented to a primary care setting and had acute uncomplicated lower respiratory tract infection. Patients were assigned to 1 of 6 groups: information leaflet or no leaflet and 1 of 3 antibiotic groups (no offer of antibiotics [n=273], a delayed antibiotic prescription [n=272], and immediate antibiotics prescribed [n=262]). Approximately half of each group received an information leaflet (129 for immediate antibiotics, 136 for delayed antibiotic prescription, and 140 for no antibiotics).

A total of 562 patients (70 percent) returned complete diaries and 78 (10 percent) provided information about both symptom duration and severity. The researchers found that cough rated at least "a slight problem" lasted an average 11.7 days (25 percent of patients had a cough lasting 17 days or more). An information leaflet had no effect on the main outcomes. Compared with no offer of antibiotics, other strategies did not alter cough duration (delayed 0.75 days; immediate 0.11 days) or other primary outcomes. Compared with the immediate antibiotic group, slightly fewer patients in the delayed and control groups used antibiotics (96 percent, 20 percent, and 16 percent, respectively), fewer patients were "very satisfied" (86 percent, 77 percent, and 72 percent, respectively), and fewer patients believed in the effectiveness of antibiotics (75 percent, 40 percent, and 47 percent, respectively).

"In conclusion, in our patients from primary care who presented with acute uncomplicated lower respiratory tract infection, the use of delayed antibiotics or no antibiotics was acceptable, resulted in little difference in duration or severity of symptoms compared with immediate treatment with antibiotics, and considerably reduced both antibiotic use and belief in antibiotics. These findings suggest that adopting these strategies would help limit the vicious circle of the medicalization of self-limiting illness when antibiotics are prescribed. Immediate antibiotic prescribing is likely to limit the number of patients who return for cough within the next month but only by a little more than delayed antibiotic prescription. The challenge now is for clinicians and researchers to determine which groups are at risk of adverse outcomes and identify those patients who might selectively benefit from immediate antibiotic prescription," the researchers write.

In an accompanying editorial, Mark H. Ebell, M.D., M.S., of Michigan State University, East Lansing, Mich., comments on the findings of the study by Little et al.

"What can a clinician gain from the study by Little et al? First, antibiotics provide little or no benefit for patients with cough that is accompanied by lower respiratory tract symptoms provided the patient does not have pneumonia. This is true even for patients who are older and who have a low-grade fever or green sputum production. Second, physicians should be sure to inform patients that whether or not they take antibiotics, they can expect that a cough will last about 3 weeks, and that for at least 25 percent of patients it will last nearly a month. Third, by prescribing antibiotics it is clear that clinicians are training patients to expect these drugs. Physicians who feel compelled to give an antibiotic should at least use the tactic of delayed prescriptions to mitigate the effects of this prescribing error. Fourth, the patient's agenda for the visit must be addressed. Physicians should be sure to answer their questions, provide symptomatic care, and consider an inhaled beta-agonist if there is evidence of bronchospasm or a history of asthma."

"For patients in whom pneumonia is suspected, appropriate treatment must be promptly initiated. However, if the clinician does not suspect pneumonia, the patient should be informed of that assessment, but should be advised to return if symptoms progress. However, physicians should not give antibiotics to 100 patients on the chance that 1 patient may develop pneumonia at some point in the future," Dr. Ebell writes.

"In the current market-based health care system, it is tempting to confuse patient satisfaction with better outcomes, and to confuse more care with better quality care. Physicians have a duty to listen carefully to patients' symptoms, to examine them carefully, and to take the time to explain their illness to them. However, physicians have no duty to fulfill patients expectations for inappropriate care, such as prescribing antibiotics when they are not indicated, and must be mindful of the duty to the larger community that suffers financially and medically when antibiotics are overused," Dr. Ebell concludes.

Key milestone in antifungal treatment for severe asthma

Thu, 16 Jun 2005 18:00:00 PST

( from http://www.rxpgnews.com ) University of Manchester researchers announced today that they have reached a key milestone in their study of the antifungal treatment of asthma.

It is hoped that the study, by clinical researchers based at Manchester's Wythenshawe Hospital, will reduce steroid use and serious attacks requiring hospital intervention for asthma sufferers. It could also help those with cystic fibrosis and chronic sinusitis.

Severe asthma in adults affects 10 - 20% of the UK's 5m asthmatics, and skin tests indicate that up to 70% of these sufferers are allergic to one or more common fungi in the air.

Previous studies have shown the benefits of one antifungal drug [itraconazole or Sporonoxâ] for the asthma subgroup known as 'allergic bronchopulmonary aspergillosis' or 'ABPA'. The University of Manchester researchers are studying the more common association between fungal allergy and those with severe asthma who do not have ABPA. Volunteers are screened and, if testing shows allergy to one or more fungi, allocated itraconazole capsules or matching dummy capsules for 8 months. So far 26 patients (25% of the total required) have been enrolled.

Allergy to fungi is relatively common, affecting asthmatics, those with cystic fibrosis and others with chronic sinusitis (usually with nasal polyps). Fungi commonly implicated include airborne molds, such as Aspergillus, Cladosporium, Alternaria and Penicillium, with airborne fungal spores outnumbering pollen grains in outside air almost 1000-fold. Inside the home fungi are also very common, particularly in bedrooms and cellars, and compost is particularly rich in fungi.

The clinical study is funded by the charity The Moulton Trust as a grant to the University of Manchester. Its lead investigator Dr Robert Niven, of the North West Lung Centre, Wythenshawe Hospital, said: "We have few options for patients with severe asthma other than prescribing more steroids, and those we do have can have side effects worse than steroids themselves.

"Antifungal treatment for those sensitized to fungi may be a useful additional strategy to improve the breathing and overall health of these patients. Certainly our limited treatment experience with itraconazole suggests fewer admissions to hospital for asthma and reduced numbers of steroid courses."

Another rung on the Asthma ladder

Sun, 29 May 2005 16:26:00 PST

( from http://www.rxpgnews.com ) Results of a clinical study presented at a leading international medical congress show that Xolair® (omalizumab) halved the rate of severe asthma exacerbations and reduced the rate of hospital emergency visits by 44% in patients with inadequately controlled severe persistent asthma, who are at high risk of life-threatening attacks.1 Xolair also significantly improved patients' asthma-related quality of life, according to data from the same study presented at the centenary congress of the American Thoracic Society this week.

Xolair is a first-in-class therapy that is given by injection every two or four weeks and blocks the action of IgE, the antibody responsible for triggering the cascade of allergic symptoms in patients with diseases such as allergic asthma. It offers a novel therapeutic approach to the control of asthma symptoms such as wheezing and shortness of breath, even in the most difficult-to-treat patients whose condition remains poorly-controlled despite receiving the best available therapy.

A total of 419 such patients, aged 12-75, were recruited for a double-blind, placebo-controlled, parallel-group, multicenter study called INNOVATE to assess the effect of add-on Xolair therapy on the rate of severe asthma exacerbations and emergency visits.1 The participants all had reduced lung function and a recent history of clinically significant exacerbations, despite receiving step 4 therapy as defined in the GINA guidelines, including high-dose inhaled corticosteroids, long-acting beta2-agonists and other controller medication (including oral corticosteroids) if required.

Severe exacerbations halved
The severe exacerbation rate (i.e. where lung function measured by PEF or FEV1 was less than 60% of personal best, requiring systemic corticosteroids) and the rate of emergency visits (i.e. hospital admissions, emergency room visits and unscheduled doctor's visits) were calculated during the treatment phase. Results showed that add-on Xolair therapy significantly reduced both the severe exacerbation rate (0.24 vs 0.48, p=0.002) and emergency visit rate (0.24 vs 0.43, p=0.038) compared with placebo. The authors concluded: "Omalizumab should be considered as add-on therapy for patients with inadequately controlled severe persistent asthma who have a significant unmet need despite best available therapy."

The rate of clinically significant asthma exacerbations (i.e. those requiring rescue systemic corticosteroid therapy) was significantly reduced by 26% (p = 0.043), when adjusted for an observed imbalance in asthma exacerbation history prior to randomisation into the trial. Without taking this baseline imbalance into account, a similar magnitude of effect was seen (i.e. a 19% reduction) but this did not reach statistical significance.

Around 300 million people in the world have asthma,4 of whom an estimated 15 million suffer from severe persistent disease.5 Their health and quality of daily life are severely affected, and asthma is estimated to cause more than 180,000 deaths worldwide each year.Until now there have been few additional therapeutic options available for these patients.

A further analysis of data from the INNOVATE study evaluated the impact of Xolair treatment on patients' quality of life, measured by the Asthma QoL Questionnaire (AQLQ) (i.e. individual domains, overall score and clinically meaningful more than or equal to0.5-point improvement).2 Add-on Xolair therapy produced significantly greater improvements than placebo for each individual AQLQ domain (p0.002) and overall score (p less than 0.001). In addition, a significantly greater proportion of patients receiving Xolair achieved a clinically meaningful more than or equal to 0.5-point improvement from baseline in their AQLQ score than patients receiving placebo (60.8% vs 47.8%, p=0.008).

Well-tolerated in children
Another study presented at the ATS congress evaluated the long-term safety and tolerability of Xolair in children aged 6-12 years at entry, who were eligible to join a three-year multicenter, open-label extension on completion of a one-year clinical trial (28-week double-blind core trial and 24-week open-label extension).

The percentage of patients who experienced adverse events (AEs) in the core trial was similar in the Xolair and placebo groups (89.3%, n=201 and 87.2%, n=95 respectively). Of the 309 patients who entered the 24-week extension of the core trial, 244 (79.0%) experienced an AE. A total of 188 patients continued into the three-year extension, of whom 103 completed the study. Of the 85 patients who discontinued, the majority withdrew consent due to study duration and maintaining study commitments.

Xolair was generally well-tolerated and most AEs were mild to moderate in severity. When evaluated by 28-week increments, the incidence of AEs was generally comparable or lower than that seen in the 28-week core trial. No AEs suggestive of immunological reactions were reported. Overall, there were 13 AEs that investigators suspected were drug-related. There were eight serious AEs of which only one (dyspnea) was considered to be drug-related. No evidence of clinically significant changes in vital signs, spirometry or laboratory parameters, including platelets, were observed following Xolair treatment.

Xolair was launched in the US in July 2003, and is also approved in Australia, Brazil, Canada, Dominican Republic, Guatemala, Israel, New Zealand and Venezuela. It has been developed under an agreement between Novartis Pharma AG, Genentech, Inc., and Tanox, Inc. The European Medicines Agency (EMEA) is due to announce its decision on Xolair approval later this year.

The foregoing release contains certain forward-looking statements that can be identified by terminology such as "could fulfill," "should be considered," "is due to," or similar expressions, or by discussions regarding the potential that Xolair will be approved for marketing, or regarding any potential revenues from Xolair. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with Xolair to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Xolair will be approved for sale in any market. In particular, management's expectations regarding commercialization of Xolair could be affected by, among other things, uncertainties relating to clinical trials; new clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures; as well as other risks and factors referred to in the Company's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise

Interferon alpha Therapy for the Treatment of Idiopathic Pulmonary Fibrosis - Study

Wed, 25 May 2005 11:47:00 PST

( from http://www.rxpgnews.com ) Amarillo Biosciences, Inc. (ABI) (OTC BB: AMAR) today announced that the Company has been supplying its low-dose orally administered interferon alpha (IFNa) to a pilot clinical trial in the treatment of idiopathic pulmonary fibrosis (IPF).

The study, is being conducted by Lorenz O. Lutherer, M.D., Ph.D. and Cynthia Jumper, MD, Professors of Internal Medicine at Texas Tech University Health Sciences Center. The study which commenced in 2001 and is ongoing, was funded by a grant from the State of Texas Higher Education Coordinating Board, Applied Technology Program.

IPF is a lung disease of unknown origin that causes scarring of lung tissue, which in turn leads to difficulty in supplying oxygen into the blood stream. The disease is relatively rare, with an incidence of 20 per 100,000, and current treatments are ineffective.

The disease's symptoms include: the gradual onset of a persistent cough, difficulty breathing, a progressive inability to perform physical activities, changes in lung function tests, and a marked decrease in the quality of life. The prognosis is a limited expected life span of 3.2 to 5 years after diagnosis.

"IFNa was selected as a potentially effective therapy for IPF for a number of reasons," stated Dr. Lutherer. "There exists a low level of interferon in the lungs of IPF patients. IFNa is known to stimulate the body's interferon production; modify immune responses; prevent activation of fibroblasts and deposition of collagen (scarring process); and, activate aquaporins in lungs, thereby preventing drying of the tissue across which oxygen enters the blood."

The study has enrolled 17 of 20 planned subjects who are being administered 150 units of IFNa three times daily in the form of orally dissolving lozenges. Originally designed for one year, subsequent FDA approval was obtained to continue the IFNa treatment in those subjects who demonstrate stabilization of IPF. The subjects are evaluated with pulmonary function tests quarterly and chest x-rays and high resolution computed tomography (HRTC) annually.

Results to date suggest that while IFNa treatment has not reversed existing damage, it appears to be arresting the progression of the disease, and the duration of the stability is impressive given the short expected survival time after diagnosis. The stability -- arrest of IPF -- was confirmed by pulmonary function tests in 6 of 7 patients treated at least 1 year, including one subject who has been on IFNa treatment for three years. "Subjects also experienced a marked decrease in cough and have expressed a positive response to the lack of progression of the disease," stated Dr. Lutherer.

Accordingly, ABI, in conjunction with Dr. Lutherer, will continue to follow those on treatment; use current data to apply for Orphan Drug Designation from the Food and Drug Administration (FDA); and, submit a Phase II development program to FDA. Dr. Lutherer will present his findings and answer questions at the ABI Annual Shareholder's Meeting on May 27th.

Indacaterol : A Novel Beta2-agonist for Asthma and COPD

Tue, 24 May 2005 10:54:00 PST

( from http://www.rxpgnews.com ) Novartis' development compound indacaterol (QAB149) may provide a new standard for beta2-agonist therapy in
patients with asthma and chronic obstructive pulmonary disease (COPD), according to data presented at the centenary meeting of the American Thoracic Society (ATS) this week. The collective data from Phase II studies show
indacaterol provides bronchodilation for up to 24-hours, with convenient once-daily dosing.

"Respiratory disease is an important therapeutic area of focus at Novartis," said Alex Gorsky, Chief Operating Officer, Novartis Pharmaceuticals Corporation. "We have designed an ambitious development program for indacaterol and other compounds, such as the recently licensed anticholinergic AD237. We look forward to making new single and combination treatments available for the millions of patients who need them."

Results in Patients

A randomized, double-blind, dose-ranging study (50, 100, 200, 400 ug or placebo) in 42 patients with intermittent or mild to moderate persistent asthma demonstrated effective 24-hour bronchodilation within five minutes and a favorable safety profile with once-daily dosing. Improvements in efficacy were generally dose dependent, while safety and tolerability were similar to placebo.(i)

"Despite advances in the management of these chronic conditions, the numbers of individuals affected by asthma and COPD are large and growing," said James Donohue, M.D., Professor of Medicine, Chief, Division of Pulmonary Critical Care, University of North Carolina School of Medicine. "These data show indacaterol has significant therapeutic potential, including single-dose 24-hour control, for asthma and COPD patients."

A further randomized, double-blind, placebo-controlled, parallel-group, multicenter study involving 156 patients aged 13-75 demonstrated that indacaterol was shown to have a favorable cardiovascular safety profile, with no clinically significant effect on ECG measurements, vital signs or laboratory tests commonly affected by long-duration beta2-agonists.

No clinically notable changes occurred in the mean QTc intervals for any treatment group at any time point (calculated using Fridericia's formula). No clinically or statistically significant changes in serum potassium and blood glucose, or evidence of dose-related increases in adverse events were detected. In addition, no serious adverse events occurred in any active treatment group.(ii)

Indacaterol pre-clinical studies

In addition, extensive pre-clinical studies involving indacaterol also were presented. In isolated human bronchi, indacaterol provides effective bronchodilation with a longer duration of action than albuterol and formoterol
and an onset of action more rapid than salmeterol and comparable to albuterol.

At resting tone, the onset of action of indacaterol (9.2 plus or minus 1.5min, n=8) was not significantly different from that of formoterol (5.8 plus or minus 0.8min, n=8) and albuterol (11.0 plus or minus 3.6min, n=8) but was significantly faster than that of salmeterol (18.0 plus or minus 3.5min, n=8; p less than 0.05).(iii)

In addition, indacaterol was shown to be a potent beta2-agonist that, in contrast to salmeterol, does not antagonize the bronchorelaxant effect of a short-acting beta2-agonist.

Other pre-clinical data demonstrate that indacaterol provides a long duration of action and fast onset in vitro and in vivo in the guinea-pig. The risk of tachyphylaxis, or rapidly decreasing response to a drug, was assessed
in once-daily intratracheal (IT) dosing of indacaterol compared with formoterol and salmeterol. Conscious guinea-pigs were then challenged with aerosolized 5-HT (175ug/mL, 1 min) 2 hours after beta2-agonist exposure following both single and 5 daily IT treatments and bronchoconstriction
quantified by plethysmography. No tachyphylaxis was observed with indacaterol, formoterol or salmeterol.(iv)

Significant Disease Burden

COPD incurs a significant burden on the U.S. healthcare system in terms of number of visits and medications prescribed. Among the papers presented at the ATS meeting was an analysis of data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey conducted by a team of researchers from Novartis Pharmaceuticals, Rutgers University and Duke University that assessed the disease burden. Results showed that during 2002, 9.9 million ambulatory visits were made to physician offices, outpatient departments and emergency departments in the U.S., representing a 50.1% increase from 2001. In addition, the annual rate of visits for COPD across
all settings was 34.4 visits per 1,000 persons in the U.S. population.(v)

"Asthma-related suffering, cost and death can be greatly reduced through treatment with effective medications," said Mike Tringale, M.S.M., Director of Marketing and Communications at the Asthma and Allergy Foundation of America. "We look forward to seeing what benefit this new treatment will provide and to having a new treatment option for patients."

About Asthma and COPD

Exploring new treatments for asthma and COPD is critical. Despite a wide range of currently available therapeutic options, respiratory diseases affect millions of patients around the world. For example, asthma, which affects
more than 23 million people in the U.S., is the sixth most common chronic condition overall. In addition, the estimated number of asthma-related deaths is approximately 5,000 per year.(vi) COPD is presently the fourth leading
cause of death worldwide and is expected to be the third leading cause of death by 2020. While COPD death rates are very low under the age of 45, complications and deaths increase steeply with age.(vii)

Data Presented for Iloprost Therapy for the Treatment of Pulmonary Arterial Hypertension

Mon, 23 May 2005 19:57:00 PST

( from http://www.rxpgnews.com ) CoTherix,Inc. (Nasdaq: CTRX) announced today that researchers have presented results involving inhaled iloprost therapy for the treatment of pulmonary arterial
hypertension(PAH), a debilitating and potentially fatal disease characterized by high blood pressure in the pulmonary arteries.

Results were presented at the American Thoracic Society (ATS) International Conference in San Diego during the Thematic Poster Session for Pulmonary Hypertension.

Ventavis(R) (iloprost) Inhalation Solution was approved by the U.S. Food and Drug Administration (FDA) on December 29, 2004 for the treatment of PAH (World Health Organization Group I) in patients with NYHA Class III or IV symptoms.

"These data demonstrated the long-term safety and efficacy of inhaled iloprost in NYHA Class III and IV patients. In addition, the efficacy of inhaled iloprost after an overnight break supports the value of intermittent dosing," said Horst Olschewski, M.D., Professor and Chair, Division of Pulmonology, Medical University, Graz, Austria. "For physicians considering prostacylin therapy for their PAH patients, inhaled iloprost provides them with a non-invasive treatment option."

Inhaled Iloprost Effective for Long-Term Treatment of PH H. Olschewski et al. (A57; Poster K29) presented data from a follow-up study investigating the long-term (LT) safety, dosing and clinical benefit of therapy with inhaled iloprost over a two-year period. 52 pulmonary hypertension (PH) patients who completed an initial 12-week randomized
controlled study were given open-label inhaled iloprost treatment for two years.

The study demonstrated that inhaled iloprost was effective for the long-term treatment of PH in those patients, with two-year data suggesting sustained clinical benefit. In addition, no significant dose increase was required to maintain clinical benefit. Heart failure due to PH was the most common serious adverse event.

Among 4/30 (13%) of iloprost-treated patients who met composite clinical response criteria (more than 10% increase in 6 minute walk test (MWT) + improvement in
NYHA class + no deterioration/death) at 12 weeks, all maintained their response after 2 years. No patients in the control group met the response criteria at 12 weeks; however, five met the criteria upon long-term treatment
with inhaled iloprost.

Patients with primary or idiopathic pulmonary hypertension (n=39) had a two-year survival rate of 91% (95% CI: 75.8%-97.6%) compared with a predicted survival of 63% for an untreated historical cohort (based upon the NIH registry).

"Intermittent therapy with inhaled iloprost improved exercise capacity and pulmonary hemodynamics while reducing the risk of developing tolerance and rebound. It also avoids the inconvenience and complications that are
associated with chronic indwelling catheters. This study shows that inhaled iloprost can safely and effectively be administered long-term, with maintenance of efficacy," said Dr. Olschewski.

Study Supports Use of Inhaled Iloprost in Patients with NYHA Class IV Pulmonary Hypertension H. Olschewski et al. (A57; Poster K28) also presented subgroup analyses from a 12-week randomized controlled study which included 83 patients with NYHA Class IV PH (chronic thrombotic and/or embolic disease).

The study was designed to compare the efficacy of treatment with inhaled iloprost to placebo.

Researchers reported that patients in the study treated with inhaled iloprost showed a statistically significant improvement in clinically relevant measures of efficacy. The primary clinical endpoint for the trial was a composite of:

(1) an improvement in NYHA functional class,
(2) an increase in the distance walked in six minutes of at least 10%, and
(3) no clinical deterioration.

For these Class IV patients, the difference between the two
groups was statistically significant (P=0.022) with patients in the inhaled iloprost group performing significantly better than those in the placebo group. The response rate for the primary efficacy endpoint among PH patients was 17 percent for patients treated with inhaled iloprost compared with two percent for the placebo treated patients (p=0.022).

Clinical Benefit of Inhaled Iloprost Maintained during Period between Dosages L.J. Rubin et al. (A57; Poster K61) presented data from a placebo-controlled study of 203 PH patients investigating the effects of intermittent dosing of inhaled iloprost. The study showed that inhaled
iloprost had a sustained treatment benefit in PH patients when assessed at the point of lowest concentration during the dosage cycle. Inhaled iloprost is given regularly during the day via direct pulmonary delivery, but patients do not administer the therapy while they sleep.

In iloprost-treated patients, the absolute change in six-minute walk distance (6-MWD) following 12 weeks of therapy when measured after periods of two to 12 hours since the last inhalation was +11 +/- 69 m (mean +/- SD), compared to a decrease of -11 +/- 82 m in the placebo group. This represents a placebo-corrected improvement of 22 meters (p=0.052). Hemodynamic parameters evaluated before inhalation (trough drug effect) improved or remained stable
for the iloprost group versus significant deterioration in the placebo group when compared with baseline (10% increase in PVR, a 5% decrease in CO, and a 5% decrease in SVO2 over 12 weeks in the placebo group).

About PAH

PAH affects an estimated 50,000 patients in the United States, with only about 15,000 diagnosed and under treatment. Its cause may be unknown, or result from other diseases that cause a restriction of blood flow to the
lungs, including scleroderma, HIV and lupus. Symptoms of the disease include fatigue, shortness of breath on exertion, chest pain and dizziness. Left untreated, the median survival time following diagnosis may be as short as
three years.

About Ventavis

Ventavis(R) (iloprost) Inhalation Solution was approved by the U.S. Food and Drug Administration (FDA) on December 29, 2004 for the treatment of PAH (WHO Group I) in patients with NYHA Class III or IV symptoms. Ventavis is the
newest entry into the prostacyclin class of PAH treatments. Prior to the introduction of Ventavis, prostacyclin therapies for PAH required continuous delivery through subcutaneous or intravenous routes -- invasive treatments
which are difficult to tolerate and/or require complicated maintenance.

Ventavis provides PAH patients with a non-invasive, inhaled treatment option.

Ventavis is not approved for the treatment of pulmonary hypertension due to chronic thrombotic and/or embolic disease.

In clinical studies of Ventavis monotherapy in treating PAH, common adverse reactions due to Ventavis included: vasodilation (flushing, 27%),
cough (39%),
headache (30%),
flu syndrome (14%),
nausea (13%),
jaw pain (12%),
hypotension (11%),
insomnia (8%) and
syncope (8%);

other serious adverseevents reported included congestive heart failure, chest pain, supraventricular tachycardia, dyspnea, peripheral edema, and kidney failure.

FDA Gives Clearance to the First Cystic Fibrosis DNA test

Tue, 10 May 2005 09:18:00 PST

( from http://www.rxpgnews.com ) Tm Bioscience Corporation (Toronto, Ontario; TSX: TMC), a leader in the commercial genetic testing market, is pleased to announce that its Tag-It(TM) Cystic Fibrosis (CF) Kit is the first multiplexed human disease genotyping test to be cleared by the U.S. Food and Drug Administration (FDA) as an in vitro device (IVD) for diagnostic use in the United States.

This DNA based test is used to simultaneously detect and identify mutations and variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene in human blood specimens in order to determine CF carrier status in adults, as an aid in newborn screening, and in confirmatory diagnostic testing in newborns and children. Performance testing has established that the Tag-It(TM) CF Kit operates with 100% accuracy and greater than 99.9% reproducibility and precision.

"This clearance establishes Tm as a unique supplier of CF tests to our rapidly expanding customer base against such competitors as ABI (NYSE:ABI - News) and Third Wave (NASDAQ:TWTI - News)," said Greg Hines, President and CEO of Tm Bioscience. "The Tag-It(TM) Cystic Fibrosis Kit is the only CF testing system that has performance characteristics which have been established through extensive studies reviewed by the FDA. Having the first CF test and second multiplexed genetic test behind Roche's (RHHBF.PK) AmpliChip CYP450 to be cleared as an IVD, sets the regulatory pathway for other tests in our broad and growing pipeline and positions Tm as a leader in the commercial genetic testing market."

"Clearance by the FDA of a genetic assay for cystic fibrosis provides a highly standardized product for laboratories that offers tremendous benefits to the genetic testing industry, physicians and to patients." said Dr. Michael Watson, Executive Director, American College of Medical Genetics.

Cystic Fibrosis (CF) is the most common autosomal recessive disorder in the Caucasian population, with an incidence of approximately 1 in 3,200 live births. The Tag-It(TM) Cystic Fibrosis Kit simultaneously screens for the 23 cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and 4 variants (polymorphisms), as recommended by the American College of Medical Genetics (ACMG) and the American College of Obstetricians and Gynecologists (ACOG) in 2004. In addition, the kit screens for 16 additional mutations prevalent in North America or the world.

Performance Results

The Tag-It(TM) Cystic Fibrosis Kit is sold with the following FDA cleared performance characteristics:

-Accuracy of the Tag-It(TM) CF Kit was established in a method comparison study using DNA sequencing as reference methods. Based on comparison of 2,924 genotyping calls for the 43 mutations and variants tested for by the Tag-It(TM) CF Kit, concordance between the Tag-It(TM) CF Kit and the reference tests was 100% (95% CI(equal sign)99.9% to 100%).

-Reproducibility was established as greater than 99.9% in a multi-site study by testing DNA samples obtained from the Coriell Institute for Medical Research (Camden, NJ) repository using three different lots and three operators.

-Precision was tested using synthetic positive controls representing all potential genotyping calls for all 43 mutations and variants tested for by the Tag-It(TM) CF Kit. Overall, study results showed that all genotyping calls that can be made by the Tag-It(TM) CF Kit were made correctly and reproducibly under the evaluated conditions with a precision of greater than 99.9%.

The kit is not indicated for fetal diagnostic, pre-implantation testing or for stand-alone diagnostic purposes.

About Tag-It(TM) reagents and genetic tests

Tm Bioscience's product menu is focused in the fields of human genetic disorders, pharmacogenetics and infectious disease. The Company has commercialized Analyte Specific Reagents(x) and a series of Tag-It(TM) tests(xx) for a variety of genetic disorders. All genetic tests from Tm Bioscience are based on the Tag-It(TM) Universal Array platform, which utilizes a proprietary universal tag system that allows for easy optimization, product development and expansion. Assays from Tm operate on the Luminex xMAP® system, a well-established bead based instrument. Combined, the Universal Array and Luminex instrument enable the rapid production of flexible, high-throughput, low-cost DNA-based tests.

Pirfenidone Shows Favorable Effects in Idiopathic Pulmonary Fibrosis

Wed, 04 May 2005 10:28:00 PST

( from http://www.rxpgnews.com ) InterMune, Inc. today announced that the American Journal of Respiratory and Critical Care Medicine (AJRCCM) published results from a double-blind, randomized, placebo-controlled Phase II trial evaluating pirfenidone for the treatment of patients with idiopathic pulmonary fibrosis (IPF).

This 107- patient study with a planned 12-month treatment period was conducted in Japan by Shionogi & Co., LTD and was terminated after only nine months based on the recommendation of the Data Safety Monitoring Board following an interim analysis. This analysis suggested favorable effects of pirfenidone on acute exacerbations and other efficacy parameters, prompting the decision to stop the trial.

In the 9-months of treatment, acute exacerbations had occurred in 14% and 0% of placebo and pirfenidone patients, respectively (p=0.0031). All of these patients required hospitalization and one patient died.

The analysis of the primary endpoint, change from baseline in the lowest oxygen saturation during a 6-minute exercise test, revealed a trend in the overall population (p=0.072) with a more pronounced treatment effect in a pre-specified subgroup of patients with milder disease (p=0.0305). Pirfenidone had a favorable effect on vital capacity, analyzed as both a change from baseline (p=0.0366) and a categorical assessment of the proportion of patients who improved, were stable, or declined (p=0.0028).

Changes in total lung capacity, carbon monoxide diffusing capacity, resting partial pressure of arterial oxygen, dyspnea, and quality of life were not statistically significant after nine months of treatment.

Gastrointestinal symptoms, photosensitivity and fatigue occurred more frequently in the pirfenidone group, although rates of treatment adherence were similar between the two groups. The main cause for patients discontinuing from study treatment was photosensitivity in the pirfenidone group (6.8% vs. 0%) and acute exacerbation (0% vs. 14%) in the placebo group.

"This study suggests that treatment with pirfenidone may prevent acute exacerbation of IPF and reduce the rate of decline in vital capacity," said Dan Welch, InterMune's President and CEO. "We are encouraged by these promising results and are moving forward with our discussions with the U.S. Food and Drug Administration and the European Medicines Agency regarding the design of a Phase III development program for pirfenidone in IPF, which we expect to initiate in the first half of 2006."

InterMune acquired an exclusive license relating to the manufacture, use and sale of pirfenidone for antifibrotic use worldwide, excluding Japan, Korea, and Taiwan, where rights are held by Shionogi & Co., LTD.

About IPF

IPF is a disabling and ultimately fatal disease that affects approximately 83,000 people in the United States, with an estimated 30,000 new cases developing each year. Those diagnosed with IPF are usually between the ages of 50 and 70, and the disease tends to affect men more than women. IPF causes inflammation and scarring (fibrosis) in the lungs, hindering a person's ability to process oxygen and causing shortness of breath (dyspnea) and cough. IPF is a progressive disease, meaning that over time, lung scarring and symptoms increase in severity. Median survival time from diagnosis is two to five years in patients with IPF. There are currently no drugs approved by the FDA for the treatment of IPF.

Home-Away®Oxygen System Approved by FDA for Easy Oxygen at Home

Mon, 25 Apr 2005 08:15:00 PST

( from http://www.rxpgnews.com ) In-X Corporation, of Denver, CO, developer and manufacturer of home oxygen liquefaction systems received FDA Clearance today for the Home-Away® System. The Home-Away System enables patients with Long Term Oxygen Therapy (LTOT) needs to produce liquid oxygen in their home, thus eliminating the need for expensive deliveries.

The revolutionary Home-Away System will enable patients on LTOT to remain mobile and maintain their quality of life. Additionally, it is exciting news for home healthcare providers because it eliminates costly and time-consuming deliveries while offering patients full mobility with the preferred form of ambulatory oxygen, said Doug Powell, president of In-X Corporation.

The Home-Away System works in conjunction with any In-X approved oxygen concentrator to create liquid oxygen within the patients home. The system directs a portion of the oxygen flow from the concentrator directing it to a cryogenic cooling device, where it is condensed into liquid and stored within the system until it is ready to be transfilled into a portable liquid unit. The remaining oxygen gas produced by the concentrator is available for patient use at a flow of up to 3 lpm. The portable liquid unit is worn around the patients waist (similar to a fanny pack); weighs just 4.2 lbs when full and provides a typical patient with 6-8 hours of mobility per fill. The Home-Away System produces enough liquid oxygen for a patient to fill the portable liquid unit 3 times per day.

In-X anticipates having the Home-Away System ready for sale to home healthcare providers in the last quarter of 2005 with product delivery the first quarter of 2006.

AD 237 : An Inhaled Long-acting Anti-muscarinic for the Treatment of Chronic Obstructive Pulmonary Disease in Phase II

Mon, 18 Apr 2005 09:03:00 PST

( from http://www.rxpgnews.com ) Novartis announced that it has signed a global development and commercialization agreement with Vectura Group plc and Arakis Ltd. for AD 237, an inhaled, long-acting, anti-muscarinic agent for the treatment of chronic obstructive pulmonary disease (COPD).

Novartis will be responsible for further development of AD 237 both as monotherapy and in combination with QAB149, its once-daily, long-acting beta2 agonist currently in Phase II clinical development.

Developed to date through a joint venture between Arakis and Vectura, AD 237 is a once-daily, long-acting muscarinic antagonist (LAMA) with a fast onset of action.

The compound is in Phase II trials for the treatment of COPD and studies have thus far demonstrated that it is well-tolerated and effective over 24 hours after a single dose. AD 237 has been developed using Vectura's proprietary PowderHale® inhalation technology for delivering product to the lung and optimizing fine particle fraction delivery through a commercially available dry-powder inhaler device.

"With this agreement, our late stage pipeline now contains two promising bronchodilator drugs, QAB149 and AD 237 for the treatment of COPD," said Joerg Reinhardt, Head of Development, Novartis Pharma AG. "Both products have significant therapeutic potential, either as single agents or combination therapies. Respiratory disease is one of our key therapeutic areas of focus, and we are delighted to expand our franchise and provide patients with important new therapeutic solutions."

COPD, the world's fourth largest cause of death, is an irreversible and chronic obstruction of the airways which is caused primarily by smoking. It is estimated that the disease is prevalent in 4% of the population in the USA, Europe and Japan, and that at least one in 15 smokers suffers from it. Symptoms include chronic bronchitis and emphysema or both conditions, which slowly progress and eventually lead to a largely irreversible loss of lung function. The current market for COPD drug therapy is estimated to be worth $4 billion per annum and is predicted to grow to $10 billion by 2010.

Under the terms of the agreement Arakis and Vectura will receive an initial payment and additional milestone payments based upon the achievement of agreed clinical, regulatory and commercialisation targets. In addition, royalties on product sales will be paid for both the monotherapy and combination products. All payments by Novartis will be shared equally by Arakis and Vectura.

Cockroach Allergens Have Greatest Impact on Childhood Asthma

Fri, 08 Apr 2005 04:11:00 PST

( from http://www.rxpgnews.com ) New results from a nationwide study on factors that affect asthma in inner-city children show that cockroach allergen appears to worsen asthma symptoms more than either dust mite or pet allergens. This research, funded by the National Institute of Environmental Health Sciences (NIEHS) and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is the first large-scale study to show marked geographic differences in allergen exposure and sensitivity in inner-city children. Most homes in northeastern cities had high levels of cockroach allergens, while those in the south and northwest had dust mite allergen levels in ranges known to exacerbate asthma symptoms.

The study results are published in the March issue of the Journal of Allergy and Clinical Immunology.

"These data confirm that cockroach allergen is the primary contributor to childhood asthma in inner-city home environments," said NIEHS Director Kenneth Olden, Ph.D. "However, general cleaning practices, proven extermination techniques and consistent maintenance methods can bring these allergen levels under control."

Cockroach allergens come from several sources such as saliva, fecal material, secretions, cast skins, and dead bodies. People can reduce their exposure to cockroach allergen by eating only in the kitchen and dining room, putting non-refrigerated items in plastic containers or sealable bags, and taking out the garbage on a daily basis. Other measures include repairing leaky faucets, frequent vacuuming of carpeted areas and damp-mopping of hard floors, and regular cleaning of counter tops and other surfaces.

NIH provided $7.5 million to researchers at the University of Texas Southwestern Medical Center at Dallas and seven other research institutions, including the Data Coordinating Center at Rho, Inc., for the three-year study.

"We found that a majority of homes in Chicago, New York City and the Bronx had cockroach allergen levels high enough to trigger asthma symptoms, while a majority of homes in Dallas and Seattle had dust mite allergen levels above the asthma symptom threshold," said Dr. Rebecca Gruchalla, associate professor of internal medicine and pediatrics at the University of Texas Southwestern Medical Center and lead author of the study.

"We also discovered that the levels of both of these allergens were influenced by housing type," noted Gruchalla. "Cockroach allergen levels were highest in high-rise apartments, while dust mite concentrations were greatest in detached homes."

While cockroach allergen exposure did produce an increase in asthma symptoms, researchers did not find an increase in asthma symptoms as a result of exposure to dust mite and pet dander. "Children who tested positive for, and were exposed to, cockroach allergen experienced a significant increase in the number of days with cough, wheezing and chest tightness, number of nights with interrupted sleep, number of missed school days, and number of times they had to slow down or discontinue their play activity," said Gruchalla.

While cockroaches are primarily attracted to water sources and food debris, house dust mites, microscopic spider-like creatures that feed on flakes of human skin, reside in bedding, carpets, upholstery, draperies and other "dust traps." Dust mite allergens are proteins that come from the digestive tracts of mites and are found in mite feces.

Researchers tested 937 inner-city children with moderate to severe asthma symptoms. The children, ages 5 to 11, were given skin tests for sensitivity to cockroach and dust mite allergens, pet dander, and mold. Bedroom dust samples were analyzed for the presence of each allergen type.

A1 lets lungs breathe a sigh of relief

Sun, 03 Apr 2005 13:11:00 PST

( from http://www.rxpgnews.com ) Patients with lung and heart disease are commonly given supplemental oxygen, however very high concentrations of oxygen administered for extended periods of time can trigger lung injury.

The mechanism underlying this lung injury has not been characterized. In a study appearing in the April 1 issue of The Journal of Clinical Investigation, Jack Elias and colleagues from Yale University demonstrate that a protein called A1 is a critical regulator in this type of lung injury.

The authors also show that high oxygen concentration stimulates A1, that A1 regulates death of cells in the lung, and that it plays a central role in the induction of other proteins that modulate programmed cell death. In mice lacking A1, the harmful effects of oxygen are intensified whereas overexpressing A1 decreases lung cell death in the presence of oxygen.

In an accompanying commentary, G.R.Scott Budinger and Jacob Sznajder writes that these studies will "influence future investigations into the molecular mechanisms by which these [A1] pathways become activated to contribute tolung injury."

Asthma patients' immune systems respond differently with allergies

Sun, 03 Apr 2005 10:33:00 PST

( from http://www.rxpgnews.com ) Researchers from the University of Chihuahua in Mexico report that immune systems of patients with asthma responded differently to a common laboratory challenge, depending on whether their white blood cells had been obtained during a time when they were suffering from common season allergic rhinitis or when they were free of such allergic symptoms.

Asthma is a chronic obstructive inflammatory lung disease with symptoms including wheezing, coughing, chest tightness, and shortness of breath. Asthma attacks can be triggered by viral upper respiratory infections, exercise, extreme temperature condition, and chemical irritants and also by the same allergens that cause seasonal allergies to pollen or mold spore or perennial allergies to dust mites, cockroaches, feathers, animal fur and other allergens. In fact, the vast majority of patients with asthma also experience one or both of these forms of allergy, with the same symptoms of frequent sneezing, itchy eyes, runny nose and nasal stuffiness.

In people with and without asthma, the body's response to allergens is based in the leukocytes, or white blood cells, that rush to defend the body against foreign agents. The leukocytes produce cytokines that mediate and regulate immunity and inflammation to an immune stimulus. Because people with asthma and allergy share this common etiological pathway, they show different expressions of their disease with a wide variety of therapeutic responses. That's why Dr. Leal-Berumen's laboratory became interested in studying the different response of these cytokines in asthma patients when they were and were not experiencing allergies.

The study involved 10 patients with clinical diagnosis for allergic rhinitis, who also have or had had asthma. Peripheral blood leucocytes were obtained both during rhinitis symptoms and during a period when the patients were not experiencing rhinitis symptoms, then cultured with a type of prostaglandin, a substance that causes inflammation. In nine of the ten asthma patients, leucocytes produced a greater amount of the cytokine IL-5 when isolated during the no symptoms season, whereas five of the nine showed a greater production of IL-13, another cytokine, during the symptoms season. These results indicate that leucocytes from the same patient present different susceptibility to IL-5 and IL-13 production depending on the presence or absence of allergic rhinitis symptoms.

Dr. Leal-Berumen says the group now plans to study cell response to more specific allergens similar to what was done with the prostaglandin challenge. They believe these studies will contribute to a better understanding of asthma, allergy and other inflammatory disease and guide the pharmacogenetic development of new therapies.

Zileuton Shows Significant Benefit in Prevention and Chronic Treatment of Asthma

Sat, 02 Apr 2005 08:39:00 PST

( from http://www.rxpgnews.com ) Critical Therapeutics, Inc. (Nasdaq: CRTX), today announced that it has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for the Company's investigational asthma drug ZYFLO(R) Filmtab(R) (zileuton tablets). Approval of the sNDA would allow Critical Therapeutics to begin marketing its version of ZYFLO in the United States.

"This is an exciting event that moves us one step closer toward our goal of becoming a fully integrated biopharmaceutical company," said Paul Rubin, M.D., president and chief executive officer of Critical Therapeutics. "We anticipate launching ZYFLO in the second half of 2005, contingent upon regulatory approval of our sNDA."

The FDA approved ZYFLO in 1996 for the prevention and chronic treatment of asthma in patients 12 years of age and older. Critical Therapeutics in-licensed worldwide rights to ZYFLO in March 2004 and to other formulations of zileuton for a range of inflammatory diseases and conditions in December 2003.

ZYFLO has been commercially unavailable since early 2004 when commercial supply was depleted. Critical Therapeutics is required to submit an sNDA for ZYFLO because it is changing the manufacturing process and transferring production of the zileuton active pharmaceutical ingredient and the tablet formulation to third-party sites.

"ZYFLO is the only asthma treatment that blocks the activity of the enzyme responsible for producing an array of inflammatory mediators, most notably leukotrienes," Dr. Rubin said. "We believe this novel mechanism will allow ZYFLO to occupy a unique position in the treatment of asthma."

Clinical supply of ZYFLO currently is available through an open-label Phase IIIb study for patients who previously used and benefited from ZYFLO and need it to control their asthma symptoms. For more information regarding the open-label study, please visit the related link.

ZYFLO is not indicated for use in the reversal of bronchospasm in acute asthma attacks, including status asthmaticus. For full prescribing information, please visit the related link.

Mometasone furoate Shows Substantial Improvement in Lung Function in Persistent Asthma

Fri, 01 Apr 2005 09:14:00 PST

( from http://www.rxpgnews.com ) Schering-Plough Corporation today announced that the U.S. Food and Drug Administration (FDA) has approved the use of ASMANEX® TWISTHALER® 220 mcg (mometasone furoate inhalation powder) for the first-line maintenance treatment of asthma as preventive therapy in patients 12 years of age and older.

Mometasone furoate is also the only inhaled asthma controller therapy approved for once daily initiation and management of asthma in patients previously treated with bronchodilators alone or inhaled corticosteroids. Clinical studies with Mometasone furoate have shown substantial improvement in lung function, decreased use of rescue medication, decreased incidence of nighttime awakenings and significant improvements in daytime symptoms such as coughing and wheezing.

"Mometasone furoate is a highly effective first-line therapy that offers health care professionals and their patients a once daily therapy to help prevent persistent asthma symptoms," said Harold Nelson MD, Professor of Medicine, Department of Medicine, National Jewish Medical and Research Center, University of Colorado Health Science Center in Denver, Colo.

In a clinical trial, Mometasone furoate showed substantial improvement in lung function and decreased albuterol (rescue medication) use compared with placebo, as evidenced by a 12-week, multicenter, randomized, double-blind, placebo-controlled study of 400 patients with persistent asthma previously dependent on inhaled corticosteroid therapy.

At endpoint, patients who received Mometasone furoate had a significant improvement in nighttime awakenings and daytime symptoms -- providing night and day relief.

The NAEPP (National Asthma Education and Prevention Program) asthma treatment guidelines recommend single-ingredient, low-dose inhaled corticosteroid as the foundation of therapy for mild persistent asthma management.

Asthma is a chronic inflammatory lung disease that affects a growing number of Americans each year. The number of cases has grown steadily in the past 20 years, making it one of the leading public health problems in the U.S.

As many as 20 million people suffer from asthma. On an annual basis, this leads to at least two million emergency room visits and more than 5,000 deaths. Additionally, this accounts for an annual direct cost of treatment of $9.4 billion and approximately 14.5 million missed work days. Asthma symptoms such as coughing, wheezing, and shortness of breath occur during the day and night, impacting multiple aspects of patients' lives. Daytime symptoms can affect activities ranging from exercise to going to school or work. Nighttime symptoms interfere with patients' ability to sleep.

Mometasone furoate was discovered and developed by Schering-Plough Research Institute and is currently approved for asthma treatment in more than 40 countries. Mometasone furoate, the active ingredient in Mometasone furoate, was first introduced in the U.S. in 1987 as the dermatologic ointment, ELOCON (mometasone furoate ointment) and in 1997 as the nasal spray,NASONEX (mometasone furoate monohydrate).

In clinical trials with Mometasone furoate, adverse events were generally mild to moderate in severity. The following incidence of common adverse experiences is based on double-blind data from ten placebo-controlled clinical trials involving a total of 2,809 patients previously maintained on inhaled steroids and/or bronchodilators (1,140 males, 1,669 females, age 12-83 years), who were treated for up to 12 weeks with the Mometasone furoate product, an active comparator, or placebo.

Adverse events were generally mild to moderate in severity and included headache, allergic rhinitis, pharyngitis, upper respiratory infection, sinusitis, oral candidiasis, dysmenorrhea, musculoskeletal pain, back pain, dyspepsia, myalgia, abdominal pain, and nausea.

Mometasone furoate offers an effective inhaled corticosteroid to control asthma symptoms in an easy to use device that was awarded the DuPont Award for innovation in packaging. The Mometasone furoate Inhaler employs an inhalation- driven device that does not use a propellant, thus eliminating the need for hand-breath coordination, and it provides patients with a numeric dose counter that provides a visual indication of the remaining doses.

Recommended starting dose of Mometasone furoate is one inhalation daily in the evening for patients previously treated with bronchodilators alone or inhaled corticosteroids. For patients previously maintained on oral corticosteroids, the recommended starting dose of Mometasone furoate is two inhalations twice daily.

Mometasone furoate is expected to be available in the U.S. in the autumn of 2005.

Association found between high body mass index (BMI) and asthma

Tue, 01 Mar 2005 17:34:00 PST

( from http://www.rxpgnews.com ) In a cohort of New Zealand children who were followed from birth to age 26, overweight, expressed as higher body mass index, was significantly associated with asthma wheeze in females, but not in males.

The investigators found that the association between high body mass index (BMI) and asthma occurred in females who became overweight during late adolescence and early adulthood.

At age 9, there was no evidence of an association, but by 26 it was statistically significant. Analysis of data was performed in 1,037 children at ages 9, 11, 13, 15, 18, 21, and 26. Information on asthma and measurements of lung function, airway responsiveness, and atopy (inherited tendency toward allergic reaction) were obtained on each of these occasions. At each age checked, investigators calculated the young person's age, height, and weight in light clothing without shoes to determine BMI. The association between raised BMI and asthma appeared to emerge in late adolescence, according to the investigators.

The participants were part of the Dunedin Multidisciplinary Health and Development Study which involved children (52 percent male) who were born between April 1971 and March 1973. At age 26, 980 (96 percent of the 1,019 living study members were still participating.

Pulmonary complications after nonthoracic surgery are more frequent than cardiac complications

Tue, 01 Mar 2005 17:34:00 PST

( from http://www.rxpgnews.com ) Of the approximately 45 million North Americans who will undergo nonthoracic surgery during the next year, over 1 million will experience a postoperative pulmonary complication, an event which could have enormous implications for both the patient and health care system. Canadian investigators checked 1,055 consecutive patients attending a presurgical admission clinic at a university hospital to uncover risk factors for pulmonary complications after elective nonthoracic surgery.

According to the authors, pulmonary complications after nonthoracic surgery are more frequent than cardiac complications and are associated with a greater increase in hospital length of stay. Of the 1,055 patients in the study, 28 (2.7 percent) suffered a postoperative pulmonary complication within 7 days after surgery.

Thirteen patients developed respiratory failure requiring ventilatory support, 9 contracted pneumonia, 5 had collapse of lung tissue (atelectasis) requiring bronchoscopic intervention, and 1 suffered a collection of air or gas in the pleural cavity causing the lung to collapse. One patient who had pneumonia subsequently died. The length of stays for patients with postsurgical pulmonary complications were almost 28 days, as contrasted with 4.5 days for patients who had no postsurgical complications.

The four factors associated with an increased risk for pulmonary complications following nonthoracic surgery were: age over 65; a positive cough test (meaning the patient continued to cough after taking a deep breath and providing a voluntary cough); placement of a nasogastric tube at the time of the operation; and long-duration anesthesia (2.5 hours or longer). The researchers called for steps to minimize perioperative intubation unless it is judged very necessary on clinical grounds.

Montelukast significantly reduced Asthma exacerbations in young children

Wed, 16 Feb 2005 19:33:00 PST

( from http://www.rxpgnews.com ) Montelukast, a leukotriene receptor antagonist, significantly decreased the rate of exacerbations and lengthened the time between exacerbations in 2- to 5-year-old asthma patients who suffered from intermittent symptoms. The researchers pointed out that montelukast significantly reduced by almost 32 percent the rate of exacerbations over 12 months, as compared with results from patients on placebo. The average rate of exacerbation episodes was 1.60 episodes per patient per year, compared with 2.34 for placebo. (Leukotrienes are biologically active compounds that function as chemical mediators. They have vasoactive properties that help regulate allergic and inflammatory reactions. Medical antagonists are designed to counteract specific functions.) According to the authors, asthma usually begins and has its greatest prevalence in children younger than 5 years.

This age group often has intermittent symptoms, which include long assymptomatic periods interrupted by episodes of asthma generally in association with the common cold. Viral infections, predominately with rhinovirus, account for up to 85 percent of childhood asthma exacerbations and daily symptoms. The investigators claim that there are usually minimal symptoms between episodes. The 1-year study directed at exacerbation control was conducted at 68 sites in 23 countries. It involved 278 children receiving low-dose montelukast once a day for 12 months, along with 271 young participants receiving placebo. According to the authors, montelukast delayed the median time to first exacerbation by approximately 2 months. It also significantly reduced the overall rate of corticosteroid use by almost 32 percent and the rate of inhaled corticosteroid use by almost 40 percent. However, although the use of montelukast reduced exacerbations in intermittent asthma, the investigators said that they do not necessarily advocate year-round regular treatment with the compound. They noted that since exacerbations tended to be seasonal, therapy should begin before the viral season when the exacerbation rate is high.

Data shows care of patients with COPD not good enough in UK

Fri, 11 Feb 2005 21:07:00 PST

( from http://www.rxpgnews.com ) More than one in ten patients with Chronic Obstructive Pulmonary Disease (COPD) admitted to hospital is dead within 90 days of admission, and over 1 in 3 are readmitted to hospital during that time.

These startling figures are outlined in the first ever comprehensive national audit of this condition, undertaken by the Royal College of Physicians (RCP) and the British Thoracic Society (BTS) between 2003/4. 234 hospitals in the UK took part in the audit, which is aimed at finding out ways of improving quality of care this is the first time the audit covered the whole of the UK.

COPD is a chronic disabling condition in which the patients airways have become obstructed, making it difficult to breathe, and the lungs themselves may have become damaged. It is the fifth most common cause of death in England and Wales. COPD accounts for more than 10% of all acute admissions, which makes it a priority area for all hospitals concerned with effective management of acute medical admissions, and for Primary Care Trusts trying to improve care for long-term conditions.

Patients have a better chance of survival if the unit they are admitted to has a respiratory consultant. However, only 30% of patients are admitted under a respiratory specialist, and 33% of Trusts have fewer than the BTS recommended minimum of 2 on any one site. Over half of patients (52%) are not under the care of a respiratory specialist whilst in hospital. The results of the audit show that an increase in the number of respiratory physicians and nurse specialists is needed to improve the care of patients with COPD.

Length of stay is also reduced in units led by respiratory specialists - these units are more likely to have an Early Discharge Scheme, which also reduces length of stay. More hospitals should implement Early Discharge Schemes and pulmonary rehabilitation. Non-invasive ventilation was available in 89% of units but the audit showed that this wasnt always used for patients who needed it. Fewer than one in seven patients who die in hospital receive added ventilatory support.

To prevent the wide variations in practice between hospitals the NICE guidelines should be implemented nationally. The Healthcare Commission could play a vital role in the long-term success of these measures by monitoring standards of care and management of COPD patients as part of their standards assessment. National Service Frameworks in key clinical areas have proved effective in raising standards of care - a National Service Framework for Respiratory Medicine would be a powerful tool to drive up standards of care nationally.

Dr Mike Roberts, COPD Associate Director of the RCPs Clinical Effectiveness and Evaluation Unit, said:

Care received by COPD patients remains a lottery with many not benefiting from the potentially life-saving and life-enhancing care provided by a specialist Respiratory team.

Professor Andrew Peacock of the BTS said:

This research is really worrying and underlines the need for more lung specialists across the board. It also underlines why the Government must give the green light as soon as possible for a National Service Framework (NSF) for respiratory disease. COPD must be given a greater priority within the NHS at both a local and national level.

An NSF is vital if we are to achieve uniform standards of care for patients with all lung conditions. It will send a priority signal to local NHS Trusts that COPD management is a real priority helping converts services such as non invasive ventilation and pulmonary rehabilitation from nice to to must do.

Dame Helena Shovelton, Chief Executive of the British Lung Foundation said:

This audit highlights the huge problem of COPD in the UK. The British Lung Foundation has campaigned for many years for better care and treatment for patients with COPD, and petitioned Downing Street for pulmonary rehabilitation to be available to everyone.

There are more than 900,000 people diagnosed with COPD in the UK and a suspected further 1.5 million undiagnosed - and it is time that the Government made COPD a priority.

Marijuana smoking may increase risk of respiratory infections

Thu, 13 Jan 2005 14:51:00 PST

( from http://www.rxpgnews.com ) Smoking marijuana is associated with increased risk of many of the same symptoms as smoking cigarettes--chronic bronchitis, coughing on most days, phlegm production, shortness of breath, and wheezing, according to a Yale study published in the Journal of General Internal Medicine.

In addition, marijuana smoking may increase risk of respiratory exposure by infectious organisms, such as fungi and molds, since cannabis plants are contaminated with a range of fungal spores, said Brent Moore, assistant professor of psychiatry at Yale School of Medicine and lead author of the study.

"Because more than two million adult Americans are heavy marijuana smokers, these risks represent a potentially large health burden," Moore said. "Marijuana smokers use more medical services for respiratory problems, and these demands are likely to increase as the population of heavy marijuana smokers ages."

The findings were based on 6,728 questionnaires completed by adult men and women, 20 to 59 years old, in 1988 and 1994. The data was from the National Health and Nutrition Examination Survey and was thought to provide the broadest snapshot to date of marijuana use and its effect on the lungs in a sample of U.S. citizens.

Current marijuana use was defined as self-reported lifetime use and use at least one day in the prior month. Seventy seven percent of marijuana smokers also smoked tobacco. The analysis statistically controlled for the number of cigarettes smoked per day. Individuals who smoked both marijuana and tobacco had increased rates of respiratory symptoms compared to those who smoked tobacco only.

"Our interest is in the additive effect of marijuana," Moore said.

Role for the A1 adenosine receptor in protecting against asthma

Tue, 04 Jan 2005 19:35:00 PST

( from http://www.rxpgnews.com ) Levels of the signaling molecule adenosine are increased in the lungs of asthmatics, and elevations of adenosine correlate with the degree of airway inflammation, suggesting that adenosine may play a provocative role in acute asthma attacks. Therefore much research has been focused on drugs that may potentially interact with known adenosine receptors the activation of which can have proinflammatory or anti-inflammatory effects, depending on the receptor type. Theophylline, the most widely prescribed drug for the treatment of airway disease worldwide, is able to block both pro- and anti-inflammatory actions of adenosine, potentially decreasing its efficiency. Researchers are now focused on determining the role of each adenosine receptor so that they may design drugs to interact with specific receptors and reduce airway inflammation.

As described in a report in the January 3 issue of the Journal of Clinical Investigation, Michael Blackburn led a team of researchers at the University of Texas Health Science Center and the National Institutes of Health to examine the role of the A1 adenosine receptor (A1AR) in a mouse model of lung injury and inflammation in which these mice possess elevated adenosine levels.

Blackburn et al. show that mice lacking A1AR die shortly after birth from severe inflammatory lung disease, indicating that A1AR serves an anti-inflammatory and thus protective role in the development of lung inflammation. The findings are particularly relevant in light of the fact that drugs that block A1AR are currently being investigated as a potential treatment for asthma.

In an accompanying commentary, Stephen Tilley and Richard Boucher from the University of North Carolina discuss this study and the potential clinical benefits of blocking A1 receptors in the airways of asthma patients.

Higher procalcitonin levels are strong predictors of unfavorable outcome in ventilator-associated pneumonia

Mon, 03 Jan 2005 18:36:00 PST

( from http://www.rxpgnews.com ) Higher procalcitonin levels on days 1, 3, and 7 following diagnosis are strong predictors of unfavorable outcome in microbiologically confirmed ventilator-associated pneumonia (VAP), the most frequent hospital-acquired infection in patients on mechanical ventilation. The investigators studied procalcitonin as a prognostic marker in VAP among 63 patients enrolled in the study. Among the 63 patients, 38 (60 percent) had unfavorable outcomes. There were 14 deaths, 21 recurrences, and 3 documented extra-pulmonary infections, with the average time to unfavorable outcome at about 16 days. Their results showed that serum procalcitonin concentrations decreased during the clinical course of VAP but were higher in patients with unfavorable outcomes than in those with favorable results. (Procalcitonin is the precursor molecule of calcitonin, which regulates calcium concentrations in the blood.

Procalcitonin levels rise during bacterial infections but not during either viral infections or inflammatory reactions of a non-infectious origin. Serum levels of procalcitonin are very low in healthy individuals.) Other clinical and biologic factors, such as white blood cell counts or C-reactive protein, were not able to discriminate between patients whose outcome would be unfavorable, as compared with favorable outcomes. The investigators commented that early identification of patients at high risk of death or VAP recurrence could provide an opportunity to change the treatment strategy to improve outcome. The study appears in the first issue for January 2005 of the American Thoracic Society's peer-reviewed American Journal of Respiratory and Critical Care Medicine.

BERYLLIUM SENSITIZATION PROGRESSES TO CHRONIC BERYLLIUM DISEASE

Mon, 03 Jan 2005 18:34:00 PST

( from http://www.rxpgnews.com ) In a clinical follow-up study lasting almost 5 years, researchers have shown that individuals who are beryllium sensitive progress to chronic beryllium disease at a rate of 6 to 8 percent per year. Seventeen of 55 persons identified over 10-year period with beryllium sensitization who had had no evidence of chronic beryllium disease on initial lung biopsy showed diseased tissue on later clinical evaluations. The investigators found that 38 of the 55 remained beryllium sensitized after an average follow-up of 4.8 years.

(Chronic beryllium disease is a lung inflammation caused by inhaling dust or fumes that contain beryllium. Beryllium is a silvery-white metallic chemical element that forms strong, hard alloys with several metals, including copper and nickel. Today, the metal is used in the aerospace industry and in the atomic energy and weapons industries.) The researchers studied 55 individuals who showed beryllium sensitization during tests at their institution. Eighty percent were employed in the nuclear weapons field. On average, it had been almost 25 years since their first exposure to beryllium. Beryllium sensitization was defined as beryllium-specific immune response demonstrated by two or more abnormal beryllium lymphocyte proliferation test results, with no evidence of nodular granulated tissue from a lung biopsy. Chronic beryllium disease was defined as abnormal blood test results plus cell infiltrates in lung tissue from a biopsy. The investigators said that it would be important to monitor this cohort over future years in order to determine whether all individuals with beryllium sensitization would eventually develop granulomatous disease. They also wanted to expand their follow-up to more recently identified sensitized individuals.

Longterm airflow obstruction in survivors of bronchopulmonary dysplasia

Mon, 03 Jan 2005 18:30:00 PST

( from http://www.rxpgnews.com ) In a study of school-age children who were survivors of bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, researchers uncovered long-term airflow limitation as demonstrated by impaired lung function test results, while at the same time finding low levels of a marker of pulmonary cellular dysfunction, exhaled nitric oxide. The investigators studied 31 school-age survivors of BPD, comparing their test results with 31 patients with asthma, 31 preterm children without BPD, and 31 healthy control children born at term. (BPD was first described in premature neonates in neonatal intensive care units who survived respiratory distress syndrome after suffering chronic lung injury induced by mechanical ventilation and exposure to high oxygen concentrations.)

According to the researchers, the children with BPD in the study had significantly lower exhaled nitric oxide levels than did either the healthy control subjects or the preterm children without BPD. For their individual lung function test values, 9 of the subjects with BPD had results that were 70 percent or less of the normal predicted value. The children with asthma had a similar degree of airflow limitation. The authors said that although BPD survivors and those with asthma share some clinical and functional features, the remarkable difference in exhaled nitric oxide values suggests that airflow limitation in the two obstructive lung diseases is related to distinctive individual pathophysiologic pathways that ought to be properly identified. Unfortunately, to date, studies on the problem beyond infancy are lacking. The research appears in the first issue for January 2005 of the American Thoracic Society's peer-reviewed American Journal of Respiratory and Critical Care Medicine.

High-risk asthma patients reduce asthma medication use in days after hospitalization

Thu, 16 Dec 2004 16:37:00 PST

( from http://www.rxpgnews.com ) In a study of high-risk patients with severe asthma who were hospitalized for serious exacerbations, researchers showed that within 7 days of discharge their use of prescribed inhaled corticosteroids and oral steroids had fallen rapidly to approximately 50 percent of their prescribed dose. The investigators measured post-hospital adherence in 52 inner city asthmatics by means of electronic medication monitors, self-report, canister weight (for inhaled corticosteroids) and pill counts (for oral corticosteroids). The researchers noted that their results provided strong evidence that even under optimal conditions with free medications and intensive inpatient education, discontinuation of both inhaled corticosteroids and oral corticosteroids was common within 7 days of discharge from the hospital.

The participants were almost exclusively African-American with 65 percent (34 patients) being female, and almost half having a history of near-fatal asthma. For the most part, they were unemployed and unmarried. Asthma affects 15 to 20 million people in the U.S. Although effective medical therapies are available, the illness results in severe asthma exacerbations, causing 465,000 hospitalizations and 5,000 deaths per year.

Hospitalization and death related to asthma exacerbations are two to three times more likely among African-Americans and minority patients, according to the authors. The research appears in the second issue for December 2004 of the American Thoracic Society's peer-reviewed American Journal of Respiratory and Critical Care Medicine.