RxPG News : COPD

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

Tue, 15 Dec 2009 04:59:12 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."

Mediterranean diet halves risk of progressive lung disease

Mon, 14 May 2007 20:08:56 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.

COPD patients using beta-agonist inhalers are at risk

Mon, 10 Jul 2006 06:14:37 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 more than double death rate in COPD patients

Wed, 05 Jul 2006 15:17:37 PST

Lung function test underused in patients with COPD

Wed, 14 Jun 2006 20:13:37 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 20:04:37 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 20:20:37 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 20:01:37 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."

Breathing Heliox 28 significantly improve the exercise performance in COPD

Sat, 15 Apr 2006 18:47:37 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."

Combined treatment cuts inflammatory cells in chronic obstructive pulmonary disease

Mon, 03 Apr 2006 06:47:37 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.

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

Mon, 13 Mar 2006 20:30:37 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.

Study Shows Benefits of Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease

Mon, 15 Aug 2005 18:01:38 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.

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

Thu, 21 Jul 2005 23:22:38 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."

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

Mon, 18 Apr 2005 09:02:38 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.

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

Fri, 11 Feb 2005 21:06:38 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.