Common Gene Disorder Doubles Risk Of Lung Cancer, Even Among Nonsmokers

Mayo Clinic researchers have found that carrying a common genetic disorder doubles the risk of developing lung cancer in smokers and nonsmokers.


The study is published in the May 26 issue of the Archives of Internal Medicine, a journal published by the American Medical Association.


Researchers found that the genetic disorder, alpha-1 antitrypsin deficiency (?▒1ATD), could explain up to about 12 percent of lung cancer patients in this study and likely represents the same widespread risk in the general population. "This is a seriously underdiagnosed disorder and suggests that people who have lung cancer and chronic obstructive pulmonary diseases (COPD) in their families should be screened for these gene carriers," says Ping Yang, M.D., Ph.D., a Mayo Clinic epidemiologist and lead investigator on the study.


The current standard diagnostic test measures protein produced by the gene. Because of the cost and limited availability of the test, it's not suitable for general screenings. A less expensive DNA-based gene panel test is being developed.


The World Health Organization estimates that at least 10 million Americans and 120 million people worldwide are ?▒1ATD carriers. According to Dr. Yang, this study shows that the disorder "is among the highest for major gene effects on the risk of a common cancer."


A normal ?▒1AT gene produces a protein that stops enzymes from breaking down elastin, which keeps lung tissue elastic for normal function. Carriers of ???1ATD commonly develop emphysema and/or chronic obstructive pulmonary disease (COPD). Prior to this study, the connection between ?▒1ATD, COPD and lung cancer risk had not been established.


"It has been suspected that ?▒1ATD increased susceptibility to lung cancer," says Dr. Yang, "but this is the first solid evidence that supports and quantifies this risk.


"Importantly, our results support the hypothesis that the excess risk of lung cancer among patients with COPD may be a result of lung tissue damage from emphysema, or chronic infection or inflammation of the lungs, or both," she says.


Individuals who are ?▒1ATD carriers should have lung function checked on a routine basis and should avoid potential lung carcinogens. "We found people who carry these genes are more vulnerable to carcinogen-containing tobacco smoke, even secondhand smoke, than noncarriers," says Dr. Yang.


In this study, a team of 12 researchers looked at three different groups: 1,443 patients with lung cancer treated at Mayo Clinic from 1997 to 2003; a control group of 797 residents in the community; and a second control group of 902 siblings of the lung cancer patients.


They found that:


The ?▒1ATD carrier rate among 1,443 genotyped patients with lung cancer was 13.4 percent, compared to 7.8 percent among unrelated control participants.















All ?▒1ATD gene carriers were at a similarly greater risk of developing lung cancer, regardless of smoking status. Those who had never smoked were at a 2.2-fold higher risk; light smokers had a twofold greater risk; and moderate to heavy smokers had a 2.3-fold increased risk. Although there's no absolute definition, less than 20 pack-years of smoking cigarettes is defined as light; more than 40 pack-years as heavy. A pack-year is the number of packs of cigarettes smoked per day multiplied by the number of years the person has smoked.


A history of COPD increased lung cancer risk significantly for light, moderate and heavy smokers, but affected those who had never smoked the most an almost sixfold increased risk.


Increased lung cancer risk among ?▒1ATD carriers is independent of a family history of lung or other cancers.


The estimated attributable risk for ?▒1ATD carriers in this study among those who never smoked and among heavy smokers was 11 percent to 12 percent, suggesting that the genetic disorder might explain a significant proportion of lung cancer in the general population. The majority of study participants were of European descent, the population in which this genetic disorder is common.


Although the study helps explain why people who have never smoked can develop lung cancer, it doesn't mean that people who don't have the gene won't develop lung cancer, says Dr. Yang. "Smoking remains the overwhelming risk factor for lung cancer development."

NLHEP Educational Materials Available For RC Week And COPD Month

The National Lung Health Education Program (NLHEP), a sister organization of the AARC, has both patient and professional educational materials available for distribution during these important upcoming events on the respiratory therapist's calendar:


For patients:


"Save Your Breath America" (revised in 2006) is an easy-to-read booklet containing important information for patients with COPD. "COPD Wallet Card" is designed to allow the patient to carry pertinent medical information in his or her wallet-including doctors' names, emergency contact and insurance information, record of vaccinations, along with a list of COPD and other medications. This folded card is about the size of a credit card and comes in a plastic sleeve. "NLHEP brochure" outlines our mission to increase awareness and also has 20 FAQs for patients.


For professionals:


"Long Term Oxygen Therapy: History, Scientific Foundations, and Emerging Technologies" presents the history of LTOT and the state of our knowledge about the scientific basis for LTOT. This booklet is an ideal addition to your departmental library-and as a handout to those who prescribe supplemental oxygen. The booklet "Simple Office Spirometry for Primary Care Practitioners" is perfect to share with the primary care doctors you work with in your health care setting. It can also be the perfect workshop tool for teaching their staffs about spirometry. "COPD Pocket Consultant" has just been revised to reflect changes to the GOLD Guidelines, which outline recommended treatment for COPD. This handy pocket guide is intended for use by physicians and other health care professionals who work with COPD patients. It contains the Fletcher Curve, risk factors for COPD, and suggested therapies for each stage of the disease.

aarc

First Patient Enrols In Aridol COPD Trial

Pharmaxis
(ASX: PXS; Nasdaq: PXSL) today announced that the first patients have been
enrolled in a Swiss clinical trial evaluating the ability of Aridol to
predict the response to inhaled steroids in patients with Chronic
Obstructive Pulmonary Disease (COPD).


The independent investigator-led trial will test the hypothesis that
patients with COPD are more likely to have a good clinical response to
inhaled steroids if they have a positive Aridol challenge test. The global
prescribing guidelines recommend the use of steroids only for patients with
moderate to severe COPD.



COPD is a lung disease in which the lungs are damaged, restricting
airflow and making it difficult for sufferers to breathe. COPD is a major
cause of illness and the fourth leading cause of death in the developed
world.



Pharmaxis CEO, Alan Robertson said, "When to add inhaled steroids to
bronchodilator therapy in COPD remains an important clinical dilemma and it
is not ideal to wait until the patient has developed severe disease. To
date, there is no proven method available to guide physicians in this
decision. We believe that an early and objective indicator could lead to
changes in treating one of the world's most prevalent diseases affecting
over 20 million people in the U.S. alone."



The trial follows on from two earlier studies: a pilot study by the
same investigator, and an Australian Phase II trial completed by Pharmaxis
earlier this year. The trial will follow a larger group of patients
diagnosed with COPD and receiving baseline bronchodilator therapy with
Spiriva(TM). The trial is scheduled to complete during the first half of
2008.



After a one month period during which patients inhale Spiriva alone,
the 100 participants will be tested with Aridol then randomised to receive
inhaled steroids or placebo. Lung function, response to Aridol,
exacerbations and changes in quality of life will be measured at the end of
the trial.



To find out more about Pharmaxis, go to pharmaxis.au.



Aridol is a registered trade mark of Pharmaxis



Spiriva is a registered trade mark of Boehringer-Ingelheim



Forward-Looking Statements



The statements contained in this press release that are not purely
historical are forward-looking statements within the meaning of Section 21E
of the Securities Exchange Act of 1934, as amended. Forward-looking
statements in this press release include statements regarding our
expectations, beliefs, hopes, goals, intentions, initiatives or strategies,
including statements regarding the potential for Aridol and/or Bronchitol.
All forward-looking statements included in this press release are based
upon information available to us as of the date hereof, and we assume no
obligation to update any such forward-looking statement as a result of new
information, future events or otherwise. We can not guarantee that any
product candidate will receive FDA or other regulatory approval or that we
will seek any such approval. Factors that could cause or contribute to such
differences include, but are not limited to, factors discussed in the "Risk
Factors and Other Uncertainties" section of our Form 20-F lodged with the
U.S. Securities and Exchange Commission.


Pharmaxis Ltd

pharmaxis.au


View drug information on Spiriva HandiHaler.

Understanding Shortness Of Breath And Limitations In COPD

Chronic obstructive pulmonary disease (COPD) is a major public health problem, and a deeper understanding of its most prominent symptom, dyspnea, may lead to improvements in the manner in which it is assessed and treated.


The objective of this study was to identify important patient-centered concepts of dyspnea and associated activities in order to develop a dyspnea-specific conceptual model for COPD.


We identified five primary areas of the dyspnea experience: breathlessness, fatigue, activity modification, activity limitation and emotional response. Major influences on dyspnea were individual exertion, exposure to environmental factors, dyspnea-related fear, needing to stop or scale back activities, taking more time to do things, and using adaptive measures or equipment.


Estimates of the number of US patients affected by COPD ranges from 10 million to 24.5 million. It is currently the fourth cause of death in the US, and a significant degree of health care utilization is attributed to it, including some 726,000 hospitalizations, 1.5 million visits to the emergency room and approximately 8 million outpatient physician visits. COPD is also a major source of disability and impaired health-related quality of life.


Says Dr. Victorson, "Such a patient-centered approach to better understanding dyspnea within the context of COPD has not been conducted, yet it is essential to evaluating disease and treatment effects. Our next step is to develop a new self report measurement tool based on these findings that will assess important components of our proposed model.


This will be discussed in Value in Health, the official journal of the International Society for Pharmacoeconomics and outcomes Research.


Value in Health (ISSN 1098-3015) publishes papers, concepts, and ideas that advance the field of pharmacoeconomics and outcomes research and help health care leaders to make decisions that are solidly evidence-based. The journal is published bi-monthly and has a regular readership of over 4,000 clinicians, decision-makers, and researchers worldwide.


ISPOR is a nonprofit, international organization that strives to translate pharmacoeconomics and outcomes research into practice to ensure that society allocates scarce health care resources wisely, fairly, and efficiently.


Source
ISPOR

Significant Improvements Shown In Concomitant Use Of Perforomist & Tiotropium For COPD

Data presented at the International Conference of the American Thoracic Society (ATS) demonstrate that concomitant therapy with Perforomist™ Inhalation Solution (formoterol fumarate inhalation solution; FFIS), delivered by nebulization, and Spiriva® (tiotropium; TIO) is significantly more effective than treatment with tiotropium alone.



Perforomist™ Inhalation Solution was approved in 2007 by the FDA for long-term, twice-daily maintenance treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. It is the only FDA-approved nebulized formoterol fumarate.



Donald P. Tashkin, MD, FACP, FCCP, Professor of Medicine, David Geffen School of Medicine at the University of California at Los Angeles and lead clinical investigator, presented the results from "Addition of Nebulized Formoterol Fumarate to Tiotropium Treatment Relieves Dyspnea and Symptoms in COPD Patients" in a poster session.



"In this study there was a significant improvement in patients treated concomitantly with Perforomist™ nebulized formoterol fumarate and tiotropium over tiotropium alone," said Dr. Tashkin. "These data provide physicians with a new and valuable treatment option for COPD patients with moderate to severe manifestations of the disease."



This randomized, placebo-controlled double-blind trial was conducted in 130 patients with moderate to severe COPD to evaluate the efficacy and safety of Perforomist™, nebulized FFIS, when added to Spiriva maintenance treatment. Patient-centered outcomes were measured by the baseline/transitional dyspnea index, daily recording of COPD symptoms, rescue albuterol use and St. George's Respiratory Questionnaire (SGRQ).



In this trial there was a statistical significance between the mean transitional dyspnea index scores in the Perforomist™/TIO and TIO/placebo groups (2.30 and 0.16, respectively; p=0.0002). Shortness of breath, chest tightness, nighttime awakenings, and total symptom scores all improved significantly with the Perforomist™/TIO treatment compared with TIO/placebo (p







"DEY is very pleased with the results of this study and the benefit that patients are seeing with Perforomist™ Inhalation Solution," said Carolyn Myers, Ph.D., President of Dey, L.P. "We wish to thank Dr. Tashkin and the other members of the research team for their careful investigation into the clinical benefits of concomitant therapy of Perforomist and tiotropium. At DEY, we are committed to developing effective new treatments for serious and complex diseases, and with Perforomist are proud to provide physicians and patients a twice-daily COPD maintenance medication that offers the flexibility of dosing via nebulization."

Session ID C42 COPD Pharmacotherapy I: Effects of Bronchodilators.


Poster # F4: Addition of Nebulized Formoterol Fumarate to Tiotropium Treatment Relieves Dyspnea and Symptoms in COPD Patients







The research presented at ATS 2008 was supported through grants provided by Dey, L.P., which developed and markets Perforomist™ Inhalation Solution. Dey, L.P. is a subsidiary of Mylan Inc. (NYSE: MYL).



About Perforomist™ Inhalation Solution



Indication



Perforomist™ Inhalation Solution is indicated for the long-term, twice-daily (morning and evening) administration in the maintenance treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease (COPD) including chronic bronchitis and emphysema.



Important Safety Information



Perforomist™ Inhalation Solution belongs to a class of medications known as long-acting beta2-adrenergic agonists (LABAs). LABAs may increase the risk of asthma-related death. Data from a large placebo-controlled US study comparing the safety of another LABA (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol may apply to formoterol (a LABA), the active ingredient in Perforomist™ Inhalation Solution.



Perforomist™ Inhalation Solution should not be used in patients with acutely deteriorating COPD or to treat acute symptoms. Acute symptoms should be treated with fast-acting rescue inhalers. Perforomist™ Inhalation Solution should not be used with other medications containing LABAs. Do not use more than one nebule twice daily. Perforomist™ Inhalation Solution should be used with caution in patients with cardiovascular disorders. Perforomist™ Inhalation Solution is not a substitute for inhaled or oral corticosteroids. The safety and efficacy of Perforomist™ Inhalation Solution in asthma has not been established.



In COPD clinical trials, the most common adverse events reported with Perforomist™ Inhalation Solution were diarrhea, nausea, nasopharyngitis, dry mouth, vomiting, dizziness, and insomnia.



Please see full Prescribing Information, including Boxed Warning, at perforomist/.



About COPD



COPD refers to a number of chronic lung disorders in which the airways to the lungs become narrowed and breathing becomes increasingly difficult. The most common forms of COPD are chronic bronchitis and emphysema and many patients suffer from a combination of the two diseases.



COPD is the fourth leading cause of death in America, behind heart disease, cancer and stroke. Twelve million Americans have been diagnosed with COPD and at least another 12 million have symptoms but have not been diagnosed. COPD is not well understood or recognized - most Americans have not heard of it, not even those who may be living with the condition. The most common cause of COPD is cigarette smoking, which is responsible for an estimated 80 to 90 percent of COPD cases. Estimates of the total incidence of COPD in America range from 24 to 30 million.



About Nebulization



Of the three types of devices used to deliver bronchodilators - nebulizers, metered-dose inhalers, and dry powder inhalers - nebulizers require no special technique or coordination, as the medication is converted into a fine mist that the patient inhales through a mouthpiece or face-mask while breathing naturally. Nebulization is an easy and effective method of delivering medicine directly into the lungs for patients, particularly as their symptoms worsen.



With Perforomist™ Inhalation Solution, nebulization may become a more widely used treatment option for many COPD patients at earlier treatment stages who could benefit from twice-daily maintenance dosing of a nebulized LABA such as Perforomist™ Inhalation Solution. For example, this new COPD treatment may be a valuable clinical option for many patients whose symptoms are not adequately controlled with their current therapy. COPD patients should consider asking their doctor whether nebulized treatment may be right for them.



About Dey, L.P.



Dey, L.P., a subsidiary of Mylan Inc. (NYSE: MYL), is a specialty pharmaceutical company focused on the development, manufacturing and marketing of prescription drug products for the treatment of respiratory diseases, respiratory-related allergies, and emergency care medicine. As the U.S. leader in sales of nebulized respiratory medication, Dey, L.P. puts patients first through its development of innovative and affordable therapies. dey/



Perforomist™ is a trademark of Dey, L.P.



Spiriva® is a registered trademark of Boehringer Ingelheim Pharmaceuticals, Inc.

Education For Health Study Highlights Devastating Global Economic And Social Impact Of COPD

A study presented today at the American Thoracic Society (ATS) Conference in New Orleans by leading charity, Education for Health (EFH), shows that the economic toll of COPD is set to soar1 as the disease heads towards being the third biggest cause of death globally by 20202. The international and expert-led survey is the first of its kind detailing the impact of COPD on a working-age population and highlights an urgent need to keep individuals with COPD active and contributing to society for the benefit of all1.


The survey highlights that society faces a double economic impact from the growing COPD crisis. Patients are losing an average of $1800 per year in lost income due to their COPD, which equates to lifetime losses of nearly $20,000. Nearly 1 in 5 of 45-68 year olds are forced to retire prematurely due to the condition, thereby incurring increased health costs and reducing personal contribution from taxation1.


In addition to the global financial impact of COPD, the survey also illustrates the personal and quality of life consequences for individuals, including effects on their household income, certainty for the future and being able to maintain the same level of lifestyle prior to diagnosis1,3. This not only affects individuals with the disease but other family members, potentially restricting their lifestyle choices and earning abilities - further compounding the problem.


Education for Health Chief Executive, Monica Fletcher said: "The survey results clearly demonstrate the social and economic consequences of COPD between the ages of 45-68. In order to stem the rising economic and social costs of this disease we must look at practical ways in which policy makers, the medical community and other stakeholders such as employers can take a more active role in supporting people with COPD to remain active and in the workplace for longer."


COPD has, by many, been considered a disease which only affects elderly populations. However, this data clearly demonstrates that the social and economic effect on a younger working population has been overlooked. Therefore, early diagnosis and management of COPD within this age group may enable this important group to maintain active and product lives for longer, helping to reduce the economic burden of the condition and improve patient quality of life1,3.


Monica Fletcher continued, "There is a vital need for both patient and healthcare professionals to ensure that they are up-to-date with new developments in the management of COPD but we must not forget that those responsible for workforce education need to be part of the solution."


Approximately 210 million people worldwide are currently known to be living with COPD4. Symptoms are often mistakenly attributed to aging or other respiratory diseases such as asthma, resulting in COPD being undetected in about 50% of cases5 and misdiagnosed in about 23%6. A 30% increase in prevalence is expected by the year 20303. The estimated prevalence of COPD includes approximately 4-13% of adults in Europe7-11 and approximately 7% of adults in the United States12. While COPD was previously more common in men, an increase in smoking among women has led to the disease affecting men and women almost equally4.















About Education for Health


Education for Health is the largest international charity that undertakes research which contributes to the evidence base for health professional education as a health improvement intervention; and trains health professionals to make a real difference to the lives of patients with long term conditions. With an active advocacy programme, lobbying strategy and sustainable educational projects across the globe, Education for Health unveiled new elearning plans last week. These will enable the Charity to support stakeholders across the global COPD community to improve their health and social care workforce skills in earlier COPD diagnosis and management and ultimately contribute to reducing the economic impact of COPD.


About the Survey


The survey is directed by a multi-disciplinary committee of international experts and led by research and training specialist organization Education for Health. Monica Fletcher, Chief Executive, Education for Health, is the lead investigator. The research was supported by an educational grant from Novartis Pharma A.G.


References


1. Fletcher MJ et al COPD has significant social and economic impact on a working-age population of COPD sufferers; an international survey. Abstract and poster presented at The American Thoracic Society Congress, 18 May 2010


2. GOLD Executive Committee, Global Strategy for the Diagnosis, Management, and Prevention of COPD 2009 Click here (accessed March 2010)


3. Fletcher MJ et al. Patients of working age with COPD have reduced quality of life in comparison to available population norms; an international survey. Abstract and poster presented at The American Thoracic Society Congress 18 May 2010


4. World Health Organization. Factsheet No 315 Chronic obstructive pulmonary disease (COPD), Last updated November 2009 Click here last accessed 30 March 2010


5. Halbert RJ, et al. Global burden of COPD: systematic review and meta-analysis. Eur Respir J 2006;28:523-532


6. T??lamo C, et al. Diagnostic Labeling of COPD in Five Latin American Cities. CHEST 2007;131(1):60-67


7. Stang P, Lydick E, Silberman C et al. The prevalence of COPD: using smoking rates to estimate disease frequency in the general population. Chest 2000;117;354S-9S.


8. Buist AS, McBurnie MA, Vollmer WM, Gillespie S, Burney P, Mannino DM, et al. International variation in the prevalence of COPD (the BOLD Study): a population-based prevalence study. Lancet 2007 Sep 1;370(9589):741-50.


9. Viegi G, Pedreschi M, Pistelli F et al. Prevalence of Airways Obstruction in a General Population: European Respiratory Society vs American Thoracic Society Definition. Chest 2000; 117:339S-345S.


10. Pe??a VS, Miravitlles M, Gabriel R et al. Geographic variations in prevalence and underdiagnosis of COPD: results of the IBERPOC multicenter epidemiological study. Chest 2000; 118:981-9.


11. Shahab L, Jarvis M, Britton J, West R (2006) Prevalence, diagnosis and relation to tobacco dependence of chronic obstructive pulmonary disease in a nationally representative population sample. Thorax 2006;61:1043-7


12. Mannino DM, et al. Obstructive and restrictive lung disease and functional limitation: data from the Third National Health and Nutrition Examination. Journal of Internal Medicine 2003;254:540-547

Source
Education for Health

COPD May Be A Problem With Autoimmunity

Moderate to severe chronic obstructive pulmonary disease (COPD) may be an auto-immunity problem, according to researchers in Spain, who studied the presence of auto-antibodies in patients with COPD and compared them to levels of control subjects. They found that a significant number of patients with COPD had significant levels of auto-antibodies circulating in their blood, about 5 to 10 times the level in controls.


The findings were published online ahead of the print edition of the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.


"We showed that between one third and one quarter of patients with clinically stable COPD present abnormal levels of circulating auto-antibodies in the blood," said Jaume Sauleda M.D., coordinator of respiratory medicine department, Hospital Universitari Son Dureta, Palma Mallorca, Spain. "Our findings provide further support for the hypothesis that the pathogenesis of COPD involves an auto-immune component."


The researchers recruited 328 patients with clinically stable COPD three months after hospitalization for the first time with an exacerbation of the disease at nine participating hospitals in Spain, and 67 healthy volunteers from primary care clinics, blood donors and hospital workers. They collected information on current and past smoking habits, comorbidities, and data such as body mass index, degree of dyspnea and six-minute walk distance. They tested lung function with spirometry.


They then took blood samples and tested the blood for antinuclear antibodies (ANA), anti-tissue antibodies (AT) including mitochondrial (AMA), liver-kidney microsomal (LKM), smoothmuscle (SMA), and parietal gastric cell (PGC) antibodies. The serum levels of C-reactive protein were also tested in patients.


"We wanted to quantify the levels of auto-antibodies in COPD with respect to the patients' lung function and disease severity. By doing so, we hoped to determine whether in fact COPD had an auto-immune aspect," said Dr. Sauleda. "COPD is the fourth-leading cause of death in the world, and is becoming increasingly common in the developing world as generations of heavy smokers age. Understanding its pathogenesis is key to developing effective treatments that go beyond symptom palliation."


The researchers found that, overall, 34 percent of COPD patients had abnormally high levels of ANA titer-a prevalence 11 times higher than seen in the control group, and 7 times higher than reported in healthy subjects in previous studies. Furthermore, 26 percent of the patients were positive for AT, a prevalence 4.5 times higher than in the controls, and 4 times higher than reported in healthy subjects in other studies.


Patients with AT tended to be younger and active smokers, and the level of these auto-antibodies was related to impairment of lung function. There were no other associations between auto-antibodies and other patient characteristics.


The much higher prevalence of auto-antibodies in COPD patients has several implications and possible explanations. Other studies have found that patients with "severe bronchitis" (which would probably be characterized as COPD today) had high levels of circulating ANA, and these results confirm those earlier findings. Recent reports have also suggested that circulating antibodies are directed against components of the lung matrix and epithelium in patients with COPD.


"We can only speculate on the mechanisms underlying the observed associations," said Dr. Sauleda. "The prevalence of ANA and AT may be non-specific markers of an ongoing auto-immune response or may be directly involved in the pathogenesis of the disease. However, these alternatives are not mutually exclusive. "Future longitudinal studies in general population evaluating the relationships between these auto-antibodies and lung function during several years can help us to unravel this issue."


Dr. Sauleda continued, "If future research confirms the suspected auto-immune component of COPD, it raises the possibility of future clinical trials evaluating possible new therapies for this disease, for instance, immunomodulators."

"Microparticles" Useful In Identifying Earliest Signs Of Emphysema

Monitoring blood for tiny particles released by cells lining the lungs may help clinicians diagnose emphysema in its earliest stages, according to researchers from Weill Cornell Medical College. The particles, called endothelial microparticles (EMPs), are shed during the disease process as tiny blood vessels in the lungs, called pulmonary capillaries, are injured and die.


The findings were published online ahead of the print edition of the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.


"This study confirmed that levels of EMPs are elevated in the blood samples of smokers, consistent with the concept that emphysema is associated, in part, with the death of cells lining the pulmonary capillaries, and suggesting that the early development of emphysema might be monitored with blood tests to measure EMP levels," said Ronald Crystal, MD, chairman and professor of genetic medicine at Weill Cornell Medical College.


Previous studies have linked vascular disease with elevated blood levels of EMPs. In light of growing evidence that early emphysema is associated with the loss of pulmonary capillaries, Dr. Crystal and his colleagues hypothesized that EMP levels might also be elevated in patients in the early stages of emphysema.


To conduct their study, the researchers used two lung function tests: spirometry, which measures the amount and speed at which a patient exhales; and a lung diffusion test which measures the lung's ability to diffuse, or transfer, carbon monoxide (DLCO). Patients with early emphysema typically have normal levels of inhalation and exhalation, but exhibit low DLCO.


"One of the key differences between spirometry, which is commonly used in physicians' offices, and DLCO, which is a more sophisticated test usually used only by pulmonologists, is that spirometry is less sensitive to the changes that occur in the lungs in the early stages of lung disease," Dr. Crystal said. "The DLCO test is much more sensitive and is able to pick up the earliest signs of emphysema."


In their study, the researchers assessed the levels of circulating EMPs in an initial patient population of 92 subjects, including healthy nonsmokers, healthy and symptomatic smokers with normal lung function and healthy smokers with normal spirometry but low DLCO. Because smoking is known to affect blood vessels in many areas of the body, EMPs were assessed for a specific enzyme that occurs primarily in pulmonary vessels. To confirm their findings, the assessment was repeated in two prospective cohorts, including a group of 92 patients similar to the initial patient population and a group of 15 patients with HIV.


Assessing their results, the researchers found both symptomatic smokers and healthy smokers with normal spirometry and normal DLCO had mild increases in EMP levels compared to healthy nonsmokers, and there was no difference in EMP levels between healthy and symptomatic smokers. In striking contrast, healthy smokers with normal spirometry but low DLCO had a significant increase in EMP levels.


"The data in these patient populations demonstrate that smokers with normal spirometry and normal DLCO have levels of circulating EMPs that are mildly elevated compared to healthy nonsmokers, but smokers who have normal spirometry and reduced DLCO have marked increases in the levels of circulating EMPs," Dr. Crystal said.


"Interestingly, the smokers with the highest EMP levels are healthy smokers with normal spirometry and low DLCO," he added. "This suggests that the vascular-based contributions to the development of emphysema may contribute to the early development of the disease, and may identify a point in time where intervention with smoking cessation therapy may prevent the irreversible lung destruction associated with the development of COPD."


A blood test to monitor for levels of EMPs may offer an alternative to high-resolution computed tomography (HRCT), which is currently used to identify early-onset emphysema, with varying degrees of success.


"Assessment of EMP levels may provide an early and inexpensive approach to identifying early evidence of emphysema, without the radiation exposure associated with chest computed tomography (CT) scans," Dr. Crystal noted. "Elevated EMP levels may be a useful biomarker to identify smokers with early emphysema at a stage where intervention may prevent further permanent lung destruction."


Link to original article




Source
American Journal of Respiratory and Critical Care Medicine

Researchers Link Novel Biomarkers To Asthma And COPD

Four novel biomarkers have been identified which may aid in the diagnosis and management of asthma and chronic obstructive pulmonary disease (COPD), according to a study conducted by researchers in Australia, who determined the biomarkers may be used in different combinations to successfully identify patients with either of the airway diseases. In conducting the study, the researchers relied on proteomics, an emerging field of science that focuses on the structure and functions of an organism's proteins.


The findings were published online ahead of the print edition of the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.


"Using a proteomics approach, we have identified a panel of four blood-based biomarkers that, when used in combination, can discriminate between healthy controls, asthmatics and individuals with COPD, and has the potential to be a valuable tool in the clinical diagnosis of respiratory disease," said Peter G. Gibson, MD, conjoint professor at the University of Newcastle's.


School of Medicine and Public Health. "The proteins in the diagnostic biomarker panel are all involved in the regulation of inflammation, and usually function as anti-inflammatory proteins.


"These results were confirmed in a second clinical population of older adults with airflow obstruction," he added.


The proteins identified in the study are predominantly liver-synthesized proteins that can have important anti-inflammatory activity through the inhibition of oxidative stress, which has been implicated in several diseases, including heart disease, Alzheimer's disease and Parkinson's disease.


To identify potential biomarkers, blood samples were collected from 43 subjects with a mean age of 48 years, including 21 with asthma, five with COPD and 17 healthy controls. Using proteomic techniques, plasma proteins were separated from all blood samples. Once protein biomarkers were identified and selected, the researchers measured the biomarkers' abilities, singly and in combination, to distinguish between the groups of patients.


To validate their results, the researchers conducted two additional assessments. In the first assessment, the original group was supplemented with an additional seven asthmatics and nine patients with COPD and repeated the biomarker assessment. The second assessment involved a separate population of 73 older subjects (over 55 years), including 14 with asthma, 22 with COPD, 14 with both conditions and 23 healthy controls. Results were confirmed in both validation groups.


Identifying biomarkers that are involved in the development of airway diseases may allow clinicians to diagnose the diseases in their earlier, and often more treatable, stages, Dr. Gibson noted.


"Our study identified a panel of highly discriminatory proteins that could be extremely useful in a clinical context," Dr. Gibson said. "Since these biomarkers are detectable in blood, which is readily obtainable from patients, and substances are currently available for testing the abundance of these proteins, this panel of biomarkers has the potential to become an extremely useful addition to the clinical diagnosis and management of respiratory disease."


Dr. Gibson noted proteomics played a vital role in the study, which was funded by the Australian government as part of its Cooperative Research Centre for Asthma and Airways program, and suggests the protein-based techniques may prove vital in future studies of biomarkers.


"Combined with well-defined clinical groups and advanced statistical analyses, we have shown that proteomics is a powerful tool for the identification of novel disease biomarkers," he said.


"The study is a good example of how high quality biological science can be translated effectively to a useful result for people with asthma and COPD. Future work is planned to study these markers in the lungs of patients with asthma and COPD, and apply the results in different clinical settings."


Source
American Journal of Respiratory and Critical Care Medicine

Faces Of COPD Campaign Profiles Canadians Living With COPD

The Lung Association launches today the 2008 Faces of COPD campaign. Faces of COPD features twelve personal stories - of Canadians with COPD, of their family members, and of healthcare professionals who research and treat this chronic condition.


"We're sharing these personal stories because we're hoping that people at risk for COPD may see themselves in these stories and be inspired to get help," says Nora Sobolov, President and CEO of The Lung Association.


One Face of COPD is Doug Cooper of Ottawa. He's been living with COPD for five years. "I couldn't walk more than eight steps without stopping to catch my breath. It was frightening and frustrating. When my doctor told me I had COPD, I was stunned. I had never heard of this disease before. I'm sharing my story in the hope that someone will read it and recognize that they may have COPD."


Read more personal stories of people affected by COPD



Learn more about COPD

The Lung Association

Wireless Monitoring Of Patients

A wireless monitoring system for people with debilitating conditions such as Parkinson's disease or chronic obstructive pulmonary disorder (COPD) could allow healthcare workers to assess a patient's health and the development of their disease without hindering their movements. Details of the system are reported in the International Journal of Biomedical Engineering and Technology.



Pallikonda Rajasekaran of Kalasalingam University, in Tamil Nadu, India, and colleagues say that assessment of a patient's disease state under the normal conditions of their everyday lives is becoming increasingly important in improving treatment and following the progression of many conditions as well as keeping costs down by avoiding unnecessary medical call outs and hospital visits. So-called ambulatory investigations are also providing important clues to researchers about a range of health problems associated with the likes of PD and COPD.



Rajasekaran and colleagues have developed a real-time monitoring system for patients. The system consists of vital signs sensors, a sensor network, electronic patient records and web portal technology that calls on medical personnel when life-threatening events occur. Their system circumvents some of the issues associated with current monitoring technology, such as unwieldy equipment and inconvenient wires between sensors and processing unit, a lack of integration of different sensors, the non-existent support for data collection and knowledge discovery that technology could offer medical research.



The team explains that recent advances in sensor technology, low-power integrated circuits and wireless communications have facilitated the design of low-cost, miniature, and lightweight sensors, such as movement, temperature, blood pressure, and heart rate sensors. These devices can monitor various signals, process the data from them, and seamlessly integrate with wireless networks for health monitoring.



The team has demonstrated efficacy with their integrated wireless system in terms of wireless connectivity and monitoring of vital signs of rehabilitating patients with PD and COPD. They have also programmed the sensors to send out alert signals above a certain unhealthy body temperature, below a specific heart rate, or if blood pressure changes by more than 10 percent. The system itself hinges on standard wireless networking technology with a 750-metre range. The system hooks into a previously available web-based information portal and provides an effective emergency response information system to support the need for multiple parties to share information about patient's status and locations, the team adds.



Article: "Ambulatory monitoring of free living patients affected by Chronic Obstructive Pulmonary Disease (COPD) and Parkinson's Disease (PD) using Wireless Sensor Networks" in Int. J. Biomed. Eng.Technol., 2010, 4, 111-122

Clinical Data, Inc. Reports Results Of Phase I Studies Of Stedivaze™ Demonstrating Safety And Tolerability In Patients With Asthma And COPD

Clinical Data, Inc. (NASDAQ: CLDA), announced results from two Phase I studies of Stedivaze™ (apadenoson), which demonstrated that Stedivaze was safe and well tolerated in patients with asthma and chronic obstructive pulmonary disease (COPD). Stedivaze is a potent and highly selective agonist of the adenosine A2A receptor subtype in development as a pharmacologic stress agent for myocardial perfusion imaging (MPI). Currently available adenosine agonists must be used with caution or are contraindicated in patients with asthma and COPD. The high selectivity of Stedivaze offers a potential advantage for the safe use in this population, accounting for approximately 10 percent of the 7.6M MPI tests performed annually.1 The Company is also actively enrolling patients in ASPECT 1, a Phase III trial designed to demonstrate the safety and effectiveness of Stedivaze.


"The positive results from our preliminary studies in asthmatics and COPD patients are encouraging and represent a milestone toward our goal of developing a coronary vasodilator that is both safe and well tolerated in these populations," said Carol R. Reed, M.D., Executive Vice President and Chief Medical Officer of Clinical Data. "We intend to expand these findings by initiating further safety studies of Stedivaze in patients with asthma and COPD, while continuing to evaluate the efficacy and potential for superior tolerability of Stedivaze in our ongoing Phase III program."


In both of these placebo-controlled studies, Stedivaze was administered as a single IV bolus, at the same dose utilized in the ASPECT 1 trial. In 49 patients with mild to moderate asthma and 50 patients with moderate to severe COPD, Stedivaze had no effects on pulmonary function tests. Adverse events overall were similar in both incidence and severity to the adverse event profile seen in previous studies of Stedivaze in patients without lung disease, and continue to support its potential for improved tolerability. Most frequently observed adverse events, common to this class of agents, included palpitations, flushing, chest discomfort and shortness of breath. Results of both of these trials support the continued study of Stedivaze in patients with asthma and COPD.


In addition to completing these Phase I studies, the Company is continuing to enroll patients in its ASPECT 1 trial of Stedivaze, a Phase III randomized, double blind, active control study initiated in November 2009, which is designed to demonstrate both efficacy and the potential for improved tolerability for Stedivaze in patients undergoing SPECT MPI. ASPECT 2, a second Phase III trial similar in design to ASPECT 1, is expected to begin in the second half 2010.


About Stedivaze


Stedivaze (apadenoson) is a potent agonist of the adenosine A2A receptor subtype and offers improved selectivity for this receptor over other subtypes (A1 and A2B). Phase II studies suggest that Stedivaze produces ample coronary artery vasodilation required for SPECT MPI testing and has a pharmacokinetic profile that will allow it to be administered as a fixed dose bolus injection. Because of its superior selectivity for the A2A receptor subtype and its optimal pharmacokinetic profile, Stedivaze may offer improved tolerability over other adenosine receptor agonists currently marketed for use in pharmacologic stress MPI.















About Myocardial Perfusion Imaging


Myocardial perfusion imaging is used as a primary screen to identify the presence of coronary artery disease (CAD) as evidenced by detection of areas of poor blood flow in the heart that can be caused by the presence of plaques that can reduce or block the normal flow of blood to the heart. A pharmacologic stress agent is used to temporarily increase blood flow through normal coronary arteries in order to define areas of the heart that may be receiving reduced blood flow under rest and then stress conditions. The A2A adenosine receptor is the receptor subtype responsible for coronary vasodilation, or the widening of blood vessels that supply the heart muscle.2


The U.S. market for MPI testing is projected to be $800 million in 2011. Over 7.6 million MPI tests were performed in the U.S. in 2008 and approximately 3.5 million of these tests required the use of a pharmacological agent to generate maximum coronary blood flow in lieu of exercise.3 The market is expected to continue to grow due to an aging population, a rise in the number of patients unable to perform exercise during diagnostic procedures, and emerging imaging modalities that require the use of a vasodilator.


1. Eliana Reyes, MD, et al. Adenosine myocardial perfusion scintigraphy in obstructive airway disease. Journal of Nuclear Cardiology, November/December 2007



2. Shryock, J.C., Snowdy, S., Baraldi, P.G., et al. "A2A - adenosine Receptor Reserve for Coronary Vasodilation," Circulation, 1998, pp. 711-718.


3. AMR Monthly Monitor SNM: Advanced Molecular Imaging and Therapy, September 15, 2008.



Source

Clinical Data, Inc.

COPD Patient Benefits From Treatment With Seretide

The INSPIRE (Investigating New Standards for Prophylaxis In Reduction of Exacerbations) trial demonstrated that while the two study medications; Seretide™ 50/500?µgDiskus™ (salmeterol/fluticasone propionate) and tiotropium bromide 18?µg Handihaler® had a comparable effect on exacerbation rates, those who received Seretide experienced substantial health status improvements and better survival periods than those who received tiotropium. INSPIRE is the first prospective trial to report a statistically significant difference in the relative risk of all-cause mortality between two recognized for COPD treatments. 1


The study is published in The American Journal of Respiratory and Critical Care Medicine.


INSPIRE study is the first to look at variations in exacerbation rates and related outcomes linked to two frequently used drugs COPD treatment. The primary endpoint of the INSPIRE study was a comparative decrease in exacerbations, an abrupt deterioration of symptoms, which are debilitating and grow as the disease advances.


While the total exacerbations described between the two study groups were not substantially different, overall rates were 1.28 for Seretide and 1.32 for tiotropium bromide (p=0.656), the treatment for the acute exacerbation chosen by investigators whilst blinded was different. Exacerbations that needed antibiotics happened more often among those taking Seretide, while exacerbations that required systemic steroids happen more often among those taking tiotropium - this suggests that the nature of the exacerbations was different and that people are affected in different ways by COPD treatments.


The study also revealed that COPD patients taking Seretide had a 52% lower risk of dying from any cause, compared to those taking tiotropium bromide a statistically significant finding (p=0.012). This lowering of mortality risk was observed by the thirteenth week of treatment and continued to increase as the study progressed. The study also showed that the Seretide patients had significant improvements in quality of life from early in the study compared to patients on tiotropium bromide (2.07 unit improvement at 2 years, p=0.038), as measured by the St George's Respiratory Questionnaire (SGRQ), a validated instrument used to assess the impact of airway disease on overall health, daily life, and perceived well-being. These benefits lasted through the length of the 104 week study.


"The results seen in INSPIRE showing improvements in quality of life and survival are important for patients with COPD. There is no cure for COPD so we must manage the disease as effectively as possible to provide patients with the best outcomes," Professor Wisia Wedzicha, Royal Free Hospital, London, said.


Safety and tolerability


The study reported an 8% increase in pneumonias among those taking Seretide, compared to a 4% increase among those receiving tiotropium bromide. 6% of the Seretide group reported candidiasis, compared to 3% in the tiotropium group.















Those receiving tiotropium were 29% more likely to drop out from the study. The probability of withdrawing prior to week 104 was 34.5% on Seretide and 41.7% on tiotropium bromide (p=0.005). The withdrawals were much higher among participants who had worse health status and who deteriorated faster. As more patients drop out of a study it can lead to a 'health survivor' effect with less severe patients in one treatment group being compared to more severe patients in the other treatment group.


INSPIRE was a European, 2-year multicentre, randomized, double-blind, double-dummy controlled trial involving 1,300 COPD patients - it compared the effects of Seretide and tiotropium bromide.


"The study raises important questions regarding the nature of this progressive disease. Patients appeared to experience differences in the nature of their exacerbations, with different treatment being prescribed for each group, Seretide patients received more antibiotics during their exacerbations, and tiotropium patients more oral corticosteroid treatments and this resulted in different outcomes for patients. This study therefore could have important implications for the choice of medication used to manage patients with COPD," Wedzicha concluded.


"The Prevention of Chronic Obstructive Pulmonary Disease Exacerbations by Salmeterol/Fluticasone Propionate or Tiotropium Bromide"

Jadwiga A. Wedzicha, Peter M. A. Calverley, Terence A. Seemungal, Gerry Hagan, Zainab Ansari and Robert A. Stockley for the INSPIRE Investigators

American Journal of Respiratory and Critical Care Medicine Vol 177. pp. 19-26, (2008)
doi: 10.1164/rccm.200707-973OC

Click here to view abstract online


Written by -

Study Shows Need To Test More COPD And Asthma Patients For Underdiagnosed Pulmonary Disease

A new study finds that a
higher than expected number of COPD and severe asthma patients had abnormal
low levels of alpha-1 antitrypsin (AAT), suggesting the need for broader
criteria for AAT deficiency testing. AAT deficiency, also known as Alpha-1,
is a widely undiagnosed hereditary disorder that is usually fatal in its
severe form.


Alpha-1 is estimated to affect up to 100,000 Americans, but up to 95
percent are undiagnosed or have been misdiagnosed as having another form of
chronic obstructive pulmonary disorder (COPD). Details of the study were
presented at CHEST, the annual meeting of the American College of Chest
Physicians held in Chicago from October 20 to 25. Study results are being
announced on World COPD Day to focus attention on the need for wider
testing for AAT deficiency.



"Findings from this study suggest that simply all patients with
moderate or severe persistent asthma and/or COPD with chronic pulmonary
symptoms should be tested for AAT deficiency," said Gary Rachelefsky, MD,
Professor of Allergy and Immunology and Director of the Executive Care
Center for Asthma, Allergy and Respiratory Diseases at UCLA School of
Medicine and study investigator. "It is imperative that clinicians become
more vigilant about Alpha-1 testing as many patients are going undiagnosed
or misdiagnosed due to screening criteria and practices."



The study, conducted by the Respiratory & Allergic Disease Foundation,
recruited 40 office based pulmonologists across the United States who
tested 454 adult patients using the following simple screening criteria:
persistent asthma and/or COPD patients with loss of lung function defined
by either a FEV1 (forced expiratory volume at 1 second) or a ratio of FEV1
to forced vital capacity (FEV1/FVC) of less than 70 percent. Blood tests
were taken to assess levels of AAT, and additional lab results and patient
histories were noted and tabulated.



Of the 454 patients studied, 3.3 percent showed deficient levels of
AAT. Low blood levels of AAT are commonly associated with progressive
severe emphysema that becomes clinically evident by the third to fourth
decade of life; a recent registry showed that 54 percent of AAT deficient
patients had emphysema. Less commonly, low levels of AAT are associated
with liver disease and cirrhosis.



Interestingly, patients who tested with low AAT did not significantly
differ from the COPD/persistent asthma patients with normal levels of AAT
in several key pulmonary function criteria, including levels of FEV1,
ratios of FEV1 to forced vital capacity (FEV1/FVC), or the number of
bronchial infections within the past 12 months. This lack of
differentiating characteristics in deficient subjects indicates that if
pulmonologists rely on standard screening criteria for Alpha-1 testing, the
result will be incorrect and missed diagnoses.
















"Our surveillance study found that physicians cannot depend on typical
patient profiles to assess whether AAT deficiency screening is necessary.
There is no 'face' to AAT deficiency," said D. Kyle Hogarth, MD, FCCP,
Assistant Professor of Medicine, University Chicago Medical Center,
Director of the Alpha-1 Antitrypsin Deficiency Clinical Resource Center at
the University of Chicago and lead author of the study. "A number of
patients who would not normally be screened based on suggested guidelines
turned out in fact to be positive for AAT deficiency. In the real-world
setting, this suggests that thousands of patients who have been diagnosed
with COPD or severe asthma may actually have Alpha-1."



The RAD study was supported by an unrestricted educational grant from
CSL Behring, maker of the Alpha1 Proteinase Inhibitor (Human), Zemaira(R).



About Alpha-1 Antitrypsin Deficiency (Alpha-1)



Alpha-1 antitrypsin is an anti-inflammatory protein that protects the
tissue of the body. One of its most important roles is to shield the
delicate tissues of the lungs by binding to neutrophil elastase, an enzyme
released by certain white blood cells that digests bacteria and other
foreign substances in the lungs. When a person with deficient levels of AAT
inhales irritants or contracts a lung infection, the neutrophil elastase
released to protect the lungs is uncontrolled and can injure healthy lung
tissue. Repeated injury to the normal structure of the lungs can eventually
result in emphysema, a condition affecting 54 percent of diagnosed AAT
deficient patients, according to a recent registry. Identifying patients
with AAT deficiency can be problematic, however. Because AAT deficiency
typically involves such common symptoms as shortness of breath on exertion,
wheezing, and coughing, the condition is often misdiagnosed as another
chronic lung condition. In fact, retrospective studies show that even after
an Alpha-1 patient has developed symptoms, it can take an average of seven
years and visits to five different healthcare professionals before the
correct diagnosis is made. Researchers estimate that up to 100,000 adults
and children in the U.S. have severe Alpha- 1, and 25 million people
nationwide may be carriers. Only about 5,000 patients are currently
diagnosed as AAT deficient, meaning that up to 95 percent of people with
the deficiency remain undiagnosed.



CSL Behring to Launch National Campaign to Improve Detection of AAT
Deficiency



To advance the early diagnosis and treatment of AAT deficiency, CSL
Behring, a leader in alpha-1 research and treatment, is launching a
national education and support program called Test Today. Change Tomorrow.
The initiative will target patients, caregivers and healthcare
professionals with activities and services, such as a national disease
awareness campaign about Alpha-1 deficiency, a toll-free information center
and website, educational materials, and a program to support Alpha-1
testing in healthcare settings, called Champions for Alpha-1 Testing. Test
Today. Change Tomorrow. will begin the week of November 18 with the launch
of a national television show as part of the series Today's Health.



CSL Behring is the maker of Alpha1-Proteinase Inhibitor (Human),
Zemaira(R), which is indicated for chronic augmentation and maintenance
therapy for individuals with established AAT deficiency and clinical
evidence of emphysema. Zemaira(R) is not indicated as therapy for lung
disease patients in whom severe congenital A1-PI deficiency has not been
established. Clinical data demonstrating the long-term effects of chronic
augmentation therapy with Zemaira are not available.



As with other Alpha-1 therapies, Zemaira may not be appropriate for the
following adult individuals as they may experience severe reactions,
including anaphylaxis: individuals with a known hypersensitivity and/or
history of anaphylaxis or severe systemic reaction to Alpha-1 Proteinase
Inhibitor products or their components and individuals with selective IgA
deficiencies who have known antibodies against IgA.



In clinical studies, the following treatment-related adverse reactions
were reported in 1 percent of subjects: asthenia (fatigue), injection-site
pain, dizziness, headache, paresthesia (tingling) and pruritus (itching).
Zemaira is derived from human plasma. As with all plasma-derived products,
the risk of transmission of infectious agents, including viruses and,
theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be
completely eliminated.



About CSL Behring



CSL Behring is a global leader in the plasma protein biotherapeutics
industry. Passionate about improving the quality of patients' lives, CSL
Behring manufactures and markets a range of safe and effective
plasma-derived and recombinant products and related services. The company's
therapies are used in the treatment of immune deficiency disorders,
hemophilia, von Willebrand disease, other bleeding disorders and inherited
emphysema. Other products are used for the prevention of hemolytic diseases
in the newborn, in cardiac surgery, organ transplantation and in the
treatment of burns. The company also operates one of the world's largest
plasma collection networks, ZLB Plasma. CSL Behring is a subsidiary of CSL
Limited, a biopharmaceutical company with headquarters in Melbourne,
Australia. For more information, visit cslbehring.



About the Respiratory & Allergic Disease Foundation



The Respiratory & Allergic Disease Foundation (RAD) is a physician-led
501(c)(3) non-profit corporation that provides education for patients and
clinicians on allergic and respiratory diseases that affect millions of
people in the United States. As new approaches evolve for the treatment of
respiratory and allergic diseases, RAD is committed to developing
scientific and educational programs for healthcare professionals that
incorporate the latest developments in understanding and treating these
conditions. With the assistance of our world-class steering committee,
network of faculty and participants across the United States, RAD provides
healthcare professionals with the cutting-edge, practical education needed
to move respiratory medicine forward. Learn more at rad-foundation.


CSL Behring

cslbehring


View drug information on Zemaira.

Osiris Therapeutics Reports Interim Data For COPD Stem Cell Study

Therapeutics, Inc. (NASDAQ:OSIR) announced six-month interim data from a Phase II clinical trial evaluating Prochymal, the Company's proprietary formulation of adult mesenchymal stem cells, for the treatment of chronic obstructive pulmonary disease (COPD). Sixty-two patients were enrolled and are being followed for two years in the placebo-controlled study. At the six-month time-point, the data revealed several important findings.


Important Findings:


- The trial met its primary goal of demonstrating the safety of Prochymal in patients with compromised pulmonary function at the six-month evaluation point.


- Prochymal significantly decreased systemic inflammation in patients when compared to those receiving placebo, as determined by C-reactive protein (CRP).


- Despite the reduction in inflammation, pulmonary function in patients receiving Prochymal was not significantly improved compared to those receiving placebo.


"We are very pleased with the interim outcome of this study and that the data continues to support the strong safety profile of this therapy, particularly given the severity of these patients' pulmonary disease," said C. Randal Mills, Ph.D., President and CEO of Osiris Therapeutics. "Importantly, we are gratified to obtain clear, objective data that helps bolster our understanding of the anti-inflammatory effects of these remarkable cells. Short-term, these anti-inflammatory effects did not appear to improve pulmonary function in patients with advanced destructive changes of the lung. Collectively however, these findings add to our confidence about the safety and effectiveness of the drug."


Six-Month Interim Data


Prochymal was evaluated in a total of 62 patients, 58% of them male. The patients ranged in age from 47 to 80 years and suffered from moderate (n=23) to severe (n=39) COPD. Patients had been suffering with COPD for an average of 7.8 years. Patients with asthma were excluded from the trial.


All patients in the trial completed the planned course of four infusions without any evidence of infusional toxicity. Oxygen saturation levels were measured throughout each infusion and showed no adverse effects of the infusion. Adverse event rates were comparable for patients receiving Prochymal and placebo. There were no signs of adverse immune reaction after any of the four infusions and no differences in the reported incidence of infection of any kind.


Prochymal significantly decreased the levels of CRP compared to placebo in those patients with elevated CRP (>4 mg/L) at the time of study entry (p

Even Mild COPD Limits Heart Function

A common lung condition, COPD (chronic obstructive pulmonary disease) diminishes the heart's ability to pump effectively even when the disease has no or mild symptoms, according to research published in the Jan. 21 issue of the New England Journal of Medicine. The study is the first time researchers have shown strong links between heart function and mild COPD. The research was funded by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health.



Researchers have long known that severe cases of COPD have harmful effects on the heart, decreasing its ability to pump blood effectively. The new results suggest that these changes in the heart occur much earlier than previously believed, in mild cases and even before symptoms appear. One in five Americans over the age of 45 has COPD, but as many as half of them may not even be aware of it.



"This study shows that COPD, even in its mildest form, is associated with diminished heart function," said NHLBI Acting Director Susan B. Shurin, M.D. "We now have evidence that the presence of even mild COPD may have important health implications beyond the lungs."



COPD is the fourth leading cause of death in the United States, and it is strongly associated with smoking. COPD often involves destruction of lung tissue, called emphysema, as well as narrowed airways, persistent cough, and mucus production, known as chronic obstructive bronchitis. These abnormalities impair the flow of air in the lungs and make breathing more difficult.



Although damage to the airways from COPD is not fully reversible, treatments can substantially improve a patient's daily life. "COPD is one of the big killers in the United States, yet it is unknown to many," said James P. Kiley, Ph.D., director of the NHLBI Division of Lung Diseases. "Unfortunately, many people with COPD don't recognize common symptoms such as having shortness of breath while doing activities they used to be able to do. It's important that we continue to increase awareness of the signs of COPD and available treatments."



Using breathing tests and imaging studies of the chest, researchers measured heart and lung structure and function in 2,816 generally healthy adults (average age of 61 years). Study participants were part of the MESA Lung Study, an extension of the Multi-Ethnic Study of Atherosclerosis (MESA), a large, NHLBI-supported study focused on finding early signs of heart, lung, and blood diseases before symptoms appear.



Sensitive magnetic resonance imaging (MRI) and computed tomography (CT) scans uncovered mild abnormalities in heart and lung function in many participants. They discovered that the link between lung and heart function was strongest in current smokers, who are at risk for both diseases, and especially in those with emphysema. The findings also appeared, to a lesser extent, in people with mild COPD who had never smoked.



"These results raise the intriguing possibility that treating lung disease may, in the future, improve heart function," said Graham Barr, M.D., Dr. P.H., assistant professor of medicine and epidemiology at Columbia University Medical Center in New York City, principal investigator of the MESA Lung Study, and lead author of the paper. "Further research is needed to prove whether treating mild COPD will help the heart work better."



The larger MESA project involves more than 6,000 middle-aged and older men and women from six urban communities across the United States. Participants in MESA come from diverse races and ethnic groups, including African Americans, Latinos, Asians and whites. They have been tracked since enrollment began in 2000.



Because the MESA study population is ethnically mixed and covers a broad age range of apparently healthy people, the results of this study may be widely applicable to the general U.S. population.



The NHLBI also supports a national campaign, COPD Learn More Breathe Better, to help people with COPD and those at risk to become more aware of COPD, get diagnosed early, better understand this disease and live better with it.



More information about the MESA Lung Study, Endothelial Dysfunction, Biomarkers, and Lung Function (NCT00843271), can be found at clinicaltrials/ct2/show/NCT00843271.



Reference: Barr, RG, Bluemke, DA, Ahmed, F, Carr, JJ, Enright, PL, Hoffman, EA, Jiang, R, Kawut, SM, Kronmal, RA, Lima, JA, Shahar, E, Smith, J, Watson KE. Left Ventricular Filling in Emphysema and Airflow Obstruction. N Engl J Med Online Jan. 21, 2010.

Beta Blockers Reduce Mortality In Patients With COPD After Vascular Surgery

In the first study to directly examine the effects of beta-blockers on surgical patients with chronic obstructive pulmonary disease (COPD), researchers have found that, contrary to previous thought, beta-blockers significantly reduce mortality in COPD patients.


"Patients with COPD frequently have unrecognized, atherosclerotic disease. This is also a major cause for late morbidity and mortality," said principle investigator Don Poldermans, M.D., Ph.D., of the Erasmus Medical Center in Rotterdam, the Netherlands.


The results were published in the first issue for October of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.


Clinical trials on the benefits of using preoperative beta-blockers to lower the risk of cardiovascular events in patients undergoing noncardiac surgery have yielded inconsistent results. Recent guidelines from the American Heart Association, however, recommend beta-blockers before noncardiac surgery for patients who are at high risk for or who have known cardiovascular disease.


But patients with COPD, who have an increased risk of cardiovascular disease, often do not receive preoperative beta-blockers because of concerns that the drugs will aggravate bronchospasm and worsen their airway obstruction. Moreover, the benefits of beta-blockers have not been examined in a population of patients with COPD undergoing noncardiac disease.


To determine the effect of beta-blockers on COPD patients undergoing vascular surgery, the researchers evaluated the mortality outcomes of more than 3,000 consecutive patients who underwent vascular surgery at the Erasmus Medical Center in Rotterdam between 1990 and 2006. They specifically looked at the effect of a low dose of beta-blockers (less than 25 percent maximum recommended therapeutic dose) versus an "intensified" dosage (more than 25 percent maximum recommended therapeutic dose).


Of the 3,371 patients evaluated, 31 percent more than 1000 received cardio-selective beta-blockers at their initial hospitalization. There was no apparent clinical differences between the patients with COPD 39 percent of the entire study sample and those without in terms of the likelihood of them receiving blockers.


They found that cardio-selective beta-blockers were independently associated with reduced 30-day mortality in both patients with and without COPD. In the 30 days after surgery, COPD patients did not receive beta-blockers were twice as likely to die as those who did (eight percent versus four percent.) Over the long term, a similar trend, though not statistically significant, emerged. During the follow-up period, 40 percent of COPD patients on beta-blockers died, whereas 67 percent who were not on beta-blockers died.


"What was observed in the population, beta blockers, especially, cardioselective beta blockers like bisoprolol are well tolerated by COPD patients without inducing respiratory adverse effects. More importantly, they improve outcome, by preventing late cardiac events, a major cause for late morbidity and mortality," said Dr. Poldermans.















They also found that in COPD patients, an intensified dose, but not a low dose, of beta-blockers was associated with reduced 30-day mortality, but in the long term, both intensified and low dosages were associated with similar reductions in mortality. In patients without COPD, both low and intensified doses were associated with reduced mortality in 30-days but in the long term, only the intensified dose was associated with a nonsignificant trend in reduced mortality.


"We found that an intensified dosing regimen appeared to be superior to low-dose therapy in terms of its impact on 30-day mortality," wrote Dr. Poldermans. "We [demonstrated] among a large group of well-characterized patients with COPD??¦that beta-blockers were safe and beneficial in prolonging survival after major vascular surgery."


"The indications of our findings are that a high-dose might be preferred in the COPD population," said Dr. Poldermans. "The safety of cardioselective beta blockers in the COPD population will support their use."


These findings demonstrate that carefully selected patients with COPD can tolerate cardioselective beta-blockers without experiencing respiratory complications. They also show that COPD patients may be protected by beta-blocker therapy from cardiovascular complications of surgery, such as myocardial infarction. These findings need to be put in context with the recent POISE (Perioperative Ischemic Evaluation) study that demonstrated higher mortality among general populations of patients those with and without COPD treated with preoperative beta-blockers.


Dr. John E. Heffner, past president of ATS and Garnjobst Chair at Providence Portland Medical Center, observed that "the jury remains out regarding the utility of preoperative beta-blockers for all patients at risk of cardiovascular complications from noncardiac surgery. But this study suggests that carefully selected patients with COPD, which is an extreme risk factor for cardiovascular disease, at best may benefit but at least appear to tolerate cardioselective beta-blocker therapy. "


American Thoracic Society (ATS)

61 Broadway

New York, NY 10006

United States

thoracic

Clinical And Familial Risk Factors For COPD Exacerbations

Exacerbations of chronic obstructive pulmonary disease (COPD) substantially impair quality of life and increase the burden of illness in individuals with COPD. Though relatives of COPD patients have increased risk for COPD, increased risk for COPD exacerbations in relatives has not been demonstrated. Edwin Silverman (Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA) and his colleagues analysed data from participants in the Boston Early-Onset COPD Study, a family-based study of the epidemiological and genetic determinants of COPD, for risk factors influencing COPD exacerbations.


This study shows that environmental tobacco smoke exposure significantly increases episodes of cough and phlegm in subjects with severe, early-onset COPD. In first-degree relatives of these subjects, a substantial proportion of whom had a history of smoking or severe airflow obstruction, those with prior pneumonia, chronic bronchitis, episodic wheezing and active smoking were at increased risk of exacerbations. First-degree relatives of individuals with COPD exacerbations were demonstrated to be more likely to experience exacerbations using one definition of COPD exacerbation, episodes of increased cough and phlegm.


These findings highlight the risk of passive tobacco smoke exposure in patients with COPD. The demonstration of increased risk for exacerbations in first-degree relatives of COPD patients suggests a genetic basis for susceptibility to COPD exacerbations.


The European Respiratory Journal is the peer-reviewed scientific publication of the European Respiratory Society (more than 8,000 specialists in lung diseases and respiratory medicine in Europe, the United States and Australia).

European Respiratory Society

Long-Term Use Of Vitamin E May Decrease COPD Risk

Long-term, regular use of vitamin E in women 45 years of age and older may help decrease the risk of chronic obstructive pulmonary disease (COPD) by about 10 percent in both smokers and non-smokers, according to a study conducted by researchers at Cornell University and Brigham and Women's Hospital.


"As lung disease develops, damage occurs to sensitive tissues through several proposed processes, including inflammation and damage from free radicals," said Anne Hermetet Agler, doctoral candidate with Cornell University's Division of Nutritional Sciences. "Vitamin E may protect the lung against such damage."


The results of the study will be presented at the ATS 2010 International Conference in New Orleans.


"The findings from our study suggest that increasing vitamin E prevents COPD," said Ms. Agler. "Previous research found that higher intake of vitamin E was associated with a lower risk of COPD, but the studies were not designed to answer the question of whether increasing vitamin E intake would prevent COPD. Using a large, randomized controlled trial to answer this question provided stronger evidence than previous studies."


Ms. Agler and colleagues reviewed data compiled by the Women's Health Study, a multi-year, long-term effort ending in 2004 that focused on the effects of aspirin and vitamin E in the prevention of cardiovascular disease and cancer in nearly 40,000 women aged 45 years and older. Study participants were randomized to receive either 600 mg of vitamin E or a placebo every other day during the course of the research.


Although fewer women taking vitamin E developed COPD, Ms. Agler noted the supplements appeared to have no effect on asthma, and women taking vitamin E supplements were diagnosed with asthma at about the same rate as women taking placebo pills. Importantly, Ms. Agler noted the decreased risk of COPD in women who were given vitamin E was the same for smokers as for non-smokers.


Ms. Agler said further research will explore the way vitamin E affects the lung tissue and function, and will assess the effects of vitamin E supplements on lung diseases in men.


"If results of this study are borne out by further research, clinicians may recommend that women take vitamin E supplements to prevent COPD," Ms. Agler noted. "Remember that vitamin E supplements are known to have detrimental effects in some people; for example vitamin E supplementation increased risk of congestive heart failure in cardiovascular disease patients. Broader recommendations would need to balance both benefits and risks. "


"Randomized Vitamin E Supplementation and Risk of Chronic Lung Disease (CLD) in the Women's Health Study" (Session C103, Tuesday, May 18, 1:30- 4:00 p.m., CC-Room 353-355 (Third Level), Morial Convention Center; Abstract 3727)

Key To Potential Vaccine For COPD Bacteria

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.



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.


For the complete text of these articles, please see the American Thoracic Society Online Web Site at atsjournals. For either contact information or to request a complimentary journalist subscription to ATS journals online, or if you would like to add your name to the Society's twice monthly journal news e-mail list, contact Cathy Carlomagno at 212-315-6442, or at ccarlomagnothoracic.


Cathy Carlomagno

ccarlomagnothoracic

212-315-6442

American Thoracic Society

American Thoracic Society Journal news tips for July 2005 (second issue)

thoracic

Guidelines For Diagnosis And Treatment Of Stable COPD Issued By The ACP, Accompanying Video Included

The ACP (American College of Physicians) has released its latest clinical practice guidelines for the diagnosis and treatment of COPD (chronic obstructive pulmonary disease). COPD is a lung disease which progresses slowly - lung function is progressively lost. COPD is more common among smokers.


The guidelines appear in Annals of Internal Medicine, November 6th, 2007 issue.


Over 5% of US adults have COPD. It is the fourth primary cause of death and the twelfth leading cause of illness in the USA. A COPD patient will typically have a chronic cough, wheezing - some patients may also have shortness of breath and considerable activity limitation.


Chronic bronchitis and emphysema are both types of COPDs. As patients usually have overlapping symptoms, it has become more common today for doctors to use the broader term COPD.


Some of the recommendations are:


-- If a patient has respiratory symptoms, in particular shortness of breath, Spirometry should be performed to diagnose airflow obstruction. Spirometry is a test - the patient blows into a machine which measures how much gas is breathed into it over a specified time. Asymptomatic patients should not undergo Spirometry.


-- Treatment of stable COPD should be reserved for patients who have respiratory symptoms and forced expiratory volume in one second (FEV1) less than 60 percent predicted, as documented by Spirometry.


-- Doctors should prescribe long-acting inhaled ??-agonists, long-acting inhaled anticholinergics, or inhaled corticosteroids for patients with COPD symptoms and FEV1 of under 60% predicted.


-- If a patient's oxygen levels in the circulating blood (while resting) are insufficient doctors should prescribe oxygen therapy.






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Watch the video documentary that accompanies this article

Guideline author, Steven Weinberger, MD, FACP, Senior Vice President, Medical Education and Publishing at ACP, said "The evidence does not support using Spirometry as a diagnostic strategy for individuals not reporting respiratory symptoms. However, adding Spirometry to clinical examinations for individuals with respiratory symptoms, especially shortness of breath, has demonstrated benefits."















The guidelines are based on a systematic evidence review of published studies by Timothy J. Wilt, MD, MPH, and the Agency for Healthcare Research and Quality-sponsored Minnesota Evidence-based Practice Center evidence report.


Weinberger said "It is important that all individuals with COPD stop smoking to prevent progression of the disease. Of course, even smokers without COPD should stop smoking to decrease the risk of both COPD and lung cancer. It's never too late to stop."


The guidelines are aimed at all doctors, while the target patient population is all COPD adult patients.


"Diagnosis and Management of Stable Chronic Obstructive Pulmonary Disease: A Clinical Practice Guideline from the American College of Physicians"

Amir Qaseem, MD, PhD, MHA; Vincenza Snow, MD; Paul Shekelle, MD, PhD; Katherine Sherif, MD; Timothy J. Wilt, MD, MPH; Steven Weinberger, MD; Douglas K. Owens, MD, MS, for the Clinical Efficacy Assessment Subcommittee of the American College of Physicians*

Annals of Internal Medicine - 6 November 2007 | Volume 147 Issue 9 | Pages 633-638

Click here to view the guidelines online


"Management of Stable Chronic Obstructive Pulmonary Disease: A Systematic Review for a Clinical Practice Guideline"

Timothy J. Wilt, MD, MPH; Dennis Niewoehner, MD; Roderick MacDonald, MS; and Robert L. Kane, MD

Annals of Internal Medicine - 6 November 2007 | Volume 147 Issue 9 | Pages 639-653

Click here to view the guidelines online


Annals of Internal Medicine is published by the American College of Physicians, the largest medical specialty organization and the second-largest physician group in the United States. ACP members include 124,000 internal medicine physicians (internists), related subspecialists, and medical students. Internists specialize in the prevention, detection, and treatment of illness in adults.


Written by -

One Thing Leads To Another In Exacerbations In COPD

New research shows that individual exacerbations in chronic obstructive lung disease (COPD) themselves increase the likelihood of repeat exacerbations, even after five days of full, asymptomatic recovery - bad news for patients with COPD, where each exacerbation can drive the progression of the disease.



"This concept that exacerbations are not random has important implication for the analysis of clinical trial data and identifies a specific high-risk period for recurrent exacerbation during which preventative interventions might be targeted," wrote lead author, John Hurst, M.D., of the Royal Free and University College Medical School, in London.



The results appeared in the first issue for March of the American Journal of Respiratory and Critical Care Medicine, a publication of the American Thoracic Society.



In patients with COPD, exacerbations are generally defined as an acute worsening of symptoms. Exacerbations in and of themselves are inherently dangerous and can lead to hospitalization and serious complications. But beyond their acute dangers, exacerbations drive lung function decline, and many patients never recover their baseline level of lung function after exacerbations. Prior to this research, however, exacerbations were assumed to be isolated events unrelated to one another despite observational data that suggested a dependency.



To test the validity of this assumption, which not only informs treatment plans for patients with COPD, but also forms the basis of research design and analysis, Dr. Hurst and colleagues analyzed daily symptom diaries that were kept for at least one year by 297 COPD patients, describing nearly 2,000 distinct exacerbation events. Two or more new or worsening symptoms, one of which must be "major" (e.g., dyspnea, more sputum, or a change in color of sputum) constituted an exacerbation, and after five days of symptoms reverting to baseline severity, the exacerbation was considered to be over. A second exacerbation occurring within an eight-week period was considered to be a recurrent exacerbation. The researchers further analyzed seasonality of exacerbations, comparing their winter (November to January) frequency with their summer (June-August) frequency.



In addition to the finding that exacerbations were clustered in time within individuals, the researchers found that they were significantly more common in the winter than the summer. They also noted that "isolated" exacerbations tended on average to be about 25 percent more severe than the first of serial exacerbations.



But most importantly, the researchers identified an eight-week period of time during which monitoring and follow-up is crucial to prevent or minimize further exacerbations in the COPD patient. "Our finding of a high-risk period for recurrent exacerbation may be important in guiding patient follow-up," wrote Dr. Hurst.



"The mechanisms of exacerbation recurrence remain unexplored, and it is unknown whether recurrence is due to persistence of an existing organism or to acquisition of a new one," noted Dr. Hurst. However, there are some clues that may guide future research. "The failure to eradicate bacteria with exacerbation therapy has been associated with an incomplete recovery in inflammatory markers and we have recently reported a relationship between elevated C-reactive protein during the recovery period of an initial exacerbation and shorter time to the next." Furthermore, the paper noted that "symptoms more typical of viral infection are significantly more common during isolated events."



"This knowledge is very important for physicians," wrote Shawn D. Aaron, M.D., of the Ottawa Health Research Institute, in Canada, in an editorial in the same issue of the journal. "Clinicians should now be aware that their patients with COPD who experience an exacerbation may be particularly 'brittle' during a subsequent eight-week period. Close monitoring and follow-up during this time would hopefully lead to earlier therapy for recurrent exacerbations that may improve clinical outcomes."

Long-Term Antibiotics Reduce COPD Exacerbations, Raise Questions

Long-term use of a macrolide antibiotic may reduce the frequency of exacerbations in patients with moderate to severe chronic obstructive pulmonary disease (COPD) by as much as 35 percent, according to a London-based study.


"Our results show a significant effect of low-dose macrolide therapy, reducing exacerbation frequency and severity with moderate to severe COPD," wrote lead author of the paper, Terence A. R. Seemungal, Ph.D., and Jadwiga Wedzicha, M.D., principle investigator.


The encouraging news comes on the heels of World COPD Day 2008 and a new report from the Centers for Disease Control and Prevention (CDC) that detailed the rising number of deaths related to COPD. More women than men now die of COPD, and while death rates for men have leveled, the rate is still increasing for women, according to the CDC.


The latest study is the first ever year-long randomized, double-blind, placebo-controlled study of the effects of erythromycin in COPD. The results were published in the first issue for December of the American Journal of Respiratory and Critical Care Medicine, which is published by the American Thoracic Society.


The researchers assessed and followed 109 patients with moderate to severe COPD for a year, after randomly assigning them to receive either a placebo or a twice daily 250 mg dose of erythromycin. The patients recorded their exacerbations and hospitalizations in a daily diary card, and they were assessed using spirometry, sputum testing and blood testing for lung function, bacterial infection and markers of inflammation.


The researchers found that not only did the patients randomized to receive erythromycin have fewer exacerbations, but among the patients studied, 60 percent of the exacerbations that occurred were within the placebo group. While the number of exacerbation-related hospitalizations was small, more than twice as many occurred among the placebo group-14 versus 6. The median duration of exacerbations from onset to resolution of symptoms was 9 days in the erythromycin group and 13 days in the placebo group.


"Our results did not allow us to determine a mechanism for these findings. However based on in-vitro studies we suspect that the mechanism is likely to involve the anti-inflammatory properties of erythromycin," noted Dr. Seemungal.


While their findings are encouraging, Dr. Seemungal points out that they must be put in context with future findings. Furthermore, the threat of growing antibiotic resistance resulting from widespread prophylactic use of erythromycin is not a trivial concern. "In this scenario, substantial, widespread emergence of macrolide bacterial resistance is virtually foreordained, with attendant reduction in the antimicrobial usefulness of this drug class," wrote Ken M. Kunisaki, M.D. and Denise E. Niewoehner, M.D., of the Veterans Affairs Medical Center in Minneapolis, in the accompanying editorial. "Balancing benefit against harm could pose a dilemma for which there might be no clear answers."















Moreover, not all of the study patients were treated with guideline-recommended therapy, such as inhaled corticosteroids or inhaled long-acting bronchodilators, which have been shown to decrease exacerbation frequency. The degree of added benefit of erythromycin over and above standard therapy will require further study.


"Observations that any intervention might decrease the frequency and severity of acute exacerbations in COPD present considerable public health implications," observed John Heffner, M.D., past president of the ATS. "Exacerbations occur about once a year among patients with moderate to severe COPD and account for more than $30 billion dollars in direct and indirect costs annually in the United States alone."


"Many patients with advanced COPD receive highly potent, extended spectrum antibiotics during acute exacerbations," commented Dr. Heffner. "The relative risks of breeding resistance with a long-term preventative use of erythromycin versus more frequent short-term dosing of highly potent antibiotics for acute exacerbations require careful analysis. If future studies demonstrate similar efficacy of prolonged erythromycin therapy, especially if patients are already receiving inhaled steroids and long-acting bronchodilators, the benefits likely will outweigh the risks."


PODCAST


Full text of original article

Full text of original editorial


American Thoracic Society

The Effectiveness Of Telemonitoring Vital Signs Examined By Study

Like the bleeps of an alarm clock, TeleCare, a home monitoring device, gives the chronically ill a wake-up call: "It's time to take your vitals."



Researchers from Case Western Reserve University and Cleveland State University will study how effective TeleCare, a device the size of an alarm clock, is in keeping individuals with complex health issues healthy and out of the hospital.



CWRU's University Center on Aging and Health awarded a one-year pilot grant to investigators Elizabeth Madigan from the Frances Payne Bolton School of Nursing, Rebecca Boxer from the School of Medicine at CWRU, and Amir Poreh from Cleveland State, for the study, "Supporting Self-Management with Telehealth for Patients with Multiple Morbidity."



The researchers will work with the 40 patients under the care of the Cleveland Visiting Nurses Association (VNA) of Ohio, headquartered in Cleveland. The patients suffer from one or more of the following illnesses: heart failure, chronic obstructive pulmonary disease (COPD) and diabetes. They also experience symptoms of depression, anxiety or difficulties making decisions.



The Cleveland VNA has about 100 TeleCare monitors in use to track heart rates, blood pressures, oxygen saturation, temperature, weight and blood sugar of patients on days when the visiting nurses do not make house calls.



When the device announces the time to take vital signs, the patient plugs the device into the telephone jack, attaches various pieces of medical equipment (like a blood pressure cuff or scales) to the device and then records the data. The information is sent directly to a specially-trained VNA nurse at a computer station, who tracks the data for health changes that signify a potential medical issue.



According to Madigan, the technology allows health care organizations like the VNA to monitor and extend care beyond the regular home visit and find changes in the health condition before it might reach a critical stage.



An example says Madigan, who is a professor of nursing, is an elevated weight gain in a person with heart failure - a sign of potential fluid overload.



"Generally patients like this monitoring," said. While it is distant monitoring, "it's another set of eyes on their health conditions."



The VNA has used the monitors for about seven years, but past studies on home telehealth monitoring have been done on the ideal or controlled patients.



Because the targeted illnesses in this study also are associated with cognitive or mental health changes, the researchers want to see if the technology is effective in helping "the real patient with real issues" manage their illnesses.



"We hope to find out which patients benefit the most from telehealth monitoring," Madigan said.