COPD World News Week of December 27, 2009
Pittsburgh, PA - Experts have long known that "low-tar" and "light" cigarettes aren't any healthier than regular cigarettes. New research suggests that they have another drawback and that is that people who switch to them are less likely to quit, even those who switch specifically because they want to stop smoking.
In fact, "switching to 'light' cigarettes for any reason is associated with continuing to smoke," said study author Dr. Hilary Tindle, a researcher at the University of Pittsburgh's Division of General Internal Medicine. However, she acknowledged that the research does not prove that switching leads directly to a lower rate of quitting.
According to the authors, an estimated 84 percent of cigarettes sold in the United States are so-called low-tar and low-nicotine, with many of them called "lights." Some smokers may assume they're healthier than other cigarettes, but medical researchers say smokers still suck in about the same level of carcinogens. And, research has shown that "lighter" cigarettes don't reduce smoking-related illness and death. Regardless of what brand they smoke, "the average smoker dies 13 to 14 years earlier than he or she would die if he or she did not smoke," Tindle said.
In the new study, published in the journal Tobacco Control, researchers examined the results of a 2003 survey of 30,800 people in the United States who had smoked within the past year. Thirty-eight percent of them had switched to "lighter" cigarettes, with the largest percentage of those, 26 percent, saying they'd done so for better flavor. Forty-three percent mentioned one, two or three reasons for switching, with quitting smoking being one of those reasons. However, those who had switched were 46 percent less likely to have quit smoking.
Why might switchers be more likely to continue smoking? "Prior research suggests that switching may resolve smokers' cognitive dissonance about smoking - something along the lines of, 'Well, since I'm smoking a supposedly healthier cigarette, I really don't have to worry about lung cancer, heart disease, impotence, wrinkles, early death, COPD because my health is not at risk,'" Tindle said.
"This type of rationale may keep more health-conscious smokers smoking. "But there are other possible explanations, added Robert West, a researcher who studies tobacco use at University College London in England. It's possible, for example, that people who switch are already more dependent on cigarettes and less able to quit, he said.
"In Europe, tobacco companies are not allowed to call cigarettes low tar or imply that they are in any way safer," West said. Regardless of how cigarettes are marketed, Tindle said, "the best solution for the problem of how to live longer and healthier is to quit smoking now."
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COPD World News Week of December 20, 2009
Boston, MA - A gene variant that plays a role in inflammation seems to protect the lungs of children with asthma as well as adults who smoke. Researchers also found that adult smokers with this variant of the MMP12 gene had a lower risk of developing chronic obstructive pulmonary disease (COPD), a progressive condition often brought on by smoking.
"The gene seems to be protective of the lungs in both asthma and COPD," said Dr. Norman Edelman, chief medical officer of the American Lung Association. Any new gene identified raises the hope that it will provide ways to prevent or treat the disease to which it is allied and this is no exception."
Levels of the MMP12 gene may impact the quality of life for those individuals with asthma and COPD, and may allow us to come up with potential therapeutic approaches," added Jeffrey Cirillo, professor of microbial and molecular pathogenesis at Texas A&M Health Science Center College of Medicine in College Station. "By understanding more about this specific gene we can find ways to induce or oppress that protein expression in the lungs."
"The real question is not why people who smoke get COPD. We kind of know the answer to that. The question is why do people who don't smoke get COPD," added Edelman. "If we understood that, we could find ways to reverse it and protect people."
The MMP12 gene has been implicated in the development of emphysema in mice that are exposed to smoke, suggesting that the gene may also be important in the onset of emphysema in humans. The gene is also linked with other genes involved in asthma. This information, combined with the fact that factors that can cause the onset of asthma in children are also involved with how well your lungs function in adulthood spurred investigators to undertake this study.
Dr. Juan C. Celedon, an associate professor of medicine at Brigham and Women's Hospital and Harvard Medical School in Boston and his colleagues looked at seven different groups of people, in all comprising 8,300 children and adults. A variant of MMP12 was associated with better lung function in children with asthma. In adults, the variant led to better lung function in adult smokers and reduced the risk of COPD in former or current smokers. The findings, published online Dec. 16 in the New England Journal of Medicine, also shed new light on the connections between asthma and COPD.
"This suggests that there are some genes that may influence both asthma and COPD, so that for a subgroup of people there may be common determinants," said study senior author Celedon. "There is certainly overlapping in that how you get asthma and how you get COPD is related and probably very closely related," Cirillo said. "That's exciting because it suggests that if we can decrease or increase expression of genes that are common to both, we could potentially affect both. It's nice to have one treatment."
All of which makes sense, Edelman said. "This gene is involved in the inflammatory process, and asthma is a disease of inflammation and COPD is a disease of inflammation," he noted. "The results are different and the pathways are different but you're still talking about inflammation of the lung. It's not terribly surprising that it appears to be protective in both circumstances."
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COPD World News Week of December 13, 2009
Stem cells may offer alternative to lung transplants
Brussels, Belgium - Belgian scientists who used embryonic stem cells to create lung tissue say this technique could provide an alternative to lung transplants for patients with COPD and cystic fibrosis. This is the first time it's been shown that embryonic stem cells can be converted into airway epithelial-like cells without the use of specific growth factors or embryoid body formation. The researchers achieved this using an "air-liquid interface" system that mimics the conditions found in an adult trachea.
"Efforts will be made to further improve this novel culture protocol,trying to increase the number of differentiated cells or to guide the differentiation into particular cell types by adding certain growth factors to this system," Lindsey Van Haute, of the department of embryology and genetics at the Free University of Brussels, said in a news release.
She and her colleagues may start with fibroblast growth factors, which play an important role in lung development. Human embryonic stem cells "have the capacity to differentiate in vivo and in vitro into cells from all three germ lineages, making them particularly important in developmental biology, regenerative medicine and in vitro pharmacological studies," Van Haute said.
The study was published in the journal Respiratory Research.
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COPD World News Week of December 6, 2009
London, ON - A University of Western Ontario researcher is providing new insight into COPD. Grace Parraga of Robarts Research Institute is using various imaging techniques to learn more about the disease. Parraga is a scientist in the Imaging Research Laboratories.
Currently, Parraga and her collaborators at Western hold two large grants valued at $2.5 million from the Canadian Institutes of Health Research - to characterize COPD using Magnetic Resonance Imaging and to compare three different types of lung imaging in COPD patients over time. "The idea is that if we can understand the structural and functional imaging changes that happen over time, we can start to understand the patients in a different way, with the potential to change the way they are treated," says Parraga.
Parraga and her collaborators believe that two major COPD groups exist: those with dysfunctional airways, and those with lung tissue damage. She says current methods of evaluating COPD don't consider the differences imaging methods can detect and therefore these often are not predictive of how patients feel and how their disease progresses.
She and her colleagues directly address this shortcoming by helping to categorize COPD patients using computed tomography (CT), MRI, and optical coherence tomography. The goal is to help improve patient treatment.
Parraga’s research uses a nation-wide interdisciplinary collaboration, a unique lung imaging core facility and a unique capability to image lungs to make an impact on the millions suffering from the disease. Their collaborative work was also recently recognized by the Radiological Society of North America (RSNA) that awarded one her graduate students in Medical Biophysics (Hassaan Ahmed) the prestigious RSNA Trainee Prize.
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COPD World News Week of November 29, 2009
Atlanta, GA - The CDC is warning about a "worrisome" rise in the incidence of pneumococcal disease associated with the pandemic H1N1 flu.
"We're seeing increases in serious pneumococcal infections around the country," Anne Schuchat, MD, director of the CDC's National Center for Immunization and Respiratory Diseases, said at a recent briefing. The rise appears to be linked to the H1N1 pandemic and is affecting adults between 20 and 59.
"In a typical nonpandemic year," she said, "most serious pneumococcal infections occur in people 65 and over." But in previous pandemics, the pattern has shifted, with younger people being affected, she said. Currently, she said, "we are seeing an increase in pneumococcal infections in younger persons.
"The finding comes from the agency's 10 Active Bacterial Surveillance sites, Schuchat said. As an example, she cited the Denver metro area, one of the 10 sites, where the five-year average for October is 20 cases. This October -- coinciding with a jump in H1N1 flu -- the region recorded 58 cases, Schuchat said. "Most of that increase has been in adults under the age of 60," she said.
The majority had underlying conditions that made them more susceptible to pneumococcal disease, she added. The findings probably reflect what's going on elsewhere in the country, where surveillance is less intensive, she said. "We don't think Denver is the only place this is going on," she said.
Schuchat added that only 25% of high-risk adults -- those with a range of underlying conditions, including diabetes, emphysema, heart disease, and cancer -- have been vaccinated against pneumococcus.
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COPD World News Week of November 22, 2009
San Diego, CA - Indacaterol, an investigational long-acting beta2-agonist, showed benefits over both placebo and salmeterol (Serevent) for moderate-to-severe chronic obstructive pulmonary disease (COPD) in a randomized trial, researchers reported here.
Through 26 weeks, the drug significantly improved bronchodilation, health status, and dyspnea over both control arms, although the benefits reached clinical importance over the placebo group only, according to Oliver Kornmann, MD, of Mainz University Hospital in Germany.
Indacaterol "shows a trend toward improvement over salmeterol," he reported at the American College of Chest Physicians meeting. At the very least, he said, if indacaterol is approved by regulators, it could be a viable alternative to salmeterol for COPD. He said indacaterol was awaiting approval by the European Medicines Agency within the next three months, although he didn't know the drug's status in the U.S.
The INLIGHT-2 study was a randomized, double-blind, placebo-controlled trial that compared once-daily treatment with 150 mcg of indacaterol, twice-daily treatment with 50 mcg of salmeterol, and placebo. A total of 998 patients were randomized in equal numbers to each group. The mean age of the patients was 63.5. About 25% of the patients were female. Concomitant use of Inhaled corticosteroids was allowed.
Both indacaterol and salmeterol caused significant improvement in FEV1 over placebo at 12 weeks. At 26 weeks, health status with indacaterol remained significantly better than with placebo, but not better than treatment with salmeterol. At 12 and 26 weeks, both indacaterol and salmeterol improved dyspnea compared with placebo.
The most common events were a worsening of COPD and nasopharyngitis. Upper respiratory tract infections were more common in the indacaterol group than in the other two groups, a safety signal that had not been seen in previous indacaterol trials, Kornmann said. He said the reasons for the increase are unclear, but that it's likely a result of "an imbalance by chance."
Serious adverse events were more common with indacaterol than salmeterol, perhaps driven by the difference in upper respiratory tract infections, Kornmann said. There were five deaths reported - one each in the two active-treatment groups and three in the placebo group - although none was attributed to treatment.
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COPD World News Week of November 15, 2009
San Diego, CA - Men and women with chronic obstructive pulmonary disorder (COPD) derive comparable benefits from treatment with tiotropium (Spiriva), researchers presented here. A secondary analysis of a large clinical trial found improvements of similar magnitude in lung function, exacerbations, and health-related quality of life in both genders, according to Donald Tashkin, MD, of the University of California Los Angeles.
The proportion of women with COPD is steadily increasing, Tashkin said at the American College of Chest Physicians meeting. Some studies have suggested that women may be more susceptible to developing COPD from smoking, may have a harder time quitting smoking, and may respond differently to COPD therapy than men, he said.
To find out whether women reacted differently to tiotropium, Tashkin and his colleagues took a second look at data from the UPLIFT (Understanding Potential Long-Term Impacts on Function with Tiotropium) trial. This four-year, randomized, double-blind, placebo-controlled trial found that 18 mcg of tiotropium delivered via HandiHaler had significant benefits over placebo for patients with COPD.
All 5,993 patients had a post-bronchodilator FEV1 of no more than 70% the predicted value, were 40 and older, and had at least 10 pack-years of smoking with no history of asthma. A quarter of the patients were women, who were slightly younger than the men (mean age 63 versus 65). A higher proportion of women were current smokers, but, on average, they had fewer pack-years than men.
The female patients had worse health-related quality of life at baseline, according to scores on St. George’s Respiratory Questionnaire. Even though women started out with worse health-related quality of life, both men and women improved to a similar degree throughout the study.
The improvement in survival was of similar magnitude for patients of both sexes, but the reduced risk of dying during treatment was significant only for men. Tashkin said this wasn’t surprising because women are less likely to die overall, reducing the statistical power of the analysis.
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COPD World News Week of November 8, 2009
San Diego, CA - In the U.S., patients of Asian origin appear to have a substantially lower risk of hospitalization for chronic obstructive pulmonary disease than whites, researchers reported here.
After adjusting for several potential confounders, Asians were half as likely to be admitted for the disease, according to Arthur Klatsky, MD, of the Kaiser Permanente Medical Care Program in Oakland, Calif. Most specifically, the risk was reduced in people of Chinese and Japanese ancestry, Klatsky told attendees at at the American College of Chest Physicians meeting.
Klatsky said that the reasons for the reduced risk were unclear, but that he and his colleagues suspected a genetic difference. A racial disparity in the occurrence of bronchial asthma in which blacks have a higher risk than whites has been shown in previous studies, but it had been unclear whether the difference applied to COPD, Klatsky said. There had also been little information on how risk of both conditions differed in Asian groups, he said.
To explore the issue, he and his colleagues examined data from 126,263 patients who received treatment at Kaiser Permanente from 1978 to 1985. They were followed until 2008. According to self report, 56% were white, 27% were black, 11% were Asian, and 4% were Hispanic.
During follow-up, there were 726 hospitalizations for a primary diagnosis of bronchial asthma and 760 for COPD. After adjustment for age, sex, body mass index, education, smoking, and alcohol intake, both blacks and Asians had increased risks of being admitted for bronchial asthma compared with whites. Hispanics did not have an elevated risk.
The risk in Asians was confined to those of Filipino heritage, who made up about 3% of the total patient population. The reason is unclear, Klatsky said.
The risk of being hospitalized for COPD was lower for all other racial or ethnic groups compared with whites. Among blacks, the association was strongest in women, patients 50 and older, and those with cardiorespiratory symptoms at baseline. The lower risk in Asians was consistent when the patients were stratified by sex, age, smoking, baseline cardiorespiratory symptoms, and specific COPD diagnoses, including chronic bronchitis and others. But risk was not reduced in Filipinos and patients in the "other" category.
Klatsky said the study was limited in that the researchers had access to baseline smoking data only. In addition, he said, the findings reflect information about hospitalizations only, and not general rates of bronchial asthma and COPD.
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COPD World News Week of November 1, 2009
Madison, Wisconsin - Out of five different smoking cessation modalities, the nicotine patch plus lozenges proved to be the most efficacious Megan E. Piper, PhD, of the University of Wisconsin School of Medicine and Public Health, Madison, and colleagues reported in the November issue of Archives of General Psychiatry.
The findings suggest that a “combination pharmacotherapy comprising the nicotine patch and an ad libitum nicotine replacement therapy should be routinely considered for use as a smoking cessation treatment,” the researchers said. According to background information in the study, there’s little comparative research on the efficacy of different smoking cessation pharmacotherapies. But that kind of evidence is necessary to make informed decisions about which products to use and prescribe, the researchers said.
They conducted a randomized, double-blind, placebo-controlled trial of 1,504 adults who had smoked at least 10 cigarettes a day for the preceding six months. Patients were disqualified if they used any form of tobacco other than cigarettes, were currently taking bupropion (Zyban), or had a diagnosis of psychosis or schizophrenia. They were randomized to one of five treatment scenarios—nicotine lozenge, nicotine patch, sustained-release bupropion, patch plus lozenge, or bupropion plus lozenge—or to placebo for eight to 12 weeks. Smoking rates were assessed at one week, eight weeks, and six months after the quit date.
The researchers found that all quitting modalities were better than placebo for initial cessation and seven-day point-prevalence abstinence rates at one week, at the end of treatment, and six months later. However, only the patch-plus-lozenge group had significantly higher abstinence rates after six months than placebo.
”These therapies ... would have been found to be efficacious relative to placebo had they been tested in a typical randomized clinical trial involving only a single active treatment and a placebo control,” the researchers said. “Thus, the current results suggest that there was a relatively strong effect of the patch plus lozenge versus placebo, rather than unusually weak effects of the other interventions.”
They added that adverse events were consistent with previous research: skin irritation associated with patch use, sleep disturbances and abnormal dreams for those on bupropion, and nausea for those on lozenges. Patients in the combination therapies reported more adverse events than those on monotherapy or placebo. There was only one serious adverse event—hospitalization for seizures—which was possibly related to study medication, the researchers said.
The study was limited because of the short period of time assessed (eight to 12 weeks) and because it did not assess varenicline because the drug was not FDA approved at the start of the trial.
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COPD World News Week of October 25, 2009
Ottawa, ON - Current guidelines for the management of chronic obstructive pulmonary disease (COPD) recommend the regular use of inhaled bronchodilator therapy in order to relieve symptoms and prevent exacerbations. A recently published scientific abstract reviewed patient preferences for inhaler devices used by COPD patients.
According to researchers Richard Hodder and David Price of the University of Ottawa, a variety of inhaler devices are currently available to COPD patients, and the choice of device is an important consideration because it can influence patients’ adherence to treatment, and thus potentially affect the long-term outcome.
The researchers reviewed clinical studies of inhaler satisfaction and preference comparing Respimat® SMI against other inhalers in COPD patients. Using objective and validated patient satisfaction instruments, Respimat® SMI was consistently shown to be well accepted by COPD patients, largely due to its inhalation and handling characteristics.
In comparative studies with pMDIs, the patient total satisfaction score with Respimat® SMI was statistically and clinically significantly higher than with the pMDI. In comparative studies with DPIs, the total satisfaction score was statistically significantly higher than for the Turbuhaler® DPI, but only the performance domain of satisfaction was clinically significantly higher for Respimat® SMI.
Whether the observed higher levels of patient satisfaction reported with Respimat® SMI might be expected to result in improved adherence to therapy and thus provide benefits consistent with those recently shown to be associated with sustained bronchodilator treatment in patients with COPD remains to be proven.
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COPD World News Week of October 18, 2009
Hannover, Germany - For moderate-to-severe chronic obstructive pulmonary disease (COPD), a triple regimen of a long-acting beta-agonist (LABA), an inhaled corticosteroid, and an antimuscarinic agent substantially reduced exacerbations compared with monotherapy in a randomized trial.
Severe exacerbations dropped 62% when combination budesonide and formoterol (Symbicort) was added to tiotropium (Spiriva), according to Tobias Welte, MD, of Hannover Medical School in Germany, and colleagues. Triple therapy also significantly improved lung function, COPD symptoms, and quality of life, they reported in the American Journal of Respiratory and Critical Care Medicine. These findings were reassuring, since triple therapy "appears to have become routine practice," commented Paul W. Jones, MD, PhD, of St. George's at the University of London.
In an accompanying editorial, he noted that 40% of trial participants were already on triple-agent regimens before enrollment. Current guidelines recommend the addition of an inhaled corticosteroid to a long-acting bronchodilator for patients with more severe COPD and a history of exacerbations. But they suggest using both LABA or muscarinic antagonists and inhaled corticosteroids, or all three, for only a small subgroup of patients.
Welte's group conducted a double-blind study in 660 COPD patients from nine countries. All had a prebronchodilator forced expiratory volume in one minute (FEV1) of 50% or less of the predicted normal value, along with a history of exacerbations requiring systemic steroids, antibiotics, or both. Patients all received 18 μg of tiotropium once daily and were randomized to either placebo or one inhalation of 320 μg of budesonide and 9 μg of formoterol each day for 12 weeks.
All COPD symptoms measured showed greater improvements both day and night with more extensive treatment, including improvements in breathlessness, nighttime awakening, chest tightness, and cough. Benefits involving morning symptoms and ability to perform routine morning activities was particularly notable, the researchers wrote, because "patients with COPD indicate morning as the time when their symptoms particularly are most severe, impacting negatively on social and physical morning activities. "For the more serious outcome of severe exacerbations, rates were substantially lower with the three-drug combination compared with tiotropium monotherapy.
The researchers said this magnitude of reduction is unprecedented in COPD, but Jones cautioned against making comparisons across trials. Exacerbation events were defined by worsening of COPD leading to treatment with systemic corticosteroids, or hospitalization or emergency department visits, or both; whereas some prior trials have used acute change in COPD medications as the sole criterion.
Welte's group acknowledged that the study was limited by its short duration, as well as lack of a budesonide, formoterol, or budesonide/formoterol arm that would have allowed researchers to tease apart the impact of individual agents.
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COPD World News Week of October 11, 2009
Modena, Italy - The benefits of exercises to strengthen muscles in the upper arms, shoulders, and chest of patients with COPD extend beyond the upper extremities, results of a clinical trial indicate.
Unsupported upper extremity exercises "may ameliorate the patients' general exercise capacity and autonomy, over and above standard pulmonary rehabilitation," physical therapist Stefania Costi and associates in Italy report in the August issue of Chest.
The current guideline on pulmonary rehabilitation for COPD patients advocates exercise training targeted at the muscles of the upper extremities in COPD patients. The theoretical rationale for this advice involves the dual role of upper extremity muscles that sustain the upper girdle while also acting as accessory respiratory muscles. However, Dr. Costi, from the University of Modena and Reggio Emilia, and her team found that the quality of previous clinical trials has been so poor that there are no reliable data to support this type of training. They therefore conducted their own randomized trial among patients with stable COPD who had been referred for inpatient pulmonary rehabilitation, to study the effects of 15 sessions of unsupported upper extremity exercise training.
Twenty-five patients each (mean age 69 years) were randomly assigned to regular rehabilitation or rehabilitation plus the upper extremity training. All patients completed the trial. The training consisted of five movements while holding dumbbells to activate the pectoralis, deltoids, triceps brachii, trapezius, and biceps brachii.
The primary outcome was change in the 6-minute ring test, in which the total number of rings moved were counted and change in physiologic measures — heart rate, pulse oximetry, respiratory rate, perceived dyspnea and arm fatigue — were monitored. Secondary outcomes were an activities of daily living field test, the 6-minute walking test, and scales to assess the extent and effect of breathlessness on daily activities. Evaluations carried out at the end of the study period indicated that patients in the intervention group improved significantly.
At a 6-month follow-up, the intervention group maintained the greater improvement in the 6-minute ring test and in the degree of dyspnea experienced during daily activities. Besides corroborating the efficacy of unsupported upper extremity exercise testing in improving exercise capacity, "this trial provides new and relevant data regarding the benefits of this specific training on clinically important outcomes, such as the ability to perform activities of daily living that involve the upper extremities and the fatigue related to those activities," Costi and associates conclude.
Unexpected - was the improvement of general exercise capacity, surpassing the minimal clinically important difference for patients with COPD.
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COPD World News Week of October 4, 2009
Gainesville, FL - Researchers at the University of Massachusetts Medical School and the University of Florida in Gainesville have safely given new, functional geneto patients with a hereditary defect that can lead to fatal lung and liver diseases, according to clinical trial findings slated to appear soon in the online early edition of the Proceedings of the National Academy of Science.
"This trial represents a very important step toward a potential gene therapy for the 100,000 or more Americans who suffer with alpha-1 antitrypsin deficiency," said Terence R. Flotte, MD, dean of the School of Medicine and provost & executive deputy chancellor of U Mass Medical School.Patients with alpha-1 antitrypsin deficiency cannot produce a protective form of the protein alpha-1 antitrypsin, which is normally produced in the liver and protects the lungs from inflammation.
Those lacking alpha-1 antitrypsin are vulnerable to infections or irritants in the air, such as cigarette smoke, and often develop life-threatening lung disease. Some people with the deficiency lead disease-free lives, never knowing they have defective genes. In others, the deficiency can lead to emphysema and cirrhosis, both progressive diseases that can be fatal.
In the clinical trial, three patients who received injections of a harmless virus containing copies of a correct gene for alpha-1 protein in their upper arms were able to produce trace amounts of alpha-1 antitrypsin for up to one year. Although the levels produced were not considered therapeutic, the study provided critical "proof of principle" that a corrected, functioning gene could trigger production of the protein.
The National Heart, Lung and Blood Institute recently awarded a five-year, $2 million grant to Dr. Flotte for further clinical trials studying the use of an adeno-associated virus to deliver the alpha-1 antitrypsin gene.
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COPD World News Week of September 27, 2009
Liverpool, England - An investigational phosphodiesterase 4 (PDE4) inhibitor called roflumilast may help some patients with chronic obstructive pulmonary disease, four multicenter, randomized controlled trials showed.
In two trials of patients with severe COPD, the drug improved lung function and reduced the rate of exacerbations compared with placebo, according to Peter Calverley, MD, of University Hospital Aintree in Liverpool, England, and colleagues. In the other two trials, involving patients with moderate-to-severe COPD, roflumilast provided lung function benefits beyond treatment with long-acting inhaled bronchodilators. But it did not affect the rate of exacerbations, according to Klaus Rabe, MD, of Leiden University Medical Center in The Netherlands, and colleagues. The results of all four trials were reported in two papers published in the Aug. 29 issue of The Lancet. Calverley and Rabe were listed as authors on both.
Current COPD treatments alleviate some of the clinical symptoms of the disease but do not address the underlying inflammatory processes, the researchers said. Previous studies had suggested that roflumilast can improve lung function and prevent exacerbations in some patients with moderate-to-severe and severe COPD, but the findings had not been confirmed in large, randomized controlled trials.
For the two trials evaluating severe COPD the researchers recruited patients older than 40 who had severe airflow limitation, symptoms of chronic bronchitis, and a history of exacerbations. In the two trials combined, 1,537 patients were assigned to roflumilast (500 µg/day taken orally) and 1,554 to placebo for one year. Roflumilast bested placebo on both primary outcomes.
The benefits were independent of smoking status and the use of other COPD medications. "The results show that carefully defined patient groups that are particularly at risk of exacerbations benefit from treatment with roflumilast," the researchers said.
In an accompanying editorial, Paul O'Byrne, MD, and Gail Gauvreau, PhD, of McMaster University in Hamilton, Ontario, cautioned that "several issues remain to be resolved before the place of PDE4 inhibitors in the range of drugs available for COPD is clarified. "For instance, the functional benefits of the improvements in lung function have yet to be established, they said. In addition, the trials evaluating roflumilast added to long-acting inhaled bronchodilators were not designed to compare the combinations, and it remains unclear which would be superior.
Finally, they said, future studies need to resolve whether the benefits of roflumilast will persist when compared to treatment with inhaled corticosteroids and long-acting bronchodilators.
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COPD World News Week of September 20, 2009
Basel, Switzerland - Novartis announced results from Phase III trials showing its experimental bronchodilator indacaterol significantly improved lung function and provided a significant reduction in breathlessness compared to Pfizer and Boehringer Ingelheim's Spiriva (tiotropium) in patients with chronic obstructive pulmonary disease.
Novartis noted that it plans to use the drug "to form the foundation of a new portfolio of products" for respiratory health. Commenting on the data, Vontobel analyst Andrew Weiss noted that "the potential superiority of [indacaterol] over gold standard treatment Spiriva is very reassuring and could lead to increased revenue forecasts going forward."
Many analysts expect indacaterol to reach over $1 billion in sales, however, Birgit Kuhlhoff of Rahn & Bodmer cautioned that the other gold standard treatment for COPD, GlaxoSmithKline's Advair, is losing patent protection in the United States in 2011, so pricing will become an issue for Novartis.
Indacaterol is currently under review by EU and US regulators.
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COPD World News Week of September 13, 2009
Vancouver, BC - Pooled data from seven large prospective trials show that inhaled budesonide (Pulmicort) does not increase COPD patients' risk of developing pneumonia, researchers said.
An adjusted hazard ratio for pneumonia of 1.05 was found for budesonide as an adverse event in the trials, compared with either placebo or inhaled formoterol (Perforomist, Foradil), reported Don D. Sin, MD, of the University of British Columbia in Vancouver, and colleagues. The findings of the meta-analysis, reported in the August 29 issue of The Lancet, were similar when Sin and colleagues looked at pneumonia classified as a serious adverse event.
The seven trials included a total of 7,042 patients, for whom the authors were able to obtain individual data. "Results from our study have shown that budesonide was not significantly associated with one-year risk of pneumonia in patients with COPD and therefore is safe for clinical use in such patients," they wrote. The findings contradicted two meta-analyses published in 2008 and earlier this year, the researchers noted.
Sin and colleagues sought randomized studies comparing budesonide, alone or in combination with formoterol (sold as Symbicort), with a control regimen that could be either placebo or formoterol alone, in patients with stable COPD and with at least six months of follow-up.
The seven trials meeting their criteria had a total of 5,212 patient-years of exposure to the study drugs. The primary outcome in the meta-analysis was cases of pneumonia listed as adverse events or serious adverse events, during the trial or up to 15 days after treatment ended. Results were adjusted for age, sex, smoking status, body mass index, and one-second forced expiratory volume (FEV1) after bronchodilator dosing.
In an accompanying editorial, Tobias Welte, MD, of the University of Hannover in Germany, said the findings still left room for concern, largely because of the uncertainties in pneumonia diagnoses reported in the trials. He noted that chest x-rays were not required. "Diagnoses of community-acquired pneumonia on the basis of only clinical observations has proven unreliable," Welte wrote, adding that mistakes are possible even in diagnosing the condition in hospitalized patients.
But he found the data reassuring overall. "In assessment of the role of inhaled corticosteroids, the rate of community-acquired pneumonia might affect the clinical use of such drugs if there is any suspicion of additional morbidity or mortality," Welte said. "But this signal was not found in any of the studies discussed here."
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COPD World News Week of September 6, 2009
Leuven, Belgium - Inhaling the long-acting bronchodilator tiotropium (Spiriva) appears to be beneficial for patients with early-stage chronic obstructive pulmonary disease, researchers found. Through four years of treatment, lung function declined at a slightly but significantly slower rate in patients taking tiotropium than in those taking placebo, according to Marc Decramer, MD, of the University of Leuven in Belgium, and colleagues.
The results, reported in The Lancet, came from a prespecified subgroup analysis of the UPLIFT (Understanding Potential Long-Term Impacts on Function with Tiotropium) trial, which found that tiotropium improved lung function and quality of life in patients with all stages of COPD.
The current findings "suggest that treatment with a long-acting anticholinergic drug has substantial benefits in patients with moderate COPD, and therefore provides a rational basis for starting treatment in patients with this stage of the disease," the researchers said.
Agreeing in an accompanying editorial were Lisa Davies, MBChB, and Peter Calverley, MD, of University Hospital Aintree in Liverpool, England. The results "should encourage those developing plans for the early identification of COPD . . . that identifying such patients is indeed worthwhile and can provide the patient with better symptomatic control of their condition and improvements in their overall well-being," they said.
Previously, there was little data involving the benefits of starting treatment in the early stages of COPD, according to Decramer and his colleagues. So for this analysis, they looked only at patients with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage II, or moderate, COPD. Among their subjects, 1,218 received tiotropium (18 µg/day) and 1,157 received placebo.
Through four years, the rate of decline of the mean postbronchodilator FEV1 was 12% lower in the tiotropium group. Though statistically significant, the researchers acknowledged that this effect "was small and might not be clinically significant." The rate of decline of prebronchodilator FEV1 did not differ significantly between the two groups. Compared with those taking placebo, tiotropium patients had significantly better health status, according to the St. George's Respiratory Questionnaire, at all times during the study. The time to first exacerbation was 18% longer and the time to hospital admission due to an exacerbation was 26% longer in the tiotropium group.
The risk of mortality from lower respiratory tract conditions and from all causes tended to be lower for the tiotropium group, but the differences did not reach statistical significance, perhaps because of the lack of statistical power to detect an effect.
The authors acknowledged the study had limitations inherent to a subgroup analysis, albeit a prespecified one. Additional limitations included the possibility that the patients may not have been representative of all patients with moderate disease, and the exclusion of patients with less severe GOLD stage II disease and those without symptoms.
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COPD World News Week of August 30, 2009
San Diego , CA - Bio-Matrix Scientific Group, Inc. announced its majority owned subsidiary, Entest BioMedical unit has filed a patent application for the use of *adipose derived stem cells in the treatment of COPD. BMSN is excited with the progress achieved by Entest BioMedical, Inc. in identifying diseases it believes will be treatable through Stem Cell Therapy.
COPD is a major health disorder that appears to be treatable through adipose derived stem cell therapy. Currently, this disease is treated in similar fashion to asthma, utilizing inhalers and /or oxygen therapy. These methods are not solutions to the disease but merely provide the patient with greater level of comfort.
Steven Josephs, PhD. noted, “The approach is intended at the very least to alleviate the chronic inflammation in COPD. This is done by using agents known to coax adult stem cells that are delivered to the diseased lung tissue (blood monocyte cells) to release cytokines (biologically active molecules) which in addition to the anti-inflammatory effects may actually promote the regeneration of functional lung tissue.”
The goal of Entest BioMedical, Inc. is to develop a stem cell therapy that reverses the effects of COPD on the respiratory system. The Company is working with Dr. Feng Lin, its Scientific Director and Steven Josephs, PhD in developing this stem cell treatment.
Adipose tissue, commonly known as fat, is the human body’s richest known source of stem cells, as well as other cells that are believed to contribute to repair and healing, referred to as “regenerative cells.” Due to its abundance and accessibility in the body, adipose tissue represents an ideal source for immediate access to a patient’s own stem and regenerative cells.
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COPD World News Week of August 23, 2009
Barcelona, Spain - Early, noninvasive mechanical ventilation may help prevent complications in patients with chronic respiratory conditions who experience hypercapnia when they first try to breathe on their own after intubation, a small study found. Respiratory failure following extubation developed in 15% of patients randomized to noninvasive ventilation compared with 48% of those receiving conventional oxygen therapy according to Miquel Ferrer, MD, of Hospital Clinic, Barcelona, and colleagues.
Cumulative 90-day mortality on Kaplan-Meier curves also was lower in the noninvasive ventilation group the researchers reported online in The Lancet. Respiratory failure requiring reintubation has been reported in up to 23% of patients after extubation, but reintubation is an independent risk factor for complications including nosocomial pneumonia and death.
Previous studies evaluating noninvasive ventilation as an alternative to reintubation have had mixed results. But a subgroup analysis by Ferrer and colleagues determined that the potential benefits were limited to patients who experienced hypercapnia during a spontaneous breathing (weaning) trial before extubation. To confirm this finding, they undertook a controlled trial of 106 consecutive patients with chronic respiratory disorders who had been intubated for at least 48 hours and became hypercapnic when they tried to breathe on their own.
Patients who developed major predefined clinical events such as cardiac or respiratory arrest were immediately reintubated, but those from either group who had respiratory failure but did not meet the criteria for reintubation were given rescue therapy with noninvasive ventilation. Rescue therapy permitted avoidance of reintubation in two of seven patients in the noninvasive ventilation group and in 15 of 20 patients in the control group.
The study findings suggest that noninvasive ventilation has protective effects beyond avoidance of reintubation, with differences in mortality between the groups occurring after discharge from the intensive care unit, according to the investigators.
Intensive-care and in-hospital mortality did not differ between the groups, but 90-day mortality was 11% in the noninvasive ventilation group and 22% in the control group. The investigators noted that, unlike some previous researchers, they used a ventilator specifically designed for this purpose, which may have helped account for their success. They also applied the ventilation continuously, rather than intermittently. Among the limitations of the study were its open design and potential bias and the fact that the study centers had extensive experience in this type of ventilation.
"This trial confirms the effectiveness of noninvasive ventilation in this clinical setting and provides scientific evidence for routine implementation of this strategy for management of mechanically ventilated patients with chronic respiratory disorders," the researchers concluded. In an accompanying editorial, Peter M.A. Calverley, MD, of University Hospital Aintree in Liverpool, U.K., noted that work such as this, which defines a subgroup that can benefit from the therapy, "moves clinical care forward." "Hopefully, data such as these will change our perceptions of how and when aggressive treatment should be offered to the many patients with chronic obstructive pulmonary disease who still need this form of help," he wrote.
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COPD World News Week of August 16, 2009
Amsterdam, The Netherlands - People with chronic obstructive pulmonary disease (COPD) suffer from muscle dysfunction which seems to be partly caused by systemic inflammation. Muscle protein breakdown as well as synthesis might be affected by this systemic inflammation. Additionally, it seems to induce excessive oxidative stress and reduce the level of growth-stimulating factors.
As exercise training can have an anti-inflammatory effect in healthy people, the main question is whether exercise (training) can also induce such effects in patients with COPD. However, because of the known inflammatory response after an acute bout of exercise, some researchers are afraid that exercise might actually worsen the inflammation in COPD.
Recent evidence suggests, however, that the response might actually be anti-inflammatory and thus beneficial. Unfortunately, the evidence about the response of the inflammatory cytokines tumor necrosis factor- and interleukin-6 to exercise in patients with COPD is inconsistent, making it impossible to conclude whether a single exercise bout is harmful or beneficial in patients with COPD.
Long-term exercise training in healthy people as well as in patients with chronic heart failure, another chronic inflammatory disease, seems to have beneficial effects on the inflammatory response. In patients with COPD, however, no training-induced changes in cytokine levels have been found and it must be concluded that physical exercise training does not seem to have an anti-inflammatory effect in COPD.
On the other hand, it does not have a proinflammatory effect, and since patients with COPD benefit from exercise training with regard to other health parameters it is still recommended that they exercise regularly.
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COPD World News Week of August 9, 2009
San Francisco, CA - Treating asymptomatic ex-smokers with oral iloprost can mitigate the changes that lead to non-small cell lung cancer and other diseases, researchers suggested here.
Former smokers who received iloprost showed a statistically significant improvement in histologic measurements of lung tissue after six months of treatment," said Robert Keith, MD, of the Veterans Affairs Medical Center in Denver. "Smokers did not exhibit any improvement," Keith told attendees at the International Association for the Study of Lung Cancer's world conference.
Animal studies have indicated that prostacyclin supplementation prevented development of lung cancer. With those studies as background, Keith and his colleagues enrolled patients in a multicenter, double-blind, placebo- controlled, phase II trial of iloprost in patients at increased risk for lung cancer. The 152 participants were either smokers or former smokers who had been exposed to at least 20 pack/years of cigarettes and had at least mild cytologic atypia on sputum cytology or a history of endobronchial dysplasia, and no previous history of cancer.
The patients were required to undergo two bronchoscopy procedures -- one at baseline and the other after six months of treatment -- and 125 completed those studies. "We found that the smokers and ex-smokers had a variety of lung conditions -- from normal tissue to carcinoma in situ and actual cancer," Keith said. "Even ex-smokers who had stopped 30 years previously had some high-level changes in tissue that put them at risk of developing lung cancer."
The participants were graded on the basis of pathology on a 1 to 6 scale, with 1 being normal. Individuals found to have carcinoma in situ were removed from the study and received treatment. The others took either iloprost (60) or placebo (65).
In the iloprost group, 31 individuals were current smokers and 29 were former smokers; in the placebo group 37 were current smokers and 28 were former smokers. Patients who were on iloprost who had stopped smoking for at least a year showed statistically significant changes in their airway biopsy scores after six months of treatment. Former smokers randomized to iloprost treatment showed significantly greater improvement in all histology measures, he said.
Keith said the greatest change was recorded among ex-smokers who showed some forms of lung changes at baseline. "The people who were normal at baseline remained normal after six months." Side effects were related to the vasodilation effects of iloprost, such as headaches and flushing. Generally, the drug was well tolerated, he said.
Iloprost is prescribed for treatment of pulmonary arterial hypertension in an inhaled formulation. Oral iloprost is not available in the U.S. The researchers said that the results of their trial warrant a phase III study of iloprost as a way to prevent lung cancer among high-risk groups.
"This is a promising study," said Erik Thunnissen, MD, PhD, a consultant pathologist at VU Medical Center in Amsterdam and a discussant on the study. "But this is a single institution study, and the classifications were performed by the institution's pathology department. "We would hope to see that in a larger study multiple institutions would be able to replicate the classifications as well as the results seen here."
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COPD World News Week of August 2, 2009
Princeton, N.J. - Lung volume reduction surgery can prolong and improve the quality of life for patients with severe emphysema, according to the first head-to-head study comparing the surgery to nonsurgical medical care.
Patients with severe emphysema in their upper lung lobes who had lung volume reduction surgery (LVRS) went an average of two years before experiencing a serious deterioration in quality of life or dying, compared to only one year for patients who received medical treatment, according a report in the American Journal of Respiratory and Critical Care Medicine.
"The trajectory for the LVRS group remained clinically and statistically different than that of the medical treatment group in the second year and throughout the five-year period," Roberto P. Benzo, MD, MSc, of the Mayo Clinic, and colleagues wrote. "These findings confirm a palliative effect of LVRS, with initial improvement of [quality of life] and subsequent maintenance of the improvement over time."
The authors cautioned that LVRS carries a 5% risk of death in the postoperative period. In fact, during the first six months after randomization, the medical treatment group fared better than the LVRS group, a finding the researchers attribute to surgery-related mortality.
During the study, known as the National Emphysema Treatment Trial, 1,218 patients with severe emphysema were randomized to receive either medical treatment or LVRS . The mean age of patients in both groups was 67. During the lung reduction surgeries, emphysematous lung tissue was removed to decrease air trapping and, consequently, shortness of breath. Nonsurgical treatment generally consisted of customized use of medication, oxygen support, smoking cessation, and pulmonary rehabilitation. Before they were randomized, the participants completed the St. George's Respiratory Questionnaire, a standardized measure of quality of life for patients with chronic respiratory disease.
The patients were followed for five years, or until they died. The subjects completed the quality of life questionnaire at regular intervals during the studies. In addition to characterizing the patients based on upper-lobe and lower-lobe-predominant emphysema, the researchers graded them on their exercise capacity as determined by a cycle ergometry test. The primary outcome of the study was a composite endpoint consisting of death or an "unquestionable and meaningful deterioration" in quality of life, defined as an 8-point or greater drop on the respiratory questionnaire.
Patients who suffered from emphysema that was predominantly in the upper lobes of their lungs (about 65% of the participants), saw significant improvements in survival and quality of life in the first two years. While the benefit began to diminish after two years, some improvement over the medical treatment group persisted for the entire five years of the study.
Among the upper-lobe-predominant patients, those with high exercise capacity faired particularly well with LVRS. The researchers found no significant effect for patients who had non-upper-lobe predominant emphysema.
The authors wrote that the inclusion of quality of life assessments provides support for the use of LVRS in the clinical care of patients with severe emphysema. "[Quality of life] measures are highly relevant to patient choices and confirm the rationale for using LVRS as a palliative tool," they wrote.
"Our findings are relevant for recommending LVRS for patients with upper-lobe-predominant emphysema and, in particular, those with high exercise capacity, a subset of patients in whom the survival benefits may be marginal but in whom the combined survival and [quality of life] benefits are pronounced.
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COPD World News Week of July 26, 2009
Coal Dust Worsens Miners' Emphysema
Princeton, N.J. - Breathing coal dust is directly linked to the severity of emphysema among coal miners, regardless of whether they were smokers, according to a new study. Emphysema was significantly more severe in coal miners compared with nonminers, in both smokers and nonsmokers, according to the report in the American Journal of Respiratory and Critical Care Medicine.
The study found that cumulative exposure to coal mine dust or coal dust retained in the lungs was a strong predictor of emphysema severity after accounting for cigarette smoking, age at death, and race. It also found that breathing coal dust and smoking cigarettes were tied to similar severity of emphysema, according to Eileen Kuempel, PhD, of the National Institute for Occupational Safety and Health, and colleagues.
While previous studies established the link between coal dust and emphysema, the authors said the new study adds to understanding of various factors, including cigarette smoking and dust exposure, in pulmonary impairment. "Better recognition of the key disease predictors may enhance opportunities for the primary prevention, diagnosis, and medical management of occupational dust-related lung diseases," the researchers asserted. "This is the first study of autopsied coal miners from the U.S. to address these issues with high-quality pathology data from whole lung sections, and smoking histories and work histories with sufficient detail to reconstruct cumulative coal mine dust exposures."
The researchers compared lung autopsy results of 616 coal miners from West Virginia with 106 nonminers from West Virginia and Vermont. The lungs from West Virginia were collected during autopsies from 1957 and 1973 at the Beckley Southern Appalachian Regional Hospital as part of a black lung study. Those from Vermont were taken from autopsies performed at the University of Vermont between 1972 and 1978.
The researchers established the age at death, race, occupation, and smoking history of the deceased when possible and estimated individual exposure to coal dust using work history data and job-specific dust exposure estimates. They examined sections of the lungs to determine the presence and extent of emphysema and analyzed the lung tissue of a subset of the study group for coal dust content.
They rated the individuals on a 1,000-point emphysema severity index. Miners tended to be older at death than nonminers due to a higher proportion of accidental or other sudden deaths among the nonminers. Miners also tended to smoke less, although this result was not statistically significant. But the researchers found that the individuals with greater concentration of coal dust in their lungs or greater exposure to coal dust had more severe emphysema.
Although the study was conducted on miners who worked before a 1972 federal standard that limited exposure to coal dust, Dr. Kuempel and colleagues argued that the findings have immediate relevance to current safety standards. The noted that exposure over a miner's lifetime career today would produce a cumulative exposure similar to the levels found in the autopsied miners. They also wrote that the study is relevant for miners in developing nations, who may be exposed to more coal dust than in the U.S.
In an accompanying editorial, Benoit Nemery, MD, PhD, of Katholieke Universiteit Leuven in Belgium, noted that global coal production has almost doubled in the past 25 years, with the fastest growth in Asia, and China in particular. "The environmental and climatic impacts of burning coal are, quite rightly, a source of concern," Dr. Nemery writes. "However, the direct consequences of extracting coal on the health of millions of coal miners must be an equal concern.
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COPD World News Week of July 19, 2009
Princeton, NJ - Patients with chronic obstructive pulmonary disease (COPD) so severe it curtails their activities or forces them to use oxygen may be at risk for cognitive decline that impairs their ability to perform daily tasks, researchers found.
The average cognition scores of older adults with severe COPD were about a point lower on a 35-point scale than adults without COPD, according to a study published in the American Journal of Respiratory and Critical Care Medicine.
"Our findings should raise awareness that adults with severe COPD are at greater risk for developing cognitive impairment, which may make managing their COPD more challenging, and will likely further worsen their general health and quality of life," William W. Hung, MD, MPH, of Mount Sinai School of Medicine, and colleagues wrote.
COPD patients suffer periods of hypoxia that previous studies have suggested may lead to brain abnormalities or aggravate Alzheimer's disease and other conditions that are associated with cognitive impairment. Although prior cross-sectional and clinical studies suggested a relationship between COPD and cognitive decline, longitudinal evidence was lacking prior to the research by Dr. Hung and his colleagues.
Dr. Hung and colleagues analyzed data from patients who participated in the Health and Retirement Study, a national prospective biennial survey of Americans 50 and older sponsored by the National Institute on Aging. The participants initially completed cognitive testing in 1996 and then took a follow-up survey in 1998, 2000, or 2002. Of the 4,150 individuals included in the study, 492 had COPD and about one-third (153) of those had severe disease, which was defined as COPD serious enough to curtail their activities or require them to use oxygen.
The mean cognition scores of older adults with both severe and nonsevere COPD were significantly lower than adults without COPD the study found. After multivariable adjustment, the scores of the adults with milder forms of COPD were no longer significantly different from those of the non-COPD adults, while the means scores of adults with severe COPD remained about a point lower.
Dr. Hung and his colleagues noted that such cognitive declines can impair a person's ability to performed everyday activities, particularly executive functions such as handling money and medication. "For patients with severe COPD, this decline in cognition and function is likely to have important clinical consequences," the authors wrote. "In order for patients with COPD to maintain independence, cognitive abilities are necessary for being adherent to complex medication regimens, such as inhalers and oxygen, and to manage other chronic diseases often associated with COPD, among other daily tasks made more difficult by activity limitations due to COPD."
The study has a number of limitations including the inability to "determine the timing of clinical diagnosis or the onset of symptoms of COPD from the HRS data. Another limitation is that "we did not have pulmonary function test data, which is the standard method to assess COPD severity, and that the clinical diagnosis of COPD relies on self-report." The authors also noted that they had failed to ask a number of questions that would have improved the quality of data obtained, "particularly with respect to other characteristics, such as atrial fibrillation, exercise, and body size parameters; these characteristics were associated with or likely to be associated with cognitive abilities." Nonetheless, they suggested that their findings could indicate a 22% increase in the number of difficulties severe COPD patients experience on daily tasks such as driving, cooking, shopping, medication, and money management.
"Often, patients with cognitive difficulties, if undetected and untreated, have lower adherence to their treatment and follow-up regimens, and, as a consequence, may deteriorate more rapidly and have worse health outcomes," they wrote.
They recommended that COPD patients whose activity level is limited by the disease or who are dependent on oxygen undergo periodic cognition screening and that physicians watch for cognitive changes in patients. "Physicians and other clinical staff managing the care of these patients should be aware of their increased risk for cognitive decline and the greater needs and challenges associated with caring for cognitively impaired older adults," they wrote.
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COPD World News Week of July 12, 2009
Silver Spring, MD - Two drugs prescribed to help people quit smoking, Chantix and Zyban, will now carry "black-box" warnings on the potential risks of psychiatric problems, including depression and suicidal thoughts, said U.S. health officials.
The U.S. Food and Drug Administration said it was mandating the black-box warnings, the strictest possible, based on reports to the agency of these side effects and on a review of clinical trials and scientific literature. "We are requiring the manufacturers of the smoking-cessation drugs Chantix and Zyban to add a new boxed warning highlighting the risk of serious mental health symptoms with use of these products," Dr. Curt Rosebraugh, director of the FDA's Office of Drug Evaluation II, said during a recent teleconference.
The agency's review found that some people who used Chantix (varenicline) and Zyban (bupropion) experienced unusual changes in behavior, became depressed, or had their depression worsen and had thoughts of suicide or dying, the FDA said.
Rosebraugh said there were reports of 98 suicides and 188 suicide attempts involving Chantix, and 14 suicides and 17 attempts reported with Zyban. For many users, the problems started soon after they began taking the drugs and ended when they stopped taking them. Some users, however, continued to have symptoms even after stopping the drugs.
In a few cases, the problems started after the drugs were stopped, Rosebraugh said. People taking these drugs who develop any of these symptoms should be monitored until their symptoms clear up, even if symptoms develop after stopping these drugs, Rosebraugh added. The drugs don't contain nicotine, and some of the symptoms may be caused by nicotine withdrawal.
People who stop smoking can suffer from depression, anxiety, irritability, restlessness, and sleep disturbances, the FDA noted. Some patients who were using the drugs experienced the side effects while they were still smoking, the agency said. Rosebraugh said the risk of using these drugs needs to be balanced with the substantial benefits of quitting smoking as these drugs can be very effective.
"Stopping smoking is a goal we all want to work towards, and if people need medication to do it they should have access to it. So we don't want to scare people off from trying to use a medication to stop smoking; we just want them to be carefully monitored," he said. In addition to the warning, the FDA is requesting more prescribing information in the warning section of the label, and new information in the Medication Guide for patients that discusses the risk of mental health events while using these products.
The makers of the drugs will also be required to do a clinical trial to see how often serious psychiatric symptoms occur in patients using a variety of therapies to help them quit smoking, including patients who currently have psychiatric disorders, Rosebraugh said. Results of this trial won't be known for several years, he added. Chantix is manufactured by Pfizer Inc. - Zyban is made by GlaxoSmithKline.
"The labeling update underscores the important role of health-care providers in treating smokers attempting to quit and provides specific information about Chantix and instructions that physicians and patients should follow closely," Dr. Briggs W. Morrison, senior vice president for the Primary Care Development Group at Pfizer, said in a prepared statement. "Quitting smoking is one of the best things people can do for their health, but the quitting process is both difficult and complex."
The FDA's review of consumers using nicotine patches did not find a link between patches and psychiatric side effects. The antidepressant Wellbutrin, which contains the same active ingredient as Zyban, already carries a black-box warning.
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COPD World News Week of July 5, 2009
Munich, Germany - Women typically get heart disease much later than men, but not if they smoke, researchers here said last month. In fact, women who smoke have heart attacks nearly 14 years earlier than women who don't smoke, Norwegian doctors reported in a study presented to the European Society of Cardiology.
For men, the gap is not so dramatic; male smokers have heart attacks about six years earlier than men who don't smoke. "This is not a minor difference,'' said Dr. Silvia Priori, a cardiologist at the Scientific Institute in Pavia, Italy. "Women need to realize they are losing much more than men when they smoke,'' she said. Priori was not connected to the research.
Dr. Morten Grundtvig and colleagues from the Innlandet Hospital Trust in Lillehammer, Norway, based their study on data from 1,784 patients admitted for a first heart attack at a hospital in Lillehammer.Their study found that the men on average had their first heart attack at age 72 if they didn't smoke, and at 64 if they did.
Women in the study had their first heart attack at age 81 if they didn't smoke, and at age 66 if they did. After adjusting for other heart risk factors like blood pressure, cholesterol and diabetes, researchers found that the difference for women was about 14 years and for men, about six years.
Previous studies looking at a possible gender difference have been inconclusive.
Doctors have long suspected that female hormones protect women against heart disease. Estrogen is thought to raise the levels of good cholesterol as well as enabling blood vessel walls to relax more easily, thus lowering the chances of a blockage. Grundtvig said that smoking might make women go through menopause earlier, leaving them less protected against a heart attack.
With rising rates of smoking in women, compared with falling rates in men, Grundtvig said that doctors expect to see increased heart disease in women. "Smoking might erase the natural advantage that women have,'' said Dr. Robert Harrington, a professor of medicine at Duke University and spokesman for the AmericanCollege of Cardiology.
Doctors aren't yet sure if other cardiac risk factors like cholesterol and obesity also affect women differently."The difference in how smoking affects women and men is profound,'' Harrington said. "Unless women don't smoke or quit, they risk ending up with the same terrible diseases as men, only at a much earlier age."
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