Study Finds COPD Patients Taking Inhaled Steroids are at Greater Risk for Severe Pneumonia
NEW YORK, July 16, 2007--Patients with COPD (chronic obstructive pulmonary disease) are increasingly being prescribed inhaled corticosteroids to control exacerbations of the disease, but a new study finds that the anti-inflammatory drugs increase the chances that these patients will be hospitalized for pneumonia.
"In a large cohort of patients with COPD, we found that current inhaled corticosteroid use was associated with a significant 70 percent increase in the risk of being hospitalized for pneumonia," said the researchers. "Furthermore, for the severest pneumonias leading to death within 30 days of hospitalization, the risk with current inhaled corticosteroid use was also significantly increased."
These and other findings of the population-based study were reported in the second issue of the July American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.
Pierre Ernst, M.D., a clinical epidemiologist at McGill University, Canada, along with three other researchers from the university's department of medicine, analyzed the hospitalization and drug prescription information from 1988 to 2003 of 175,906 patients with COPD living in Quebec, Canada. During that time, 23,942 of the patients were hospitalized for pneumonia.
In their report, the researchers noted that the admission rate for pneumonia increased with higher doses of inhaled steroids and that reduction in risk was observed once the medications were stopped. Among all patients taking inhaled steroids, there was a 53 percent increase in pneumonia deaths within 30 days of being admitted to the hospital.
The investigators noted that these findings are particularly relevant, given that pneumonia is the third leading cause of hospitalization in the United States and that inhaled corticosteroid use among patients with COPD increased from 13.2 to 41.4 percent from 1987 to 1995.
"Adverse effects of inhaled corticosteroids in patients with COPD," the authors said, "are particularly troublesome given the limited evidence for their efficacy."
In an accompanying editorial, Mark Woodhead, D.M, of Manchester (U.K.) Royal Infirmary, wrote that this report confirms secondary findings from a prospective, placebo-controlled study of an inhaled corticosteroid with long-acting ?-agonist that was recently published. Given that this earlier study was not designed to analyze pneumonia frequency, its small size and high drop-out rate, he suggested, might lead a reader to reasonably conclude that its "pneumonia findings were spurious."
Now, with the addition of the Canadian population-based study, Dr. Woodhead wrote, the unexpected conclusion--that drugs prescribed to prevent COPD exacerbations put patients at greater risk for severe pneumonia-deserves further consideration and study through large prospective studies with objective pneumonia definitions.
"The finding of an association," he said, "between pneumonia frequency and inhaled corticosteroid use in studies of different design, in different populations, and with evidence of a dose-response relations means that the findings may be real and that these observations cannot simply be dismissed."
Contact for study: Pierre Ernst, M.D., Division of Clinical Epidemiology, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, PQ, H3A 1A1, Canada Phone: (514) 934-8014 E-mail: Pierre.Ernst@mcgill.ca
Contact for editorial: Mark Woodhead, D.M., University of Manchester, Manchester Royal Infirmary, Department of Respiratory Medicine, Oxford Road, Manchester M13 9WL, United Kingdom Phone: +44 161 276 4381 E-mail: Mark.Woodhead@CMMC.nhs.uk
Nasal Cannula May be Viable Treatment for Sufferers of Sleep Apnea
Researchers at Johns Hopkins University have found that symptoms in patients with obstructive sleep apnea and hypopnea can be significantly reduced through treatment with nasal insufflation (TNI), using a nasal cannula to deliver warm, humidified air at a high flow rate.
"Our findings provide evidence that TNI may offer a viable treatment alternative to patients with obstructive hypopneas and apneas," said lead researcher Hartmut Schneider, M.D., of Johns Hopkins Asthma and Allergy Center.
The research was reported in the second issue for July 2007 of the American Journal of Respiratory and Critical Care Medicine published by the American Thoracic Society.
The proof of concept study included 11 patients with mild to severe apnea-hypopnea disorders, who were selected to provide a balanced range of disease severity. Apnea was defined as complete cessation of airflow for more than 10 seconds. Hypopnea was defined as a greater than 30 percent reduction of airflow.
After baseline data were established for each patient while undergoing TNI at 0, 10 and 20L/minute, subjects were randomized to receive either no treatment or treatment with TNI at 20L/minute on separate nights. Researchers then measured airflow and superglottic pressure and monitored body position, sleep arousals and respiratory events.
At TNI of 10L/minute, some indications of disordered breathing showed improvement, but airflow limitations and snoring persisted. However, at TNI of 20L/minute, all patients showed a marked improvement. "When TNI was administered, sleep and breathing patterns stabilized," said Dr. Schneider.
Furthermore, the results showed that even patients with more severe disorders gained significantly from TNI. "Although we expected marked improvements in the apnea-plus-hypopnea index (AHI) primarily in patients with hypopneas rather than obstructive apneas, TNI lowered the AHI in all subjects," the researchers wrote.
These findings suggest that TNI may be a more viable treatment option for patients with hypopnea and sleep apnea. "Current treatment options.are often intrusive or invasive and not well-tolerated, leaving a vast number of patients untreated," said Dr. Schneider. "Improved therapeutic strategies are required to treat sleep apneas and hypopneas and their associated morbidity and mortality."
Sleep apnea affects more than 12 million Americans, according to the National Institutes of Health, and is especially prevalent in overweight or obese individuals. Many more have the milder form of sleep-associated respiratory disorders, hypopnea. Untreated sleep apnea can increase the chance of having high blood pressure and risk of heart attack, stroke and diabetes, as well as putting patients at risk for work-related accidents and driving accidents.
"At present, CPAP [continuous positive airway pressure] is most effective at eliminating apneas and hypopneas, [but] long-term effectiveness is compromised by low adherence," wrote the researchers. "We developed a simplified method for increasing pharyngeal pressure by delivering warm and humidified air at a continuous high flow rate through the open nasal cannula."
While patients with severe sleep apneas may be more highly motivated to adhere to treatment with CPAP or surgery, younger, thinner and healthier patients with milder disorders may find the TNI approach appealing, according to Dr. Safwan Badr, chief of pulmonary, critical care and sleep medicine at Haper University Hospital in Detroit and chair of the American Thoracic Society's Assembly on Respiratory Neurobiology and Sleep.
The authors noted that the minimally intrusive nasal interface of TNI may improve patient adherence, and may ultimately prove more effective at managing long-term morbidity and mortality of sleep apnea." Furthermore, the fact that one flow rate and one cannula size were sufficient to stabilize breathing patterns in the majority of subjects suggests that titration of TNI may be unnecessary, streamlining the initiation of treatment.
The present study is a proof of concept, the authors wrote, and will require replication in clinical trials. However, the study represents the first step in developing a new potential alternative to current sleep apnea treatments that may lower the barrier for care in patients with sleep-associated breathing disorders.
Contact for study: Hartmut Schneider, M.D., Assistant Professor, Johns Hopkins Asthma and Allergy Center, 5501 Bayview Blvd., Baltimore, MD 21224 Phone: (410) 550-4706 E-mail: hschnei3@jhmi.edu
A Marker for Cardiovascular Disease May Also Indicate Severity of Cognitive Disability among Children with OSA
C-reactive protein, a marker of inflammation that is often used to detect cardiovascular disease, may also indicate cognitive impairment in children with obstructive sleep apnea (OSA), according to a new study of children ages 5 to 7.
"Children with OSA have increased levels of hsCRP [high-sensitivty C-reactive protein] and also exhibit decreased cognitive performances," said lead researcher David Gozal, M.D., of the University of Louisville in Kentucky. "Furthermore, hsCRP levels are significantly increased among patients with OSA and cognitive dysfunction."
These findings were published in the second issue of the July American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.
To identify children for the study, parents in the Jefferson County (KY) Public School system were invited to complete a questionnaire about their children's sleeping habits. Responses indicating almost no likelihood of OSA and those indicating a high likelihood of OSA were randomly selected, and the children were invited to a sleep research center. (Obese children were excluded from the study, because the condition "is now viewed as a low-grade systemic inflammatory disorder, and is associated with increased risk for cognitive deficits.")
At the sleep center, the children underwent overnight polysomnographic assessment and then, in the morning, completed tests to determine their reasoning and conceptual abilities. The results of the individual tests were aggregated into a General Conceptual Ability (GCA) score, with a mean of 100 and a standard deviation of 15
Of a total of 278 children who completed all phases of the evaluation, 73 served as controls. They had no evidence of OSA and their cognitive scores were all normal.
Among the 102 children with OSA, 57 had GCA scores less than 85 percent. The mean level of hsCRP in children with OSA and abnormal scores was approximately 250 percent higher than the control group and approximately 200 percent higher than the level for children with OSA who did not exhibit cognitive impairment.
The authors suggest that an important question yet to be answered is whether OSA treatment would eliminate any cognitive deficits. They cite an earlier study they conducted which found that after an adenotonsillectomy, hsCRP levels in children with OSA were usually reduced.
According to the authors, however, the current findings "reinforce the concept that systemic inflammation is a constitutive component and consequence of OSA" and that the "presence of increased systemic inflammation, as dictated by hsCRP levels and potentially the levels of other inflammatory markers, will increase the probability for decreased neurocognitive function."
Contact for study: David Gozal, M.D., Kosair Children's Hospital Research Institute, University of Louisville School of Medicine, 570 S. Preston Street, Ste. 204, Louisville, KY 40202 Phone: (502) 852-2323 E-mail: david.gozal@louisville.edu
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These news briefs are based on articles published in the American Thoracic Society's peer-reviewed journal, the American Journal of Respiratory and Critical Care Medicine. In reporting on these finding, contact information is for your use only, not for publication. Journalists may obtain the full text of these articles, request a complimentary subscription to the journal, or identify an expert not related to the research to comment on the article by contacting Suzy Martin, Communications Manager, at smartin@thoracic.org or (212) 315-8631 or Brian Kell, Director of Communications, at (212) 315-6442 or bkell@thoracic.org.
Founded in 1905, the American Thoracic Society is the world's leading medical association dedicated to advancing pulmonary, critical care and sleep medicine. The Society has more than 18,000 members who prevent and fight respiratory disease around the globe, through research, education, patient care and advocacy.
American Thoracic Society Journal News Briefs for July 15, 2007 (Second Issue) For More Information, Contact: Suzy Martin, (212) 315-8631 smartin@thoracic.org
Posted: July 2007
