Benefit of Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease
Researchers involved in two different studies designed to reduce potentially biased results among chronic obstructive pulmonary (COPD) patients who used inhaled corticosteroids reported a 30 percent reduction in risk for either re-hospitalization or death from the disease.
Writing in the second issue for August 2005 of the American Thoracic Society's peer-reviewed American Journal of Respiratory and Critical Care Medicine, Joan B. Soriano, M.D., Ph.D., of Worldwide Epidemiology at GlaxoSmithKline Research and Development in Collegeville, Pennsylvania, along with three associates, described the effectiveness of inhaled corticosteroids (ICS) for reducing re-hospitalization and mortality, using the United Kingdom's General Practice Research Database.
In an effort to avoid "immortal time bias," the authors created two matched sets of patients, based on a cohort hospitalized for a COPD-related condition between 1990 and 1999. In the first study, each group of matched patients included 393 individuals with one set having been treated with ICS and the other remaining untreated. In the second study, also free of potential bias, a case-control analysis of 2,222 patients was designed without regard to ICS exposure status. Both found an approximately 30 percent reduction in the risk for either re-hospitalization or death among patients who used ICS over a one-year follow-up period.
"Immortal time bias results from cohort studies with follow-up time during which a subject cannot, by definition, incur the outcome study," said Dr. Soriano. "That is, when exposure time overlaps follow-up time, patients who die during the exposure time cannot by definition obtain the medication in question and, as such, will be classified as non-exposed. This is believed to lead to underestimation of person-time without ICS treatment, leading to overestimation of any treatment effect."
COPD is lung disease characterized by airflow obstruction that interferes with normal breathing. The two most frequent disease conditions that underlie COPD are severe emphysema and chronic bronchitis. Years of smoking are the primary cause for these problems.
According to the authors, COPD is currently the fourth leading cause of death worldwide, causing more than 2.5 million deaths per year. The illness is also the leading cause of hospitalization in the United States, and is particularly prevalent among older patients.
The Global Initiative for Obstructive Lung Disease (GOLD) Guidelines now recommend long-term use of ICS for patients with COPD whose lung function test result is less than 50 percent of the predicted age-related value and who experience repeated exacerbations. The American Thoracic Society and European Respiratory Society advocate similar guidelines.
"With different study designs reducing potential bias, we consistently found an association between ICS use and the reduction of risk of re-hospitalization and death," concluded Dr. Soriano.
In an editorial on the study in the same issue, Jonathan M. Samet, M.D. of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, wrote: "This pair of endpoints (mortality and hospitalization) is particularly crucial to the evaluation of inhaled corticosteorids because a beneficial effect would indicate an improved natural history, the most crucial objective of therapy."
He also wrote: "Further evidence is needed, both from clinical trials with sufficient sample sizes to address hospitalization and mortality and from rigorous analysis of administrative databases. The Toward a Revolution in COPD Health (TORCH) study, which includes 6,000 participants, may provide informative results. Another approach for gaining information is pooling data from individual trials; at the 2005 American Thoracic Society meeting, a reduction in all-cause mortality associated with inhaled corticosteroid therapy was reported based on 5,082 participants in seven trials."
Dr. Samet concluded that the still-evolving evidence does provide some indication of the potential magnitude of the benefits associated with inhaled corticosteroids associated with COPD. The new report by Dr. Soriano and his colleagues suggests a 30 percent reduction in risk for re-hospitalization or death, which is a meaningful gain in COPD treatment.