Use of Inhaled Corticosteroids For COPD Does Not Appear to Improve Survival, But May Increase Risk For Pneumonia

An analysis of randomized trials indicates that use of inhaled corticosteroids for the treatment of chronic obstructive pulmonary disease (COPD) does not improve the rate of survival after one year, but is associated with an increased risk of pneumonia, according to an article in the November 26 issue of JAMA.


COPD, a lung disease characterized by recurrent episodes of coughing and breathlessness, represents a substantial public health burden, affecting 10-15 million persons in the United States. COPD is currently the fourth leading cause of death in the United States, accounting for 120,000 deaths annually, and is expected to be the third leading cause of death by 2020, according to background information in the article. No pharmacotherapy and few interventions, other than smoking cessation and supplemental oxygen, have been shown to improve the rate of death in patients with COPD. Recent studies regarding the use of inhaled corticosteroid (ICS) therapy for managing stable COPD have yielded conflicting results regarding survival and risk of adverse events.


M. Bradley Drummond, M.D., M.H.S., of Johns Hopkins University, Baltimore, and colleagues conducted a review and meta-analysis of 11 randomized controlled trials (14,426 participants) to determine associations of ICS use of 6 or more months’ duration with all-cause death and risk of pneumonia in patients with stable COPD.


All-cause mortality at 1-year follow-up was reported in five studies (9,233 patients), and analysis indicated that ICS therapy was not associated with a decreased risk of death after one year. There were 128 deaths among 4,636 individuals in the treatment group, and 148 deaths among 4,597 individuals in the control group.


Seven studies (10,776 patients) reported pneumonia outcomes, and indicated that patients receiving ICS had a 34 percent higher incidence of pneumonia. These studies included 777 events among 5,405 individuals in the treatment group and 561 events among 5,371 individuals in the control group.


“The association of ICS therapy with increased rates of pneumonia reported in our meta-analysis should be considered by clinicians and guideline developers when evaluating the role of ICS therapy in the management of stable COPD. This finding must be balanced with those of other reports describing beneficial effects of ICS therapy,” the authors write.

Subgroup analyses indicated an increased risk of pneumonia in the following groups: highest ICS dose, shorter duration of ICS use, lowest baseline forced expiratory volume in the first second of expiration (a measure of lung function) and combined ICS and bronchodilator therapy.


“Recognizing the adverse events associated with ICS use is especially important, since clinicians may increase ICS therapy from moderate to high doses in patients who are not responding. Our data suggest that increasing to higher ICS doses may place patients at greater risk for pneumonia. While the results of our subgroup analysis suggest the existence of subpopulations of patients with COPD who might be at higher risk for pneumonia, our evidence is not conclusive and is only hypothesis-generating.


Analysis of existing observational studies and future clinical trials may help physicians determine an optimal ICS dose that balances the potential risks and benefits of this therapy. Until studies can confirm an unequivocal benefit of ICS therapy in a group of patients with COPD, patients should receive the lowest effective ICS dose to minimize potential adverse effects,” the authors write.


JAMA. 2008;300[20]:2407-2416.