Key Point

Inhaled corticosteroid therapy reduces mortality in patients with COPD.

WINNIPEG, MANITOBA—To maximize the survival of patients hospitalized for COPD, physicians should prescribe postdischarge treatment with inhaled corticosteroids, a recent study suggests.¹ The findings are among the latest contributions to the debate about whether patients hospitalized for COPD should routinely receive inhaled steroids to reduce their mortality rate, which on an age-adjusted basis has risen by more than 160% since 1965.

Among 4,022 COPD patients, inhaled steroid therapy resulted in a 25% reduction in mortality 90 to 365 days after discharge in the 65-and-older age-group. "Inhaled steroids were associated with an even larger mortality reduction in people aged 35 to 64 years," the study authors added.

The four-year study included two types of analysis: cohort and nested case-control. The cohort analysis compared mortality between the patients who were and were not prescribed an inhaled steroid in the 90 days after hospital discharge. The patients who were treated with a bronchodilator during that time served as a reference group.

In the nested case-control analysis, the inhaled steroid exposure of patients who died 90 to 365 days after hospital discharge was compared to that of age- and gender-matched controls who survived during that period. "It was thus possible for the same individual to be a case patient and a control subject," noted the authors. Of the study subjects, 1,629 (40.4%) received inhaled steroids within 90 days of discharge and 2,393 (59.5%) did not. In the 35-to-64 age-group, mortality between 90 and 365 days after discharge was 3.3% for patients treated with inhaled steroids and 6% for those who were not (a 53% reduction in the steroid group).

Among patients 65 and older, mortality in the steroid and nonsteroid groups was 11.7% and 13.1%, respectively. Ipratropium and theophylline use, age, sex, comorbidity, and the number of prior physician visits were associated with increased mortality. In the cohort analysis, inhaled steroid therapy reduced the risk of death by 23%, compared to bronchodilator treatment. This reduction was significant for cardiovascular deaths but not for COPD, the authors related. The case-control analysis found that excluding inhaled steroids, patients who died between 90 and 365 days after discharge received more respiratory medications other than inhaled steroids compared to patients who survived during that period. Also, inhaled steroid therapy within 30 days of death decreased all-cause mortality; it lowered cardiovascular and COPD death by 46% and 39%, respectively. When patients who survived for six months after discharge were compared to those who died between five months and one year, treatment with inhaled steroids within 30 days of death was again associated with lower all-cause mortality.

IMPRESSIVE, BUT NOT DEFINITIVE

In an accompanying editorial, Don D. Sin, MD, and S.F. Paul Man, MD, observed that adjusting for confounders, using a nested case-control design, eliminating the immortal time bias, and excluding patients with a previous asthma diagnosis did not alter the findings much, indicating their robustness.² "These data add to the growing body of evidence indicating the beneficial effects of therapy with inhaled corticosteroids in reducing mortality in COPD patients," the two physicians remarked.

However, despite the authors’ careful analysis and sophisticated statistical techniques, the possibility of residual or external confounding or biases cannot be discounted, cautioned Drs. Sin and Man. "Furthermore, the present study did not confirm the diagnosis of COPD by lung function measurements and could not stratify (or even document) the severity of the airflow limitation in this population," they added. "For these and other reasons, ... the present study should not be considered definitive."

Although this and other studies collectively present a compelling argument for using inhaled steroids to reduce mortality in COPD, more clinical and animal trials are needed first. The goal of such trials should be to better understand the mechanisms behind the observed relationship between inhaled steroids and improved survival and to identify novel therapeutic targets for COPD, Drs. Sin and Man asserted.

—Timothy Begany

References
1. Macie C, Wooldrage K, Manfreda J, Anthonisen NR. Inhaled corticosteroids and mortality in COPD. Chest. 2006;130:640-646.
2. Sin DD, Man SFP. Cooling the fire within: inhaled corticosteroids and cardiovascular mortality in COPD. Chest. 2006;130:629-631.

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