Systemic corticosteroids in stable chronic obstructive pulmonary disease. Do they work?

D espite more than 30 years of clinical use and research, the value of systemic corticosteroids for patients with stable chronic obstructive pulmonary disease (chronic bronchitis and/or emphysema) remains uncertain. The controversy over steroid efficacy began in the 1950s with disagreements found in reports of early case series and observational cohort studies, and the dispute still has not been resolved because randomized trials have continued to reach conflicting conclusions, As ofthis writing, 14 studies1’ of therapy with systemic steroids in stable chronic obstructive pulmonary disease have been performed as doubleblind randomized clinical trials (RCTs), a design which is widely regarded as the most reliable way to evaluate therapy. The results ofthese trials differ. Overall, eight of the 14 trials show that systemic corticosteroids produce some measured benefit, whereas six trials report no effect. Ofthe 13 trials that examined FEV1 as an outcome event, six show greater improvement with steroids than with placebo, and seven do not. Two of the four trials that measure exercise tolerance (12minute walk distance in three and treadmill exercise performance in one) show improvement following steroid therapy, whereas two do not. As a result of these basic disagreements among the available RCTs, confusion about steroid efficacy is understandable, but interested clinicians will look for strategies to resolve this conflict, Of the available strategies for resolving conflicts in the literature, ie, informal review (which combines the literature with personal clinical experience); formal pooled analysis (in which data from all available studies are combined and re-analyzed as a single data set); and methodologic “meta-analysis” (in which the design and conduct of each trial is evaluated to identify the most reliable study), “meta-analysis” has proven useful to clarify several clinical controversies,’5 including the role of steroids in stable COPD.16 Specifically, by crediting trials that used a crossover design with a washout (to assure optimal matching of compared groups and study conditions), we identified a subset of eight betterdesigned trials.4’570’3’4 By also requiring trials to assure that patients were stable at baseline (to exclude acute-on-chronic bronchitics, for whom steroids are known to ), we narrowed this subset to six preferred tria1s,4T #{176}’ ofwhich four showed steroids to work. The remaining two trials4’4 examined small numbers of patients (12 and 16 respectively), and did not exclude the possibility oftype II error (ie, failing to appreciate a steroid effect that was present). Thus, the best available RCTs do suggest that steroids can work, but in none ofthese six trials was the benefit universal. Even in the study with the greatest fraction of steroid 10 only 56 percent of patients experienced improved airflow with steroids (versus 13 percent of placebo recipients). Despite the evidence that steroids can be effective in stable COPD, we remain unable to reliably predict steroid-responsiveness, so that clinicians must rely on careful steroid trials in individual patients whose COPD remains disabling despite usual treatment. Strategies like the “N of 1” crossover trial, recently advocated by Guyatt et al,lh may improve these clinical assessments, which should certainly consider the patient’s functional capacity and dyspnea, in addition to measurements ofairfiow. Recent work shows that both of these outcomes can be measured y’9 and that COPD patients can experience treatment responses that are not measurable by spirometry alone.2#{176} Because we know that steroids can work but cannot predict who will not respond, we will continue to rely on individual empiric trials until better information becomes available. James K. Stoller, M. D. , F C . C . F, Cletela nd