CHARLESTON, SC—Because chronic obstructive pulmonary disease (COPD), like asthma, has an inflammatory component, inhaled corticosteroids are commonly administered as part of treatment. Although these drugs may be effective in reducing symptoms in some COPD patients, a recent meta-analysis suggests that inhaled corticosteroids have little effect on the decrease in lung function that is characteristic of the disease—at least in patients with no evidence of concomitant asthma.[1]

In contrast with their vital role in asthma management, inhaled corticosteroids “do not change the rate of decline of FEV1 [forced expiratory volume in one second] in patients with COPD,” said primary author Kristin B. Highland, MD, Assistant Professor of Medicine at the Medical University of South Carolina in Charleston. Evidence about the effect of these agents on FEV1 has been conflicting. “Some of the studies showed a potential trend towards improvement of FEV1,” she pointed out. This raised the question of whether the studies were merely underpowered—“whether if you had enough patients, you would actually show that there was a FEV1 benefit,” said Dr. Highland. “Once we compiled all the studies together, we saw that there wasn’t.”

She and her collaborators also found FEV1 to be of little value for predicting the efficacy of corticosteroid inhalation in COPD patients. Guidelines developed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD)[2] had “recommended the use of inhaled corticosteroids … in patients with an FEV1 less than 50% who require frequent oral steroids and antibiotics,” noted Dr. Highland. But based on the meta-analysis’ results, this value appears to be arbitrary: “There wasn’t a cutoff,” she emphasized. “There was no difference whether we stratified for FEV1 greater or less than 50% of predicted.”

Six studies of inhaled corticosteroid therapy in COPD patients that used FEV1 as a primary end point were included in the meta-analysis, generating a total of 1,784 active treatment recipients and 1,787 patients given placebo. Although two of the studies had reported trends toward decreased rates of FEV1 decline with corticosteroid use, no overall trend was observed when the patients from all six studies were considered together. “There seemed to be a trend toward improvement in FEV1 decline with the higher-dose steroids, but it wasn’t statistically significant,” Dr. Highland observed. (A beneficial effect on rate of FEV1 decline had been observed in an earlier meta-analysis that included COPD patients who received higher doses of inhaled corticosteroids.)

Various secondary end points also were examined. Of the four studies that measured respiratory symptoms, two showed a significant treatment effect. Inhaled corticosteroids also significantly lowered exacerbation rates in two studies.

The ways in which patients were chosen for each study might, in part, explain variability in the findings. “Some of the inclusion criteria were a bit different from study to study, based on bronchodilator response, severity of lung function, and smoking or not smoking,” said Dr. Highland. Because the studies aimed to distinguish the benefits of inhaled corticosteroids in COPD from their well-recognized effects in asthma, five of the six studies “excluded patients with any kind of bronchial reactivity, which really … biases things toward the null [hypothesis],” Dr. Highland said. This desire to delineate effects on asthma from those on COPD may have created an artificial picture of COPD patients in general. Although inflammation in COPD is largely neutrophilic rather than eosinophilic (as it is in asthma), the two diseases share some effects of inflammation. “The average patient with COPD likely has some bronchial reactivity—it’s not necessarily a ‘pure’ disease,” she noted. COPD’s definition includes irreversible obstruction, said Dr. Highland, “but most patients do have some component of bronchoreactivity and have improvement in FEV1 after bronchodilator use. And a lot of those patients were excluded from these studies.”

Given the heterogeneity among COPD patients, “we should … probably follow the GOLD recommendations,” said Dr. Highland. “If patients are tried on inhaled corticosteroids and show a spirometric response, [they] should be continued on inhaled steroids.” However, if a patient’s pulmonary function fails to respond to a six-week trial, the drug should be discontinued.

Patients with severe symptoms, numerous exacerbations and hospitalizations, and frequent prescriptions for antibiotics and oral corticosteroids might benefit from inhaled corticosteroid use, Dr. Highland added. However, she disagreed with the 50% cutoff recommended by the GOLD guidelines. When considering inhaled corticosteroids for COPD patients, “I don’t really care what their FEV1 is,” she remarked. “If their FEV1 is 60% of predicted but they’re very symptomatic, I’d probably try inhaled steroids.” Otherwise, Dr. Highland suggested, “I would stick to [the GOLD] recommendations until there is more evidence that shows … whether the benefits outweigh the risks of these drugs.”

While most of the studies that she and her colleagues surveyed focused on FEV1 as a measure of inhaled corticosteroid efficacy, other effects need to be considered, Dr. Highland argued. “Only a few of the big studies focused on issues like quality of life, symptoms, and health care utilization.”Corticosteroid use may also improve quality of life, decrease use of health care resources, and provide relief from symptoms. “That needs to be balanced with cost and potential side effects of these medications,” said Dr. Highland. “Those questions really need to be looked at prospectively.”

—Mimi Zucker, PhD