Early ReportSputum eosinophilia and short-term response to prednisolone in chronic obstructive pulmonary disease: a randomised controlled trial
Introduction
The role of corticosteroids in stable chronic obstructive pulmonary disease (COPD) is uncertain.1 Guidelines reflect the perception that a subgroup of patients respond to this treatment,2 although identification of characteristics associated with a positive response to short-term or long-term treatment with corticosteroids has been difficult.3 Corticosteroids effectively modify eosinophilic airway inflammation in asthma,4, 5 but there is less evidence that they effect the neutrophilic inflammation that predominates in COPD.5 One possibility is that corticosteroids are effective in COPD patients who have eosinophilic airway inflammation.
Early reports suggested that sputum eosinophilia could predict clinical benefit from corticosteroids,6 but the methods of sputum assessment were crude and the findings were not consistent.7 Over the past 10 years, important advances have been made in the technique of sputum induction and analysis and methods are now reliable, valid,8 responsive, and safe.9 Pizzichini and colleagues10 used these methods to show, in a small, single-blind study, that patients with sputum eosinophilia had a greater improvement in forced expiratory volume in 1 s (FEV1) and health status after a short course of prednisone than those without. We did a double-blind placebo-controlled crossover study to define the sputum characteristics of patients with COPD and to investigate the relation between the sputum eosinophil count and the response to 2 weeks of treatment with prednisolone.
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Patients
We recruited, from respiratory clinics, patients who had symptoms of chronic airflow obstruction, postbronchodilator FEV1 of less than 70% predicted, and an FEV1/forced vital capacity (FVC) ratio of less than 70%. We enrolled those who had no substantial improvement in FEV1 after taking 2·5 mg nebulised salbutamol (<15% or, if FEV1 <1·2 L, <200 mL improvement). We excluded patients if they had a clinical diagnosis of asthma, a history of childhood respiratory disorders, variability in symptoms
Results
83 patients were recruited, of whom 67 were randomised (figure 1). Seven of 45 patients taking inhaled corticosteroids at recruitment were excluded before randomisation because they developed moderate exacerbations in the run-in period. The baseline characteristics of the remaining 38 patients did not differ significantly from the corticosteroid-naïve patients. Eight patients withdrew during the washout period (figure 1). Treatment period or order did not influence values before treatment or
Discussion
Eosinophilic airway inflammation was common among patients who had stable moderate and severe COPD, and postbronchodilator FEV1, health status, and exercise capacity were improved by prednisolone. Greater improvements were seen in patients with higher baseline sputum eosinophil counts than for those with lower counts, and were associated with striking reductions in sputum eosinophil count and sputum concentration of the activated eosinophil product eosinophilic cationic protein. Cell and
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