Elsevier

The Lancet

Volume 356, Issue 9240, 28 October 2000, Pages 1480-1485
The Lancet

Early Report
Sputum eosinophilia and short-term response to prednisolone in chronic obstructive pulmonary disease: a randomised controlled trial

https://doi.org/10.1016/S0140-6736(00)02872-5Get rights and content

Summary

Background

Some patients with chronic obstructive pulmonary disease (COPD) respond to corticosteroid therapy. Whether these patients have different airway pathology from other COPD patients is unclear. We tested the hypothesis that response to prednisolone is related to the presence of eosinophilic airway inflammation.

Methods

We did a randomised, double-blind, crossover trial. Patients who had COPD treated with bronchodilators only were assigned placebo and 30 mg prednisolone daily for 2 weeks each, in a random order, separated by a 4-week washout period. Before and after each treatment period, we assessed patients with spirometry, symptom scores, the chronic respiratory disease questionnaire (CRQ), incremental shuttle walk test, and induced sputum. Analysis was done by intention to treat.

Findings

83 patients were recruited, of whom 67 were randomised. The geometric mean sputum eosinophil count fell significantly after prednisolone (from 2·4% to 0·4%; mean difference six-fold [95% CI 3·1–11·4]) but not after placebo. Other sputum cell counts did not change. After stratification into tertiles by baseline eosinophil count, postbronchodilator forced expiratory volume in 1 s (FEV1) and total scores on the CRQ improved progressively after prednisolone from the lowest to the highest eosinophilic tertile, compared with placebo. The mean change in postbronchodilator FEV1, total CRQ score, and shuttle walk distance with prednisolone compared with placebo in the highest tertile was 0·19 L (0·06–0·32), 0·62 (0·31–0·93), and 20 m (5–35), respectively.

Interpretation

Our findings suggest that eosinophilic airway inflammation contributes to airflow obstruction and symptoms in some patients with COPD and that the shortterm effects of prednisolone are due to modification of this feature of the inflammatory response. The possibility that sputum eosinophilia identifies a subgroup of patients who particularly respond to long-term treatment with inhaled corticosteroids should be investigated.

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.

Section snippets

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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