Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids

Abstract

Background: The debate as to whether asthma is a single or heterogeneous disease remains unresolved although pathological studies, mostly using fibreoptic bronchoscopy on small numbers of subjects, have emphasised the similarities between different clinical phenotypes. Methods: Lower airway inflammation was assessed non-invasively using induced sputum in 34 normal controls and 259 adults with symptomatic asthma receiving treatment at steps 1–3 of the British Thoracic Society (BTS) guidelines. A subgroup of 49 patients treated with as required β₂ agonists only who met BTS criteria for a step up in treatment were studied before and 2 months after treatment with inhaled budesonide 400 μg twice daily. Results: There was considerable heterogeneity in induced sputum cell counts, particularly in non-atopic patients. A subgroup of 60 patients had a distinctive sputum cell profile with a neutrophil count higher than our normal range (>65.3%) and a normal sputum eosinophil count (v –19.4 mm; mean difference 13.9; 95% CI 0.7 to 27.0), forced expiratory volume in 1 second (FEV₁) (–0.08 v 0.13 l; mean difference 0.21; 95% CI 0.03 to 0.39), and concentration of methacholine provoking a fall in FEV₁ of 20% or more (PC₂₀) (0.15 v 1.29 doubling doses; mean difference 1.11; 95% CI 0.13 to 2.15) than the remaining 38 patients. Conclusions: These results suggest the presence of a distinct subgroup of patients with mild to moderate asthma who have predominantly neutrophilic airway inflammation and who respond less well to treatment with inhaled corticosteroids.