Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma

Mike A Berry ^1*, Angela Morgan ¹, Dominick E Shaw ¹, Deborah Parker ¹, Ruth H Green ¹, Chris E Brightling ², Peter Bradding ¹, Andrew J Wardlaw ¹ and Ian D Pavord ¹

¹ University Hospitals of Leicester, United Kingdom
² University of Leicester, United Kingdom

^* To whom correspondence should be addressed. E-mail: mike.berry{at}mac.com.

Accepted 2 February 2007

Abstract

Introduction Non-eosinophilic asthma is a potentially important clinicopathological phenotype since there is evidence that it responds poorly to inhaled corticosteroid therapy. However, little is known about the underlying airway immunopathology and there are no data from placebo controlled studies examining the effect of inhaled corticosteroids.

Methods We have investigated airway immunopathology using induced sputum, bronchial biopsies, bronchial wash and bronchioalveolar lavage in 12 patients with symptomatic eosinophilic and 11 patients with non-eosinophilic asthma and 10 healthy controls. The patients with non-eosinophilic asthma and 6 different patients with eosinophilic asthma entered a randomised, double blinded, placebo controlled cross over study in which we investigated the effects of inhaled mometasone 400µg once daily for 8 weeks on airway responsiveness and asthma quality of life.

Results Patients with non-eosinophilic asthma had absence of eosinophils in the mucosa (median 4.4 cells/mm2 vs. 23 cells/mm2 in eosinophilic asthma and vs. 0 cells/mm2 in normal controls; p=0.03) and normal subepithelial layer thickness (5.8µm vs. 10.3µm in eosinophilic asthma and vs. 5.1µm in controls, p=0.002). Non eosinophilic and eosinophilic asthma groups had increased mast cell numbers in the airway smooth muscle compared to normal controls (9 vs. 8 vs. 0 cells/mm2, p=0.016). Compared to placebo 8 weeks treatment with inhaled mometasone led to less improvement in methacholine PC20 (0.5 vs. 5.5 doubling concentrations, 95% C.I. of difference 1.1, 9.1; p=0.018) and asthma quality of life (0.2 vs. 1.0 points, 95% C.I. of the difference 0.27, 1.43; p=0.008).

Conclusions Non-eosinophilic asthma represents a pathologically distinct disease phenotype, which is characterised by absence of airway eosinophilia, normal subepithelial layer thickness and a poor short-term response to treatment with inhaled corticosteroids.

Keywords: Asthma, eosinophil, immunopathology, inhaled steroid

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