Responsiveness to oral prednisolone in severe asthma is related to the degree of eosinophilic airway inflammation

Abstract

Background

Patients with severe asthma appear relatively corticosteroid resistant. Corticosteroid responsiveness is closely related to the degree of eosinophilic airway inflammation. The extent to which eosinophilic airway inflammation in severe asthma responds to treatment with systemic corticosteroids is not clear.

Objective

To relate the physiological and inflammatory response to systemic corticosteroids in asthma to disease severity and the baseline extent of eosinophilic inflammation.

Methods

Patients with mild/moderate and severe asthma were investigated before and after two-weeks of oral prednisolone (Clintrials. gov NCT00331058 and NCT00327197). We pooled the results from 2 studies with common protocols. The US study contained 2 independent centres and the UK 1 independent centre. The effect of oral corticosteroids on FEV₁, Pc20, airway inflammation and serum cytokines were investigated. Baseline measurements were compared with healthy subjects.

Results

32 mild/moderate asthmatics, 50 severe asthmatics and 35 healthy subjects took part. At baseline both groups of asthmatics had a lower FEV₁ and Pc20 and increased eosinophilic inflammation compared to healthy subjects. The severe group had a lower FEV₁ and more eosinophilic inflammation compared to mild/moderate asthmatics. Oral prednisolone caused a similar degree of suppression of eosinophilic inflammation in all compartments in both groups of asthmatics. There were small improvements in FEV₁ and Pc20 for both mild/ moderate and severe asthmatics with a correlation between the baseline eosinophilic inflammation and the change in FEV₁. There was a ~50% reduction in the serum concentration of CXCL10 (IP-10), CCL22 (MDC), CCL17 (TARC), CCL-2 (MCP-1) and CCL-13 (MCP-4) in both asthma groups after oral corticosteroids.

Conclusions and Clinical Relevance

Disease severity does not influence the response to systemic corticosteroids. The study does not therefore support the concept that severe asthma is associated with corticosteroid resistance. Only baseline eosinophilic inflammation was associated with the physiological response to corticosteroids, confirming the importance of measuring eosinophilic inflammation to guide corticosteroid use.

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