Endurance athletes show an increased prevalence of airway hyperresponsiveness. The aim of the present study was to evaluate the long-term effects of training on airway responsiveness, inflammation and epithelial damage in swimmers and cold-air athletes.In total, 64 elite athletes (32 swimmers and 32 cold-air athletes), 32 mild asthmatic subjects and 32 healthy controls underwent allergy skin prick testing, methacholine challenge and induced sputum analysis.Overall, 69% of swimmers and 28% of cold-air athletes had airway hyperresponsiveness. Sputum neutrophil count correlated with the number of training hours per week in both swimmers and cold-air athletes. Eosinophil counts were higher in swimmers than in healthy subjects, although they were lower than in asthmatic subjects, and correlated with airway hyperresponsiveness in swimmers only. The eosinophil count in cold-air athletes was similar to that in healthy subjects. Bronchial epithelial cell count was not correlated with airway hyperresponsiveness but was significantly increased in swimmers, compared with healthy and asthmatic controls.In conclusion, the present authors observed significant airway inflammation only in competitive athletes with airway hyperresponsiveness. However, the majority of elite athletes showed evidence of bronchial epithelial damage that could possibly contribute to the development of airway hyperresponsiveness.

BackgroundIn clinical trials, the two anti-IL-5 monoclonal antibodies (mAbs, mepolizumab and reslizumab) that are approved to treat severe eosinophilic asthma, reduce exacerbations by approximately 50–60%.ObjectiveTo observe response to anti-IL-5 mAbs in real-life clinical setting, and to evaluate predictors of sub-optimal response.MethodsIn four Canadian academic centres, pre-defined clinical end-points in 250 carefully characterised moderate-to-severe asthmatics were collected prospectively to assess response to the two anti-IL-5 mAbs. Sub-optimal responses was determined based on failure to reduce maintenance corticosteroid (MCS) or asthma symptoms scores (ACQ) or exacerbations, in addition to persistence of sputum/blood eosinophils. Worsening in suboptimal responders were assessed based on reduced lung function by 25% or any increase in MCS/ACQ. A representative sub-set of 39 patients were evaluated for inflammatory mediators, autoantibodies and complement activation in sputum (by ELISA) and for immune-complex deposition by immunostaining formalin-fixed paraffin-embedded sputum plugs.ResultsSub-optimal responses were observed in 42.8% (107/250) patients treated with either mepolizumab/reslizumab. Daily prednisone requirement, sinus disease, and late-onset asthma diagnoses were the strongest predictors of sub-optimal response. Asthma worsened in 13% (34/250) of these patients. Majority (79%) of them were prednisone-dependent. Presence of sputum anti-eosinophil peroxidase immunoglobulin (Ig)G was a predictor of sub-optimal response to an anti-IL-5 mAb. An increase in sputum C3c (marker of complement activation) and deposition of C1q-bound/IL-5-bound IgG were observed in the sputa of those patients who worsened on therapy, suggesting an underlying autoimmune-mediated pathology.ConclusionA significant number of patients who meet currently approved indications for anti-IL5 mAbs show sub-optimal response to them in real-life clinical practice. Monitoring blood eosinophil count is not helpful to identify these patients. The concern of worsening of symptoms associated with immune-complex mediated complement-activation in a small proportion of these patients highlights the relevance of recognising airway autoimmune phenomena and this requires further evaluation.

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