Abstract

BackgroundPhysical activity is an important part of life, and hence exercise-induced bronchoconstriction (EIB) can reduce the quality of life. A standardized test is needed to diagnose EIB. The American Thoracic Society (ATS) guidelines recommend an exercise challenge in combination with dry air. We investigated the feasibility of a new, ATS guidelines conform exercise challenge in a cold chamber (ECC) to detect EIB. The aim of this study was to investigate the surrogate marker reaction to methacholine, ECC and exercise challenge in ambient temperature for the prediction of a positive reaction and to re-evaluate the reproducibility of the response to an ECC.MethodsSeventy-eight subjects aged 6 to 40 years with suspected EIB were recruited for the study. The subjects performed one methacholine challenge, two ECCs, and one exercise challenge at an ambient temperature. To define the sensitivity and specificity of the predictor, a receiver-operating characteristic curve was plotted. The repeatability was evaluated using the method described by Bland and Altman (95% Limits of agreement).ResultsThe following cut-off values showed the best combination of sensitivity and specificity: the provocation dose causing a 20% decrease in the forced expiratory volume in 1 s (PD20FEV1) of methacholine: 1.36 mg (AUC 0.69, p < 0.05), the maximal decrease in FEV1 during the ECC: 8.5% (AUC 0.78, p < 0.001) and exercise challenges at ambient temperatures: FEV1 5.2% (AUC 0.64, p = 0.13). The median decline in FEV1 was 14.5% (0.0–64.2) during the first ECC and 10.7% (0.0–52.5) during the second ECC. In the comparison of both ECCs, the Spearman rank correlation of the FEV1 decrease was r = 0.58 (p < 0.001). The 95% limits of agreement (95% LOAs) for the FEV1 decrease were − 17.7 to 26.4%.ConclusionsThe surrogate markers PD20FEV1 of methacholine and maximal decrease in FEV1 during ECC can predict a positive reaction in another ECC, whereas the maximal FEV1 decrease in an exercise challenge at an ambient temperature was not predictive. Compared with previous studies, we can achieve a similar reproducibility with an ECC.Clinical trial registrationNCT02026492 (retrospectively registered 03/Jan/2014).

Highlights

  • Physical activity is an important part of life, and exercise-induced bronchoconstriction (EIB) can reduce the quality of life

  • Four participants dropped out between V2 and V3 as follows: one participant had a viral infection of the upper airway tract, and three participants were lost to follow-up

  • In summary, the parameters PD20FEV1 of methacholine and the maximal Forced expiratory volume in 1 s (FEV1) decrease in cold air were statistically significant in predicting a positive reaction during an exercise challenge in a cold chamber (ECC), whereas the maximal FEV1 decrease during an exercise challenge at an ambient temperature was not predictive

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Summary

Introduction

Physical activity is an important part of life, and exercise-induced bronchoconstriction (EIB) can reduce the quality of life. The classical symptoms, such as Dreßler et al BMC Pulmonary Medicine (2019) 19:94 dyspnoea, coughing or wheezing during sports, are known to have low sensitivity and specificity in predicting EIB [2, 5, 6] Due to these reasons, a standardized test is essential for correctly diagnosing EIB. Methacholine or histamine directly bind a smooth muscle receptor and cause bronchoconstriction In indirect challenges, such as exercise, the inhalation of mannitol or hypertonic saline lead to increased osmolarity in the airway surfaces and consecutively to the activation of mast cells and epithelial cells, which are stimulated to release proinflammatory mediators (histamine, leukotrienes, and prostaglandins) that provoke airway smooth muscle contraction [2, 3, 7, 8]

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