Predictors and reproducibility of exercise-induced bronchoconstriction in cold air

Abstract

Background: Physical 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.

Methods: Seventy-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).

Results: The 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%.

Conclusions: The 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 registration: NCT02026492 (retrospectively registered 03/Jan/2014).

Keywords: Exercise challenge at an ambient temperature; Exercise challenge in a cold chamber; Exercise-induced bronchoconstriction; Methacholine challenge test.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1

Screened subjects, included subjects, drop outs and outcome

Fig. 2

Overview of the reaction in the different bronchoprovocation tests. a Comparison of the maximal decrease in FEV1. Comparison of the maximal decrease in FEV1 in both ECCs (V2, V3) and the exercise challenge at the ambient temperature (V4) (*** = p < 0.001; * = p < 0.05) with median, interquartile range and min/max. b Overlap of the positive reactions in the first ECC and MCT (n = 67). c Overlap of the positive reactions in the first ECC, MCT and exercise challenge at an ambient temperature (n = 51)

Fig. 3

Receiver-operating characteristic curve for predicting a positive decrease in FEV1 after ECC. PD20FEV1 of methacholine: Optimal cut-off, 1.36 mg; sensitivity, 86%; specificity, 52%; and AUC, 0.69 (p < 0.05). FEV1 decrease during exercise challenge in a cold chamber: Optimal cut-off, 8.5%; sensitivity, 75%; specificity, 78%; and AUC, 0.78 (p < 0.001)

Fig. 4

Bland and Altman plot for the maximal FEV1 decrease (a) and for AUC0-30min (b).The difference between the first and second exercise challenges in the cold chamber is plotted against the mean of the two exercise challenges in the cold chamber for maximum FEV1 decrease and AUC0-30min, as described by Bland and Altman