The Effect of a Cold Air Eucapnic Hyperventilation Test on Lower Respiratory Airways in Healthy Volunteers and Patients With Asthma

Overview

In this study, we want to evaluate the feasibility and safety of a CAEH test in healthy volunteers and patients with asthma. We want to develop a CAEH test to differentiate patients with different types of asthma and exercise-induced bronchoconstriction from healthy volunteers and to evaluate whether the respiratory phenotype induced by cold air inhalation differs between subjects with asthma and healthy subjects. Furthermore, we want to evaluate whether the CAEH test is more robust over time compared to the EVH test. Previously, our lab has demonstrated that submaximal exercise at subfreezing temperatures in a climate chamber (-5°C) induces an acute respiratory response in patients with asthma and in healthy subjects who have been exposed to high PM10 (unpublished data). Finally, This study will serve as a preliminary study for a subsequent prospective study in which the results and optimized protocol obtained in this study will be used to further evaluate the feasibility of using this CAEH as a diagnostic tool in asthma compared to EIB (CLARINET2). The present study is required to develop a standardized CAEH test in a safe and feasible manner. This study will also help to identify appropriate endpoints (FEV1, multiple breath washout test, biomarkers…) of the subsequent studies.

In this study, we aim to develop a safe and feasible cold air (-15°C) eucapnic hyperventilation (CAEH) test protocol in which we can compare the lower airway responses between healthy volunteers and subjects with asthma. Consequently, we want to evaluate the effect of cold air inhalation on FEV1, respiratory symptoms, airway integrity, and local and systemic inflammation. Primary endpoints The primary endpoint of this study is to compare proportional change in FEV1, (% decrease) after a CAEH test in healthy volunteers and patients with mild to moderate asthma. Post-exposure will be calculated as a time-weighted average over the 30 min after the CAEH test. At each time point (pre-, 5, 10, 15, and 30 minutes post-exposure), FEV1 will be measured in triplicate. Secondary endpoints We want to evaluate whether and to what extent the inhalation of cold air during this CAEH test can induce changes in respiratory symptoms (including dyspnea, cough, mucus production, etc.), affects lower airway integrity (airway obstruction (FEV1/FVC), small airway dysfunction (FEF 25/75, lung ventilation inhomogeneity (LCI), bronchial hyperreactivity (PC20 AMP)) and whether it induces (local or systemic) inflammation (different biomarkers in sputum and blood, as defined in section 5.2). These changes will be compared between healthy volunteers and predisposed subjects with mild to moderate asthma. The abovementioned responses and the proportional change in FEV1 after the CAEH test will be compared to a standard (21°C room air) eucapnic hyperventilation (EVH) test. Furthermore, we will compare the results obtained in this study to the results obtained in the ALASCAIR study of dr. Tatjana Decaesteker. Finally, the effects of the CAEH will be correlated to the amount of air pollution the subject was exposed to, in the days prior to the test (as this may have an effect on the responses to cold air inhalation in healthy volunteers, as found in the Alascair study (unpublished data)), by means of different questionnaires evaluating life style and exposure to air pollution (SF-36, AQLQ, ACQ, SQUASH,…).