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

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this may have an effect on the responses to cold air inhalation in healthy volunteers, as found in the Alascair study (unpublished data)), by means of different questionnaires evaluating life style and exposure to air pollution (SF-36, AQLQ, ACQ, SQUASH,…).