Methodological issues
asthma-like symptoms, wheezing, exacerbations
RECRUITMENT
We decided to choose a RCT design for the following reasons: 1) to assess the full potential of the breath test in health gain and costs of care, a comparative study design is needed; 2) the breath test is not standard care yet; 3) in the usual care group, it is not unethical to provide the test result in a later phase, eventually all children/parents will benefit from the breath test result; 4) a safety rule will be applied in the usual care group so that parents/treating doctors can get the result of the breath test in an urgent situation (e.g. severe exacerbations, hospital admissions).At first, we did not expect any problems with the feasibility of patient recruitment based on the high prevalence of children with asthma-like symptoms and our experiences during the first ADEM study. However, the outbreak of the SARS-CoV-2 pandemic in 2020 significantly affected the recruitment of participants. In the beginning of the pandemic, we were not allowed to perform research anymore by the Board of Directors of our hospitals. In a later phase, less preschool children with wheezing symptoms presented themselves at the outpatient clinic, emergency departments, and primary care facilities than before the crisis, which probably was the consequence of preventive measures taken (e.g. the lock-downs and temporary closure of schools and day-care facilities). As most of our patients were selected during and after the pandemic, this influenced intervention and control group equally.We do not expect problems with drop-outs during the study because the breath test and the questionnaires are non-invasive, and the parents, children and treating doctors are highly motivated. Moreover, the ADEM study had a comparable design and burden with only 2% loss to follow-up [