Methods
The study sample included 60 children with treatment-refractory wheeze/asthma referred to a university-based specialty clinic serving a mixed urban-rural population in central Virginia. Enrollees underwent a HHe-3 lung MRI within eight weeks of characterization procedures adapted from the NIH/NHLBI Severe Asthma Research Program 16. Participants were treated according to GINA guidelines17 by an asthma specialist for a minimum of three months before severity assignment 18. Details regarding recruiting procedures and characterization16, treatment 17,19, and indications for bronchoscopy 19 have been published previously.
Inclusion criteria included ages 3-17 years, diagnosis of problematic wheeze (n = 11) or confirmed asthma (n= 49) based on change in FEV­1­% ≥ 12% from baseline post-bronchodilator (BD), and/or a previous positive methacholine bronchoprovocation test, and treatment for a minimum of three months with ≥1 asthma controllers. Inadequate control was defined according to an asthma control test (ACT/cACT) <20, 2 or more exacerbations in the year prior to enrollment, and/or persistent airflow limitation (FEV­1­/FVC < 90th % predicted) 20. Exclusion criteria included premature birth < 36 weeks gestation, inability to cooperate with the MRI procedures, and significant non-asthmatic diagnoses including cardiac disease, cystic fibrosis, and a documented lower respiratory infection within six weeks of the enrollment visit. Study participation required informed consent and protocols were approved by the University of Virginia Institutional Revew Board (IRB# 157200 and #18422). The study was listed on ClinicalTrials.gov (NCT02577497).