Clinical validation of digital biomarkers for pediatric patients with asthma and cystic fibrosis - Potential for clinical trials and clinical care

Abstract

BackgroundDigital biomarkers are a promising novel method to capture clinical data in a home-setting. However, clinical validation prior to implementation is of vital importance. The aim of this study was to clinically validate physical activity, heart rate, sleep and FEV1 as digital biomarkers measured by a smartwatch and portable spirometer in children with asthma and cystic fibrosis (CF).MethodsThis was a prospective cohort study including 60 children with asthma and 30 children with CF (age 6–16). Participants wore a smartwatch, performed daily spirometry at home and completed a daily symptom questionnaire for 28-days. Physical activity, heart rate, sleep and FEV1 were considered candidate digital endpoints. Data from 128 healthy children was used for comparison. Reported outcomes were compliance, difference between patients and controls, correlation with disease-activity and potential to detect clinical events. Analysis was performed with linear mixed effect models.ResultsMedian compliance was 88%. On average, patients exhibited lower physical activity and FEV1 compared to healthy children, whereas the heart rate of children with asthma was higher compared to healthy children. Days with a higher symptom score were associated with lower physical activity for children with uncontrolled asthma and CF. Furthermore, FEV1 was lower and (nocturnal) heart rate was higher for both patient groups on days with more symptoms. Candidate biomarkers and showed a distinct pattern before- and after a pulmonary exacerbation.ConclusionPortable spirometer- and smartwatch-derived digital biomarkers show promise as candidate endpoints for use in clinical trials or clinical care in pediatric lung disease.