A subject-based association network defines new pediatric sleep apnea phenotypes with different odds of recovery after treatment

Abstract

Background and objectives: Timely treatment of pediatric obstructive sleep apnea (OSA) can prevent or reverse neurocognitive and cardiovascular morbidities. However, whether distinct phenotypes exist and account for divergent treatment effectiveness remains unknown. In this study, our goal is threefold: i) to define new data- driven pediatric OSA phenotypes, ii) to evaluate possible treatment effectiveness differences among them, and iii) to assess phenotypic information in predicting OSA resolution. Methods: We involved 22 sociodemographic, anthropometric, and clinical data from 464 children (5–10 years old) from the Childhood Adenotonsillectomy Trial (CHAT) database. Baseline information was used to auto- matically define pediatric OSA phenotypes using a new unsupervised subject-based association network. Follow- up data (7 months later) were used to evaluate the effects of the therapeutic intervention in terms of changes in the obstructive apnea-hypopnea index (OAHI) and the resolution of OSA (OAHI < 1 event per hour). An explainable artificial intelligence (XAI) approach was also developed to assess phenotypic information as OSA resolution predictor at baseline. Results: Our approach identified three OSA phenotypes (PHOSA1-PHOSA3), with PHOSA2 showing significantly lower odds of OSA recovery than PHOSA1 and PHOSA3 when treatment information was not considered (odds ratios, OR: 1.64 and 1.66, 95 % confidence intervals, CI: 1.03–2.62 and 1.01–2.69, respectively). The odds of OSA recovery were also significantly lower in PHOSA2 than in PHOSA3 when adenotonsillectomy was adopted as treatment (OR: 2.60, 95 % CI: 1.26–5.39). Our XAI approach identified 79.4 % (CI: 69.9–88.0 %) of children reaching OSA resolution after adenotonsillectomy, with a positive predictive value of 77.8 % (CI: 70.3 %-86.0 %). Conclusions: Our new subject-based association network successfully identified three clinically useful pediatric OSA phenotypes with different odds of therapeutic intervention effectiveness. Specifically, we found that chil- dren of any sex, >6 years old, overweight or obese, and with enlarged neck and waist circumference (PHOSA2) have less odds of recovering from OSA. Similarly, younger female children with no enlarged neck (PHOSA3) have higher odds of benefiting from adenotonsillectomy.