A Novel Model to Estimate Key OSA Endotypes from Standard Polysomnography and Clinical Data and Their Contribution to OSA Severity.

Abstract

There are at least four key pathophysiological endotypes that contribute to obstructive sleep apnea (OSA) pathophysiology. These include: 1) upper-airway collapsibility (Pcrit), 2) arousal threshold, 3) loop gain and 4) pharyngeal muscle responsiveness. However, an easily interpretable model to examine the different ways and extent to which these OSA endotypes contribute to conventional polysomnography defined OSA severity (i.e. the apnea/hypopnea index: AHI) has not been investigated. Additionally, clinically deployable approaches to estimate OSA endotypes to advance knowledge on OSA pathogenesis and targeted therapy at scale are not currently available. Develop an interpretable data-driven model to: 1) determine the different ways and extent to which the four key OSA endotypes contribute to polysomnographic defined OSA severity and 2) gain insight into how standard polysomnographic and clinical variables contribute to OSA endotypes and whether they can be used to predict OSA endotypes. Age, BMI plus standard polysomnography parameters from a standard diagnostic study were collected. OSA endotypes were also quantified in 52 participants (43-OSA, 9-controls) using gold-standard physiologic methodology on a separate night. Unsupervised multivariate principal component analyses (PCA) and data driven supervised machine learning (decision tree learner: DTL) were used to develop a predictive algorithm to address the study objectives. Maximum predictive performance accuracy of the trained model to identify standard polysomnography defined OSA severity levels (no OSA, mild-moderate or severe) using the using the 4 OSA endotypes was approximately twice that of chance. Similarly, performance accuracy to predict OSA endotype categories ("good", "moderate" or "bad") from standard polysomnographic and clinical variables was approximately twice that of chance for Pcrit and slightly lower for arousal threshold. This novel approach provides new insights into the different ways in which OSA endotypes can contribute to polysomnographic defined OSA severity. While further validation work is required, these findings also highlight the potential for routine sleep study and clinical data to estimate at least two of the key OSA endotypes using data driven predictive analysis methodology as part of a clinical decision support system to inform scalable research studies to advance OSA pathophysiology and targeted therapy for OSA.