Dynamic Models of Obstructive Sleep Apnea Provide Robust Prediction of Respiratory Event Timing and a Statistical Framework for Phenotype Exploration.

Obstructive sleep apnea (OSA), in which breathing is reduced or ceased during sleep, affects at least 10% of the population and is associated with numerous comorbidities. Current clinical diagnostic approaches characterize severity and treatment eligibility using the average respiratory event rate over total sleep time (apnea hypopnea index). This approach, however, does not characterize the time-varying and dynamic properties of respiratory events that can change as a function of body position, sleep stage, and previous respiratory event activity. Here, we develop a statistical model framework based on point process theory that characterizes the relative influences of all these factors on the moment-to-moment rate of event occurrence. Our results provide new insights into the temporal dynamics of respiratory events, suggesting that most adults have a characteristic event pattern that involves a period of normal breathing followed by a period of increased probability of respiratory event occurrence, while significant differences in event patterns are observed among gender, age, and race/ethnicity groups. Statistical goodness-of-fit analysis suggests consistent and substantial improvements in our ability to capture the timing of individual respiratory events using our modeling framework. Overall, we demonstrate a more statistically robust approach to characterizing sleep disordered breathing that can also serve as a basis for identifying future patient-specific respiratory phenotypes, providing an improved pathway towards developing individualized treatments.