State and respiratory variability in obstructive sleep apnea: A modeling perspective

A complex and dynamically varying combination of three main factors, changes in chemoreflex controller response, external disturbances, and sleep state fluctuations may be at play during sleep disordered breathing. In this study, we utilize the framework provided by a mathematical modeling approach to understand these interactions in obstructive sleep apnea (OSA). In patients with OSA, sleep is fragmented by brief but frequent arousals. The transient arousals from sleep in OSA represent a defense mechanism that protects the subject from asphyxiation during episodes of upper airway collapse. The recurring episodes of upper airway occlusion in OSA lead to diminished amounts of sleep and significantly contributes to the important symptom of chronic daytime sleepiness found in OSA patients. So far, existing research on OSA has focused primarily on the pathophysiology of upper airway obstruction itself. The problem of how obstruction affects the overall respiratory control system is not studied in detail. As opposed to steady changes in sleep, arousals represent very brief (transient) state changes. To quantify transient state changes associated with arousals, we developed a state index. We tracked the changes in respiratory drive through the deflections in esophageal pressure. We then used these input and output signals in several modeling approaches to identify the state related changes in the respiratory control system in OSA and normal subjects, where we considered the state index as either explicit or implicit input to the system. Our studies involving 6 OSA and 5 normal subjects revealed that the closed loop transfer function of the respiratory control system which is a series combination of the gas exchanger (lungs) and the chemoreflex controller, has a broader frequency response in OSA patients. This shorter impulse response (kernel) for the chemoreflex loop implies an increased susceptibility for instability in respiratory control system in OSA subjects.