Obstructive sleep apnea (OSA) is a common disorder characterized by recurrent collapse of the pharyngeal airway during sleep. There is evidence to suggest that respiratory control instability (RCI) is an important contributor to OSA pathogenesis. A novel technique for quantifying RCI has recently been introduced and involves the measurement of respiratory system loop gain (LG). LG is an engineering term that describes the instability in a mechanical or physiologic system governed by feedback control loops. Mathematically, it is defined as the ratio of a corrective response (e.g., hyperpnea) to a disturbance (e.g., apnea). If the corrective action is greater in magnitude than the disturbance (LG > 1), the system is said to be unstable and has the potential for sustained, periodic fluctuations (e.g., in ventilation and blood gases) when disturbed. The purpose of this proposal is to use this new technique to better define the role of RCI and OSA pathogenesis. Specifically, we propose to: ? ? 1. Modify the current technique by measuring LG under mildly hypoxic conditions, which we believe will allow us to quantify RCI in individuals with stable (LG close to zero) respiratory control. ? 2. Measure LG and upper airway collapsibility (pharyngeal closing pressure, Pcrit) in patients with a spectrum of apnea severity to determine if: ? a. Individuals with relatively upper airway collapsibility (Pcrit) require a high LG (LG close to 1) to develop OSA. ? b. High LG, independent of upper airway collapsibility, is associated with more severe (more frequently apneas) OSA. ? c. Lower LG will reduce OSA severity in patients with high LG. ? ?
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