Flow-regulatory function of upper airway in health and disease: a unified pathogenetic view of sleep-disordered breathing

Although the Starling resistor behavior of the upper airway during sleep has been well established in health and disease, its physiological implications have not been fully appreciated. The purposes of the present communication are to reassess the current state of knowledge within the framework of the Starling resistor concept and to examine the implications of the concept on homeostatic feedback respiratory control and the pathogenesis of the sleep apnea syndrome. The main inferences drawn from the assessment include: (1) Owing to the Starling resistor properties of the upper airway and the well-organized neurochemical control mechanism, the upper airway performs important homeostatic flow regulatory function; it appropriately dampens the potentially unstable breathing during sleep and prevents the PaCO2 from falling below the apneic threshold; (2) Under certain conditions, the upper airway flow regulatory function fails to achieve appropriate dampening, leading to development of a variety of sleep-related breathing disorders that include underdamping due to overly sensitive central chemoresponsiveness and/or excessive lung to chemoreceptor transport lag--central sleep apnea; overdamping due to upper airway obstructive dysfunction--obstructive sleep apnea and/or hypopnea; and, finally, conditions with mixed features of central underdamping with coexisting collapsible upper airway; and (3) Successful treatment of these conditions requires restoration of appropriate damping. The overdamping imposed by the faulty upper airway is effectively reduced by surgical and medical approaches, and by application of nasal continuous positive airway pressure (CPAP). Reduction of PaCO2 by use of acetalzolamide and/or aminophylline reduces the plant gain, thus effectively offsetting the underdamping of central origin. Owing to the dual effect of nasal CPAP on the upper airway and respiratory pump, use of nasal CPAP can also effectively reduce the plant gain, accounting for the therapeutic effect of nasal CPAP on the central sleep apnea.