The contribution of neuromechanical mechanisms to the pathogenesis of upper airway obstruction during sleep

Background. The relative contributions of passive mechanical loads and dynamic compensatory neuromuscular responses to pharyngeal collapsibility in obstructive sleep apnea (OSA) are largely unknown. The overall objective of the dissertation was to determine the contribution of passive mechanical loads and dynamic neuromuscular responses to the pathogenesis of OSA. Specific objectives of the dissertation were: (1) To review the pathogenesis of OSA, (2) To develop a standardized approach to the acquisition and analysis of pressure-flow data used to measure pharyngeal collapsibility, and (3) To determine the relative contributions of passive mechanical loads and active compensatory neuromuscular responses to pharyngeal collapsibility during sleep. Methods. (1) Summary of the literature concerning the pathogenesis of OSA, (2) Development of a standardized approach to the acquisition and analysis of upper airway pressure-flow relationships in a consecutive sample of OSA patients, (3) Measurements of passive mechanical loads and active compensatory neuromuscular responses and their contributions to pharyngeal collapsibility (PCRIT) were assessed in a sample of normal subjects and OSA patients matched on age, gender, and body-mass index. Results. Two series of measurements acquired at varying nasal pressure levels with two or more breaths per level were comparable to three series in determining the PCRIT. OSA patients demonstrated elevated mechanical loads as demonstrated by a higher passive PCRIT (-0.05 cm H2O (SD 2.4) vs. -4.5 cm H 2O (SD 3.0), P = 0.0003) and reduced dynamic responses to upper airway obstruction as suggested by failure to lower their active PCRIT (-1.6 cm H 2O (SD 3.5) vs. -11.1 cm H2O (SD 5.3), P < 0.0001) compared to normal subjects. Moreover, a subset of normal subjects at risk for OSA due to elevations in mechanical loads similar to OSA patients was identified that maintained airway patency by lowering the active PCRIT. Conclusions. Ascertainment of PCRIT can be performed in a standardized fashion. Patients with OSA demonstrate both increased upper airway mechanical loads and blunted neuromuscular responses during sleep. Normal subjects with passive mechanical loads in a range similar to patients with OSA are protected from the disorder due to the presence of vigorous compensatory neuromuscular responses during sleep