Phenotyping Pharyngeal Pathophysiology Using Polysomnography in Patients with Obstructive Sleep Apnea.

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Therapies for obstructive sleep apnea (OSA) could be administered based on a patient's own phenotypic causes ("traits") if a clinically-applicable approach were available. Here we present a novel approach to quantify two key contributors to OSA-pharyngeal collapsibility and compensatory muscle responsiveness-that is applicable to diagnostic polysomnography.


Based on physiological definitions, pharyngeal collapsibility determines the ventilation at normal (eupneic) ventilatory drive during sleep, and pharyngeal compensation determines the rise in ventilation accompanying a rising ventilatory drive. Thus, measuring ventilation and ventilatory drive (e.g. during spontaneous cyclic events) should reveal a patient's phenotypic traits without specialized intervention. We demonstrate this concept in OSA patients (N=29) using a novel automated non-invasive method to estimate ventilatory drive (polysomnographic method) and using gold standard ventilatory drive (intraesophageal diaphragm EMG) for comparison. Specialized physiological measurements using CPAP manipulation were employed for further comparison. The validity of nasal pressure as a ventilation surrogate was also tested (N=11).


Polysomnography-derived collapsibility and compensation estimates correlated favorably with those quantified using gold standard ventilatory drive (R=0.83, P<0.0001; R=0.76, P<0.0001 respectively) and using CPAP manipulation (R=0.67, P<0.0001; R=0.64, P<0.001 respectively). Polysomnographic estimates effectively stratified patients into high versus low subgroups (accuracy 69-86% vs. ventilatory drive measures, P<0.05). Traits were near-identical using nasal pressure versus pneumotach (N=11, R≥0.98 both traits, P<0.001).


Phenotypes of pharyngeal dysfunction in OSA are evident from spontaneous changes in ventilation and ventilatory drive during sleep, enabling non-invasive phenotyping in the clinic. Our approach may facilitate precision therapeutic interventions for OSA.

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