Scott A Sands1,2,3, Bradley A Edwards1,4,5, Philip I Terrill6, Luigi Taranto-Montemurro1, Ali Azarbarzin1, Melania Marques1,7, Lauren B Hess1, David P White1, Andrew Wellman1. 1. 1 Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 2. 2 Department of Allergy, Immunology and Respiratory Medicine, Melbourne, Victoria, Australia. 3. 3 Central Clinical School. 4. 4 Sleep and Circadian Medicine Laboratory, Department of Physiology, and. 5. 5 School of Psychological Sciences and Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Melbourne, Victoria, Australia. 6. 6 School of Information Technology and Electrical Engineering, University of Queensland, Brisbane, Queensland, Australia; and. 7. 7 Laboratorio do Sono, Instituto do Coracao (InCor), Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brasil.
Abstract
RATIONALE: Therapies for obstructive sleep apnea (OSA) could be administered on the basis of a patient's own phenotypic causes ("traits") if a clinically applicable approach were available. OBJECTIVES: Here we aimed to provide a means to quantify two key contributors to OSA-pharyngeal collapsibility and compensatory muscle responsiveness-that is applicable to diagnostic polysomnography. METHODS: 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 patients with OSA (N = 29), using a novel automated noninvasive method to estimate ventilatory drive (polysomnographic method) and using "gold standard" ventilatory drive (intraesophageal diaphragm EMG) for comparison. Specialized physiological measurements using continuous positive airway pressure manipulation were employed for further comparison. The validity of nasal pressure as a ventilation surrogate was also tested (N = 11). MEASUREMENTS AND MAIN RESULTS: Polysomnography-derived collapsibility and compensation estimates correlated favorably with those quantified using gold standard ventilatory drive (R = 0.83, P < 0.0001; and R = 0.76, P < 0.0001; respectively) and using continuous positive airway pressure manipulation (R = 0.67, P < 0.0001; and 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). CONCLUSIONS: Phenotypes of pharyngeal dysfunction in OSA are evident from spontaneous changes in ventilation and ventilatory drive during sleep, enabling noninvasive phenotyping in the clinic. Our approach may facilitate precision therapeutic interventions for OSA.
RATIONALE: Therapies for obstructive sleep apnea (OSA) could be administered on the basis of a patient's own phenotypic causes ("traits") if a clinically applicable approach were available. OBJECTIVES: Here we aimed to provide a means to quantify two key contributors to OSA-pharyngeal collapsibility and compensatory muscle responsiveness-that is applicable to diagnostic polysomnography. METHODS: 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 patients with OSA (N = 29), using a novel automated noninvasive method to estimate ventilatory drive (polysomnographic method) and using "gold standard" ventilatory drive (intraesophageal diaphragm EMG) for comparison. Specialized physiological measurements using continuous positive airway pressure manipulation were employed for further comparison. The validity of nasal pressure as a ventilation surrogate was also tested (N = 11). MEASUREMENTS AND MAIN RESULTS: Polysomnography-derived collapsibility and compensation estimates correlated favorably with those quantified using gold standard ventilatory drive (R = 0.83, P < 0.0001; and R = 0.76, P < 0.0001; respectively) and using continuous positive airway pressure manipulation (R = 0.67, P < 0.0001; and 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). CONCLUSIONS: Phenotypes of pharyngeal dysfunction in OSA are evident from spontaneous changes in ventilation and ventilatory drive during sleep, enabling noninvasive phenotyping in the clinic. Our approach may facilitate precision therapeutic interventions for OSA.
Entities:
Keywords:
endotype; pathophysiology; personalized medicine
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