A simplified method for determining phenotypic traits in patients with obstructive sleep apnea

Andrew Wellman, Bradley A. Edwards, Scott A. Sands, Robert L Owens, Shamim Nemati, James P Butler, Chris L. Passaglia, Andrew C. Jackson, Atul Malhotra, David P. White

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113 Citations (Scopus)


We previously published a method for measuring several physiological traits causing obstructive sleep apnea (OSA). The method, however, had a relatively low success rate (76%) and required mathematical modeling, potentially limiting its application. This paper presents a substantial revision of that technique. To make the measurements, continuous positive airway pressure (CPAP) was manipulated during sleep to quantify 1) eupneic ventilatory demand, 2) the level of ventilation at which arousals begin to occur, 3) ventilation off CPAP (nasal pressure = 0 cmH2O) when the pharyngeal muscles are activated during sleep, and 4) ventilation off CPAP when the pharyngeal muscles are relatively passive. These traits could be determined in all 13 participants (100% success rate). There was substantial intersubject variability in the reduction in ventilation that individuals could tolerate before having arousals (difference between ventilations # 1 and # 2 ranged from 0.7 to 2.9 liters/min) and in the amount of ventilatory compensation that individuals could generate (difference between ventilations # 3 and # ranged from -0.5 to 5.5 liters/min). Importantly, the measurements accurately reflected clinical metrics; the difference between ventilations # 2 and # 3, a measure of the gap that must be overcome achieve stable breathing during sleep, correlated with the apneahypopnea index (r = 0.9, P < 0.001). An additional procedure was added to the technique to measure loop gain (sensitivity of the ventilatory control system), which allowed arousal threshold and upper airway gain (response of the upper airway to increasing ventilatory drive) to be quantified as well. Of note, the traits were generally repeatable when measured on a second night in 5 individuals. This technique is a relatively simple way of defining mechanisms underlying OSA and could potentially be used in a clinical setting individualize therapy.

Original languageEnglish
Pages (from-to)911-922
Number of pages12
JournalJournal of Applied Physiology
Issue number7
Publication statusPublished - 1 Apr 2013
Externally publishedYes


  • Arousal threshold
  • Loop gain
  • Pathophysiology of sleep apnea
  • Pharyngeal critical closing pressure
  • Upper airway

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