Enhanced upper-airway muscle responsiveness is a distinct feature of overweight/obese individuals without sleep apnea

Scott A. Sands, Danny J. Eckert, Amy S. Jordan, Bradley A. Edwards, Robert L. Owens, James P. Butler, Richard J. Schwab, Stephen H. Loring, Atul Malhotra, David P. White, Andrew Wellman

Research output: Contribution to journalArticlepeer-review

99 Citations (Scopus)


Rationale: Body habitus is a major determinant of obstructive sleep apnea (OSA). However, many individuals do not have OSA despite being overweight/obese (body mass index > 25 kg/m2) for reasons that are not fully elucidated. Objectives: To determine the key physiologic traits (upper-airway anatomy/collapsibility, upper-airway muscle responsiveness, chemoreflex control of ventilation, arousability from sleep) responsible for the absence of OSA in overweight/obese individuals. Methods: We compared key physiologic traits in 18 overweight/ obese subjects without apnea (apnea-hypopnea index < 15 events per hour) with 25 overweight/obese matched patients with OSA (apnea-hypopnea index ≥ 15 events per hour) and 11 normal-weight nonapneic control subjects. Traits were measured by repeatedly lowering continuous positive airway pressure to subtherapeutic levels for 3 minutes during non-REM sleep. Measurements and Main Results: Overweight/obese subjects without apnea exhibited a less collapsible airway than overweight/ obese patients with apnea (critical closing pressure: -3.7 ± 1.9 vs. 0.6 ± 1.2 cm H2O; P = 0.003; mean ± 95% confidence interval), but a more collapsible airway relative to normal-weight control subjects (-8.8 ± 3.1 cmH2O; P < 0.001). Notably, overweight/obese subjects without apnea exhibited a threefold greater upper-airway muscle responsiveness than both overweight/obese patients with apnea (Δgenioglossus EMG/Δepiglottic pressure: -0.49 [-0.22 to -0.79] vs. -0.15 [-0.09 to -0.22] %max/cm H2O; P = 0.008; mean [95% confidence interval]) and normal-weight control subjects (-0.16 [-0.04 to -0.30] %max/cm H2O; P = 0.02). Loop gain was elevated (more negative) in both overweight/obese groups and normal-weight control subjects (P = 0.02). Model-based analysis demonstrated that overweight/obese individuals without apnea rely on both more favorable anatomy and collapsibility and enhanced upper-airway dilator muscle responses to avoid OSA. Conclusions: Overweight/obese individuals without apnea have a moderately compromised upper-airway structure that is mitigated by highly responsive upper-airway dilator muscles to avoid OSA. Elucidating the mechanisms underlying enhanced muscle responses in this population may provide clues for novel OSA interventions.

Original languageEnglish
Pages (from-to)930-937
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number8
Publication statusPublished - 15 Oct 2014


  • Apnea phenotypes
  • Control of breathing
  • Mathematical model
  • Obesity
  • Upper airway muscles


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