title: Enhanced upper-airway muscle responsiveness is a distinct feature of overweight/obese individuals without sleep apnea.
abstract: BACKGROUND
  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/m(2)) for reasons that are not fully elucidated.
  
  
  OBJECTIVE
  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.
  
  
  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 cm H2O; 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.
authors.affiliation: 1 Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Sands
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Eckert
authors.forename: Amy S
authors.initials: AS
authors.lastname: Jordan
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Edwards
authors.forename: Robert L
authors.initials: RL
authors.lastname: Owens
authors.forename: James P
authors.initials: JP
authors.lastname: Butler
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Schwab
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Loring
authors.forename: Atul
authors.initials: A
authors.lastname: Malhotra
authors.forename: David P
authors.initials: DP
authors.lastname: White
authors.forename: Andrew
authors.initials: A
authors.lastname: Wellman
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D045422:Continuous Positive Airway Pressure; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009130:Muscle, Smooth / Q000503:physiopathology*; D009765:Obesity / Q000150:complications / Q000503:physiopathology; D050177:Overweight / Q000150:complications / Q000503:physiopathology*; D010614:Pharynx / Q000503:physiopathology*; D017286:Polysomnography; D012129:Respiratory Function Tests; D020181:Sleep Apnea, Obstructive / Q000209:etiology* / Q000503:physiopathology; D012894:Sleep Stages
keywords: apnea phenotypes; control of breathing; mathematical model; obesity; upper airway muscles