title: Leptin and the control of pharyngeal patency during sleep in severe obesity.
abstract: BACKGROUND
  Obesity imposes mechanical loads on the upper airway, resulting in flow limitation and obstructive sleep apnea (OSA). In previous animal models, leptin has been considered to serve as a stimulant of ventilation and may prevent respiratory depression during sleep. We hypothesized that variations in leptin concentration among similarly obese individuals will predict differences in compensatory responses to upper airway obstruction during sleep.
  
  
  METHODS
  An observational study was conducted in 23 obese women [body mass index (BMI): 46 ± 3 kg/m(2), age: 41 ± 12 yr] and 3 obese men (BMI: 46 ± 3 kg/m(2), age: 43 ± 4 yr). Subjects who were candidates for bariatric surgery were recruited to determine upper airway collapsibility under hypotonic conditions [pharyngeal critical pressure (passive PCRIT)], active neuromuscular responses to upper airway obstruction during sleep, and overnight fasting serum leptin levels. Compensatory responses were defined as the differences in peak inspiratory airflow (ΔVImax), inspired minute ventilation (ΔVI), and pharyngeal critical pressure (ΔPCRIT) between the active and passive conditions.
  
  
  RESULTS
  Leptin concentration was not associated with sleep disordered breathing severity, passive PCRIT, or baseline ventilation. In the women, increases in serum leptin concentrations were significantly associated with increases in ΔVImax (r(2) = 0.44, P < 0.001), ΔVI (r(2) = 0.40, P < 0.001), and ΔPCRIT (r(2) = 0.19, P < 0.04). These responses were independent of BMI, waist-to-hip ratio, neck circumference, or sagittal girth.
  
  
  CONCLUSIONS
  Leptin may augment neural compensatory mechanisms in response to upper airway obstruction, minimizing upper airway collapse, and/or mitigating potential OSA severity. Variability in leptin concentration among similarly obese individuals may contribute to differences in OSA susceptibility.
authors.affiliation: Johns Hopkins Sleep Disorders Center, Division of Pulmonary & Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland;
authors.forename: Steven D
authors.initials: SD
authors.lastname: Shapiro
authors.affiliation: Johns Hopkins Sleep Disorders Center, Division of Pulmonary & Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; and.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Chin
authors.affiliation: Johns Hopkins Sleep Disorders Center, Division of Pulmonary & Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland;
authors.forename: Jason P
authors.initials: JP
authors.lastname: Kirkness
authors.affiliation: Johns Hopkins Sleep Disorders Center, Division of Pulmonary & Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland;
authors.forename: Brian M
authors.initials: BM
authors.lastname: McGinley
authors.affiliation: Johns Hopkins Sleep Disorders Center, Division of Pulmonary & Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland;
authors.forename: Susheel P
authors.initials: SP
authors.lastname: Patil
authors.affiliation: Johns Hopkins Sleep Disorders Center, Division of Pulmonary & Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland;
authors.forename: Vsevolod Y
authors.initials: VY
authors.lastname: Polotsky
authors.affiliation: Johns Hopkins Sleep Disorders Center, Division of Pulmonary & Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland; Hospital Universitario (HU-USP), Sao Paulo, Brasil.
authors.forename: Paolo Jose Cesare
authors.initials: PJ
authors.lastname: Biselli
authors.affiliation: Johns Hopkins Sleep Disorders Center, Division of Pulmonary & Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland;
authors.forename: Philip L
authors.initials: PL
authors.lastname: Smith
authors.affiliation: Johns Hopkins Sleep Disorders Center, Division of Pulmonary & Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland;
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schneider
authors.affiliation: Johns Hopkins Sleep Disorders Center, Division of Pulmonary & Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland; aschwar2@jhmi.edu.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Schwartz
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood*; D009767:Obesity, Morbid / Q000150:complications / Q000503:physiopathology*; D010614:Pharynx / Q000503:physiopathology*; D012123:Pulmonary Ventilation; D012890:Sleep; D020181:Sleep Apnea, Obstructive / Q000209:etiology / Q000503:physiopathology*
chemical_list: D020738:Leptin
keywords: leptin; obesity; obstructive sleep apnea; upper airway control