title: Altitude illness is related to low hypoxic chemoresponse and low oxygenation during sleep.
abstract: Altitude illness remains a major cause of mortality. Reduced chemosensitivity, irregular breathing leading to central apnoeas/hypopnoeas, and exaggerated pulmonary vasoconstriction may compromise oxygenation. All factors could enhance susceptibility to acute mountain sickness (AMS). We compared 12 AMS-susceptible individuals with recurrent and severe symptoms (AMS+) with 12 "AMS-nonsusceptible" subjects (AMS-), assessing sleep-breathing disorders in simulated altitude as well as chemoresponsive and pulmonary vasoconstrictive responses to hypoxia. During exposure to simulated altitude, mean blood oxygen saturation during sleep was lower in AMS+ subjects (81.6 ± 2.6 versus 86.0 ± 2.4%, p<0.01), associated with a lower central apnoea/hypopnoea index (18.2 ± 18.1 versus 33.4 ± 24.8 events · h(-1) in AMS+ and AMS- subjects, respectively; p=0.038). A lower hypoxic (isocapnic) chemoresponsiveness was observed in AMS+ subjects (0.40 ± 0.49 versus 0.97 ± 0.46 L · min(-1)·%; p<0.001). This represented the only significant and independent predictive factor for altitude intolerance, despite a higher increase in pulmonary artery systolic pressure in response to hypoxia, a lower lung diffusing capacity and a higher endothelin-1 level at baseline in AMS+ subjects (p<0.05). AMS+ subjects were more hypoxaemic whilst exhibiting fewer respiratory events during sleep owing to lower hypoxic (isocapnic) chemoresponsiveness. In conclusion, the reduction in peripheral hypoxic chemosensitivity appears to be a major causative factor for altitude intolerance.
authors.affiliation: HP2 Laboratory, INSERM Unit 1042, Grenoble, France.
authors.forename: Hugo
authors.initials: H
authors.lastname: Nespoulet
authors.forename: Bernard
authors.initials: B
authors.lastname: Wuyam
authors.forename: Renaud
authors.initials: R
authors.lastname: Tamisier
authors.forename: Carole
authors.initials: C
authors.lastname: Saunier
authors.forename: Denis
authors.initials: D
authors.lastname: Monneret
authors.forename: Judith
authors.initials: J
authors.lastname: Remy
authors.forename: Olivier
authors.initials: O
authors.lastname: Chabre
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Pépin
authors.forename: Patrick
authors.initials: P
authors.lastname: Lévy
mesh_terms: D000208:Acute Disease; D000328:Adult; D000532:Altitude Sickness / Q000097:blood / Q000503:physiopathology*; D001049:Apnea / Q000097:blood / Q000503:physiopathology; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood*; D011651:Pulmonary Artery / Q000503:physiopathology; D011653:Pulmonary Diffusing Capacity; D012720:Severity of Illness Index; D012890:Sleep / Q000502:physiology*
chemical_list: D019332:Endothelin-1; D010100:Oxygen