title: Biomarkers of hypoxia, endothelial and circulatory dysfunction among climbers in Nepal with AMS and HAPE: a prospective case-control study.
abstract: BACKGROUND
  The mechanisms underlying acute mountain sickness (AMS) and high-altitude pulmonary edema (HAPE) are not fully understood. We hypothesized that regulators of endothelial function, circulatory homeostasis, hypoxia and cell stress contribute to the pathobiology of AMS and HAPE.
  
  
  METHODS
  We conducted a prospective case-control study of climbers developing altitude illness who were evacuated to the CIWEC clinic in Kathmandu, compared to healthy acclimatized climbers. ELISA was used to measure plasma biomarkers of the above pathways.
  
  
  RESULTS
  Of the 175 participants, there were 71 cases of HAPE, 54 cases of AMS and 50 acclimatized controls (ACs). Markers of endothelial function were associated with HAPE: circulating levels of endothelin-1 (ET-1) were significantly elevated and levels of sKDR (soluble kinase domain receptor) were significantly decreased in cases of HAPE compared to AC or AMS. ET-1 levels were associated with disease severity as indicated by oxygen saturation. Angiopoietin-like 4 (Angptl4) and resistin, a marker of cell stress, were associated with AMS and HAPE irrespective of severity. Corin and angiotensin converting enzyme, regulators of volume homeostasis, were significantly decreased in HAPE compared to AC.
  
  
  CONCLUSIONS
  Our findings indicate that regulators of endothelial function, vascular tone and cell stress are altered in altitude illness and may mechanistically contribute to the pathobiology of HAPE.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital, Toronto, ON, Canada.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Barker
authors.affiliation: Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital, Toronto, ON, Canada.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Conroy
authors.affiliation: Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital, Toronto, ON, Canada, Division of Infectious Diseases, Department of Pediatrics, University of Alberta, Edmonton, AB, Canada and.
authors.forename: Michael
authors.initials: M
authors.lastname: Hawkes
authors.affiliation: CIWEC Hospital and Travel Medicine Center, Kathmandu, Nepal.
authors.forename: Holly
authors.initials: H
authors.lastname: Murphy
authors.affiliation: CIWEC Hospital and Travel Medicine Center, Kathmandu, Nepal.
authors.forename: Prativa
authors.initials: P
authors.lastname: Pandey
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital, Toronto, ON, Canada, The Tropical Disease Unit, Department of Medicine, University of Toronto, Toronto, ON, Canada, kevin.kain@uhn.ca.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Kain
mesh_terms: D000064:Acclimatization; D000208:Acute Disease; D000328:Adult; D000532:Altitude Sickness / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood*; D000860:Hypoxia / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009051:Mountaineering; D009390:Nepal; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011446:Prospective Studies; D012769:Shock / Q000097:blood*; D014195:Travel
chemical_list: D015415:Biomarkers; D019332:Endothelin-1; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A
keywords: Acute mountain sickness; altitude illness; circulatory homeostasis; endothelial dysfunction; endothelin-1; high-altitude pulmonary edema; hypoxia