title: Changes in plasma bradykinin concentration and citric acid cough threshold at high altitude.
abstract: OBJECTIVE
  Altitude-related cough is a troublesome condition of unknown etiology. Inhaled tussive agents are used to quantify cough, and the citric acid cough threshold has been shown to fall on ascent to altitude. Cough can occur in patients taking angiotensin-converting enzyme inhibitors due to stimulation of airway sensory receptors by increased levels of bradykinin. We hypothesized that increased levels of bradykinin could be responsible for the decrease in citric acid cough threshold on exposure to altitude and a possible etiologic factor in altitude-related cough.
  
  
  METHODS
  Twenty healthy volunteers underwent baseline tests at 700 m before a 2-week stay at 3800 m. Angiotensin-converting enzyme activity and plasma bradykinin were measured at baseline and altitude. Citric acid cough threshold and nocturnal cough frequency were measured at baseline and throughout the 2 weeks at altitude.
  
  
  RESULTS
  Citric acid cough threshold fell from 3.7 g/dL at baseline to 2.1 g/dL on the second day at 3800 m (geometric mean difference 1.8, 95% CIs 1.0-5.0, P = .025) and remained reduced throughout the stay at altitude. Nocturnal cough frequency was unchanged compared to baseline. Plasma bradykinin fell from 0.43 ng/mL at baseline to 0.08 ng/mL at altitude (geometric mean difference 5.7, 95% CIs 2.1-15.5, P = .002), but angiotensin-converting enzyme activity was unchanged (mean difference 0.06, 95% CIs -2.7-2.8, P = .97). There was no correlation between plasma bradykinin and citric acid cough threshold.
  
  
  CONCLUSIONS
  Increased levels of bradykinin are unlikely to be a significant factor in the increased sensitivity to citric acid seen in hypobaric hypoxia. Further studies are required to elucidate the etiology of altitude-related cough.
authors.affiliation: Department of Anaesthesia and Intensive Care Medicine, Royal Gwent Hospital, Newport, UK. npmason@doctors.org.uk
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Mason
authors.forename: Merete
authors.initials: M
authors.lastname: Petersen
authors.forename: Christian
authors.initials: C
authors.lastname: Mélot
authors.forename: Elena V
authors.initials: EV
authors.lastname: Kim
authors.forename: Almaz
authors.initials: A
authors.lastname: Aldashev
authors.forename: Akpay
authors.initials: A
authors.lastname: Sarybaev
authors.forename: Mirsaid M
authors.initials: MM
authors.lastname: Mirrakhimov
authors.forename: Robert
authors.initials: R
authors.lastname: Naeije
mesh_terms: D000293:Adolescent; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects; D001920:Bradykinin / Q000097:blood*; D019343:Citric Acid / Q000008:administration & dosage* / Q000009:adverse effects; D003371:Cough / Q000139:chemically induced*; D006339:Heart Rate; D006801:Humans; D008297:Male; D010100:Oxygen / Q000097:blood; D055815:Young Adult
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D019343:Citric Acid; D010100:Oxygen; D001920:Bradykinin