The effects of a 5-lipoxygenase inhibitor on acute mountain sickness and urinary leukotriene e4 after ascent to high altitude.
BACKGROUND
Elevated urine and blood leukotriene levels have been reported after ascent to high altitude in association with acute mountain sickness (AMS) and high-altitude pulmonary edema. Zileuton is an inhibitor of the enzyme 5-lipoxygenase that catalyzes conversion of arachidonic acid to leukotrienes. Study objectives and design: The objectives of this randomized, double-blind, placebo-controlled clinical trial were to determine whether zileuton (600 mg po qid) is effective prophylaxis for AMS, and to measure the effect of ascent to high altitude and zileuton on urinary leukotriene E(4) levels.


METHODS
The study group consisted of volunteers from among climbers on the West Buttress of Mt. McKinley (Denali), Alaska. After baseline urine samples at sea level, subjects flew by airplane to 2,300 m, and then ascended to the 4,200-m camp in 5 to 10 days.


RESULTS
Using an enzyme immunoassay, urinary leukotriene E(4) was found to decrease after ascent to high altitude in both the zileuton and placebo groups. Urinary leukotriene E(4) in the zileuton group (n = 9) decreased from 67 +/- 35 pg/mg creatinine at sea level to 33 +/- 22 pg/mg creatinine at high altitude (p = 0.003) [mean +/- SD]. Urinary leukotriene E(4) in the placebo group (n = 9) decreased from 97 +/- 82 pg/mg creatinine at sea level to 44 +/- 21 pg/mg creatinine at high altitude (p = 0.045). One subject in the zileuton group and three subjects in the placebo group met Lake Louise criteria for AMS after arriving at 4,200 m (p = 0.257).


CONCLUSIONS
Elevated leukotrienes are not associated with ascent to high altitude. In subjects with AMS, urinary leukotrienes were not elevated, suggesting that leukotrienes may not be a component of the pathophysiology of AMS. The low incidence of AMS and the small sample size in this study prevented determination of whether zileuton is effective prophylaxis for AMS.
Grissom
Colin K
CK
Pulmonary Division, LDS Hospital, Eighth Ave and C St, Salt Lake City, UT 84143, USA. LDCGRISS@ihc.com
Richer
Lori D
LD
Elstad
Mark R
MR
D000064:Acclimatization / Q000187:drug effects / Q000502:physiology; D000284:Administration, Oral; D000328:Adult; D000413:Alaska; D000532:Altitude Sickness / Q000503:physiopathology / Q000517:prevention & control*; D001094:Arachidonate 5-Lipoxygenase / Q000502:physiology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood; D017999:Leukotriene E4 / Q000652:urine; D016859:Lipoxygenase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009051:Mountaineering / Q000502:physiology*; D010092:Oximetry; D011292:Premedication; D013223:Statistics as Topic; D016896:Treatment Outcome
D018836:Inflammation Mediators; D016859:Lipoxygenase Inhibitors; D017999:Leukotriene E4; D001094:Arachidonate 5-Lipoxygenase; C063449:zileuton; D006918:Hydroxyurea