Effect of altitude on urinary leukotriene (LT) E4 excretion and airway responsiveness to histamine in children with atopic asthma

Abstract

Asthmatic subjects who are resident at altitude may experience a deterioration in lung function following a stay at sea level. To determine whether measurement of urinary leukotriene E4 (LTE4) reflects changes in asthma severity and airway responsiveness, 14 allergic asthmatic subjects resident at altitude (1560 m, Davos, Switzerland) were studied. Subjects were randomly divided into two groups. Measurements of baseline forced expiratory volume in one second (FEV1), the concentration of histamine producing a 20% decrease in FEV1, (PC20 FEV1), serum total immunoglobulin E (IgE), eosinophil count, and urinary LTE4 concentration were determined prior to and following a 2 week stay in The Netherlands (sea level) in eight subjects (4 males and 4 females, aged 14±0.5 yrs) (mean±SEM) and over a similar time period in six subjects (4 males and 2 females, aged 15±0.3 yrs) resident in Davos, Switzerland. There was no significant difference in total IgE and eosinophil count, and no significant correlation between urinary LTE4 and PC20FEV1 histamine, FEV1, total IgE, and eosinophil count. In subjects returning to Davos from The Netherlands there was a significant increase in urinary LTE4 from a baseline value of 16.9 pg · mg-1 creatinine (GM, range 0.3-101.7 pg · mg-1 creatinine) to 52.3 pg · mg-1 creatinine (GM, range 8.8-301.6 pg · mg-1 creatinine), a significant decrease in PC20FEV1 from 1.7 mg · ml-1 (GM, range 0.3-16.4 mg · ml-1) to 0.9 mg · ml-1 (GM, range 0.1->32 mg · ml-1), and a significant fall in FEV1 from 3.0±0.3 to 2.8±0.3 l (mean±SEM). There was no significant change in urinary LTE4, FEV1 or PC20FEV1 histamine during a similar period of time in subjects resident in Davos. Thus, following a visit to sea level, children with atopic asthma who are usually resident at altitude exhibit a fall in FEV1 and an increase in airway responsiveness to histamine, which is associated with a threefold increase in urinary LTE4 excretion.