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

Abstract

E Ef ff fe ec ct t o of f a al lt ti it tu ud de e o on n u ur ri in na ar ry y l le eu uk ko ot tr ri ie en ne e ( (L LT T) ) E E 4 4e ex xc cr re et ti io on n a an nd d a ai ir rw wa ay y r re es sp po on ns si iv ve en ne es ss s t to o h hi is st ta am mi in ne e i in n c ch hi il ld dr re en n w wi it th h a at to op pi ic c a as st th hm ma a Subjects were randomly divided into two groups. Measurements of baseline forced expiratory volume in one second (FEV 1 ), the concentration of histamine producing a 20% decrease in FEV 1 , (PC20 FEV 1 ), serum total immunoglobulin E (IgE), eosinophil count, and urinary LTE 4 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 LTE 4 and PC20FEV 1 histamine, FEV 1 , total IgE, and eosinophil count. In subjects returning to Davos from The Netherlands there was a significant increase in urinary LTE 4 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 PC20FEV 1 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 FEV 1 from 3.0±0.3 to 2.8±0.3 l (mean±SEM). There was no significant change in urinary LTE 4 , FEV 1 or PC20FEV 1 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 FEV 1 and an increase in airway responsiveness to histamine, which is associated with a threefold increase in urinary LTE 4 excretion. Eur Respir J., 1995, 8, 357-363 The cysteinyl leukotrienes (LTC 4 , LTD 4 and LTE 4 ) are derived from arachidonic acid by the action of 5-lipoxygenase, which generates 5-hydroperoxyeicosatetraenoic acid and then leukotriene A 4 (LTA 4 ) [1][2][3]. LTA 4 is metabolized by the addition of glutathione to form LTC 4 . LTC 4 may be converted by γ-glutamyltranspeptidase to generate LTD 4 , which is converted by a dipeptidase to yield LTE 4 [4,5]. In vitro the cysteinyl leukotrienes, LTC 4 , LTD 4 and LTE 4 , contract smooth muscle and enhance microvascular permeability [6][7][8]. In humans they are potent bronchoconstrictor agents when inhaled, and increase nonspecific bronchial hyperresponsiveness [9][10][11][12].In man, there is rapid metabolism of LTC 4 to LTD 4 and then to LTE 4 . LTE 4 may be further metabolized to oxidation products, which are excreted into bile and urine [13][14][15][16]. Combined reversed-phase high performance liquid chromatography (RP-HPLC) and radioimmunoassay (RIA) enables urinary LTE 4 to be measured [17], and the values have been used as an estimate of th...

High‐altitude treatment: a therapeutic option for patients with severe, refractory asthma?

“…Simon et al [37] studied 14 HDM-allergic asthmatic children and showed an improvement of lung function and reduction of peripheral blood eosinophils after 3 weeks at high altitude in Davos. Christie et al [38] performed a randomized-controlled study in Dutch children who were staying at the Asthma Centre in Davos for at least 1 month, and returned home for a short period of 2 weeks. As compared with the children who remained in Davos, the children who returned from the Netherlands showed a significant decline in FEV 1 , an increase in airway responsiveness to histamine, accompanied by a threefold increase in urinary leukotriene E 4 (LTE 4 ).…”

The effects of flight and altitude

“…51 As a marker of inflammatory response, eight patients with asthma and a mean age of 14 years who returned to an altitude of 1560 m after a 14 day break at sea level, showed increases in airway reactivity and inflammatory mediators, compared to controls who stayed at altitude. 52 More recently, it has been shown that genetic factors may play an important role in protection against the effects of altitude. The presence of a specific angiotensin converting enzyme (ACE) genotype (I allele), resulting in low ACE activity, is associated with protection of SaO 2 levels in climbers who ascend rapidly to over 5000 m. 53 In addition, climbers susceptible to high altitude pulmonary oedema were more likely to have certain genetic markers associated with low levels of nitric oxide production in the lung.…”

High-altitude treatment in atopic and nonatopic patients with severe asthma

“…High-altitude treatment has been applied for decades in patients with asthma, especially in children and adolescents with moderate-tosevere atopic disease [6][7][8][9]. The success of this treatment has long been attributed to the absence of house dust mite allergens at altitudes .1,600 m [10].…”