Acute mountain sickness (AMS) is a syndrome of neurologic symptoms, experienced by non-acclimatized individuals at altitudes >2500m. The cardinal symptom is headache, accompanied by anorexia, nausea, dizziness, and sleep disturbances. AMS is thought to have its origin in the brain. However, recent data indicate that the lung may play a primary role in the pathophysiology of AMS by releasing pathogenic signals that induce inflammatory and oxidative processes in the brain. 
The present prospective, randomized, double-blind and placebo-controlled trial investigated whether inhalation of the corticosteroid budesonide improves the incidence and severity of AMS at 4559m. Fifty-one subjects were randomized into 3 groups (n=17 per group) to receive either placebo or budesonide at 200 or 800 µg twice/day. Inhalation was started 1 day prior to ascent from 1130m to 4559m in <20h with an intervening overnight stay at 3611m. AMS was evaluated by the Lake Louise score (LLS) and the AMS-C score of the Environmental Symptom Questionnaire. Individuals were scored AMS-positive when they had a LLS ≥5 and an AMS-C score ≥0,70. Pulmonary artery systolic pressure (PASP) was assessed by transthoracic echocardiography, and plasma and urine concentrations of ACTH and cortisol, respectively, were measured to evaluate systemic effects of inhaled budesonide. Capillary blood samples were analysed for the determination of PO2. The study was approved by the Ethical Committee Salzburg, Austria, and the Ethical Committee of the University Torino, Italy. Statistics: 2-Way-RM-ANOVA. Data are given as mean±SD.
Ascent to high-altitude decreased capillary PO2 from 84±7 mmHg to 47±5mmHg (P<0,001), and increased AMS-scores without a difference between the 3 study groups (for placebo, budesonide 200 and 800 µg b.i.d.: incidence 44% vs 50% and 63%; LLS: 6,4±4,0 vs 6,6±2,8 and 8,2±3,5; AMS-C: 0,8±0,8 vs 1,0±0,9 and 1,3±1,1 after the first night at 4559m (all P>0,23). At high-altitude PASP increased about 2-fold and was not affected by budesonide (all P>0,25). Neither ACTH nor free cortisol in 24-h urine samples differed significantly between the 3 study groups (all P>0,41). 
This study demonstrates that inhalation of budesonide has no beneficial effect on the incidence and severity of AMS after active and rapid ascent from low-altitude to 4559m. Therefore, budesonide cannot be recommended of prevention of AMS. Our data do not support a primary role of the lung in the pathophysiology of AMS.

Inhaled budesonide does not improve the incidence and severity of acute mountain sickness