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Background It is unknown how high altitude exposure causes inflammatory bowel disease (IBD) flares. We assessed disease activity in healthy controls, IBD patients after 3h exposure in a hypobaric pressure chamber (imitating an altitude of 4000m above sea level). Methods In a prospective study, 11 Crohn’s disease (CD, 6 males, 35.6y±13.7), 9 ulcerative colitis (UC, 3 males, 31.4y±10.8) patients and 10 healthy controls (7 males, 27.7y±4.9) underwent rectosigmoidoscopy in our outpatient clinic (490m, baseline T1) and after 3h exposure in a hypobaric pressure chamber (follow-up day 1 T2 and day 7 T3). Symptoms were assessed using the Harvey Bradshaw Index and the partial Mayo Score before and after hypobaric pressure chamber exposure (baseline T1, day 1 T2, day 7 T3 and day 30 T4). Disease activity was further assessed using CRP levels and fecal calprotectin. Intestinal mucosa-associated microbial composition was analyzed using high-throughput sequencing. Results The 3h exposure in a hypobaric pressure chamber was well tolerated in all subjects. Mean oxygen saturation decreased from 97.5%±1.3 to 80.9%±4.1, and increased back to normal levels (98.8%±1.2%) after the hypobaric intervention (p&amp;lt;0.0001). Clinical and endoscopic disease activity were not significantly changed before vs. after intervention. However, mild flare was seen in 2 UC patients and another UC patient was lost to follow-up due to a disease flare. New endoscopic lesions were detected in one healthy subject and one UC patient. Fecal calprotectin levels significantly increased in CD patients during the follow-up period (p=0.031), but not in UC and healthy controls. No changes in CRP levels were observed. Percentage of calprotectin-based disease remission (fecal calprotectin &amp;lt;100ug/g) decreased in all groups after hypobaric pressure chamber exposure, and increased thereafter (Figure 1) with a significant decrease in the control group (100% at baseline vs. 50% at day 1, p=0.029) and all patients combined (73.3% at baseline vs. 36.7% at day 7, p=0.013). No differences in alpha and beta diversity of stool microbiota composition before vs. after hypobaric pressure chamber exposure were observed. Conclusion In this prospective study involving IBD patients and healthy controls, a 3h exposure in a hypobaric pressure chamber (corresponding to an altitude of 4000m) did not result in higher disease activity. However, mild flares and development of endoscopic lesions were seen in a subset of patients. Calprotectin-based remission rates significantly decreased between baseline and day 7 suggesting a subclinical effect of short-term hypoxia, not explained by changes in the microbiome. (Clinicaltrials.gov number, NCT02849821)

journal of crohn s and colitis

P525 A prospective interventional study to evaluate the effect of hypoxia on healthy volunteers and patients with inflammatory bowel disease: The altitude IBD study