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

Abstract 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<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 <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)