Effect of Nocturnal Oxygen Therapy on Nocturnal Hypoxemia and Sleep Apnea Among Patients With Chronic Obstructive Pulmonary Disease Traveling to 2048 Meters: A Randomized Clinical Trial

IMPORTANCE: There are no established measures to prevent nocturnal breathing disturbances and other altitude-related adverse health effects (ARAHEs) among lowlanders with chronic obstructive pulmonary disease (COPD) traveling to high altitude. OBJECTIVE: To evaluate whether nocturnal oxygen therapy (NOT) prevents nocturnal hypoxemia and breathing disturbances during the first night of a stay at 2048 m and reduces the incidence of ARAHEs. DESIGN, SETTING, AND PARTICIPANTS: This randomized, placebo-controlled crossover trial was performed from January to October 2014 with 32 patients with COPD living below 800 m with forced expiratory volume in the first second of expiration (FEV(1)) between 30% and 80% predicted, pulse oximetry of at least 92%, not requiring oxygen therapy, and without history of sleep apnea. Evaluations were performed at the University Hospital Zurich (490 m, baseline) and during 2 stays of 2 days and nights each in a Swiss Alpine hotel at 2048 m while NOT or placebo treatment was administered in a randomized order. Between altitude sojourns, patients spent at least 2 weeks below 800 m. Data analysis was performed from January 1, 2015, to December 31, 2018. INTERVENTION: During nights at 2048 m, NOT or placebo (room air) was administered at 3 L/min by nasal cannula. MAIN OUTCOMES AND MEASURES: Coprimary outcomes were differences between NOT and placebo intervention in altitude-induced change in mean nocturnal oxygen saturation (SpO(2)) as measured by pulse oximetry and apnea-hypopnea index (AHI) measured by polysomnography during night 1 at 2048 m and analyzed according to the intention-to-treat principle. Further outcomes were the incidence of predefined ARAHE, other variables from polysomnography results and respiratory sleep studies in the 2 nights at 2048 m, clinical findings, and symptoms. RESULTS: Of the 32 patients included, 17 (53%) were women, with a mean (SD) age of 65.6 (5.6) years and a mean (SD) FEV(1) of 53.1% (13.2%) predicted. At 490 m, mean (SD) SpO(2) was 92% (2%) and mean (SD) AHI was 21.6/h (22.2/h). At 2048 m with placebo, mean (SD) SpO(2) was 86% (3%) and mean (SD) AHI was 34.9/h (20.7/h) (P < .001 for both comparisons). Compared with placebo, NOT increased SpO(2) by a mean of 9 percentage points (95% CI, 8-11 percentage points; P < .001), decreased AHI by 19.7/h (95% CI, 11.4/h-27.9/h; P < .001), and improved subjective sleep quality measured on a visual analog scale by 9 percentage points (95% CI, 0-17 percentage points; P = .04). During visits to 2048 m or within 24 hours after descent, 8 patients (26%) using placebo and 1 (4%) using NOT experienced ARAHEs (P < .001). CONCLUSIONS AND RELEVANCE: Lowlanders with COPD experienced hypoxemia, sleep apnea, and impaired well-being when staying at 2048 m. Because NOT significantly mitigated these undesirable effects, patients with moderate to severe COPD may benefit from preventive NOT during high altitude travel. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02150590