Acetazolamide to Prevent Adverse Altitude Effects in COPD and Healthy Adults.

Autor: Furian M; Department of Respiratory Medicine, University Hospital of Zurich, Zurich, Switzerland.; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic., Mademilov M; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic.; Department of Respiratory Medicine, National Center for Cardiology and Internal Medicine, Bishkek, Kyrgyz Republic., Buergin A; Department of Respiratory Medicine, University Hospital of Zurich, Zurich, Switzerland.; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic., Scheiwiller PM; Department of Respiratory Medicine, University Hospital of Zurich, Zurich, Switzerland.; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic., Mayer L; Department of Respiratory Medicine, University Hospital of Zurich, Zurich, Switzerland.; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic., Schneider S; Department of Respiratory Medicine, University Hospital of Zurich, Zurich, Switzerland.; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic., Emilov B; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic.; Department of Respiratory Medicine, National Center for Cardiology and Internal Medicine, Bishkek, Kyrgyz Republic., Lichtblau M; Department of Respiratory Medicine, University Hospital of Zurich, Zurich, Switzerland.; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic., Bitos K; Department of Respiratory Medicine, University Hospital of Zurich, Zurich, Switzerland.; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic., Muralt L; Department of Respiratory Medicine, University Hospital of Zurich, Zurich, Switzerland.; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic., Groth A; Department of Respiratory Medicine, University Hospital of Zurich, Zurich, Switzerland.; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic., Reiser AE; Department of Respiratory Medicine, University Hospital of Zurich, Zurich, Switzerland.; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic., Sevik A; Department of Respiratory Medicine, University Hospital of Zurich, Zurich, Switzerland.; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic., Sheraliev U; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic.; Department of Respiratory Medicine, National Center for Cardiology and Internal Medicine, Bishkek, Kyrgyz Republic., Marazhapov NH; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic.; Department of Respiratory Medicine, National Center for Cardiology and Internal Medicine, Bishkek, Kyrgyz Republic., Aydaralieva S; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic.; Department of Respiratory Medicine, National Center for Cardiology and Internal Medicine, Bishkek, Kyrgyz Republic., Muratbekova A; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic.; Department of Respiratory Medicine, National Center for Cardiology and Internal Medicine, Bishkek, Kyrgyz Republic., Tabyshova A; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic.; Department of Respiratory Medicine, National Center for Cardiology and Internal Medicine, Bishkek, Kyrgyz Republic., Abdraeva A; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic.; Department of Respiratory Medicine, National Center for Cardiology and Internal Medicine, Bishkek, Kyrgyz Republic., Buenzli S; Department of Respiratory Medicine, University Hospital of Zurich, Zurich, Switzerland.; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic., Sooronbaev TM; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic.; Department of Respiratory Medicine, National Center for Cardiology and Internal Medicine, Bishkek, Kyrgyz Republic., Ulrich S; Department of Respiratory Medicine, University Hospital of Zurich, Zurich, Switzerland.; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic., Bloch KE; Department of Respiratory Medicine, University Hospital of Zurich, Zurich, Switzerland.; Swiss-Kyrgyz High-Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic.
Jazyk: angličtina
Zdroj: NEJM evidence [NEJM Evid] 2022 Jan; Vol. 1 (1), pp. EVIDoa2100006. Date of Electronic Publication: 2021 Dec 22.
DOI: 10.1056/EVIDoa2100006
Abstrakt: BACKGROUND: We evaluated the efficacy of acetazolamide in preventing adverse altitude effects in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and in healthy lowlanders 40 years of age or older. METHODS: Trial 1 was a randomized, double-blind, parallel-design trial in which 176 patients with COPD were treated with acetazolamide capsules (375 mg/day) or placebo, starting 24 hours before staying for 2 days at 3100 m. The mean (±SD) age of participants was 57±9 years, and 34% were women. At 760 m, COPD patients had oxygen saturation measured by pulse oximetry of 92% or greater, arterial partial pressure of carbon dioxide less than 45 mm Hg, and mean forced expiratory volume in 1 second of 63±11% of predicted. The primary outcome in trial 1 was the incidence of the composite end point of altitude-related adverse health effects (ARAHE) at 3100 m. Criteria for ARAHE included acute mountain sickness (AMS) and symptoms or findings relevant to well-being and safety, such as severe hypoxemia, requiring intervention. Trial 2 comprised 345 healthy lowlanders. Their mean age was 53±7 years, and 69% were women. The participants in trial 2 underwent the same protocol as did the patients with COPD in trial 1. The primary outcome in trial 2 was the incidence of AMS assessed at 3100 m by the Lake Louise questionnaire score (the scale of self-assessed symptoms ranges from 0 to 15 points, indicating absent to severe, with 3 or more points including headache, indicating AMS). RESULTS: In trial 1 of patients with COPD, 68 of 90 (76%) receiving placebo and 42 of 86 (49%) receiving acetazolamide experienced ARAHE (hazard ratio, 0.54; 95% confidence interval [CI], 0.37 to 0.79; P<0.001). The number needed to treat (NNT) to prevent one case of ARAHE was 4 (95% CI, 3 to 8). In trial 2 of healthy individuals, 54 of 170 (32%) receiving placebo and 38 of 175 (22%) receiving acetazolamide experienced AMS (hazard ratio, 0.48; 95% CI, 0.29 to 0.80; chi-square statistic P=0.035). The NNT to prevent one case of AMS was 10 (95% CI, 5 to 141). No serious adverse events occurred in these trials. CONCLUSIONS: Preventive treatment with acetazolamide reduced the incidence of adverse altitude effects requiring an intervention in patients with COPD and the incidence of AMS in healthy lowlanders 40 years of age or older during a high-altitude sojourn. (Funded by the Swiss National Science Foundation [Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung], Lunge Zürich, and the Swiss Lung Foundation; ClinicalTrials.gov numbers, NCT03156231 and NCT03561675.)
Databáze: MEDLINE