From Pages to Practice

By Leslie Chang, MD

Published July 20, 2022


Lauren is a healthy, physically active 28-year-old medical student who is looking forward to graduating from medical school next month. She has exactly one month off between the end of medical school and the start of residency, and she plans to make the most of it. Although the COVID pandemic has made planning difficult, she is looking forward to climbing Mount Kilimanjaro, the world’s tallest free-standing mountain at nearly 5900 meters high. She is considering traveling with her mother, although her mother has a history of moderate chronic obstructive pulmonary disease (COPD). Lauren asks whether her mother should travel with her to the base of the mountain while she climbs and whether her mother can take something to prevent altitude sickness while at the base.

As technology and transportation have enabled an increasing number of individuals to reach high altitudes for purposes of adventure travel, advanced consideration and counseling targeting individuals with pre-existing medical conditions is necessary, but challenging given the lack of data. Specifically, individuals with cardiopulmonary diseases may be at a higher risk for experiencing altitude-related health effects, and evidence is lacking for efficacy of medications to prevent these effects in patients with COPD. In the new journal, NEJM Evidence, Furian et al. report the results of two separate randomized-controlled trials that examined the effects of preventative acetazolamide in reducing the incidence of adverse effects of altitude in patients with COPD (trial 1) and in healthy adults (trial 2).  To help address Lauren’s concerns regarding her mother’s ability to travel, let’s focus on trial 1, the study that included patients with COPD.

Trial 1 consisted of 185 patients with COPD, who were either randomized to receive acetazolamide (125 mg in the morning and 250 mg in the evening) or placebo capsules before climbing to 3100 meters of elevation and being monitored for altitude illness. The primary outcome was the incidence of altitude-related adverse health effects (ARAHE), which included hypoxemia, headache, and other severe symptoms. The results demonstrated a significant reduction in the incidence of AHARE in COPD patients who received acetazolamide as compared with those who received placebo (49% vs.76%).

Although acetazolamide reduced the incidence of adverse effects of altitude in a population of patients with COPD, nearly half the  patients still experienced severe symptoms related to altitude. Given this, Lauren’s mother may want to reconsider traveling with her daughter to Mount Kilimanjaro and opt to explore the rest of Tanzania instead.

The following NEJM Journal Watch summary provides more details of these studies.


Acetazolamide in Patients at High Risk for Altitude Illness

Thomas L. Schwenk, MD, reviewing Furian M et al. NEJM Evidence 2022 Jan 

The increasing frequency of adventure travel to mountain destinations by patients considered to be at excess risk for high-altitude illness prompted investigators from Switzerland and the Kyrgyz Republic to conduct two randomized trials of acetazolamide to prevent altitude illness. One study involved 185 patients with mostly moderate chronic obstructive pulmonary disease (COPD; mean forced expiratory volume in 1 second [FEV1], 63%), and another involved 349 healthy lowlanders (mean age, 53). In both trials, participants were assessed at 2500 feet elevation and treated with acetazolamide (125 mg in the morning and 250 mg at night) or placebo starting 24 hours before ascending to 10,100 feet for 48 hours. (This is a U.S. FDA-approved indication for acetazolamide.) 

In the COPD study, patients were assessed with a composite measure of acute mountain sickness (i.e., headache, myalgia, nausea), more-severe symptoms of hypoxemia (oxygen saturation, <80% for >30 minutes, or <75% for >15 minutes), and other severe cardiovascular symptoms. The incidence of altitude illness was reduced from 76% in the placebo group to 49% in the acetazolamide group. In the healthy population, only acute mountain sickness was assessed; incidence was reduced from 32% to 22% with acetazolamide treatment.

Comment: Acetazolamide prevented some COPD patients from experiencing severe high-altitude symptoms, but nearly half still had substantial symptoms that required descent to a lower level. In my prior experience practicing at altitude, these results would not reassure me in advising patients with moderate-to-severe COPD about vacationing at high altitude, even with acetazolamide. The study that addressed healthy middle-aged lowlanders supports my experience with those patients; lack of cardiovascular comorbidity is more important than age. Risk for minor symptoms of acute mountain sickness is modest and is lowered further by acetazolamide.

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Leslie is a 2021-2022 NEJM Editorial Fellow and a hospitalist at Massachusetts General Hospital. She graduated from Duke University School of Medicine in 2018 and completed her internal medicine residency at Massachusetts General Hospital in 2021.