According to a study published online ahead of the print edition of the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine, physicians can determine who is likely to have a higher risk of severe high altitude illness (SHAI) by measuring specific, exercise-related responses. They also discovered risk factors linked to SHAI could be reduced by taking acetazolamide (ACZ), a commonly prescribed drug for altitude illness.

Researchers identified three exercise-related factors:

  • Oxygen desaturation at exercise (Sae), which measures the amount of oxygen in the blood whilst exercising
  • Hypoxic cardiac response at exercise (HCRe), which measures the heart’s response to exercising in a hypoxic (low in oxygen) setting
  • Hypoxic ventilatory response at exercise (HVRe), in which respiratory changes, such as notably rapid breathing during exercise in a hypoxic setting is measured. All parameters were measured in controlled, hypoxic conditions in a lab setting simulating high-altitude conditions

Jean-Paul Richalet, MD, PhD, a professor of physiology at Université Paris 13 commented: “These results suggest that HCRe, HVRe and substantial decreases in Sae are independent risk factors of SHAI, and that decreases in Sae and HVRe can be used to accurately predict the risk of developing SHAI,” adding that, “To date, this is the largest epidemiological study of subjects exposed to high altitude-related illness, who were previously evaluated for their responses to hypoxia.”

Researchers assessed data obtained from 1,326 men and women before leaving on a high-altitude excursion. High-altitude excursions were defined as spending a minimum of 3 days higher than 4,000 meters above sea level, whilst sleeping at over 3,500 meters above sea level. All participants completed a questionnaire reporting details regarding their personal and family medical history, usual physical and mountaineering activity and other factors. Researchers then performed routine hypoxic exercise tests in all participants during which they measured heart rate, breathing and blood oxygen levels. The tests consisted of four, 4-minute intervals, such as rest at normal oxygen levels, rest at hypoxic levels, exercise in hypoxia and exercise in normal levels of oxygen.

When the participants returned from their excursions, they completed another questionnaire reporting if they had used ACZ and to determine whether they had experienced any symptoms of SHAI, including high altitude pulmonary edema (HAPE), swelling of lung tissue, high altitude cerebral edema (HACE), a swelling of the brain tissue, or severe acute mountain sickness (AMS) that can consist of a variety of symptoms, such as nausea, headache, fatigue and dizziness.

From a total of 1,326 respondents, 318 reported to have experienced a severe altitude illness, including 105 who used ACZ and 213 who did not. Based on these results, researchers identified which factors were linked to SHAI considering pre- and post-excursion data. In addition, they also established the efficacy of ACZ on the development of SHAI.

Dr. Richalet explained:

“We found that among those who did not use ACZ, factors including young age, female gender, history of migraine, regular physical activity, previous history of severe altitude illness, rapid ascent, HCRe, substantial changes in Sae and HVRe were significantly associated with SHAI. Geographically, the area of Ladakh, India, was associated with a higher risk of SHAI among non-ACZ users.”

Dr. Richalet remarked that in those participants who used ACZ as a preventative measure in the Alps, such as younger females with a history of migraine who were physically active on a regular basis and reported significant changes in HCRe and Sae, the link was no longer substantial to SHAI, although the Ladakh mountain range retained borderline significance. In participants who used ACZ, a history of SHAI, rapid ascent and HVRe were still linked to SHAI; however, the associations were not as significant compared with those who did not take ACZ. The researchers also established that using ACZ as a preventative reduced the risk of developing SHAI by 44%.

Dr. Richalet commented:

“Although it was not double-blinded and placebo-controlled, this study confirms in a large number of subjects the efficacy of the preventive use of ACZ in high-altitude-related illness. These results indicate that preventive use of ACZ may reduce the risk of SHAI in susceptible subjects to the same level as that of non-susceptible subjects.”

Researchers also associated frequent physical activity to an increased risk of SHAI, which according to Dr. Richalet supports the common belief among mountaineering experts that increasing the body’s ability to absorb oxygen during exercise is not a predictor of success in high-altitude expeditions.

He said:

“Of course, that does not mean that those who visit high altitudes should stop training before an expedition, but they should realize that intense aerobic training is not a protective factor against altitude-related disorders.”

This study is the first to indicate a possible link between a geographical location of ascent and SHAI. Dr. Richalet stated:

“When adjusted for all other risk factors, especially rate of ascent, one location – Ladakh – remained associated with a higher risk of SHAI in both ACZ and non-ACZ users. No clear explanation, linked to the climate or the difficulty of the terrain, is available, although many informal reports mention the higher risk of this location.”

He continued saying that even though previous episodes of SHAI continue to remain the best predictor for new episodes; study results support the use of hypoxic exercise testing, especially in individuals who are planning their first high-altitude excursions.

He concluded:

“Ideally, testing should be aimed both at subjects with no previous experience of high altitude, who therefore lack information about potential risk factors, and those who have experienced severe symptoms in the past, in order to determine if those episodes of SHAI were due to physiological characteristics. And of course, during a visit to high altitude regions, it must be emphasized that the best way to avoid severe symptoms is to ascend slowly – less than 400m of altitude difference between two consecutive nights above 3000 meters during the acclimatization period.”

Written by Petra Rattue