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Altitude illnesses

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Abstract

Millions of people visit high-altitude regions annually and more than 80 million live permanently above 2,500 m. Acute high-altitude exposure can trigger high-altitude illnesses (HAIs), including acute mountain sickness (AMS), high-altitude cerebral oedema (HACE) and high-altitude pulmonary oedema (HAPE). Chronic mountain sickness (CMS) can affect high-altitude resident populations worldwide. The prevalence of acute HAIs varies according to acclimatization status, rate of ascent and individual susceptibility. AMS, characterized by headache, nausea, dizziness and fatigue, is usually benign and self-limiting, and has been linked to hypoxia-induced cerebral blood volume increases, inflammation and related trigeminovascular system activation. Disruption of the blood–brain barrier leads to HACE, characterized by altered mental status and ataxia, and increased pulmonary capillary pressure, and related stress failure induces HAPE, characterized by dyspnoea, cough and exercise intolerance. Both conditions are progressive and life-threatening, requiring immediate medical intervention. Treatment includes supplemental oxygen and descent with appropriate pharmacological therapy. Preventive measures include slow ascent, pre-acclimatization and, in some instances, medications. CMS is characterized by excessive erythrocytosis and related clinical symptoms. In severe CMS, temporary or permanent relocation to low altitude is recommended. Future research should focus on more objective diagnostic tools to enable prompt treatment, improved identification of individual susceptibilities and effective acclimatization and prevention options.

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Fig. 1: Suggested pathophysiological pathways involved in the development of acute mountain sickness and high-altitude cerebral oedema.
Fig. 2: Suggested pathophysiological pathways of high-altitude pulmonary oedema.
Fig. 3: MRI scans in high altitude cerebral oedema.
Fig. 4: Chest radiograph in a patient with high-altitude pulmonary oedema.
Fig. 5: Signs of chronic mountain sickness.
Fig. 6: Prevention and management of acute HAIs.

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Acknowledgements

The authors thank the patients for their contributions in Supplementary Box 2.

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Introduction (H.G. and M.B.); Epidemiology (H.G., M.B., L.E.K. and F.C.V.); Mechanisms/pathophysiology (H.G., M.B., L.E.K. and F.C.V.); Diagnosis, screening and prevention (H.G., S.U., M.B., L.E.K. and F.C.V.); Management (S.U., M.B., L.E.K. and F.C.V.); Quality of life (H.G., F.C.V. and S.S.B.); Outlook (L.E.K. and F.C.V.); overview of the Primer (H.G.).

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Nature Reviews Disease Primers thanks T. Debevec, L. Huang, C. Sartori and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Gatterer, H., Villafuerte, F.C., Ulrich, S. et al. Altitude illnesses. Nat Rev Dis Primers 10, 43 (2024). https://doi.org/10.1038/s41572-024-00526-w

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