History

High-altitude pulmonary edema (HAPE) generally occurs 2-4 days after rapid ascent to altitudes in excess of 2500 m (8000 ft). Young people and previously acclimatized people reascending to a high altitude following a short stay at low altitude seem more predisposed to HAPE. Cold weather and physical exertion at high altitude are other predisposing factors.

The earliest indications are decreased exercise tolerance and slow recovery from exercise, and a dry cough.^[7]

The person usually notices fatigue, weakness, and dyspnea on exertion.

The condition typically worsens at night, and tachycardia and tachypnea occur at rest. Periodic breathing during sleep is almost universal in sojourners at high altitude. Patients may also complain of chest tightness or congestion.^[18]

Cough, frothy sputum (may be pink or contain frank blood^[1]), cyanosis, rales, and dyspnea progressing to severe respiratory distress are symptoms of the disease.^{[1, 4]}

A low-grade fever, respiratory alkalosis, and leukocytosis are other common features.

In severe cases, an altered mental status, hypotension, and death may result.

Physical Examination

In addition to the symptoms discussed, signs of high-altitude pulmonary edema (HAPE) may include the following signs:

Tachycardia
Prominent P₂ and right-ventricular heave on auscultation/palpation
Tachypnea
Crackles on auscultation (generally first appreciated in the right mid-lung field^[7])
Central cyanosis
Productive cough, with pink, frothy sputum or frank blood^[1]
Disproportionately low oxygen saturation relative to altitude (eg, 10-20 points lower than asymptomatic individuals at the same altitude^[7])

Differential Diagnoses

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[Guideline] Luks AM, Auerbach PS, Freer L, et al. Wilderness Medical Society clinical practice guidelines for the prevention and treatment of acute altitude illness: 2019 update. Wilderness Environ Med. 2019 Dec. 30 (4S):S3-S18. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Hackett PH, Shlim DR. CDC Yellow Book 2018. Chapter 3: Environmental hazards & other noninfectious health risks. High-altitude travel & altitude illness. Centers for Disease Control and Prevention. Available at https://wwwnc.cdc.gov/travel/yellowbook/2018/the-pre-travel-consultation/altitude-illness. Reviewed: October 18, 2019; Accessed: April 6, 2020.
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Guo L, Tan G, Liu P, et al. Three plasma metabolite signatures for diagnosing high altitude pulmonary edema. Sci Rep. 2015 Oct 13. 5:15126. [QxMD MEDLINE Link].
Wu AL, Xiong YS, Li ZQ, Liu YG, Quan Q, Wu LJ. Correlation between single nucleotide polymorphisms in hypoxia-related genes and susceptibility to acute high-altitude pulmonary edema. Genet Mol Res. 2015 Sep 28. 14 (3):11562-72. [QxMD MEDLINE Link].
Eldridge MW, Braun RK, Yoneda KY, Walby WF. Effects of altitude and exercise on pulmonary capillary integrity: evidence for subclinical high-altitude pulmonary edema. J Appl Physiol. 2006 Mar. 100(3):972-80. [QxMD MEDLINE Link].
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Luks AM, Swenson ER, Bartsch P. Acute high-altitude sickness. Eur Respir Rev. 2017 Jan. 26 (143):[QxMD MEDLINE Link]. [Full Text].
American Academy of Orthopaedic Surgeons, Paramedic Association of Canada. Environmental emergencies. In: MacDonald RD, ed. Nancy Caroline's Emergency Care in the Streets Advantage Package (Canadian Edition). 8th ed. Burlington, MA: Jones & Bartlett Learning; 2021. ch 38.
Pandey P, Lohani B, Murphy H. Pulmonary embolism masquerading as high altitude pulmonary edema at high altitude. High Alt Med Biol. 2016 Dec. 17 (4):353-8. [QxMD MEDLINE Link]. [Full Text].
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Hartmann G, Tschop M, Fischer R, et al. High altitude increases circulating interleukin-6, interleukin-1 receptor antagonist and C-reactive protein. Cytokine. 2000 Mar. 12(3):246-52. [QxMD MEDLINE Link].
Grunig E, Mereles D, Hildebrandt W, et al. Stress Doppler echocardiography for identification of susceptibility to high altitude pulmonary edema. J Am Coll Cardiol. 2000 Mar 15. 35(4):980-7. [QxMD MEDLINE Link].
Fagenholz PJ, Gutman JA, Murray AF, Noble VE, Thomas SH, Harris NS. Chest ultrasonography for the diagnosis and monitoring of high-altitude pulmonary edema. Chest. 2007 Apr. 131(4):1013-8. [QxMD MEDLINE Link].
Fagenholz PJ, Gutman JA, Murray AF, Harris NS. Treatment of high altitude pulmonary edema at 4240 m in Nepal. High Alt Med Biol. 2007 Summer. 8(2):139-46. [QxMD MEDLINE Link].
Maggiorini M, Brunner-La Rocca HP, Peth S, et al. Both tadalafil and dexamethasone may reduce the incidence of high-altitude pulmonary edema: a randomized trial. Ann Intern Med. 2006 Oct 3. 145(7):497-506. [QxMD MEDLINE Link].
Mounier R, Amonchot A, Caillot N, et al. Pulmonary arterial systolic pressure and susceptibility to high altitude pulmonary edema. Respir Physiol Neurobiol. 2011 Dec 15. 179 (2-3):294-9. [QxMD MEDLINE Link].
van Patot MC, Leadbetter G 3rd, Keyes LE, Maakestad KM, Olson S, Hackett PH. Prophylactic low-dose acetazolamide reduces the incidence and severity of acute mountain sickness. High Alt Med Biol. 2008 Winter. 9 (4):289-93. [QxMD MEDLINE Link].
Bartsch P, Maggiorini M, Ritter M, Noti C, Vock P, Oelz O. Prevention of high-altitude pulmonary edema by nifedipine. N Engl J Med. 1991 Oct 31. 325 (18):1284-9. [QxMD MEDLINE Link].
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[Guideline] Sorbello M, El-Boghdadly K, Di Giacinto I, et al, for the Societa Italiana di Anestesia Analgesia Rianimazione e Terapia Intensiva (SIAARTI) Airway Research Group, The European Airway Management Society. The Italian coronavirus disease 2019 outbreak: recommendations from clinical practice. Anaesthesia. 2020 Mar 27. [QxMD MEDLINE Link]. [Full Text].
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Media Gallery

High-altitude pulmonary edema (HAPE). Plain chest x-ray (radiograph) of a patient diagnosed with HAPE. There are patchy infiltrates throughout the lung tissue, with predominant changes in the right middle lobe/right central hemithorax. Courtesy of Wikipedia (https://en.wikipedia.org/wiki/File:Chest_XR_of_HAPE.png).
High-altitude pulmonary edema (HAPE). Medical students demonstrate the use of a portable hyperbaric chamber. Courtesy of Wikipedia (https://en.wikipedia.org/wiki/File:Portable_hyperbaric_chamber.jpg).
High-altitude pulmonary edema (HAPE). Initial chest x-ray showing pulmonary infiltrates in the right lung especially in the right mid and lower lung zones indicative of pulmonary edema. The patient was a middle-aged woman trekker who was emergency air-lifted from an altitude of 4410 m in the Nepal Himalayas to 1300 m in Kathamandu. She had continued ascending despite experiencing mild altitude symptoms at Namche (3440 m), with considerably worsened symptoms at Tengboche (3860 m). Courtesy of Extreme Physiology & Medicine (PMID: 24636661, online at https://extremephysiolmed.biomedcentral.com/track/pdf/10.1186/2046-7648-3-6).
High-altitude pulmonary edema (HAPE). Repeat chest x-ray after 2 days showing rapid resolution of the pulmonary edema in the same Himalayan trekker discussed in the previous image. The patient received bed rest, supplemental oxygen, and oral sustained-release nifedipine 20 mg twice daily. Courtesy of Extreme Physiology & Medicine (PMID: 24636661, online at https://extremephysiolmed.biomedcentral.com/track/pdf/10.1186/2046-7648-3-6).
High-altitude pulmonary edema (HAPE). Pulmonary embolism masquerading as HAPE. Axial computed tomography (CT) pulmonary angiogram showing thrombi as filling defects in the right main pulmonary artery (right arrow) extending into its branch and in the distal left pulmonary artery (left arrow) with extension into its superior branch. Courtesy of High Altitude Medicine & Biology (PMID: 27768392, online at https://www.liebertpub.com/doi/full/10.1089/ham.2016.0008).

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Author

Rohit Goyal, MD Fellow, Division of Pulmonary Medicine, Lenox Hill Hospital, New York University School of Medicine

Rohit Goyal, MD is a member of the following medical societies: American College of Chest Physicians, American Medical Association, American Thoracic Society

Disclosure: Nothing to disclose.

Coauthor(s)

Mir Omar Ali, MD Fellow, Department of Pulmonary Medicine, Lenox Hill Hospital, New York University

Mir Omar Ali, MD is a member of the following medical societies: American College of Physicians, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Samia Qazi, MD Chief, Division of Primary Care, Nassau University Medical Center; Clinical Assistant Professor of Clinical Medicine, Renaissance School of Medicine at Stony Brook University

Samia Qazi, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine

Disclosure: Nothing to disclose.

Laurie A Ward, MD, FACP Director of Population Health, Wyckoff Heights Medical Center

Laurie A Ward, MD, FACP is a member of the following medical societies: American College of Physicians, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation

Disclosure: Nothing to disclose.

Qazi Qaisar Afzal, MD Clinical Instructor, Department of Medicine, State University of New York at Stony Brook

Qazi Qaisar Afzal, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, Medical Society of the State of New York

Disclosure: Nothing to disclose.

Mir Mustafa Ali Deccan College of Medical Sciences, Owaisi Hospital and Research Center, Princess Esra Hospital

Disclosure: Nothing to disclose.

Klaus-Dieter Lessnau, MD, FCCP Former Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory, Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital

Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Thoracic Society, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.

Additional Contributors

Gregory Tino, MD Director of Pulmonary Outpatient Practices, Associate Professor, Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania Medical Center and Hospital

Gregory Tino, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

High-Altitude Pulmonary Edema (HAPE) Clinical Presentation

History

Physical Examination

References

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