There have recently been suggestions that covid-19 lung disease is similar to high altitude pulmonary oedema (HAPE). There have been proposals to treat covid-19 with medications that are used for HAPE.  Although innovative treatment measures may be required for the treatment of covid-19 it is vital to examine the differences in pathophysiology before proposing similar treatments.
HAPE is a hypobaric hypoxic phenomenon, but covid-19 occurs in normobaric conditions. Both HAPE and covid-19 can cause non-cardiogenic pulmonary oedema with extreme hypoxaemia, fluffy patches on chest x-ray and a ground glass appearance on chest computed tomography (CT). [2,3] However the pathophysiologies are vastly different.
Pulmonary oedema in HAPE is caused by increased pulmonary artery pressures due to hypoxic pulmonary vasoconstriction.  In covid-19, the pulmonary oedema, is usually referred to as acute respiratory distress syndrome (ARDS). The aetiology is infectious. Proinflammatory markers are probably triggered by the virus.  Crucially, patients with HAPE, respond rapidly and dramatically to oxygen therapy and do not require mechanical ventilation unlike in patients with covid-19 who may require non-invasive, or even invasive ventilation, including extracorporeal support. 
In HAPE, hypoxaemia triggers global, but patchy, pulmonary vasoconstriction, leading to overperfusion in some vascular beds. Pulmonary oedema results from elevated hydrostatic pressure with disruption of the endothelium. HAPE does not occur in the absence of pulmonary hypertension. At one time, when bronchoscopy in HAPE patients was delayed until patients arrived at the hospital from high altitude, it was thought that inflammation played a major role in the aetiology of HAPE, as bronchoalveolar fluid was rich with inflammatory markers. [5,6] When bronchoscopy began to be performed in the field, inflammatory markers were absent.  Inflammation is clearly a secondary phenomenon in HAPE. In covid-19, pulmonary hypertension can occur late in the course and is not the cause of ARDS. 
Ground glass appearance on chest CT in both HAPE and covid-19 is not due to shared pathophysiology. Ground glass appearance on CT is a common finding in viral and bacterial pneumonia as well as in ARDS.
There are also anecdotal reports among patients with covid-19 of variability in hypoxic pulmonary vasoconstriction (HPV) and hypoxic ventilatory response (HVR). Variability in HPV and HVR is also found amongst HAPE patients. Both HPV and HVR are genetically determined. Variability due to genetic variation is a common finding in human populations that does not imply a common pathophysiology.
Increasing the inspired oxygen is the best treatment for HAPE. In many cases, increased oxygen is easily provided by descent to a lower altitude. Oxygen is a true antidote to HAPE that reverses pulmonary hypertension. In covid-19, oxygen is required to treat hypoxaemia, but is not a cure especially in the absence of other effective treatment modalities that are currently being investigated.
Nifedipine is a calcium- channel blocker that is commonly used adjunctively with oxygen in HAPE to decrease pulmonary artery pressure. Use of nifedipine is likely to be counterproductive in ARDS due to covid-19, because decreasing HPV may worsen ventilation-perfusion matching causing increased hypoxaemia. Phosphodiesterase inhibitors also limit HPV and may cause the same deleterious results. Acetazolamide, the most commonly used medication in the prevention and treatment of acute mountain sickness (AMS), has no role in covid-19 treatment. AMS is a neurological condition that is not associated with pulmonary pathology.
There is no logical reason to treat covid-19 using medications intended for AMS or HAPE, a disease with a completely different aetiology. The use of medications for high altitude illness to treat covid-19 is likely to be unhelpful and could have a potentially dangerous outcome. These are desperate times, but we should not try treatments for which there is no good rationale. Primum non nocere.
Buddha Basnyat, Past President of the International Society for Mountain Medicine, ISMM, Medical Director, Himalayan Rescue Association, Oxford University Clinical Research Unit-Patan Academy of Health Sience, Kathmandu, Nepal. Competing interests: None declared
Hermann Brugger, President of the International Society for Mountain Medicine, ISMM. Head of Institute of Mountain Emergency Medicine, Bolzano, Italy. Associate Professor, Innsbruck Medical University, Innsbruck, Austria. Competing interests: Funding for research and educational activities from non profit EURAC Research, Bolzano, Italy
David Hillebrandt, Vice-President of the International Society for Mountain Medicine, ISMM, General Medical Practitioner, Holsworthy, Devon, England. Member and ex president UIAA Medical Commission. Hon Medical Advisor to British Mountaineering Council. Competing interests: Provided medical advice to Jagged Globe commercial High altitude expedition company.
Annalisa Cogo, Associate Professor of Exercise Science Center for Sport and Exercise Science and Respiratory Unit, University of Ferrara, Italy. Italian Society Mountain Medicine
Matiram Pun, Department of Physiology and Pharmacology. Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. Competing interests: None declared
Ken Zafren, Staff Physician, Department of Emergency Medicine, Alaska Native Medical Center, Anchorage, AK, USA and Clinical Professor of Emergency Medicine, Department of Emergency Medicine, Stanford University Medical Center, Stanford, CA, USA and Honorary Member, International Commission for Alpine Rescue (ICAR), Zürich, Switzerland. Competing interests: KZ is the Associate Medical Director of the Himalayan Rescue Association, a nongovernmental organization in Nepal that provides services related to high altitude illness.
Commissioned and peer reviewed.
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