{"id":47333,"date":"2020-04-28T15:38:41","date_gmt":"2020-04-28T14:38:41","guid":{"rendered":"https:\/\/blogs.bmj.com\/bmj\/?p=47333"},"modified":"2020-05-07T11:47:35","modified_gmt":"2020-05-07T10:47:35","slug":"there-is-no-relationship-between-covid-19-and-altitude-illness","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/bmj\/2020\/04\/28\/there-is-no-relationship-between-covid-19-and-altitude-illness\/","title":{"rendered":"There is no relationship between covid-19 and altitude illness"},"content":{"rendered":"<p><span style=\"font-weight: 400\">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. [<\/span><span style=\"font-weight: 400\">1]<\/span><span style=\"font-weight: 400\"> 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.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">HAPE is a hypobaric hypoxic phenomenon, but covid-19 occurs in normobaric condition<\/span><span style=\"font-weight: 400\">s.<\/span><span style=\"font-weight: 400\"> Both HAPE<\/span><span style=\"font-weight: 400\"> and covid-19<\/span><span style=\"font-weight: 400\"> 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.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">Pulmonary oedema in HAPE is caused by increased pulmonary artery pressures due to hypoxic pulmonary vasoconstriction. [<\/span><span style=\"font-weight: 400\">2]<\/span><span style=\"font-weight: 400\"> 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. [<\/span><span style=\"font-weight: 400\">3]<\/span><span style=\"font-weight: 400\"> 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. [<\/span><span style=\"font-weight: 400\">4]<\/span><\/p>\n<p><span style=\"font-weight: 400\">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. [<\/span><span style=\"font-weight: 400\">5,6]<\/span><span style=\"font-weight: 400\"> When bronchoscopy began to be performed in the field, inflammatory markers were absent. [<\/span><span style=\"font-weight: 400\">7]<\/span><span style=\"font-weight: 400\"> Inflammation is clearly a secondary phenomenon in HAPE. In covid-19, pulmonary hypertension can occur late<\/span><span style=\"font-weight: 400\"> in the course and is not the cause of ARDS. [4]<\/span><\/p>\n<p><span style=\"font-weight: 400\">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.<\/span><\/p>\n<p><span style=\"font-weight: 400\">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.<\/span><\/p>\n<p><span style=\"font-weight: 400\">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.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">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.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">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. <\/span><i><span style=\"font-weight: 400\">Primum non nocere<\/span><\/i><span style=\"font-weight: 400\">.<\/span><\/p>\n<p><em><span style=\"font-weight: 400\"><strong>Buddha Basnyat<\/strong>, <\/span><span style=\"font-weight: 400\">Past President of the International Society for Mountain Medicine, ISMM, <\/span><span style=\"font-weight: 400\">Medical Director, Himalayan Rescue Association, Oxford University Clinical Research Unit-Patan Academy of Health Sience, Kathmandu, Nepal. <strong>Competing interests<\/strong>: None declared<\/span><\/em><\/p>\n<p><em><span style=\"font-weight: 400\"><strong>Hermann Brugger<\/strong>, <\/span><span style=\"font-weight: 400\">President of the International Society for Mountain Medicine, ISMM. <\/span><span style=\"font-weight: 400\">Head of Institute of Mountain Emergency Medicine, Bolzano, Italy. <\/span><span style=\"font-weight: 400\">Associate Professor, Innsbruck Medical University, Innsbruck, Austria. <strong>Competing interests<\/strong>: Funding for research and educational activities from non profit EURAC Research, Bolzano, Italy<\/span><\/em><\/p>\n<p><em><span style=\"font-weight: 400\"><strong>David Hillebrandt<\/strong>, <\/span><span style=\"font-weight: 400\">Vice-President of the International Society for Mountain Medicine, ISMM, <\/span><span style=\"font-weight: 400\">General Medical Practitioner, <\/span><span style=\"font-weight: 400\">Holsworthy, Devon, England. <\/span><span style=\"font-weight: 400\">Member and ex president UIAA Medical Commission. <\/span><span style=\"font-weight: 400\">Hon Medical Advisor to British Mountaineering Council. <strong>Competing interests<\/strong>: Provided medical advice to Jagged Globe commercial High altitude expedition company.<\/span><\/em><\/p>\n<p><em><span style=\"font-weight: 400\"><strong>Annalisa Cogo<\/strong>, <\/span><span style=\"font-weight: 400\">Associate Professor of Exercise Science Center for Sport and Exercise Science and Respiratory Unit, University of Ferrara, Italy. <\/span><span style=\"font-weight: 400\">Italian Society Mountain Medicine<\/span><\/em><\/p>\n<p><em><span style=\"font-weight: 400\"><strong>Matiram Pun<\/strong>, <\/span><span style=\"font-weight: 400\">Department of Physiology and Pharmacology. <\/span><span style=\"font-weight: 400\">Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. <strong>Competing interests<\/strong>: None declared<\/span><\/em><\/p>\n<p><em><span style=\"font-weight: 400\"><strong>Ken Zafren<\/strong>, <\/span><span style=\"font-weight: 400\">Staff Physician, <\/span><span style=\"font-weight: 400\">Department of Emergency Medicine, <\/span><span style=\"font-weight: 400\">Alaska Native Medical Center, <\/span><span style=\"font-weight: 400\">Anchorage, AK, USA <\/span><span style=\"font-weight: 400\">and <\/span><span style=\"font-weight: 400\">Clinical Professor of Emergency Medicine, <\/span><span style=\"font-weight: 400\">Department of Emergency Medicine, <\/span><span style=\"font-weight: 400\">Stanford University Medical Center, <\/span><span style=\"font-weight: 400\">Stanford, CA, USA <\/span><span style=\"font-weight: 400\">and\u00a0<\/span><span style=\"font-weight: 400\">Honorary Member, <\/span><span style=\"font-weight: 400\">International Commission for Alpine Rescue (ICAR), <\/span><span style=\"font-weight: 400\">Z<\/span><span style=\"font-weight: 400\">\u00fcrich, Switzerland. <strong>Competing interests<\/strong>: KZ is the Associate Medical Director of the Himalayan Rescue Association, a nongovernmental organization in Nepal that provides services related to high altitude illness.<\/span><\/em><\/p>\n<p><i>Commissioned<\/i><em> and peer reviewed.<\/em><\/p>\n<p><b>References:<\/b><\/p>\n<ol>\n<li><span style=\"font-weight: 400\">Solaimanzadeh I. Acetazolamide, Nifedipine and Phosphodiesterase Inhibitors: Rationale for Their Utilization as Adjunctive Countermeasures in the Treatment of Coronavirus Disease 2019 (COVID-19). <\/span><i><span style=\"font-weight: 400\">Cureus<\/span><\/i><span style=\"font-weight: 400\"> 2020; <\/span><b>12<\/b><span style=\"font-weight: 400\">(3): e7343.<\/span><\/li>\n<li><span style=\"font-weight: 400\">Basnyat B, Murdoch DR. High-altitude illness. <\/span><i><span style=\"font-weight: 400\">Lancet (London, England)<\/span><\/i><span style=\"font-weight: 400\"> 2003; <\/span><b>361<\/b><span style=\"font-weight: 400\">(9373): 1967-74.<\/span><\/li>\n<li><span style=\"font-weight: 400\">Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. <\/span><i><span style=\"font-weight: 400\">The Lancet Respiratory medicine<\/span><\/i><span style=\"font-weight: 400\"> 2020; <\/span><b>8<\/b><span style=\"font-weight: 400\">(4): 420-2.<\/span><\/li>\n<li><span style=\"font-weight: 400\">Gattinoni L CD, Caironi P, Busana M, Romitti F, Brazzi L, and Camporota L. COVID-19 pneumonia: different respiratory treatment for different phenotypes? . <\/span><i><span style=\"font-weight: 400\">Intensive Care Medicine 2020<\/span><\/i><span style=\"font-weight: 400\">.<\/span><\/li>\n<li><span style=\"font-weight: 400\">Schoene RB, Hackett PH, Henderson WR, et al. High-altitude pulmonary edema. Characteristics of lung lavage fluid. <\/span><i><span style=\"font-weight: 400\">Jama<\/span><\/i><span style=\"font-weight: 400\"> 1986; <\/span><b>256<\/b><span style=\"font-weight: 400\">(1): 63-9.<\/span><\/li>\n<li><span style=\"font-weight: 400\">Kubo K, Hanaoka M, Yamaguchi S, et al. Cytokines in bronchoalveolar lavage fluid in patients with high altitude pulmonary oedema at moderate altitude in Japan. <\/span><i><span style=\"font-weight: 400\">Thorax<\/span><\/i><span style=\"font-weight: 400\"> 1996; <\/span><b>51<\/b><span style=\"font-weight: 400\">(7): 739-42.<\/span><\/li>\n<li><span style=\"font-weight: 400\">Swenson ER, Maggiorini M, Mongovin S, et al. Pathogenesis of high-altitude pulmonary edema: inflammation is not an etiologic factor. <\/span><i><span style=\"font-weight: 400\">Jama<\/span><\/i><span style=\"font-weight: 400\"> 2002; <\/span><b>287<\/b><span style=\"font-weight: 400\">(17): 2228-35.<\/span><\/li>\n<\/ol>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>There have recently been suggestions that covid-19 lung disease is similar to high altitude pulmonary oedema (HAPE). 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