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Cochrane Database Syst Rev 2018 06 30;6:CD009567. Epub 2018 Jun 30.

Cochrane Ecuador. Centro de Investigación en Salud Pública y Epidemiología Clínica (CISPEC). Facultad de Ciencias de la Salud Eugenio Espejo, Universidad Tecnológica Equinoccial, Quito, Ecuador.

Background: Acute high altitude illness is defined as a group of cerebral and pulmonary syndromes that can occur during travel to high altitudes. It is more common above 2500 metres, but can be seen at lower elevations, especially in susceptible people. Acute high altitude illness includes a wide spectrum of syndromes defined under the terms 'acute mountain sickness' (AMS), 'high altitude cerebral oedema' and 'high altitude pulmonary oedema'. Read More

Cochrane Database Syst Rev 2018 03 12;3:CD012983. Epub 2018 Mar 12.

Methodology Research Unit, National Institute of Pediatrics, Insurgentes Sur 3700 - C, Col. Insurgentes Cuicuilco, Coyoacan, Mexico City, Distrito Federal, Mexico, 04530.

Background: High altitude illness (HAI) is a term used to describe a group of mainly cerebral and pulmonary syndromes that can occur during travel to elevations above 2500 metres (˜ 8200 feet). Acute mountain sickness (AMS), high altitude cerebral oedema (HACE) and high altitude pulmonary oedema (HAPE) are reported as potential medical problems associated with high altitude ascent. In this second review, in a series of three about preventive strategies for HAI, we assessed the effectiveness of five of the less commonly used classes of pharmacological interventions. Read More

Cochrane Database Syst Rev 2017 06 27;6:CD009761. Epub 2017 Jun 27.

Department of Critical Care Medicine, Hospital de San José, Fundación Universitaria de Ciencias de la Salud, Bogotá, Colombia.

Background: High altitude illness (HAI) is a term used to describe a group of cerebral and pulmonary syndromes that can occur during travel to elevations above 2500 metres (8202 feet). Acute hypoxia, acute mountain sickness (AMS), high altitude cerebral oedema (HACE) and high altitude pulmonary oedema (HAPE) are reported as potential medical problems associated with high altitude. In this review, the first in a series of three about preventive strategies for HAI, we assess the effectiveness of six of the most recommended classes of pharmacological interventions. Read More

High Alt Med Biol 2017 Mar;18(1):11-19

1 Division of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, School of Medicine, Johns Hopkins University , Baltimore, Maryland.

Pham, Luu V., Christopher Meinzen, Rafael S. Arias, Noah G. Read More

Eur Respir Rev 2017 Jan 31;26(143). Epub 2017 Jan 31.

Dept of Internal Medicine, University Clinic Heidelberg, Heidelberg, Germany.

At any point 1-5 days following ascent to altitudes ≥2500 m, individuals are at risk of developing one of three forms of acute altitude illness: acute mountain sickness, a syndrome of nonspecific symptoms including headache, lassitude, dizziness and nausea; high-altitude cerebral oedema, a potentially fatal illness characterised by ataxia, decreased consciousness and characteristic changes on magnetic resonance imaging; and high-altitude pulmonary oedema, a noncardiogenic form of pulmonary oedema resulting from excessive hypoxic pulmonary vasoconstriction which can be fatal if not recognised and treated promptly. This review provides detailed information about each of these important clinical entities. After reviewing the clinical features, epidemiology and current understanding of the pathophysiology of each disorder, we describe the current pharmacological and nonpharmacological approaches to the prevention and treatment of these diseases. Read More

Anesth Analg 2017 01;124(1):146-153

From the *Department of Anesthesia and Perioperative Care, University of California at San Francisco School of Medicine, San Francisco, California, †Clinimark Labs, Louisville, Colorado, and ‡Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina.

Extended periods of oxygen deprivation can produce acidosis, inflammation, energy failure, cell stress, or cell death. However, brief profound hypoxia (here defined as SaO2 50%-70% for approximately 10 minutes) is not associated with cardiovascular compromise and is tolerated by healthy humans without apparent ill effects. In contrast, chronic hypoxia induces a suite of adaptations and stresses that can result in either increased tolerance of hypoxia or disease, as in adaptation to altitude or in the syndrome of chronic mountain sickness. Read More

Sports Health 2016 Mar-Apr;8(2):126-32

Context: Athletes at different skill levels perform strenuous physical activity at high altitude for a variety of reasons. Multiple team and endurance events are held at high altitude and may place athletes at increased risk for developing acute high altitude illness (AHAI). Training at high altitude has been a routine part of preparation for some of the high level athletes for a long time. Read More

Chest 2016 Apr 12;149(4):991-8. Epub 2016 Jan 12.

Department of Cardiology and Clinical Research, Inselspital, University of Bern, Bern, Switzerland; Facultad de Ciencias, Departamento de Biología, Universidad de Tarapacá, Arica, Chile. Electronic address:

Background: Chronic mountain sickness (CMS) is often associated with vascular dysfunction, but the underlying mechanism is unknown. Sleep-disordered breathing (SDB) frequently occurs at high altitude. At low altitude, SDB causes vascular dysfunction. Read More

Eur J Intern Med 2015 Dec 17;26(10):743-51. Epub 2015 Oct 17.

Department of Internal Medicine, Albert Einstein College of Medicine, Jacobi Medical Center, New York, NY, United States.

The foramen ovale is a remnant of the fetal circulation that remains patent in 20-25% of the adult population. Although long overlooked as a potential pathway that could produce pathologic conditions, the presence of a patent foramen ovale (PFO) has been associated with a higher than expected frequency in a variety of clinical syndromes including cryptogenic stroke, migraines, sleep apnea, platypnea-orthodeoxia, deep sea diving associated decompression illness, and high altitude pulmonary edema. A unifying hypothesis is that a chemical or particulate matter from the venous circulation crosses the PFO conduit between the right and left atria to produce a variety of clinical syndromes. Read More

Eur J Clin Invest 2015 Aug;45(8):875-82

Department of Cardiology, University Hospital, Bern, Switzerland.

Patent foramen ovale (PFO) is an embryologic remnant with incomplete postnatal adhesion of the cardiac atrial septum primum and secundum. After birth, the prevalence of PFO decreases from about 35% at young to approximately 20% at old age. PFO has been associated with numerous conditions such as decompression illness in divers, migraine, high-altitude pulmonary oedema, cerebrovascular and coronary ischaemia, and obstructive sleep apnoea syndrome. Read More

Lakartidningen 2015 May 26;112. Epub 2015 May 26.

Adventure Medicine - Stockholm, Sweden - Stockholm, Sweden.

With the increasing amount of people traveling to high altitude regions, the number of people at risk of acquiring altitude illness increases. Altitude illness entails three syndromes; acute mountain sickness, high-altitude cerebral edema, and high-altitude pulmonary edema. These syndromes are potentially lethal acquired medical conditions that in most cases are preventable. Read More

High Alt Med Biol 2015 Jun 6;16(2):80-8. Epub 2015 Apr 6.

1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington , Seattle, Washington.

Luks, Andrew M., and Erik R. Swenson. Read More

High Alt Med Biol 2014 Apr;15(1):46-51

1 Department of Respiratory Medicine, Xinqiao Hospital, Third Military Medical University , Chongqing, China .

Objective: High altitude illness can be life-threatening if left untreated. Acute mountain sickness and high altitude pulmonary hypertension are two syndromes of high altitude illness. Recent clinical studies showed the beneficial effects of phosphodiesterase type 5 (PDE-5) inhibitors on the treatment of pulmonary hypertension. Read More

PLoS One 2014 22;9(1):e81229. Epub 2014 Jan 22.

Apex (Altitude Physiology Expeditions), c/o Dr. J. K. Baillie, Critical Care Medicine, University of Edinburgh, Royal Infirmary of Edinburgh, United Kingdom ; Division of Genetics and Genomics, Roslin Institute, Edinburgh, United Kingdom.

Acute mountain sickness (AMS) is a common problem among visitors at high altitude, and may progress to life-threatening pulmonary and cerebral oedema in a minority of cases. International consensus defines AMS as a constellation of subjective, non-specific symptoms. Specifically, headache, sleep disturbance, fatigue and dizziness are given equal diagnostic weighting. Read More

Subcell Biochem 2014 ;75:361-86

VA Puget Sound Health Care System and Department of Medicine, University of Washington, Seattle, WA, USA,

Carbonic anhydrase (CA) inhibitors, particularly acetazolamide, have been used at high altitude for decades to prevent or reduce acute mountain sickness (AMS), a syndrome of symptomatic intolerance to altitude characterized by headache, nausea, fatigue, anorexia and poor sleep. Principally CA inhibitors act to further augment ventilation over and above that stimulated by the hypoxia of high altitude by virtue of renal and endothelial cell CA inhibition which oppose the hypocapnic alkalosis resulting from the hypoxic ventilatory response (HVR), which acts to limit the full expression of the HVR. The result is even greater arterial oxygenation than that driven by hypoxia alone and greater altitude tolerance. Read More

J Pediatr (Rio J) 2013 Nov-Dec;89(6):531-43. Epub 2013 Sep 12.

Pediatrics Department, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brazil.

Objective: to assess the epidemiological and genetic factors associated with severity of acute viral bronchiolitis (AVB) by respiratory syncytial virus (RSV).

Data Source: the key words "bronchiolitis", "risk factor", "genetics" and "respiratory syncytial virus", and all combinations among them were used to perform a search in the PubMed, SciELO, and Lilacs databases, of articles published after the year 2000 that included individuals younger than 2 years of age.

Data Synthesis: a total of 1,259 articles were found, and their respective summaries were read. Read More

Curr Pharm Des 2010 ;16(31):3497-502

Cardiology Unit, Department of Medical Pathophysiology, University La Sapienza, Rome, Italy.

The foramen ovale, an atrial septal defect which is essential in the fetal circulation, remains patent through adulthood in approximately 25% of the general population and so it represents the most common persistent abnormality of fetal origin. Patent foramen ovale (PFO) allows interatrial right-to-left blood shunting during those periods of the cardiac cycle in which the right atrial pressure exceeds the left one. An increasing number of pathological manifestations of PFO has been recently identified; among these, paradoxical systemic embolism, refractory hypoxemia in patients with right ventricular myocardium infarction or severe pulmonary disease, orthostatic oxygen desaturation in the rare platypnea-orthodeoxia syndrome, neurological decompression illness in divers, high altitude pilots and astronauts, and finally, migraine headache with aura. Read More

Prog Cardiovasc Dis 2010 May-Jun;52(6):467-84

Warwick Medical School, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK.

Barometric pressure falls with increasing altitude and consequently there is a reduction in the partial pressure of oxygen resulting in a hypoxic challenge to any individual ascending to altitude. A spectrum of high altitude illnesses can occur when the hypoxic stress outstrips the subject's ability to acclimatize. Acute altitude-related problems consist of the common syndrome of acute mountain sickness, which is relatively benign and usually self-limiting, and the rarer, more serious syndromes of high-altitude cerebral edema and high-altitude pulmonary edema. Read More

Curr Sports Med Rep 2010 Mar-Apr;9(2):79-85

Tri-Service Military Primary Care Sports Medicine Program, Uniformed Services University, Bethesda, MD 20814, USA.

Expanding athlete participation in high-altitude environments highlights the importance for a sports physician to have a good understanding of the high-altitude illness (HAI) syndromes: acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE). All may occur in the setting of acute altitude exposure higher than 2500 m; incidence and severity increases as altitudes or ascent rates increase. Once HAI is recognized, proven therapies should be instituted to alleviate symptoms and avert the possibility of critical illness. Read More

Evid Based Complement Alternat Med 2011 15;2011:574524. Epub 2010 Sep 15.

Defence Institute of Physiology and Allied Sciences, DRDO, Ministry of Defence, Timarpur, Delhi 110054, India.

Cerebral and pulmonary syndromes may develop in unacclimatized individuals shortly after ascent to high altitude resulting in high altitude illness, which may occur due to extravasation of fluid from intra to extravascular space in the brain, lungs and peripheral tissues. The objective of the present study was to evaluate the potential of seabuckthorn (SBT) (Hippophae rhamnoides L.) leaf extract (LE) in curtailing hypoxia-induced transvascular permeability in the lungs by measuring lung water content, leakage of fluorescein dye into the lungs and further confirmation by quantitation of albumin and protein in the bronchoalveolar lavage fluid (BALF). Read More

Pediatr Ann 2009 Apr;38(4):218-23

The Children's Hospital, Denver, Colorado, USA.

Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2009 Feb;21(2):95-8

Department of High Altitude Disease, High Altitude Medicine College, Third Military Medical University, Chongqing 400038, China.

Objective: To investigate the relationship between gastrointestinal dysfunction (GD) and multiple organ dysfunction syndrome (MODS) in acute severe mountain sickness (ASMS), including high altitude pulmonary edema (HAPE), and high altitude cerebral edema (HACE), by a retrospective study of medical records and prospective study of hospitalized patients.

Methods: In retrospective study, the clinical data of 3 184 inpatients of General Hospital of Tibetan Military Command suffering from ASMS in the past 50 years (from June, 1958 to June, 2007) were collected. Statistical analysis was performed to study the relationship between GD and MODS in these patients. Read More

G Ital Cardiol (Rome) 2008 Sep;9(9):593-602

U.O.C. di Cardiologia, Ospedale S. Eugenio, ASL Rm C, Roma.

Patent foramen ovale (PFO) is a remnant of the normal fetal circulation consisting in a communication between septum primum and septum secundum. Postnatally, the two septa fuse completing separation of the atria. In 25% of normal individuals incomplete fusion leads to the persistence of the flap valve leaving a PFO. Read More

Minerva Cardioangiol 2007 Oct;55(5):681-91

Swiss Cardiovascular Center, Bern University Hospital, Bern, Switzerland.

A patent foramen ovale (PFO) is a common finding present in 25% of the population. A relationship between PFO and several clinical conditions such as stroke, migraine, platypnea-orthodeoxia syndrome, neurological decompression illness in divers, high altitude pulmonary edema, sleep apnea, and economy class syndrome have been documented. Observational non-randomized studies have shown percutaneous PFO closure more effective than medical treatment for stroke prevention, in particular in patients with complete closure as well as in patients with more than one cerebrovascular event at baseline. Read More

High Alt Med Biol 2007 ;8(2):117-23

Neonatology University of Colorado School of Medicine, Denver, Colorado, USA.

Fetal life conditions the responses of a newborn infant to high altitude. The fetal circulation is characterized by high pulmonary vascular resistance and low pulmonary blood flow, as well as intra and extracardiac shunts that serve to route blood to and from the placenta and around the fetal lungs. At birth, rapid changes occur in the pulmonary circulation under normoxia; pulmonary vascular resistance falls, pulmonary blood flow increases dramatically, and the fetal shunts close functionally, then anatomically. Read More

Respir Physiol Neurobiol 2006 Apr 28;151(2-3):96-108. Epub 2005 Dec 28.

Colorado Center for Altitude Medicine and Physiology (CCAMP), Campus Box B123, University of Colorado at Denver and Health Sciences Center, 4200 E. 9th Ave., Denver, CO 80262, USA.

John T. (Jack) Reeves' science is reviewed across the 37 years of his research career at the University of Colorado Health Sciences Center, a period which occupied approximately half his remarkable life. His contributions centered on understanding the inter-relatedness as well as the underlying mechanisms controlling the various components of the O(2) transport system. Read More

Eur J Appl Physiol 2005 Aug 7;94(5-6):569-75. Epub 2005 Jun 7.

Department of Physiology, Australian Institute of Sport, Canberra, PO Box 176, Belconnen ACT, 2616, Australia.

At high altitudes, the clinically defined respiratory disturbance index (RDI) and high hypoxic ventilatory response (HVR) have been associated with diminished sleep quality. Increased RDI has also been observed in some athletes sleeping at simulated moderate altitude. In this study, we investigated relationships between the HVR of 14 trained male endurance cyclists with variable RDI and sleep quality responses to simulated moderate altitude. Read More

Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2005 Apr;17(4):217-22

Lanzhou General Hospital of Lanzhou Command, Lanzhou 730050, Gansu, China.

Objective: To compare the diagnostic parameters of acute respiratory distress syndrome/multiple organ dysfunction syndrome (ARDS/MODS) at high altitude (H-ARDS/MODS) with that on plain, and to establish a more practical diagnostic criterion of H-ARDS/MODS.

Methods: Five hundred and five cases fulfilled the criteria for the diagnosis of ARDS/MODS were divided into three groups according to the altitude of their habitation: control group including inhabitants (<430 m) on plain (CG, n=113), moderate high altitude group 1 inhabitants at the altitude of 1,517 m (H1G, n=314), moderate high altitude group 2 inhabitants at the altitude of 2,261 m to 2,400 m (H2G, n=78). The ARDS/MODS scores of the three groups were made according to the diagnostic criteria of Lushan conference, Marshall(1995) and Lanzhou criteria drafted by the authors respectively to set up three data analyzing models, followed by plotting of receiver operating characteristic curves (ROC curve) and calculation of the Yordon Index and the optimum cutoff points of the parameters,in order to study the accuracy of the three diagnostic criteria in predicting the outcome of the patients suffering from ARDS/MODS. Read More

Emerg Med Clin North Am 2004 May;22(2):329-55, viii

Department of Emergency Medicine, Aspen Valley Hospital, CO 81611, USA.

Travel to a high altitude requires that the human body acclimatize to hypobaric hypoxia. Failure to acclimatize results in three common but preventable maladies known collectively as high-altitude illness: acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE). Capillary leakage in the brain (AMS/HACE) or lungs (HAPE) accounts for these syndromes. Read More

Curr Infect Dis Rep 2004 Feb;6(1):43-49

Department of Pathology, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch, New Zealand.

High-altitude illness is the collective term for acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE). These syndromes can affect unacclimatized travelers shortly after ascent to high altitude (especially higher than 2500 m). AMS is relatively common and usually is mild and self-limiting; HACE and HAPE are uncommon but life-threatening. Read More

Lancet 2003 Jun;361(9373):1967-74

Nepal International Clinic, Kathmandu, Nepal; Himalayan Rescue Association, Kathmandu, Nepal.

High-altitude illness is the collective term for acute mountain sickness (AMS), high-altitude cerebral oedema (HACE), and high-altitude pulmonary oedema (HAPE). The pathophysiology of these syndromes is not completely understood, although studies have substantially contributed to the current understanding of several areas. These areas include the role and potential mechanisms of brain swelling in AMS and HACE, mechanisms accounting for exaggerated pulmonary hypertension in HAPE, and the role of inflammation and alveolar-fluid clearance in HAPE. Read More

Ital Heart J Suppl 2001 Aug;2(8):845-9

Divisione di Cardiologia Fondazione Salvatore Maugeri, IRCCS Via per Revislate, 13 28010 Veruno, NO.

Ascent to high altitudes arouses the sympathetic nervous system in non-acclimatized healthy humans. Such activation is provoked by hypobaric hypoxia combined with other stressors. While this is an adaptive response, it also contributes to the general physical deterioration consequent to prolonged exposure to high altitudes, and is even implied in specific syndromes: acute mountain sickness, high altitude pulmonary edema (HAPE), and high altitude cerebral edema. Read More

Wilderness Environ Med 2001 ;12(3):190-4

Qinghai High Altitude Medical Science Institute, China.

High-altitude heart disease, a form of chronic mountain sickness, has been well established in both Tibet and Qinghai provinces of China, although little is known regarding this syndrome in other countries, particularly in the West. This review presents a general overview of high-altitude heart disease in China and briefly summarizes the existing data with regard to the prevalence, clinical features, and pathophysiology of the illness. The definition of high-altitude heart disease is right ventricular enlargement that develops primarily (by high-altitude exposure) to pulmonary hypertension without excessive polycythemia. Read More

Dtsch Med Wochenschr 1999 Jun;124(23):721-6

Abteilung für Innere Medizin, Krankenhauses Mittersill.

History And Admission Findings: A 51-year-old man without significant previous illness presented with treatment-resistant arterial hypertension, dyspnoea, increased fatigue and headaches. Except for a florid face and fine tremor the physical examination was unremarkable.

Investigations: The chest x-ray showed pulmonary congestion. Read More

Aviat Space Environ Med 1998 Dec;69(12):1182-5

Copenhagen Muscle Research Center, Denmark.

Background: Acute mountain sickness (AMS) is a usually self-limiting syndrome encompassing headache, nausea and dizziness. AMS is seen in those that go from low to high altitudes too quickly, without allowing sufficient time to acclimatize. At present, susceptibility to AMS cannot be predicted. Read More

Br Med Bull 1993 Apr;49(2):305-25

Institute of Naval Medicine, Alverstoke, UK.

Significant health hazards to the traveller arise from altitude, heat, cold and water. Altitude-induced illness encompasses the benign but common syndrome of acute mountain sickness and also life-threatening pulmonary and cerebral oedema; inadequate acclimatization and rapid ascent are important precipitating factors in each case. Prophylaxis and up to date choices of treatment are discussed in the context of underlying physiological changes. Read More

Aust Fam Physician 1990 Feb;19(2):205, 208-10

South Australian Travellers' Medical and Vaccination Centre, Queen Elizabeth Hospital, Adelaide.

Altitude sickness is a clinical syndrome that occurs with abrupt ascents to altitudes of 3000 metres and above. Symptoms include headache, malaise, fatigue, dizziness, anorexia, nausea and vomiting, and oliguria. At higher altitudes more severe illness resulting from pulmonary oedema or cerebral oedema can occur. Read More

Ann Emerg Med 1987 Sep;16(9):965-73

Nearly 40 million persons worldwide live permanently at elevation above 8,000 ft (2,439 m) and perhaps as great a number visit high-altitude regions annually. Health effects include the well-recognized altitude-specific syndromes of acute mountain sickness and high-altitude pulmonary edema. Emphasis is placed in this article on altitude-aggravated illness or those preexisting conditions that may be adversely affected by reduced O2 availability at high altitude. Read More