Professional Documents
Culture Documents
Medical Conditions and High-Altitude Travel Luks Et Al NEJM 2022
Medical Conditions and High-Altitude Travel Luks Et Al NEJM 2022
Review Article
A
From the Division of Pulmonary, Critical s interest in adventure travel grows and transportation net-
Care, and Sleep Medicine, University of works expand, more people are traveling to terrestrial high altitudes for
Washington, Seattle (A.M.L.); and the Al-
titude Research Center, Division of Pul- active and sedentary endeavors, including hiking, skiing, sightseeing, reli-
monary Sciences and Critical Care Medi- gious pilgrimages, and work.1 Often, travelers seek medical advice on trip safety,
cine, Department of Medicine, University with the primary focus on prevention and treatment of acute altitude illnesses,
of Colorado Anschutz Medical Campus,
Aurora (P.H.H.). Dr. Luks can be contact- including high-altitude headache, acute mountain sickness, high-altitude cerebral
ed at a luks@uw.edu or at the Division of edema, and high-altitude pulmonary edema. Given the prevalence of diseases such
Pulmonary, Critical Care, and Sleep Medi- as asthma and hypertension,2 many people planning high-altitude travel are likely
cine, Harborview Medical Center, 325 Ninth
Ave., Box 359762, Seattle, WA 98104. to have a preexisting medical condition. In such cases, clinicians should broaden
their pretravel counseling and consider how reductions in barometric pressure and
N Engl J Med 2022;386:364-73.
DOI: 10.1056/NEJMra2104829 subsequent decreases in the ambient partial pressure of oxygen (Po2) — known as
Copyright © 2022 Massachusetts Medical Society. hypobaric hypoxia — will affect the underlying condition and the safety of a
planned high-altitude excursion.
Clinicians and patients may be unaware of these concerns, and patients may
either proceed with travel in the face of unrecognized risks or be overly cautious
and forgo travel when it is actually feasible. This review is intended to help clini-
cians by providing a framework for advising persons with medical conditions who
are considering high-altitude travel. After reviewing the prevalence of common
diseases among high-altitude travelers and the physiological responses to hypo-
baric hypoxia, we discuss the altitudes at which persons with medical issues are
at risk for problems and offer general advice that clinicians can provide for all
travelers. We then consider the safety of travel for persons with preexisting condi-
tions and describe an approach to evaluation and counseling. Although some is-
sues covered in this review have relevance for people traveling on commercial
aircraft when the cabin altitude at cruising elevation ranges from 1500 to 2400 m,
depending on the distance traveled,3 the focus throughout is on unacclimatized
lowlanders ascending to terrestrial high altitude. Commercial flight for persons
with medical conditions is reviewed elsewhere.4
t o H y p ob a r ic H y p ox i a EPO
altitude pulmonary edema at an elevation of only increase in the sleeping elevation. For this rea-
1500 m in persons with unilateral absence of a son, a review of the planned ascent rate, which
pulmonary artery.17 varies substantially among commonly visited
In addition to the absolute altitude reached, areas, should be part of the pretravel evaluation.
the risk is a function of the time and degree of In general, the slower the ascent, the greater the
exertion at that altitude, with multiday expo- time for acclimatization and the lower the risk
sures and heavy exertion associated with in- of altitude illness. More specifically, once above
creased risk. A traveler with underlying health 3000 m, travelers should not increase their
problems might tolerate a sedentary ride on a sleeping elevation by more than 500 m per night
cable car for a short visit (e.g., 1 to 2 hours) to a and should include rest days every 3 to 4 days;
mountain lodge, whereas a longer stay at that during rest days, they should sleep at the same
altitude or the addition of physical exertion elevation for at least 2 consecutive nights. Al-
might pose problems. though widely recommended in published re-
Ultimately, the altitude at which the risk in- views and guidelines,20,26,27 this rule of thumb is
creases is based on the particular medical condi- supported primarily by observational data22 and
tion and its severity. As a result, strict altitude by only one randomized study.28 Exposure to
thresholds should be avoided in considering the hypoxia (preacclimatization) or spending time at
need for further evaluation and planning. intermediate altitudes before ascending to the
target elevation (referred to as staged ascent)
may also reduce the risk of altitude illness, de-
A dv ice for A l l High-A lt i t ude
T r av el er s pending on the duration and timing before the
planned trip.29,30
The physiological responses to hypoxia are gen- Pharmacologic prophylaxis is readily available
erally protective, but in some cases maladaptive and typically directed toward prevention of acute
responses occur, leading to some form of acute mountain sickness. Prophylaxis is not necessary
altitude illness. All high-altitude travelers, re- in all travelers; it is reserved for those with a
gardless of their underlying health, are at risk history of acute altitude illness, particularly re-
for these problems and should receive counsel- current episodes, and those planning a moder-
ing regarding recognition, prevention, and treat- ate-to-high-risk ascent, as defined in current
ment. Key features of these illnesses are sum- guidelines.27 Prediction rules have been devel-
marized in Table 1, and further information is oped to assess the risk of severe altitude illness
provided in several reviews.18-20 High-altitude and guide decisions about pharmacologic pro-
headache and acute mountain sickness are by far phylaxis31,32 but can be difficult to implement
the most common illnesses, with the former in routine practice. Pharmacologic prophylaxis
noted in 37% of people ascending to 4559 m21 against high-altitude pulmonary edema with pul-
and the latter developing in 25 to 43% of travel- monary vasodilators, including nifedipine33 and
ers at altitudes between 2000 and 4300 m, depend- tadalafil,34 is reserved for persons with a history
ing on the altitude attained and the rate and of this condition.27 Descent remains the best
method of ascent.7,22 Some of the highest rates of treatment for all acute altitude illnesses but is
acute mountain sickness have been reported on necessary only for persons with acute mountain
Mt. Kilimanjaro (5895 m)23 and among religious sickness that worsens or fails to improve with
pilgrims traveling to high-altitude festivals24 be- standard treatment (Table 1) and for persons
cause of very rapid ascent rates. Although precise with high-altitude cerebral edema or high-alti-
data are lacking, the incidences of high-altitude tude pulmonary edema.
cerebral edema and of high-altitude pulmonary
edema are quite low, but each condition is poten- Pr e t r av el E va luat ion for
tially fatal if not recognized and treated appro- Per sons w i th Medic a l
priately. Disrupted sleep and central sleep apnea C ondi t ions
are common at high altitude, even in the absence
of acute altitude illness.25 In addition to these general recommendations,
The primary risk factor for acute altitude ill- further counseling should be provided to people
ness is rapid ascent, as measured by the rate of with medical problems regarding their particu-
lar condition and the potential risks at high alti- risk for severe hypoxemia or impaired oxygen
tude. Evaluation and planning are challenging delivery at high altitude. Persons with lung dis-
because of the wide spectrum of medical prob- eases of sufficient severity, such as chronic ob-
lems and the paucity of data for many condi- structive pulmonary disease (COPD),35 interstitial
tions. In light of these challenges, clinicians can lung disease36 or cystic fibrosis,37 and cyanotic
use a general approach, framed by four ques- congenital heart disease,38 are at risk for exag-
tions, to identify persons who require further gerated hypoxemia at any elevation, which may
attention before their intended trip. increase dyspnea, decrease exercise tolerance,
The first question is whether the traveler is at and increase the risk of acute altitude illness.
questions. The former group is at risk for prob- versing hypoxemia and preventing problems that
lems at high altitude, which warrants further might occur at high altitude, but its use poses
pretravel evaluation, and persons in this group logistical challenges. Although commercial
may even need to cancel their travel plans. The airlines prohibit transport of personal oxygen
latter group can travel safely without further as- cylinders, they do permit small, battery-powered
sessment but may benefit from disease-specific oxygen concentrators, which can be useful at the
planning. Each situation is considered below. intended destination if electricity is available for
recharging batteries. Alternatively, travelers may
be able to rent portable or stationary oxygen
F ur ther E va luat ion a nd R isk
Mi t ig at ion for High-R isk concentrators or other devices at some high-alti-
Per sons tude destinations, such as a ski-resort commu-
nity, although prescriptions are usually required
Depending on the medical condition, various in North America.51 The cost of these interven-
assessments can be performed to evaluate the tions is another consideration, since insurance
risks of planned high-altitude travel. Multiple coverage for persons not already using supple-
prediction rules incorporating values obtained mental oxygen at home is limited, if available at
on pulmonary-function testing,45 measurement all. Use of hypoxic tents for several weeks before
of arterial blood gases,46 and cardiopulmonary a planned trip may reduce the risk of acute alti-
exercise testing,47 as well as the hypoxia altitude tude illness,52 but there is no evidence to support
simulation test,48 have been used to assess the the safety or effectiveness of hypoxic tents in
risk of hypoxemia and guide supplemental oxy- mitigating the effects of high altitude on people
gen use during commercial flight. However, the with high-risk medical conditions.
applicability of these tools to high-altitude travel
has not been established. The tools were de- T r ip Pl a nning for L ow-R isk
signed to assess the risk of hypoxemia at a nar- Per sons
row range of elevations — the maximum al-
lowed cabin altitude — and do not adequately Most people with medical conditions can safely
reflect the duration of or the anticipated degree travel to high altitude without further evalua-
of exertion while engaging in high-altitude tion. In fact, many persons with common condi-
travel. Echocardiography or cardiopulmonary tions, such as diabetes mellitus, and even those
exercise testing under hypoxic conditions can with uncommon issues, such as a history of
provide information about physiological re- solid-organ transplantation, have summitted very
sponses to hypoxia but are available only in high mountains, including Kilimanjaro (5895 m)
specialized centers that have the capacity to ad- and Cho Oyu (8201 m).53,54 Nevertheless, pre-
minister normobaric or hypobaric hypoxia.31 travel planning may still be necessary because of
Given these challenges, perhaps the best tool for the risk that hypobaric hypoxia or other aspects
assessing the safety of exposure to hypobaric of travel may alter disease control. A detailed
hypoxia is graded exposure to high altitude in consideration of the effects of high altitude on
safe settings. Tolerance can be assessed with common conditions is beyond the scope of this
travel to areas such as a ski-resort community in review, but a summary of key issues with com-
Colorado, where medical resources are readily mon diseases, as well as appropriate mitigation
available or descent to a lower altitude can eas- measures, is provided in Table 3. More detailed
ily be achieved in the event of problems. After a information can be found in reviews of common
period of rest and monitoring of symptoms and conditions.55-65 Data are lacking regarding high-
pulse oximetry49 at moderate altitude, persons altitude travel for persons who have had corona-
who do well can move to steadily higher eleva- virus disease 2019 (Covid-19), but recommenda-
tions or increase their physical activity. Exercise tions drawing on return-to-play guidelines for
is feasible for some persons with cardiopulmo- sports66 have been published.67
nary diseases, although tolerance of exertion Regardless of the specific condition, several
varies among such persons.35,50 principles should guide pretravel planning. For
Supplemental oxygen is the best tool for re- diseases such as asthma or heart failure, in
Table 3. Approach to Common Medical Conditions in Travelers Planning Ascent to High Altitude.*
Table 3. (Continued.)
* ACS denotes acute coronary syndrome, BP blood pressure, CAD coronary artery disease, CPAP continuous positive airway pressure,
DOAC direct oral anticoagulant, INR international normalized ratio, LASIK laser-assisted in situ keratomileusis, NYHA New York Heart
Association, PASP pulmonary-artery systolic pressure, SARS-CoV-2 severe acute respiratory syndrome coronavirus 2, Spo2 peripheral oxygen
saturation, and VTE venous thromboembolism.
which symptoms can fluctuate over time, high- A ddi t iona l C onsider at ions
altitude travel should be undertaken only when
the disease is under good control. Providers Additional considerations apply to all travelers
should adhere to guideline-directed medical with medical conditions, regardless of their
therapy ahead of planned travel. Travelers should risk category. Care is warranted in choosing
continue taking their medications during their medications for altitude illness. Dose adjust-
trip, and for many conditions, such as heart ments are necessary for persons with chronic
failure or difficult-to-control hypertension, they kidney or liver disease, whereas others may be
should establish plans for monitoring and re- at risk for drug–drug interactions or other side
sponding to changes in disease activity. Persons effects, such as hyperglycemia with the use of
with diseases subject to exacerbations, such as dexamethasone in persons with diabetes melli-
asthma, atrial fibrillation, migraine, or inflam- tus or hypokalemia with concurrent use of
matory bowel disease, should travel with the acetazolamide and loop diuretics. These issues
necessary medications for treating an exacerba- have been reviewed elsewhere.70
tion until definitive care can be obtained. Hypo- Travelers with medical conditions should
baric hypoxia and extremely cold temperatures check on the availability of medical resources
at high altitude can affect the function of certain in the area to which they will travel and in-
medical devices, such as glucose monitors,60 in- form a designated trip leader about their con-
sulin pumps,68 and metered-dose inhalers.69 In dition, since worsening of the condition could
addition, many devices are certified for use only affect the plans of the entire travel party. Be-
up to certain elevations, and accuracy at ex- cause unanticipated problems can arise even
tremely high altitude is unknown. Travelers with thorough pretravel planning, it is recom-
should therefore protect devices from the cold mended that persons obtain travel insurance
and travel with alternative means for monitoring to facilitate evacuation to a medical facility at
or administering medications in the event that a lower elevation, if necessary.
the primary method fails.
References
1. Luks AM, Ainslie PN, Lawley JS, responsiveness and renal hormones. J Appl 27. Luks AM, Auerbach PS, Freer L, et al.
Roach RC, Simonson TS. Travelers and Physiol (1985) 1995;78:377-83. Wilderness Medical Society clinical prac-
workers at high altitude. In:High altitude 14. Dehnert C, Grünig E, Mereles D, von tice guidelines for the prevention and
medicine and physiology. 6th ed. Boca Lennep N, Bärtsch P. Identification of treatment of acute altitude illness: 2019
Raton, FL:CRC Press, 2021:75-90. individuals susceptible to high-altitude update. Wilderness Environ Med 2019;30:
2. Hvidberg MF, Johnsen SP, Davidsen pulmonary oedema at low altitude. Eur Suppl:S3-S18.
M, Ehlers L. A nationwide study of preva- Respir J 2005;25:545-51. 28. Bloch KE, Turk AJ, Maggiorini M, et al.
lence rates and characteristics of 199 15. Swenson ER. Hypoxic pulmonary vaso- Effect of ascent protocol on acute moun-
chronic conditions in Denmark. Pharma- constriction. High Alt Med Biol 2013;14: tain sickness and success at Muztagh Ata,
coecon Open 2020;4:361-80. 101-10. 7546 m. High Alt Med Biol 2009;10:25-32.
3. Hampson NB, Kregenow DA, Ma- 16. Lucas SJE, Burgess KR, Thomas KN, 29. Beidleman BA, Fulco CS, Muza SR,
honey AM, et al. Altitude exposures dur- et al. Alterations in cerebral blood flow et al. Effect of six days of staging on phys-
ing commercial flight: a reappraisal. Aviat and cerebrovascular reactivity during 14 iologic adjustments and acute mountain
Space Environ Med 2013;84:27-31. days at 5050 m. J Physiol 2011;589:741- sickness during ascent to 4300 meters.
4. Silverman D, Gendreau M. Medical is- 53. High Alt Med Biol 2009;10:253-60.
sues associated with commercial flights. 17. Hackett PH, Creagh CE, Grover RF, 30. Muza SR, Beidleman BA, Fulco CS.
Lancet 2009;373:2067-77. et al. High-altitude pulmonary edema in Altitude preexposure recommendations
5. Shlim DR, Houston R. Helicopter res- persons without the right pulmonary ar- for inducing acclimatization. High Alt
cues and deaths among trekkers in Nepal. tery. N Engl J Med 1980;302:1070-3. Med Biol 2010;11:87-92.
JAMA 1989;261:1017-9. 18. Hackett PH, Roach RC. High altitude 31. Richalet J-P, Larmignat P, Poitrine E,
6. Keyes LE, Mather L, Duke C, et al. cerebral edema. High Alt Med Biol 2004; Letournel M, Canouï-Poitrine F. Physio-
Older age, chronic medical conditions 5:136-46. logical risk factors for severe high-alti-
and polypharmacy in Himalayan trekkers 19. Bärtsch P, Mairbäurl H, Maggiorini tude illness: a prospective cohort study.
in Nepal: an epidemiologic survey and case M, Swenson ER. Physiological aspects Am J Respir Crit Care Med 2012;185:192-8.
series. J Travel Med 2016;23(6):t aw052. of high-altitude pulmonary edema. J Appl 32. Beidleman BA, Fulco CS, Cymerman
7. Honigman B, Theis MK, Koziol- Physiol (1985) 2005;98:1101-10. A, Staab JE, Buller MJ, Muza SR. New
McLain J, et al. Acute mountain sickness 20. Bärtsch P, Swenson ER. Clinical prac- metric of hypoxic dose predicts altitude
in a general tourist population at moder- tice: acute high-altitude illnesses. N Engl acclimatization status following various
ate altitudes. Ann Intern Med 1993;118: J Med 2013;368:2294-302. ascent profiles. Physiol Rep 2019; 7(20):
587-92. 21. Schneider M, Bärtsch P. Characteris- e14263.
8. Faulhaber M, Flatz M, Gatterer H, tics of headache and relationship to acute 33. Bärtsch P, Maggiorini M, Ritter M,
Schobersberger W, Burtscher M. Preva- mountain sickness at 4559 meters. High Noti C, Vock P, Oelz O. Prevention of
lence of cardiovascular diseases among Alt Med Biol 2018;19:321-8. high-altitude pulmonary edema by nife-
alpine skiers and hikers in the Austrian 22. Hackett PH, Rennie D, Levine HD. dipine. N Engl J Med 1991;325:1284-9.
Alps. High Alt Med Biol 2007;8:245-52. The incidence, importance, and prophy- 34. Maggiorini M, Brunner-La Rocca H-P,
9. Faulhaber M, Gatterer H, Burtscher laxis of acute mountain sickness. Lancet Peth S, et al. Both tadalafil and dexa-
M. Preexisting cardiovascular diseases 1976;2:1149-55. methasone may reduce the incidence of
among high-altitude mountaineers in the 23. Karinen H, Peltonen J, Tikkanen H. high-altitude pulmonary edema: a ran-
Alps. J Travel Med 2011;18:355-7. Prevalence of acute mountain sickness domized trial. Ann Intern Med 2006;145:
10. Semenza GL. Hypoxia-inducible fac- among Finnish trekkers on Mount Kili- 497-506.
tors in physiology and medicine. Cell manjaro, Tanzania: an observational study. 35. Furian M, Flueck D, Latshang TD,
2012;148:399-408. High Alt Med Biol 2008;9:301-6. et al. Exercise performance and symp-
11. Schödel J, Ratcliffe PJ. Mechanisms of 24. Basnyat B, Subedi D, Sleggs J, et al. toms in lowlanders with COPD ascending
hypoxia signalling: new implications for Disoriented and ataxic pilgrims: an epide- to moderate altitude: randomized trial.
nephrology. Nat Rev Nephrol 2019; 15: miological study of acute mountain sick- Int J Chron Obstruct Pulmon Dis 2018;13:
641-59. ness and high-altitude cerebral edema at a 3529-38.
12. Weil JV, Byrne-Quinn E, Sodal IE, sacred lake at 4300 m in the Nepal Hima- 36. Christensen CC, Ryg MS, Refvem OK,
et al. Hypoxic ventilatory drive in normal layas. Wilderness Environ Med 2000;11: Skjønsberg OH. Effect of hypobaric hy-
man. J Clin Invest 1970;49:1061-72. 89-93. poxia on blood gases in patients with re-
13. Swenson ER, Duncan TB, Goldberg 25. Weil JV. Sleep at high altitude. High strictive lung disease. Eur Respir J 2002;
SV, Ramirez G, Ahmad S, Schoene RB. Alt Med Biol 2004;5:180-9. 20:300-5.
Diuretic effect of acute hypoxia in hu- 26. Basnyat B, Murdoch DR. High-altitude 37. Fischer R, Lang SM, Brückner K, et al.
mans: relationship to hypoxic ventilatory illness. Lancet 2003;361:1967-74. Lung function in adults with cystic fibro-
sis at altitude: impact on air travel. Eur 50. Agostoni P, Cattadori G, Guazzi M, 62. Luks AM. Travel to high altitude fol-
Respir J 2005;25:718-24. et al. Effects of simulated altitude- lowing solid organ transplantation. High
38. Harinck E, Hutter PA, Hoorntje TM, induced hypoxia on exercise capacity in Alt Med Biol 2016;17:147-56.
et al. Air travel and adults with cyanotic patients with chronic heart failure. Am 63. Luks AM, Hackett PH. High altitude
congenital heart disease. Circulation 1996; J Med 2000;109:450-5. and preexisting medical conditions. In:
93:272-6. 51. Luks AM. Do lung disease patients Auerbach PS, ed. Auerbach’s wilderness
39. Roeggla G, Roeggla M, Wagner A, need supplemental oxygen at high alti- medicine. 7th ed. Philadelphia:Elsevier,
Laggner AN. Poor ventilatory response to tude? High Alt Med Biol 2009;10:321-7. 2017:29-39.
mild hypoxia may inhibit acclimatization 52. Dehnert C, Böhm A, Grigoriev I, Me- 64. Parati G, Agostoni P, Basnyat B, et al.
at moderate altitude in elderly patients nold E, Bärtsch P. Sleeping in moderate Clinical recommendations for high alti-
after carotid surgery. Br J Sports Med hypoxia at home for prevention of acute tude exposure of individuals with pre-ex-
1995;29:110-2. mountain sickness (AMS): a placebo-con- isting cardiovascular conditions: a joint
40. Basnyat B, Litch J. Another patient trolled, randomized double-blind study. statement by the European Society of Car-
with neck irradiation and increased sus- Wilderness Environ Med 2014;25:263-71. diology, the Council on Hypertension of
ceptibility to acute mountain sickness. 53. Pavan P, Sarto P, Merlo L, et al. Meta- the European Society of Cardiology, the
Wilderness Environ Med 1997;8:176. bolic and cardiovascular parameters in European Society of Hypertension, the In-
41. Pugh LG, Gill MB, Lahiri S, Milledge type 1 diabetes at extreme altitude. Med ternational Society of Mountain Medi-
JS, Ward MP, West JB. Muscular exercise Sci Sports Exerc 2004;36:1283-9. cine, the Italian Society of Hypertension
at great altitudes. J Appl Physiol 1964;19: 54. van Adrichem EJ, Siebelink MJ, Rotti- and the Italian Society of Mountain Medi-
431-40. er BL, et al. Tolerance of organ transplant cine. Eur Heart J 2018;39:1546-54.
42. Dunham-Snary KJ, Wu D, Sykes EA, recipients to physical activity during a high- 65. Cornwell WK III, Baggish AL, Bhatta
et al. Hypoxic pulmonary vasoconstric- altitude expedition: climbing Mount Kili- YKD, et al. Clinical implications for exer-
tion: from molecular mechanisms to med- manjaro. PLoS One 2015;10(11):e0142641. cise at altitude among individuals with
icine. Chest 2017;151:181-92. 55. Hackett P. High altitude and common cardiovascular disease: a scientific state-
43. Luks AM. Can patients with pulmo- medical conditions. In:Hornbein TF, ment from the American Heart Associa-
nary hypertension travel to high altitude? Schoene RB, eds. High altitude: an explo- tion. J Am Heart Assoc 2021; 10(19):
High Alt Med Biol 2009;10:215-9. ration of human adaptation. New York: e023225.
44. DeLoughery TG. Anemia at altitude: Marcel Dekker, 2001:839-85. 66. Kim JH, Levine BD, Phelan D, et al.
thalassemia, sickle cell disease, and other 56. Luks AM, Swenson ER. Travel to high Coronavirus disease 2019 and the athletic
inherited anemias. High Alt Med Biol altitude with pre-existing lung disease. heart: emerging perspectives on pathol-
2021;22:113-8. Eur Respir J 2007;29:770-92. ogy, risks, and return to play. JAMA Car-
45. Dillard TA, Berg BW, Rajagopal KR, 57. Cogo A, Fiorenzano G. Bronchial diol 2021;6:219-27.
Dooley JW, Mehm WJ. Hypoxemia during asthma: advice for patients traveling to 67. Luks AM, Grissom CK. Return to
air travel in patients with chronic ob- high altitude. High Alt Med Biol 2009;10: high altitude after recovery from corona-
structive pulmonary disease. Ann Intern 117-21. virus disease 2019. High Alt Med Biol
Med 1989;111:362-7. 58. Latshang TD, Bloch KE. How to treat 2021;22:119-27.
46. Gong H Jr, Tashkin DP, Lee EY, Sim- patients with obstructive sleep apnea syn- 68. King BR, Goss PW, Paterson MA,
mons MS. Hypoxia-altitude simulation drome during an altitude sojourn. High Crock PA, Anderson DG. Changes in alti-
test. Evaluation of patients with chronic Alt Med Biol 2011;12:303-7. tude cause unintended insulin delivery
airway obstruction. Am Rev Respir Dis 59. Jean D, Moore LG. Travel to high alti- from insulin pumps: mechanisms and
1984;130:980-6. tude during pregnancy: frequently asked implications. Diabetes Care 2011; 34:
47. Christensen CC, Ryg M, Refvem OK, questions and recommendations for clini- 1932-3.
Skjønsberg OH. Development of severe hy- cians. High Alt Med Biol 2012;13:73-81. 69. Röggla G, Moser B. The function of
poxaemia in chronic obstructive pulmo- 60. Richards P, Hillebrandt D. The practi- metered dose inhalers at moderate alti-
nary disease patients at 2,438 m (8,000 ft) cal aspects of insulin at high altitude. tude. J Travel Med 2006;13:248-9.
altitude. Eur Respir J 2000;15:635-9. High Alt Med Biol 2013;14:197-204. 70. Luks AM, Swenson ER. Medication
48. Dine CJ, Kreider ME. Hypoxia altitude 61. Luks AM, Hackett P. High altitude and dosage considerations in the prophy-
simulation test. Chest 2008;133:1002-5. and common medical conditions. In: laxis and treatment of high-altitude ill-
49. Luks AM, Swenson ER. Pulse oxime- Swenson ER, Bartsch P, eds. High alti- ness. Chest 2008;133:744-55.
try at high altitude. High Alt Med Biol tude: human adaptation to hypoxia. New Copyright © 2022 Massachusetts Medical Society.
2011;12:109-19. York: Springer, 2014:449-77.