This Article  • Full text  • PDF  • Correction  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (66)  • Contact me when this article is cited  Related Content  • Related articles  • Similar articles in JAMA  Social Bookmarking   What's this?

Inflammation Is Not an Etiologic Factor

Erik R. Swenson, MD; Marco Maggiorini, MD; Stephen Mongovin, BS; J. Simon R. Gibbs, MD; Ilona Greve, MD; Heimo Mairbäurl, PhD; Peter Bärtsch, MD

JAMA. 2002;287:2228-2235.

Context  The pathogenesis of high-altitude pulmonary edema (HAPE) is considered an altered permeability of the alveolar-capillary barrier secondary to intense pulmonary vasoconstriction and high capillary pressure, but previous bronchoalveolar lavage (BAL) findings in well-established HAPE are also consistent with inflammatory etiologic characteristics.

Objectives  To determine whether inflammation is a primary event in HAPE and to define the temporal sequence of events in HAPE.

Design, Setting, and Participants  Case study from July through August 1999 of 10 subjects with susceptibility to HAPE and 6 subjects resistant to HAPE, all of whom are nonprofessional alpinists with previous mountaineering experience above 3000 m.

Main Outcome Measures  Pulmonary artery pressure measurements and BAL findings at low altitude (490 m) and shortly before or at the onset of HAPE at an altitude of 4559 m.

Results  Subjects who were HAPE susceptible had higher mean (SD) pulmonary artery systolic blood pressures at 4559 m compared with HAPE-resistant subjects (66 vs 37 mm Hg; P = .004). Despite development of HAPE in the majority of HAPE-susceptible subjects, there were no differences in BAL fluid total leukocyte counts between resistant and susceptible subjects or between counts taken at low and high altitudes. Subjects who developed HAPE had BAL fluid with high concentrations of plasma-derived proteins and erythrocytes, but there was no increase in plasma concentrations of surfactant protein A and Clara cell protein. The chest radiograph score was 12.7 for the 3 HAPE-susceptible subjects who developed HAPE before BAL was performed; they were lavaged within 3 to 5 hours. The remainder of the HAPE-susceptible group was lavaged before edema was apparent on radiographs. However, 6 subjects from the HAPE-susceptible group who developed HAPE on the following day had a score on bronchoscopy of 1.5, which increased to 4.6, reflective of mild pulmonary edema. In HAPE cases, there were no elevations in a number of proinflammatory cytokines and eicosanoid and nitric oxide metabolites.

Conclusions  Early HAPE is characterized by high pulmonary artery pressures that lead to a protein-rich and mildly hemorrhagic edema, with normal levels of leukocytes, cytokines, and eicosanoids. HAPE is a form of hydrostatic pulmonary edema with altered alveolar-capillary permeability.

Author Affiliations: Medical and Research Services, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle (Dr Swenson and Mr Mongovin); Medical Intensive Care Unit, Department of Internal Medicine, University Hospital, Zurich, Switzerland (Drs Maggiorini and Greve); National Heart and Lung Institute, Imperial College School of Science, Technology, and Medicine, London, England (Dr Gibbs); and Division of Sports Medicine, Department of Medicine, University Clinic, Heidelberg, Germany (Drs Mairbäurl and Bärtsch).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLES

High-Altitude Pulmonary Edema
and
JAMA. ;287():2275-2278.
FULL TEXT  

May 1, 2002
JAMA. ;287():2295-2296.
FULL TEXT  

Altitude Illness
JAMA. ;287():2314-2314.
 

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Continuous positive airway pressure increases haemoglobin O2 saturation after acute but not prolonged altitude exposure
Agostoni et al.
Eur Heart J 2009;0:ehp472v1-ehp472.
ABSTRACT | FULL TEXT  

Dexamethasone But Not Tadalafil Improves Exercise Capacity in Adults Prone to High-Altitude Pulmonary Edema
Fischler et al.
Am. J. Respir. Crit. Care Med. 2009;180:346-352.
ABSTRACT | FULL TEXT  

Oral antioxidant supplementation does not prevent acute mountain sickness: double blind, randomized placebo-controlled trial
Baillie et al.
QJM 2009;102:341-348.
ABSTRACT | FULL TEXT  

The increase in pulmonary arterial pressure caused by hypoxia depends on iron status
Smith et al.
J. Physiol. 2008;586:5999-6005.
ABSTRACT | FULL TEXT  

Illnesses at High Altitude
Schoene
Chest 2008;134:402-416.
ABSTRACT | FULL TEXT  

Evidence supportive of impaired myocardial blood flow reserve at high altitude in subjects developing high-altitude pulmonary edema
Kaufmann et al.
Am. J. Physiol. Heart Circ. Physiol. 2008;294:H1651-H1657.
ABSTRACT | FULL TEXT  

Effect of Altitude on the Heart and the Lungs
Bartsch and Gibbs
Circulation 2007;116:2191-2202.
FULL TEXT  

Travel to high altitude with pre-existing lung disease
Luks and Swenson
Eur Respir J 2007;29:770-792.
ABSTRACT | FULL TEXT  

Both tadalafil and dexamethasone may reduce the incidence of high-altitude pulmonary edema: a randomized trial.
Maggiorini et al.
ANN INTERN MED 2006;145:497-506.
ABSTRACT | FULL TEXT  

Hypoxic lung whiteout: further clearing but more questions from on high.
Swenson
ANN INTERN MED 2006;145:550-552.
FULL TEXT  

Hypoxia causes permeability oedema in the constant-pressure perfused rat lung.
Dehler et al.
Eur Respir J 2006;27:600-606.
ABSTRACT | FULL TEXT  

Effects of altitude and exercise on pulmonary capillary integrity: evidence for subclinical high-altitude pulmonary edema
Eldridge et al.
J. Appl. Physiol. 2006;100:972-980.
ABSTRACT | FULL TEXT  

Platelet count and function at high altitude and in high-altitude pulmonary edema
Lehmann et al.
J. Appl. Physiol. 2006;100:690-694.
ABSTRACT | FULL TEXT  

Hypoxia Impairs Systemic Endothelial Function in Individuals Prone to High-Altitude Pulmonary Edema
Berger et al.
Am. J. Respir. Crit. Care Med. 2005;172:763-767.
ABSTRACT | FULL TEXT  

Cellular Stress Failure in Ventilator-injured Lungs
Vlahakis and Hubmayr
Am. J. Respir. Crit. Care Med. 2005;171:1328-1342.
ABSTRACT | FULL TEXT  

Exercise training prevents the inflammatory response to hypoxia in cremaster venules
Orth et al.
J. Appl. Physiol. 2005;98:2113-2118.
ABSTRACT | FULL TEXT  

Physiological aspects of high-altitude pulmonary edema
Bartsch et al.
J. Appl. Physiol. 2005;98:1101-1110.
ABSTRACT | FULL TEXT  

The Effects of a 5-Lipoxygenase Inhibitor on Acute Mountain Sickness and Urinary Leukotriene E4 After Ascent to High Altitude
Grissom et al.
Chest 2005;127:565-570.
ABSTRACT | FULL TEXT  

Strenuous physical exercise inhibits granulocyte activation induced by high altitude
Chouker et al.
J. Appl. Physiol. 2005;98:640-647.
ABSTRACT | FULL TEXT  

Pulmonary Blood Flow Heterogeneity during Hypoxia and High-Altitude Pulmonary Edema
Hopkins et al.
Am. J. Respir. Crit. Care Med. 2005;171:83-87.
ABSTRACT | FULL TEXT  

The Physiologic Basis of High-Altitude Diseases
West
ANN INTERN MED 2004;141:789-800.
FULL TEXT  

Pathophysiological significance of peroxidative stress, neuronal damage, and membrane permeability in acute mountain sickness
Bailey et al.
J. Appl. Physiol. 2004;96:1459-1463.
ABSTRACT | FULL TEXT  

Altered ion transporter expression in bronchial epithelium in mountaineers with high-altitude pulmonary edema
Mairbaurl et al.
J. Appl. Physiol. 2003;95:1843-1850.
ABSTRACT | FULL TEXT  

Thoughts on the pulmonary blood-gas barrier
West
Am. J. Physiol. Lung Cell. Mol. Physiol. 2003;285:L501-L513.
ABSTRACT | FULL TEXT  

Vascular endothelial growth factor in patients with high-altitude pulmonary edema
Hanaoka et al.
J. Appl. Physiol. 2003;94:1836-1840.
ABSTRACT | FULL TEXT  

Alveolar Flooding at High Altitude: Failure of Reabsorption?
Hoschele and Mairbaurl
Physiology 2003;18:55-59.
ABSTRACT | FULL TEXT  

Nasal Epithelium Potential Difference at High Altitude (4,559 m): Evidence for Secretion
Mairbaurl et al.
Am. J. Respir. Crit. Care Med. 2003;167:862-867.
ABSTRACT | FULL TEXT  

Altitude Pulmonary Edema Below 8,000 Feet: What Are We Missing?
Raymond
Chest 2003;123:5-7.
FULL TEXT  

Salmeterol for the Prevention of High-Altitude Pulmonary Edema
Cruden et al.
NEJM 2002;347:1282-1285.
FULL TEXT  

Inflammation Doesn't Cause High-Altitude Pulmonary Edema
JWatch Emergency Med. 2002;2002:2-2.
FULL TEXT  

High-Altitude Pulmonary Edema
Hackett and Rennie
JAMA 2002;287:2275-2278.
FULL TEXT