(Chest. 2003;123:49-53.)
© 2003
American College of Chest Physicians
High-Altitude Pulmonary Edema at Moderate Altitude (< 2,400 m; 7,870 feet)*
A Series of 52 Patients
André Louis Gabry, MD;
Xavier Ledoux, MD;
Monique Mozziconacci, MD and
Claude Martin, MD, FCCP
* From the Emergency Department (Dr. Gabry) and Department of Anesthesia and Intensive Care (Dr. Ledoux), Hopital de Moutiers, Moutiers; and Department of Anesthesia and Intensive Care (Drs. Mozziconacci and Martin), Hopital Nord, Marseilles University, Hospital System, Marseilles School of Medicine, Marseilles, France.
Correspondence to: Claude Martin, MD, FCCP, Hopital Nord, 13915 Marseille cedex 20, France; e-mail: cmartin{at}ap-hm.fr
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Abstract
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Study objectives: To describe a group of patients who acquired pulmonary edema at a moderate altitude of 1,400 to 2,400 m.
Design: Observational, retrospective chart review (1992–2000) of a series of 52 consecutive patients admitted for high-altitude pulmonary edema (HAPE) that occurred at 1,400 to 2,400 m.
Setting: Emergency department of a community hospital in the French Alps (altitude, 500 m).
Patients: Vacationing skiers who met criteria for altitude-related pulmonary edema, and in whom other causes (infectious, cardiogenic, neurogenic, and toxic) were excluded.
Measurements and results: All patients presented with signs of pulmonary edema. Diagnoses of infectious, cardiogenic, neurogenic, or toxic edema were ruled out in each patient. All patients were hypoxemic and had radiographic signs of pulmonary edema. Virtually all patients (96%) had dyspnea, and most (77%) had moist rales. All patients were treated with supplemental oxygen (3 to 12 L/min), bed rest, moderate fluid restriction, and continuous positive airway pressure. All recovered fully and were discharged after 4 ± 2 days (mean ± SD).
Conclusion: This study suggests that HAPE at moderate altitudes is more frequent than usually reported. Patients are likely to be young, vacationing men, with no history of prior disease. The disease has a favorable prognosis, and requires simple treatment and a short hospital stay.
Key Words: acute mountain sickness • high-altitude illness • high-altitude pulmonary edema • pulmonary edema
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Introduction
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High-altitude pulmonary edema (HAPE) is a life-threatening condition that occurs in persons who ascend rapidly to heights of > 2,500 to 3,000 m.1
2
3
4
5
6
HAPE refers to the pulmonary abnormalities of high-altitude illness, while acute mountain sickness and high-altitude cerebral edema refer to the cerebral abnormalities.4
The occurrence of pulmonary edema at moderate altitude is very uncommon but is probably underestimated.2
3
7
We report a series of 52 patients admitted for HAPE occurring at moderate altitude (1,400 to 2,400 m) over a 9-year period in a community hospital in the French Alps.
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Materials and Methods
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During the 9-year study period (1992–2000), 11,420 patients were admitted to the emergency department of Moutiers Hospital (altitude, 500 m), and 52 patients presented with HAPE. Patients’ charts were extracted from the database of the emergency department after authorization from the Patient Chart Review Board. All patients were on vacation in different ski resorts around Moutiers. Diagnosis of HAPE was suspected on the following criteria: tachypnea, dyspnea, cough, cyanosis, moist rales (unilateral or bilateral), decreased PaO2 and arterial oxygen saturation (with normal or low PaCO2), and pulmonary infiltrate (unilateral or bilateral) on the chest radiograph.8
In all patients, the diagnoses of infectious, cardiogenic, neurogenic, or toxic edema were ruled out on the following criteria: no signs of infection, negative blood culture results (drawn in each patient), no sign of cardiac hypokinesia or dyskinesia or valvular abnormality at the echocardiographic examination (performed in each patient), and no history of intoxication, previous infectious diseases, cardiac diseases, or head trauma. Relief of airway obstruction was also ruled out as a possible cause. A thorough head and neck examination was performed. A chest examination was performed to exclude a prolonged expiratory time and wheezing, and the chest radiograph was carefully examined for the presence of hilar adenopathy or asymmetric lung field size on expiration. Aspiration pneumonitis was ruled out on the absence of marked disturbance of consciousness, such as that resulting from drug overdose, seizures, or a massive cerebrovascular accident. Patients were carefully monitored during their hospital stay for any signs of infection or cardiac diseases. Treatment consisted of bed rest (all patients), fluid restriction (all patients), nasal oxygen (all patients), continuous positive airway pressure (all patients), and sometimes oral nicardipine.
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Results
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The clinical characteristics of the patients are presented in Table 1
. Patients skied at altitudes between 1,400 m and 2,400 m. Mean sleeping altitude was 1,300 m (range, 900 to 1,800 m). First symptoms started around the second day of the stay. Clinical signs on hospital admission are presented in Table 2
. Virtually all patients had dyspnea, and most of them had moist rales on pulmonary examination.
In addition to cardiorespiratory signs, patients presented with rectal temperature 38°C (44%), sleep disturbance (62%), headache (53%), digestive disturbance (28%), stupor (9%), and coma (4%). The two comatose patients underwent cerebral CT scan, which showed moderate signs of cerebral edema. All patients with neurologic abnormalities dramatically improved within a few hours with treatment. All patients had radiographic pulmonary infiltrates, most often bilateral in most patients (43 of 52 patients; Table 3
, Fig 1
). All patients were hypoxemic on hospital admission (Table 4
), and PaO2 improved significantly over the treatment period.
On entry, no patients had signs of infectious, cardiogenic, neurogenic, or toxic pulmonary edema. All blood culture findings were negative, and WBC count on hospital admission was 8,200 ± 1,700/µL (range, 5,200 to 13,800/µL).
All patients were treated with supplemental oxygen (3 to 12 L/min), bed rest, moderate fluid restriction, and continuous positive airway pressure (5 to 10 cm H2O). Oral nicardipine was administered to 43% of the patients. No patients were treated with nitric oxide or antibiotics.
During their hospital stay, patients were carefully followed up and did not present any clinical signs of infectious, cardiogenic, neurogenic, or toxic pulmonary edema. All patients fully recovered their episode of HAPE and were discharged after 4 ± 2 days (mean ± SD).
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Discussion
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HAPE is a form of noncardiogenic pulmonary edema that typically occurs in healthy, young people who ascend rapidly to altitude and engage in vigorous physical activity. The occurrence of HAPE at an altitude < 2,500 m is said to be rare,1
2
3
4
but its incidence is probably underestimated.2
3
The patients are often skiers or hikers who have easy access to moderate altitude and start physical activity without prior training. The clinical presentation is similar to HAPE, the difference being the maximal altitude reached: < 2,500 m. We did our best to eliminate infectious, cardiogenic, neurogenic, or toxic causes of pulmonary edema. One limitation to our study is that we did not perform urine examination for the presence of toxins such as cocaine, amphetamines, opiates, etc. We relied on family and patient interviews and a physical examination to exclude intoxication as a cause of illness. Viral pneumonia should also be discussed, since it shares some features with HAPE: presence of cough, fever, and sometimes a short hospital stay.9
However, other very important features make HAPE different from viral pneumonia, at least that which is due to influenza: patients are older (mean age 60 years) and most of them have comorbid illnesses (chronic lung disease 40%, heart or renal disease, diabetes).9
In addition, patients are more severely affected. Ten of 17 in the series of Oliviera et al9
required admission to the ICU, and the associated mortality was 29.4%.
The occurrence of HAPE, according to several case reports, may be related to preexistent abnormalities. In some cases, patients had no right pulmonary artery and acquired pulmonary edema at altitudes between 2,750 m and 2,900 m.10
11
The absence of the right pulmonary artery has also been reported in a child.11
Other case reports have been published12
13
14
15
16
suggesting that pulmonary edema tends to occur at lower altitudes when pulmonary circulation is abnormal: thromboembolic pulmonary hypertension, anomalous pulmonary venous drainage into the superior vena cava, and unilateral pulmonary artery occlusion from granulomatous mediastinitis. In our series of patients, we did not undertake exploration of the pulmonary vascular bed and thus were not able to determine whether a preexistent anomaly was a predisposing factor for the pulmonary edema. It would be surprising that 52 persons in apparent good health at sea level but with pulmonary circulation abnormalities could have escaped detection for an average of almost 40 years.
It has also been suggested that HAPE could occur following pulmonary hypertension in patients taking diet pills containing fenfluramine and diethylpropion.17
The pharmacologic properties of anorexigens mainly stem from an inhibition of serotonin uptake together with a release from nerve endings and platelets.18
19
Anorexigens structurally related to amphetamine are no longer on the market in France and could not be implicated. Thus, although their use cannot be excluded, we consider it similarly unlikely in these skiers. We were surprised that our retrospective chart review identified an average of five to six cases per year among patients referred to our department for all causes over the 9 years of our review. No actual incidence estimate is possible, however, since we do not know the base population from which the cases were derived, nor how many persons with subclinical HAPE may have directly returned to sea level with or without professional care. Our report is in agreement with several other series reporting cases of HAPE occurring in populations in ski areas.6
7
The pathogenesis of HAPE is still controversial. An intense and uneven hypoxic vasoconstriction could lead to excessive pressure in the pulmonary capillaries of overperfused lung regions.2
In addition to hydrostatic pulmonary hypertension, a change in alveolar-capillary membrane permeability can contribute to pulmonary edema. Indeed, an increase in pressure exposes the capillary wall to severe stresses, and this will cause a high permeability edema or even frank hemorrhage. However, we have no direct evidence of uneven hypoxic pulmonary vasoconstriction.20
It has also been speculated that oxygen-free radicals may play a role in altitude-related problems and antioxidants may play a role in its treatment.21
It is also possible that pulmonary inflammation may trigger, potentiate, or exacerbate the formation and degree of edema.22
Leukotrienes are important mediators of inflammation and cause pulmonary vasoconstriction, increased mucus production, and increased vascular permeability.23
24
Kaminsky et al25
found elevated airway leukotriene E4 (the major airway metabolite of the leukotrienes C10 and D4) in a group of 71 patients with HAPE, supporting the view that the disease involves inflammatory mechanisms.
In conclusion, this study strongly suggests that HAPE at altitudes 
2,400 m is more frequent than usually reported. Patients are likely to be young, vacationing men, with no history of prior disease. The disease has a favorable prognosis. It requires simple treatment and a short hospital stay. Although we do not have experience with repeat HAPE in any of our patients on reexposure, caution should be considered in case of future altitude travel.
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Footnotes
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Abbreviation: HAPE = high-altitude pulmonary edema
Received for publication November 13, 2000.
Accepted for publication June 3, 2002.
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Abstract
Introduction
