Unilateral Agenesis of the Pulmonary Artery andHigh-Altitude Pulmonary Edema (HAPE) at

Moderate Altitude

M. Sebbane, MD,1 B. Wuyam, MD, PhD,2* I. Pin, MD,3 S. Pendlebury, MB, MRCP,1 M. Plasse, MD,4C. Durand, MD,5 and P. Le vy, MD, PhD2,6

Key words: altitude; acute respiratory failure; pulmonary edema; agenesis of thepulmonary artery.

INTRODUCTION

High-altitude pulmonary edema (HAPE) is a poten-tially fatal form of non-cardiogenic pulmonary edema. Itusually occurs in healthy young subjects exercising vig-orously after arrival at high altitude (above 3,000 m). Itoccurs rarely and is less florid at moderate altitude (be-tween 2,000 and 3,000 m). We report the case of a 51⁄2-year-old boy who presented with features consistent withHAPE at a moderate altitude of 2,000 m. Agenesis of thepulmonary artery was subsequently discovered and mayhave contributed to the development of HAPE.1–4

CASE REPORT

At the time of presentation, the patient was living inNoumea, which lies 200 m above sea level. In 1991 hehad bronchopneumonia of the left lung at the age of 21⁄2years while staying at Chamonix (900 m above sealevel); he gradually recovered over several weeks. Anelectrocardiogram taken at that time was normal. He wasotherwise an active child who took part in physical ac-tivities; however, his parents had noted some respiratorydifficulty, characterized by a reduced voluntary breathholding time and delayed recovery following exercise.

In December 1993 the patient presented with a febrileepisode thought to be secondary to an upper airway in-fection for which he was given amoxicillin. He re-sponded well and was afebrile prior to his departure 8days later for a winter holiday at La Plagne. On arrival atLa Plagne, situated close to Albertville, the patient waswell, and he skied the first 2 days without difficulties atan altitude of approximately 1,500–2,000 m. He slept atan altitude of 1,800 m. On the third night he slept poorlyand vomited twice. The following day he felt tired withthe slightest exertion and had difficulty keeping up withhis ski class. Twenty-four hours later, he got short ofbreath with cyanosed extremities, and the resort doctorwas consulted. Examination revealed a fever of 38.5°C,

a pulse rate of 130/min, and a respiratory rate of 56/minwith bilateral basal crepitations in the lungs. Pulse ox-imetry showed a saturation of 40% on air, rising to 90%on 3 L/min of oxygen.

The patient was immediately transferred to Albertvillehospital, at an altitude of 250 m, and his clinical stateimproved. On admission, the patient was dyspneic at restwith a temperature of 37.5°C, a pulse rate of 130/min,respiratory rate of 40/min, and intercostal retraction, butno crepitations. On 2 L/min of oxygen pulse oximetryshowed an oxygen saturation of 92% and arterial bloodgas analysis revealed aPaO2 of 68 mmHg,PaCO2 of 31mmHg, and pH of 7.46. The chest radiograph (Fig. 1)showed alveolar shadowing scattered unevenly through-out the right lung. In addition, there was a small lefthemithorax with mediastinal herniation of the right lung.These findings were suggestive of left pulmonary hypo-plasia. There was no cardiomegaly. Blood tests showed awhite cell count of 14,000/mm3 (65% neutrophils), CRPof 50 mg/L, and positive cold agglutinins with presenceof mycoplasma IgG but no IgM. There was no subse-quent elevation in mycoplasma antibody titers after 15days. A diagnosis of infection of the right lung coexisting

1Department of Respiratory Medicine, CHU, Grenoble, France.

2Laboratory EFCR, CHU, Grenoble, France.

3Department of Pediatrics, CHU, Grenoble, France.

4Department of Pediatrics, CHR, Albertville, France.

5Department of Radiology, CHU, Grenoble, France.

6PRETA-TIMC, UMR CNRS 5525, CHU, Grenoble, France.

*Correspondence to: Dr. B. Wuyam, Laboratoire EFCR, Hoˆpital A.Michallon, BP 217 X, 38043 Grenoble-Ce´dex, France.

Received 1 November 1996; accepted 13 April 1997.

Pediatric Pulmonology 24:111–114 (1997)

© 1997 Wiley-Liss, Inc.

with an abnormality of the left lung was made. The patientwas treated with oxygen at 2 L/min, a macrolide antibiotic,and intravenous steroids. The patient improved over thenext few hours, with resolution of dyspnea, and the pulserate decreased to 55/min. The oxygen saturation was 92%on room air the following day. The alveolar infiltrates onthe chest radiograph took 4 days to disappear, leaving anappearance consistent with left pulmonary hypoplasia.

Further investigations were undertaken to evaluate theexact nature of the pulmonary abnormality. A chest ra-diograph confirmed a significant loss of volume of theleft lung, a shift of the mediastinum to the left, and me-diastinal herniation of the right lung. The left hilum couldnot be identified. Density of the left lung was near nor-mal, and no air trapping was noted on expiration (Fig. 2).Echocardiography revealed complete absence of the leftpulmonary artery with an abrupt termination of the leftside of the pulmonary trunk. There was no evidence ofpulmonary hypertension. The estimated systolic pulmo-nary artery pressure was 30 mmHg. There was no cardiacabnormality, but the position of the aortic arch was morecentral than normal. Pulmonary ventilation/perfusion

scanning showed ventilation of the left lung reduced to25% of total ventilation and perfusion of the left lungreduced to 5% of total perfusion. Lung function testswere consistent with a restrictive defect, with a total lungcapacity of 1,706 mL (82% of the predicted value) and avital capacity of 1,180 mL (78% of predicted). There wasno evidence of airway obstruction (FEV1/FVC of 86%).Exercise testing over 7 minutes revealed normal exercisetolerance with a maximal oxygen consumption of 980mL/min and a predicted value of 900 mL/min. Pulse ratereached 80% of maximal predicted rate without oxyhe-moglobin desaturation. However, there was a reductionin breathing reserve at the end of exercise, consistentwith a restrictive lung defect.

DISCUSSION

HAPE is characterized by the acute onset of respira-tory symptoms on ascent to high altitude. The primarysymptom is dyspnea. It is frequently preceded or accom-panied by symptoms of mountain sickness such as head-

CRP C-reactive proteinHAPE High-altitude pulmonary edemaFEV1 Forced expiratory volume in 1 secondFVC Forced vital capacityIgG Immunoglobulin GIgM Immunoglobulin MPaO2 Arterial partial pressure of oxygenPaCO2 Arterial partial pressure of carbon dioxide

Fig. 1. Admission chest radiograph showing infiltrates of theright lung and a small left hemithorax, a shift of the mediatinumto the left, and a mediastinal herniation of the right lung.

Fig. 2. Chest radiograph in expiration. Note that there is neithera shift of the mediastinum to the right nor an asymmetricaldiaphragmatic excursion, suggesting the absence of significantair trapping.

112 Sebbane et al.

ache, nausea, and vomiting. The major pathological fea-ture of HAPE is an alveolar transudate rich in high mo-lecular weight proteins.5 HAPE is often associated withpyrexia and leukocytosis, which may make distinctionbetween infection and HAPE difficult.6,7 In the case de-scribed, the rapid improvement in the child’s conditionon descent to lower altitude and the disappearance of thepreviously noted crepitations on arrival at low altitude inthe absence of any therapeutic intervention other thanoxygen administration are suggestive of the diagnosis ofHAPE.

On further investigation agenesis of the left pulmonaryartery was discovered. In view of the past history ofpneumonia of the left lung at the age of 21⁄2 years, uni-lateral left bronchiolitis (Swyer-James-McLeod syn-drome) may have caused left pulmonary hypoplasia.However, careful examination of the chest radiograph onfull expiration (Fig. 2) did not reveal air trapping due tobronchiolar obstruction, which characterizes the Swyer-James-McLeod syndrome.8 Perfusion was virtually ab-sent in the left lung, although a residual 5% of back-ground signal was noted on the ventilation/perfusionscan, possibly due to herniation of the right lung. A re-duced but higher proportion of ventilation was preservedin the left lung. Finally, no left branch of the pulmonarytrunk was visualized on echocardiography, and this isunlikely in the Swyer-James-McLeod syndrome, inwhich the pulmonary artery circulation is patent althoughdiminished.8 These findings are suggestive of a proximalinterruption of the left pulmonary artery and resulting leftpulmonary hypoplasia, rather than an acquired conse-quence of pneumonia in early life.

It is of note that this case of HAPE occurred in a youngchild skiing at a moderate altitude of approximately2,000 m and sleeping at an altitude of 1,800 m. This isone of the lowest altitudes at which HAPE has beenreported.9 The occurrence of HAPE in this case wasprobably secondary to a combination of factors. Some ofthese factors are known to favor the occurrence of HAPEsuch as exercise, cold, and sleep at an altitude that mayhave led to significant hypoxemia and oxygen desatura-tion.9 The young age of our patient may have played anadditional role since epidemiological studies conductedat La Oroya, Peru (4,059 m) have suggested that childrenare more susceptible to HAPE than adults. The incidenceof HAPE in a period of 4–6 hours after arrival at LaOroya from sea level was 6.4% in children (5–18 years)vs 0.4% in adults.10

In addition, agenesis of a pulmonary artery and a prob-able viral respiratory tract infection prior to arriving ataltitude may have played a contributing role in this child.Agenesis of a pulmonary artery has been proposed as afactor favoring the development of HAPE. Hackett et al.1

reported four cases of severe HAPE, one of which wasfatal, occurring at moderate altitudes of 2,000–3,000 in

adults in whom unilateral agenesis of a pulmonary arterywas subsequently discovered. Additional reports havebeen published of cases of HAPE with coexisting unilat-eral congenital2 or acquired3 pulmonary artery occlusion.Some of these patients had recurrent symptoms on returnto altitude. To date, only a single case of HAPE has beenreported in a child aged 10 years with congenital agenesisof a pulmonary artery.4 Among the numerous factorsthought to contribute to the development of HAPE, theimportance of transient pulmonary hypertension (medi-ated by vasoconstriction and hypoxia) and overperfusionof certain regions of the pulmonary vascular bed has longbeen recognized.11,12 Clinical observations indicate in-creased susceptibility to HAPE in patients with pulmo-nary vascular abnormalities at lower altitudes than ex-pected, which gives support to the importance of theabove mechanisms in humans. We propose that the re-duction in the pulmonary vascular bed secondary to uni-lateral pulmonary artery agenesis leads to a greater de-gree of pulmonary hypertension at a given altitude, over-perfusion of certain regions in response to unevenpulmonary vasoconstriction, and subsequent pulmonaryedema.

In our patient, the episode of an upper airway infectionand associated increases in cold agglutinins a week be-fore the arrival at La Plagne suggest a viral infectionbefore arrival at high altitude. Several authors have pro-posed that certain respiratory infections can favor thedevelopment of HAPE.7,13 In a recent series of 27 chil-dren who developed HAPE, 79% were found to havepre-existing illness such as upper airway respiratory in-fection, otitis media, or streptococcal pharyngitis.14 Theauthors suggested that in contrast to adults in whom only13% had a preceding respiratory tract infection, the pres-ence of such infections may explain, at least in part, theparticular vulnerability of children to HAPE.9,10We pro-pose that a number of interacting predisposing factors ledto the development of HAPE in this child, namely, youngage, probable viral infection prior to arrival at altitude,cold temperatures, exercise, sleep at altitude, and absenceof the left pulmonary artery. Recurrent symptoms ofHAPE on returning to altitude have been observed incases of abnormality of the pulmonary vasculature.1–3

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HAPE and Pulmonary Artery Agenesis 113

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