High altitude pulmonary oedema: who gets it and why?
Authors: AJ Peacock
Journal: European Respiratory Journal (1995)

High altitude pulmonary oedema is a life-threatening condition which can affect otherwise healthy individuals travelling at altitude. Common clinical features are breathlessness, chest pain, cough and haemoptysis, and these features often occur against a background of symptoms of mountain sickness, such as headache, nausea, insomnia and dizziness. The incidence of high altitude pulmonary oedema is difficult to assess but attempts have been made; in 1976 HACKETT and RENNIS [1] showed that 2.5% of trekkers passing through Pheriche (4243 m) in the Khumbu region of Nepal suffered from high altitude pulmonary oedema (HAPE). Since the syndrome occurs in otherwise fit people and high altitude travel is becoming more common due to the increasing adventurousness of holiday makers, it would be very useful to be able to predict which individuals are likely to get into trouble if they travel to altitude. In order to make this prediction, we need to know the cause of high altitude pulmonary oedema but, at the present time, no single cause has been found. Excessive breathlessness with high altitude travel has been known about since pre-Christian times but it was not until 1960 that the condition was recognized as a separate entity [2]. Since this clinical description, there have been many attempts to explain the cause of the syndrome. These have included left ventricular failure, pulmonary thromboembolism, pneumonia, excessive pulmonary hypertensive response to hypoxia, inadequate ventilatory response to hypoxia, excessively leaky pulmonary capillaries on exposure to hypoxia and stress failure of the pulmonary capillaries. There are several important clinical features of the syndrome which may point to its aetiology. It is rare below 2,000 m altitude. The incidence is increased by exercise at altitude and also if cold conditions prevail. There is no relationship between HAPE and physical fitness, as measured by maximum oxygen consumption, but there is marked individual susceptibility an individual who has suffered HAPE before is likely to get it again even though they are apparently otherwise entirely well. When catheter studies have been performed prior to treatment, it has been found that HAPE is often associated with severe pulmonary hypertension. In addition, bronchoalveolar lavage studies have shown that the pulmonary oedema fluid is rich in protein [3], and the fluid may contain inflammatory mediators [4]. It is now clear that HAPE is not due to left ventricular dysfunction. We know this because the oedema is protein-rich and the wedge pressure, when measured, is usually normal. HAPE is also unlikely to be due to pulmonary thromboembolism. Where intravascular pulmonary artery thrombosis is seen on postmortem, it is likely that these thrombi have occurred in situ rather than embolising from other parts of the body. For many years, it was held that HAPE was due to pneumonia but this is now known to be untrue, although the patients are often feverish and inflammation may be important [5]. The more likely factors in the aetiology of HAPE are: 1) abnormally brisk vasoconstrictor response to hypoxia; 2) inadequate ventilatory response to hypoxia; and 3) leak or stress failure of the pulmonary capillaries. There now appears to be no doubt that the response of the pulmonary vasculature to hypoxia is extremely important in the aetiology of HAPE. The reasons for this assertion are as follows. Cardiac catheterization usually demonstrates severe pulmonary hypertension prior to treatment. The condition is more common where there is absence of a pulmonary artery [6, 7] and pulmonary flows are higher. Cold, a known precipitating factor in HAPE, is known to raise pulmonary artery pressure [8]. Even when pulmonary artery pressure has not actually been measured, chest radiographic images will often show an increase in pulmonary artery size suggesting high intraluminal pressures [9]. Humans and animals who live successfully at high altitude tend to have thinner pulmonary arteries and a diminished pulmonary vasoconstrictive response to hypoxia [10, 11]. High altitude pulmonary oedema can be both prevented and treated with calcium antagonists, which are known pulmonary vasodilators [12]. From the above, it is clear that the pulmonary circulation is implicated but additional factors, such as leaking capillaries, may also be important, particularly since it is necessary to explain the high protein content of the oedema [13]. Although it is difficult to prove that hypoxia per se causes leak in the pulmonary capillaries, it is likely that the finding of diminished vital capacity on exposure to hypobaric hypoxia is due to leak of fluid into the interstitium [14]. A major argument against the view that high pulmonary artery pressures cause HAPE is that the leak occurs downstream from the vasoconstriction. This anomaly may be explained by HULTGREN'S observation that the pulmonary oedema is patchy [15]. If the vasoconstriction that occurs in response to hypoxia occurs more in some pulmonary arteries than others then this would account for the fact that some capillaries are exposed to very high pressures whereas others are protected. This patchy vasoconstriction would also explain West's theory of HAPE stress failure of the pulmonary EDITORIAL