Speaker's Highlight

• Don Sin University of British Columbia, St. Paul Hospital (Canada)
  Kenneth R. Chapman Toronto General Hospital Research Institute (Canada)
• Parameswaran Nair McMaster University (Canada)
  Carolyn Calfee UCSF (U.S.A.)
• Gregory P. Downey University of Colorado School of Medicine (U.S.A.)
  David A. Schwartz University of Colorado School of Medicine (U.S.A.)
• Neil Schluger Tuberculosis Control Branch, California Department of Public Health (U.S.A.)
  Nick Kim Critical Care & Sleep Medicine, University of California San Diego (U.S.A.)
• Nicola Hananiah Baylor College of Medicine (U.S.A.)
  Jae-Joon Yim Seoul National University College of Medicine (Republic of Korea)
• Koichiro Asano Tokai University School of Medicine (Japan)
  Diahn-Warng Perng Taipei Veterans General Hospital (Taiwan)
• Konstantinos Kostikas University of Ioannina (Greece)
  Karin Klooster University Medical Center Groningen (Kingdom of the Netherlands)

• The Pathophysiology of High-Altitude Pulmonary Edema

  Imagine climbing toward Mt Kosciuszko on a crisp morning, your breath thinning with every metre of ascent. High-altitude pulmonary edema is a non-cardiogenic form of pulmonary overflow that develops within days of arriving above 2,500 metres. In Australia, where peaks sit well below that mark, returning trekkers on international trips can carry the condition home undiagnosed. The pathophysiology behind the syndrome begins before symptoms surface, rooted in hypoxia, uneven vascular reactivity, and the structural limits of the pulmonary capillary bed.

  For clinicians reading the APSR 2022 welcome message, revisiting the cascade that drives this edema remains relevant, particularly on the eastern seaboard where travellers returning from the Himalayas, the Andes, or East Africa often present first to local services. With timely recognition and descent the syndrome usually resolves within two days; without treatment, mortality approaches half.

  The Hypoxic Vascular Trigger

  The pivotal driver is hypoxic pulmonary vasoconstriction, a reflex useful in utero but pathological in the adult lung. Unlike systemic vessels, pulmonary arterioles constrict when alveolar oxygen falls, and the response is uneven. Some beds contract far more than others, and that heterogeneity is what makes the syndrome more than a uniform rise in pulmonary artery pressure.

  Reduced barometric pressure lowers the inspired partial pressure of oxygen, reducing alveolar and arterial saturation. Arterioles detect the drop through oxygen-sensitive potassium channels in vascular smooth muscle, producing regional rather than global constriction. Vessels serving well-ventilated regions tighten most, while vessels serving poorly ventilated regions dilate, diverting blood toward already hypoxic lung units.

  Hemodynamic Stress and Capillary Leak

  Heterogeneous constriction drives regional overperfusion, and capillaries fed by the least-reactive vessels receive a disproportionate share of cardiac output. Capillary wall stress rises, endothelial junctions separate, and fluid together with erythrocytes enters the alveolar space.

  Feature	High-Altitude Pulmonary Edema	High-Altitude Cerebral Edema
  Primary site	Pulmonary microvasculature	Cerebral white matter
  Core insult	Pressure-driven capillary leak	Vasogenic and cytotoxic oedema
  Defining symptom	Dyspnoea with frothy cough	Ataxia out of proportion to headache
  Typical onset	2–4 days	3–7 days
  First-line field response	Descent, oxygen, nifedipine	Descent, oxygen, dexamethasone

  The edema is driven by capillary leak rather than left-heart dysfunction. Echocardiography in affected climbers typically shows preserved left ventricular function alongside elevated pulmonary artery pressures, an important distinction for clinicians used to diagnosing cardiac failure.

  Inflammation and the Endothelial Interface

  Hypoxia does not act on the vasculature alone. Reactive oxygen species accumulate, nitric oxide bioavailability falls, and circulating neutrophils prime for adhesion to the pulmonary capillary wall. Interleukin-6 and tumour necrosis factor alpha appear in bronchoalveolar lavage from affected climbers, mirroring acute lung injury.

  The Australian context adds a wrinkle. Travellers flying from Sydney or Melbourne to La Paz within a single day arrive without acclimatisation, leaving little time to upregulate protective antioxidant enzymes. Even experienced bushwalkers who have spent years on the Overland Track can find their physiology unready for a jump from sea level to a thin-air base camp, and moderate training at local altitudes does little to condition the lungs for partial pressures encountered above 4,000 metres.

  Genetics and Individual Susceptibility

  Not every traveller ascending to the same altitude develops pulmonary edema. Susceptibility clusters in families, and candidate genes include those encoding endothelial nitric oxide synthase and components of the renin-angiotensin system. Reduced nitric oxide production translates into stronger vasoconstrictive tone, and altered surfactant function may accelerate alveolar flooding once fluid leak begins.

  Men outnumber women in published series, reflecting both behavioural exposure and possible hormonal protection from oestrogen-mediated vasodilation. Children appear vulnerable, and even mild pre-existing pulmonary hypertension raises risk substantially. Repeat episodes are common, which is why clinicians often advise a permanent ceiling of 2,000 metres or routine use of pulmonary vasodilators for susceptible climbers.

  Clinical Presentation and Early Recognition

  The hallmarks are dyspnoea at rest, productive cough with pink frothy sputum, cyanosis, and rales confined to the lung bases. Symptoms usually begin two to four days after arrival and frequently worsen overnight as respiration slows and saturation drifts lower. Fatigue disproportionate to exertion is often the first clue, easily misattributed to jet lag.

  The Lake Louise criteria remain the standard bedside tool used by trek organisers. Any climber showing reduced exercise tolerance or unexplained fatigue above 3,000 metres should be evaluated for early pulmonary overload rather than dismissed as poor fitness. Pulse oximetry at rest and after mild exertion provides an objective measure, and a falling value across successive mornings should prompt immediate descent regardless of subjective feeling.

  Prevention Strategies and Modern Management

  Gradual ascent is the cornerstone. Climbers should sleep no more than 500 metres higher than the previous night once above 3,000 metres, with a rest day every three or four days. Travellers flying directly to Cusco or Lhasa need a full day of rest on arrival before any exertion.

  Field-tested recommendations for trekkers and their medical officers:

  • Plan a staged ascent rather than direct helicopter or vehicle drops to base camp.
  • Treat acute mountain sickness promptly, since headache and nausea often precede overt pulmonary edema.
  • Use acetazolamide 125 mg twice daily starting the day before ascent, continuing for two to four days at altitude.
  • Reserve nifedipine 30 mg slow-release daily for known susceptible individuals or when descent is delayed.
  • Carry a portable pulse oximeter and record resting saturation each morning; values below 80 percent warrant immediate action.
  • Coordinate evacuation plans with local rescue services before departure, including bilingual contacts.
  • Avoid alcohol and sedatives during the first forty-eight hours at altitude.

  Oxygen supplementation, a portable hyperbaric chamber, and continuous positive airway pressure have been used successfully in remote settings, including drills run by Australian state ambulance services and by the Royal Flying Doctor Service during remote clinic visits. Hospital-level care adds diuretics cautiously, recognising that the edema is driven by capillary leak rather than volume overload, and phosphodiesterase inhibitors such as sildenafil have a place where nifedipine is poorly tolerated.

  Before you book your next trekking expedition or your next conference flight, schedule a short travel medicine consultation with a respiratory clinician to map your physiology against the altitude profile of your planned itinerary.

  Richard Russell Nuffield Department of Clinical Medicine, University of Oxford (United Kingdom)
• Mona Bafadhel King’s College London (United Kingdom)
  David Jackson Guy’s and St Thomas’ Hospital, King’s College London (United Kingdom)
• James Chalmers University of Dundee (United Kingdom)
  David Price University of Aberdeen (United Kingdom)