A 27-year-old man presents to the emergency department with symptoms of dyspnea and cough for the past 3 days. Four days earlier, the patient (Mr M) and a friend arrived at Woodland Park, Colorado (elevation: 8400 ft) from their hometown of Atlanta, Georgia (elevation: 1050 ft). The patient states that their goal was to hike a 21-mile trail to the top of Pike’s Peak (elevation: 14,100 ft) in 2 days.
On the second day of their arrival at Woodland Park, they embarked on their hike covering 10 miles, climbing 4000 ft (elevation: 12,400 ft), before setting up camp for the night. During the first evening, Mr M reported the onset of a nonproductive cough, mild headache, and shortness of breath when lying down to sleep. The following day, Mr M’s cough worsened and was associated with dyspnea during the ascent. He states that he had to take multiple breaks to catch his breath. Based on these symptoms, his friend decided to discontinue the hike and begin their descent. During the descent, Mr M began coughing up pink, frothy sputum and experienced dyspnea during rest. A park ranger was notified and Mr M was taken to the nearest hospital.
Upon arrival at the emergency department, Mr M reports chest tightness, drowsiness, and headache. He denies nausea, vomiting, abdominal pain, chest pain, edema, hemoptysis, or medical history of asthma. No significant family history of cardiac or respiratory conditions is noted. Mr M lives a healthy lifestyle, is an avid hiker in the Appalachian Mountains of Georgia, is physically fit, and does not have a history of smoking cigarettes or use of any street drugs.
Upon physical examination, the patient is alert and oriented to person, place, time, and situation. He appears to be in mild respiratory distress with signs of dyspnea while sitting with his arms leaning on his legs to assist in breathing. The patient also has a productive-sounding cough. Cyanosis is present around his lips and throughout his oral mucosa. The patient is tachypneic and tachycardic and has decreased oxygen saturation (Table 1). Upon auscultation of the posterior lung fields, inspiratory crackles and bronchial breath sounds are heard bilaterally. No other abnormalities are noted on his physical examination.
Based on the patient’s history and presentation, the emergency department physician suspects high-altitude pulmonary edema (HAPE) and wants to confirm the diagnosis by ruling out other possible differentials through laboratory tests and imaging studies. Given the patient’s condition, he is quickly started on high-flow supplemental oxygen therapy via facemask. Complete blood cell count and metabolic panel findings indicate a mild elevation of white blood cells (11,000/µL).
A respiratory pathogen panel was negative for common viral and bacterial causes such as pneumonia, influenza, and SARS-CoV-2. Electrocardiography findings are normal, ruling out any associated cardiac complications. Bedside ultrasonography of the lung parenchyma reveals comet tail artifact, also known as lung rockets. This type of artifact is the ultrasonography equivalent of Kerley B lines indicating interstitial edema (Figure). Chest radiography reveals patchy opacities and alveolar infiltrates bilaterally.
High-Altitude Pulmonary Edema
High-altitude pulmonary edema is defined as noncardiogenic pulmonary edema caused by exaggerated hypoxic pulmonary vasoconstriction, high pulmonary artery pressure, and increased capillary pressure in individuals exposed to altitudes above 8200 ft.1 Environmental conditions at elevations above 8200 ft include lower oxygen concentrations, lower barometric air pressure, and lower temperatures. Hypobaric hypoxia causes the body to go through maladaptive responses, which can result in impairment of gas exchange from abnormal accumulation of plasma and reticulocytes in alveoli because of breakdown of pulmonary blood-gas barriers.2 Impairment of gas exchange can be fatal if no interventions are performed during initial symptom onset.
High-altitude pulmonary edema can occur in 2 distinct forms. The first form occurs in people who live at low altitudes and ascend rapidly to altitudes greater than 8200 ft. The second form, also known as re-entry HAPE, occurs in people who live at high altitudes and return home after a period of being at a lower altitude.3 The onset of HAPE usually presents within 2 to 4 days of ascent at an elevation above 8200 ft and rarely occurs after more than 4 to 5 days at the same altitude because of remodeling and adaptation.4
Major risk factors for HAPE include higher or greater changes in altitude, rapid ascent rate, and individual susceptibility; the effects of these risk factors are cumulative (Table 2).2 Furthermore, individuals with cardiopulmonary circulation abnormalities that may lead to pulmonary hypertension, such as mitral stenosis, primary pulmonary hypertension, unilateral absence of pulmonary artery, and patent foramen ovale, may be at an increased risk for HAPE at moderate and even low altitudes.5
Genetics can also play a role in susceptibility to developing HAPE. The genes associated with the occurrence of HAPE include polymorphisms in renin-angiotensin-aldosterone system (RAAS) pathway genes, more specifically with the angiotensin conversion enzyme (ACE), nitric oxide (NO) pathway genes (ie, NOS3), endothelin-1, and pulmonary surfactant proteins A1 and A2.6 Hypoxia-inducible factors (HIF), also known as the master regulators of oxygen homeostasis, are key transcription factors consisting of 1α (or 2α) and 1β subunits that form active transcriptional complexes under hypoxic conditions to stimulate expression of target genes.7 Hypoxia-inducible factors are involved in the release of vascular endothelial growth factor (VEGF) in the brain, erythropoiesis, and other pulmonary and cardiac functions at high altitudes.7 EPAS1 is a gene that codes for transcriptional regulator HIF-2α and is involved in decreasing inflammatory and vasoconstrictive responses to hypoxia, which allowed for the adaptation of people from Tibet and the Andes to live at high altitudes.5,7 Genetic predisposition determines how different groups of individuals will be affected and be able to adapt to high-altitude stress by a mechanism of minute ventilation.8
The incidence of HAPE among individuals at 14,763 ft is 0.6% to 6% and at 18,044 ft is 2% to 15%, with a faster ascent resulting in a higher incidence.8 In addition, those with a prior history of HAPE have a recurrence rate as high as 60% and should be managed accordingly.8
Signs and Symptoms of High-Altitude Pulmonary Edema
High-altitude pulmonary edema presents within 2 to 4 days of ascent to a high altitude and it is rarely observed at altitudes below 8200 ft or after 1 week of acclimatization to the exposed altitude.3 High-altitude pulmonary edema symptoms have an insidious onset and include nonproductive cough, decreased exercise tolerance, chest pain, and exertional dyspnea.8 As HAPE progresses, the cough and dyspnea worsen and orthopnea develops.2 In advanced HAPE progression, individuals can experience dyspnea at rest, severe exertional dyspnea, and the cough may become productive of blood-tinged, frothy sputum.8
Physical examination reveals tachycardia, tachypnea, cyanosis, and elevated body temperature that generally does not exceed 38.5 °C.4 Auscultation of the lung fields reveals discrete initial rales located over the middle lung fields.3 Furthermore, crackles may be unilateral or bilateral, but initially are auscultated in the right middle lobe and are heard first in the right axilla.9 Oxygen saturation is often 10% less than expected for altitude and the patient will often appear better than expected given their level of hypoxemia and oxygen saturation value.8
Treatment of High-Altitude Pulmonary Edema
Depending on the resources that are available at a medical facility, nonpharmacologic or pharmacologic interventions may be used. In the nonpharmacologic approach, immediate improvement of oxygenation either by supplemental oxygen, hyperbaric treatment, or rapid descent is the treatment of choice.3 Further studies have found that descent is the mainstay of treatment and individuals should try to passively descend at least 3280 ft or until symptom resolution.8 It is vital to minimize exertion on descent because exertion may increase hypoxemia from metabolic demands that can further increase pulmonary artery pressure and exacerbate edema formation.10
A suitable alternative to descent is supplemental oxygen delivery by nasal cannula or face mask at flow rates sufficient enough to achieve an oxygen saturation greater than 90%.10 Additionally, patients who have access to oxygen, whether in a hospital or high-altitude medical clinic, can be treated with oxygen at the current elevation without needing to descend to a lower elevation.10 When descent and supplemental oxygen administration are not feasible, simulated descent with the use of a portable hyperbaric chamber should be used at 2 to 4 pounds per square inch for several hours as a temporary measure until real descent can be achieved.4
Pharmacotherapy should not be regarded as a substitute for descent or supplemental oxygen and should only be used when the nonpharmacologic approaches are not feasible or available.11 Staying at the same altitude, receiving supplemental low flow oxygen for 24 to 48 hours to maintain an arterial saturation above 90%, and bed rest can lead to relief of symptoms within hours and complete clinical recovery within several days.4
Pharmacotherapy focuses on reduction of pulmonary artery pressure through the use of vasodilators, such as the calcium channel blocker nifedipine, which can reduce systolic pulmonary artery pressure by 50%.11 In hikers who develop HAPE at 14,957 ft elevation, taking extended-release nifedipine 20 mg every 6 hours leads to “a persistent relief of symptoms, improvement of gas exchange, and radiographic clearance of pulmonary edema over an observational period of 34 hours.”3 If nifedipine is unavailable, phosphodiesterase inhibitors such as tadalafil or sildenafil may help decrease pulmonary artery and capillary pressure.8 In one study, tadalafil was found to be effective in reducing the incidence of HAPE in susceptible adults, those with a previous history of HAPE, and those exposed to hypoxic high-altitude
High-altitude pulmonary edema is the more severe end of the high-altitude illness spectrum and it is the leading cause of death from altitude illness.13 If HAPE is left untreated, it can progress to dyspnea at rest and cyanosis. In a report by Jensen et al, the mortality rate from untreated HAPE is as high as 50%; when treated, the mortality rate is up to 11%.8 However, HAPE is completely and easily reversible if recognized early and treated properly.3 Individuals treated for HAPE may consider resuming ascent at an appropriate rate once they are asymptomatic, no longer require oxygen or vasodilator therapy, and have an increased exercise tolerance compared with symptom onset.8,9
The diagnosis of HAPE is based on results of a thorough history and physical examination.14 This case demonstrates the importance of recognizing the initial signs and symptoms of HAPE. If symptoms are recognized early, High-altitude pulmonary edema is an easily and completely reversible condition. Not only is it imperative for providers to accurately identify early signs of HAPE, but also it is important to educate patients traveling to high-altitude environments about the effects of hypoxic conditions. Simple interventions, such as having information readily available at trailheads warning of the condition and how to avoid it with acclimatization techniques, could better inform the public and decrease the incidence of HAPE. It is vital for hikers to recognize initial symptoms of HAPE so they can pursue treatment without developing long-term consequences.
Danila Teptsov, PA-S, is currently a PA student at Augusta University in Georgia. E. Rachel Fink, MPA, PA-C, is an assistant professor at the Augusta University Physician Assistant Program.
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This article originally appeared on Clinical Advisor