A 45-year-old healthy man wishes to climb Mount Kilimanjaro (5895 m) in a 5-day period, starting at 1800 m. The results of a recent exercise stress test were normal; he runs 10 km 4 or 5 times per week and finished a marathon in less than 4 hours last year. He wants to know how he can prevent becoming ill at high altitude and whether training or sleeping under normobaric hypoxic conditions in the weeks before the ascent would be helpful. What would you advise?

No abstract

At any point 1-5 days following ascent to altitudes ⩾2500 m, individuals are at risk of developing one of three forms of acute altitude illness: acute mountain sickness, a syndrome of nonspecific symptoms including headache, lassitude, dizziness and nausea; high-altitude cerebral oedema, a potentially fatal illness characterised by ataxia, decreased consciousness and characteristic changes on magnetic resonance imaging; and high-altitude pulmonary oedema, a noncardiogenic form of pulmonary oedema resulting from excessive hypoxic pulmonary vasoconstriction which can be fatal if not recognised and treated promptly. This review provides detailed information about each of these important clinical entities. After reviewing the clinical features, epidemiology and current understanding of the pathophysiology of each disorder, we describe the current pharmacological and nonpharmacological approaches to the prevention and treatment of these diseases.

Background Pulmonary hypertension (PH) is associated with increased morbidity across the cardiopulmonary disease spectrum. Based largely on expert consensus opinion, PH is defined by a mean pulmonary artery pressure (mPAP) ≥25 mmHg. Although mPAP levels below this threshold are common among populations at risk for PH, the relevance of mPAP <25 mmHg to clinical outcome is unknown. Methods and Results We analyzed retrospectively all US veterans undergoing right heart catheterization (RHC)(2007–2012) in the Veterans Affairs health care system (N=21,727; 908 day median follow-up). Cox proportional hazards models were used to evaluate the association between mPAP and outcomes of all-cause mortality and hospitalization, adjusted for clinical covariates. When treating mPAP as a continuous variable, the mortality hazard increased beginning at 19 mmHg (HR=1.183, 95% CI [1.004–1.393]) relative to 10 mmHg. Therefore, patients were stratified into three groups: referent (≤18 mmHg; N=4,207), borderline PH (19–24 mmHg; N=5,030), and PH (≥25 mmHg; N=12,490). The adjusted mortality hazard was increased for borderline PH (HR=1.23, 95% CI [1.12–1.36], P<0.0001) and PH (HR=2.16, 95% CI [1.96–2.38], P<0.0001) compared to the referent group. The adjusted hazard for hospitalization was also increased in borderline PH (HR=1.07, 95% CI [1.01–1.12], P=0.0149) and PH (HR=1.15, 95% CI [1.09–1.22], P<0.0001). The borderline PH cohort remained at increased risk for mortality after excluding the following high-risk subgroups: patients with pulmonary artery wedge pressure >15 mmHg, pulmonary vascular resistance ≥3.0 Wood units, or inpatient status at the time of RHC. Conclusions These data illustrate a continuum of risk according to mPAP level, and that borderline PH is associated with increased mortality and hospitalization. Future investigations are needed to test the generalizability of our findings to other populations and study the effect of treatment on outcome in borderline PH.

High-altitude pulmonary edema (HAPE) develops in rapidly ascending nonacclimatized healthy individuals at altitudes above 3,000 m. An excessive rise in pulmonary artery pressure (PAP) preceding edema formation is the crucial pathophysiological factor because drugs that lower PAP prevent HAPE. Measurements of nitric oxide (NO) in exhaled air, of nitrites and nitrates in bronchoalveolar lavage (BAL) fluid, and forearm NO-dependent endothelial function all point to a reduced NO availability in hypoxia as a major cause of the excessive hypoxic PAP rise in HAPE-susceptible individuals. Studies using right heart catheterization or BAL in incipient HAPE have demonstrated that edema is caused by an increased microvascular hydrostatic pressure in the presence of normal left atrial pressure, resulting in leakage of large-molecular-weight proteins and erythrocytes across the alveolarcapillary barrier in the absence of any evidence of inflammation. These studies confirm in humans that high capillary pressure induces a high-permeability-type lung edema in the absence of inflammation, a concept first introduced under the term "stress failure." Recent studies using microspheres in swine and magnetic resonance imaging in humans strongly support the concept and primacy of nonuniform hypoxic arteriolar vasoconstriction to explain how hypoxic pulmonary vasoconstriction occurring predominantly at the arteriolar level can cause leakage. This compelling but as yet unproven mechanism predicts that edema occurs in areas of high blood flow due to lesser vasoconstriction. The combination of high flow at higher pressure results in pressures, which exceed the structural and dynamic capacity of the alveolar capillary barrier to maintain normal alveolar fluid balance. pulmonary artery pressure; hypoxic pulmonary vasoconstriction; nitric oxide; inflammation; alveolar fluid clearance; pathophysiology; review CLINICAL PICTUREHigh-altitude pulmonary edema (HAPE) is noncardiogenic pulmonary edema that usually occurs at altitudes above 3,000 m in rapidly ascending nonacclimatized individuals within the first 2-5 days after arrival. It may also occur in high-altitude dwellers who return from sojourns at low altitude. The first medical description of HAPE was published in Peru and recognized the latter form, also called reentry HAPE, as a pulmonary edema associated with electrographic signs of right ventricular overload (67). The first cases of HAPE in unacclimatized lowlanders climbing to high altitude were reported from the Rocky Mountains (53). The two forms very probably share the same pathophysiology.The reader is referred to other reviews (9,41,96,97) for an extensive presentation of the clinical picture. In this review, we point out some particular characteristics that might elucidate the underlying pathophysiology and are revealed by classical and newly evolving pathophysiological concepts.The prevalence of HAPE depends on the degree of susceptibility, the rate of ascent, and the final altitude. At an altitude of 4,500 m, the prevalence may ...

BackgroundAppropriate interpretation of pulmonary function tests (PFTs) involves the classification of observed values as within/outside the normal range based on a reference population of healthy individuals, integrating knowledge of physiologic determinants of test results into functional classifications, and integrating patterns with other clinical data to estimate prognosis. In 2005, the American Thoracic Society and the European Respiratory Society jointly adopted technical standards for the interpretation of PFTs. We aimed to update the 2005 recommendations and incorporate evidence from recent literature to establish new standard for PFT interpretation.MethodsThis technical standards document was developed by an international joint task force, appointed by the European Respiratory Society and the American Thoracic Society with multidisciplinary expertise in conducting and interpreting pulmonary function tests, and developing international standards. A comprehensive literature review was conducted, and published evidence was reviewed.ResultsRecommendations for the choice of reference equations and limits of normal of the healthy population to identify individuals with unusually low or high results, respectively are discussed. Interpretation strategies for bronchodilator responsiveness testing, limits of natural changes over time and severity are also updated. Interpretation of measurements made by spirometry, lung volumes and gas transfer are described as they relate to underlying pathophysiology with updated classification protocols of common impairments.ConclusionsPFTs interpretation must be complemented with clinical expertise and consider the inherent biological variability of the test and the uncertainty of the test result to ensure appropriate interpretation of an individual's lung function measurements.

These data indicate that HAPE-S subjects may have abnormal pulmonary vascular responses not only to hypoxia but also to supine bicycle exercise under normoxic conditions. Thus, Doppler echocardiography during supine bicycle exercise or after 90 min of hypoxia may be useful noninvasive screening methods to identify subjects susceptible to HAPE.

During the ongoing coronavirus disease (COVID-19) pandemic, reports in social media and the lay press indicate that a subset of patients are presenting with severe hypoxemia in the absence of dyspnea, a problem unofficially referred to as “silent hypoxemia.” To decrease the risk of complications in such patients, one proposed solution has been to have those diagnosed with COVID-19 but not sick enough to warrant admission monitor their arterial oxygenation by pulse oximetry at home and present for care when they show evidence of hypoxemia. Though the ease of use and low cost of pulse oximetry makes this an attractive option for identifying problems at an early stage, there are important considerations with pulse oximetry about which patients and providers may not be aware that can interfere with successful implementation of such monitoring programs. Only a few independent studies have examined the performance of pocket oximeters and smart phone–based systems, but the limited available data raise questions about their accuracy, particularly as saturation falls below 90%. There are also multiple sources of error in pulse oximetry that must be accounted for, including rapid fluctuations in measurements when the arterial oxygen pressure/tension falls on the steep portion of the dissociation curve, data acquisition problems when pulsatile blood flow is diminished, accuracy in the setting of severe hypoxemia, dyshemoglobinemias, and other problems. Recognition of these issues and careful counseling of patients about the proper means for measuring their oxygen saturation and when to seek assistance can help ensure successful implementation of needed monitoring programs.