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Background: Many patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension (PH) wish to travel to altitude or by airplane, but their risk of hypoxia-related adverse health effects is insufficiently explored., Research Question: How does hypoxia, compared with normoxia, affect constant work-rate exercise test (CWRET) time in patients with PH, and which physiologic mechanisms are involved?, Study Design and Methods: Stable patients with PH with resting Pao 2  ≥ 7.3 kPa underwent symptom-limited cycling CWRET (60% of maximal workload) while breathing normobaric hypoxic air (hypoxia; Fio 2 , 15%) and ambient air (normoxia; Fio 2 , 21%) in a randomized cross-over design. Borg dyspnea score, arterial blood gases, tricuspid regurgitation pressure gradient, and mean pulmonary artery pressure/cardiac output ratio (mean PAP/CO) by echocardiography were assessed before and during end-CWRET., Results: Twenty-eight patients (13 women) were included: median (quartiles) age, 66 (54; 74) years; mean pulmonary artery pressure, 41 (29; 49) mm Hg; and pulmonary vascular resistance, 5.4 (4; 8) Wood units. Under normoxia and hypoxia, CWRET times were 16.9 (8.0; 30.0) and 6.7 (5.5; 27.3) min, respectively, with a median difference (95% CI) of -0.7 (-3.1 to 0.0) min corresponding to -7 (-32 to 0.0)% (P = .006). At end-exercise in normoxia and hypoxia, respectively, median values and differences in corresponding variables were as follows: Pao 2 : 8.0 vs 6.4, -1.7 (-2.7 to -1.1) kPa; arterial oxygen content: 19.2 vs 17.2, -1.7 (-3 to -0.1) mL/dL; Paco 2 : 4.7 vs 4.3, -0.3 (-0.5 to -0.1) kPa; lactate: 3.7 vs 3.7, 0.9 (0.1 to 1.6) mM (P < .05 all differences). Values for Borg scale score: 7 vs 6, 0.5 (0 to 1); tricuspid pressure gradient: 89 vs 77, -3 (-9 to 16) mm Hg; and mean PAP/CO: 4.5 vs 3.3, 0.3 (-0.8 to 1.4) Wood units remained unchanged. In multivariable regression, baseline pulmonary vascular resistance was the sole predictor of hypoxia-induced change in CWRET time., Interpretation: In patients with PH, short-time exposure to hypoxia was well tolerated but reduced CWRET time compared with normoxia in association with hypoxemia, lactacidemia, and hypocapnia. Because pulmonary hemodynamics and dyspnea at end-exercise remained unaltered, the hypoxia-induced exercise limitation may be due to a reduced oxygen delivery causing peripheral tissue hypoxia, augmented lactic acid loading and hyperventilation., Trial Registry: ClinicalTrials.gov; No.: NCT03592927; URL: www.clinicaltrials.gov., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Patients with COPD may experience acute mountain sickness (AMS) and other altitude-related adverse health effects (ARAHE) when traveling to high altitudes. This study evaluated whether dexamethasone, a drug used for the prevention of AMS in healthy individuals, would prevent AMS/ARAHE in patients with COPD., Methods: This placebo-controlled, double-blind, parallel-design trial included patients with COPD and Global Initiative for Obstructive Lung Disease grade 1 to 2 who were living below 800 m. Patients were randomized to receive dexamethasone (8 mg/d) or placebo starting on the day before ascent and while staying in a high-altitude clinic at 3,100 m for 2 days. The primary outcome assessed during the altitude sojourn was the combined incidence of AMS/ARAHE, defined as an Environmental Symptoms Questionnaire cerebral score evaluating AMS ≥ 0.7 or ARAHE requiring descent or an intervention., Results: In 60 patients randomized to receive dexamethasone (median [quartiles] age: 57 years [50; 60], FEV 1 86% predicted [70; 104]; PaO 2 at 760 m: 9.6 kPa [9.2; 10.0]), the incidence of AMS/ARAHE was 22% (13 of 60). In 58 patients randomized to receive placebo (age: 60 y [53; 64]; FEV 1 94% predicted [76; 103]; PaO 2 : 10.0 kPa [9.1; 10.5]), the incidence of AMS/ARAHE was 24% (14 of 58) (χ 2 statistic vs dexamethasone, P = .749). Dexamethasone mitigated the altitude-induced PaO 2 reduction compared with placebo (mean between-group difference [95% CI], 0.4 kPa [0.0-0.8]; P = .028)., Conclusions: In lowlanders with mild to moderate COPD, the incidence of AMS/ARAHE at 3,100 m was moderate and not reduced by dexamethasone treatment. Based on these findings, dexamethasone cannot be recommended for the prevention of AMS/ARAHE in patients with COPD undertaking high-altitude travel, although the drug mitigated the altitude-induced hypoxemia., Trial Registry: ClinicalTrials.gov; No.: NCT02450968; URL: www.clinicaltrials.gov., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)