The purpose of the current trial was to test the hypothesis that breathing oxygen-enriched air increases exercise performance of patients with pulmonary arterial or chronic thrombo-embolic pulmonary hypertension (PAH/CTEPH) and to investigate involved mechanisms. Twenty-two patients with PAH/CTEPH, eight women, means ± SD 61 ± 14 years, resting mPAP 35 ± 9mmHg, PaO₂ ambient air >7.3 kPa, underwent four bicycle ergospirometries to exhaustion on different days, while breathing oxygen-enriched (FiO₂ 0.50, hyperoxia) or ambient air (FiO₂ 0.21, normoxia) using progressively increased or constant load protocols (with 75% maximal work rate under FiO₂ 0.21), according to a randomized, sham-controlled, single-blind, cross-over design. ECG, pulmonary gas-exchange, arterial blood gases, cerebral and quadriceps muscle tissue oxygenation (CTO and QMTO) by near-infrared spectroscopy were measured. In ramp exercise, maximal work rate increased from 113 ± 38 W with normoxia to 132 ± 48 W with hyperoxia, mean difference 19.7 (95% CI 10.5–28.9) W, P < 0.001. Constant load exercise endurance increased from 571 ± 443 to 1242 ± 514 s, mean difference 671 (95% CI 392–951) s, P < 0.001. At end-exercise with hyperoxia PaO₂, CTO, QMTO, and PaCO₂ were increased, and ventilatory equivalents for CO₂ were reduced while the physiological dead space/tidal volume ratio remained unchanged. In patients with PAH/CTEPH, breathing oxygen-enriched air provides major increases in exercise performance. This is related to an improved arterial oxygenation that promotes oxygen availability in muscles and brain and to a reduction of the excessive ventilatory response to exercise thereby enhancing ventilatory efficiency. Patients with PAH/CTEPH may therefore benefit from oxygen therapy during daily physical activities and training. clinicaltrials.gov Identifier: NCT01748474.

The question addressed by the study: Chronic exposure to hypoxia increases pulmonary artery pressure (PAP) in highlanders, but the criteria for diagnosis of high-altitude pulmonary hypertension (HAPH) are debated. We assessed cardiac function and PAP in highlanders at 3250 m and explored HAPH prevalence using different definitions.Patients and methods: Central Asian highlanders free of overt cardiorespiratory disease, permanently living at 2500–3500 m compared to age-matched lowlanders living <800 m. Participants underwent echocardiography close to their altitude of residence (at 3250 mversus760 m).Results: 173 participants (97 highlanders, 76 lowlanders), mean±sdage 49±9 years (49% females) completed the study. Results in lowlandersversushighlanders were systolic PAP (23±5versus30±10 mmHg), right ventricular fractional area change (42±6%versus39±8%), tricuspid annular plane systolic excursion (2.1±0.3versus2.0±0.3 cm), right atrial volume index (20±6versus23±8 mL·m⁻²), left ventricular ejection fraction (62±4%versus57±5%) and stroke volume (64±10versus57±11 mL); all between-group comparisons p<0.05. Depending on criteria, HAPH prevalence varied between 6% and 35%.The answer to the question: Chronic exposure to hypoxia in highlanders is associated with higher PAP and slight alterations in right and left heart function compared to lowlanders. The prevalence of HAPH in this large highlander cohort varies between 6% according to expert consensus definition of chronic high-altitude disease to 35% according to the most recent definition of pulmonary hypertension proposed for lowlanders.

Study question: We investigated whether domiciliary oxygen therapy (DOXT) increases exercise capacity and quality of life in patients with pulmonary arterial or distal chronic thromboembolic pulmonary hypertension (PAH/CTEPH) presenting with mild resting hypoxaemia and exercise-induced oxygen desaturation.Materials and methods: 30 patients with PAH/CTEPH, mean±sdage 60±15 years, pulmonary artery pressure 39±11 mmHg, resting arterial oxygen saturation measured by pulse oximetry (SpO₂) ≥90%,SpO₂drop during a 6-min walk test ≥4%, on pulmonary hypertension-targeted medication, were randomised in a double-blind crossover protocol to DOXT and placebo (ambient air) treatment, each over 5 weeks, at 3 L·min⁻¹vianasal cannula overnight and when resting during the day. Treatment periods were separated by 2 weeks of washout. Co-primary outcomes were changes in 6-min walk distance (6MWD, breathing ambient air) and physical functioning scale of the 36-item short-form medical outcome questionnaire during treatment periods.Results: DOXT increased the 6MWD from baseline 478±113 m by a mean (95% CI) of 19 (6–32) m, and physical functioning from 52±29 by 4 (0–8) points. Corresponding changes with placebo were 1 (−11–13) m in 6MWD and −2 (−6–2) points in physical functioning. Between-treatment differences in changes were 6MWD 18 (1–35) m (p=0.042) and physical functioning 6 (1–11) points (p=0.029). DOXT significantly improved the New York Heart Association functional classversusplacebo.Answer to the question: This first randomised trial in PAH/CTEPH patients with exercise-induced hypoxaemia demonstrates that DOXT improves exercise capacity, quality of life and functional class. The results support large long-term randomised trials of DOXT in PAH/CTEPH.

Importance: With increasing altitude, the partial pressure of inspired oxygen decreases and, consequently, the Pao₂ decreases. Even though this phenomenon is well known, the extent of the reduction as a function of altitude remains unknown.Objective: To calculate an effect size estimate for the decrease in Pao₂ with each kilometer of vertical gain among healthy unacclimatized adults and to identify factors associated with Pao₂ at high altitude (HA).Data Sources: A systematic search of PubMed and Embase was performed from database inception to April 11, 2023. Search terms included arterial blood gases and altitude.Study Selection: A total of 53 peer-reviewed prospective studies in healthy adults providing results of arterial blood gas analysis at low altitude (<1500 m) and within the first 3 days at the target altitude (≥1500 m) were analyzed.Data Extraction and Synthesis: Primary and secondary outcomes as well as study characteristics were extracted from the included studies, and individual participant data (IPD) were requested. Estimates were pooled using a random-effects DerSimonian-Laird model for the meta-analysis.Main Outcomes and Measures: Mean effect size estimates and 95% CIs for reduction in Pao₂ at HA and factors associated with Pao₂ at HA in healthy adults.Results: All of the 53 studies involving 777 adults (mean [SD] age, 36.2 [10.5] years; 510 men [65.6%]) reporting 115 group ascents to altitudes between 1524 m and 8730 m were included in the aggregated data analysis; 13 of those studies involving 305 individuals (mean [SD] age, 39.8 [13.6] years; 185 men [60.7%]) reporting 29 ascents were included in the IPD analysis. The estimated effect size of Pao₂ was −1.60 kPa (95% CI, −1.73 to −1.47 kPa) for each 1000 m of altitude gain (τ² = 0.14; I² = 86%). The Pao₂ estimation model based on IPD data revealed that target altitude (−1.53 kPa per 1000 m; 95% CI, −1.63 to −1.42 kPa per 1000 m), age (−0.01 kPa per year; 95% CI, −0.02 to −0.003 kPa per year), and time spent at an altitude of 1500 m or higher (0.16 kPa per day; 95% CI, 0.11-0.21 kPa per day) were significantly associated with Pao₂.Conclusions and Relevance: In this systematic review and meta-analysis, the mean decrease in Pao₂ was 1.60 kPa per 1000 m of vertical ascent. This effect size estimate may improve the understanding of physiological mechanisms, assist in the clinical interpretation of acute altitude illness in healthy individuals, and serve as a reference for physicians counseling patients with cardiorespiratory disease who are traveling to HA regions.

Objective: Neurocognitive functions are affected by high altitude, however the altitude effects of acclimatization and repeated exposures are unclear. We investigated the effects of acute, subacute and repeated exposure to 5,050 m on cognition among altitude-naïve participants compared to control subjects tested at low altitude. Methods: Twenty-one altitude-naïve individuals (25.3 ± 3.8 years, 13 females) were exposed to 5,050 m for 1 week (Cycle 1) and re-exposed after a week of rest at sea-level (Cycle 2). Baseline (BL, 520 m), acute (Day 1, HA1) and acclimatization (Day 6, HA6, 5,050 m) measurements were taken in both cycles. Seventeen control subjects (24.9 ± 2.6 years, 12 females) were tested over a similar period in Calgary, Canada (1,103 m). The Reaction Time (RTI), Attention Switching Task (AST), Rapid Visual Processing (RVP) and One Touch Stockings of Cambridge (OTS) tasks were administered and outcomes were expressed in milliseconds/frequencies. Lake Louise Score (LLS) and blood oxygen saturation (SpO₂) were recorded. Results: In both cycles, no significant changes were found with acute exposure on the AST total score, mean latency and SD. Significant changes were found upon acclimatization solely in the altitude group, with improved AST Mean Latency [HA1 (588 ± 92) vs. HA6 (526 ± 91), p < 0.001] and Latency SD [HA1 (189 ± 86) vs. HA6 (135 ± 65), p < 0.001] compared to acute exposure, in Cycle 1. No significant differences were present in the control group. When entering Acute SpO₂ (HA1-BL), Acclimatization SpO₂ (HA6-BL) and LLS score as covariates for both cycles, the effects of acclimatization on AST outcomes disappeared indicating that the changes were partially explained by SpO₂ and LLS. The changes in AST Mean Latency [ΔBL (−61.2 ± 70.2) vs. ΔHA6 (−28.0 ± 58), p = 0.005] and the changes in Latency SD [ΔBL (−28.4 ± 41.2) vs. ΔHA6 (−0.2235 ± 34.8), p = 0.007] across the two cycles were smaller with acclimatization. However, the percent changes did not differ between cycles. These results indicate independent effects of altitude across repeated exposures. Conclusions: Selective and sustained attention are impaired at altitude and improves with acclimatization.The observed changes are associated, in part, with AMS score and SpO₂. The gains in cognition with acclimatization during a first exposure are not carried over to repeated exposures.