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Red blood cell (RBC) metabolic reprogramming upon exposure to high altitude contributes to physiological human adaptations to hypoxia, a multifaceted process critical to health and disease. To delve into the molecular underpinnings of this phenomenon, first, we performed a multi-omics analysis of RBCs from six lowlanders after exposure to high-altitude hypoxia, with longitudinal sampling at baseline, upon ascent to 5,100 m and descent to sea level. Results highlighted an association between erythrocyte levels of 2,3-bisphosphoglycerate (BPG), an allosteric regulator of hemoglobin that favors oxygen off-loading in the face of hypoxia, and expression levels of the Rhesus blood group RHCE protein. We then expanded on these findings by measuring BPG in RBCs from 13,091 blood donors from the Recipient Epidemiology and Donor Evaluation Study. These data informed a genome-wide association study using BPG levels as a quantitative trait, which identified genetic polymorphisms in the region coding for the Rhesus blood group RHCE as critical determinants of BPG levels in erythrocytes from healthy human volunteers. Mechanistically, we suggest that the Rh group complex, which participates in the exchange of ammonium with the extracellular compartment, may contribute to intracellular alkalinization, thus favoring BPG mutase activity.

Abstract Chronic mountain sickness is a maladaptive syndrome that affects individuals living permanently at high altitude and is characterized primarily by excessive erythrocytosis (EE). Recent results concerning the impact of EE in Andean highlanders on clotting and the possible promotion of hypercoagulability, which can lead to thrombosis, were contradictory. We assessed the coagulation profiles of Andeans highlanders with and without excessive erythrocytosis (EE+ and EE−). Blood samples were collected from 30 EE+ and 15 EE− in La Rinconada (Peru, 5100–5300 m a.s.l.), with special attention given to the sampling pre‐analytical variables. Rotational thromboelastometry tests were performed at both native and normalized (40%) haematocrit using autologous platelet‐poor plasma. Thrombin generation, dosages of clotting factors and inhibitors were measured in plasma samples. Data were compared between groups and with measurements performed at native haematocrit in 10 lowlanders (LL) at sea level. At native haematocrit, in all rotational thromboelastometry assays, EE+ exhibited hypocoagulable profiles (prolonged clotting time and weaker clot strength) compared with EE− and LL (all P

Background Hypoxia is a trigger for sympathetic activation and autonomic cardiovascular dysfunction. Pulmonary vascular disease (PVD) is associated with hypoxaemia, which increases with altitude. The aim was to investigate how exposure of patients with PVD to hypobaric hypoxia at altitude affects autonomic cardiovascular regulation. Methods In a randomised crossover study, patients with PVD were studied for 1 day and one night at an altitude of 2500 m (hypobaric hypoxia) and low altitude at 470 m in a random order. Outcomes were heart rate variability (HRV) in the time domain and in the frequency domain (low frequency (LF)/high frequency (HF) and LF/HF) and heart rate (HR) during day and night and baroreflex sensitivity (BRS). Results In 25 patients with PVD (72% pulmonary arterial hypertension and 28% distal chronic thromboembolic pulmonary hypertension; mean±sd age 60.7±13.6 years), exposure to altitude resulted in significant increases in awake HR by 9.4 bpm (95% confidence interval (CI) 6.3–12.4, p

Background: Hypoxia and old age impair postural control and may therefore enhance the risk of accidents. We investigated whether acetazolamide, the recommended drug for prevention of acute mountain sickness, may prevent altitude-induced deterioration of postural control in older persons.Methods: In this parallel-design trial, 95 healthy volunteers, 40 years of age or older, living

Background and aims: Chinese herbal medicine (CHM) was used to prevent and treat coronavirus disease 2019 (COVID-19) in clinical practices. Many studies have demonstrated that the combination of CHM and Western medicine can be more effective in treating COVID-19 compared to Western medicine alone. However, evidence-based studies on the prevention in undiagnosed or suspected cases remain scarce. This systematic review and meta-analysis aimed to investigate the effectiveness of CHM in preventing recurrent, new, or suspected COVID-19 diseases.Methods: We conducted a comprehensive search using ten databases including articles published between December 2019 and September 2023. This search aimed to identify studies investigating the use of CHM to prevent COVID-19. Heterogeneity was assessed by a random-effects model. The relative risk (RR) and mean differences were calculated using 95% confidence intervals (CI). The modified Jadad Scale and the Newcastle-Ottawa Scale (NOS) were employed to evaluate the quality of randomized controlled trials and cohort studies, respectively.Results: Seventeen studies with a total of 47,351 patients were included. Results revealed that CHM significantly reduced the incidence of COVID-19 (RR = 0.24, 95% CI = 0.11–0.53, p = 0.0004), influenza (RR = 0.37, 95% CI = 0.18–0.76, p = 0.007), and severe pneumonia exacerbation rate (RR = 0.17, 95% CI = 0.05–0.64, p = 0.009) compared to non-treatment or conventional control group. Evidence evaluation indicated moderate quality evidence for COVID-19 incidence and serum complement components C3 and C4 in randomized controlled trials. For the incidence of influenza and severe pneumonia in RCTs as well as the ratio of CD4+/CD8+ lymphocytes, the evidence quality was low. The remaining outcomes including the disappearance rate of symptoms and adverse reactions were deemed to be of very low quality.Conclusion: CHM presents a promising therapeutic option for the prevention of COVID-19. However, additional high-quality clinical trials are needed to further strengthen evidential integrity.

Introduction: This prospective cohort study assessed the effects of chronic hypoxaemia due to high-altitude residency on the cerebral tissue oxygenation (CTO) and cerebrovascular reactivity.Methods: Highlanders, born, raised, and currently living above 2,500 m, without cardiopulmonary disease, participated in a prospective cohort study from 2012 until 2017. The measurements were performed at 3,250 m. After 20 min of rest in supine position while breathing ambient air (FiO2 0.21) or oxygen (FiO2 1.0) in random order, guided hyperventilation followed under the corresponding gas mixture. Finger pulse oximetry (SpO2) and cerebral near-infrared spectroscopy assessing CTO and change in cerebral haemoglobin concentration (cHb), a surrogate of cerebral blood volume changes and cerebrovascular reactivity, were applied. Arterial blood gases were obtained during ambient air breathing.Results: Fifty three highlanders, aged 50 ± 2 years, participated in 2017 and 2012. While breathing air in 2017 vs. 2012, PaO2 was reduced, mean ± SE, 7.40 ± 0.13 vs. 7.84 ± 0.13 kPa; heart rate was increased 77 ± 1 vs. 70 ± 1 bpm (p < 0.05) but CTO remained unchanged, 67.2% ± 0.7% vs. 67.4% ± 0.7%. With oxygen, SpO2 and CTO increased similarly in 2017 and 2012, by a mean (95% CI) of 8.3% (7.5–9.1) vs. 8.5% (7.7–9.3) in SpO2, and 5.5% (4.1–7.0) vs. 4.5% (3.0–6.0) in CTO, respectively. Hyperventilation resulted in less reduction of cHb in 2017 vs. 2012, mean difference (95% CI) in change with air 2.0 U/L (0.3–3.6); with oxygen, 2.1 U/L (0.5–3.7).Conclusion: Within 5 years, CTO in highlanders was preserved despite a decreased PaO2. As this was associated with a reduced response of cerebral blood volume to hypocapnia, adaptation of cerebrovascular reactivity might have occurred.

Background The course of pulmonary arterial wedge pressure (PAWP) during exercise in patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension (PAH/CTEPH), further abbreviated as pulmonary vascular disease (PVD), is still unknown. The aim of the study was to describe PAWP during exercise in patients with PVD. Methods In this cross-sectional study, right heart catheter (RHC) data including PAWP, recorded during semi-supine, stepwise cycle exercise in patients with PVD, were analysed retrospectively. We investigated PAWP changes during exercise until end-exercise. Results In 121 patients (59 female, 66 CTEPH, 55 PAH, 62±17 years) resting PAWP was 10.2±4.1 mmHg. Corresponding peak changes in PAWP during exercise were +2.9 mmHg (95% CI 2.1–3.7 mmHg, p2 WU are common in patients with PVD aged ≥50 years without exceeding the PAWP of 25 mmHg during exercise.

Background COPD may predispose to symptomatic pulmonary hypertension at high altitude. We investigated haemodynamic changes in lowlanders with COPD ascending to 3100 m and evaluated whether preventive acetazolamide treatment would attenuate the altitude-induced increase in pulmonary artery pressure (PAP). Methods In this randomised, placebo-controlled, double-blind, parallel-group trial, patients with COPD Global Initiative for Chronic Obstructive Lung Disease grades 2–3 who were living 92% and arterial carbon dioxide tension

Background/aims Amongst numerous travellers to high altitude (HA) are many with the highly prevalent COPD, who are at particular risk for altitude-related adverse health effects (ARAHE). We then investigated the hypoxia-altitude simulation test (HAST) to predict ARAHE in COPD patients travelling to altitude. Methods This prospective diagnostic accuracy study included 75 COPD patients: 40 women, age 58±9 years, forced expiratory volume in 1 s (FEV1) 40–80% pred, oxygen saturation measured by pulse oximetry (SpO2) ≥92% and arterial carbon dioxide tension (PaCO2) 30 min or 75% for >15 min) or intercurrent illness was observed. Results ARAHE occurred in 50 (66%) patients and 23 out of 75 (31%) were positive on HAST according to SpO2, and 11 out of 64 (17%) according to PaO2. For SpO2/PaO2 we report a sensitivity of 46/25%, specificity of 84/95%, positive predictive value of 85/92% and negative predictive value of 44/37%. Conclusion In COPD patients ascending to HA, ARAHE are common. Despite an acceptable positive predictive value of the HAST to predict ARAHE, its clinical use is limited by its insufficient sensitivity and overall accuracy. Counselling COPD patients before altitude travel remains challenging and best focuses on early recognition and treatment of ARAHE with oxygen and descent.

Hypoxia at high altitude facilitates changes in ventilatory control that can lead to nocturnal periodic breathing (nPB). Here, we introduce a placebo‐controlled approach to prevent nPB by increasing inspiratory CO2 and used it to assess whether nPB contributes to the adverse effects of hypoxia on sleep architecture. In a randomized, single‐blinded, crossover design, 12 men underwent two sojourns (three days/nights each, separated by 4 weeks) in hypobaric hypoxia corresponding to 4000 m altitude, with polysomnography during the first and third night of each sojourn. During all nights, subjects' heads were encompassed by a canopy retaining exhaled CO2, and CO2 concentration in the canopy (i.e. inspiratory CO2 concentration) was controlled by adjustment of fresh air inflow. Throughout the placebo sojourn inspiratory CO2 was ≤0.2%, whereas throughout the other sojourn it was increased to 1.76% (IQR, 1.07%–2.44%). During the placebo sojourn, total sleep time (TST) with nPB was 54.3% (37.4%–80.8%) and 45.0% (24.5%–56.5%) during the first and the third night, respectively (P = 0.042). Increased inspiratory CO2 reduced TST with nPB by an absolute 38.1% (28.1%–48.1%), the apnoea–hypopnoea index by 58.1/h (40.1–76.1/h), and oxygen desaturation index ≥3% by 56.0/h (38.9.1–73.2/h) (all P < 0.001), whereas it increased the mean arterial oxygen saturation in TST by 2.0% (0.4%–3.5%, P = 0.035). Increased inspiratory CO2 slightly increased the percentage of N3 sleep during the third night (P = 0.045), without other effects on sleep architecture. Increasing inspiratory CO2 effectively prevented hypoxia‐induced nPB without affecting sleep macro‐architecture, indicating that nPB does not explain the sleep deterioration commonly observed at high altitudes. Key points: Periodic breathing is common during sleep at high altitude, and it is unclear how this affects sleep architecture.We developed a placebo‐controlled approach to prevent nocturnal periodic breathing (nPB) with inspiratory CO2 administration and used it to assess the effects of nPB on sleep in hypobaric hypoxia.Nocturnal periodic breathing was effectively mitigated by an increased inspiratory CO2 fraction in a blinded manner.Prevention of nPB did not lead to relevant changes in sleep architecture in hypobaric hypoxia.We conclude that nPB does not explain the deterioration in sleep architecture commonly observed at high altitude. [ABSTRACT FROM AUTHOR]

Exposure to chronic hypobaric hypoxia imposes a significant physiological burden to more than 80 million humans living above 2500 m throughout the world. Among them, 50 000 live in the world's highest city, La Rinconada, located at 5000–5300 m in southern Peru. Expedition 5300 is the first scientific and medical programme led in La Rinconada to investigate the physiological adaptations and altitude‐related health issues in this unique population. Dwellers from La Rinconada have very high haemoglobin concentration (20.3 ± 2.4 g/dL; n = 57) and those with chronic mountain sickness (CMS) exhibit even higher concentrations (23.1 ± 1.7 g/dL; n = 150). These values are associated with large total haemoglobin mass and blood volume, without an associated iron deficit. These changes in intravascular volumes lead to a substantial increase in blood viscosity, which is even larger in CMS patients. Despite these large haematological changes, 24 h blood pressure monitoring is essentially normal in La Rinconada, but some results suggest impaired vascular reactivity. Echocardiography revealed large right heart dilatation and high pulmonary arterial pressure as well as left ventricle concentric remodelling and grade I diastolic dysfunction. These changes in heart dimension and function tend to be more severe in highlanders with CMS. Polygraphy evaluations revealed a large reduction in nocturnal pulse oxygen saturation (median SpO2 = 79%), which is even more severe in CMS patients who also tended to show a higher oxygen desaturation index. The population of La Rinconada offers a unique opportunity to investigate the human responses to chronic severe hypoxia, at an altitude that is probably close to the maximum altitude human beings can permanently tolerate without presenting major health issues. [ABSTRACT FROM AUTHOR]

Background: Pulmonary endarterectomy (PEA) is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension (CTEPH) with accessible lesions. Breathing pure oxygen (hyperoxia) during right heart catheterization (RHC) allows for the calculation of the right-to-left shunt fraction (Qs/Qt). In the absence of intracardiac shunt, Qs/Qt can be used as a marker of ventilation–perfusion mismatch in patients with CTEPH. This study involved investigating Qs/Qt after PEA and its relation to other disease-specific outcomes. Study design and Methods: This study is a retrospective study that focuses on patients with operable CTEPH who had Qs/Qt assessment during RHC before and 1 year after PEA. Additionally, 6 min walking distance (6MWD), WHO functional class (WHO-FC), and NT-proBNP were assessed to calculate a four-strata risk score. Results: Overall, 16 patients (6 females) with a median age of 66 years (quartiles 55; 74) were included. After PEA, an improvement in mean pulmonary artery pressure (38 [32; 41] to 24 [18; 28] mmHg), pulmonary vascular resistance (5.7 [4.0; 6.8] to 2.5 [1.4; 3.8] WU), oxygen saturation (92 [88; 93]% to 94 [93; 95]%), WHO-FC, and risk score was observed (all p < 0.05). No improvement in median Qs/Qt could be detected (13.7 [10.0; 17.5]% to 13.0 [11.2; 15.6]%, p = 0.679). A total of 7 patients with improved Qs/Qt had a significant reduction in risk score compared to those without improved Qs/Qt. Conclusion: PEA did not alter Qs/Qt assessed after 1 year in operable CTEPH despite an improvement in hemodynamics and risk score, potentially indicating a persistent microvasculopathy. In patients whose shunt fraction improved with PEA, the reduced shunt was associated with an improvement in risk score.

Abstract Cerebral autoregulation (CA) is impaired during acute high-altitude (HA) exposure, however, effects of temporarily living high and working higher on CA require further investigation. In 18 healthy lowlanders (11 women), we hypothesized that the cerebral autoregulation index (ARI) assessed by the percentage change in middle cerebral artery peak blood velocity (Δ%MCAv)/percentage change in mean arterial blood pressure (Δ%MAP) induced by a sit-to-stand maneuver, is (i) reduced on Day1 at 5050 m compared to 520 m, (ii) is improved after 6 days at 5050 m, and (iii) is less impaired during re-exposure to 5050 m after 7 days at 520 m compared to Cycle1. Participants spent 4-8 h/day at 5050 m and slept at 2900 m similar to real-life working shifts. High/low ARI indicate impaired/intact CA, respectively. With the sit-to-stand at 520 m, mean (95% CI) in ΔMAP and ΔMCAv were − 26% (− 41 to − 10) and − 13% (− 19 to − 7), P

ObjectiveAltitude travel is increasingly popular also for middle-aged and older tourists and professionals. Due to the sensitivity of the central nervous system to hypoxia, altitude exposure may impair visuomotor performance although this has not been extensively studied. Therefore, we investigated whether a sojourn at moderately high altitude is associated with visuomotor performance impairments in healthy adults, 40y of age or older, and whether this adverse altitude-effect can be prevented by acetazolamide, a drug used to prevent acute mountain sickness.MethodsIn this randomized placebo-controlled parallel-design trial, 59 healthy lowlanders, aged 40-75y, were assigned to acetazolamide (375 mg/day, n = 34) or placebo (n = 25), administered one day before ascent and while staying at high altitude (3100m). Visuomotor performance was assessed at 760m and 3100m after arrival and in the next morning (post-sleep) by a computer-assisted test (Motor-Task-Manager). It quantified deviation of a participant-controlled cursor affected by rotation during target tracking. Primary outcome was the directional error during post-sleep recall of adaptation to rotation estimated by multilevel linear regression modeling. Additionally, adaptation, immediate recall, and correct test execution were evaluated.ResultsCompared to 760m, assessments at 3100m with placebo revealed a mean (95%CI) increase in directional error during adaptation and immediate recall by 1.9° (0.2 to 3.5, p = 0.024) and 1.1° (0.4 to 1.8, p = 0.002), respectively. Post-sleep recall remained unchanged (p = NS), however post-sleep correct test execution was 14% less likely (9 to 19, pConclusionIn healthy individuals, 40y of age or older, altitude exposure impaired adaptation to and immediate recall and correct execution of a visuomotor task. Preventive acetazolamide treatment improved visuomotor performance after one night at altitude and increased the probability of correct test execution compared to placebo.Clinicaltrials.gov identifierClinicalTrials.gov NCT03536520.

Abstract This trial evaluates whether nocturnal oxygen therapy (NOT) during a stay at 2048 m improves altitude-induced exercise intolerance in lowlanders with chronic obstructive pulmonary disease (COPD). 32 lowlanders with moderate to severe COPD, mean ± SD forced expiratory volume in the first second of expiration (FEV1) 54 ± 13% predicted, stayed for 2 days at 2048 m twice, once with NOT, once with placebo according to a randomized, crossover trial with a 2-week washout period at

Background: Effects of prolonged and repeated high-altitude exposure on oxygenation and control of breathing remain uncertain. We hypothesized that prolonged and repeated high-altitude exposure will improve altitude-induced deoxygenation and breathing instability.Methods: 21 healthy lowlanders, aged 18-30y, underwent two 7-day sojourns at a high-altitude station in Chile (4–8 hrs/day at 5,050 m, nights at 2,900 m), separated by a 1-week recovery period at 520 m. Respiratory sleep studies recording mean nocturnal pulse oximetry (SpO2), oxygen desaturation index (ODI, >3% dips in SpO2), breathing patterns and subjective sleep quality by visual analog scale (SQ-VAS, 0–100% with increasing quality), were evaluated at 520 m and during nights 1 and 6 at 2,900 m in the 1st and 2nd altitude sojourn.Results: At 520 m, mean ± SD nocturnal SpO2 was 94 ± 1%, ODI 2.2 ± 1.2/h, SQ-VAS 59 ± 20%. Corresponding values at 2,900 m, 1st sojourn, night 1 were: SpO2 86 ± 2%, ODI 23.4 ± 22.8/h, SQ-VAS 39 ± 23%; 1st sojourn, night 6: SpO2 90 ± 1%, ODI 7.3 ± 4.4/h, SQ-VAS 55 ± 20% (p < 0.05, all differences within corresponding variables). Mean differences (Δ, 95%CI) in acute effects (2,900 m, night 1, vs 520 m) between 2nd vs 1st altitude sojourn were: ΔSpO2 0% (-1 to 1), ΔODI -9.2/h (-18.0 to -0.5), ΔSQ-VAS 10% (-6 to 27); differences in acclimatization (changes night 6 vs 1), between 2nd vs 1st sojourn at 2,900 m were: ΔSpO2 -1% (-2 to 0), ΔODI 11.1/h (2.5 to 19.7), ΔSQ-VAS -15% (-31 to 1).Conclusion: Acute high-altitude exposure induced nocturnal hypoxemia, cyclic deoxygenations and impaired sleep quality. Acclimatization mitigated these effects. After recovery at 520 m, repeated exposure diminished high-altitude-induced deoxygenation and breathing instability, suggesting some retention of adaptation induced by the first altitude sojourn while subjective sleep quality remained similarly impaired.

Introduction Obstructive sleep apnoea (OSA) is a highly prevalent disease that causing systemic hypertension. Furthermore, altitude-dependent hypobaric hypoxic condition and Tibetan ethnicity have been associated with systemic hypertension independent of OSA, therefore patients with OSA living at high altitude might be at profound risk to develop systemic hypertension. Acetazolamide has been shown to decrease blood pressure, improve arterial oxygenation and prevent high altitude periodic breathing in healthy volunteers ascending to high altitude and decrease blood pressure in patients with systemic hypertension at low altitude. However, the effect of acetazolamide on 24-hour blood pressure, sleep-disordered disturbance and daytime cognitive performance in patients with OSA permanently living at high altitude has not been studied.Methods and analysis This study protocol describes a randomised, placebo-controlled, double-blinded crossover trial. Highland residents of both sexes, aged 30–60 years, Tibetan ethnicity, living at an elevation of 3650 m and apnoea–hypopnoea index over 15/hour will be included. Participants will be randomly assigned to a 2×2 week treatment period starting with 750 mg/day acetazolamide followed by placebo treatment or vice versa, separated by a 1-week wash-out phase. Clinical assessments, 24-hour ambulatory blood pressure monitoring (ABPM), polysomnography (PSG), near-infrared spectroscopy, nocturnal fluid shift and cognitive performance will be assessed before and at the end of each treatment period. The primary outcome will be the difference in 24-hour mean blood pressure between acetazolamide therapy and placebo; secondary outcomes will be the difference in other 24-hour ABPM-derived parameters, PSG-derived parameters, cognitive performance and overnight change in different segments of fluid volume between acetazolamide therapy and placebo. Accounting for potential dropouts, 40 participants will be recruited.Ethics and dissemination The protocol was approved by the West China Hospital of Sichuan University Biomedical Research Ethics Committee. Recruitment will start in spring 2022. Dissemination of the results include presentations at conferences and publications in peer-reviewed journals.Trial registration number ChiCTR2100049304.

BackgroundPure oxygen breathing (hyperoxia) may improve hemodynamics in patients with pulmonary hypertension (PH) and allows to calculate right-to-left shunt fraction (Qs/Qt), whereas breathing normobaric hypoxia may accelerate hypoxic pulmonary vasoconstriction (HPV). This study investigates how hyperoxia and hypoxia affect mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) in patients with PH and whether Qs/Qt influences the changes of mPAP and PVR.Study Design and MethodsAdults with pulmonary arterial or chronic thromboembolic PH (PAH/CTEPH) underwent repetitive hemodynamic and blood gas measurements during right heart catheterization (RHC) under normoxia [fractions of inspiratory oxygen (FiO2) 0.21], hypoxia (FiO2 0.15), and hyperoxia (FiO2 1.0) for at least 10 min.ResultsWe included 149 patients (79/70 PAH/CTEPH, 59% women, mean ± SD 60 ± 17 years). Multivariable regressions (mean change, CI) showed that hypoxia did not affect mPAP and cardiac index, but increased PVR [0.4 (0.1–0.7) WU, p = 0.021] due to decreased pulmonary artery wedge pressure [−0.54 (−0.92 to −0.162), p = 0.005]. Hyperoxia significantly decreased mPAP [−4.4 (−5.5 to −3.3) mmHg, p < 0.001] and PVR [−0.4 (−0.7 to −0.1) WU, p = 0.006] compared with normoxia. The Qs/Qt (14 ± 6%) was >10 in 75% of subjects but changes of mPAP and PVR under hyperoxia and hypoxia were independent of Qs/Qt.ConclusionAcute exposure to hypoxia did not relevantly alter pulmonary hemodynamics indicating a blunted HPV-response in PH. In contrast, hyperoxia remarkably reduced mPAP and PVR, indicating a preserved vasodilator response to oxygen and possibly supporting the oxygen therapy in patients with PH. A high proportion of patients with PH showed increased Qs/Qt, which, however, was not associated with changes in pulmonary hemodynamics in response to changes in FiO2.

Background The aim of the present work was to study the influence of body position on resting and exercise pulmonary hemodynamics in patients assessed for pulmonary hypertension (PH). Methods and Results Data from 483 patients with suspected PH undergoing right heart catheterization for clinical indications (62% women, age 61±15 years, 246 precapillary PH, 48 postcapillary PH, 106 exercise PH, 83 no PH) were analyzed; 213 patients (main cohort, years 2016–2018) were examined at rest in upright (45°) and supine position, such as under upright exercise. Upright exercise hemodynamics were compared with 270 patients (historical cohort) undergoing supine exercise with the same protocol. Upright versus supine resting data revealed a lower mean pulmonary artery pressure 31±14 versus 32±13 mm Hg, pulmonary artery wedge pressure 11±4 versus 12±5 mm Hg, and cardiac index 2.9±0.7 versus 3.1±0.8 L/min per m2, and higher pulmonary vascular resistance 4.1±3.1 versus 3.9±2.8 Wood P

Background: Exact and simultaneous measurements of mean pulmonary artery pressure (mPAP) and cardiac output (CO) are crucial to calculate pulmonary vascular resistance (PVR), which is essential to define pulmonary hypertension (PH). Simultaneous measurements of mPAP and CO are not feasible using the direct Fick (DF) method, due to the necessity to sample blood from the catheter-tip. We evaluated a modified DF method, which allows simultaneous measurement of mPAP and CO without needing repetitive blood samples.Methods: Twenty-four patients with pulmonary arterial or chronic thromboembolic PH had repetitive measurements of CO at rest and end-exercise during three phases of a crossover trial. CO was assessed by the original DF method using oxygen uptake, measured by a metabolic unit, and arterial and mixed venous oxygen saturations from co-oximetry of respective blood gases served as reference. These CO measurements were then compared with a modified DF method using pulse oximetry at the catheter- and fingertip.Results: The bias among CO measurements by the two DF methods at rest was −0.26 L/min with limits of agreement of ±1.66 L/min. The percentage error was 28.6%. At the end-exercise, the bias between methods was 0.29 L/min with limits of agreement of ±1.54 L/min and percentage error of 16.1%.Conclusion: Direct Fick using a catheter- and fingertip pulse oximetry (DFp) is a practicable and reliable method for assessing CO in patients with PH. This method has the advantage of allowing simultaneous measurement of PAP and CO, and frequent repetitive measurements are needed during exercise.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT02755259, identifier: NCT02755259.

Question addressed by the study To investigate exercise performance and hypoxia-related health effects in patients with pulmonary hypertension (PH) during a high-altitude sojourn. Patients and methods In a randomised crossover trial in stable (same therapy for >4 weeks) patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) with resting arterial oxygen tension (PaO2) ≥7.3 kPa, we compared symptom-limited constant work-rate exercise test (CWRET) cycling time during a day-trip to 2500 m versus 470 m. Further outcomes were symptoms, oxygenation and echocardiography. For safety, patients with sustained hypoxaemia at altitude (peripheral oxygen saturation 30 min or 15 min) received oxygen therapy. Results 28 PAH/CTEPH patients (n=15/n=13); 13 females; mean±sd age 63±15 years were included. After >3 h at 2500 m versus 470 m, CWRET-time was reduced to 17±11 versus 24±9 min (mean difference −6, 95% CI −10 to −3), corresponding to −27.6% (−41.1 to −14.1; p

IntroductionWe investigated whether nocturnal oxygen therapy (NOT) mitigates the increase of pulmonary artery pressure in patients during daytime with chronic obstructive pulmonary disease (COPD) traveling to altitude.MethodsPatients with COPD living below 800 m underwent examinations at 490 m and during two sojourns at 2,048 m (with a washout period of 2 weeks < 800 m between altitude sojourns). During nights at altitude, patients received either NOT (3 L/min) or placebo (ambient air 3 L/min) via nasal cannula according to a randomized crossover design. The main outcomes were the tricuspid regurgitation pressure gradient (TRPG) measured by echocardiography on the second day at altitude (under ambient air) and various other echocardiographic measures of the right and left heart function. Patients fulfilling predefined safety criteria were withdrawn from the study.ResultsTwenty-three COPD patients [70% Global Initiative for Chronic Obstructive Lung Disease (GOLD) II/30% GOLD III, mean ± SD age 66 ± 5 years, FEV1 54% ± 13% predicted] were included in the per-protocol analysis. TRPG significantly increased when patients traveled to altitude (from low altitude 21.7 ± 5.2 mmHg to 2,048 m placebo 27.4 ± 7.3 mmHg and 2,048 m NOT 27.8 ± 8.3 mmHg) difference between interventions (mean difference 0.4 mmHg, 95% CI −2.1 to 3.0, p = 0.736). The tricuspid annular plane systolic excursion was significantly higher after NOT vs. placebo [2.6 ± 0.6 vs. 2.3 ± 0.4 cm, mean difference (95% confidence interval) 0.3 (0.1 − 0.5) cm, p = 0.005]. During visits to 2,048 m until 24 h after descent, eight patients (26%) using placebo and one (4%) using NOT had to be withdrawn because of altitude-related adverse health effects (p < 0.001).ConclusionIn lowlanders with COPD remaining free of clinically relevant altitude-related adverse health effects, changes in daytime pulmonary hemodynamics during a stay at high altitude were trivial and not modified by NOT.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT02150590.

Aims: To test the acute hemodynamic effect of acetazolamide in patients with pulmonary hypertension (PH) under ambient air and hypoxia.Methods: Patients with pulmonary arterial or chronic thromboembolic PH (PAH/CTEPH) undergoing right heart catheterization were included in this randomized, placebo-controlled, double-blinded, crossover trial. The main outcome, pulmonary vascular resistance (PVR), further hemodynamics, blood- and cerebral oxygenation were measured 1 h after intravenous administration of 500 mg acetazolamide or placebo-saline on ambient air (normoxia) and at the end of breathing hypoxic gas (FIO2 0.15, hypoxia) for 15 min.Results: 24 PH-patients, 71% men, mean ± SD age 59 ± 14 years, BMI 28 ± 5 kg/m2, PVR 4.7 ± 2.1 WU participated. Mean PVR after acetazolamide vs. placebo was 5.5 ± 3.0 vs. 5.3 ± 3.0 WU; mean difference (95% CI) 0.2 (−0.2–0.6, p = 0.341). Heart rate was higher after acetazolamide (79 ± 12 vs. 77 ± 11 bpm, p = 0.026), pH was lower (7.40 ± 0.02 vs. 7.42 ± 0.03, p = 0.002) but PaCO2 and PaO2 remained unchanged while cerebral tissue oxygenation increased (71 ± 6 vs. 69 ± 6%, p = 0.017). In acute hypoxia, acetazolamide decreased PVR by 0.4 WU (0.0–0.9, p = 0.046) while PaO2 and PaCO2 were not changed. No adverse effects occurred.Conclusions: In patients with PAH/CTEPH, i.v. acetazolamide did not change pulmonary hemodynamics compared to placebo after 1 hour in normoxia but it reduced PVR after subsequent acute exposure to hypoxia. Our findings in normoxia do not suggest a direct acute pulmonary vasodilator effect of acetazolamide. The reduction of PVR during hypoxia requires further corroboration. Whether acetazolamide improves PH when given over a prolonged period by stimulating ventilation, increasing oxygenation, and/or altering vascular inflammation and remodeling remains to be investigated.

Objective: To evaluate the effects of breathing oxygen-enriched air (oxygen) on exercise performance in patients with pulmonary hypertension due to heart failure with preserved ejection fraction (PH-HFpEF).Methods: Ten patients with PH-HFpEF (five women, age 60 ± 9 y, mPAP 37 ± 14 mmHg, PAWP 18 ± 2 mmHg, PVR 3 ± 3 WU, resting SpO2 98 ± 2%) performed two-cycle incremental exercise tests (IET) and two constant-work-rate exercise test (CWRET) at 75% maximal work-rate (Wmax), each with ambient air (FiO2 0.21) and oxygen (FiO2 0.5) in a randomized, single-blinded, cross-over design. The main outcomes were the change in Wmax (IET) and cycling time (CWRET) with oxygen vs. air. Blood gases at rest and end-exercise, dyspnea by Borg CR10 score at end-exercise; continuous SpO2, minute ventilation (V'E), carbon dioxide output (V'CO2), and cerebral and quadricep muscle tissue oxygenation (CTO and QMTO) were measured.Results: With oxygen vs. air, Wmax (IET) increased from 94 ± 36 to 99 ± 36 W, mean difference (95% CI) 5.4 (0.9–9.8) W, p = 0.025, and cycling time (CWRET) from 532 ± 203 to 680 ± 76 s, +148 (31.8–264) s, p = 0.018. At end-exercise with oxygen, Borg dyspnea score and V'E/V'CO2 were lower, whereas PaO2 and end-tidal PaCO2 were higher. Other parameters were unchanged.Conclusion: Patients with PH-HFpEF not revealing resting hypoxemia significantly improved their exercise performance while breathing oxygen-enriched air along with less subjective dyspnea sensation, a better blood oxygenation, and an enhanced ventilatory efficiency. Future studies should investigate whether prolonged training with supplemental oxygen would increase the training effect and, potentially, daily activity for PH-HFpEF patients.Clinical Trial Registration: [clinicaltrials.gov], identifier [NCT04157660].

Introduction: Acetazolamide (AZA) improves nocturnal and daytime blood oxygenation in patients with pulmonary vascular disease (PVD), defined as pulmonary arterial and distal chronic thromboembolic pulmonary hypertension (CTEPH), and may improve exercise performance. Methods: We investigated the effect of 5 weeks of AZA (250 mg bid) versus placebo on maximal load during incremental cycling ramp exercise in patients with PVD studied in a randomized controlled, double-blind, crossover design, separated by > 2 weeks of washout. Results: Twenty-five patients (12 pulmonary arterial hypertension, 13 CTEPH, 40% women, age 62 ± 15 years) completed the trial according to the protocol. Maximum load was similar after 5 weeks of AZA versus placebo (113 ± 9 vs. 117 ± 9 watts [W]), mean difference −4 W (95% CI: −9 to 1, p = 0.138). With AZA, maximum (max)-exercise partial pressure of O2 (PaO2) was significantly higher by 1.1 kPa (95% CI: 0.5–1.8, p = 0.003), while arterial pH and partial pressure of CO2 were significantly lower. Gas exchange threshold was reached at a higher load with AZA (108 ± 8 W vs. 97 ± 8 W) and was therefore delayed by 11 W (95% CI: 3–19, p = 0.013), while the ventilatory equivalent for O2 and CO2 were significantly higher at both the max-exercise and gas exchange threshold with AZA versus placebo. Conclusion: AZA for 5 weeks did not significantly change maximum exercise capacity in patients with PVD despite a significant increase in PaO2. The beneficial effects of increased blood oxygenation may have been diminished by increased ventilation due to AZA-induced metabolic acidosis and increased dyspnea. [ABSTRACT FROM AUTHOR]

Abstract Background To investigate the effect of asthma rehabilitation at high altitude (3100 m, HA) compared to low altitude (760 m, LA). Methods For this randomized parallel-group trial insufficiently controlled asthmatics (Asthma Control Questionnaire (ACQ) > 0.75) were randomly assigned to 3-week in-hospital rehabilitation comprising education, physical-&breathing-exercises at LA or HA. Co-primary outcomes assessed at 760 m were between group changes in peak expiratory flow (PEF)-variability, and ACQ) from baseline to end-rehabilitation and 3 months thereafter. Results 50 asthmatics were randomized [median (quartiles) LA: ACQ 2.7(1.7;3.2), PEF-variability 19%(14;33); HA: ACQ 2.0(1.6;3.0), PEF-variability 17%(12;32)]. The LA-group improved PEF-variability by median(95%CI) -7%(− 14 to 0, p = 0.033), ACQ − 1.4(− 2.2 to − 0.9, p

The aim of the study was to investigate the pulmonary haemodynamic response to exercise in Central Asian high- and lowlanders. This was a cross-sectional study in Central Asian highlanders (living >2500 m) compared with lowlanders (living

Background: Chronic obstructive pulmonary disease (COPD) is associated with cardiovascular disease. We investigated whether sleeping at altitude increases nocturnal heart rate (HR) and other markers of cardiovascular risk or arrhythmias in lowlanders with COPD and whether this can be prevented by nocturnal oxygen therapy (NOT).Methods: Twenty-four COPD patients, with median age of 66 years and forced expiratory volume in 1 s (FEV1) 55% predicted, living