We investigated whether nocturnal oxygen therapy (NOT) mitigates the altitude-induced increase of pulmonary artery pressure in patients with chronic obstructive pulmonary disease (COPD) when staying overnight at moderate altitude. Patients with COPD living below 800m, underwent examinations at 490m and during 2 sojourns at 2048m (with a washout period of 2 weeks <800m 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 cross-over design. The main outcome was the difference of the tricuspid regurgitation pressure gradient (TRPG) measured by echocardiography on the 2nd day at altitude (performed under ambient air) between sojourns with NOT and placebo. Additional outcomes were other echocardiographic measures of the right and left heart function. Twenty-three COPD-patients (70% GOLD II / 30% GOLD III, mean±SD age 66±5years, FEV1 54±13% predicted) were included. TRPG significantly increased when patients travelled from 490m to 2048m (21.7±5.2mmHg; 2048m placebo 27.4±7.3mmHg; and 2048m NOT 27.8±8.3mmHg) without difference between interventions. The tricuspid annular plane systolic excursion was significantly higher after NOT vs. placebo (2.6±0.6 vs. 2.3±0.4cm, mean difference (95% confidence interval) 0.3(0.1 to 0.5)cm, p=0.005). NOT did not mitigate the acute effect of altitude on the TRPG in COPD lowlanders travelling to altitude compared to placebo. Whether NOT during prolonged altitude sojourns affects right heart function remains to be studied.
In patients with chronic obstructive pulmonary disease (COPD), oxygen delivery to the heart may be impaired during travel at altitude. We assessed electrocardiogram (ECG)-derived signs of cardiac ischemia and the effects of preventive acetazolamide therapy in COPD patients traveling to high altitudes. Patients with COPD [Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) grades 2-3] and a predicted forced expiratory volume in 1 s (FEV1) of 66 ± 11% (mean ± SD), aged 57 ± 8 years, and living <1,000 m were included in this analysis of secondary outcomes from a randomized placebo-controlled double-blind trial (www.clinicaltrials.gov, NCT03156231). Exercise electrocardiograms were recorded at the National Center of Internal Medicine and Cardiology, Bishkek (760 m) and on the day of arrival at the Tuja Ashu high-altitude clinic (3,100 m), Kyrgyzstan. Acetazolamide (375 mg/day) or placebo was administered 24 h before the ascent and during the stay at 3,100 m. The incidence of a post-exercise ST elevation (STE) ≥0.3 mm in aVR (J + 80 ms) was the main outcome. At 760 m, 3 of 49 (6%) patients randomized to placebo and 3 of 50 (6%) randomized to acetazolamide showed a post-exercise STE. At 3,100 m under placebo, two (4%) new STEs developed and one (2%) disappeared compared to 760 m (P = 0.564, McNemar's test). At 3,100 m under acetazolamide, one (2%) new STE developed and two (4%) disappeared compared to 760 m (P = 0.564). No treatment effect was detected (P = 0.242, Fisher's exact test). The mean difference (95% CI) in STE between post-peak exercise between 3,100 m and 760 m was 0.22 mm (0.06 to 0.39) and 0.09 mm (-0.06 to 0.24) under placebo and acetazolamide therapy [treatment effect, -0.13 mm (-0.35 to 0.08, P = 0.230)], respectively. In lowlanders with moderate to severe COPD ascending to 3,100 m, no ECG-derived signs of cardiac ischemia emerged neither at rest nor post-exercise and this was not modified by preventive acetazolamide therapy.
Background: Acetazolamide is established for preventing acute mountain sickness (AMS) in young, healthy individuals. We evaluated whether acetazolamide prevents AMS in healthy persons older than 40y, an age group not included in previous studies. Methods: In a randomized, placebo-controlled, double-blind parallel-design trial, 345 healthy lowlanders, mean±SD age 53±7y, 69% women, were treated with acetazolamide capsules (375mg/day) or placebo, starting 24h before ascent to and while staying 2 days at 3100m. Primary outcome: incidence of AMS, i.e., Lake Louise score ≥3 including headache at 3100m. Secondary outcomes: incidence of other altitude-related illnesses, nocturnal pulse oximetry (mean SpO2 and number of SpO2 dips >3%/h as index of periodic breathing), and treatment-related side effects. (ClinicalTrials.gov NCT03561675) Results: Fifty-four of 170 (32%) participants receiving placebo and 38 of 175 (22%) receiving acetazolamide experienced AMS (Chi-Square statistic P=0.035), hazard ratio 0.48, 95%CI, 0.29 to 0.80, number needed to prevent one case of AMS 10 (95%CI, 5 to 141). In participants using placebo, mean nocturnal SpO2 was lower (84.6±0.2%) and SpO2 dips/h were more prevalent (21.7±1.1) compared to participants using acetazolamide (mean difference 3.1% (2.5 to 3.7) and 10.5/h (8.4 to 12.7), P<0.001, both comparisons. Other altitude-related illnesses occurred in 5(3%) using placebo and 3(2%) using acetazolamide (P=0.497). Conclusion: Among healthy lowlanders ≥40 years staying at 3100m, the incidence of AMS was relatively low and further reduced by preventive treatment with acetazolamide. Acetazolamide improved nocturnal oxygenation and stabilized the breathing pattern.
Exercise performance is determined by oxygen supply to working muscles and vital organs. In healthy individuals, exercise performance is limited in the hypoxic environment at altitude, when oxygen delivery is diminished due to the reduced alveolar and arterial oxygen partial pressures. In patients with pulmonary hypertension (PH), exercise performance is already reduced near sea level due to impairments of the pulmonary circulation and gas exchange, and, presumably, these limitations are more pronounced at altitude. In studies performed near sea level in healthy subjects, as well as in patients with PH, maximal performance during progressive ramp exercise and endurance of submaximal constant-load exercise were substantially enhanced by breathing oxygen-enriched air. Both in healthy individuals and in PH patients, these improvements were mediated by a better arterial, muscular, and cerebral oxygenation, along with a reduced sympathetic excitation, as suggested by the reduced heart rate and alveolar ventilation at submaximal isoloads, and an improved pulmonary gas exchange efficiency, especially in patients with PH. In summary, in healthy individuals and in patients with PH, alterations in the inspiratory Po 2 by exposure to hypobaric hypoxia or normobaric hyperoxia reduce or enhance exercise performance, respectively, by modifying oxygen delivery to the muscles and the brain, by effects on cardiovascular and respiratory control, and by alterations in pulmonary gas exchange. The understanding of these physiological mechanisms helps in counselling individuals planning altitude or air travel and prescribing oxygen therapy to patients with PH.
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.
