Background This study investigated whether nocturnal oxygen therapy (NOT) improves next-day cerebrovascular function in lowlanders with COPD staying at moderate altitude. Methods This randomized, placebo-controlled crossover trial was performed in stable patients with moderate to severe COPD (FEV1/FVC <0.7 and FEV1 30-80%predicted), living <800m and pulse oximetry (SpO2) ≥92%. Patients underwent assessments at 490m and during 2 stays of 2 days at 2048m while NOT or placebo (each at 3L min-1 through nasal cannula) were applied according to a randomized cross-over design. At both altitudes, SpO2, cerebral tissue oxygenation (CTO, near-infrared spectroscopy), mean arterial blood pressure (MAP, finger plethysmography) and middle cerebral artery systolic peak blood flow velocity (sMCAv, transcranial Doppler ultrasound) were assessed while patients were (0) quietly breathing FiO2 0.21; (i) quietly breathing FiO2 1.0, (ii) voluntarily hyperventilating, (iii) voluntarily hyperventilating under FiO2 1.0, and (iv) during head-up tilting. Indices of cerebrovascular responsiveness to changes in blood gases and blood pressure were computed. Results A total of 18 patients (8 women aged mean±SD 65±5y, FEV1 54.7±13.9%predicted) were analyzed. At 2048m under placebo, patients became hypoxemic, mean±SE SpO2 90.3±0.4% vs. 93.7±0.4% at 490m, while MAP, CTO and sMCAv remained unchanged compared to 490m. All ventilatory maneuvers at 2048 m induced greater increases in SpO2 compared to 490m while changes in MAP, CTO and sMCAv were similar. Head-up tilting induced a similar blood pressure fall at 2048m compared to 490m, whereas cerebral blood flow velocity changed less in response to systemic hypotension (mean±SE ΔsMCAv/ΔMAP 0.9±0.3 vs. 2.3±0.4cm s-1 mmHg-1) at 2048m. No alteration in cerebrovascular function as a treatment effect of NOT was observed in either maneuver. Conclusion This randomized clinical trial in moderate-to-severe COPD patients ascending to 2048m showed that moderate daytime systemic hypoxemia does not translate to cerebral hypoxia nor cerebrovascular autoregulatory impairments while at rest or under ventilatory or orthostatic challenges. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT02150590 ### Funding Statement The study was supported by the Swiss National Science Foundation (143875) and Lunge Zurich. Siemens Health Engineers provided some equipment for the study. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of the University Hospital of Zurich gave ethical approval for this work (EK-2013-0088). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.

Background:Amongst the millions of travelers to high altitude worldwide are many with chronic obstructive pulmonary disease (COPD), but data regarding the effects of acute exposure to altitude on exercise performance are limited. The current study investigated how acute exposure to moderate altitude influences exercise performance in COPD patients, providing novel insights to the underlying physiological mechanisms. Methods:Twenty-nine COPD patients, GOLD grade 2-3, median (quartile) forced expiratory volume in 1 second (FEV1) of 60% predicted (46; 69) performed cycling incremental ramp exercise test (IET) at 490 m and after acute exposure of 2-6 hours to 2048 m or vice versa, according to a randomized cross-over design. Exercise performance and breath-by-breath analyses of the last 30 seconds of each IET were compared between locations. Results:At 2048 m compared to 490 m, the maximum power output (Wmax) was 77 watts (62;104) vs 88 watts (75;112), median reduction 5 watts (95% CI, 2 to 8, P<0.05), corresponding to a median reduction of 6% (95% CI, 2 to 11, P<0.05) compared to 490 m. The peak oxygen uptake (V'O2peak) was 70% predicted (56;86) at 2048 m vs 79% predicted (63;90) at 490 m, median reduction of 6% (95% CI, 3 to 9, P<0.05). The oxygen saturation by pulse oximetry (SpO2) at 2048 m was reduced by 8% (95% CI, 4 to 9, P<0.05) compared to 490 m. The minute ventilation (V'E) increased by 2.8L/min (95% CI, 0.9 to 4.2, P<0.05) at 2048 m. The maximum heart rate and the subjective sense of dyspnea and leg fatigue did not change. Conclusion:Lowlanders with moderate-to-severe COPD acutely exposed to 2048 m reveal small but significant reduction in cycling IET along with a reduced V'O2peak. As dyspnea perception and maximal heart rate were unchanged, the lower blood oxygenation and exaggerated ventilatory response were culprit factors for the reduced performance.

1Department of Pulmonology and Sleep Disorders Centre, University Hospital Zurich, Zurich, Switzerland; 2Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland; 3Centre of Competence Sleep & Health, University of Zurich, Zurich, Switzerland Purpose: Patients with chronic obstructive pulmonary disease (COPD) are particularly vulnerable to hypoxia-induced autonomic dysregulation. Hypoxemia is marked during sleep. In COPD, altitude exposure is associated with an increase in blood pressure (BP) and a decrease in baroreflex-sensitivity (BRS). Whether nocturnal oxygen therapy (NOT) may mitigate these cardiovascular autonomic changes in COPD at altitude is unknown. Materials and Methods: In a randomized placebo-controlled cross-over trial, 32 patients with moderate-to-severe COPD living <800 m were subsequently allocated to NOT and placebo during acute exposure to altitude. Measurements were done at low altitude at 490 m and during two stays at 2048 m on NOT (3 L/min) and placebo (3 L/min, ambient air) via nasal cannula. Allocation and intervention sequences were randomized. Outcomes of interest were BP, BRS (from beat-to-beat BP measurement), BP variability (BPV), and heart rate. Results: About 23/32 patients finished the trial per protocol (mean (SD) age 66 (5) y, FEV1 62 (14) % predicted) and 9/32 experienced altitude-related illnesses (8 vs 1, p < 0.05 placebo vs NOT). NOT significantly mitigated the altitude-induced increase in systolic BP compared to placebo (Δ median −5.8 [95% CI −22.2 to −1.4] mmHg, p = 0.05) but not diastolic BP (−3.5 [95% CI −12.6 to 3.0] mmHg; p = 0.21) or BPV. BRS at altitude was significantly higher in NOT than in placebo (1.7 [95% CI 0.3 to 3.4] ms/mmHg, p = 0.02). Conclusion: NOT may protect from hypoxia-induced autonomic dysregulation upon altitude exposure in COPD and thus protect from a relevant increase in BP and decrease in BRS. NOT may provide cardiovascular benefits in COPD during conditions of increased hypoxemia and may be considered in COPD travelling to altitude.

SummaryAltitude exposure induces hypoxaemia in patients with chronic obstructive pulmonary disease (COPD), particularly during sleep. The present study tested the hypothesis in patients with COPD staying overnight at high altitude that nocturnal arterial hypoxaemia is associated with impaired cerebral tissue oxygenation (CTO). A total of 35 patients with moderate‐to‐severe COPD, living at <800 m (mean [SD] age 62.4 [12.3] years, forced expiratory volume in 1 s [FEV1] 61 [16]% predicted, awake pulse oximetry ≥92%) underwent continuous overnight monitoring of pulse oximetry (oxygen saturation [SpO2]) and near‐infrared spectroscopy of prefrontal CTO, respectively, at 490 m and 2,590 m. Regression analysis was used to evaluate whether nocturnal arterial desaturation (COPDDesat, SpO2 <90% for >30% of night‐time) at 490 m predicted CTO at 2,590 m when controlling for baseline variables. At 2,590 m, mean nocturnal SpO2 and CTO were decreased versus 490 m, mean change −8.8% (95% confidence interval [CI] −10.0 to −7.6) and −3.6% (95% CI −5.7 to −1.6), difference in change ΔCTO‐ΔSpO2 5.2% (95% CI 3.0 to 7.3; p < .001). Moreover, frequent cyclic desaturations (≥4% dips/hr) occurred in SpO2 and CTO, mean change from 490 m 35.3/hr (95% CI 24.9 to 45.7) and 3.4/hr (95% CI 1.4 to 5.3), difference in change ΔCTO‐ΔSpO2 −32.8/hr (95% CI −43.8 to −21.8; p < .001). Regression analysis confirmed an association of COPDDesat with lower CTO at 2,590 m (coefficient −7.6%, 95% CI −13.2 to −2.0; p = .007) when controlling for several confounders. We conclude that lowlanders with COPD staying overnight at 2,590 m experience altitude‐induced hypoxaemia and periodic breathing in association with sustained and intermittent cerebral deoxygenation. Although less pronounced than the arterial deoxygenation, the altitude‐induced cerebral tissue deoxygenation may represent a risk of brain dysfunction, especially in patients with COPD with nocturnal hypoxaemia at low altitude.

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 (FEV 1 ) 55% predicted, living <800 m underwent sleep studies at Zurich (490 m) and during 2 sojourns of 2 days each at St. Moritz (2,048 m) separated by 2-week washout at <800 m. During nights at 2,048 m, patients received either NOT (2,048 m NOT) or ambient air (2,048 m placebo) 3 L/min via nasal cannula according to a randomized, placebo-controlled crossover trial. Sleep studies comprised ECG and pulse oximetry to measure HR, rhythm, HR-adjusted QT interval (QTc), and mean oxygen saturation (SpO 2 ). Results: In the first nights at 490 m, 2,048 m placebo, and 2,048 m NOT, medians (quartiles) of SpO 2 were 92% (90; 94), 86% (83; 89), and 97% (95; 98) and of HR were 73 (66; 82), 82 (71; 85), and 78 bpm (67; 74) ( P < 0.05 all respective comparisons). QTc increased from 417 ms (404; 439) at 490 m to 426 ms (405; 440) at 2,048 m placebo ( P < 0.05) and was 420 ms (405; 440) at 2,048 m NOT ( P = NS vs. 2,048 m placebo). The number of extrabeats and complex arrhythmias was similar over all conditions. Conclusions: While staying at 2,048 m, lowlanders with COPD experienced nocturnal hypoxemia in association with an increased HR and prolongation of the QTc interval. NOT significantly improved SpO 2 and lowered HR, without changing QTc. Whether oxygen therapy would reduce HR and arrhythmia during longer altitude sojourns remains to be elucidated.

AbstractThis 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 < 800 m in-between. Semi-supine, constant-load cycle exercise to exhaustion at 60% of maximal work-rate was performed at 490 m and after the first night at 2048 m. Endurance time was the primary outcome. Additional outcomes were cerebral tissue oxygenation (CTO), arterial blood gases and breath-by-breath measurements (http://www.ClinicalTrials.gov NCT02150590). Mean ± SE endurance time at 490 m was 602 ± 65 s, at 2048 m after placebo 345 ± 62 s and at 2048 m after NOT 293 ± 60 s, respectively (P < 0.001 vs. 490 m). Mean difference (95%CI) NOT versus placebo was − 52 s (− 174 to 70), P = 0.401. End-exercise pulse oximetry (SpO2), CTO and minute ventilation ($${\dot{\text{V}}}_{{\text{E}}}$$ V ˙ E ) at 490 m were: SpO2 92 ± 1%, CTO 65 ± 1%, $${\dot{\text{V}}}_{{\text{E}}}$$ V ˙ E 37.7 ± 2.0 L/min; at 2048 m with placebo: SpO2 85 ± 1%, CTO 61 ± 1%, $${\dot{\text{V}}}_{{\text{E}}}$$ V ˙ E 40.6 ± 2.0 L/min and with NOT: SpO2 84 ± 1%; CTO 61 ± 1%; $${\dot{\text{V}}}_{{\text{E}}}$$ V ˙ E 40.6 ± 2.0 L/min (P < 0.05, SpO2, CTO at 2048 m with placebo vs. 490 m; P = NS, NOT vs. placebo). Altitude-related hypoxemia and cerebral hypoxia impaired exercise endurance in patients with moderate to severe COPD and were not prevented by NOT.

Background: Patients with COPD are vulnerable to hypoxia-induced autonomic dysregulation. Hypoxaemia is marked during sleep. In COPD, altitude exposure is associated with an increase in blood pressure (BP) and a decrease in baroreflex-sensitivity (BRS). Whether nocturnal oxygen therapy (NOT) mitigates these cardiovascular autonomic changes in COPD at altitude is unknown. Methods: In a randomised placebo-controlled cross-over trial, 32 patients with moderate-to-severe COPD living <800m were allocated to NOT or placebo during acute exposure to altitude. Measurements were done at low altitude at 490m and during two stays at 2048m on NOT (3 l/min) or placebo (ambient air) via nasal cannula. Allocation and intervention sequence were randomised. Outcomes of interest were BP, BRS, and heart rate. Results: 23 patients finished the trial per protocol (mean(SD) age 66(5)y, FEV1 62(14)%predicted). The others had altitude-related adverse health effects. NOT significantly decreased the altitude-induced increase in systolic BP compared to placebo (-10.6 [95%CI -20.1 to -1.0] mmHg, p=0.05) but not diastolic BP (-4.4 mmHg, 95%CI -11.4 to 2.6; p=0.29). BRS at altitude was significantly higher in NOT than in placebo (+1.5 [95%CI 0.01 to 2.95], p=0.02). Conclusions: NOT may protect from hypoxia-induced autonomic dysregulation upon altitude exposure in COPD. Oxygen supplementation may provide cardiovascular benefits in COPD during conditions of increased hypoxaemia.

PURPOSE:Patients with chronic obstructive pulmonary disease (COPD) are particularly vulnerable to hypoxia-induced autonomic dysregulation. Hypoxemia is marked during sleep. In COPD, altitude exposure is associated with an increase in blood pressure (BP) and a decrease in baroreflex-sensitivity (BRS). Whether nocturnal oxygen therapy (NOT) may mitigate these cardiovascular autonomic changes in COPD at altitude is unknown. MATERIALS AND METHODS:In a randomized placebo-controlled cross-over trial, 32 patients with moderate-to-severe COPD living <800 m were subsequently allocated to NOT and placebo during acute exposure to altitude. Measurements were done at low altitude at 490 m and during two stays at 2048 m on NOT (3 L/min) and placebo (3 L/min, ambient air) via nasal cannula. Allocation and intervention sequences were randomized. Outcomes of interest were BP, BRS (from beat-to-beat BP measurement), BP variability (BPV), and heart rate. RESULTS:About 23/32 patients finished the trial per protocol (mean (SD) age 66 (5) y, FEV1 62 (14) % predicted) and 9/32 experienced altitude-related illnesses (8 vs 1, p < 0.05 placebo vs NOT). NOT significantly mitigated the altitude-induced increase in systolic BP compared to placebo (Δ median -5.8 [95% CI -22.2 to -1.4] mmHg, p = 0.05) but not diastolic BP (-3.5 [95% CI -12.6 to 3.0] mmHg; p = 0.21) or BPV. BRS at altitude was significantly higher in NOT than in placebo (1.7 [95% CI 0.3 to 3.4] ms/mmHg, p = 0.02). CONCLUSION:NOT may protect from hypoxia-induced autonomic dysregulation upon altitude exposure in COPD and thus protect from a relevant increase in BP and decrease in BRS. NOT may provide cardiovascular benefits in COPD during conditions of increased hypoxemia and may be considered in COPD travelling to altitude.

Key Points Question Can nocturnal oxygen therapy prevent hypoxemia and sleep apnea among lowlanders with chronic obstructive pulmonary disease when traveling to high altitude? Findings In this randomized crossover trial of 32 lowlanders with chronic obstructive pulmonary disease, nocturnal oxygen therapy improved their mean nocturnal oxygen saturation and apnea-hypopnea index during a night at 2048 m. Nocturnal oxygen therapy also reduced the incidence of altitude-induced adverse health effects requiring medical treatment or descent to lower altitude by 85% compared with placebo. Meaning Patients with chronic obstructive pulmonary disease may benefit from nocturnal oxygen therapy during travel to high altitude because it reduces nocturnal hypoxemia, sleep disordered breathing, and other adverse health effects.

Purpose: During altitude travel, exercise performance in patients with chronic obstructive pulmonary disease (COPD) is strongly reduced (Furian 2018). We evaluated whether nocturnal oxygen therapy (NOT) during a stay at 2048m improves next-day exercise performance in lowlanders with COPD. Methods: 32 lowlanders with COPD, mean±SE FEV1 54±9%predicted, living <800m, stayed for 2 days at 2048m twice, once with NOT, once with placebo according to a randomized, crossover trial with a 2-week washout period at <800m in-between. Constant-load bicycle exercise to exhaustion at 60% of maximal workload was performed at 490m and on day 2 of sojourns at 2048m to measure endurance time as the primary outcome. Additional outcomes were altitude-related adverse effects (ARAHE) requiring treatment or descent. www.ClinicalTrials.gov NCT02150590. Results: Mean±SE endurance time at 490m was 602±64s, at 2048m with placebo 326±62s and with NOT 296±60s, mean difference (95%CI) NOT-placebo -30s (-149 to 89), P=0.619. End-exercise values in pulse oximetry, cerebral tissue oxygenation and minute ventilation at 490m were: SpO2=92±1%, CTO=65±1%, V’E=37.7±2.0 l/min; during sojourns at 2048m with placebo: SpO2=85±1%, CTO=61±1%, V’E=40.6±2.0 l/min and during sojourns with NOT: SpO2=84±1%; CTO=61±1%; V’E=40.6±2.0 l/min (P=NS, all comparisons NOT vs. placebo). Eight patients experienced ARAHE during the stay at 2048m with placebo vs. one with NOT (Fisher’s Exact Test, P<0.001). Conclusion: Altitude exposure impaired exercise endurance in patients with COPD due to arterial and cerebral hypoxemia. Nocturnal oxygen therapy prior to exercise did not improve performance but reduced ARAHE. Grants: Lunge Zürich, SNSF

Study Objectives: Patients with chronic obstructive pulmonary disease (COPD) have impaired pulmonary gas exchange near sea level. The purpose of the current study was to investigate whether exposure to hypobaric hypoxia during a stay at altitude affects nocturnal oxygen saturation, breathing pattern, and sleep in patients with moderate to severe COPD. Methods: Thirty-two patients with COPD, median age 67 years, FEV1 59% predicted, PaO2 68 mmHg, living below 800 m, underwent polysomnography and questionnaire evaluations in Zurich (490 m), and in Swiss Alpine villages at 1650 and 2590 m, for two nights each, in random order. Mean nocturnal oxygen saturation (SpO(2)), the apnea-hypopnea index (AHI), and sleep structure were compared between altitudes. Results: Polysomnography during the first night at each altitude revealed a reduced SpO(2) at 1650 and 2590 m (medians 89% and 85%) compared with 490 m (92%, p < 0.05 vs. higher altitudes) and a higher AHI (medians 26.8/hr and 55.7/hr) vs. 490 m (15.4/hr, p < 0.05 vs. higher altitudes) due to emergence of frequent central apneas/hypopneas. At 2590 m, sleep efficiency (median 59%) and slow-wave sleep (median 17% of total sleep time) were reduced compared with 490 m (72% and 20%, respectively, p < 0.05). In the morning after one night at 2590 m, patients estimated to have spent more time awake (median 110 min) than at 490 m (43 min, p < 0.05) and felt slightly less alert. Conclusions: During a stay at moderate altitude, lowlanders with moderate to severe COPD experience nocturnal hypoxemia that induces central sleep apneas, altered sleep structure, and insomnia. These novel findings help us to counsel patients with COPD planning altitude travel. Statement of Significance Exposure to high altitude may disturb sleep and control of breathing. Compared with healthy mountaineers, patients with chronic obstructive pulmonary disease (COPD) may be more susceptible to altitude-related sleep and breathing disturbances due to their impaired pulmonary gas exchange already near sea level although this has not been studied. To address this point, the current randomized trial was performed. It revealed that low-altitude residents with moderate to severe COPD staying for 2 days/nights each at 1650 and 2590 m experienced nocturnal hypoxemia, a reduced sleep efficiency and slow-wave sleep, and emergence of predominantly central sleep apneas/hypopneas. These novel findings help us to counsel patients with COPD planning mountain travel and serve as a basis for future studies on preventive measures.

Objective: To evaluate the effects of altitude travel on exercise performance and symptoms in lowlanders with COPD. Design: Randomized crossover trial. Setting: University Hospital Zurich (490 m), research facility in mountain villages, Davos Clavadel (1,650 m) and Davos Jakobshorn (2,590 m). Participants: Forty COPD patients, Global Initiative for Obstructive Lung Disease (GOLD) grade 2-3, living below 800 m, median (quartiles) age 67 y (60; 69), forced expiratory volume in 1 second 57% predicted (49; 70). Intervention: Two-day sojourns at 490 m, 1,650 m, and 2,590 m in randomized order. Outcome measures: Six-minute walk distance (6MWD), cardiopulmonary exercise tests, symptoms, and other health effects. Results: At 490 m, days 1 and 2, median (quartiles) 6MWD were 558 m (477; 587) and 577 m (531; 629). At 2,590 m, days 1 and 2, mean changes in 6MWD from corresponding day at 490 m were -41 m (95% C I -51 to -31) and -40 m (-53 to -27), n=40, P<0.05, both changes. At 1,650 m, day 1, 6MWD had changed by -22 m (-32 to -13), maximal oxygen uptake during bicycle exercise by -7% (-13 to 0) vs 490 m, P<0.05, both changes. At 490 m, 1,650 m, and 2,590 m, day 1, resting Pa0 2 were 9.0 (8.4; 9.4), 8.1 (7.5; 8.6), and 6.8 (6.3; 7.4) k Pa, respectively, P<0.05 higher altitudes vs 490 m. While staying at higher altitudes, nine patients (24%) experienced symptoms or adverse health effects requiring oxygen therapy or relocation to lower altitude. Conclusion: During sojourns at 1,650 m and 2,590 m, lowlanders with moderate to severe COPD experienced a mild reduction in exercise performance and nearly one quarter required oxygen therapy or descent to lower altitude because of adverse health effects. The findings may help to counsel COPD patients planning altitude travel.

Background: Effects of hypobaric hypoxia at altitude on exercise performance of lowlanders with chronic obstructive pulmonary disease (COPD) have not been studied in detail. Objectives: To quantify changes in exercise performance and associated physiologic responses in lowlanders with COPD travelling to moderate altitude. Methods: A total of 31 COPD patients with a median age (quartiles) of 66 years (59; 69) and FEV1 of 56% predicted (49; 69) living below 800 m performed a constant-load bicycle exercise to exhaustion at 60% of the maximal work rate at 490 m (Zurich) and at an identical work rate at 2,590 m (Davos) in randomized order. Pulmonary gas exchange, pulse oximetry (SpO2), cerebral tissue oxygenation (CTO; near-infrared spectroscopy), and middle cerebral artery peak blood flow velocity (MCAv) by Doppler ultrasound during 30 s at end exercise were compared between altitudes. Results: With ascent from 490 to 2,590 m, the median endurance time (quartiles) was reduced from 500 s (256; 795) to 205 s (139; 297) by a median (95% CI) of 303 s (150–420) (p < 0.001). End exercise SpO2 decreased from 92% (89; 94) to 81% (77; 84) and CTO from 62% (56; 66) to 55% (50; 60); end exercise minute ventilation increased from 40.6 L/min (35.5; 47.8) to 47.2 L/min (39.6; 58.7) (p < 0.05; all comparisons 2,590 vs. 490 m). MCAv increased similarly from rest to end exercise at 490 m (+25% [17; 36]) and at 2,590 m (+21% [14; 30]). However, the ratio of MCAv increase to SpO2 drop during exercise decreased from +6%/% (3; 12) at 490 m to +3%/% (2; 5) at 2,590 m (p < 0.05). Conclusions: In lowlanders with COPD travelling to 2,590 m, exercise endurance is reduced by more than half compared to 490 m in association with reductions in systemic and cerebral oxygen availability.

Objectives: We evaluated whether nocturnal oxygen administration improves sleep and breathing disturbances in lowlanders with chronic obstructive pulmonary disease (COPD) staying for 2 nights at 2048m. Methods: 21 lowlanders with COPD, median age 68y, FEV1 55%predicted, travelled to a mountain village at 2048m (St. Moritz) twice for 2 days, separated by a 2 week washout period at <800m. During nights at 2048m, oxygen or ambient air (sham) was administered by nasal cannula at 3l/min according to a randomized, blinded, cross-over design. Co-primary outcomes were mean nocturnal oxygen saturation (SpO2) and apnea/hypopnea index (AHI) measured during polysomnography. Results: Oxygen supplementation decreased AHI and increased SpO2 compared to sham at 2048m (table). Conclusion: Lowlanders with COPD experience pronounced hypoxemia and restriction of sleep in the first night at 2048m that prevents by nocturnal oxygen supplementation. Our study provides novel data to counsel COPD patients travel to altitude

Introduction: Altitude travel in patients with COPD may be hampered by limitation in exercise performance but the extent and underlying physiological mechanisms have not been conclusively studied. Objective: To evaluate exercise performance in patients with COPD living below 600m travelling to 2048m. Methods 29 COPD patients, GOLD grade 2-3, mean±SD aged 65±6y, FEV1 59±13%pred. underwent bicycle spiroergometry with an identical ramp protocol to exhaustion at 490m (Zurich) and, within 2h after rapid ascent, at 2048m (St. Moritz). Physiological variables during the final 30sec of exercise were compared between altitudes. Results: Altitude-induced hypoxemia at 2048m reduced maximal work rate and oxygen uptake while heart rate, breathing reserve, and dyspnoea did not change (table). Conclusions: Ascent to 2048m, an altitude corresponding to that of many alpine resorts, reduced exercise performance of lowlanders with COPD only slightly. Since neither breathing nor heart rate reserve were altered, the altitude-induced performance impairment may have been due to effects of hypoxia on dyspnoea perception and muscle function rather than due to aggravated ventilatory or cardiovascular constraints. Grant: Swiss National Science Foundation, Lunge Zurich.

Objective There are concerns that altitude travel may induce cerebral hypoxia, in particular in patients with preexisting lung disease and during sleep. Therefore, we investigated cerebral tissue oxygenation (CTO) by near-infrared spectroscopy in lowlanders with COPD spending one night at 2590 m. Methods 37 COPD patients living below 800m (mean±SD age 62.4±12.3y, FEV1 61±16 %pred.) underwent sleep studies including pulse oximetry (SpO2) and prefrontal CTO recordings at 490m and in the first night after arrival at 2590m. Results During the night at 2590m, SpO2 and CTO were decreased and unstable due to apneas/hypopneas compared to 490m. These changes were less pronounced in CTO than in SpO2 (table). Conclusions Lowlanders with COPD travelling to 2590m experience persistent arterial hypoxemia and cerebral tissue deoxygenation due to reduced barometric pressure and high altitude periodic breathing. The decreases in CTO are less pronounced than those of SpO2 possibly due to cerebrovascular autoregulation. Grant: Swiss National Science Foundation, Lung League Zurich

Objective: We quantified exercise performance of lowlanders with COPD travelling to moderate altitude and investigated whether reduced cerebral oxygen availability would limit performance. Methods: 31 COPD patients, GOLD grade 2-3, underwent constant-load bicycle spiroergometry to exhaustion at 60% of maximal work rate (mean±SD 65±29W) at 490m and 2590m in randomized order. Pulmonary gas exchange, arterial blood gases, cerebral tissue oxygenation (CTO) by near-infrared spectroscopy, and middle cerebral artery peak blood flow velocity (MCAv) by transcranial Doppler ultrasound were measured. The final 30sec of exercise were compared between altitudes. Results: At 2590m endurance was significantly reduced in association with reduced CTO compared to 490m. The exercise-induced increase in MCAv was similar at both altitudes while MCAv sensitivity to exercise-induced hypoxia was reduced at 2590m (table). Conclusions: In lowlanders with COPD travelling to 2590m exercise endurance was reduced compared to 490m. Our data suggest that impaired cerebral oxygen availability limits exercise performance in patients with COPD at 2590m. Grant:SNF, Lunge Zürich.

Introduction: Patients with COPD experience poor sleep at sea level. We investigated whether this was aggravated during a stay at altitude. Methods: 32 COPD patients, GOLD 2-3, living below 800 m, mean±SD age 64±6 yrs, FEV1 60±15% pred., underwent polysomnography and questionnaire evaluations during one night at 490m, 1650m and 2590m, in random order. Results: Compared to 490m sleep studies at the higher altitudes revealed reduced oxygen saturation, a rise in central apnoea/hypopnoea index, reduced slow wave sleep and sleep efficiency, and an impaired subjective sleep quality. The latter was correlated with the nocturnal oxygen saturation (Spearman r=0.22, P=0.03) but not with the AHI (Spearman r=-0.12, P=0.24). Conclusions: During a stay at moderate altitude lowlanders with COPD experience pronounced hypoxemia that induces central sleep apnoea and sleep disturbances. Grant: Swiss National Science Foundation, Zurich Lung League.

Background Chronic obstructive pulmonary disease (COPD) is associated with exercise intolerance at sea level and further limitations are expected at altitude. We quantified exercise performance of COPD patients travelling to moderate altitude and analyzed responsible mechanisms.Methods 37 patients with COPD, (mean±SD FEV1 54±15%) performed submaximal, constant-load bicycle spiroergometry to exhaustion in Zurich (490m) at 60% of maximal work rate (63±30watts), and on the 2nd day after arrival at Davos Jakobshorn (2590m). Performance was compared between altitudes.Results At 2590m exercise endurance was reduced by 57%, and this was associated by a reduced oxygen uptake and PaO2 compared to 490m.View this table:Results of exercise testsConclusion In COPD patients, exposed to hypobaric hypoxia at 2590m submaximal exercise endurance was reduced by more than half compared to 490m. The exercise limitation at altitude was related to hypoxemia due to low barometric pressure but not to ventilatory limitation.Grant:Swiss National Science Foundation.