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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.
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Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Estudios Cruzados , Altitud , Ciclismo , DisneaRESUMEN
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 < 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 ([Formula: see text]) at 490 m were: SpO2 92 ± 1%, CTO 65 ± 1%, [Formula: see text] 37.7 ± 2.0 L/min; at 2048 m with placebo: SpO2 85 ± 1%, CTO 61 ± 1%, [Formula: see text] 40.6 ± 2.0 L/min and with NOT: SpO2 84 ± 1%; CTO 61 ± 1%; [Formula: see text] 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.
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Altitud , Ejercicio Físico , Terapia por Inhalación de Oxígeno , Oxígeno , Enfermedad Pulmonar Obstructiva Crónica , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxígeno/administración & dosificación , Oxígeno/sangre , Rendimiento Físico Funcional , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/terapiaRESUMEN
Altitude 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.
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Altitud , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Hipoxia , Persona de Mediana Edad , Oximetría , Oxígeno , Enfermedad Pulmonar Obstructiva Crónica/complicacionesRESUMEN
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 <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 (SpO2). Results: In the first nights at 490 m, 2,048 m placebo, and 2,048 m NOT, medians (quartiles) of SpO2 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 SpO2 and lowered HR, without changing QTc. Whether oxygen therapy would reduce HR and arrhythmia during longer altitude sojourns remains to be elucidated.
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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.
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Altitud , Enfermedad Pulmonar Obstructiva Crónica , Anciano , Presión Sanguínea , Estudios Cruzados , Humanos , Hipoxia/diagnóstico , Hipoxia/terapia , Oxígeno , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/terapiaRESUMEN
Importance: There are no established measures to prevent nocturnal breathing disturbances and other altitude-related adverse health effects (ARAHEs) among lowlanders with chronic obstructive pulmonary disease (COPD) traveling to high altitude. Objective: To evaluate whether nocturnal oxygen therapy (NOT) prevents nocturnal hypoxemia and breathing disturbances during the first night of a stay at 2048 m and reduces the incidence of ARAHEs. Design, Setting, and Participants: This randomized, placebo-controlled crossover trial was performed from January to October 2014 with 32 patients with COPD living below 800 m with forced expiratory volume in the first second of expiration (FEV1) between 30% and 80% predicted, pulse oximetry of at least 92%, not requiring oxygen therapy, and without history of sleep apnea. Evaluations were performed at the University Hospital Zurich (490 m, baseline) and during 2 stays of 2 days and nights each in a Swiss Alpine hotel at 2048 m while NOT or placebo treatment was administered in a randomized order. Between altitude sojourns, patients spent at least 2 weeks below 800 m. Data analysis was performed from January 1, 2015, to December 31, 2018. Intervention: During nights at 2048 m, NOT or placebo (room air) was administered at 3 L/min by nasal cannula. Main Outcomes and Measures: Coprimary outcomes were differences between NOT and placebo intervention in altitude-induced change in mean nocturnal oxygen saturation (SpO2) as measured by pulse oximetry and apnea-hypopnea index (AHI) measured by polysomnography during night 1 at 2048 m and analyzed according to the intention-to-treat principle. Further outcomes were the incidence of predefined ARAHE, other variables from polysomnography results and respiratory sleep studies in the 2 nights at 2048 m, clinical findings, and symptoms. Results: Of the 32 patients included, 17 (53%) were women, with a mean (SD) age of 65.6 (5.6) years and a mean (SD) FEV1 of 53.1% (13.2%) predicted. At 490 m, mean (SD) SpO2 was 92% (2%) and mean (SD) AHI was 21.6/h (22.2/h). At 2048 m with placebo, mean (SD) SpO2 was 86% (3%) and mean (SD) AHI was 34.9/h (20.7/h) (P < .001 for both comparisons). Compared with placebo, NOT increased SpO2 by a mean of 9 percentage points (95% CI, 8-11 percentage points; P < .001), decreased AHI by 19.7/h (95% CI, 11.4/h-27.9/h; P < .001), and improved subjective sleep quality measured on a visual analog scale by 9 percentage points (95% CI, 0-17 percentage points; P = .04). During visits to 2048 m or within 24 hours after descent, 8 patients (26%) using placebo and 1 (4%) using NOT experienced ARAHEs (P < .001). Conclusions and Relevance: Lowlanders with COPD experienced hypoxemia, sleep apnea, and impaired well-being when staying at 2048 m. Because NOT significantly mitigated these undesirable effects, patients with moderate to severe COPD may benefit from preventive NOT during high altitude travel. Trial Registration: ClinicalTrials.gov Identifier: NCT02150590.
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Altitud , Hipoxia , Terapia por Inhalación de Oxígeno , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Síndromes de la Apnea del Sueño , Anciano , Femenino , Humanos , Hipoxia/complicaciones , Hipoxia/terapia , Masculino , Persona de Mediana Edad , Oximetría , Oxígeno/sangre , Síndromes de la Apnea del Sueño/complicaciones , Síndromes de la Apnea del Sueño/terapia , ViajeRESUMEN
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 (SpO2), the apnea-hypopnea index (AHI), and sleep structure were compared between altitudes. Results: Polysomnography during the first night at each altitude revealed a reduced SpO2 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. Trial Registration: ClinicalTrials.gov: NCT01870830.
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Altitud , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Intercambio Gaseoso Pulmonar/fisiología , Apnea Obstructiva del Sueño/fisiopatología , Sueño/fisiología , Anciano , Estudios Cruzados , Femenino , Humanos , Hipoxia/fisiopatología , Pulmón/fisiología , Masculino , Persona de Mediana Edad , Polisomnografía , Respiración , Encuestas y Cuestionarios , ViajeRESUMEN
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% CI -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 PaO2 were 9.0 (8.4; 9.4), 8.1 (7.5; 8.6), and 6.8 (6.3; 7.4) kPa, 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. REGISTRATION: ClinicalTrials.gov: NCT01875133.
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Altitud , Tolerancia al Ejercicio , Pulmón/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Viaje , Anciano , Análisis de los Gases de la Sangre , Estudios Cruzados , Progresión de la Enfermedad , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Terapia por Inhalación de Oxígeno , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/terapia , Índice de Severidad de la Enfermedad , Suiza , Factores de Tiempo , Prueba de PasoRESUMEN
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.