Effect of breathing oxygen-enriched air on exercise performance in patients with precapillary pulmonary hypertension: randomized, sham-controlled cross-over trial

Ulrich, Silvia; Hasler, Elisabeth; Saxer, Stéphanie; Furian, Michael; Müller-Mottet, Séverine; Keusch, Stephan; Bloch, Konrad E.

doi:10.1093/eurheartj/ehx099

Cited by 69 publications

(75 citation statements)

References 27 publications

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“…To address this point, our laboratory performed a randomized, sham-controlled trial demonstrating that nocturnal oxygen therapy in PAH/ CTEPH patients with nocturnal oxygen desaturation improves not only sleep-disordered breathing, but also exercise capacity (i.e., the 6-min walk distance) and symptoms during daytime already after 1 wk (70). In recent further randomized trials in patients with PAH/CTEPH, our laboratory has found that breathing oxygen-enriched air (FI O 2 0.50) compared with breathing ambient air (FI O 2 0.21) significantly enhanced maximal work rate in cycling ramp exercise tests and substantially increased endurance in submaximal constant-load exercise (69). These improvements were associated with a higher Pa CO 2 at end-exercise and a reduced ratio of V E/V CO 2 (Fig.…”

Section: Effect Of Hyperoxia On Exercise Performance In Patients With Phmentioning

confidence: 98%

“…The main symptom is exertional dyspnea, which is typically associated with oxygen desaturation, and leads to reduced quality of life (59). In terms of lung function, the characteristic alteration in patients with PAH/CTEPH is a reduction in diffusing capacity while lung volumes are generally within normal limits (69). Exposure to hypobaric hypoxia at altitude or during air flights increases PAP through hypoxic pulmonary vasoconstriction already in healthy individuals and, presumably, even more in patients with PH due to their impaired hemodynamics and gas exchange (10,34,67).…”

Section: Effect Of Hypobaric Hypoxia On Exercise Performance In Patiementioning

confidence: 99%

“…A systematic review of the literature cited in PubMed did not identify any further randomized trials investigating the effect of breathing oxygen-enriched air on exercise performance in PAH/CTPEH, in addition to the ones described above (Table A2) (69).…”

Section: Effect Of Hyperoxia On Exercise Performance In Patients With Phmentioning

confidence: 99%

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Effect of hypoxia and hyperoxia on exercise performance in healthy individuals and in patients with pulmonary hypertension: a systematic review

Ulrich

Schneider

Bloch

2017

Journal of Applied Physiology

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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, 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 pulmonary hypertension (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 pulmonary hypertension, alterations in the inspiratory PO2 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 physiologic mechanisms helps counselling individuals planning altitude or air travel and prescribing oxygen therapy to patients with pulmonary hypertension. 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 deliv...

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Section: Effect Of Hyperoxia On Exercise Performance In Patients With Phmentioning

confidence: 98%

Section: Effect Of Hypobaric Hypoxia On Exercise Performance In Patiementioning

confidence: 99%

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Effect of hypoxia and hyperoxia on exercise performance in healthy individuals and in patients with pulmonary hypertension: a systematic review

Ulrich

Schneider

Bloch

2017

Journal of Applied Physiology

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“…Our initial literature search retrieved 743 records. From them, 31 potentially eligible RCTs were identified . Studies were excluded from the analysis if they did not include CTEPH patients as the study population, did not have a completely randomized design, were letter and review articles, or were low‐quality studies.…”

Section: Resultsmentioning

confidence: 99%

A meta‐analysis of randomized controlled trials in targeted treatments of chronic thromboembolic pulmonary hypertension

Zhang

Huang

et al. 2019

Clinical Respiratory J

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Background Chronic thromboembolic pulmonary hypertension (CTEPH) results in a progressively worsening course associated with substantial morbidity and mortality. The purpose of this comprehensive study was to determine the clinical efficacy of targeted therapeutic interventions for this disease. Methods We searched Medline, Embase, Cochrane databases and Pubmed for relevant clinical studies. Randomized controlled trials comparing the effects of targeted treatments to control in CTEPH population were included. Pooled estimates were calculated using a random effect model. Heterogeneity was determined using the I2 statistic. Results This analysis included 6 studies with a total of 565 patients. We found that targeted treatments approved for pulmonary arterial hypertension (PAH) were associated with a larger improvement in exercise capacity, haemodynamic parameters, functional status and clinical symptom. There were no statistically significant differences associated with targeted treatments compared with control in all‐cause mortality and safety outcomes. Conclusions This is the first systematic review and meta‐analysis of randomized controlled trials revealing a positive role of PAH‐targeted therapies in CTEPH. Future larger randomized trials with a focus on long‐term clinical outcomes are urgently needed.

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“…As such, patients have been characterized by impaired baroreflex sensitivity, increased sympathetic nerve traffic and hypocapnia . Recently, reduced cerebral oxygenation and its impact on exercise capacity and reduced cerebrovascular reactivity to CO 2 have been documented in PAH, using near‐infrared spectroscopy; however, the associated integrative physiological mechanisms were not thoroughly investigated. Therefore, the aim of this study was to conduct a comprehensive assessment of the cerebrovascular function in patients with PAH to determine whether it is associated with abnormal cerebral vascular regulation and oxygenation and their physiological and clinical consequences.…”

Section: Introductionmentioning

confidence: 99%

Compromised Cerebrovascular Regulation and Cerebral Oxygenation in Pulmonary Arterial Hypertension

Malenfant

Brassard

Paquette

et al. 2017

JAHA

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BackgroundFunctional cerebrovascular regulatory mechanisms are important for maintaining constant cerebral blood flow and oxygen supply in heathy individuals and are altered in heart failure. We aim to examine whether pulmonary arterial hypertension (PAH) is associated with abnormal cerebrovascular regulation and lower cerebral oxygenation and their physiological and clinical consequences.Methods and ResultsResting mean flow velocity in the middle cerebral artery mean flow velocity in the middle cerebral artery (MCAvmean); transcranial Doppler), cerebral pressure‐flow relationship (assessed at rest and during squat‐stand maneuvers; analyzed using transfer function analysis), cerebrovascular reactivity to CO 2, and central chemoreflex were assessed in 11 patients with PAH and 11 matched healthy controls. Both groups also completed an incremental ramp exercise protocol until exhaustion, during which MCAvmean, mean arterial pressure, cardiac output (photoplethysmography), end‐tidal partial pressure of CO 2, and cerebral oxygenation (near‐infrared spectroscopy) were measured. Patients were characterized by a significant decrease in resting MCAvmean (P<0.01) and higher transfer function gain at rest and during squat‐stand maneuvers (both P<0.05). Cerebrovascular reactivity to CO 2 was reduced (P=0.03), whereas central chemoreceptor sensitivity was increased in PAH (P<0.01), the latter correlating with increased resting ventilation (R 2=0.47; P<0.05) and the exercise ventilation/CO2 production slope (trueV˙normalE/normalV˙CO2 slope; R 2=0.62; P<0.05) during exercise for patients. Exercise‐induced increases in MCAvmean were limited in PAH (P<0.05). Reduced MCAvmean contributed to impaired cerebral oxygen delivery and oxygenation (both P<0.05), the latter correlating with exercise capacity in patients with PAH (R 2=0.52; P=0.01).ConclusionsThese findings provide comprehensive evidence for physiologically and clinically relevant impairments in cerebral hemodynamic regulation and oxygenation in PAH.

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Effect of breathing oxygen-enriched air on exercise performance in patients with precapillary pulmonary hypertension: randomized, sham-controlled cross-over trial

Abstract: clinicaltrials.gov Identifier: NCT01748474.

Cited by 69 publications

References 27 publications

Effect of hypoxia and hyperoxia on exercise performance in healthy individuals and in patients with pulmonary hypertension: a systematic review

Effect of hypoxia and hyperoxia on exercise performance in healthy individuals and in patients with pulmonary hypertension: a systematic review

A meta‐analysis of randomized controlled trials in targeted treatments of chronic thromboembolic pulmonary hypertension

Compromised Cerebrovascular Regulation and Cerebral Oxygenation in Pulmonary Arterial Hypertension

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