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

Eur Heart J. 2017 Apr 14;38(15):1159-1168. doi: 10.1093/eurheartj/ehx099.


Aims: The purpose of the current trial was to test the hypothesis that breathing oxygen-enriched air increases exercise performance of patients with pulmonary arterial or chronic thrombo-embolic pulmonary hypertension (PAH/CTEPH) and to investigate involved mechanisms.

Methods and results: Twenty-two patients with PAH/CTEPH, eight women, means ± SD 61 ± 14 years, resting mPAP 35 ± 9mmHg, PaO2 ambient air >7.3 kPa, underwent four bicycle ergospirometries to exhaustion on different days, while breathing oxygen-enriched (FiO2 0.50, hyperoxia) or ambient air (FiO2 0.21, normoxia) using progressively increased or constant load protocols (with 75% maximal work rate under FiO2 0.21), according to a randomized, sham-controlled, single-blind, cross-over design. ECG, pulmonary gas-exchange, arterial blood gases, cerebral and quadriceps muscle tissue oxygenation (CTO and QMTO) by near-infrared spectroscopy were measured. In ramp exercise, maximal work rate increased from 113 ± 38 W with normoxia to 132 ± 48 W with hyperoxia, mean difference 19.7 (95% CI 10.5-28.9) W, P < 0.001. Constant load exercise endurance increased from 571 ± 443 to 1242 ± 514 s, mean difference 671 (95% CI 392-951) s, P < 0.001. At end-exercise with hyperoxia PaO2, CTO, QMTO, and PaCO2 were increased, and ventilatory equivalents for CO2 were reduced while the physiological dead space/tidal volume ratio remained unchanged.

Conclusion: In patients with PAH/CTEPH, breathing oxygen-enriched air provides major increases in exercise performance. This is related to an improved arterial oxygenation that promotes oxygen availability in muscles and brain and to a reduction of the excessive ventilatory response to exercise thereby enhancing ventilatory efficiency. Patients with PAH/CTEPH may therefore benefit from oxygen therapy during daily physical activities and training.

Trial registration: clinicaltrials.gov Identifier: NCT01748474.

Keywords: Exercise; Oxygen therapy; Precapillary pulmonary hypertension; Pulmonary hypertension.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbon Dioxide / blood
  • Cross-Over Studies
  • Exercise / physiology
  • Exercise Test
  • Exercise Tolerance / physiology*
  • Female
  • Heart Rate / physiology
  • Humans
  • Hypertension, Pulmonary / physiopathology
  • Hypertension, Pulmonary / therapy*
  • Male
  • Middle Aged
  • Oxygen / administration & dosage*
  • Oxygen / blood
  • Oxygen Consumption / physiology
  • Partial Pressure
  • Pulmonary Gas Exchange / physiology
  • Single-Blind Method


  • Carbon Dioxide
  • Oxygen

Associated data

  • ClinicalTrials.gov/NCT01748474