Effect of Normobaric Hypoxia on Exercise Performance in Pulmonary Hypertension

Exercise machine equipped with an ergometer (apparatus for measuring the work performed and the effort and reaction of the patient) and spirometer (intrument for measuring the air entering and leaving the lungs)
Patients with pulmonary hypertension exhibited a reduced exercise capacity under hypoxic conditions, although with high inter-individual variability.

Patients with pulmonary hypertension (PH) exhibited a reduced exercise capacity under hypoxic conditions, although with high inter-individual variability, according to the results of a clinical trial published in CHEST.

Investigators conducted a randomized controlled, single-blinded, crossover trial (ClinicalTrials.gov Identifier: NCT03592927) between August 2018 and April 2019 at the University Hospital Zürich in Zürich, Switzerland. They sought to explore the effect of hypoxia compared to normoxia on constant-work-rate-exercise-test (CWRET) time in patients with PH and to evaluate the physiologic mechanisms that are involved in the process. Adult patients who had been diagnosed with pulmonary arterial hypertension (PAH)/chronic thromboembolic pulmonary hypertension (CTEPH) — both summarized as PH herein — were recruited from outpatients of the PH-center Zürich.

All of the participants were randomly assigned to breathe ambient air (normoxia, fraction of inspired oxygen [FiO2]: 21%) initially, followed by normobaric hypoxia (FiO2: 15%), or vice versa, using a sealed facemask with a non-rebreathing 2-way valve during 20 or more minutes of rest. This was followed by use of a symptom-limited cycle-ergometer CWRET until exhaustion.

The primary study outcome was the difference in CWRET time under conditions of normobaric hypoxia compared to ambient air. Arterial blood gases, Borg-dyspnea, tricuspid regurgitation pressure gradient, and mean pulmonary artery pressure (mPAP)/cardiac output ratio by echocardiography were evaluated before and after CWRET.

A total of 28 participants were included in the study. The median patient age was 66 years; 13 of the participants were women. The mean PAP was 41 mm Hg; pulmonary vascular resistance (PVR) was 5.4 Wood Units. CWRET times were 16.9 minutes and 6.7 minutes under normoxia and hypoxia, respectively (P =.006).

At the end of exercise under conditions of normoxia and hypoxia, the median values were as follows: partial pressure of oxygen (PaO2): 8.0 kPa vs 6.4 kPa, respectively; arterial oxygen content: 19.2 mL/dL vs 17.2 mL/dL, respectively; partial pressure of carbon dioxide (PaCO2): 4.7 kPa vs 4.3 kPa, respectively; and lactate: 3.7 mmol/L vs

3.7 mmol/L, respectively (P <.05 for all). The following measurements remained unchanged: Borg scale: 7 vs 6, respectively; tricuspid pressure gradient: 89 mm Hg vs 77 mm Hg, respectively; and mPAP/cardiac output: 4.5 Wood Units vs 3.3 Wood Units, respectively. Per multivariable regression, baseline PVR was the sole factor that predicted hypoxia-induced change in CWRET time.

The investigators concluded that additional studies at real altitude are warranted to explore longer-term changes and adaptive mechanisms to hypoxia in patients with PH, the potential adverse effects, and their risk factors.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Schneider SR, Mayer LC, Lichtblau M, et al. Effect of normobaric hypoxia on exercise performance in pulmonary hypertension – randomized trial. CHEST. Published online September 8, 2020. doi:10.1016/j.chest.2020.09.004