How Hypoxia Affects Exercise Capacity Among Patients With PH

A new study1 highlights the effects of normobaric hypoxia on exercise performance among patients with pulmonary hypertension. To learn more about the study and its findings, Pulmonology Consultant reached out to lead author Silvia Ulrich, MD, who is the head of Pulmonary Hypertension in the Clinic of Pulmonology at the University Hospital of Zurich in Switzerland.

PULMONOLOGY CONSULTANT: For your study, you and your team aimed to determine how hypoxia, compared with normoxia, affects constant-work-rate-exercise-test time in patients with pulmonary hypertension and which physiological mechanisms are involved. To start, what prompted you to conduct this review?

Silvia Ulrich: In our daily practice, many chronically ill patients with pulmonary arterial or distal chronic thromboembolic pulmonary hypertension who are stable on medical therapy ask whether they can join friends and relatives for altitude sojourns in the nearby Alps. They ask about the health effects and threats of exposure to hypoxia. However, very little is known about the effects of hypoxia on patients with pre-existing pulmonary vascular disease.

Preliminary data obtained in the right heart catheterization laboratory suggests that the hemodynamic only slightly changes upon short-term exposure to hypoxia. However, the effect on patient-relevant outcomes, such as exercise capacity, has not been studied so far.

PULM CON: Your analysis included 28 patients with pulmonary hypertension who underwent symptom-limited cycle exercise testing and were randomly assigned to breathe normobaric hypoxic air or ambient air. Can you talk more about the exercise testing and how the type of air affected performance?

SU: We have chosen constant-work-rate exercise time as the primary outcome for this randomized cross-over trial in order to have a patient-relevant outcome, which is exercise capacity, and still have an outcome where we could expect to see an effect of short-term exposure to a hypoxic environment whilst investigating an achievable number of patients affected by pulmonary vascular disease.

We knew from healthy patients and patients with chronic obstructive pulmonary diseases that exercise capacity is reduced in a hypoxic environment. Usually one could say that the lower the inspiratory oxygen content, the lower the exercise capacity. This even more true for patients with hypoxic lung diseases. However, the interindividual variability is very high. So, we did expect to find a reduced exercise capacity in a hypoxic environment also in patients with pulmonary vascular diseases. And this was the case.

PULM CON: Ultimately, your team found that “short-time exposure to hypoxia was well tolerated but reduced CWRET-time compared to normoxia.” What physiological mechanisms might have affected this?

SU: Indeed, the median constant-work-rate exercise time was significantly reduced whilst breathing normobaric hypoxia vs ambient air. However, it is noteworthy, that there was a high interindividual variability, with more than half of the patients with stable pulmonary vascular disease revealing a similar exercise time whilst breathing hypoxic air or ambient air. As the baseline pulmonary vascular resistance was the main predictor of the reduction in exercise time, it is reasonable to postulate that hemodynamically more severely compromised patients are at higher risk.

The oxygen content in the blood and tissue was significantly lower whilst breathing under hypoxic air; thus, in order to have similar oxygen delivery, the body had to increase its heart rate and cardiac output for a given exercise load, which was not possible for too long among some patients with more-severe pulmonary hypertension. Thus, the lower oxygen content in the blood led to peripheral tissue hypoxia, lactic acidosis, and excessive hyperventilation, which all limited exercise capacity.

PULM CON: How might your findings inform clinical practice and improve the treatment of pulmonary hypertension among patients who wish to travel to altitude or by airplane?

SU: With the present study, we have a first important step to know more about the effects of hypoxia on patients with pulmonary vascular disease. However, there are still many more gaps in knowledge until we can reliably counsel our patients concerning altitude exposure or air travel.

We have learned from this short-term study, that patients with more-severe hemodynamic impairment reflected by the higher baseline pulmonary vascular resistance are at higher risk to have a reduced exercise time. However, we have also learned that more than half of stable patients reveal a similar exercise time under both conditions, which is reassuring. Further, longer-term studies are highly warranted. Until performing such field studies, though, we had to perform these first studies under laboratory conditions in order to know more about the risks of hypoxia exposure.

PULM CON: What clinical pearls can chest physicians take away from your study? What is the take home message here?

SU: The most important message from this study is that short-term exposure to hypoxia, including up to 60 minutes of rest followed by symptom-limited constant work-rate exercise, was well tolerated and safe. None of the patients experienced serious adverse events, and the hemodynamics, as assessed by echocardiography, remained stable. Median exercise capacity, however, was significantly reduced with a high interindividual variability, with more than half of the patients even revealing similar performance under both conditions.

This may indicate that for some patients with chronic pulmonary vascular disease, altitude and air travel is safe and feasible. But we still need to know more about risk factors and predictors of altitude-related adverse effects by performing further longer-term studies at real attitude.


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