Feasibility of Delivering 5-Day Normobaric Hypoxia Breathing in a Hospital Setting

Abstract

Background: Beneficial effects of breathing at [Formula: see text] < 0.21 on disease outcomes have been reported in previous preclinical and clinical studies. However, the safety and intra-hospital feasibility of breathing hypoxic gas for 5 d have not been established. In this study, we examined the physiologic effects of breathing a gas mixture with [Formula: see text] as low as 0.11 in 5 healthy volunteers.

Methods: All 5 subjects completed the study, spending 5 consecutive days in a hypoxic tent, where the ambient oxygen level was lowered in a stepwise manner over 5 d, from [Formula: see text] of 0.16 on the first day to [Formula: see text] of 0.11 on the fifth day of the study. All the subjects returned to an environment at room air on the sixth day. The subjects' [Formula: see text], heart rate, and breathing frequency were continuously recorded, along with daily blood sampling, neurologic evaluations, transthoracic echocardiography, and mental status assessments.

Results: Breathing hypoxia concentration dependently caused profound physiologic changes, including decreased [Formula: see text] and increased heart rate. At [Formula: see text] of 0.14, the mean [Formula: see text] was 92%; at [Formula: see text] of 0.13, the mean [Formula: see text] was 93%; at [Formula: see text] of 0.12, the mean [Formula: see text] was 88%; at [Formula: see text] of 0.11, the mean [Formula: see text] was 85%; and, finally, at an [Formula: see text] of 0.21, the mean [Formula: see text] was 98%. These changes were accompanied by increased erythropoietin levels and reticulocyte counts in blood. All 5 subjects concluded the study with no adverse events. No subjects exhibited signs of mental status changes or pulmonary hypertension.

Conclusions: Results of the current physiologic study suggests that, within a hospital setting, delivering [Formula: see text] as low as 0.11 is feasible and safe in healthy subjects, and provides the foundation for future studies in which therapeutic effects of hypoxia breathing are tested.

Keywords: high-altitude; hypoxemia; hypoxia; hypoxia-inducible factor; pulmonary hypertension.

Fig. 1.

Demographic data (A) and schema of changes of concentrations of ${\text{F}}_{{\text{IO}}_{\text{2}}}$ during the study period (B). Target ${\text{F}}_{{\text{IO}}_{\text{2}}}$ (0.11) is shown in red.

Fig. 2.

Heart rate (beats/min) increases with decreasing ${\text{F}}_{{\text{IO}}_{\text{2}}}$ and recovers to baseline with return to normoxia. A: During the day, and B: during the night.

Fig. 3.

A: ${\text{S}}_{{\text{pO}}_{\text{2}}}$ over time during the day. B: ${\text{S}}_{{\text{pO}}_{\text{2}}}$ over time during the night. C: Arterial blood gas levels at ${\text{F}}_{{\text{IO}}_{\text{2}}}$ 0.11.

Fig. 4.

Daily erythropoietin concentration (A) and reticulocyte count. (B). Data are shown as mean, with whiskers depicting SD. * P < .05.