Cardiorespiratory Adaptation to Short-Term Exposure to Altitude vs. Normobaric Hypoxia in Patients with Pulmonary Hypertension

Abstract

Prediction of adverse health effects at altitude or during air travel is relevant, particularly in pre-existing cardiopulmonary disease such as pulmonary arterial or chronic thromboembolic pulmonary hypertension (PAH/CTEPH, PH). A total of 21 stable PH-patients (64 ± 15 y, 10 female, 12/9 PAH/CTEPH) were examined by pulse oximetry, arterial blood gas analysis and echocardiography during exposure to normobaric hypoxia (NH) (FiO2 15% ≈ 2500 m simulated altitude, data partly published) at low altitude and, on a separate day, at hypobaric hypoxia (HH, 2500 m) within 20−30 min after arrival. We compared changes in blood oxygenation and estimated pulmonary artery pressure in lowlanders with PH during high altitude simulation testing (HAST, NH) with changes in response to HH. During NH, 4/21 desaturated to SpO2 < 85% corresponding to a positive HAST according to BTS-recommendations and 12 qualified for oxygen at altitude according to low SpO2 < 92% at baseline. At HH, 3/21 received oxygen due to safety criteria (SpO2 < 80% for >30 min), of which two were HAST-negative. During HH vs. NH, patients had a (mean ± SE) significantly lower PaCO2 4.4 ± 0.1 vs. 4.9 ± 0.1 kPa, mean difference (95% CI) −0.5 kPa (−0.7 to −0.3), PaO2 6.7 ± 0.2 vs. 8.1 ± 0.2 kPa, −1.3 kPa (−1.9 to −0.8) and higher tricuspid regurgitation pressure gradient 55 ± 4 vs. 45 ± 4 mmHg, 10 mmHg (3 to 17), all p < 0.05. No serious adverse events occurred. In patients with PH, short-term exposure to altitude of 2500 m induced more pronounced hypoxemia, hypocapnia and pulmonary hemodynamic changes compared to NH during HAST despite similar exposure times and PiO2. Therefore, the use of HAST to predict physiological changes at altitude remains questionable. (ClinicalTrials.gov: NCT03592927 and NCT03637153).

Keywords: chronic thromboembolic pulmonary hypertension; high altitude; hypobaric hypoxia; normobaric hypoxia; pulmonary hypertension.

Conflict of interest statement

S.R. Schneider has nothing to disclose. M. Lichtblau has nothing to disclose. M. Furian has nothing to disclose. L. Mayer has nothing to disclose. C. Berlier has nothing to disclose. J. Müller has nothing to disclose. S. Saxer has nothing to disclose. E.I. Schwarz has nothing to disclose. K.E. Bloch has nothing to disclose. S. Ulrich reports grants from Johnson and Johnson SA, Switzerland, during the conduct of the study; and grants from the Swiss National Science Foundation and Zurich Lung, grants and personal fees from Orpha Swiss, and personal fees from Actelion SA and MSD SA, outside the submitted work.

Figures

Figure 1

Flow chart: HAST = High altitude simulation test.

Figure 2

SpO2 (triangles, blue) and PaO2 (circles, green) in normobaric normoxia (470 m), normobaric hypoxia (470 m) and at high altitude (2500 m). HAST = High altitude simulation test. Measurements are summarized as means and 95% Confidence Intervals. Data are computed from a mixed-effect regression model with fixed effects variables as time, age, gender and New York Heart Association class.

Figure 3

Physiological outcomes after 20–30 min under normobaric (FiO2: 15%) vs. hypobaric hypoxia (2500 m). Triangles and circles indicate mixed-effect model derived means and 95% confidence intervals (CI) of outcomes during normobaric hypoxia (FiO2: 15%) and hypobaric hypoxia (2500 m) after 20–30 min of exposure. Fixed effects variables are Time, Age, Gender and New York Heart Association class and random effect is the subject ID. Cubes indicate the mixed-effect model derived mean-differences with associated 95% CI.

Figure 4

Predictions for oxygen at altitude. NYHA = New York Heart Association class, HAST = High altitude simulation test, numbers in bar represent absolute numbers. PaO2 (n = 20).

Figure 5

Receiver Operator Characteristic Curve for altitude related adverse health effects at 2500 m. HAST = High altitude simulation test including an exposure to normobaric hypoxia FiO2: 15%, NYHA = New York Heart Association class, ROC = Receiver Characteristic Operator Curve, AUC = Area under Curve.