The Influence of 17 Hours of Normobaric Hypoxia on Parallel Adjustments in Exhaled Nitric Oxide and Airway Function in Lowland Healthy Adults

Abstract

Van Iterson, Erik H., Eric M. Snyder, and Bruce D. Johnson. The influence of 17 hours of normobaric hypoxia on parallel adjustments in exhaled nitric oxide and airway function in lowland healthy adults. High Alt Med Biol. 18:1-10, 2017.-Currently, there is a disparate understanding of the role that normobaric hypoxia plays in affecting nitric oxide (NO) measured in exhaled air (eNO) and airway function in lowland healthy adults. Compared to normobaric normoxia, this study aimed to test the effect of 17 hours of normobaric hypoxia on relationships between eNO and airway function in healthy adults. In a crossover study including 2 separate visits, 26 lowland healthy Caucasian adults performed eNO and pulmonary function tests on visit 1 in normobaric normoxia, while repeating all tests on visit 2 following 17 hours of normobaric hypoxia (12.5% O₂). Compared to normobaric normoxia, eNO (29 ± 24 vs. 36 ± 28 ppb), forced expiratory volume in one second (FEV₁) (4.1 ± 0.7 vs. 4.3 ± 0.8 L), mean forced expiratory flow between 25% and 75% FVC (FEF_25-75) (3.9 ± 1.0 vs. 4.2 ± 1.2 L/s), and forced expiratory flow at 75% FVC (FEF₇₅) (2.0 ± 0.7 vs. 2.3 ± 0.8 L/s) increased in normobaric hypoxia, respectively (all p < 0.05). Correlations at normoxia between eNO and FEV₁ (r = 0.39 vs. 0.44), FEF_25-75 (r = 0.51 vs. 0.51), and FEF₇₅ (r = 0.53 vs. 0.55) persisted as both parameters increased in hypoxia, respectively. For the first time, these data suggest that 17 hours of hypoxic breathing in the absence of low ambient pressure contribute to increased eNO and airway function in lowland healthy adults.

Keywords: NO hypoxia; NOS hypoxia; altitude hypoxia; ambient pressure hypoxia; hypobaric hypoxia; pulmonary function hypoxia.

FIG. 1.

eNO in normobaric normoxia or 17 hours of normobaric hypoxia. (A) Absolute eNO at normobaric normoxia compared to 17 hours of normobaric hypoxia (N = 26). (B) Middle horizontal line is the mean. Upper and lower horizontal lines are standard deviation. The relative % (open circles, left axis) or absolute (Δ, closed circles, right axis) change in eNO from normobaric normoxia to 17 hours of normobaric hypoxia (N = 26). (C) Absolute eNO at normobaric normoxia compared to 17 hours of normobaric hypoxia in participants demonstrating eNO <55 ppb (N = 20). (D) The relative % (open circle, left axis) or Δ (closed circles, right axis) change in eNO from normobaric normoxia to 17 hours of normobaric hypoxia in participants demonstrating eNO <55 ppb (N = 20). Effect size can be interpreted as small = 0.2; medium = 0.5; and large ≥0.8. eNO, exhaled nitric oxide.

FIG. 2.

Airway function in normobaric normoxia or 17 hours of normobaric hypoxia. (A) FVC (N = 26). (B) FVC in participants demonstrating eNO <55 ppb (N = 20). (C) FEV₁ (N = 26). (D) FEV₁ in participants demonstrating eNO <55 ppb (N = 20). (E) Forced expiratory flow at 25%–75% FVC (FEF_25–75) (N = 26). (F) FEF_25–75 in participants demonstrating eNO <55 ppb (N = 20). (G) Forced expiratory flow at 75% of FVC (FEF₇₅). (H) FEF₇₅ in participants demonstrating eNO <55 ppb (N = 20). FEV₁, forced expiratory volume in one second; FVC, forced vital capacity.

FIG. 3.

Change in airway function from normobaric normoxia to 17 hours of normobaric hypoxia. Relative % (open circles, left axis) or absolute (Δ, closed circles, right axis) change. (A) FVC (N = 26). (B) FVC in participants demonstrating eNO <55 ppb (N = 20). (C) FEV₁ (N = 26). (D) FEV₁ in participants demonstrating eNO <55 ppb (N = 20). (E) Forced expiratory flow at 25%–75% FVC (FEF_25–75) (N = 26). (F) FEF_25–75 in participants demonstrating eNO <55 ppb (N = 20). (G) Forced expiratory flow at 75% of FVC (FEF₇₅) (N = 26). (H) FEF₇₅ in participants demonstrating eNO <55 ppb (N = 20). For all panels: middle horizontal line is the mean, whereas the upper and lower horizontal lines are standard deviation. Effect size can be interpreted as small = 0.2; medium = 0.5; and large ≥0.8.

FIG. 4.

Pearson product moment correlations (correlation coefficient, r, and 95% CL) between eNO and resting airway function at normobaric normoxia (closed circles and solid line) or 17 hours of normobaric hypoxia (open circles and dashed line). (A) FVC (N = 26). (B) FVC in participants demonstrating eNO <55 ppb (N = 20). (C) FEV₁ (N = 26). (D) FEV₁ in participants demonstrating eNO <55 ppb (N = 20). (E) Forced expiratory flow at 25%–75% FVC (FEF_25–75) (N = 26). (F) FEF_25–75 in participants demonstrating eNO <55 ppb (N = 20). (G) Forced expiratory flow at 75% of FVC (FEF₇₅) (N = 26). (H) FEF₇₅ in participants demonstrating eNO <55 ppb (N = 20). Correlation coefficients can be interpreted as small = 0.10; medium = 0.30; and large ≥0.50. CL, confidence limits.