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Post-exercise accumulation of interstitial lung water is greater in hypobaric than normobaric hypoxia in adults born prematurely

https://doi.org/10.1016/j.resp.2021.103828Get rights and content

Highlights

  • Interstitial lung water accumulation at altitude might precede high-altitude pulmonary oedema development.

  • We studied independent effects of hypobaria on interstitial lung water accumulation following hypoxic exercise in prematurely born adults.

  • Short, moderate-intensity exercise provokes a significant increase in the interstitial lung water accumulation after 8 h of exposure to terrestrial but not simulated altitude.

Abstract

We aimed to gauge the interstitial lung water accumulation following moderate-intensity exercise under normobaric and hypobaric hypoxic conditions in a group of preterm born but otherwise healthy young adults.

Sixteen pre-term-born individuals (age = 21±2yrs.; gestational age = 29±3wk.; birth weight = 1160±273 g) underwent two 8 -h hypoxic/altitude exposures in a cross-over manner: 1) Normobaric hypoxic exposure (NH; FIO2 = 0.142±0.001; PIO2  = 90.6±0.9 mmHg) 2) Hypobaric hypoxic exposure (HH; terrestrial high-altitude 3840 m; PIO2  = 90.2±0.5 mmHg). Interstitial lung water was assessed via quantification of B-Lines (using lung ultrasound) before (normoxia) and after 4-h and 8-h of respective exposures. At each time point, B-Lines were quantified before (Pre) and immediately after (Post) a 6-min moderate-intensity exercise.

The baseline B-lines count were comparable between both conditions (P = 0.191). A higher B-lines count was noted at Pre-H4 in HH versus NH (P = 0.0420). At Post-H8 B-lines score was significantly higher in HH (4.6 ± 1.6) than in NH (3.1 ± 1.4; P = 0.0073). Furthermore, at this time point, a significantly higher number of individuals with B-line scores ≥5 was observed in HH (n = 7) than in NH (n = 3; P = 0.0420).

These findings suggest that short moderate-intensity exercise provokes a significant increase in the interstitial lung water accumulation after 8 h of exposure to terrestrial but not simulated altitude (≈3840 m) in prematurely born adults. Further work is needed to elucidate the exact mechanisms of (moderate-intensity) exercise-induced interstitial lung water accumulation in this population and directly compare the obtained data to full-term born adults.

Introduction

The number of individuals travelling and/or residing at high-altitude regions for both, work, and leisure is constantly increasing. Accordingly, there is a growing number of people exposed to altitude-related hypoxia along with its physiological effect, with some of them having a higher risk for deleterious physiological responses. Individuals born prematurely might represent one such cohort. Indeed, premature birth is known to be associated with numerous long-term respiratory and cardiovascular dysfunctions that present during both rest and exercise (Duke and Lovering, 2020; Lovering et al., 2014). However, whether these long-term impairments result in higher susceptibility for high-altitude ailments or compromised altitude adaptation capacity remains unclear. For example, some evidence from our lab and others suggest that preterm born individuals exhibit reduced hypoxic ventilatory response (Bates et al., 2014; Debevec et al., 2019) which has been associated with the development of high-altitude pulmonary oedema (HAPE), a life-threatening form of non-cardiogenic oedema (Hackett et al., 1988). However, several other studies do not suggest any clear influence of prematurity on hypoxia-related changes on gas exchange (Duke et al., 2014) and/or pulmonary vascular responses (Laurie et al., 2018) during exercise. While the prevailing evidence does suggest that pre-term born as compared to full term-born individuals exhibit altered pulmonary responses to normoxic exercise, the potential additive effects of hypoxia remain uncertain.

Altitude-related reduction in ambient and partial O2 pressure are recognised to provoke pulmonary vasoconstriction, thereby augmenting pulmonary artery pressure and can subsequently, due to related capillary stress failure, result in interstitial lung water accumulation (Bartsch et al., 2005). These pathological responses could sometimes, principally in more susceptible individuals lead to the development of HAPE and/or other altitude-related illnesses (Maggiorini et al., 2001). Up-to-date research in this regard suggests that HAPE susceptible individuals (those having at least one episode of HAPE previously) display both, greater exercise-related pulmonary artery pressure increase (Eldridge et al., 1996) and greater pulmonary artery occlusion pressure reactivity (Maggiorini, 2006). These phenomena, interestingly, do not seem to be directly related to hypoxia and/or oxygenation but exercise per se.

The above-mentioned interstitial lung water accumulation can be assessed using the non-invasive lung ultrasound technique (Pratali et al., 2010; Wimalasena et al., 2013). Limited up-to-date research data suggests that interstitial lung water accumulation correlates to exercise intensity in hypoxia (Pratali et al., 2012). Furthermore, recent evidence indicates that high-intensity exercise increases pulmonary interstitial oedema at terrestrial high-altitude (hypobaric hypoxia, HH) but not at comparable simulated altitude (normobaric hypoxia, NH) (Edsell et al., 2014). Whether the same holds for moderate-intensity exercise is currently unclear. Accordingly, the present work aimed to test the hypothesis that short-term moderate-intensity exercise results in significantly greater interstitial lung water accumulation following exercise under terrestrial (HH) as opposed to simulated (NH) high-altitude conditions in prematurely born young adults. A potential difference between the two conditions is of interest, particularly in clinical populations that might have higher altitude-related illness susceptibility, which is often estimated solely using exercise testing under NH conditions (Richalet et al., 2012).

Section snippets

Methods

The present work was part of a larger (PreTerm) project aiming to comprehensively assess the effects of hypoxia/altitude exposure on physiological responses of prematurely born individuals with methodological details published previously (Debevec et al., 2019, 2020). The protocol and employed procedures were approved by the National Ethics committee (0120−101/2016−2), preregistered at ClinicalTrials.gov (NCT02780908) and conducted following the Declaration of Helsinki guidelines.

Briefly, 16

Results

The sums of B-line count along with the number of participants demonstrating ≥5 B-lines at each time point are depicted in Table 1. The baseline B-lines count were comparable between both conditions (P = 0.191). Even though none of the participants displayed a clinically significant number of B-lines, a slightly higher B-lines count was noted at Pre-H4 in HH versus NH (P = 0.042), with no differences observed at Post-H4 (P = 0.080). Also, no significant differences were observed between NH and

Discussion

In the present report, we show, for the first time, a significant increase in the interstitial lung water accumulation following a short moderate-intensity exercise after 8 h of exposure to terrestrial high-altitude (3840 m) but not during simulated altitude corresponding to the same partial oxygen pressure. Indeed, in line with previous work (Edsell et al., 2014), the obtained data further confirm the independent effect of barometric pressure on interstitial lung water accumulation during

Author statement

Tadej Debevec: Conceptualization, Methodology, Investigation, Writing - Original Draft, Writing - Review & Editing, Funding acquisition Mathias Poussel: Conceptualization, Methodology, Investigation, Data Curation, Writing - Review & Editing Damjan Osredkar: Conceptualization, Methodology, Writing - Review & Editing Sarah J. Willis: Investigation, Writing - Review & Editing Claudio Sartori: Conceptualization, Methodology, Writing - Review & Editing Grégoire P. Millet: Conceptualization,

Acknowledgements

The present project was funded by the Slovene Research Agency (Grant No. J3-7536). We would like to acknowledge the dedicated participants without whom this study would not have been possible. We are also grateful to the late Dr Emmanuel Cauchy, known as “Doctor Vertical”, for assisting us with the hypobaric hypoxic experiments at the Aiguille du Midi Ifremmont laboratory.

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    These authors contributed equally to the present work.

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