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Previous studies based on animal models have raised concerns about salbutamol use in ozone air pollution with regard to ozone related lung injury. We conducted a double-blind, randomized, placebo-controlled crossover study including 18 subjects diagnosed with EIB by a eucapnic voluntary hyperpnea (EVH) test. Participants completed 30 min of standardized moderate to vigorous exercise in four conditions: ozone plus salbutamol; room air plus salbutamol; ozone plus placebo medication; and room air plus placebo medication. Spirometry, fraction of exhaled nitric oxide, and symptoms were measured before, immediately after, 30 min after and 1 h after exercise. Measurements between the four conditions were compared using percent change from pre to post exercise. There was a statistically significant difference between the salbutamol and placebo medication groups for spirometric variables including FEV1 (Estimate = 6.3, 95% CI: 4.23-8.37, p < 0.001). No differences were observed between ozone and room air exposures. There were no significant differences in FeNO response between experimental conditions. We found that salbutamol improved pulmonary function in individuals with EIB when exercising in ozone and did not increase eosinophilic airway inflammation as indicated by FeNO. This evidence suggests that it is safe for people with EIB to continue to use salbutamol as proscribed when ozone levels are elevated., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Following high-intensity, normoxic exercise there is evidence to show that healthy females, on average, exhibit less fatigue of the diaphragm relative to males. In the present study, we combined hypoxia with exercise to test the hypothesis that males and females would develop a similar degree of diaphragm fatigue following cycle exercise at the same relative exercise intensity. Healthy young participants (n = 10 male; n = 10 female) with a high aerobic capacity (120% predicted) performed two time-to-exhaustion (TTE; ~85% maximum) cycle tests on separate days breathing either a normoxic or hypoxic (FiO 2  = 0.15) gas mixture. Fatigue of the diaphragm was assessed in response to cervical magnetic stimulation prior to, immediately post-exercise, 10-, 30-, and 60-min post-exercise. Males and females had similar TTE durations in normoxia (males: 690 ± 181 s; females: 852 ± 401 s) and hypoxia (males: 381 ± 160 s; females: 400 ± 176 s) (p > 0.05). Cycling time was significantly shorter in hypoxia versus normoxia in both males and females (p < 0.05) and did not differ on the basis of sex (p > 0.05). Following the hypoxic TTE tests, males and females experienced a similar degree of diaphragm fatigue compared to normoxia as shown by 20%-25% reductions in transdiaphragmatic twitch pressure. This occurred despite the fact that exercise time in hypoxia was substantially shorter relative to normoxia and the cumulative diaphragm work was lower. We also observed that females did not fully recover from diaphragm fatigue in hypoxia, whereas males did (p < 0.05). Sex differences in the rate of diaphragm contractility recovery following exercise in hypoxia might relate to sex-based differences in substrate utilization or diaphragm blood flow., (© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

After a bout of isolated inspiratory work, such as inspiratory pressure threshold loading (IPTL), the human diaphragm can exhibit a reversible loss in contractile function, as evidenced by a decrease in transdiaphragmatic twitch pressure (P DI,TW ). Whether or not diaphragm fatigability after IPTL is affected by neural mechanisms, measured through voluntary activation of the diaphragm (D-VA) in addition to contractile mechanisms, is unknown. It is also unknown if changes in D-VA are similar between sexes given observed differences in diaphragm fatigability between males and females. We sought to determine whether D-VA decreases after IPTL and whether this was different between sexes. Healthy females (n = 11) and males (n = 10) completed an IPTL task with an inspired duty cycle of 0.7 and targeting an intensity of 60% maximal transdiaphragmatic pressure until task failure. P DI,TW and D-VA were measured using cervical magnetic stimulation of the phrenic nerves in combination with maximal inspiratory pressure maneuvers. At task failure, P DI,TW decreased to a lesser degree in females vs. males (87 ± 15 vs. 73 ± 12% baseline, respectively, p = 0.016). D-VA decreased after IPTL but was not different between females and males (91 ± 8 vs. 88 ± 10% baseline, respectively, p = 0.432). When all participants were pooled together, the decrease in P DI,TW correlated with both the total cumulative diaphragm pressure generation (R 2  = 0.43; p = 0.021) and the time to task failure (TTF, R 2 = 0.40; p = 0.30) whereas the decrease in D-VA correlated only with TTF (R 2  = 0.24; p = 0.041). Our results suggest that neural mechanisms can contribute to diaphragm fatigability, and this contribution is similar between females and males following IPTL., (© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Acute respiratory distress syndrome (ARDS) is a lung injury characterized by noncardiogenic pulmonary edema and hypoxic respiratory failure. The purpose of this study was to investigate the effects of therapeutic hypothermia on short-term experimental ARDS. Twenty adult female Yorkshire pigs were divided into four groups (n = 5 each): normothermic control (C), normothermic injured (I), hypothermic control (HC), and hypothermic injured (HI). Acute respiratory distress syndrome was induced experimentally via intrapulmonary injection of oleic acid. Target core temperature was achieved in the HI group within 1 h of injury induction. Cardiorespiratory, histologic, cytokine, and metabolomic data were collected on all animals prior to and following injury/sham. All data were collected for approximately 12 h from the beginning of the study until euthanasia. Therapeutic hypothermia reduced injury in the HI compared to the I group (histological injury score = 0.51 ± 0.18 vs. 0.76 ± 0.06; p = 0.02) with no change in gas exchange. All groups expressed distinct phenotypes, with a reduction in pro-inflammatory metabolites, an increase in anti-inflammatory metabolites, and a reduction in inflammatory cytokines observed in the HI group compared to the I group. Changes to respiratory system mechanics in the injured groups were due to increases in lung elastance (E) and resistance (R) (ΔE from pre-injury = 46 ± 14 cmH 2 O L -1 , p < 0.0001; ΔR from pre-injury: 3 ± 2 cmH 2 O L -1  s - , p = 0.30) rather than changes to the chest wall (ΔE from pre-injury: 0.7 ± 1.6 cmH 2 O L -1 , p = 0.99; ΔR from pre-injury: 0.6 ± 0.1 cmH 2 O L -1  s - , p = 0.01). Both control groups had no change in respiratory mechanics. In conclusion, therapeutic hypothermia can reduce markers of injury and inflammation associated with experimentally induced short-term ARDS., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Airway luminal area (A i ) influences respiratory mechanics during dynamic exercise; however, previous studies have investigated the relationship between airway anatomy and physiological function in different groups of individuals. The purpose of this study was to determine the effect of A i on respiratory mechanics by making in vivo measures of airway dimensions and work of breathing (Wb) in the same individuals. Healthy participants (3F/2M; 23-45 years) completed a cycle exercise test to exhaustion. During exercise, Wb was assessed using an esophageal balloon catheter, while simultaneously assessing minute ventilation ( V ˙ E ). On a separate day, subjects underwent a bronchoscopy procedure to capture optical coherence tomography (OCT) measures of three airways in the right lung. Each participant's Wb- V ˙ E data were fit to a non-linear regression equation (Wb = a V ˙ E 3  + b V ˙ E 2 ) that partitions Wb into its turbulent resistive (a) and viscoelastic (b) components. Measures of A i and luminal diameter were made for the 4th-6th airway generations. A composite index of airway size was calculated as the sum of the A i for each generation and the total area of the 4th-6th generation was calculated based on Weibel's model. Constant a was significantly correlated to the Weibel model total airway area (r = -0.94, p = 0.017) and index of airway size (r = -0.929, p = 0.023), whereas constant b was not associated with either measure (both p > 0.05). We found that individuals who had the smallest A i had the highest resistive Wb and our findings provide the basis for further study of the relationship between airway size and respiratory mechanics during exercise., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Whether the large lungs of swimmers result from intensive training or genetic endowment has been widely debated. Given that peak lung growth velocities occur during puberty, this study examined if competitive swimming during puberty affected lung growth. Eleven- to fourteen-year-old healthy female competitive swimmers and controls were assessed before (PRE) and after (POST) one swimming season (7.4 ± 0.5 months). Pulmonary function testing included lung volumes, spirometry, diffusion capacity (D L , CO ), and maximal inspiratory (PI MAX ) and expiratory (PE MAX ) pressures. Ventilatory constraints, including end-expiratory lung volume, expiratory flow limitation, and utilization of ventilatory capacity, were assessed during an incremental cycling test. Swimmers (n = 11) and controls (n = 10) were of similar age, size, and sexual maturity (P > 0.05). However, swimmers compared to controls had a greater total lung capacity (PRE 4.73 ± 0.73 vs. 3.93 ± 0.46, POST 5.08 ± 0.68 vs. 4.19 ± 0.64 L; P < 0.01), peak expiratory flow (PRE 6.48 ± 0.92 vs. 5.70 ± 0.86, POST 6.97 ± 0.84 vs. 6.00 ± 0.77 L·s -1 ; P = 0.03), and PE MAX (P < 0.001). Although D L , CO was greater in swimmers (P = 0.01), differences were attenuated when expressed relative to alveolar volume (PRE 5.14 ± 0.60 vs. 5.44 ± 0.44, POST 4.91 ± 0.56 vs. 5.16 ± 0.38 mL min -1  mmHg -1  L -1 ; P = 0.20). The groups achieved a similar maximal oxygen uptake (P = 0.32), and ventilatory constraints experienced were not different (P > 0.05). Changes over time were not different between groups (P > 0.05). At the initial measurement, pubertal female swimmers had greater lung size, expiratory flows, and indices of respiratory muscle strength, but similar ventilatory constraints while cycling. One competitive swimming season did not further accentuate this enhanced lung size and function or alter ventilatory mechanics, suggesting that competitive swimming during puberty did not affect lung growth., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Heterogeneity in regional end expiratory lung volume (EELV) may lead to variations in regional strain (ε). High ε levels have been associated with ventilator-associated lung injury (VALI). While both whole lung and regional EELV may be affected by changes in positive end-expiratory pressure (PEEP), regional variations are not revealed by conventional respiratory system measurements. Differential rates of deflation of adjacent lung units due to regional variation in expiratory time constants (τ E ) may create localized regions of ε that are significantly greater than implied by whole lung measures. We used functional respiratory imaging (FRI) in an ex vivo porcine lung model to: (i) demonstrate that computed tomography (CT)-based imaging studies can be used to assess global and regional values of ε and τ E and, (ii) demonstrate that the manipulation of PEEP will cause measurable changes in total and regional ε and τ E values. Our study provides three insights into lung mechanics. First, image-based measurements reveal egional variation that cannot be detected by traditional methods such as spirometry. Second, the manipulation of PEEP causes global and regional changes in R, E, ε and τ E values. Finally, regional ε and τ E were correlated in several lobes, suggesting the possibility that regional τ E could be used as a surrogate marker for regional ε., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

We utilized a multicompartment model to describe the effects of changes in tidal volume (VT) and positive end-expiratory pressure (PEEP) on lung emptying during passive deflation before and after experimental lung injury. Expiratory time constants (τE) were determined by partitioning the expiratory flow-volume (V˙EV) curve into multiple discrete segments and individually calculating τE for each segment. Under all conditions of PEEP and VT, τE increased throughout expiration both before and after injury. Segmented τE values increased throughout expiration with a slope that was different than zero (P < 0. 01). On average, τE increased by 45.08 msec per segment. When an interaction between injury status and τE segment was included in the model, it was significant (P < 0.05), indicating that later segments had higher τE values post injury than early τE segments. Higher PEEP and VT values were associated with higher τE values. No evidence was found for an interaction between injury status and VT, or PEEP. The current experiment confirms previous observations that τE values are smaller in subjects with injured lungs when compared to controls. We are the first to demonstrate changes in the pattern of τE before and after injury when examined with a multiple compartment model. Finally, increases in PEEP or VT increased τE throughout expiration, but did not appear to have effects that differed between the uninjured and injured state., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Although high-altitude exposure can lead to neurocognitive impairment, even upon return to sea level, it remains unclear the extent to which brain volume and regional cerebral vascular reactivity (CVR) are altered following high-altitude exposure. The purpose of this study was to simultaneously determine the effect of 3 weeks at 5050 m on: (1) structural brain alterations; and (2) regional CVR after returning to sea level for 1 week. Healthy human volunteers (n = 6) underwent baseline and follow-up structural and functional magnetic resonance imaging (MRI) at rest and during a CVR protocol (end-tidal PCO2 reduced by -10, -5 and increased by +5, +10, and +15 mmHg from baseline). CVR maps (% mmHg(-1)) were generated using BOLD MRI and brain volumes were estimated. Following return to sea level, whole-brain volume and gray matter volume was reduced by 0.4 ± 0.3% (P < 0.01) and 2.6 ± 1.0% (P < 0.001), respectively; white matter was unchanged. Global gray matter CVR and white matter CVR were unchanged following return to sea level, but CVR was selectively increased (P < 0.05) in the brainstem (+30 ± 12%), hippocampus (+12 ± 3%), and thalamus (+10 ± 3%). These changes were the result of improvement and/or reversal of negative CVR to positive CVR in these regions. Three weeks of high-altitude exposure is reflected in loss of gray matter volume and improvements in negative CVR., (© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)