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The purpose of this study was to compare sex-based differences in the mean arterial blood pressure (MAP) response to limb and inspiratory metaboreflex activation, during relative and absolute workloads. Healthy males ( n = 9) and females ( n = 8) completed pulmonary function testing, forearm volume and circumference measurements, and bouts of limb and inspiratory muscle exercise. The exercises performed included bouts of rhythmic handgrip exercise (RHG) and inspiratory pressure threshold loading (PTL) to task failure, performed in a randomized order and separated by 30 minutes of rest. Participants performed both RHG and PTL at predetermined relative (R) and absolute (A) workloads, while cardiopulmonary measurements were recorded continuously. A time-dependent rise in MAP was observed in all participants, regardless of sex, muscle, or workload ( P < 0.001). MAP was greater in males than females during all exercise bouts regardless of muscle group or workload ( P < 0.001). The change in MAP from baseline was also greater in males (R-RHG: Δ31 ± 12 mmHg; R-PTL: Δ31 ± 9; A-RHG: Δ35 ± 6; and A-PTL: Δ30 ± 7) than females (R-RHG: Δ21 ± 7 mmHg; R-PTL: Δ13 ± 7; A-RHG: Δ21 ± 7; and A-PTL: Δ14 ± 3) ( P < 0.001). Results from this study show that when the forearm and diaphragm perform the same relative or absolute work, the blood pressure response is statistically similar, and both responses are greater in males than females. The findings from the present study suggest that the sex-based difference in the response to metaboreflex activation is similar between the limb and respiratory musculature. NEW & NOTEWORTHY With rhythmic handgrip exercise and inspiratory pressure threshold loading there was a time-dependent rise in the blood pressure that was significantly lower in females than males. The blunted blood pressure response in females was present whether handgrip or inspiratory workload was relative or absolute. An attenuated cardiovascular response to high levels of limb or respiratory muscle work may have implications for whole body exercise in health and disease.

We tested the hypothesis that the incidence and magnitude of diaphragm fatigue following high-intensity exercise would be lower in females with a high aerobic capacity (Hi-Fit) compared with healthy females with an average aerobic fitness (Avg-Fit). Participants were assigned to groups based on their peak O 2 uptake (V̇o 2peak ) obtained during cycle exercise: Hi-Fit n = 9, V̇o 2peak ≥ 56.1 ± 3.4 mL·kg -1 ·min -1 versus Avg-Fit n = 9, V̇o 2peak ≤ 35.7 ± 4.9 mL·kg -1 ·min -1 . On the second day, diaphragm fatigue was assessed before and after constant load exercise test to exhaustion. Magnetic stimulation of the phrenic nerve roots was used to nonvolitionally assess diaphragm fatigue by measurement of transdiaphragmatic twitch pressure (P di,tw ). Both groups exercised at >90% of V̇o 2peak for a similar duration (Hi-Fit: 546.1 ± 177.8 vs. Avg-Fit: 559.3 ± 175.0 s, P = 0.9). Diaphragm fatigue was defined as a ≥15% reduction in P di,tw , approximately two times greater than the coefficient of variation. The mean group average reduction in P di,tw following exercise in the Hi-Fit (17.5%) and Avg-Fit groups (12.2%) was not different between groups ( P = 0.2). The Hi-Fit group performed exercise at a higher absolute work rate that elicited significantly greater ventilatory work and inspiratory muscle force output. The Hi-Fit group did not experience greater fatigue compared with the Avg-Fit group, which we attribute to a greater reliance on accessory respiratory muscle recruitment, to training-induced increases in the aerobic capacity of the diaphragm, or a combination of the two. In summary, aerobic fitness is not predictive of exercise-induced diaphragm fatigue in healthy females. NEW & NOTEWORTHY We hypothesized that females with a high aerobic capacity would be resistant to exercise-induced diaphragm fatigue relative to healthy but untrained females. We assessed the pressure generated by the diaphragm following exhaustive exercise by stimulating the phrenic nerves. The magnitude and incidence of fatigue were similar between groups. Despite having higher ventilatory demands during exercise highly trained females were resistant to greater diaphragm fatigue. Aerobic fitness is not predictive of exercise-induced diaphragm fatigue in females.

We recently explored the cardiopulmonary interactions during partial unloading of the respiratory muscles during exercise. Expanding upon this work, we present a noteworthy case study whereby we eliminated the influence of respiration on cardiac function in a conscious but mechanically ventilated human during exercise. This human was a young healthy endurance-trained male who was mechanically ventilated during semi-recumbent cycle exercise at 75 Watts (W) (∼30% W max ). During mechanically ventilated exercise, esophageal pressure was reduced to levels indistinguishable from the cardiac artefact which led to a 94% reduction in the power of breathing. The reduction in respiratory pressures and respiratory muscle work led to a decrease in cardiac output (-6%), which was due to a reduction in stroke volume (-13%), left ventricular end-diastolic volume (-15%), and left-ventricular end-systolic volume (-17%) that was not compensated for by heart rate. Our case highlights the influence of extreme mechanical ventilation on cardiac function while noting the possible presence of a maximal physiological limit to which respiration (and its associated pressures) impacts cardiac function when the power of breathing is maximally reduced., Competing Interests: The authors declare no competing interests.

Given that there are both sex-based structural differences in the respiratory system and age-associated declines in pulmonary function, the purpose of this study was to assess the effects of age and sex on the metabolic cost of breathing (V̇o 2RM ) for exercise ventilations in healthy younger and older males and females. Forty healthy participants (10 young males 24 ± 3 yr; 10 young females 24 ± 3 yr; 10 older males 63 ± 3 yr, 10 older females 63 ± 6 yr) mimicked their exercise breathing patterns (voluntary hyperpnea) in the absence of exercise across a range of exercise intensities. At peak exercise, V̇o 2RM represented a significantly greater fraction of peak oxygen consumption (V̇o 2peak ) in young females, 12.7 ± 4.0%, compared with young males, 10.7 ± 3.0% ( P = 0.027), whereas V̇o 2RM represented 13.5 ± 2.3% of V̇o 2peak in older females and 13.2 ± 3.3% in older males. At relative ventilations, there was a main effect of age, with older males consuming a significantly greater fraction of V̇o 2RM (6.6 ± 1.9%) than the younger males (4.4 ± 1.3%; P = 0.012), and older females consuming a significantly greater fraction of V̇o 2RM (6.9 ± 2.5%) than the younger females (5.1 ± 1.4%; P = 0.004) at 65% V̇e max . Furthermore, both younger and older males had significantly better respiratory muscle efficiency than their female counterparts at peak exercise ( P = 0.011; P = 0.015). Similarly, younger participants were significantly more efficient than older participants (6.5 ± 1.5% vs. 5.5 ± 2.0%; P = 0.001). Normal age-related changes in respiratory function, in addition to sex-based differences in airway anatomy, appear to influence the ventilatory responses and the cost incurred to breathe during exercise. NEW & NOTEWORTHY Here we show that at moderate and high-intensity exercise, older individuals incur a higher cost to breathe than their younger counterparts. However, as individuals age, the sex difference in the cost of breathing narrows. Collectively, our findings suggest that the normative age-related changes in respiratory structure and function, and sex differences in airway anatomy, appear to influence the ventilatory responses to exercise and the oxygen cost to breathe.

Ground-level ozone (O 3 ) is a potent air pollutant well recognized to acutely induce adverse respiratory symptoms and impairments in pulmonary function. However, it is unclear how the hyperpnea of exercise may modulate these effects, and the subsequent consequences on exercise performance. We tested the hypothesis that pulmonary function and exercise capability would be diminished, and symptom development would be increased during peak real-world levels of O 3 exposure compared with room air. Twenty aerobically trained participants [13 M, 7 F; maximal O 2 uptake (V̇o 2max ), 64.1 ± 7.0 mL·kg -1 ·min -1 ] completed a three-visit double-blinded, randomized crossover trial. Following a screening visit, participants were exposed to 170 ppb O 3 or room air (<10 ppb O 3 ) on separate visits during exercise trials, consisting of a 25-min moderate-intensity warmup, 30-min heavy-intensity bout, and a subsequent time-to-exhaustion (TTE) performance test. No differences in O 2 uptake or ventilation were observed during submaximal exercise between conditions. During the TTE test, we observed significantly lower end-exercise O 2 uptake (-3.2 ± 4.3%, P = 0.004), minute ventilation (-3.2 ± 6.5%, P = 0.043), tidal volume (-3.6 ± 5.1%, P = 0.008), and a trend toward lower exercise duration in O 3 compared with room air (-10.8 ± 26.5%, P = 0.092). As decreases in O 2 uptake and alterations in respiratory pattern were also present at matched time segments between conditions, a limitation of oxygen transport seems likely during maximal exercise. A more comprehensive understanding of the direct mechanisms that limit oxygen transport during exercise in high-pollutant concentrations is key for mitigating performance changes. NEW & NOTEWORTHY We demonstrate that in highly trained endurance athletes, exposure to peak real-world levels of O 3 air pollution (170 ppb) significantly diminishes O 2 uptake along with corresponding changes in ventilation during maximal exercise. As no differences were observed during extended submaximal exercise, a combined effect of effective dose of pollution and exercise intensity on severity of responses seems likely.

Abstract: Nearly 40 yr ago, Professor Dempsey delivered the 1985 ACSM Joseph B. Wolffe Memorial Lecture titled: "Is the lung built for exercise?" Since then, much experimental work has been directed at enhancing our understanding of the functional capacity of the respiratory system by applying complex methodologies to the study of exercise. This review summarizes a symposium entitled: "Revisiting 'Is the lung built for exercise?'" presented at the 2022 American College of Sports Medicine annual meeting, highlighting the progress made in the last three-plus decades and acknowledging new research questions that have arisen. We have chosen to subdivide our topic into four areas of active study: (i) the adaptability of lung structure to exercise training, (ii) the utilization of airway imaging to better understand how airway anatomy relates to exercising lung mechanics, (iii) measurement techniques of pulmonary gas exchange and their importance, and (iv) the interactions of the respiratory and cardiovascular system during exercise. Each of the four sections highlights gaps in our knowledge of the exercising lung. Addressing these areas that would benefit from further study will help us comprehend the intricacies of the lung that allow it to meet and adapt to the acute and chronic demands of exercise in health, aging, and disease., (Copyright © 2023 by the American College of Sports Medicine.)

Rationale: It is unclear whether the frequency and mechanisms of expiratory flow limitation (EFL) during exercise differ between males and females., Purpose: This study aimed to determine which factors predispose individuals to EFL during exercise and whether these factors differ based on sex. We hypothesized that i) EFL frequency would be similar in males and females and ii) in females, EFL would be associated with indices of low ventilatory capacity, whereas in males, EFL would be associated with indices of high ventilatory demand., Methods: Data from n = 126 healthy adults (20-45 y, n = 60 males, n = 66 females) with a wide range of cardiorespiratory fitness (81%-182% predicted maximal oxygen uptake) were included in the study. Participants performed spirometry and an incremental cycle exercise test to exhaustion. Standard cardiorespiratory variables were assessed throughout exercise. The tidal flow-volume overlap method was used to assess EFL based on a minimum threshold of 5% overlap between the tidal and the maximum expiratory flow-volume curves. Predictors of EFL during exercise were determined via multiple logistical regression using anthropometric, pulmonary function, and peak exercise data., Results: During exercise, EFL occurred in 49% of participants and was similar between the sexes (females = 45%, males = 53%; P = 0.48). In males, low forced expired flow between 25% and 75% of forced vital capacity and high slope ratio as well as low end-expiratory lung volume, high breathing frequency, and high relative tidal volume at peak exercise were associated with EFL ( P < 0.001; Nagelkerke R2 = 0.73). In females, high slope ratio, high breathing frequency, and tidal volume at peak exercise were associated with EFL ( P < 0.001; Nagelkerke R2 = 0.61)., Conclusions: Despite sex differences in respiratory system morphology, the frequency and the predictors of EFL during exercise do not substantially differ between the sexes., (Copyright © 2022 by the American College of Sports Medicine.)

We examined the relationship between the work of breathing (W b ) during exercise and in vivo measures of airway size in healthy females and males. We hypothesized that sex differences in airway luminal area would explain the larger resistive W b during exercise in females. Healthy participants ( n = 11 females and n = 11 males; 19-30 yr) completed a cycle exercise test to exhaustion where W b was assessed using an esophageal balloon catheter. On a separate day, each participant underwent a bronchoscopy procedure for optical coherence tomography measures of seven airways. In vivo measures of luminal area were made for the fourth to eighth airway generations. A composite index of airway size was calculated as the sum of the luminal area for each generation, and the total area was calculated based on Weibel's model. We found that index of airway size (males: 37.4 ± 6.3 mm 2 vs. females: 27.5 ± 7.4 mm 2 ) and airway area calculated based on Weibel's model (males: 2,274 ± 557 mm 2 vs. females: 1,594 ± 389 mm 2 ) were significantly larger in males (both P = 0.003). When minute ventilation was greater than ∼60 L·min -1 , the resistive W b was higher in females. At the highest equivalent flow achieved by all subjects, resistance to inspired flow was larger in females and significantly associated with two measures of airway size in all subjects: index of airway size ( r = 0.524, P = 0.012) and Weibel area ( r = 0.525, P = 0.012). Our findings suggest that innate sex differences in luminal area result in a greater resistive W b during exercise in females compared with males. NEW & NOTEWORTHY We hypothesized that the higher resistive work of breathing in females compared with males during high-intensity exercise is due to smaller airways. In vivo measures of the fourth to eighth airway generations made using optical coherence tomography show that females tend to have smaller airway luminal areas of the fourth to sixth airway generations. Sex differences in airway luminal area result in a greater resistive work of breathing during exercise in females compared with males.

We compared cardiopulmonary responses to arm-ergometry in individuals with cervical spinal cord injury (C-SCI) and able-bodied controls. We hypothesized that individuals with C-SCI would have higher respiratory frequency (f b ) but lower tidal volume (VT) at a given work rate and dynamically hyperinflate during exercise, whereas able-bodied individuals would not. Participants completed pulmonary function testing, an arm-ergometry test to exhaustion, and a sub-maximal exercise test consisting of four-minute stages at 20, 40, 60, and 80% peak work rate. Able-bodied individuals completed a further sub-maximal test with absolute work rate matched to C-SCI. During work rate matched sub-maximal exercise, C-SCI had smaller VT (main effect p < 0.001) compensated by an increased f b (main effect p = 0.009). C-SCI had increased end-expiratory lung volume at 80% peak work rate vs. rest (p < 0.003), whereas able-bodied did not. In conclusion, during arm-ergometry, individuals with C-SCI exhibit altered ventilatory patterns characterized by reduced VT, higher f b , and dynamic hyperinflation that may contribute to the observed reduced aerobic exercise capacity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Historically, many studies investigating the pulmonary physiology of exercise (and biomedical research in general) were performed exclusively or predominantly with male research participants. This has led to an incomplete understanding of the pulmonary response to exercise. More recently, important sex-based differences with respect to the human respiratory system have been identified. The purpose of this review is to summarize current findings related to sex-based differences in the pulmonary physiology of exercise. To that end, we will discuss how morphological sex-based differences of the respiratory system affect the respiratory response to exercise. Moreover, we will discuss sex-based differences of the physiological integrative responses to exercise, and how all these differences can influence the regulation of breathing. We end with a brief discussion of pregnancy and menopause and the accompanying ventilatory changes observed during exercise., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To minimize transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus responsible for coronavirus disease (COVID-19), the U.S. Centers for Disease Control and Prevention and the World Health Organization recommend wearing face masks in public. Some have expressed concern that these may affect the cardiopulmonary system by increasing the work of breathing, altering pulmonary gas exchange and increasing dyspnea, especially during physical activity. These concerns have been derived largely from studies evaluating devices intentionally designed to severely affect respiratory mechanics and gas exchange. We review the literature on the effects of various face masks and respirators on the respiratory system during physical activity using data from several models: cloth face coverings and surgical masks, N95 respirators, industrial respirators, and applied highly resistive or high-dead space respiratory loads. Overall, the available data suggest that although dyspnea may be increased and alter perceived effort with activity, the effects on work of breathing, blood gases, and other physiological parameters imposed by face masks during physical activity are small, often too small to be detected, even during very heavy exercise. There is no current evidence to support sex-based or age-based differences in the physiological responses to exercise while wearing a face mask. Although the available data suggest that negative effects of using cloth or surgical face masks during physical activity in healthy individuals are negligible and unlikely to impact exercise tolerance significantly, for some individuals with severe cardiopulmonary disease, any added resistance and/or minor changes in blood gases may evoke considerably more dyspnea and, thus, affect exercise capacity.

Objective: To examine the psychological mediators of exercise adherence among older adults in a group-based physical activity randomized controlled trial., Method: Older adults (≥65 years) were randomized to one of three conditions as part of the "GrOup-based physical Activity for oLder adults" (GOAL) randomized controlled trial. These included similar age same gender (SASG) and similar age mixed gender (SAMG) exercise programs that were informed by the tenets of self-categorization theory, and a "standard" mixed age mixed gender (MAMG) exercise program. Participants represented a subgroup (n = 483, Mage = 71.41 years) from the larger trial (n = 627) who completed measures of the trial's putative psychological mediators (i.e., group cohesion and affective attitudes) over the course of the 24-week exercise programs., Results: Piecewise latent growth modeling revealed different trajectories between participants in the two intervention conditions (SASG, SAMG) when compared with the comparison MAMG condition with regard to perceptions of group cohesion and affective attitudes. Results of subsequent cross-lagged panel modeling revealed that better program adherence in the two intervention conditions, when compared with the referent MAMG condition, was mediated by perceptions of group cohesion., Conclusions: The findings provide insight into how the two intervention programs differentially strengthened perceptions of group cohesion and affective attitudes over time. Consistent with self-categorization theory, the results also shed light on the role of group cohesion, in particular, as a psychological mechanism of action to promote older adults' exercise adherence behaviors. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

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 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.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.)

New Findings: What is the central question of this study? How does sternocleidomastoid blood flow change in response to increasing ventilation and whole-body exercise intensity? What is the main finding and its importance? Sternocleidomastoid blood flow increased with increasing ventilation. For a given ventilation, sternocleidomastoid blood flow was lower during whole-body exercise compared to resting hyperpnoea. These findings suggest that locomotor muscle work exerts an effect on respiratory muscle blood flow that can be observed in the sternocleidomastoid., Abstract: Respiratory muscle work influences the distribution of blood flow during exercise. Most studies have focused on blood flow to the locomotor musculature rather than the respiratory muscles, owing to the complex anatomical arrangement of respiratory muscles. The purpose of this study was to examine how accessory respiratory (i.e. sternocleidomastoid, and muscles in the intercostal space) muscle blood flow changes in response to locomotor muscle work. Seven men performed 5 min bouts of constant load cycling exercise trials at 30%, 60% and 90% of peak work rate in a randomized order, followed by 5 min bouts of voluntary hyperpnoea (VH) matching the ventilation achieved during each exercise (EX) trial. Blood-flow index (BFI) of the vastus lateralis, sternocleidomastoid (SCM) and seventh intercostal space (IC) were estimated using near-infrared spectroscopy and indocyanine green and expressed relative to resting levels. BFI SCM was greater during VH compared to EX (P = 0.002) and increased with increasing exercise intensity (P = 0.036). BFI SCM reached 493 ± 219% and 301 ± 215% rest during VH and EX at 90% peak work rate, respectively. BFI IC increased to 242 ± 178% and 210 ± 117% rest at 30% peak work rate during VH and EX, respectively. No statistically significant differences in BFI IC were observed with increased work rate during VH or EX (both P > 0.05). Moreover, there was no observed difference in BFI IC between conditions (P > 0.05). BFI SCM was lower for a given minute ventilation during EX compared to VH, suggesting that accessory respiratory muscle blood flow is influenced by whole-body exercise., (© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.)

New Findings: What is the topic of this review? Elevated demand is placed on the respiratory muscles during whole-body exercise-induced hyperpnoea. What is the role of elevated demand in neural modulation of cardiovascular control in respiratory and locomotor skeletal muscle, and what are the mechanisms involved? What advances does it highlight? There is a sympathetic restraint of blood flow to locomotor muscles during near-maximal exercise, which might function to maintain blood pressure. During submaximal exercise, respiratory muscle blood flow might be also be reduced if ventilatory load is sufficiently high. Methodological advances (near-infrared spectroscopy with indocyanine green) confirm that blood flow is diverted away from respiratory muscles when the work of breathing is alleviated., Abstract: It is known that the respiratory muscles have a significant increasing oxygen demand in line with hyperpnoea during whole-body endurance exercise and are susceptible to fatigue, in much the same way as locomotor muscles. The act of ventilation can itself be considered a form of exercise. The manipulation of respiratory load at near-maximal exercise alters leg blood flow significantly, demonstrating a competitive relationship between different skeletal muscle vascular beds to perfuse both sets of muscles adequately with a finite cardiac output. In recent years, the question has moved towards whether this effect exists during submaximal exercise, and the use of more direct measurements of respiratory muscle blood flow itself to confirm assumptions that uphold the concept. Evidence thus far has shown that there is a reciprocal effect on blood flow redistribution during ventilatory load manipulation observed at the respiratory muscles themselves and that the effect is observable during submaximal exercise, where active limb blood flow was reduced in conditions that simulated a high work of breathing. This has clinical applications for populations with respiratory disease and heart failure, where the work of breathing is remarkably high, even during submaximal efforts., (© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.)

Purpose: To quantify the mechanical work of breathing (W b ) during an indoor rowing test in men and women. Additionally, to compare sex-based differences in the W b and its components through a rowing test., Methods: Fifteen collegiate rowers were recruited (8 women/7 men) and performed a 2000 m rowing test on a rowing ergometer. Esophageal pressure was measured during exercise via balloon catheterization, after which pressure-volume curves were used to calculate total, inspiratory resistive and elastic, and total expiratory W b ., Results: Men had significantly higher values of instantaneous and cumulative total W b at and beyond 37.5% (430.4 ± 42.5 vs. 282.1 ± 45.1 J min -1 , P < 0.05) and 62.5% (1946.8 ± 150.9 vs. 1360.1 ± 197.2 J, P < 0.05) total exercise time, respectively. However, when compared at the same minute ventilation, women had higher values of total (at and above ~ 140 L min -1 ), inspiratory resistive (at and above ~ 120 L min -1 ), and inspiratory elastic (at and above ~ 135 L min -1 ) W b , whereas men presented higher total expiratory W b compared to women at any ventilation., Conclusion: Although female rowers present higher relative values of inspiratory resistive and elastic W b , their male counterparts develop greater ventilatory efforts during a 2000 m rowing test, resulting in a larger total mechanical W b . We interpret these findings to mean that the W b reflects both anatomical (i.e., airways and lung sizes) and respiratory (i.e., minute ventilation) sex differences during rowing.

New Findings: What is the central question of this study? What is the effect of age and sex on the resistive and viscoelastic components of work of breathing (W b ) during exercise? What is the main finding and its importance? The resistive and viscoelastic components of W b were higher in older adults, regardless of sex. The resistive, but not viscoelastic, component of W b was higher in females than in males, regardless of age. These findings contribute to improving our understanding of the effects of ageing and sex on the mechanical ventilatory response to exercise., Abstract: Healthy ageing and biological sex each affect the work of breathing (W b ) for a given minute ventilation ( V ̇ E ). Age-related structural changes to the respiratory system lead to an increase in both the resistive and viscoelastic components of W b ; however, it is unclear whether healthy ageing differentially alters the mechanics of breathing in males and females. We analysed data from 22 older (60-80 years, n = 12 females) and 22 younger (20-30 years, n = 11 females) males and females that underwent an incremental cycle exercise test to exhaustion. V ̇ E and W b were assessed at rest and throughout exercise. W b - V ̇ E data for each participant were fitted to a non-linear equation (i.e. W b  = a V ̇ E 3 + b V ̇ E 2 ) that partitions W b into resistive (i.e. a V ̇ E 3 ) and viscoelastic (i.e. b V ̇ E 2 ) components. We then modelled the effects of healthy ageing and biological sex on each component of W b . Overall, the model fit was excellent (r 2 : 0.99 ± 0.01). There was a significant main effect of age and sex on the resistive component of W b (both P < 0.05), and a significant main effect of age (P < 0.001), but not sex (P = 0.309), on the viscoelastic component of W b . No significant interactions between age and sex on a V ̇ E 3 or b V ̇ E 2 were noted (both P > 0.05). Our findings indicate that during exercise: (i) the higher total W b in females relative to males is due to a higher resistive, but not viscoelastic, component of W b , and (ii) regardless of sex, the higher W b in older adults relative to younger adults is due to higher resistive and viscoelastic components of W b ., (© 2019 The Authors. Experimental Physiology © 2019 The Physiological Society.)

Unsatisfied inspiration is commonly reported during exercise by patients with interstitial lung disease (ILD). However, the physiological basis of perceived dyspnea quality in this population has not been evaluated. We examined the relationship between dyspnea quality and indices of ventilatory-mechanical limitations during exercise in patients with fibrotic ILD. Sixteen fibrotic ILD patients (12 male) with a median age of 64 years (range 49-81), FVC 71%-predicted (51-100), and DL CO 47%-predicted (27-77) performed incremental and constant work-rate cycle exercise tests to exhaustion. Ventilatory responses were recorded at rest, throughout exercise, and at peak exercise. Dyspnea quality was serially assessed using a 4-item list from which participants selected the phrase that best described their breathing compared to rest. Increased work/effort was the dominant descriptor of dyspnea throughout exercise, but with increased selection of unsatisfied inspiration following the inflection point of tidal volume relative to ventilation. Delaying or preventing ILD patients from reaching a critically reduced IRV may have implications for symptom management., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Key Points: The effect of combined inspiratory and expiratory muscle training on resting and reflexive cardiac function, as well as exercise capacity, in individuals with cervical spinal cord injury (SCI) is presently unknown. Six weeks of combined inspiratory and expiratory muscle training enhances both inspiratory and expiratory muscle strength in highly-trained athletes with cervical SCI with no significant effect on lung function. There was a significant decrease in left-ventricular filling and stroke volume at rest in response to 45° head-up tilt, which is irreversible by respiratory muscle training. Combined inspiratory and expiratory muscle training increased peak aerobic work rate and reduced end-expiratory lung volumes during exercise, which may have implications for left-ventricular filling during exercise., Abstract: To investigate the pulmonary, cardiovascular and exercise responses to combined inspiratory and expiratory respiratory muscle training (RMT) in athletes with tetraplegia, six wheelchair rugby athletes (five males and one female, aged 33 ± 5 years) completed 6 weeks of pressure threshold RMT, 2 sessions day -1 on 5 days week -1 . Resting pulmonary and cardiac function, exercise capacity, exercising lung volumes and field-based exercise performance were assessed at pre-RMT, post-RMT and after a 6-week no RMT period. RMT enhanced maximal inspiratory (pre- vs. post-RMT: -76 ± 15 to -106 ± 23 cmH 2 O, P = 0.002) and expiratory (59 ± 26 to 73 ± 32 cmH 2 O, P = 0.007) mouth pressures, as well as peak expiratory flow (6.74 ± 1.51 vs. 7.32 ± 1.60 L/s, P < 0.04). Compared to pre-RMT, peak work rate was higher at post-RMT (60 ± 23 to 68 ± 22 W, P = 0.003), whereas exercising end-expiratory lung volumes were reduced (P < 0.017). Peak oxygen uptake increased in all athletes at post-RMT (1.24 ± 0.40 vs. 1.40 ± 0.50 l min -1 , P = 0.12). After 6 weeks of no RMT all indices returned towards baseline, with peak work rate (P = 0.037), peak oxygen uptake (P = 0.041) and end-expiratory lung volume (P < 0.034) being significantly lower at follow-up than at post-RMT. There was a significant decrease in left-ventricular end-diastolic volume and stroke volume in response to 45° head-up tilt (P = 0.030 and 0.021, respectively); however, all cardiac indices in both supine and tilted positions were unchanged by RMT. Our findings demonstrate the efficacy of RMT with respect to enhancing respiratory muscle strength, lowering exercising lung volumes and increasing exercise capacity. Although the precise mechanisms by which RMT may enhance exercise capacity remain unclear, our data suggest that it is probably not the result of a direct cardiac adaptation associated with RMT., (© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.)

Healthy women have proportionally smaller lungs and airways compared with height-matched men. These anatomical sex-based differences result in greater mechanical ventilatory constraints and may influence the integrative response to exercise. Our review will examine this hypothesis in healthy humans in the context of dynamic whole-body exercise.

Exercise-induced arterial hypoxemia (EIAH) is characterized by the decrease in arterial oxygen tension and oxyhemoglobin saturation during dynamic aerobic exercise. Since the time of the initial observations, our knowledge and understanding of EIAH has grown, but many unknowns remain. The purpose of this review is to provide an update on recent findings, highlight areas of disagreement, and identify where information is lacking. Specifically, this review will place emphasis on ( i ) the occurrence of EIAH during submaximal exercise, ( ii ) whether there are sex differences in the development and severity of EIAH, and ( iii ) unresolved questions and future directions.

Reducing the work of breathing during exercise improves locomotor muscle blood flow and reduces diaphragm and locomotor muscle fatigue and is thought to be the result of a sympathetically mediated reflex., Aim: The aim of this study was to assess muscle sympathetic nerve activity (MSNA) when the work of breathing is experimentally lowered during dynamic exercise., Methods: Healthy subjects (n = 12; age = 29 ± 9 years) performed semi-recumbent cycling trials at 40%, 60%, and 80% of peak workload. Exercise trials consisted of spontaneous breathing, reduced work of breathing (proportional assist ventilator), followed by further spontaneous breathing (post-ventilator). MSNA was recorded from the median nerve., Results: There was no difference in work of breathing between PAV and post-PAV at 40% peak work. At 60% peak work, the ventilator significantly (P < 0.05) reduced work of breathing (103 ± 39 vs 144 ± 47 J min -1 ), sympathetic nerve activity (35 ± 5 vs 42 ± 8 burst min -1 ), and V ˙ O 2 (2.4 ± 0.5 vs 2.6 ± 0.5 L min -1 ) without influencing ventilation (86 ± 9 vs 82 ± 10 L min -1 ; P > 0.05), for PAV and post-PAV respectively. During 80% peak work (n = 8), the ventilator significantly (P < 0.05) reduced work of breathing (235 ± 110 vs. 361 ± 150 J min -1 ), MSNA (48 ± 7 vs 54 ± 11 burst min -1 ), and V ˙ O 2 (2.9 ± 0.6 vs 3.2 ± 0.7 L min -1 ) but not ventilation (121 ± 20 vs 123 ± 20 L min -1 ; P > 0.05), for PAV and post-PAV respectively. There was a significant relationship between MSNA and V ˙ O 2 (P < 0.0001) with a significant interaction due to the ventilator (P < 0.05)., Conclusion: Lowering the normally occurring work of breathing during exercise results in commensurate reductions in MSNA. Our findings provide evidence of a sympathetically mediated vasoconstrictor effect emanating from respiratory muscles during exercise., (© 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Key Points: The perceived intensity of exertional breathlessness (i.e. dyspnoea) is higher in older women than in older men, possibly as a result of sex-differences in respiratory system morphology. During exercise at a given absolute intensity or minute ventilation, older women have a greater degree of mechanical ventilatory constraint (i.e. work of breathing and expiratory flow limitation) than their male counterparts, which may lead to a greater perceived intensity of dyspnoea. Using a single-blind randomized study design, we experimentally manipulated the magnitude of mechanical ventilatory constraint during moderate-intensity exercise at ventilatory threshold in healthy older men and women. We found that changes in the magnitude of mechanical ventilatory constraint within the physiological range had no effect on dyspnoea in healthy older adults. When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea., Abstract: We aimed to determine the effect of manipulating mechanical ventilatory constraint during submaximal exercise on dyspnoea in older men and women. Eighteen healthy subjects (aged 60-80 years; nine men and nine women) completed two days of testing. On day 1, subjects were assessed for pulmonary function and performed a maximal incremental cycle exercise test. On day 2, subjects performed three 6-min bouts of cycling at ventilatory threshold, in a single-blind randomized manner, while breathing: (i) normoxic helium-oxygen (HEL) to reduce the work of breathing (W b ) and alleviate expiratory flow limitation (EFL); (ii) through an inspiratory resistance (RES) of ∼5 cmH 2 O L -1  s -1 to increase W b ; and (iii) ambient air as a control (CON). Oesophageal pressure, diaphragm electromyography, and sensory responses (category-ratio 10 Borg scale) were monitored throughout exercise. During the HEL condition, there was a significant decrease in W b (men: -21 ± 6%, women: -17 ± 10%) relative to CON (both P < 0.01). Moreover, if EFL was present during CON (four men and five women), it was alleviated during HEL. Conversely, during the RES condition, W b (men: 42 ± 19%, women: 50 ± 16%) significantly increased relative to CON (both P < 0.01). There was no main effect of sex on W b (P = 0.59). Across conditions, women reported significantly higher dyspnoea intensity than men (2.9 ± 0.9 vs. 1.9 ± 0.8 Borg scale units, P < 0.05). Despite significant differences in the degree of mechanical ventilatory constraint between conditions, the intensity of dyspnoea was unaffected, independent of sex (P = 0.46). When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea., (© 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.)

New Findings: What is the central question of this study? Increased respiratory muscle activation is associated with neural and cardiovascular consequences via the respiratory muscle metaboreflex. Does increased sympathetic vasoconstriction originating from the respiratory musculature elicit a reduction in blood flow to an inactive limb in order to maintain blood flow to an active limb? What is the main finding and its importance? Arm blood flow was reduced whereas leg blood flow was preserved during mild leg exercise with inspiratory resistance. Blood flow to the active limb is maintained via sympathetic control of blood flow redistribution when the respiratory muscle-induced metaboreflex is activated., Abstract: The purpose of this study was to elucidate the effect of increasing inspiratory muscle work on blood flow to inactive and active limbs. Healthy young men (n = 10, 20 ± 2 years of age) performed two bilateral dynamic knee-extension and knee-flexion exercise tests at 40% peak oxygen uptake for 10 min. The trials consisted of spontaneous breathing for 5 min followed by voluntary hyperventilation either with or without inspiratory resistance for 5 min (40% of maximal inspiratory mouth pressure, inspiratory duty cycle of 50% and a breathing frequency of 40 breaths min -1 ). Mean arterial blood pressure was acquired using finger photoplethysmography. Blood flow in the brachial artery (inactive limb) and in the femoral artery (active limb) were monitored using Doppler ultrasound. Mean arterial blood pressure during exercise was higher (P < 0.05) with inspiratory resistance (121 ± 7 mmHg) than without resistance (99 ± 5 mmHg). Brachial artery blood flow increased during exercise without inspiratory resistance (120 ± 31 ml min -1 ) compared with the resting level, whereas it was attenuated with inspiratory resistance (65 ± 43 ml min -1 ). Femoral artery blood flow increased at the onset of exercise and was maintained throughout exercise without inspiratory resistance (2576 ± 640 ml min -1 ) and was unchanged when inspiratory resistance was added (2634 ± 659 ml min -1 ; P > 0.05). These results suggest that sympathetic control of blood redistribution to active limbs is facilitated, in part, by the respiratory muscle-induced metaboreflex., (© 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.)

Purpose: To characterize the effects of age, sex, and their interaction on inspiratory muscle activation patterns during exercise., Methods: Twenty younger (20-30 yr, n = 10 women) and 20 older (60-80 yr, n = 10 women) subjects performed an incremental cycle exercise test. Electromyography (EMG) of the scalene (EMGsca) and EMG of the sternocleidomastoid (EMGscm) muscles were measured using skin surface electrodes, whereas diaphragm EMG (EMGdi) and esophageal and transdiaphragmatic pressures were measured using an esophageal catheter. Electromyography data were transformed into root mean square with a 100-ms time constant. Esophageal and diaphragmatic pressure-time products were used as indices of total inspiratory muscle pressure production and diaphragmatic pressure production, respectively., Results: At absolute minute ventilations (V˙E), women and older subjects had greater EMGdi than men and younger subjects, respectively (all P < 0.05), but no differences were noted when V˙E was expressed in relative terms (all P > 0.05). Women had greater EMGsca activity than men at absolute and relative levels of V˙E (all P < 0.05). Older subjects had greater EMGsca than younger subjects when V˙E was expressed in relative (all P < 0.05) but not absolute terms (all P > 0.05). At absolute and relative levels of V˙E, women and older subjects had greater EMGscm than men and younger subjects, respectively (all P < 0.05). Women and older subjects had a greater esophageal and diaphragmatic pressure-time products at a V˙E of 70 L·min than men and younger subjects, respectively (both P < 0.05), but no differences were noted when V˙E was expressed in relative terms (all P > 0.05). No significant interactions between age and sex were noted (all P > 0.05)., Conclusions: Age and sex significantly affect inspiratory muscle activation patterns during exercise; however, the extent of the effects depends on whether comparisons are made at absolute or relative V˙E.

Background: Despite the health benefits of regular physical activity, across the globe older adults represent the least active section of society., Purpose: The GrOup-based physical Activity for oLder adults (GOAL) trial was a three-arm parallel randomized controlled trial (RCT) that was designed to test the efficacy of two group-based exercise programs for older adults, informed by self-categorization theory (SCT), in comparison to a standard group-based exercise program., Methods: RCT conducted in Greater Vancouver, Canada, enrolled 627 older adults (Mage = 71.57 years, SD = 5.41; 71.0% female). Participants were randomized to similar age same gender (SASG), similar age mixed gender (SAMG), or 'standard' mixed age mixed gender (MAMG) exercise group conditions. In addition to group composition, the intervention programs operationalized principles from SCT designed to foster a sense of social connectedness among participants. The primary outcome of the trial was exercise adherence behavior over 12 and 24 weeks., Results: Analyses of variance revealed that older adults randomized to the SAMG (12-weeks d = .51, p < .001; 24-weeks d = .47, p < .001) and SASG (12-weeks d = .28, p = .012; 24-weeks d = .29, p = .016) conditions adhered to a greater extent than those in the MAMG comparison condition. There were no significant differences between the SAMG and SASG conditions., Conclusions: The results provide support for the efficacy of group-based physical activity programs informed by SCT. Furthermore, the results suggest that community group-based exercise programs should attempt to engage in age-targeting but not necessarily gender-targeting among older adults. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

There are known sex differences in blood pressure regulation. The differences are related to ovarian hormones that influence β-adrenergic receptors and the transduction of muscle sympathetic nerve activity. Oral contraceptives (OC) modulate the ovarian hormonal profile in women and therefore may alter the cardiovascular response. We questioned if OC would alter the absolute pressor response to static exercise and influence the day-to-day variability of the response. Healthy men (n = 11) and women (n = 19) completed a familiarization day and 2 experimental testing days. Women were divided into those taking (W-OC, n = 10) and not taking (W-NC, n = 9) OC. Each experimental testing day involved isometric handgripping exercise, at 30% of maximal force, followed by circulatory occlusion to isolate the metaboreflex. Experimental days in men were 7-14 days apart. The first experimental testing in W-OC occurred 2-7 days after the start of the active phase of their OC. Women not taking OC were tested during the early and late follicular phase of the menstrual cycle as determined by commercial ovulation monitor. The increase in mean arterial pressure (MAP) during exercise was significantly lower in W-NC (95 ± 4 mm Hg) compared with men (114 ± 4 mm Hg) and W-OC (111 ± 3 mm Hg) (P < 0.05), with the differences preserved during circulatory occlusion. The rise in MAP was significantly correlated between the 2 testing days in men (r = 0.72, P < 0.01) and W-OC (r = 0.77, P < 0.05), but not in W-NC (r = 0.17, P = 0.67), indicating greater day-to-day variation in W-NC. In conclusion, OC modulate the exercise pressor response in women and minimize day-to-day variability in the exercise metaboreflex.

We examined the effects of age, sex, and their interaction on mechanical ventilatory constraint and dyspnea during exercise in 22 older (age = 68 ± 1 yr; n = 12 women) and 22 younger (age = 25 ± 1 y, n = 11 women) subjects. During submaximal exercise, older subjects had higher end-inspiratory (EILV) and end-expiratory (EELV) lung volumes than younger subjects (both P < 0.05). During maximal exercise, older subjects had similar EILV ( P > 0.05) but higher EELV than younger subjects ( P < 0.05). No sex differences in EILV or EELV were observed. We noted that women had a higher work of breathing (W b ) for a given minute ventilation (V̇e) ≥65 l/min than men ( P < 0.05) and older subjects had a higher W b for a given V̇e ≥60 l/min ( P < 0.05). No sex or age differences in W b were present at any submaximal relative V̇e. At absolute exercise intensities, older women experienced expiratory flow limitation (EFL) more frequently than older men ( P < 0.05), and older subjects were more likely to experience EFL than younger subjects ( P < 0.05). At relative exercise intensities, women and older individuals experienced EFL more frequently than men and younger individuals, respectively (both P < 0.05). There were significant effects of age, sex, and their interaction on dyspnea intensity during exercise at absolute, but not relative, intensities (all P < 0.05). Across subjects, dyspnea at 80 W was significantly correlated with indexes of mechanical ventilatory constraint (all P < 0.05). Collectively, our findings suggest age and sex have significant impacts on W b , operating lung volumes, EFL, and dyspnea during exercise. Moreover, it appears that mechanical ventilatory constraint may partially explain sex differences in exertional dyspnea in older individuals. NEW & NOTEWORTHY We found that age and sex have a significant effect on mechanical ventilatory constraint and the perception of dyspnea during exercise. We also observed that the perception of exertional dyspnea is associated with indexes of mechanical ventilatory constraint. Collectively, our results suggest that the combined influences of age and biological sex on mechanical ventilatory constraint during exercise contributes, in part, to the increased perception of dyspnea during exercise in older women.

There is evidence suggesting diaphragmatic fatigue (DF) occurs relatively early during high-intensity exercise; however, studies investigating the temporal characteristics of exercise-induced DF are limited by incongruent methodology. Eight healthy adult males (25 ± 5 yr) performed a maximal incremental exercise test on a cycle ergometer on day 1. A constant-load time-to-exhaustion (TTE) exercise test was conducted on day 2 at 60% delta between the calculated gas exchange threshold and peak work rate. Two additional constant-load exercise tests were performed at the same intensity on days 3 and 4 in a random order to either 50 or 75% TTE. DF was assessed on days 2, 3, and 4 by measuring transdiaphragmatic twitch pressure (P di,tw ) in response to cervical magnetic stimulation. DF was present after 75 and 100% TTE (≥20% decrease in P di,tw ). The magnitude of fatigue was 15.5 ± 5.7%, 23.6 ± 6.4%, and 35.0 ± 12.1% at 50, 75, and 100% TTE, respectively. Significant differences were found between 100 to 75 and 50% TTE (both P < 0.01), and 75 to 50% TTE ( P < 0.01). There was a significant relationship between the magnitude of fatigue and cumulative diaphragm force output ( r = 0.785; P < 0.001). Ventilation, the mechanical work of breathing (WOB), and pressure-time products were not different between trials ( P > 0.05). Our data indicate that exercise-induced DF presents a relatively late onset and is proportional to the cumulative WOB; thus the ability of the diaphragm to generate pressure progressively declines throughout exercise. NEW & NOTEWORTHY The notion that diaphragmatic fatigue (DF) occurs relatively early during exercise is equivocal. Our results indicate that DF occurs during high-intensity endurance exercise in healthy men and its magnitude is strongly related to the amount of pressure and work generated by respiratory muscles. Thus we conclude that the work of breathing is the major determinant of exercise-induced DF.

Cerebral blood flow (CBF) is regulated to secure brain O 2 delivery while simultaneously avoiding hyperperfusion; however, both requisites may conflict during sprint exercise. To determine whether brain O 2 delivery or CBF is prioritized, young men performed sprint exercise in normoxia and hypoxia (P I O 2  = 73 mmHg). During the sprints, cardiac output increased to ∼22 L min -1 , mean arterial pressure to ∼131 mmHg and peak systolic blood pressure ranged between 200 and 304 mmHg. Middle-cerebral artery velocity (MCAv) increased to peak values (∼16%) after 7.5 s and decreased to pre-exercise values towards the end of the sprint. When the sprints in normoxia were preceded by a reduced P ET CO 2 , CBF and frontal lobe oxygenation decreased in parallel ( r = 0.93, P < 0.01). In hypoxia, MCAv was increased by 25%, due to a 26% greater vascular conductance, despite 4-6 mmHg lower PaCO 2 in hypoxia than normoxia. This vasodilation fully accounted for the 22 % lower CaO 2 in hypoxia, leading to a similar brain O 2 delivery during the sprints regardless of P I O 2 . In conclusion, when a conflict exists between preserving brain O 2 delivery or restraining CBF to avoid potential damage by an elevated perfusion pressure, the priority is given to brain O 2 delivery.

New Findings: What is the central question of this study? Does manipulation of the work of breathing during high-intensity exercise alter respiratory and locomotor muscle blood flow? What is the main finding and its importance? We found that when the work of breathing was reduced during exercise, respiratory muscle blood flow decreased, while locomotor muscle blood flow increased. Conversely, when the work of breathing was increased, respiratory muscle blood flow increased, while locomotor muscle blood flow decreased. Our findings support the theory of a competitive relationship between locomotor and respiratory muscles during intense exercise. Manipulation of the work of breathing (WOB) during near-maximal exercise influences leg blood flow, but the effects on respiratory muscle blood flow are equivocal. We sought to assess leg and respiratory muscle blood flow simultaneously during intense exercise while manipulating WOB. Our hypotheses were as follows: (i) increasing the WOB would increase respiratory muscle blood flow and decrease leg blood flow; and (ii) decreasing the WOB would decrease respiratory muscle blood flow and increase leg blood flow. Eight healthy subjects (n = 5 men, n = 3 women) performed a maximal cycle test (day 1) and a series of constant-load exercise trials at 90% of peak work rate (day 2). On day 2, WOB was assessed with oesophageal balloon catheters and was increased (via resistors), decreased (via proportional assist ventilation) or unchanged (control) during the trials. Blood flow was assessed using near-infrared spectroscopy optodes placed over quadriceps and the sternocleidomastoid muscles, coupled with a venous Indocyanine Green dye injection. Changes in WOB were significantly and positively related to changes in respiratory muscle blood flow (r = 0.73), whereby increasing the WOB increased blood flow. Conversely, changes in WOB were significantly and inversely related to changes in locomotor blood flow (r = 0.57), whereby decreasing the WOB increased locomotor blood flow. Oxygen uptake was not different during the control and resistor trials (3.8 ± 0.9 versus 3.7 ± 0.8 l min -1 , P > 0.05), but was lower on the proportional assist ventilator trial (3.4 ± 0.7 l min -1 , P < 0.05) compared with control. Our findings support the concept that respiratory muscle work significantly influences the distribution of blood flow to both respiratory and locomotor muscles., (© 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.)

Key Points: High work of breathing and exercise-induced arterial hypoxaemia (EIAH) can decrease O 2 delivery and exacerbate exercise-induced quadriceps fatigue in healthy men. Women have a higher work of breathing during exercise, dedicate a greater fraction of whole-body V̇O2 towards their respiratory muscles and develop EIAH. Despite a greater reduction in men's work of breathing, the attenuation of quadriceps fatigue was similar between the sexes. The degree of EIAH was similar between sexes, and regardless of sex, those who developed the greatest hypoxaemia during exercise demonstrated the most attenuation of quadriceps fatigue. Based on our previous finding that women have a greater relative oxygen cost of breathing, women appear to be especially susceptible to work of breathing-related changes in quadriceps muscle fatigue., Abstract: Reducing the work of breathing or eliminating exercise-induced arterial hypoxaemia (EIAH) during exercise decreases the severity of quadriceps fatigue in men. Women have a greater work of breathing during exercise, dedicate a greater fraction of whole-body V̇O2 towards their respiratory muscles, and demonstrate EIAH, suggesting women may be especially susceptible to quadriceps fatigue. Healthy subjects (8 male, 8 female) completed three constant load exercise tests over 4 days. During the first (control) test, subjects exercised at ∼85% of maximum while arterial blood gases and work of breathing were assessed. Subsequent constant load exercise tests were iso-time and iso-work rate, but with EIAH prevented by inspiring hyperoxic gas or work of breathing reduced via a proportional assist ventilator (PAV). Quadriceps fatigue was assessed by measuring force in response to femoral nerve stimulation. For both sexes, quadriceps force was equally reduced after the control trial (-27 ± 2% baseline) and was attenuated with hyperoxia and PAV (-18 ± 1 and -17 ± 2% baseline, P < 0.01, respectively), with no sex difference. EIAH was similar between the sexes, and regardless of sex, subjects with the lowest oxyhaemoglobin saturation during the control test had the greatest quadriceps fatigue attenuation with hyperoxia (r 2  = 0.79, P < 0.0001). For the PAV trial, despite reducing the work of breathing to a greater degree in men (men: 60 ± 5, women: 75 ± 6% control, P < 0.05), the attenuation of quadriceps fatigue was similar between the sexes (36 ± 4 vs. 37 ± 7%). Owing to a greater relative V̇O2 of the respiratory muscles in women, less of a change in work of breathing is needed to reduce quadriceps fatigue., (© 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.)

What is the central question of this study? Can a modern proportional assist ventilator (PAV) function sufficiently well to unload the respiratory muscles during exercise? What is the main finding and its importance? A PAV can be constructed with contemporary hardware and software and be used at all exercise intensities to unload the respiratory muscles by up to 70%. Previously, PAVs have allowed researchers to address many fundamental physiological problems in clinical and healthy populations, but those versions are no longer functional or available. We describe the creation of a PAV that permits researchers to use it as an experimental tool. Manipulation of the normally occurring work of breathing (WOB) during exercise can provide insights into whole-body regulatory mechanisms in clinical patients and healthy subjects. One method to reduce the WOB uses a proportional assist ventilator (PAV). Suitable commercially available units are not capable of being used during heavy exercise. This investigation was undertaken in order to create a PAV and assess the degree to which the WOB could be reduced during exercise. A PAV works by creating a positive mouth pressure (Pm ) during inspiration, which consequently reduces the WOB. Spontaneous breathing patterns can be maintained, and the amplitude of Pm is calculated using the equation of motion and predetermined proportionality constants. We generated positive Pm using a breathing apparatus consisting of rigid tubing, solenoid valves to control the airflow direction and a proportional valve connected to compressed gas. Healthy male and female subjects were able to use the PAV successfully while performing cycling exercise over a range of intensities (50-100% of maximal workload) for different durations (from 30 s to 20 min) and different protocols (constant versus progressive workload). Inspiratory WOB was reduced up to 90%, while total WOB was reduced by 70%. The greatest reduction in WOB (50-75%) occurred during submaximal exercise, but at maximal ventilations (>180 l min(-1) ) a 50% reduction was still possible. The calculated change in WOB and subsequent reduction in respiratory muscle oxygen consumption resulted in equivalent reductions in whole-body oxygen consumption. With adequate familiarization and practice, our PAV can consistently reduce the WOB across a range of exercise intensities., (© 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.)

Video slideshow introduction to the Symposium by Symposium Speaker A. William Sheel can be found here., (© 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.)

New Findings: What is the topic of this review? This review focuses on sex-based differences in the anatomy of the respiratory system, which manifest in mechanical ventilatory constraints and potentially alter the integrative response to exercise. What advances does it highlight? Recent evidence indicates that women have smaller conducting airways than men, even when matched for lung size. Consequently, women are more likely to experience mechanical ventilatory constraints to exercise hyperpnoea. Furthermore, at a given ventilation, women have a higher work and oxygen cost of breathing, both of which may lead to differences in the whole-body integrative response to dynamic exercise. Our understanding of the human ventilatory response to exercise is largely based on a historical body of literature focused primarily on male rather than female research subjects. In recent years, important sex-based differences in the anatomy of the human respiratory system have been identified; for a given lung size, women appear to have smaller-diameter conducting airways than men. The presence of such inherent differences in the tracheobronchial tree greatly affects the mechanics of airflow generation, especially during conditions of high ventilation rates, such as exercise. Data from a growing number of studies suggest that women may be more susceptible to respiratory system limitations during exercise than their male counterparts. Specifically, women are more likely to experience expiratory flow limitation and exercise-induced arterial hypoxaemia and have a higher metabolic cost of breathing for a given ventilation. Collectively, the available evidence suggests that sex differences in the ventilatory response to exercise are present and may have important ramifications for the integrated response to exercise; however, several fundamental questions remain unanswered., (© 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.)

We asked if the higher work of breathing (Wb) during exercise in women compared with men is explained by biological sex. We created a statistical model that accounts for both the viscoelastic and the resistive components of the total Wb and independently compares the effects of biological sex. We applied the model to esophageal pressure-derived Wb values obtained during an incremental cycle test to exhaustion. Subjects were healthy men (n = 17) and women (n = 18) with a range of maximal aerobic capacities (V̇o2 max range: men = 40-68 and women = 39-60 ml·kg(-1)·min(-1)). We also calculated the dysanapsis ratio using measures of lung recoil and forced expiratory flow as index of airway caliber. By applying the model we found that the differences in the total Wb during exercise in women are due to a higher resistive Wb rather than viscoelastic Wb. We also found that the higher resistive Wb is independently explained by biological sex. To account for the known effect of lung volumes on the dysanapsis ratio we compared the sexes with an analysis of covariance procedures and found that when vital capacity was accounted for the adjusted mean dysanapsis ratio is statistically lower in women (0.17 vs. 0.25 arbitrary units; P < 0.05). Our collective findings suggest that innate sex-based differences may exist in human airways, which result in significant male-female differences in the Wb during exercise in healthy subjects., (Copyright © 2015 the American Physiological Society.)

To determine the contribution of convective and diffusive limitations to V̇(O2peak) during exercise in humans, oxygen transport and haemodynamics were measured in 11 men (22 ± 2 years) during incremental (IE) and 30 s all-out cycling sprints (Wingate test, WgT), in normoxia (Nx, P(IO2): 143 mmHg) and hypoxia (Hyp, P(IO2): 73 mmHg). Carboxyhaemoglobin (COHb) was increased to 6-7% before both WgTs to left-shift the oxyhaemoglobin dissociation curve. Leg V̇(O2) was measured by the Fick method and leg blood flow (BF) with thermodilution, and muscle O2 diffusing capacity (D(MO2)) was calculated. In the WgT mean power output, leg BF, leg O2 delivery and leg V̇(O2) were 7, 5, 28 and 23% lower in Hyp than Nx (P < 0.05); however, peak WgT D(MO2) was higher in Hyp (51.5 ± 9.7) than Nx (20.5 ± 3.0 ml min(-1) mmHg(-1), P < 0.05). Despite a similar P(aO2) (33.3 ± 2.4 and 34.1 ± 3.3 mmHg), mean capillary P(O2) (16.7 ± 1.2 and 17.1 ± 1.6 mmHg), and peak perfusion during IE and WgT in Hyp, D(MO2) and leg V̇(O2) were 12 and 14% higher, respectively, during WgT than IE in Hyp (both P < 0.05). D(MO2) was insensitive to COHb (COHb: 0.7 vs. 7%, in IE Hyp and WgT Hyp). At exhaustion, the Y equilibration index was well above 1.0 in both conditions, reflecting greater convective than diffusive limitation to the O2 transfer in both Nx and Hyp. In conclusion, muscle V̇(O2) during sprint exercise is not limited by O2 delivery, O2 offloading from haemoglobin or structure-dependent diffusion constraints in the skeletal muscle. These findings reveal a remarkable functional reserve in muscle O2 diffusing capacity., (© 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.)

Background: Physical activity has health benefits across the lifespan, yet only 13 % of Canadian older adults are sufficiently active. Results from a number of observational studies indicate that adults display positive preferences for exercising with others of a similar age and same gender, and that intra-group age- and gender-similarity are associated with elevated exercise adherence. However, research has yet to experimentally examine the extent to which intra-group age- and gender-related similarity affect exercise adherence behaviors., Methods/design: The GrOup-based physical Activity for oLder adults (GOAL) trial is a three-arm randomized control trial that will examine the efficacy of two different group-based exercise programs for older adults (informed by the tenets of self-categorization theory) in relation to a standard group-based exercise program. Within this manuscript we outline the design and proposed evaluation of the GOAL trial. The first arm is comprised of exercise groups made up of participants of a similar-age and of the same gender; the second arm consists of groups with similar-aged mixed gender participants; the control arm is comprised of mixed-aged mixed gender participants. We aim to compare the adherence rates of participants across conditions, as well as potential moderation effects and mediating mechanisms., Discussion: Results from this trial will inform intervention designs to improve the exercise adherence behaviors of older adult. At a systems-level, should support be derived for the efficacy of the interventions tested in this trial, changing group composition (i.e., age, gender) represents a feasible program adaptation for physical activity centers., Trial Registration: ClinicalTrials.gov # NCT02023632 . Registered December 13, 2013.

Key Points: The oxygen cost of breathing represents a significant fraction of total oxygen uptake during intense exercise. At a given ventilation, women have a greater work of breathing compared with men, and because work is linearly related to oxygen uptake we hypothesized that their oxygen cost of breathing would also be greater. For a given ventilation, women had a greater absolute oxygen cost of breathing, and this represented a greater fraction of total oxygen uptake. Regardless of sex, those who developed expiratory flow limitation had a greater oxygen cost of breathing at maximal exercise. The greater oxygen cost of breathing in women indicates that a greater fraction of total oxygen uptake (and possibly cardiac output) is directed to the respiratory muscles, which may influence blood flow distribution during exercise., Abstract: We compared the oxygen cost of breathing (V̇O2 RM ) in healthy men and women over a wide range of exercise ventilations (V̇E). Eighteen subjects (nine women) completed 4 days of testing. First, a step-wise maximal cycle exercise test was completed for the assessment of spontaneous breathing patterns. Next, subjects were familiarized with the voluntary hyperpnoea protocol used to estimate V̇O2 RM . During the final two visits, subjects mimicked multiple times (four to six) the breathing patterns associated with five or six different exercise stages. Each trial lasted 5 min, and on-line pressure-volume and flow-volume loops were superimposed on target loops obtained during exercise to replicate the work of breathing accurately. At ∼55 l min(-1) V̇E, V̇O2 RM was significantly greater in women. At maximal ventilation, the absolute V̇O2 RM was not different (P > 0.05) between the sexes, but represented a significantly greater fraction of whole-body V̇O2 in women (13.8 ± 1.5 vs. 9.4 ± 1.1% V̇O2). During heavy exercise at 92 and 100% V̇O2max, the unit cost of V̇E was +0.7 and +1.1 ml O2 l(-1) greater in women (P < 0.05). At V̇O2max, men and women who developed expiratory flow limitation had a significantly greater V̇O2 RM than those who did not (435 ± 44 vs. 331 ± 30 ml O2  min(-1) ). In conclusion, women have a greater V̇O2 RM for a given V̇E, and this represents a greater fraction of whole-body V̇O2. The greater V̇O2 RM in women may have implications for the integrated physiological response to exercise., (© 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.)

Repeatedly performing exercise in hypoxia could elicit an independent training response and become an unintended co-intervention. The primary purposes of this study were to determine if hypoxic exercise responses changed across repeated testing and to assess the day-to-day variability of commonly used measures of cardiorespiratory and metabolic responses to hypoxic exercise. Healthy young males (aged 23 ± 2 years) with a maximal O2 consumption of 50.7 ± 4.7 mL·kg(-1)·min(-1) performed 5 trials (H1 to H5) over a 2-week period in hypoxia (fraction of inspired oxygen = 0.13). Participants completed 3-min stages at 20%, 40%, 60%, and 10% of individual peak power. With increasing cycle exercise intensity there were increases in minute ventilation, O2 consumption, CO2 production, respiratory exchange ratio, heart rate (HR), blood lactate concentration, and ratings of perceived exertion for legs and respiratory system along with a reduction in oxyhaemoglobin saturation (%SpO2) (all p < 0.001). There were no systematic changes from H1 to H5 (p > 0.05). Most measures were highly repeatable across testing sessions with the coefficient of variation (CV) averaging ≤10% of the mean value in all variables except O2 consumption (17%), CO2 production (11%) and blood lactate concentration (17%). For HR and %SpO2 the CV was <5%. The exercise protocol did not elicit a training response when repeated 5 times during a 2-week period and the variability of exercise responses was low. We conclude that this protocol allows detection of small changes in cardiorespiratory responses to hypoxic exercise that might occur during exposure to hypoxia.

In this study we tested the hypothesis that inspiring a low-density gas mixture (helium-oxygen; HeO2) would minimize mechanical ventilatory constraints and preferentially increase exercise performance in females relative to males. Trained male (n = 11, 31 yr) and female (n = 10, 26 yr) cyclists performed an incremental cycle test to exhaustion to determine maximal aerobic capacity (V̇o2max; male = 61, female = 56 ml·kg(-1)·min(-1)). A randomized, single-blinded crossover design was used for two experimental days where subjects completed a 5-km cycling time trial breathing humidified compressed room air or HeO2 (21% O2:balance He). Subjects were instrumented with an esophageal balloon for the assessment of respiratory mechanics. During the time trial, we assessed the ability of HeO2 to alleviate mechanical ventilatory constraints in three ways: 1) expiratory flow limitation, 2) utilization of ventilatory capacity, and 3) the work of breathing. We found that HeO2 significantly reduced the work of breathing, increased the size of the maximal flow-volume envelope, and reduced the fractional utilization of the maximal ventilatory capacity equally between men and women. The primary finding of this study was that inspiring HeO2 was associated with a statistically significant performance improvement of 0.7% (3.2 s) for males and 1.5% (8.1 s) for females (P < 0.05); however, there were no sex differences with respect to improvement in time trial performance (P > 0.05). Our results suggest that the extent of sex-based differences in airway anatomy, work of breathing, and expiratory flow limitation is not great enough to differentially affect whole body exercise performance., (Copyright © 2015 the American Physiological Society.)

The oxygen cost of exercise hyperpnea (V˙(O2 RM)) has been quantified using a variety of techniques with inconsistent findings. Between-study variation relates to poor control of breathing patterns and lung mechanics. We developed a methodology allowing precise matching of exercising WOB in order to estimate V˙(O2 RM). Thirteen healthy young subjects (7 male) completed an incremental cycle exercise test, familiarization and experimental days where exercise hyperpnea was mimicked. On experimental days, feedback of exercise flow, volume and the respiratory pressures were provided while end-tidal CO2 was kept at exercise levels during each 5-min trial. Minute ventilation levels between 50 and 100% maximum were mimicked 3-5 times. The r(2) between exercise and mimic trails was 0.99 for frequency, tidal volume and minute ventilation; 0.86 for esophageal pressure swings and 0.93 for WOB. The coefficient of variation for (V˙(O2) averaged 4.3, 4.4 and 5.7% for 50, 75 and 100% ventilation trials. When WOB and other respiratory parameters are tightly controlled, the V˙(O2 RM) can be consistently estimated., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Exercise-induced arterial hypoxemia (EIAH) occurs in some healthy humans at sea-level, whereby the most aerobically trained individuals develop the most severe hypoxemia. A female competitive runner completed 2 maximal exercise tests. Maximal oxygen consumption increased by 15% between testing days, but the degree of hypoxemia remained similar (PaO2, SaO2; 82 and 80 mm Hg; 93.8% and 92.8%; first and second test, respectively). Our case indicates that EIAH does not necessarily worsen with aerobic training.

The purpose of this study was to characterize exercise-induced arterial hypoxaemia (EIAH), pulmonary gas exchange and respiratory mechanics during exercise, in young healthy women. We defined EIAH as a >10 mmHg decrease in arterial oxygen tension ( ) during exercise compared to rest. We used a heliox inspirate to test the hypothesis that mechanical constraints contribute to EIAH. Subjects with a spectrum of aerobic capacities (n = 30; maximal oxygen consumption ( ) = 49 ± 1, range 28-62 ml kg(-1) min(-1)) completed a stepwise treadmill test and a subset (n = 18 with EIAH) completed a constant load test (~85% ) with heliox gas. Throughout exercise arterial blood gases, oxyhaemoglobin saturation ( ), the work of breathing (WOB) and expiratory flow limitation (EFL) were assessed. Twenty of the 30 women developed EIAH with a nadir and ranging from 58 to 88 mmHg and 87 to 96%, respectively. At maximal exercise, was inversely related to (r = -0.57, P < 0.05) with notable exceptions where some subjects with low aerobic fitness levels demonstrated EIAH. Subjects with EIAH had a greater (51 ± 1 vs. 43 ± 2 ml kg(-1) min(-1)), lower end-exercise (93.2 ± 0.5 vs. 96.1 ± 0.3%) and a greater maximal energetic WOB (324 ± 19 vs. 247 ± 23 J min(-1)), but had similar resting pulmonary function compared to those without EIAH. Most subjects developed EIAH at submaximal exercise intensities, with distinct patterns of hypoxaemia. In some subjects with varying aerobic fitness levels, mechanical ventilatory constraints (i.e. EFL) were the primary mechanism associated with the hypoxaemia during the maximal test. Mechanical ventilatory constraints also prevented adequate compensatory alveolar hyperventilation in most EIAH subjects. Minimizing mechanical ventilatory constraints with heliox inspiration partially reversed EIAH in subjects who developed EFL. In conclusion, healthy women of all aerobic fitness levels can develop EIAH and begin to do so at submaximal intensities. Mechanical ventilatory constraints are a primary mechanism for EIAH in some healthy women and prevent reversal of hypoxaemia in women for whom it is not the primary mechanism.

A healthy 36-year-old untrained (maximal oxygen consumption (V(O2max)): 39 mL/kg/min) woman completed multiple graded exercise tests on a treadmill. Temperature-corrected arterial blood samples were obtained in addition to esophageal pressure. Significant hypoxemia (-13 mm Hg arterial oxygen tension decrease) and arterial oxyhemoglobin desaturation (-6% decrease) was observed relative to rest and occurred during submaximal exercise and worsened at maximal intensities. Expiratory flow limitation (28-40% intersection of tidal volume) was present at near-maximal intensities. Relieving mechanical ventilatory constraints with a helium inspirate (79% He:21% O(2)) partially reversed the hypoxemia. Conversely, increasing chemical ventilatory stimuli, with hypercapnia (3.5% CO(2)), failed to increase ventilation. Maintaining oxyhemoglobin saturation, via a mildly hyperoxic (26% O(2)) inspirate, increased exercise duration (+45 s) and V(O2max) (+5 mL/kg/min). We attribute the hypoxemia to an excessive A-a(O2) resulting from ventilation-perfusion mismatch and secondarily to mechanical ventilatory constraints. We conclude that a healthy untrained woman can develop EIAH and this remains stable over a period of 6 months., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Aging related changes in pulmonary function may make older women (OW) more susceptible to expiratory flow limitation (EFL) and lead to higher dyspnoea ratings during exercise relative to young women (YW). Accordingly, the purpose of this study was to compare sensory responses and EFL susceptibility and magnitude in 8 YW (29 ± 7 years) and 8 healthy OW (64 ± 3 years) matched for percentage-predicted forced vital capacity (% predicted FVC) and % predicted forced expiratory volume in 1 s. EFL was calculated as the percent overlap between tidal flow-volume loops during maximal exercise and the maximal expiratory flow-volume (MEFV) curve. Peak oxygen consumption (V'O(2peak)) was lower in the OW compared to the YW (29.4 ± 3.6 vs. 49.1 ± 8.9 ml kg(-1) min(-1), P < 0.05) as was maximal ventilation (73.7 ± 18.4 vs. 108.7 ± 14.1 l min(-1), P < 0.05). EFL at maximal exercise was present in 2 of 8 YW and in 5 of 8 OW. There were no significant differences in the magnitude of EFL between OW (23 ± 24, range: 0-69 %EFL) and YW (9 ± 18, range: 0-46 %EFL, P = 0.21). The magnitude of EFL in OW was inversely related to % predicted FVC (r = -0.69, P = 0.06), but this relationships was not observed in the YW (r = -0.23, P = 0.59). The OW consistently reported greater dyspnoea and leg discomfort for any given absolute work rate, but not when work was expressed as a percentage of maximum. Reduced ventilatory and exercise capacities may cause OW to be more susceptible to EFL during exercise and experience greater dyspnoea relative to YW for a standardized physical task.

Weighted backpacks are used extensively in recreational and occupational settings, yet their effects on lung mechanics during acute exercise is poorly understood. The purpose of this study was to determine the effects of different backpack weights on lung mechanics and breathing patterns during treadmill walking. Subjects (n = 7, age = 28 ± 6 years), completed two 2.5-min exercise stages for each backpack condition [no backpack (NP), an un-weighted backpack (NW) or a backpack weighing 15, 25 or 35 kg]. A maximal expiratory flow volume curve was generated for each backpack condition and an oesophageal balloon catheter was used to estimate pleural pressure. The 15, 25 and 35 kg backpacks caused a 3, 5 and 8% (P < 0.05) reduction in forced vital capacity compared with the NP condition, respectively. For the same exercise stage, the power of breathing (POB) requirement was higher in the 35 kg backpack compared to NP (32 ± 4.3 vs. 88 ± 9.0 J min(-1), P < 0.05; respectively). Independent of changes in minute ventilation, end-expiratory lung volume decreased as backpack weight increased. As backpack weight increased, there was a concomitant decline in calculated maximal ventilation, a rise in minute ventilation, and a resultant greater utilization of maximal available ventilation. In conclusion, wearing a weighted backpack during an acute bout of exercise altered operational lung volumes; however, adaptive changes in breathing mechanics may have minimized changes in the required POB such that at an iso-ventilation, wearing a backpack weighing up to 35 kg does not increase the POB requirement.

The purpose of this study was to determine if healthy young women of various aerobic fitness levels are vulnerable to intrapulmonary arteriovenous shunts (IPAVS) at sub maximal work rates. Female volunteers (n=24) performed semi-recumbent cycling exercise to exhaustion and agitated saline contrast echocardiography was used to determine the presence of IPAVS at rest, during exercise, and post exercise. Subjects were classified as untrained (UT, n=8), moderately trained (MT, n=6) and highly trained (HT, n=10) based on their respective (V(O(2,peak)) (UT=35±5; MT=43±1 and HT = 50 ± 3 ml kg(-1) min(-1)). We found that the % (V(O(2,peak)) at IPAVS onset was not significantly different between women of varying fitness (P>0.05). The majority of individuals exhibited IPAVS during modest levels of exercise intensity. In conclusion, there is no association between aerobic capacity or exercise intensity at IPAVS onset in women performing semi-recumbent cycle exercise., (Copyright © 2012 Elsevier B.V. All rights reserved.)