Search

It has been suggested that the well-known health benefits associated with exercise can be explained by a placebo effect, and that greater effort should be given to convince people that their current behaviors have desirable health consequences. The overall purpose of this study was to test the efficacy of this "mind-set matters" hypothesis through the use of an expectancy-based intervention with adolescents. The study involved a four week randomized controlled trial with 348 Grade 9 adolescents (M (age) = 14.07 yrs, SD = 0.30), from four high schools, taking part in either a placebo-intervention condition (n = 188) or a control condition (n = 160). Participants in the placebo-intervention condition were informed that what they are already doing in school physical education lessons fulfills current recommendations for an active lifestyle. Participants in the control condition were not given this information. Four weeks after the intervention, adolescents in the placebo-intervention condition did not demonstrate significant changes in physiological health-related measures (diet, weight, body mass index, percentage body fat, heart rate, mean arterial pressure). The findings question the external validity of the "mind-set matters" hypothesis with adolescents, and suggest that simply encouraging adolescents to believe that they are healthy may not enable them to respond with improved indicators of physical health.

Respiratory modulation of sympathetic vasomotor outflow to skeletal muscles (muscle sympathetic nerve activity; MSNA) occurs in resting humans. Specifically, MSNA is highest at end-expiration and lowest at end-inspiration during quiet, resting breathing. We tested the hypothesis that within-breath modulation of MSNA would be amplified during graded leg cycling. Thirteen (n = 3 females) healthy young (age: 25.2 ± 4.7 yr) individuals completed all testing. MSNA (right median nerve) was measured at rest (baseline) and during semirecumbent cycle exercise at 40%, 60%, and 80% of maximal workload (Wmax). MSNA burst frequency (BF) was 20.0 ± 4.0 bursts/min at baseline and was not different during exercise at 40%Wmax (21.3 ± 3.7 bursts/min; P = 0.292). Thereafter, MSNA BF increased significantly compared with baseline (60%Wmax: 31.6 ± 5.8 bursts/min; P < 0.001, 80%Wmax: 44.7 ± 5.3 bursts/min; P < 0.001). At baseline and all exercise intensities, MSNA BF was lowest at end-inspiration and greatest at mid-to-end expiration. The within-breath change in MSNA BF (ΔMSNA BF; end-expiration minus end-inspiration) gradually increased from baseline to 60%Wmax leg cycling, but no further increase appeared at 80%Wmax exercise. Our results indicate that within-breath modulation of MSNA is amplified from baseline to moderate intensity during dynamic exercise in young healthy individuals, and that no further potentiation occurs at higher exercise intensities. Our findings provide an important extension of our understanding of respiratory influences on sympathetic vasomotor control., Published online 13 August 2021

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.

Voluntary activation can be used to assess central fatigue of the diaphragm after tasks such as exercise or inspiratory muscle loading. Cervical magnetic stimulation (CMS) of the phrenic nerves elicits an involuntary contraction, or twitch, of the diaphragm. This twitch is quantified based on a measure of transdiaphragmatic pressure and can be used to evaluate diaphragm contractile function and diaphragm voluntary activation (diaphragm-VA). The test–retest reliability of diaphragm-VA using CMS is currently unknown. Thirteen participants (4 male, 9 female; aged 25 ± 3 years) performed a series of interpolated twitch manoeuvres, which included a maximal inspiratory effort against a semi-occluded mouthpiece and 2 CMS-stimuli, 1 during the inspiratory manoeuvre and 1 after when the participant returned to functional residual capacity to quantify diaphragm-VA. Intraclass correlation coefficients (ICCs) and standard error of measurement (SEM) measured between-day and within-session reliability of diaphragm-VA, respectively. Maximal diaphragm-VA values were 91% (SD: 6; SEM: 3.9) and 92% (SD: 5; SEM: 2.2) during visits 1 and 2 (p = 0.68), respectively, and displayed “good” between-day reliability (ICC: 0.88; 95% confidence interval: 0.67–0.95; SEM: 2.7). Our results suggest that assessing diaphragm-VA using CMS is reliable in young healthy adults. Measuring diaphragm-VA may provide additional insight into the consequences and mechanisms of diaphragm fatigue. Novelty: Magnetic stimulation of the phrenic nerves can reliably measure voluntary activation of the diaphragm. Diaphragm voluntary activation can be used to provide additional insight into fatigability of the diaphragm.

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.

KEY POINTS Under normoxic conditions, both healthy female and male diaphragms fatigue at a similar degree when matched for absolute diaphragmatic work during inspiratory loading. We investigated whether similarities in diaphragm fatigability persist under acute hypoxic conditions. We found that, in acute hypoxia, fatigue of the diaphragm is greater in women compared to men, whereas the magnitude of fatigue in normoxia did not differ between sexes. When matched for maximal diaphragm strength, women and men had a similar pressor response to work-matched inspiratory loading, independent of oxygen availability. ABSTRACT In normoxia, women and men display a comparable magnitude of diaphragmatic fatigue (DF) after work-matched inspiratory loading. Whether these sex similarities are maintained under acute hypoxic conditions is unknown. We investigated the influence of acute hypoxia during work-matched inspiratory pressure-threshold loading (PTL) on DF in healthy women (n = 8) and men (n = 8). Two 5 min isocapnic PTL tasks targeting a transdiaphragmatic pressure (Pdi ) of 92 cmH2 O in normoxia and hypoxia (8% O2 ) were performed on separate days (≥48 h). DF was quantified by twitch Pdi (Pdi,tw ) via cervical magnetic stimulation post-PTL. Women and men had similar maximal Pdi (Pdi,max ; women: 171 ± 16, men: 178 ± 20 cmH2 O) and relative target workload (women: 54 ± 5%, men: 53 ± 6% Pdi,max ). The absolute cumulative diaphragmatic work did not differ between sexes in normoxia (women: 12,653 ± 1796 cmH2 O s-1 , men: 13,717 ± 1231 cmH2 O s-1 ; P = 0.202) or hypoxia (women: 11,624 ± 1860 cmH2 O s-1 , men: 12 722 ± 1502 cmH2 O s-1 ; P = 0.189). In normoxia, the magnitude of reduction in Pdi,tw post-PTL was similar between sexes (women: -21.1 ± 8.4%, men: -22.5 ± 4.9 %; P = 0.193); however, a higher degree of DF was observed in women compared to men following PTL in acute hypoxia (women: -27.6 ± 7.7%, men: -23.4 ± 9.6%, P = 0.019). We conclude that the female diaphragm is more susceptible to fatigue after inspiratory loading under acute hypoxic conditions. This finding may be related to sex differences in diaphragm muscle metabolism, such as fibre type composition, contractile properties, substrate utilisation and blood perfusion.

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. BFISCM was greater during VH compared to EX (P = 0.002) and increased with increasing exercise intensity (P = 0.036). BFISCM reached 493 ± 219% and 301 ± 215% rest during VH and EX at 90% peak work rate, respectively. BFIIC increased to 242 ± 178% and 210 ± 117% rest at 30% peak work rate during VH and EX, respectively. No statistically significant differences in BFIIC were observed with increased work rate during VH or EX (both P > 0.05). Moreover, there was no observed difference in BFIIC between conditions (P > 0.05). BFISCM 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.

KEY POINTS Diaphragm fatigue may increase the intensity (sensory dimension) and unpleasantness (affective dimension) of dyspnoea, which may partially explain why diaphragm fatigue negatively affects exercise performance. We hypothesized that diaphragm fatigue would negatively affect exercise performance via increases in both the intensity and unpleasantness of dyspnoea, and that the increase in dyspnoea would be mechanistically linked to an increase in diaphragmatic EMG (EMGdi ), a surrogate measure of neural respiratory drive. Fatiguing the diaphragm prior to exercise reduced cycling performance and increased both the intensity and unpleasantness of dyspnoea. The change in submaximal dyspnoea unpleasantness was significantly correlated with the change in cycling performance. Pre-fatigue of the diaphragm did not increase EMGdi during exercise and is therefore unrelated to the increase in either the sensory or affective dimension of exertional dyspnoea. ABSTRACT The purpose of this study was to examine the effect of diaphragm fatigue on the multidimensional components of dyspnoea and diaphragm electromyography (EMGdi ) during cycling. Sixteen healthy males (age = 27 ± 5 yr, VO2max = 45.8 ± 9.8 ml kg-1 min-1 ) completed two high-intensity, time-to-exhaustion cycling tests in randomized order: (i) inspiratory pressure threshold loading (PTL) prior to exercise to induce diaphragm fatigue (pre-DF) and (ii) no PTL (control). Diaphragm fatigue after PTL was confirmed via cervical magnetic stimulation of the phrenic nerves. Dyspnoea intensity and unpleasantness were measured throughout exercise with the 0-10 category-ratio Borg scale and following exercise using the Multidimensional Dyspnoea Profile (MDP). EMGdi was continuously recorded via a multipair oesophageal electrode catheter. Time-to-exhaustion decreased with pre-DF vs. control (9.0 ± 5.5 vs. 10.7 ± 7.5 min, P = 0.023). Pre-DF increased dyspnoea intensity ratings by 0.6 ± 1.0 Borg 0-10 units at the highest equivalent submaximal exercise time (HESET) a participant could achieve in both conditions (P = 0.020). Dyspnoea unpleasantness ratings increased with pre-DF by 0.5 ± 1.0, 0.7 ± 1.2 and 0.9 ± 1.4 (all P

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.

To quantify the mechanical work of breathing (Wb) during an indoor rowing test in men and women. Additionally, to compare sex-based differences in the Wb and its components through a rowing test. 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 Wb. Men had significantly higher values of instantaneous and cumulative total Wb at and beyond 37.5% (430.4 ± 42.5 vs. 282.1 ± 45.1 J min−1, P

Background: Perfusion of intrapulmonary arteriovenous anastomoses (IPAVA) is increased during exercise and in hypoxia and is associated with variations in oxygen saturation (SPO2), resulting in blo...

Adult survivors of very preterm (≤32 wk gestational age) birth without (PRE) and with bronchopulmonary dysplasia (BPD) have variable degrees of airflow obstruction at rest. Assessment of the shape of the maximal expiratory flow-volume (MEFV) curve in PRE and BPD may provide information concerning their unique pattern of airflow obstruction. The purposes of the present study were to 1) quantitatively assess the shape of the MEFV curve in PRE, BPD, and healthy adults born at full-term (CON), 2) identify where along the MEFV curve differences in shape existed between groups, and 3) determine the association between an index of MEFV curve shape and characteristics of preterm birth (i.e., gestational age, mass at birth, duration of oxygen therapy) in PRE and BPD. To do so, we calculated the average slope ratio (SR) throughout the effort-independent portion of the MEFV curve and at increments of 5% of forced vital capacity (FVC) between 20 and 80% of FVC in PRE ( n = 19), BPD ( n = 25), and CON ( n = 20). We found that average SR was significantly higher in PRE (1.34 ± 0.35) and BPD (1.33 ± 0.45) compared with CON (1.03 ± 0.22; both P < 0.05) but similar between PRE and BPD ( P = 0.99). Differences in SR between groups occurred early in expiration (i.e., 20–30% of FVC). There was no association between SR and characteristics of preterm birth in PRE and BPD groups (all P > 0.05). The mechanism(s) of increased SR during early expiration in PRE/BPD relative to CON is unknown but may be due to differences in the structural and mechanical properties of the airways.

The respiratory muscles encompass a variety of functions and roles, their action during exercise facilitates arterial blood-gas and pH regulation. Exercise hyperpnea is the first line of defense to meet increased metabolic demand. In so doing, the muscles of respiration encounter several challenges, which may lead to respiratory muscle fatigue and impaired exercise tolerance. The focus of this brief review is to summarize recent developments in the study of respiratory muscle mechanics, energetics, and fatigue during exercise. Advances in the field are highlighted and directions of potential future research identified.

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 cmH2 O, P = 0.002) and expiratory (59 ± 26 to 73 ± 32 cmH2 O, P = 0.007) mouth pressures, as well as peak expiratory flow (6.74 ± 1.51 vs. 7.32 ± 1.60 L/s, P

RATIONALE: Pulse wave velocity (PWV), as a measure of arterial stiffness, has been shown to be associated with resting heart rate (RHR) in general population studies. Yet, the evidence on this rela...

Airway luminal area (Ai) 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 Ai 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 Ai and luminal diameter were made for the 4th–6th airway generations. A composite index of airway size was calculated as the sum of the Ai 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 Ai 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., We made in vivo measures of multiple airways and modeled the work of breathing (Wb)‐minute ventilation (V˙ E) relationship during exercise in a group of healthy young adults. We found that individuals with the highest resistive Wb had the smallest 4th–6th generation airways. These findings improve our understanding of the interrelationship between human airway dimensions and respiratory mechanics during exercise.

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 (fb) 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

This chapter introduces the concept of respiratory limitation and discusses the importance of understanding differences between demand and/or capacity issues. Traditionally, the respiratory system in healthy individuals has been described as ‘overbuilt’ for the demands placed on it during intense muscular exercise. It describes the normal adaptations that occur in response to athletic training. The chapter introduces the concept that airflow limitation may impact athletic performance. It explains how exercise-induced arterial hypoxaemia may occur and its impact on exercise performance. The chapter discusses how respiratory muscle function may contribute to respiratory limitation. Oxygen delivery to the active locomotor muscles is thus impaired, which enhances the perception of exertion and catalyses the onset of quadriceps muscle fatigue. Operating lung volumes during exercise leads to augmented respiratory neural drive and a high energetic work of breathing, which may be linked with earlier onset of respiratory muscle fatigue.

The thorax undergoes unique conditions while swimming. Hydrostatic pressure from water immersion places an external load on the thorax and increases airway resistance, and the horizontal body position results in central venous engorgement and an associated reduction in lung compliance. The aforementioned factors likely increase the work of breathing (Wb); however, this hypothesis remains untested. PURPOSE This study aimed to compare Wb during freestyle swimming relative to cycling and to characterize the differences in the cardiorespiratory responses to swimming relative to cycling in the same individuals. METHODS Eight collegiate swimmers (four men and four women, age = 22 ± 2 yr) performed an incremental swim test while tethered to a resistance apparatus. On a separate day, subjects performed an incremental cycle test. During swimming and cycling, metabolic and ventilatory parameters were measured using a customized metabolic cart, and inspired Wb was quantified using an esophageal balloon catheter. RESULTS Swimming and cycling elicited statistically similar levels of peak oxygen uptake (3.87 ± 0.92 vs 4.20 ± 0.83 L·min, P = 0.143). However, peak minute ventilation (V˙E) (118 ± 3 vs 154 ± 25 L·min) and heart rate (164 ± 19 vs 183 ± 8 bpm) were significantly lower during swimming relative to cycling (both P < 0.05). Inspired Wb was higher at a V˙E of 50 L·min (+27 ± 16 J·min), 75 L·min (+56 ± 23 J·min), and 100 L·min (+53 ± 22 J·min) during swimming compared with cycling (all P < 0.05). Periods of interbreath apnea were observed while swimming (duration = 0.13-2.07 s). CONCLUSION We interpret our findings to mean that the horizontal body position and hydrostatic pressure on the chest wall requires swimmers to generate greater inspiratory pressures to sustain adequate V˙E during exercise.

International audience

Swimmers have a high prevalence of exercise-induced bronchoconstriction (EIB), which may be associated with repeated exposure to chlorinated pool water. The eucapnic voluntary hyperpnea (EVH) test is used to diagnose EIB; however, it fails to replicate the environmental conditions experienced by swimmers. The relationship between the composition of the EVH inspired gas and the development of EIB from swim exercise remains unclear. PURPOSE This study aimed to compare the bronchoconstrictive effect of a chlorinated inspirate EVH test and swim test to a laboratory-based EVH test in swimmers. METHODS Fifteen collegiate swimmers (n = 5 male, n = 10 female; 21 ± 2 yr) completed 3 d of testing in pseudorandom order; a standard EVH test (EVHL), a pool air EVH test (EVHCl), and a swimming test (Swim). Spirometry was measured at baseline, and 3, 5, 10, 15, and 20 min after each test. RESULTS EVHL elicited a forced expired volume in 1 s (FEV1) fall index of -9.7% ± 6.4% compared with -6.6% ± 9.2% and -3.0% ± 7.5% after EVHCl and Swim, respectively (P < 0.05). Using Bland-Altman analysis, we found good agreement between EVHL and EVHCl (bias = -2.8, r = 0.79; P < 0.05) with poor agreement between EVHL and Swim (bias = -6.7, r = 0.20) and between EVHCl and Swim (bias = -3.9, r = 0.50; both P < 0.05). Forced expired flow between 25% and 75% lung volume and peak expired flow were significantly reduced by the EVHL compared with the EVHCl and Swim tests (P < 0.05). CONCLUSIONS EVHL elicits a greater forced expired volume in 1-s fall index compared with EVHCl and Swim. The unique aquatic environment of swimmers potentially protects against bronchoconstriction and should be considered in the determination of EIB.

Sex-differences in the morphometry of the human respiratory system have previously been identified. Specifically, women have smaller lungs than men, even when matched for height, and women have smaller large conducting airways than men, even when matched for lung size. Moreover, the shape of the rib-cage and lungs differs based on sex. These inherent sex-differences in the structure of the respiratory system have important effects on resting pulmonary function and the integrative response to exercise. In this review, we summarize recent findings as they relate to sex-differences in the structure and function of the respiratory system. Additionally, we highlight important gaps in our understanding of the effect of sex on the anatomy and physiology of the respiratory system.

Purpose: Characterize the effects of age, sex, and their interaction on inspiratory muscle activation patterns during exercise. Methods: Twenty younger (20-30y, n=10 women) and twenty older (60-80y, n=10 women) subjects performed an incremental cycle exercise test. Electromyography of the scalene (EMGsca) and sternocleidomastoid (EMGscm) muscles were measured using skin surface electrodes, while diaphragm electromyography (EMGdi) and esophageal and transdiaphragmatic pressures were measured using an esophageal catheter. Electromyography data were transformed into root-mean-square with a 100ms time constant. Esophageal (PTPes) and diaphragmatic (PTPdi) 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 p0.05). Women had greater EMGsca activity than men at absolute and relative levels of V E (all p0.05). At absolute and relative levels of V E, women and older subjects had greater EMGscm than men and younger subjects, respectively (all p0.05). No significant interactions between age and sex were noted (all p>0.05). Conclusion: Age and sex significantly affect inspiratory muscle activation patterns during exercise; however, the extent of the effects depends on whether comparisons are made at a solute or relative V E. This study was supported by the British Columbia Lung Association (BCLA). YMS, PBD, and AHR were supported by graduate scholarships from the Natural Sciences and Engineering Research Council of Canada (NSERC). PBD and MRS were supported by fellowships from the University of British Columbia and BCLA. JAG was supported by a Scholar Award from the Michael Smith Foundation for Health Research, a New Investigator Award from the Providence Health Care Research Institute and St. Paul’s Hospital Foundation, and a Canadian Institutes of Health Research Clinical Rehabilitation New Investigator Award.

KEY POINTS Diaphragmatic fatigue (DF) elicits a sympathetically mediated metaboreflex resulting in increased heart rate, blood pressure and limb vascular resistance. Women may be more resistant to DF compared to men, and therefore it was hypothesised that women would experience an attenuated inspiratory muscle metaboreflex during inspiratory pressure-threshold loading (PTL) performed to task failure. At the time of PTL task failure, the severity of DF was not different between sexes; however, inspiratory muscle endurance time was significantly longer in women than in men. For a given cumulative diaphragmatic force output, the severity of DF was less in women than in men. Women exhibited a blunted cardiovascular response to inspiratory resistance (i.e. metaboreflex) that may have implications for exercise tolerance. ABSTRACT Diaphragmatic fatigue (DF) elicits reflexive increases in sympathetic vasomotor outflow (i.e. metaboreflex). There is some evidence suggesting women may be more resistant to DF compared to men, and therefore may experience an attenuated inspiratory muscle metaboreflex. To this end, we sought to examine the cardiovascular response to inspiratory resistance in healthy young men (n = 9, age = 24 ± 3 years) and women (n = 9, age = 24 ± 3 years). Subjects performed isocapnic inspiratory pressure-threshold loading (PTL, 60% maximal inspiratory mouth pressure) to task failure. Diaphragmatic fatigue was assessed by measuring transdiaphragmatic twitch pressure (Pdi,tw ) using cervical magnetic stimulation. Heart rate (HR) and mean arterial pressure (MAP) were measured beat-by-beat throughout PTL via photoplethysmography, and low-frequency systolic pressure (LFSBP ; a surrogate for sympathetic vasomotor tone) calculated from arterial waveforms using power spectrum analysis. At PTL task failure, the degree of DF was similar between sexes (∼23% reduction in Pdi,tw ; P = 0.33). However, time to task failure was significantly longer in women than in men (27 ± 11 vs. 16 ± 11 min, respectively; P = 0.02). Women exhibited less of an increase in HR (13 ± 8 vs. 19 ± 12 bpm; P = 0.02) and MAP (10 ± 8 vs. 14 ± 9 mmHg; P = 0.01), and significantly lower LFSBP (23 ± 11 vs. 34 ± 8 mmHg2 ; P = 0.04) during PTL compared to men. An attenuation of the inspiratory muscle metaboreflex may influence limb and respiratory muscle haemodynamics with implications for exercise performance.

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.

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 (Pdi,tw) in response to cervical magnetic stimulation. DF was present after 75 and 100% TTE (≥20% decrease in Pdi,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.

Myocardial infarction (MI) remains under-recognized in chronic lung disease (CLD) patients. Rehabilitation health professionals need accessible clinical measurements to identify the presence of prior MI in order to determine appropriate training prescription.To estimate prior MI in CLD patients entering a pulmonary rehabilitation program, as well as its association with heart rate parameters such as resting heart rate and chronotropic response index.Retrospective cohort design.Pulmonary rehabilitation outpatient clinic in a tertiary care university-affiliated hospital.Eighty-five CLD patients were studied.Electrocardiograms at rest and peak cardiopulmonary exercise testing, performed before pulmonary rehabilitation, were analyzed. Electrocardiographic evidence of prior MI, quantified by the Cardiac Infarction Injury Score (CIIS), was contrasted with reported myocardial events and then correlated with resting heart rate and chronotropic response index parameters.CIIS, resting heart rate, and chronotropic response index.Sixteen CLD patients (19%) demonstrated electrocardiographic evidence of prior MI, but less than half (8%) had a reported MI history (P.05). The Cohen's kappa test revealed poor level of agreement between CIIS and medical records (kappa = 0.165), indicating that prior MI diagnosis was under-reported in the medical records. Simple and multiple regression analyses showed that resting heart rate but not chronotropic response index was positively associated with CIIS in our population (RCLD patients entering pulmonary rehabilitation are at risk of unreported prior MI. Elevated resting heart rate appears to be an indicator of prior MI in CLD patients; therefore, careful adjustment of training intensity is recommended under these circumstances.III.

New Findings What is the central question of this study? Adult survivors of preterm birth without (PRE) and with bronchopulmonary dysplasia (BPD) have airflow obstruction at rest and significant mechanical ventilatory constraints during exercise compared with those born at full term (CON). Do PRE/BPD have smaller airways, indexed via the dysanapsis ratio, than CON? What is the main finding and its importance? The dysanapsis ratio was significantly smaller in BPD and PRE compared with CON, with BPD having the smallest dysanapsis ratio. These data suggest that airflow obstruction in PRE and BPD might be because of smaller airways than CON. Adult survivors of very preterm birth (≤32 weeks gestational age) without (PRE) and with bronchopulmonary dysplasia (BPD) have obstructive lung disease as evidenced by reduced expiratory airflow at rest and have significant mechanical ventilatory constraints during exercise. Airflow obstruction, in any conditions, could be attributable to several factors, including small airways. PRE and/or BPD could have smaller airways than their counterparts born at full term (CON) owing to a greater degree of dysanaptic airway development during the pre- and/or postnatal period. Thus, the purpose of the present study was to compare the dysanapsis ratio (DR), as an index of airway size, between PRE, BPD and CON. To do so, we calculated DR in PRE (n = 21), BPD (n = 14) and CON (n = 34) individuals and examined flow–volume loops at rest and during submaximal exercise. The DR, using multiple estimates of static recoil pressure, was significantly smaller in PRE and BPD (0.16 ± 0.05 and 0.10 ± 0.03 a.u.) compared with CON (0.22 ± 0.04 a.u.; both P

Background Reduced heart rate variability (HRV), a marker of autonomic system dysfunction, has been reported in patients with chronic obstructive pulmonary disease (COPD). Yet, limited data exists on the reliability of HRV measurement in this population. Here we investigated the reliability of short-term HRV measurement performed during spontaneous breathing in patients with COPD. Methods Thirteen individuals (8 males) with moderate-to-severe COPD (FEV 1 46 ± 16% predicted; FEV 1 /FVC 49 ± 13) underwent standard time and frequency domain HRV measurements derived from 5-minute electrocardiograms collected on two separate days using a SphygmoCor device. Absolute and relative reliability was assessed by a number of coefficients including within-subject random variation, systematic change in the mean, and retest correlations. Results Within-subject coefficients of variation (CV) ranged from 4.3% to 193.4%. The intraclass correlation coefficients (ICCs) ranged from 0.72 to 0.93 for parameters related to overall HRV, and from 0.57 to 0.59 for those related to parasympathetic tone in both time and frequency domains. Mean heart rate was the only parameter that showed excellent absolute and relative reliability (CV = 4.3%, ICC = 0.93). Conclusion The HRV measurements showed overall moderate-to-substantial reliability during spontaneous breathing in COPD population. Our findings support the use of HRV parameters for diagnosis and cardiac risk assessment, but only mean heart rate can be used reliably for monitoring changes in autonomic status following rehabilitation intervention in this population.

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

Introduction Stimulation of the phrenic nerve via cervical magnetic stimulation (CMS) elicits a compound muscle action potential (CMAP) that allows for assessment of diaphragm activation. The reliability of CMS to evoke the CMAP recorded by chest wall surface EMG has yet to be comprehensively examined. Methods CMS was performed on healthy young males ( n = 10) and females ( n = 10). Surface EMG electrodes were placed on the right and left hemi-diaphragm between the 6–8th intercostal spaces. CMAPs were analysed for: latency, duration, peak-to-peak amplitude, and area. Reliability within and between experimental sessions was assessed using intraclass correlation coefficients (ICC). Bilateral (right-left) and sex-based (male-female) comparisons were also made (independent samples t -test). Results All CMAP characteristics demonstrated high reproducibility within (ICCs > 0.96) and between (ICCs > 0.89) experimental sessions. No statistically significant bilateral or sex-based differences were found ( p > 0.05). Discussion CMS is a reliable and non-invasive method to evaluate phrenic nerve conduction.

The Natural Sciences and Engineering Research Council (NSERC) of Canada supported this study. C.M. Peters, P.B. Dominelli, and Y. Molgat-Seon were supported by NSERC postgraduate scholarships. J.F Welch was supported by a University of British Columbia graduate fellowship.

This study was supported by the Natural Science and Engineering Research Council of Canada (NSERC). PBD, YMS and CMP were supported by a graduate scholarship from NSERC. PBD was also supported by the Canadian Thoracic Society.

We investigated the interactive effect of the exercise pressor reflex (EPR) and the chemoreflex (CR) on the cardiovascular response to exercise. Eleven healthy participants (5 females) completed a total of six bouts of single-leg knee-extension exercise (60% peak work rate, 4 min each) either with or without lumbar intrathecal fentanyl to attenuate group III/IV afferent feedback from lower limbs to modify the EPR, while breathing either ambient air, normocapnic hypoxia (S(a)O(2) ~79%, P(a)O(2) ~43 mmHg, P(a)CO(2) ~33 mmHg, pH ~7.39), or normoxic hypercapnia (S(a)O(2) ~98%, P(a)O(2) ~105 mmHg, P(a)CO(2) ~50 mmHg, pH ~7.26) to modify the CR. During co-activation of the EPR and the hypoxia-induced CR (O(2)-CR), mean arterial pressure and heart rate were significantly greater, whereas leg blood flow and leg vascular conductance were significantly lower than the summation of the responses evoked by each reflex alone. During co-activation of the EPR and the hypercapnia-induced CR (CO(2)-CR), the haemodynamic responses were not different from the summated responses to each reflex response alone (P ≥ 0.1). Therefore, while the interaction resulting from the EPR:O(2)-CR co-activation is hyper-additive for blood pressure and heart rate, and hypo-additive for peripheral haemodynamics, the interaction resulting from the EPR:CO(2)-CR co-activation is simply additive for all cardiovascular parameters. Thus, EPR:CR co-activation results in significant interactions between cardiovascular reflexes, with the impact differing when the CR activation is achieved by hypoxia or hypercapnia. Since the EPR:CR co-activation with hypoxia potentiates the pressor response and restricts blood flow to contracting muscles, this interaction entails the most functional impact on an exercising human.

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.

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 (Wb ) during exercise? What is the main finding and its importance? The resistive and viscoelastic components of Wb were higher in older adults, regardless of sex. The resistive, but not viscoelastic, component of Wb 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 (Wb ) for a given minute ventilation ( VE ). Age-related structural changes to the respiratory system lead to an increase in both the resistive and viscoelastic components of Wb ; 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. VE and Wb were assessed at rest and throughout exercise. Wb - VE data for each participant were fitted to a non-linear equation (i.e. Wb = a VE3 + b VE2 ) that partitions Wb into resistive (i.e. a VE3 ) and viscoelastic (i.e. b VE2 ) components. We then modelled the effects of healthy ageing and biological sex on each component of Wb . Overall, the model fit was excellent (r2 : 0.99 ± 0.01). There was a significant main effect of age and sex on the resistive component of Wb (both P 0.05). Our findings indicate that during exercise: (i) the higher total Wb in females relative to males is due to a higher resistive, but not viscoelastic, component of Wb , and (ii) regardless of sex, the higher Wb in older adults relative to younger adults is due to higher resistive and viscoelastic components of Wb .

ObjectiveSildenafil is a pulmonary vasodilator that may reduce the decrement in endurance performance in moderate hypoxia. We assessed the efficacy of sildenafil to improve performance in hypoxia.Data sources/eligibility CriteriaWe systematically searched electronic databases (until August 2018) for randomised trials comparing sildenafil with placebo. We also examined the effect of sildenafil on pulmonary artery pressure (PAP), cardiac output (CO) and pulse oxygen saturation (SPO2) compared with placebo in hypoxia. Fourteen studies were included; 210 subjects received sildenafil 40, 50 or 100 mg/day.ResultsSildenafil showed a large effect for decreasing PAP during exercise and at rest, a small effect for increasing CO during exercise and a moderate effect at rest, a moderate effect for increasing SPO2and a small effect for improving performance. In a subgroup analysis, there was no statistically significant difference between 100 and 50 mg sildenafil dose on SPO2. Sildenafil had a moderate effect on increasing SPO2and performance at terrestrial hypobaric altitude but only a small effect on both in normobaric hypoxia. Regression analysis showed that hypoxic dose (PO2) and metabolic rate do not account for a significant portion of the variance in effect size for sildenafil on PAP, CO, SPO2and performance.ConclusionThis meta-analysis indicates that sildenafil reduces PAP, has a moderate to small effect on CO and SPO2, and no effect on performance.

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.

Purpose To evaluate changes in oxygenated (O2Hb), deoxygenated (HHb), and total hemoglobin (tHb) of the sternocleidomastoid (SCM), parasternal (PS), biceps (BC), and tibialis anterior (TA) using near-infrared spectroscopy during incremental loading of the inspiratory muscles and the elbow flexors in people with stable chronic obstructive pulmonary disease. Methods Fifteen participants with obstructive pulmonary disease were recruited in a repeated-measures crossover design. Near-infrared spectroscopy optodes were applied over the SCM, PS, BC, and TA to measure O2Hb, HHb, and tHb. Participants were randomly assigned to perform incremental inspiratory threshold loading or elbow flexor loading that imposed higher loads every 2 minutes until task failure. At least 1 week later, participants performed the other test. Arterial oxygen saturation (SpO2) was monitored continuously. Results O2Hb of the main agonist muscles, SCM and BC, decreased compared with the other muscles during inspiratory threshold loading and elbow flexor loading, respectively. SCM O2Hb and BC O2Hb decreased at higher loads compared with baseline. SCM tHb and HHb increased, whereas TA tHb decreased during inspiratory threshold loading. tHb did not change among any muscles during elbow flexor loading. SpO2 did not change from baseline to task failure. Conclusions Our data suggest that the SCM was recruited progressively during incremental inspiratory threshold loading; however, O2Hb was not maintained in this muscle. Similarly, O2Hb was not maintained in the biceps during elbow flexor loading. This regional deoxygenation in SCM and BC during incremental loading protocols was not reflected by a decrease in SpO2.

New Findings What is the central question of this study? Can a modern proportional assist ventilator (PAV) function to sufficiently 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 during 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. Manipulating the normally occurring work of breathing (WOB) during exercise can provide insights into whole-body regulatory mechanisms in clinical and healthy subjects. One method to reduce the WOB utilizes a proportional assist ventilator (PAV). Suitable commercially available units are not capable for 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 airflow direction and a proportional valve connected to compressed gas. Healthy male and female subjects were able to successfully use the PAV while performing cycle exercise over a range of intensities (50–100% maximum workload) for different durations (30 s to 20 min) and different protocols (constant vs. progressive workload). Inspiratory WOB was reduced up to 90%, while total WOB was be reduced 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. This article is protected by copyright. All rights reserved

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 DLCO 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.

The pulmonary system is a key element within the integrated network responsible for maintaining blood gas homeostasis. In all physiologic states, including rest, sleep, and dynamic exercise, its primary function is to ensure that mixed venous blood is transformed into arterial blood with appropriate partial pressures of O2 and CO2. This system faces several significant challenges to its ability to maintain blood gas homeostasis during dynamic exercise. With a simultaneous increase in mixed venous carbon dioxide content and decrease in mixed venous oxygen content, ventilatory demands are significantly greater during exercise than during rest. A reduction in transit time of red blood cells through the pulmonary capillaries, resulting from an increased cardiac output, also decreases the time available for gas exchange. To maintain blood gas homeostasis despite these challenges, medullary neural networks and sensory reflex mechanisms tightly regulate alveolar ventilation. The structural capacity for producing ventilation and increasing diffusion surface area to meet the demands of dynamic exercise in the healthy respiratory system is truly remarkable.

Sildenafil is a pulmonary vasodilator that has potential to mitigate the decrement in endurance performance caused by hypoxic pulmonary vasoconstriction. The purpose of this study was to determine the effects of sildenafil on pulmonary artery pressure, cardiac output, pulse oxygen saturation, and exercise performance at moderate simulated altitude. We hypothesized that sildenafil would reduce the decline in exercise performance in hypoxia by blunting the rise in pulmonary artery pressure and causing a relative increase in cardiac output and oxygen saturation. Twelve endurance trained men performed three experimental cycling trials at sea level and simulated moderate altitude of 3,000m (FIO2 = 0.147) after ingesting either a placebo or sildenafil 50 mg capsule in a double blinded fashion. Each test consisted of a warmup period, a 15-minute steady state period at 60% of peak power output, and a 16.1 km time-trial. All subjects experienced a decline in maximal exercise capacity in hypoxia that ranged from 6% to 24%. This decline was correlated with the reduction in pulse oxygen saturation in hypoxic maximal exercise. Sildenafil had no effect on pulmonary artery pressure, cardiac output, or pulse oxygen saturation measured during steady state exercise. There was no effect of sildenafil on mean power output during the time-trial. During high intensity cycle exercise in acute, moderate hypoxia pulmonary artery pressure is unaffected by sildenafil and does not appear to influence cardiovascular function or exercise performance.

© 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society. KEY POINT SUMMARY:The perceived intensity of exertional breathlessness (i.e. dyspnoea) is higher in older women than in older men, possibly due to sex-difference 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 submaximal exercise at a moderate intensity, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea. We sought to determine the effect of manipulating mechanical ventilatory constraint during submaximal exercise on dyspnoea in older men and women. METHODS:Eighteen healthy subjects (60-80 y; 9 men, 9 women) completed two days of testing. On Day 1, subjects performed pulmonary function testing and 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 (Wb ) and alleviate expiratory flow limitation (EFL); ii) through an inspiratory resistance (RES) of ∼5 cmH2 O·l-1 ·s-1 to increase Wb ; and iii) ambient air as a control (CON). Oesophageal pressure, diaphragm electromyography, and sensory responses (using the category-ratio 10 Borg scale) were monitored throughout exercise. RESULTS:During the HEL condition, there was a significant decrease in Wb (men: -21 ± 6%, women: -17 ± 10%) relative to CON (both p