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Purpose: Inhaled nitric oxide improves exercise capacity in patients with severe congestive heart failure and chronic obstructive pulmonary disease. We attempted to improve aerobic exercise capacity, by preventing oxyhemoglobin desaturation, in eight patients with cystic fibrosis.Methods: Patients performed two randomly assigned incremental (15 W x min-1) cycle ergometer tests to fatigue. One test involved inhalation of 20 ppm nitric oxide plus compressed air (NO), the other only compressed air (AIR). Arterial oxyhemoglobin saturation, oxygen consumption, heart rate, minute ventilation, time to exhaustion, and maximal power output were all recorded.Results: There were no significant differences in maximal oxygen consumption, time to exhaustion, or power output between AIR and NO. Nor were there any difference between heart rate and minute ventilation during the two tests. Arterial oxyhemoglobin saturation was not different at rest but was significantly lower in the NO condition at 75 and 100% of maximal oxygen consumption (75% =-1.5 +/- 0.3 vs. -2.6 +/- 0.5%; 100% = -2.8 +/- 0.7 vs. -4.7 +/- 1.2%, p < .01), There was a significant correlation between maximal oxygen consumption and the fall in arterial oxyhemoglobin saturation with AIR (r= 0.90, p = 0.005) but not with NO (r = 0.68, p = 0.096). There was no correlation between disease severity (FEV1% predicted) and the fall in arterial oxyhemoglobin saturation with NO or with AIR.Conclusions: While the difference in arterial oxyhemoglobin saturation values at 75 and 100% maximal oxygen consumption were statistically significant, physiologically they had no effect on maximal performance measures. Our results suggest that nitric oxide failed to improve exercising arterial oxyhemoglobin saturation and may not have elicited any more detrimental effect on gas transfer than breathing a normal room air mixture. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The present study was designed to examine the dose-response relationship of inhaled salbutamol and its concentration in the urine while resting at various times after inhalation, and to compare these values against the current World Anti-Doping Code limits. DESIGN: An interventional, repeated-measures design. SETTING: Sport Medicine Clinic, University of British Columbia (Vancouver, Canada). PARTICIPANTS: Eight healthy, nonasthmatic males participated in this study (age = 28 +/- 6 years, height = 179.4 +/- 5.1 cm, and weight = 77.4 +/- 5.4 kg). INTERVENTION: Administration of three different doses of inhaled salbutamol (800, 400, and 200 microg) in a randomized fashion separated by at least 72 hours. MAIN OUTCOME MEASUREMENT: Urine concentration of nonsulphated salbutamol RESULTS: Urine concentrations were highly variable between subjects and increased as dose increased, with a significant difference noted between 800 and 200 microg at 30, 60, and 120 minutes after inhalation. Urine concentrations of salbutamol peaked at 60 minutes for all doses. No samples exceeded the doping criterion of 1000 ng/mL, and the maximum value observed was 904 ng/mL. CONCLUSION: These results indicate that after inhalation of doses up to 800 microg, urinary concentrations of salbutamol are well below the limits used in doping control. [ABSTRACT FROM AUTHOR]

PURPOSE: This study determined the dose-response effects of inhaled salbutamol (SAL) on time-trial performance and urine concentrations of SAL (cSAL). METHODS: Nonasthmatic, trained male cyclists and triathletes (N = 37) were studied. Day 1 consisted of screening for airway hyperresponsiveness, using a eucapnic voluntary hyperpnea test (EVH), followed by an incremental exercise test to determine V O 2max and peak power (P max). On days 2-5, athletes performed a 20-km time trial 15 min after inhalation (PI) of placebo, 200 microg (D2), 400 microg (D4), or 800 microg (D8) of SAL. At 60 min PI, urine samples were provided. All conditions were randomized and double blinded, with repeated-measures ANOVA used to determine effects of dose. Post hoc analysis was done with Tukey's HSD test. RESULTS: Seven subjects had positive responses to the EVH test, resulting in a 19% incidence within this sample; they were excluded from further participation in this study. The remaining subjects (N = 30) had a V O 2max of 67.1 (4.3) mL x kg(-1) x min(-1) and Pmax of 457 (31) W (W). There was no effect of dose on completion time (P > 0.05), mean power (P > 0.05), or mean heart rate (P > 0.05). Similarly, SAL had no effect on any metabolic or ventilatory parameters (P > 0.05). Urine cSAL increased with dose and was highly variable, with the peak value observed being 831 ng x mL(-1) after a dose of 800 microg. Moderate but significant correlations were noted between cSAL and urine specific gravity at higher doses (D4, r = 0.42; D8, r = 0.37). CONCLUSIONS: These findings suggest that inhaled SAL does not enhance time-trial performance, regardless of dose, and that urine cSAL after exercise is related to dose, demonstrates high variability, and is partially related to hydration status. [ABSTRACT FROM AUTHOR]

PURPOSE: To quantify the cardiorespiratory responses to indoor climbing during two increasingly difficult climbs and relate them to whole-body dynamic exercise. It was hypothesized that as climbing difficulty increased, oxygen consumption ([V02] and heart rate would increase, and that climbing would require utilization of a significant fraction of maximal cycling values. METHODS: Elite competitive sport rock climbers (6 male, 3 female) completed two data collection sessions. The first session was completed at an indoor climbing facility, and the second session was an incremental cycle test to exhaustion. During indoor climbing subjects were randomly assigned to climb two routes designated as 'harder' or 'easier' based on their previous best climb. Subjects wore a portable metabolic system, which allowed measurement of oxygen consumption [V02], minute ventilation ([V02]E), respiratory exchange ratio (RER), and heart rate. During the second session, maximal values for [V02], [V02]E, RER, and heart rate were determined during an incremental cycle test to exhaustion. RESULTS: Heart rate and [VO2], expressed as percent of cycling maximum, were significantly higher during harder climbing compared with easier climbing. During harder climbing, %HR(max) was significantly higher than %[V02] (2max) (89.6% vs 51.2%), and during easier climbing, %HR(max) was significantly higher than %[V02] (2max) (66.9% vs 45.3%). CONCLUSIONS: With increasing levels of climbing difficulty, there is a rise in both heart rate and [V02]. However, there is a disproportional rise in heart rate compared with [V02], which we attribute to the fact that climbing requires the use of intermittent isometric contractions of the arm musculature and the reliance of both anaerobic and aerobic metabolism. [ABSTRACT FROM AUTHOR]

Study design:Case report.Objectives:To report on the respiratory and kinematic changes associated with body weight supported treadmill training (BWSTT) in an individual with an incomplete cervical spinal cord injury (SCI).Setting:Human Locomotion Research Laboratory, Vancouver, BC, CanadaMethods:A 38-year-old man with an incomplete SCI at the C1/C2 level, graded on the American Spinal Injury Association Impairment Scale (AIS) as AIS D, participated in this case study. He performed three BWSTT sessions (45 min) per week for 12 weeks. Before and after training, respiration was measured at the mouth using a pneumotachograph while treadmill walking at 1.6 km h(-1).Results:Completion of 12 weeks of BWSTT resulted in a lowering of minute ventilation during treadmill exercise. A coupling of locomotion and respiration was observed during treadmill walking after the training program, whereas the relationship was initially absent.Conclusion:This case illustrates that BWSTT can result in a reduced ventilatory demand and promote locomotor-respiratory coupling during walking in an individual with an incomplete cervical SCI. [ABSTRACT FROM AUTHOR]

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

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.

Abstract: Leahy, MG, Kipp, S, and Sheel, AW. The effect of waistbands on intra-abdominal pressure and respiratory mechanics during bodyweight exercise. J Strength Cond Res XX(X): 000-000, 2024-Athletic apparel is often designed with high-waisted, elastic bands around the abdomen to provide comfort and support during functional exercises. The abdominal musculature aids in both active respiration and trunk stability during the exercise, but whether high-waistband athletic garments affect pulmonary function and respiratory mechanics is unknown. Ten healthy women participated in a single-visit study. Subjects were fitted with esophageal and gastric balloon-tipped catheters and completed three bouts of isometric and dynamic bodyweight squats, lunges, and planks, during which ventilation and pulmonary pressures were continuously recorded. Resting pulmonary function was unchanged by high-waistband garments. During isometric squatting exercise, peak abdominal pressure was significantly greater while wearing high-waistband garments (17 ± 6 cmH2O), relative to low-waistband garments (15 ± 6 cmH2O, p = 0.032). The work of breathing was reduced when completing dynamic squat exercise in a high-waistband garment (16.2 ± 3.9 J·min-1), relative to a low-waistband garment (18.6 ± 5.7 J·min-1, p = 0.026). High waistbands had no effect on abdominal pressures or pulmonary mechanics during lunge or plank exercises. We believe our findings indicate that high-waistband garments have the capacity to alter abdominal and ventilatory mechanics during bodyweight squatting exercises but are unlikely to have an effect during other exercise movements., (Copyright © 2024 National Strength and Conditioning Association.)

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.

Intense inspiratory muscle work can evoke a metabolite-stimulated pressor reflex, commonly referred to as the respiratory muscle metaboreflex. When completing similar relative and absolute levels of inspiratory work, females have an attenuated blood pressure response. We sought to test the hypothesis that the lower blood pressure response to the respiratory muscle metaboreflex in females is associated with a reduced sympathetic response. Healthy young (26 ± 4 yr) males ( n = 9) and females ( n = 7) completed two experimental days. On day 1 , participants completed pulmonary function testing and became familiarized with an inspiratory pressure-threshold loading (PTL) task. On the second day, balloon-tipped catheters were placed in the esophagus and stomach to measure pleural and gastric pressures, and transdiaphragmatic pressure was calculated. A microelectrode was inserted into the fibular nerve to quantify muscle sympathetic nerve activity (MSNA), and participants then completed isocapnic PTL to task failure. There was a significant sex-by-time interaction in the mean arterial pressure (MAP, P = 0.015) and burst frequency ( P = 0.039) response to PTL. Males had a greater rise in MAP (Δ21 ± 9 mmHg) than females (Δ13 ± 5 mmHg, P = 0.026). Males also demonstrated a greater rise in MSNA burst frequency (Δ18 ± 7 bursts/min) than females (Δ10 ± 5 bursts/min, P = 0.015). The effect of sex was observed despite females and males completing the same magnitude of diaphragm work throughout the task ( P = 0.755). Our findings provide novel evidence that the lower blood pressure response to similar relative and absolute inspiratory muscle work in females is associated with lower sympathetic activation. NEW & NOTEWORTHY The blood pressure response to high levels of inspiratory muscle work is lower in females and occurs alongside a reduced sympathetic response. The reduced blood pressure and sympathetic response occur despite males and females performing similar levels of absolute inspiratory work. Our findings provide evidence that sex differences in the respiratory muscle metaboreflex are, in part, sympathetically mediated.

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.

Purpose: We set out to understand how underband tightness or pressure of a sports bra relates to respiratory function and the mechanical work of breathing ( during exercise. Our secondary purpose was to quantify the effects of underband pressure on O 2 during submaximal running., Methods: Nine highly trained female runners with normal pulmonary function completed maximal and submaximal running in three levels of underband restriction: loose, self-selected, and tight., Results: During maximal exercise, we observed a significantly greater during the tight condition (350 ± 78 J·min -1 ) compared with the loose condition (301 ± 78 J·min -1 ; P < 0.05), and a 5% increase in minute ventilation ( ) during the tight condition compared with the loose condition ( P < 0.05). The pattern of breathing also differed between the two conditions; the greater maximal during the tight condition was achieved by a higher breathing frequency (57 ± 6 vs. 52 ± 7 breaths·min -1 ; P < 0.05), despite tidal volume being significantly lower in the tight condition compared with the loose condition (1.97 ± 0.20 vs. 2.05 ± 0.23 L; P < 0.05). During steady-state submaximal running, O 2 increased 1.3 ± 1.1% (range: -0.3 to 3.2%, P < 0.05) in the tight condition compared with the loose condition., Conclusions: Respiratory function may become compromised by the pressure exerted by the underband of a sports bra when women self-select their bra size. In the current study, loosening the underband pressure resulted in a decreased work of breathing, changed the ventilatory breathing pattern to deeper, less frequent breaths, and decreased submaximal oxygen uptake (improved running economy). Our findings suggest sports bra underbands can impair breathing mechanics during exercise and influence whole-body metabolic rate., (Copyright © 2024 by the American College of Sports Medicine.)

The pulmonary system is the first and last "line of defense" in terms of maintaining blood gas homeostasis during exercise. Our review provides the reader with an overview of how the pulmonary system responds to acute exercise. We undertook this endeavor to provide a companion article to "Cardiovascular Response to Exercise," which was published in Advances in Physiological Education . Together, these articles provide the readers with a solid foundation of the cardiopulmonary response to acute exercise in healthy individuals. The intended audience of this review is level undergraduate or graduate students and/or instructors for such classes. By intention, we intend this to be used as an educational resource and seek to provide illustrative examples to reinforce topics as well as highlight uncertainty to encourage the reader to think "beyond the textbook." Our treatment of the topic presents "classic" concepts along with new information on the pulmonary physiology of healthy aging. NEW & NOTEWORTHY Our narrative review is written with the student of the pulmonary physiology of exercise in mind, be it a senior undergraduate or graduate student or those simply refreshing their knowledge. We also aim to provide examples where the reader can incorporate real scenarios.

There is a significant effect of sex and muscle mass on the cardiorespiratory response to the skeletal muscle metaboreflex during isometric exercise. We therefore tested the hypothesis that sex differences would be present when isolated following dynamic exercise. We also tested the hypothesis that single and double leg post-exercise circulatory occlusion (PECO) following heavy exercise would elicit a cardiorespiratory response proportional to the absolute muscle mass. Healthy (24 ± 4 years) males ( n  = 10) and females ( n  = 10) completed pulmonary function and an incremental cycle test to exhaustion. Participants completed two randomized, 6 min bouts of intense cycle exercise (84 ± 7% V̇O 2peak ). One exercise bout was immediately followed by 3 min PECO (220 mmHg) of the legs while the other exercise bout was followed by passive recovery. Males completed an additional session of testing with single leg PECO. The mean arterial pressure during PECO and control was greater in males compared to females ( p  = 0.004). The was a significant time by condition by sex interaction in the heart rate response to PECO ( p  = 0.027). There was also a significant condition by sex interaction in the ventilatory response to PECO ( p  = 0.026). In males, we observed a dose-dependent cardiovascular, but not ventilatory, response to muscle mass occluded (all p  < 0.05). Our findings suggest the metaboreflex contribution to cardiorespiratory control during dynamic exercise is greater in males compared to females. The ventilatory response induced by double-leg occlusion but not single-leg occlusion, suggests that the ventilatory influence of the metaboreflex is less sensitive than the cardiovascular response and may be linked to the greater afferent activation induced by double-leg occlusion., Competing Interests: The authors declare there are no competing interests.

In healthy adults, airway-to-lung (i.e., dysanapsis) ratio is lower and dyspnoea during exercise at a given minute ventilation (V̇ E ) is higher in females than in males. We investigated the relationship between dysanapsis and sex on exertional dyspnoea in healthy adults. We hypothesized that females would have a smaller airway-to-lung ratio than males and that exertional dyspnoea would be associated with airway-to-lung ratio in males and females. We analyzed data from n  = 100 healthy never-smokers aged ≥40 years enrolled in the Canadian Cohort Obstructive Lung Disease (CanCOLD) study who underwent pulmonary function testing, a chest computed tomography scan, and cardiopulmonary exercise testing. The luminal area of the trachea, right main bronchus, left main bronchus, right upper lobe, bronchus intermedius, left upper lobe, and left lower lobe were 22%-37% smaller (all p  < 0.001) and the airway-to-lung ratio (i.e., average large conducting airway diameter relative to total lung capacity) was lower in females than in males (0.609 ± 0.070 vs. 0.674 ± 0.082; p  < 0.001). During exercise, there was a significant effect of V̇ E , sex, and their interaction on dyspnoea (all p  < 0.05), indicating that dyspnoea increased as a function of V̇ E to a greater extent in females than in males. However, after adjusting for age and total lung capacity, there were no significant associations between airway-to-lung ratio and measures of exertional dyspnoea, regardless of sex (all r  < 0.34; all p  > 0.05). Our findings suggest that sex differences in airway size do not contribute to sex differences in exertional dyspnoea., Competing Interests: The authors declare there are no competing interests.

Purpose: Musculoskeletal strength can be impaired in pediatric solid organ transplant recipients. Exercise training programs can be beneficial but in-person delivery can be challenging; virtual exercise programs can alleviate some of these challenges. This feasibility study aimed to deliver an 8-week virtual exercise program in pediatric solid organ transplant recipients., Method: Program delivery occurred 3 times per week for 30 minutes. An exercise stress test was completed prior to program start. The Bruininks-Oseretsky Test of Motor Proficiency strength subtest and self-report surveys were used to assess musculoskeletal strength, quality of life, fatigue, and physical activity. Contact was maintained through a text messaging platform. Z scores were calculated using standardized normative data. Medians (interquartile range) are reported for all other data., Results: Eleven participants completed the program (2 liver, 5 kidney, 4 heart; 58% females; median age = 11.5 [10.3-13.8] y). Six participants attended ≥60% of classes, 5 participants attended <50% of classes. After 8 weeks, strength scores improved (Z score, Pre: -1.0 [-1.65 to -0.60] to Post: -0.2 [-1.30 to 0.40]; P = .007) with no change in other outcome measures., Conclusion: The virtual exercise program was delivered without technical issues and received positive participant feedback. Engagement and costs need to be considered.

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.)

Competing Interests: None.

The purpose of the study was to characterize exercise induced arterial hypoxemia (EIAH) in female masters athletes (FMA). We hypothesized that FMA would experience EIAH during treadmill running. Eight FMA (48-57 years) completed pulmonary function testing and an incremental exercise test until exhaustion (V̇O 2 max⁡ = 45.7 ± 6.5, range:35-54 ml/kg/min). On a separate day, the participants were instrumented with a radial arterial catheter and an esophageal temperature probe. Participants performed three to four constant load exercise tests at 60-70 %, 75 %, 90 %, 95 %, and 100 % of maximal oxygen uptake while sampling arterial blood and recording esophageal temperature. We found that FMA decrease their partial pressure of oxygen (86.0 ± 7.6, range:73-108 mmHg), arterial saturation (96.2 ± 1.2, range:93-98 %), and widen their alveolar to arterial oxygen difference (23.2 ± 8.8, range:5-42 mmHg) during all exercise intensities however, with variability in terms of severity and pattern. Our findings suggest that FMA experience EIAH however aerobic fitness appears unrelated to occurrence or severity (r = 0.13, p = 0.756)., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Lower airway dysbiosis contributes to disease pathogenesis in respiratory diseases. However, little is known regarding the microbiota of lower airways or the oral cavity of healthy young persons. To address this gap, 25 healthy persons (24.3 ± 3.3 years; 52% females; no current smokers) underwent bronchoscopy during which bronchial brushing (BB) and bronchoalveolar lavage (BAL) fluid were collected. Prior to the procedure, an oral wash (OW) sample was also obtained. Microbiome analyses (16S rRNA locus) were performed (alpha- and beta-diversity, taxa annotations, and predicted functional metagenomic profiles) according to the airway compartment (BB, BAL, and OW). The greatest microbial richness was observed in OW and the lowest in BB ( p < 0.001). Microbial communities differed significantly across compartments ( p < 0.001), especially between BB and OW. Taxa analyses showed a significantly higher abundance of Firmicutes (BB: 32.7%; BAL: 31.4%) compared to OW (20.9%) ( p < 0.001). Conversely, Proteobacteria predominated in OW (27.9%) as opposed to BB (7.0%) and BAL (12.5%) ( p < 0.001), mostly due to a greater abundance of the bacteria in the Haemophilus genus in the OW ( p < 0.001). The lower airway microbiota (BB and BAL) is significantly different from the OW microbiota in healthy young persons with respect to microbial diversity, taxa profiles, and predicted function.

Intense inspiratory muscle work evokes a sympathetically mediated pressor reflex, termed the respiratory muscle metaboreflex, in which young females demonstrate an attenuated response relative to males. However, the effects of ageing and female sex hormones on the respiratory muscle metaboreflex are unclear. We tested the hypothesis that the pressor response to inspiratory work would be similar between older males and females, and higher relative to their younger counterparts. Healthy, normotensive young (26 ± 3 years) males (YM; n = 10) and females (YF; n = 10), as well as older (64 ± 5 years) males (OM; n = 10) and females (OF; n = 10), performed inspiratory pressure threshold loading (PTL) to task failure. Older adults had a greater mean arterial pressure (MAP) response to PTL than young (P < 0.001). YF had a lower MAP compared to YM (+10 ± 6 vs. +19 ± 15 mmHg, P = 0.026); however, there was no difference observed between OF and OM (+26 ± 11 vs. +27 ± 11 mmHg, P = 0.162). Older adults had a lower heart rate response to PTL than young (P = 0.002). There was no effect of sex between young females and males (+19 ± 9 and +27 ± 11 bpm, P = 0.186) or older females and males (+17 ± 7 and +20 ± 7 bpm, P = 0.753). We conclude the respiratory muscle metaboreflex response is heightened in older adults, and the sex effect between older males and post-menopause females is absent, suggesting an effect of circulating sex hormones. KEY POINTS: The arterial blood pressure response to the respiratory muscle metaboreflex is greater in older males and females. Compared to sex-matched young individuals, there is no sex differences in the blood pressure response between older males and post-menopause females. Our results suggest the differences between males and females in the cardiovascular response to high levels of inspiratory muscle work is abolished with reduced circulating female sex hormones., (© 2022 The Authors. The Journal of Physiology © 2022 The Physiological Society.)

Post-hypoxia sympathoexcitation does not elicit corresponding changes in vascular tone, suggesting diminished sympathetic signalling. Blunted sympathetic transduction following acute hypoxia, however, has not been confirmed and the effects of hypoxia on the sympathetic transduction of mean arterial pressure (MAP) as a function of action potential (AP) activity is unknown. We hypothesized that MAP changes would be blunted during acute hypoxia but restored in recovery and asynchronous APs would elicit smaller MAP changes than synchronous APs. Seven healthy males (age: 24 (3) years; BMI: 25 (3) kg/m 2 ) underwent 20 min isocapnic hypoxia (P ET O 2 : 47 (2) mmHg) and 30 min recovery. Multi-unit microneurography (muscle sympathetic nerve activity; MSNA) and continuous wavelet transform with matched mother wavelet was used to detect sympathetic APs during baseline, hypoxia, early (first 7 min) and late (last 7 min) recovery. AP groups were classified as synchronous APs, asynchronous APs (occurring outside an MSNA burst) and no AP activity. Sympathetic transduction of MAP was quantified using signal-averaging, with ΔMAP tracked following AP group cardiac cycles. Following synchronous APs, ΔMAP was reduced in hypoxia (+1.8 (0.9) mmHg) and early recovery (+1.5 (0.7) mmHg) compared with baseline (+3.1 (2.2) mmHg). AP group-by-condition interactions show that at rest asynchronous APs attenuate MAP reductions compared with no AP activity (-0.4 (1.1) vs. -2.2 (1.2) mmHg, respectively), with no difference between AP groups in hypoxia, early or late recovery. Sympathetic transduction of MAP is blunted in hypoxia and early recovery. At rest, asynchronous sympathetic APs contribute to neural regulation of MAP by attenuating nadir pressure responses. KEY POINTS: Acute isocapnic hypoxia elicits lasting sympathoexcitation that does not correspond to parallel changes in vascular tone, suggesting blunted sympathetic transduction. Signal-averaging techniques track the magnitude and temporal cardiovascular responses following integrated muscle sympathetic nerve activity (MSNA) burst and non-burst cardiac cycles. However, this does not fully characterize the effects of sympathetic action potential (AP) activity on blood pressure control. We show that hypoxia blunts the sympathetic transduction of mean arterial pressure (MAP) following synchronous APs that form integrated MSNA bursts and that sympathetic transduction of MAP remains attenuated into early recovery. At rest, asynchronous APs attenuate the reduction in MAP compared with cardiac cycles following no AP activity, thus asynchronous sympathetic APs appear to contribute to the neural regulation of blood pressure. The results advance our understanding of sympathetic transduction of arterial pressure during and following exposure to acute isocapnic hypoxia in humans., (© 2022 The Authors. The Journal of Physiology © 2022 The Physiological Society.)

New Findings: What is the central question of this study? What is the effect of lowering the normally occurring work of breathing on the electrical activity and pressure generated by the diaphragm during submaximal exercise in healthy humans? What is the main finding and its importance? Ventilatory assist during exercise elicits a proportional lowering of both the work performed by the diaphragm and diaphragm electrical activity. These findings have implications for exercise training studies using proportional assist ventilation to reduce diaphragm work in patients with cardiopulmonary disease., Abstract: We hypothesized that when a proportional assist ventilator (PAV) is applied in order to reduce the pressure generated by the diaphragm, there would be a corresponding reduction in electrical activity of the diaphragm. Healthy participants (five male and four female) completed an incremental cycle exercise test to exhaustion in order to calculate workloads for subsequent trials. On the experimental day, participants performed submaximal cycling, and three levels of assisted ventilation were applied (low, medium and high). Ventilatory parameters, pulmonary pressures and EMG of the diaphragm (EMG di ) were obtained. To compare the PAV conditions with spontaneous breathing intervals, ANOVA procedures were used, and significant effects were evaluated with a Tukey-Kramer test. Significance was set at P < 0.05. The work of breathing was not different between the lowest level of unloading and spontaneous breathing (P = 0.151) but was significantly lower during medium (25%, P = 0.02) and high (36%, P < 0.001) levels of PAV. The pressure-time product of the diaphragm (PTP di ) was lower across PAV unloading conditions (P < 0.05). The EMG di was significantly lower in medium and high PAV conditions (P = 0.035 and P < 0.001, respectively). The mean reductions of EMG di with PAV unloading were 14, 22 and 39%, respectively. The change in EMG di for a given lowering of PTP di with the PAV was significantly correlated (r = 0.61, P = 0.01). Ventilatory assist during exercise elicits a reduction in the electrical activity of the diaphragm, and there is a proportional lowering of the work of breathing. Our findings have implications for exercise training studies using assisted ventilation to reduce diaphragm work in patients with cardiopulmonary disease., (© 2022 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

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

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

Rating of perceived exertion (RPE) is used to subjectively quantify the perception of physical activity, breathlessness or dyspnea, and leg discomfort (RPE legs ) during exercise. However, it is unknown how dyspnea or RPE legs can be influenced by expectations. Thirty healthy, active participants (19 males, 11 females) completed five, 5-minute submaximal cycling trials at 60% peak work rate. We deceived participants by telling them they were inspiring different hypoxic and hyperoxic gases, when in fact they breathed room air. Cardiorespiratory variables were similar between the trials, however, dyspnea and RPE legs evaluated with a Borg scale changed in a dose-response manner. When participants believed they were breathing 15% O 2 , they significantly increased dyspnea +0.70 ± 0.2 units ( p  = 0.03) compared to room air, whereas RPE legs was unchanged +0.35 ± 0.1 units ( p  = 0.70). When participants believed they were breathing 15% O 2 , they significantly increased dyspnea +1.05 ± 0.4 units ( p  = 0.003) compared to 23% hyperoxic condition, whereas RPE legs was unchanged +0.35 ± 0.1 units ( p  = 0.70). We found that dyspnea during exercise is susceptible to expectancy, without any accompanying physiological changes. Given coaches and clinicians use perceived exertion to prescribe exercise intensity and evaluate treatments, our findings show that the effect of expectations must be considered when interpreting sensations of breathlessness.

Background: Targeted exercise training is a promising strategy for promoting cognitive function and preventing dementia in older age. Despite the utility of exercise as an intervention, variation still exists in exercise-induced cognitive gains and questions remain regarding the type of training (i.e., what), as well as moderators (i.e., for whom) and mechanisms (i.e., how) of benefit. Both aerobic training (AT) and resistance training (RT) enhance cognitive function in older adults without cognitive impairment; however, the vast majority of trials have focused exclusively on AT. Thus, more research is needed on RT, as well as on the combination of AT and RT, in older adults with mild cognitive impairment (MCI), a prodromal stage of dementia. Therefore, we aim to conduct a 6-month, 2 × 2 factorial randomized controlled trial in older adults with MCI to assess the individual effects of AT and RT, and the combined effect of AT and RT on cognitive function and to determine the possible underlying biological mechanisms., Methods: Two hundred and sixteen community-dwelling adults, aged 65 to 85 years, with MCI from metropolitan Vancouver will be recruited to participate in this study. Randomization will be stratified by biological sex and participants will be randomly allocated to one of the four experimental groups: (1) 4×/week balance and tone (BAT; i.e., active control); (2) combined 2×/week AT + 2×/week RT; (3) 2×/week AT + 2×/week BAT; or (4) 2×/week RT + 2×/week BAT. The primary outcome is cognitive function as measured by the Alzheimer's Disease Assessment Scale-Cognitive-Plus. Secondary outcomes include cognitive function, health-related quality of life, physical function, actigraphy measures, questionnaires, and falls. Outcomes will be measured at baseline, 6 months (i.e., trial completion), and 18 months (i.e., 12-month follow-up)., Discussion: Establishing the efficacy of different types and combinations of exercise training to minimize cognitive decline will advance our ability to prescribe exercise as "medicine" to treat MCI and delay the onset and progression of dementia. This trial is extremely timely as cognitive impairment and dementia pose a growing threat to global public health., Trial Registration: ClinicalTrials.gov NCT02737878 . Registered on April 14, 2016., (© 2022. The Author(s).)

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.)

Optical coherence tomography (OCT) is an imaging methodology that can be used to assess human airways. OCT avoids the harmful effects of ionizing radiation and has a high spatial resolution making it well suited for imaging the structure of small airways. Analysis of OCT airway images has typically been performed manually by tracing the airway with a relatively high coefficient of variation. The purpose of this study was to develop an analysis tool to reduce the inter- and intra-observer reproducibility of OCT and improve the ability to detect differences in airways. OCT images from healthy, young human volunteers were used to develop and test the OCT software. Measurement software was developed to allow the conversion of the original image into a grayscale image and was followed by an enhancement operation to brighten the image, and contour measurement. A total of 140 OCT images, 70 small (<2 mm) and 70 medium (2-4 mm) sized airways were analyzed. The inter- and intraobserver reproducibility of airway measurements ranged for strong to very strong in the small-sized airways. For medium-sized airways the reproducibility was considered moderate. Bland-Altman bias was low between observers and observations for all measures. The minimal detectable differences in the airway measurements with our semi-automated software were lower relative to manual tracing in medium-sized airways. Our software improves the ability to perform quantitative OCT analysis and may help to quantify the extent of airway remodelling in respiratory disease or elite athletes in future studies., (© 2022 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Cervical spinal cord injury (C-SCI) negatively impacts cardiac and respiratory function. As the heart and lungs are linked via the pulmonary circuit these systems are interdependent. Here, we utilized inspiratory and expiratory loading to assess whether augmenting the respiratory pump improves left-ventricular (LV) filling and output in individuals with motor-complete C-SCI. We hypothesized LV end-diastolic volume (LVEDV) would increase and decrease with inspiratory and expiratory loading, respectively. Participants (C-SCI: 7M/1F, 35 ± 7 years; able-bodied: 7M/1F, 32 ± 6 years) were assessed under five conditions during 45° head-up tilt; unloaded, inspiratory loading with -10 and -20 cmH 2 O oesophageal pressure (P oes ) on inspiration, and expiratory loading with +10 and +20 cmH 2 O P oes on expiration. An oesophageal balloon catheter monitored P oes , and LV structure and function were assessed by echocardiography. In C-SCI only, (1) +20 cmH 2 O reduced LVEDV vs. unloaded (81 ± 15 vs. 88 ± 11 ml, P = 0.006); (2) heart rate was higher during +20 cmH 2 O compared to unloaded (P = 0.001) and +10 cmH 2 O (P = 0.002); (3) cardiac output was higher during +20 cmH 2 O than unloaded (P = 0.002); and (4) end-expiratory lung volume was higher during +20 cmH 2 O vs. unloaded (63 ± 10 vs. 55 ± 13% total lung capacity, P = 0.003) but was unaffected by inspiratory loading. In both groups, -10 and -20 cmH 2 O had no significant effect on LVEDV. These findings suggest greater expiratory positive pressure acutely impairs LV filling in C-SCI, potentially via impaired venous return, mediastinal constraint and/or direct ventricular interaction subsequent to dynamic hyperinflation. Inspiratory loading did not significantly improve LV function in C-SCI and neither inspiratory nor expiratory loading affected cardiac function or lung volumes in able-bodied participants. KEY POINTS: Cervical spinal cord injury (C-SCI) alters both the cardiac and the respiratory system, but little is known about how these systems interact following injury. Here, we manipulated inspiratory or expiratory intrathoracic pressure (ITP) to mechanistically test the role of the respiratory pump in circulatory function in highly trained individuals with C-SCI and an able-bodied reference group. In individuals with C-SCI, greater ITP during expiratory loading caused dynamic hyperinflation that was associated with impaired left-ventricular filling. More negative ITP during inspiratory loading did not significantly alter left-ventricular volumes in either group. Interventions that prevent dynamic hyperinflation and/or enhance the ability to generate expiratory pressures may help preserve left-ventricular filling in individuals with C-SCI., (© 2022 The Authors. The Journal of Physiology © 2022 The Physiological Society.)

Introduction: The female diaphragm develops less fatigue after high-intensity exercise compared with males. Diaphragm fatigability is typically defined as a decrease in transdiaphragmatic twitch pressure (Pdi,TW) and represents the contractile function of the muscle. However, it is unclear whether this sex difference persists when examining changes in voluntary activation, which represents a neural mechanism contributing to fatigability., Purpose: This study aimed to determine if high-intensity cycling results in a decrease in diaphragm voluntary activation (D-VA) and to explore if the decrease in D-VA is different between sexes., Methods: Twenty-five participants (15 females) completed a single bout of high-intensity constant load cycling. D-VA and Pdi,TW were measured before and after exercise using cervical magnetic stimulation of the phrenic nerves to assess diaphragm fatigability., Results: Participants were of similar aerobic fitness when expressed relative to predicted values (females: 114% ± 25% predicted, males: 111% ± 11% predicted; P = 0.769). Pdi,TW decreased relative to baseline to 85.2% ± 16.7% and 70.3% ± 12.4% baseline (P = 0.012) in females and males, respectively, immediately after exercise. D-VA also decreased in both females and males immediately after exercise. The decrease in D-VA was less in females compared with males (95.4% ± 4.9% baseline vs 87.4% ± 10.8% baseline, respectively; P = 0.018)., Conclusions: D-VA decreases after whole-body exercise in both females and males, although the magnitude of the decrease is not as large in females compared with males. The findings of this study suggest that the female diaphragm is more resistant to both contractile and neural mechanisms of fatigability after whole-body exercise., (Copyright © 2022 by the American College of Sports Medicine.)

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

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.