The acute effects of endurance exercise on epithelial integrity of the airways in athletes and non-athletes: A systematic review and meta-analysis.

INTRODUCTION: Acute endurance exercise may induce airway epithelium injury. However, the response of epithelial integrity markers of the airways including club cell secretory protein (CC16) and surfactant protein D (SP-D) to endurance exercise have not been systematically reviewed. Therefore, the aim of this systematic review and meta-analysis was to assess the acute effects of endurance exercise on markers of epithelial integrity of the airways (CC16, SP-D and the CC16/SP-D ratio) in athletes and non-athletes. METHODS: A systematic search was performed utilizing PubMed/Medline, EMBASE, Web of Science, and hand searching bibliographies of retrieved articles through to September 2022. Based on the inclusion criteria, articles with available data about the acute effects of endurance exercise on serum or plasma concentrations of CC16, SP-D and CC16/SP-D ratio in athletes and non-athletes were included. Quality assessment of studies and statistical analysis were conducted via Review Manager 5.4 software. RESULTS: The search resulted in 908 publications. Finally, thirteen articles were included in the review. Acute endurance exercise resulted in an increase in CC16 (P = 0.0006, n = 13) and CC16/SP-D ratio (P = 0.005, n = 2) whereas SP-D (P = 0.47, n = 3) did not change significantly. Subgroup analysis revealed that the type (P = 0.003), but not the duration of exercise (P = 0.77) or the environmental temperature (P = 0.06) affected the CC16 response to endurance exercise. CONCLUSIONS: Acute endurance exercise increases CC16 and the CC16/SP-D ratio, as markers of epithelial integrity, but not SP-D in athletes and non-athletes.

The effects of age on dyspnea and respiratory mechanical and neural responses to exercise in healthy men.

The respiratory muscle pressure generation and inspiratory and expiratory neuromuscular recruitment patterns in younger and older men were compared during exercise, alongside descriptors of dyspnea. Healthy younger (n = 8, 28 ± 5 years) and older (n = 8, 68 ± 4 years) men completed a maximal incremental cycling test. Esophageal, gastric (Pga ) and transdiaphragmatic pressures, and electromyography (EMG) of the crural diaphragm were measured using a micro-transducer and EMG catheter. EMG of the parasternal intercostals, sternocleidomastoids, and rectus abdominis were measured using skin surface electrodes. After the exercise test, participants completed a questionnaire to evaluate descriptors of dyspnea. Pga at end-expiration, Pga expiratory tidal swings, and the gastric pressure-time product (PTPga ) at absolute and relative minute ventilation were higher (p < 0.05) for older compared to younger men. There were no differences in EMG responses between older and younger men. Younger men were more likely to report shallow breathing (p = 0.005) than older men. Our findings showed younger and older men had similar respiratory neuromuscular activation patterns and reported different dyspnea descriptors, and that older men had greater expiratory muscle pressure generation during exercise. Greater expiratory muscle pressures in older men may be due to compensatory mechanisms designed to offset increasing airway resistance due to aging. These results may have implications for exercise-induced expiratory muscle fatigue in older men.

Differences in total cognition and cerebrovascular function in female breast cancer survivors and cancer-free women.

Reduced cognition is often reported by breast cancer patients and survivors, but the mechanisms for this decline are yet to be determined. We compared the differences in cerebrovascular function and cognition in breast cancer survivors (n = 15) and cancer-free women (n = 15) matched by age and body mass index. Participants undertook anthropometric, mood, cardiovascular, exercise performance, strength, cerebrovascular, and cognitive measurements. Transcranial Doppler ultrasound was used to measure the cerebrovascular responsiveness (CVR) to physiological (hypercapnia; 5% carbon dioxide) and psychological stimuli. Breast cancer survivors had a lower CVR to hypercapnia (21.5 ± 12.8 vs 66.0 ± 20.9%, P < 0.001), CVR to cognitive stimuli (15.1 ± 1.5 vs 23.7 ± 9.0%, P < 0.001) and total composite cognitive score (100 ± 12 vs. 113 ± 7, P = 0.003) than cancer-free women. These parameters remained statistically different between the groups following adjustments for covariates using an analysis of co-variance. We observed significant correlations between multiple measures and exercise capacity the only variable positively correlated to all primary measures (CVR to hypercapnia, r = 0.492, P = 0.007; CVR to cognitive stimuli r = 0.555, P = 0.003; and total composite cognitive score, r = 0.625, P < 0.001). In this study, breast cancer survivors had lower cerebrovascular and cognitive function than age-matched cancer-free women, which may be attributable to the effects of cancer and cancer treatment on brain health.

Biomarkers to measure respiratory muscle damage following inspiratory pressure threshold loading in healthy young men.

Elevated respiratory muscle work is encountered during strenuous exercise, acute and chronic respiratory disorders, and during inspiratory pressure threshold loading (ITL). ITL can induce respiratory muscle damage, evidenced by increases in fast and slow skeletal troponin-I (sTnI). However, other blood markers of muscle damage have not been measured. We investigated respiratory muscle damage following ITL using a skeletal muscle damage biomarkers panel. Seven healthy men (33 ± 2 yr) undertook 60 min of ITL at a resistance equivalent to ∼0% (Sham ITL) and 70% of their maximal inspiratory pressure 2 wk apart. Serum was collected before and at 1, 24, and 48 h after each ITL session. Creatine kinase muscle-type (CKM), myoglobin, fatty acid-binding protein-3 (FABP3), myosin light chain-3, and fast and slow sTnI were measured. Two-way ANOVA revealed time × load interaction effects (P < 0.05) for CKM, slow and fast sTnI. All of these were higher for 70% compared with Sham ITL. CKM was higher at 1 and 24 h, fast sTnI at 1 h, whereas slow sTnI was higher at 48 h. There were main effects of time (P < 0.01) for FABP3 and myoglobin, but no time × load interaction effects. Hence, CKM and fast sTnI could be used to assess respiratory muscle damage immediately (1 h), whereas CKM and slow sTnI could be used to assess respiratory muscle damage 24 and 48 h following conditions that elevate inspiratory muscle work. The specificity of these markers for different time points needs further exploration in other protocols that cause elevated inspiratory muscle work.NEW & NOTEWORTHY We investigated inspiratory pressure threshold loading-induced respiratory muscle damage using a skeletal muscle damage biomarkers panel. Our investigation showed that creatine kinase muscle-type, and fast skeletal troponin I could be used to assess respiratory muscle damage immediately (1 h), whereas creatine kinase muscle-type, and slow skeletal troponin I could be used to assess respiratory muscle damage 24 and 48 h following conditions that cause elevated inspiratory muscle work.

The benefits of regular aerobic exercise training on cerebrovascular function and cognition in older adults.

We compared the differences in cerebrovascular and cognitive function between 13 aerobic exercise trained, older adults and 13 age-, height- and sex-matched sedentary, untrained controls. We determined whether other measures accounted for differences in cerebrovascular and cognitive function between these groups and examined the associations between these functions. Participants undertook anthropometric, mood, cardiovascular, exercise performance, strength, cerebrovascular, and cognitive measurements, and a blood collection. Transcranial Doppler ultrasonography determined cerebrovascular responsiveness (CVR) to hypercapnia and cognitive stimuli. The trained group had a higher CVR to hypercapnia (80.3 ± 7.2 vs 35.1 ± 6.7%, P < 0.001), CVR to cognitive stimuli (30.1 ± 2.9 vs 17.8 ± 1.4%, P = 0.001) and total composite cognitive score (117 ± 2 vs 98 ± 4, P < 0.001) than the controls. These parameters no longer remained statistically different between the groups following adjustments for covariates. There were positive correlations between the total composite cognitive score and CVR to hypercapnia (r = 0.474, P = 0.014) and CVR to cognitive stimuli (r = 0.685, P < 0.001). We observed a relationship between cerebrovascular and cognitive function in older adults and an interaction between regular lifelong aerobic exercise training and cardiometabolic factors that may directly influence these functions.

The Effects of Aerobic Exercise Training on Cerebrovascular and Cognitive Function in Sedentary, Obese, Older Adults.

Cerebrovascular function and cognition decline with age and are further exacerbated by obesity and physical inactivity. This decline may be offset by aerobic exercise training (AT). We investigated the effects of 16 weeks AT on cerebrovascular and cognitive function in sedentary, obese, older adults. Twenty-eight participants were randomly allocated to AT or a control group. Before and after the intervention, transcranial Doppler ultrasonography was used to measure the cerebrovascular responsiveness (CVR) to physiological (hypercapnia, 5% carbon dioxide) and cognitive stimuli. AT increased the CVR to hypercapnia (98.5 ± 38.4% vs. 58.0 ± 42.0%, P = 0.021), CVR to cognitive stimuli (25.9 ± 6.1% vs. 16.4 ± 5.4%, P < 0.001) and total composite cognitive score (111 ± 14 vs. 104 ± 14, P = 0.004) compared with the control group. A very strong relationship was observed between the number of exercise sessions completed and CVR to cognitive stimuli (r = 0.878, P < 0.001), but not for CVR to hypercapnia (r = 0.246, P = 0.397) or total composite cognitive score (r = 0.213, P = 0.465). Cerebrovascular function and cognition improved following 16 weeks of AT and a dose-response relationship exists between the amount of exercise sessions performed and CVR to cognitive stimuli.

The control of respiratory pressures and neuromuscular activation to increase force production in trained martial arts practitioners.

PURPOSE: The mechanisms that explain the ability of trained martial arts practitioners to produce and resist greater forces than untrained individuals to aid combat performance are not fully understood. We investigated whether the greater ability of trained martial arts practitioners to produce and resist forces was associated with an enhanced control of respiratory pressures and neuromuscular activation of the respiratory, abdominal, and pelvic floor musculature. METHODS: Nine trained martial arts practitioners and nine untrained controls were instrumented with skin-surface electromyography (EMG) on the sternocleidomastoid, rectus abdominis, and the group formed by the transverse abdominal and internal oblique muscles (EMGtra/io). A multipair oesophageal EMG electrode catheter measured gastric (Pg), transdiaphragmatic (Pdi), and oesophageal (Pe) pressures and EMG of the crural diaphragm (EMGdi). Participants performed Standing Isometric Unilateral Chest Press (1) and Standing Posture Control (2) tasks. RESULTS: The trained group produced higher forces normalised to body mass2/3 (0.033 ± 0.01 vs. 0.025 ± 0.007 N/kg2/3 mean force in Task 1), lower Pe, and higher Pdi in both tasks. Additionally, they produced higher Pg (73 ± 42 vs. 49 ± 19 cmH2O mean Pg) and EMGtra/io in Task 1 and higher EMGdi in Task 2. The onset of Pg with respect to the onset of force production was earlier, and the relative contributions of Pg/Pe and Pdi/Pe were higher in the trained group in both tasks. CONCLUSION: Our findings demonstrate that trained martial arts practitioners utilised a greater contribution of abdominal and diaphragm musculature to chest wall recruitment and higher Pdi to produce and resist higher forces.

Pressure measurement characteristics of a micro-transducer and balloon catheters.

Respiratory pressure responses to cervical magnetic stimulation are important measurements in monitoring the mechanical function of the respiratory muscles. Pressures can be measured using balloon catheters or a catheter containing integrated micro-transducers. However, no research has provided a comprehensive analysis of their pressure measurement characteristics. Accordingly, the aim of this study was to provide a comparative analysis of these characteristics in two separate experiments: (1) in vitro with a reference pressure transducer following a controlled pressurization; and (2) in vivo following cervical magnetic stimulations. In vitro the micro-transducer catheter recorded pressure amplitudes and areas which were in closer agreement to the reference pressure transducer than the balloon catheter. In vivo there was a main effect for stimulation power and catheter for esophageal (Pes ), gastric (Pga ), and transdiaphragmatic (Pdi ) pressure amplitudes (p < 0.001) with the micro-transducer catheter recording larger pressure amplitudes. There was a main effect of stimulation power (p < 0.001) and no main effect of catheter for esophageal (p = 0.481), gastric (p = 0.923), and transdiaphragmatic (p = 0.964) pressure areas. At 100% stimulator power agreement between catheters for Pdi amplitude (bias =6.9 cmH2 O and LOA -0.61 to 14.27 cmH2 O) and pressure areas (bias = -0.05 cmH2 O·s and LOA -1.22 to 1.11 cmH2 O·s) were assessed. At 100% stimulator power, and compared to the balloon catheters, the micro-transducer catheter displayed a shorter 10-90% rise time, contraction time, latency, and half-relaxation time, alongside greater maximal rates of change in pressure for esophageal, gastric, and transdiaphragmatic pressure amplitudes (p < 0.05). These results suggest that caution is warranted if comparing pressure amplitude results utilizing different catheter systems, or if micro-transducers are used in clinical settings while applying balloon catheter-derived normative values. However, pressure areas could be used as an alternative point of comparison between catheter systems.

Benefits of exercise training on cerebrovascular and cognitive function in ageing.

Derangements in cerebrovascular structure and function can impair cognitive performance throughout ageing and in cardiometabolic disease states, thus increasing dementia risk. Modifiable lifestyle factors that cause a decline in cardiometabolic health, such as physical inactivity, exacerbate these changes beyond those that are associated with normal ageing. The purpose of this review was to examine cerebrovascular, cognitive and neuroanatomical adaptations to ageing and the potential benefits of exercise training on these outcomes in adults 50 years or older. We systematically searched for cross-sectional or intervention studies that included exercise (aerobic, resistance or multimodal) and its effect on cerebrovascular function, cognition and neuroanatomical adaptations in this age demographic. The included studies were tabulated and described narratively. Aerobic exercise training was the predominant focus of the studies identified; there were limited studies exploring the effects of resistance exercise training and multimodal training on cerebrovascular function and cognition. Collectively, the evidence indicated that exercise can improve cerebrovascular function, cognition and neuroplasticity through areas of the brain associated with executive function and memory in adults 50 years or older, irrespective of their health status. However, more research is required to ascertain the mechanisms of action.

Inspiratory flow-resistive breathing, respiratory muscle-induced systemic oxidative stress, and diaphragm fatigue in healthy humans.

We questioned whether the respiratory muscles of humans contribute to systemic oxidative stress following inspiratory flow-resistive breathing, whether the amount of oxidative stress is influenced by the level of resistive load, and whether the amount of oxidative stress is related to the degree of diaphragm fatigue incurred. Eight young and healthy participants attended the laboratory for four visits on separate days. During the first visit, height, body mass, lung function, and maximal inspiratory mouth and transdiaphragmatic pressure (Pdimax) were assessed. During visits 2-4, participants undertook inspiratory flow-resistive breathing with either no resistance (control) or resistive loads equivalent to 50 and 70% of their Pdimax (Pdimax50% and Pdimax70%) for 30 min. Participants undertook one resistive load per visit, and the order in which they undertook the loads was randomized. Inspiratory muscle pressures were higher (P < 0.05) during the 5th and Final min of Pdimax50% and Pdimax70% compared with control. Plasma F2-isoprostanes increased (P < 0.05) following inspiratory flow-resistive breathing at Pdimax70%. There were no increases in plasma protein carbonyls or total antioxidant capacity. Furthermore, although we evidenced small reductions in transdiapragmaic twitch pressures (PdiTW) after inspiratory flow-resistive breathing at Pdimax50% and Pdimax70%, this was not related to the increase in plasma F2-isoprostanes. Our novel data suggest that it is only when sufficiently strenuous that inspiratory flow-resistive breathing in humans elicits systemic oxidative stress evidenced by elevated plasma F2-isoprostanes, and based on our data, this is not related to a reduction in PdiTW.NEW & NOTEWORTHY We examined whether the respiratory muscles of humans contribute to systemic oxidative stress following inspiratory flow-resistive breathing, whether the amount of oxidative stress is influenced by the level of resistive load, and whether the amount of oxidative stress is related to the degree of diaphragm fatigue incurred. It is only when sufficiently strenuous that inspiratory flow-resistive breathing elevates plasma F2-isoprostanes, and our novel data show that this is not related to a reduction in transdiaphragmatic twitch pressure.

The effects of inspiratory muscle training in older adults.

PURPOSE: Declining inspiratory muscle function and structure and systemic low-level inflammation and oxidative stress may contribute to morbidity and mortality during normal ageing. Therefore, we examined the effects of inspiratory muscle training (IMT) in older adults on inspiratory muscle function and structure and systemic inflammation and oxidative stress, and reexamined the reported positive effects of IMT on respiratory muscle strength, inspiratory muscle endurance, spirometry, exercise performance, physical activity levels (PAL), and quality of life (QoL). METHODS: Thirty-four healthy older adults (68 ± 3 yr) with normal spirometry, respiratory muscle strength, and physical fitness were divided equally into a pressure-threshold IMT or sham-hypoxic placebo group. Before and after an 8-wk intervention, measurements were taken for dynamic inspiratory muscle function and inspiratory muscle endurance using a weighted plunger pressure-threshold loading device; diaphragm thickness by using B-mode ultrasonography; plasma cytokine concentrations by using immunoassays; DNA damage levels in peripheral blood mononuclear cells by using comet assays; spirometry, maximal mouth pressures, and exercise performance by using a 6-min walk test; PAL by using a questionnaire and accelerometry; and QoL using a questionnaire. RESULTS: Compared with placebo, IMT increased maximal inspiratory pressure (+34% ± 43%, P = 0.008), diaphragm thickness at residual volume (+38% ± 39%, P = 0.03), and peak inspiratory flow (+35% ± 42%, P = 0.049) but did not change other spirometry measures, plasma cytokine concentrations, DNA damage levels in peripheral blood mononuclear cells, dynamic inspiratory muscle function, inspiratory muscle endurance, exercise performance, PAL, or QoL. CONCLUSION: These novel data indicate that in healthy older adults, IMT elicits some positive changes in inspiratory muscle function and structure but neither attenuates systemic inflammation and oxidative stress nor improves exercise performance, PAL, or QoL.

Influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training on the plasma cytokine response to maximum sustainable voluntary ventilation.

The influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training (IMT) on the cytokine response to maximum sustainable voluntary ventilation (MSVV) is unknown. Twelve healthy males were divided equally into an IMT or placebo (PLA) group, and before and after a 6-wk intervention they undertook, on separate days, 1 h of (1) passive rest and (2) MSVV, whereby participants undertook volitional hyperpnea at rest that mimicked the breathing and respiratory muscle recruitment patterns commensurate with heavy cycling exercise. Plasma cytokines remained unchanged during passive rest. There was a main effect of time (P < 0.01) for plasma interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) concentrations and a strong trend (P = 0.067) for plasma interleukin-1 receptor antagonist concentration during MSVV. Plasma IL-6 concentration was reduced after IMT by 27 ± 18% (main effect of intervention, P = 0.029), whereas there was no change after PLA (P = 0.753). There was no increase in a systemic marker of oxidative stress [DNA damage in peripheral blood mononuclear cells (PBMC)], and diaphragm fatigue was not related to the increases in plasma IL-1ß and IL-6 concentrations. A dose-response relationship was observed between respiratory muscle work and minute ventilation and increases in plasma IL-6 concentration. In conclusion, increases in plasma IL-1ß and IL-6 concentrations during MSVV were not due to diaphragm fatigue or DNA damage in PBMC. Increases in plasma IL-6 concentration during MSVV are attenuated following IMT, and the plasma IL-6 response is dependent upon the level of respiratory muscle work and minute ventilation.

Prior upper body exercise reduces cycling work capacity but not critical power.

PURPOSE: This study examined whether metabolite accumulation, induced by prior upper body exercise, affected the power-duration relationship for leg cycle ergometry. METHODS: Seven males performed, to the limit of tolerance and both without (L) and with (AL) prior severe-intensity arm-cranking exercise, an incremental cycling test and four constant power cycling tests to determine the parameters of the power-duration relationship: critical power (CP) and W'. RESULTS: At the onset of cycling exercise plasma lactate (L vs AL: 1.2 ± 0.1 vs 11.6 ± 2.9 mEq · L) and hydrogen ion (40.4 ± 1.3 vs 53.1 ± 4.3 nEq · L), concentrations were higher during AL compared with L, whereas the strong ion difference (37.8 ± 1.8 vs 32.4 ± 2.0 mEq · L) and bicarbonate concentration (25.7 ± 0.7 vs 18.3 ± 1.9 mEq · L) were lower during AL compared with L (P < 0.01). During incremental exercise, maximum cycling power (358 ± 15 vs 332 ± 21 W) and peak oxygen uptake (VO2peak) (4.31 ± 0.36 vs 3.71 ± 0.44 L · min) were lower during AL compared with L (P < 0.05). The rate of increase in plasma potassium concentration during constant power cycling was greater during AL compared with L (0.09 ± 0.08 vs 0.14 ± 0.13 mEq · L · min) (P < 0.05), and exercise duration was 35 ± 15% shorter (P < 0.01). CP was not different between L and AL (267 ± 19 vs 264 ± 20 W), whereas W' was lower in AL (17.3 ± 5.7 vs 11.8 ± 4.2 kJ) (P < 0.01). CONCLUSION: The reduced W' after prior upper body exercise indicates that the magnitude of W' is partly dependent on metabolite accumulation.

The effects of inspiratory muscle training on plasma interleukin-6 concentration during cycling exercise and a volitional mimic of the exercise hyperpnea.

It is unknown whether the respiratory muscles contribute to exercise-induced increases in plasma interleukin-6 (IL-6) concentration, if this is related to diaphragm fatigue, and whether inspiratory muscle training (IMT) attenuates the plasma IL-6 response to whole body exercise and/or a volitional mimic of the exercise hyperpnea. Twelve healthy males were divided equally into an IMT or placebo (PLA) group, and before and after a 6-wk intervention they undertook, on separate days, 1 h of 1) passive rest, 2) cycling exercise at estimated maximal lactate steady state power (EX), and 3) volitional hyperpnea at rest, which mimicked the breathing and respiratory muscle recruitment patterns achieved during EX (HYPEX). Plasma IL-6 concentration remained unchanged during passive rest. The plasma IL-6 response to EX was reduced following IMT (main effect of intervention, P = 0.039) but not PLA (P = 0.272). Plasma IL-6 concentration increased during HYPEX (main effect of time, P < 0.01) and was unchanged postintervention. There was no evidence of diaphragm fatigue (measured by phrenic nerve stimulation) following each trial. In conclusion, plasma IL-6 concentration is increased during EX and HYPEX and this occurred in the absence of diaphragm fatigue. Furthermore, IMT reduced the plasma IL-6 response to EX but not HYPEX. These findings suggest that the respiratory muscles contribute to exercise-induced increases in plasma IL-6 concentration in the absence of diaphragm fatigue and that IMT can reduce the magnitude of the response to exercise but not a volitional mimic of the exercise hyperpnea.

Inspiratory loading intensity does not influence lactate clearance during recovery.

PURPOSE: This study examined the effects of different pressure threshold inspiratory loads on lactate clearance and plasma acid-base balance during recovery from maximal exercise. METHODS: Eight moderately trained males (V˙O(2peak) = 4.29 ± 0.46 L·min⁻¹) performed, on different days, four maximal incremental cycling tests (power started at 0 W and increased by 20 W·min⁻¹) of identical duration (exercise time during the first trial was 16.32 ± 1.12 min). During 20-min recovery, subjects either rested passively or breathed through a constant pressure threshold inspiratory load of 10 (ITL10), 15 (ITL15), or 20 (ITL20) cm H2O. Plasma lactate concentration ([La⁻]) was measured, and acid-base balance was quantified using the physicochemical approach, which describes the dependency of [H⁺] on the three independent variables: strong ion difference ([Na⁺] + [K⁺] - [Cl⁻] + [La⁻]), the total concentration of weak acids, and the partial pressure of carbon dioxide. RESULTS: Peak exercise responses were not significantly different between trials. During recovery, the area under the plasma [La] curve was not different between trials (pooled mean = 261 ± 60 mEq) and the [La] measured at the end of the 20-min recovery was also similar (passive recovery = 9.2 ± 3.1 mEq·L⁻¹, ITL10 = 9.3 ± 3.1 mEq·L⁻¹, ITL15 = 8.7 ± 2.8 mEq·L⁻¹, ITL20 = 8.7 ± 3.2 mEq·L⁻¹). Similarly, changes in other strong ions contributing to strong ion difference and total concentration of weak acids, partial pressure of carbon dioxide, and, therefore, [H⁺] were not different between trials. CONCLUSIONS: These data suggest that, in individuals of moderate endurance training status, inspiratory loading at the intensities used in the present study does not accelerate lactate clearance or modify plasma acid-base balance during recovery from maximal exercise.