Physiological Factors Associated with Unsatisfied Inspiration at Peak Exercise in Healthy Adults.

INTRODUCTION: Contrary to common belief, a growing body of evidence suggests that unsatisfied inspiration (UI), an inherently uncomfortable quality of dyspnea, is experienced by ostensibly healthy adults during high-intensity exercise. Based on our understanding of the mechanisms of UI among people with chronic respiratory conditions, this analysis tested the hypothesis that the experience of UI at peak exercise in young, healthy adults reflects the combination of high ventilatory demand and critical inspiratory constraints. METHODS: In a retrospective analysis design, data included 321 healthy individuals (129 females) aged 25 ± 5 yr. Data were collected during one visit to the laboratory, which included anthropometrics, spirometry, and an incremental cardiopulmonary cycling test to exhaustion. Metabolic and cardiorespiratory variables were measured at peak exercise, and qualitative descriptors of dyspnea at peak exercise were assessed using a list of 15 descriptor phrases. RESULTS: Thirty-four percent of participants ( n = 109) reported sensations of UI at peak exercise. Compared with the non-UI group, the UI group achieved a significantly higher peak work rate (243 ± 77 vs 235 ± 69 W, P = 0.016, d = 0.10), rate of O 2 consumption (3.32 ± 1.02 vs 3.27 ± 0.96 L·min -1 , P = 0.018, d = 0.05), minute ventilation (120 ± 38 vs 116 ± 35 L·min -1 , P = 0.047, d = 0.11), and breathing frequency (50 ± 9 vs 47 ± 9 breaths per minute, P = 0.014, d = 0.33), while having a lower exercise-induced change (peak-baseline) in inspiratory capacity (0.07 ± 0.41 vs 0.20 ± 0.49 L, P = 0.023, d = 0.29). The inspiratory reserve volume to minute ventilation ratio at peak exercise was also lower in the UI versus non-UI group. Dyspnea intensity and unpleasantness ratings were significantly higher in the UI versus non-UI group at peak exercise (both P < 0.001). CONCLUSIONS: Healthy individuals reporting UI at peak exercise have relatively greater inspiratory constraints compared with those who do not select UI.

The oxygen transport cascade and exercise: Lessons from comparative physiology.

Studies of animal physiology not only provide valuable knowledge for the species in question, but also offer insights into human physiology. This thought is best highlighted by the 'Krogh Principle', which states "for many problems there is an animal on which it can be most conveniently studied". This graphical review focuses on three distinct stages of the oxygen transport cascade in which human exercise physiology knowledge has been enhanced by studies carried out in animal models. We begin by exploring ventilation, and the detrimental effects of cold, dry air on the airways in two sets of elite athletes, the cross-country skier and the racing sled dog. We then discuss the transport of oxygen via hemoglobin in humans and deer mice with relatively shifted oxygen dissociation curves. Finally, we consider the technical difficulties of measuring respiratory muscle blood flow in exercising humans and how an equine model can provide an understanding of the distribution of blood flow during exercise. These cases illustrate the complementary nature of physiological studies across species.

Voluntary activation of the diaphragm after inspiratory pressure threshold loading.

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 (PDI,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. PDI,TW and D-VA were measured using cervical magnetic stimulation of the phrenic nerves in combination with maximal inspiratory pressure maneuvers. At task failure, PDI,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 PDI,TW correlated with both the total cumulative diaphragm pressure generation (R2  = 0.43; p = 0.021) and the time to task failure (TTF, R2 = 0.40; p = 0.30) whereas the decrease in D-VA correlated only with TTF (R2  = 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.

Effects of Face Masks on the Multiple Dimensions and Neurophysiological Mechanisms of Exertional Dyspnea.

INTRODUCTION: During the coronavirus disease 2019 pandemic, public health officials widely adopted the use of face masks (FM) to minimize infections. Despite consistent evidence that FMs increase dyspnea, no studies have examined the multidimensional components of dyspnea or their underlying physiological mechanisms. METHODS: In a randomized crossover design, 16 healthy individuals ( n = 9 women, 25 ± 3 yr) completed incremental cycling tests over three visits, where visits 2 and 3 were randomized to either surgical FM or no mask control. Dyspnea intensity and unpleasantness were assessed throughout exercise (0-10 Borg scale), and the Multidimensional Dyspnea Profile was administered immediately after exercise. Crural diaphragmatic EMG and esophageal pressure were measured using a catheter to estimate neural respiratory drive and respiratory muscle effort, respectively. RESULTS: Dyspnea unpleasantness was significantly greater with the FM at the highest equivalent submaximal work rate achieved by a given participant in both conditions (iso-work; 5.9 ± 1.7 vs 3.9 ± 2.9 Borg 0-10 units, P = 0.007) and at peak exercise (7.8 ± 2.1 vs 5.9 ± 3.4 Borg 0-10 units, P = 0.01) with no differences in dyspnea intensity ratings throughout exercise compared with control. There were significant increases in the sensory quality of "smothering/air hunger" ( P = 0.01) and the emotional response of "anxiousness" ( P = 0.04) in the FM condition. There were significant increases in diaphragmatic EMG and esophageal pressure at select submaximal work rates, but no differences in heart rate, pulse oximetry-derived arterial oxygen saturation, or breathing frequency throughout exercise with FMs compared with control. FMs significantly reduced peak work rate and exercise duration (both P = 0.02). CONCLUSIONS: FMs negatively impact the affective domain of dyspnea and increase neural respiratory drive and respiratory muscle effort during exercise, although the impact on other cardiorespiratory responses are minimal.

Sex Differences in Diaphragm Voluntary Activation after Exercise.

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.

Effects of the Elevation Training Mask® 2.0 on dyspnea and respiratory muscle mechanics, electromyography, and fatigue during exhaustive cycling in healthy humans.

OBJECTIVES: Examine the effects of the Elevation Training Mask® 2.0 (ETM) on dyspnea, and respiratory muscle function and fatigue during exercise. DESIGN: Randomized crossover. METHODS: 10 healthy participants completed 2 time-to-exhaustion (TTE) cycling tests while wearing the ETM or under a sham control condition. During the sham, participants were told they were breathing air equivalent to "9000 ft" (matched to the selected resistance valves on the ETM according to the manufacturer), but they were breathing room air. Dyspnea and leg discomfort were assessed using the modified 0-10 category-ratio Borg scale. Qualitative dyspnea descriptors at peak exercise were selected from a list of 15. Crural diaphragmatic electromyography (EMGdi) and transdiaphragmatic pressure (Pdi) were measured via a multipair esophageal electrode balloon catheter. Participants performed maximal respiratory maneuvers before and after exercise to estimate the degree of respiratory muscle fatigue. RESULTS: Exercise with the ETM resulted in a significant decrease in TTE (p = 0.015), as well as increased dyspnea at baseline (p = 0.032) and during the highest equivalent submaximal exercise time (p = 0.0001). The increase in dyspnea with the ETM was significantly correlated with the decrease in exercise time (r = 0.73, p = 0.020). EMGdi and Pdi were significantly increased with the ETM at all time points (all p < 0.05). There was a significant increase in the selection frequency of "my breath does not go in all the way" at peak exercise with the ETM (p = 0.02). The ETM did not induce respiratory muscle fatigue. CONCLUSIONS: Exercising with the ETM appears to decrease exercise performance, in part, by increasing the sensation of dyspnea.

Effects of Traffic-Related Air Pollution on Exercise Endurance, Dyspnea, and Cardiorespiratory Responses in Health and COPD: A Randomized, Placebo-Controlled, Crossover Trial.

BACKGROUND: Individuals with COPD have increased sensitivity to traffic-related air pollution (TRAP) such as diesel exhaust (DE), but little is known about the acute effects of TRAP on exercise responses in COPD. RESEARCH QUESTION: Does exposure before exercise to TRAP (DE titrated to 300 µg/m3 particulate matter < 2.5 µm in diameter [DE300]) show greater adverse effects on exercise endurance, exertional dyspnea, and cardiorespiratory responses to exercise in participants with mild to moderate COPD compared with former smokers with normal spirometry and healthy control participants? STUDY DESIGN AND METHODS: In this double-blind, randomized, placebo-controlled, crossover study, 11 healthy control participants, nine former smokers without COPD, and nine former smokers with COPD were separately exposed to filtered air (FA) and DE300 for 2 h separated by a minimum of 4 weeks. Participants performed symptom-limited constant load cycling tests within 2.5 h of exposure with detailed cardiorespiratory and exertional symptom measurements. RESULTS: A significant negative effect of TRAP on exercise endurance time was found in healthy control participants (DE300 vs FA, 10.2 ± 8.2 min vs 12.9 ± 9.5 min, respectively; P = .03), but not in former smokers without COPD (10.1 ± 6.9 min vs 12.2 ± 8.0 min, respectively; P = .57) or former smokers with COPD (9.8 ± 6.4 min vs 8.4 ± 6.6 min, respectively; P = .31). Furthermore, significant increases in inspiratory duty cycle and absolute end-expiratory and end-inspiratory lung volumes were observed, and dyspnea ratings were elevated at select submaximal measurement times only in healthy control participants. INTERPRETATION: Contrary to our hypothesis, it was the healthy control participants, rather than the former smokers with and without COPD, who were negatively impacted by TRAP during exercise. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02236039; URL: www. CLINICALTRIALS: gov.

Case Studies in Physiology: Cardiopulmonary exercise testing and inspiratory muscle training in a 59-year-old, 4 years after an extrapleural pneumonectomy.

This case report characterizes the physiological responses to incremental cycling and determines the effects of 12 wk of inspiratory muscle training (IMT) on respiratory muscle strength, exercise capacity, and dyspnea in a physically active 59-yr-old female, 4 years after a left-sided extrapleural pneumonectomy (EPP). On separate days, a symptom-limited incremental exercise test and a constant work rate (CWR) test at 75% of peak work rate (WR) were completed, followed by 12 wk of IMT and another CWR test. IMT consisted of two sessions of 30 repetitions twice daily for 5 days per week. Physiological and perceptual variables were measured throughout each exercise test. The participant had a total lung capacity that was 43% predicted post-EPP. A rapid and shallow breathing pattern was adopted throughout exercise, and the ratio of minute ventilation to carbon dioxide output was elevated for a given work rate. Oxygen uptake was 71% predicted and WR was 88% predicted. Following IMT, maximal inspiratory pressure improved by 36% (-27.1 cmH2O) and endurance time by 31 s, with no observable changes in any submaximal or peak cardiorespiratory variables during exercise. The intensity and unpleasantness of dyspnea increased by 2 and 3 Borg 0-10 units, respectively, at the highest equivalent submaximal exercise time achieved on both tests. Despite having undergone a significant reduction in lung volume post-EPP, the participant achieved a relatively normal peak incremental WR, which may reflect a high level of physical conditioning. This case report also demonstrates that IMT can effectively increase respiratory muscle strength several years following EPP.NEW & NOTEWORTHY Constraints on tidal volume expansion and the adoption of a rapid and shallow breathing pattern result in a ventilatory limitation and increased ventilatory inefficiency during exercise in a patient several years after extrapleural pneumonectomy (EPP). Inspiratory muscle training can effectively increase respiratory muscle strength after EPP.

Ventilatory responses to constant load exercise following the inhalation of a short-acting ß2-agonist in a laboratory-controlled diesel exhaust exposure study in individuals with exercise-induced bronchoconstriction.

OBJECTIVE: Individuals with exercise-induced bronchoconstriction (EIB) use ß2-agonists to reduce respiratory symptoms during acute exercise. The resultingbronchodilation could increase the dose of inhaled pollutants and impair respiratory function when exercise is performedin air pollution. We aimed to assess respiratory responses in individuals with EIB when completing a cycling bout while being exposed to diesel exhaust (DE) or filtered air (FA) with and without the inhalation of salbutamol (SAL), a short-acting ß2-agonist. METHODS: In a double-blind, repeated-measures design, 19 participants with EIB (22-33 years of age) completed four visits: FA-placebo (FA-PLA), FA-SAL, DE-PLA, DE-SAL. After the inhalation of either 400 µg of SAL or PLA, participants sat in the exposure chamber for 60 min, breathing either FA or DE (PM2.5 = 300 µg/m3). Participants then cycled for 30 min at 50 % of peak work rate while breathing FA or DE. Respiratory responses were assessed via spirometry, work of breathing (WOB), fractional use of ventilatory capacity (V̇E/V̇E,CAP), area under the maximal expiratory flow-volume curve (MEFVAUC), and dyspnea during and following cycling. RESULTS: Bronchodilation in response to SAL and acute cycling was observed, independent of FA/DE exposure. Specifically, FEV1 was increased by 7.7 % (confidence interval (CI): 7.2-8.2 %; p < 0.01) in response to SAL, and MEFVAUC was increased after cycling by 1.1 % (0.9-1.3 %; p = 0.03). Despite a significant decrease in total WOB by 6.2 J/min (4.7-7.5 J/min; p = 0.049) and a reduction in V̇E/V̇E,CAP by 5.8 % (5-6 %, p < 0.01) in the SAL exposures, no changes were observed in dyspnea. The DE exposure significantly increased V̇E/V̇E,CAP by 2.4 % (0.9-3.9 %; p < 0.01), but this did not affect dyspnea. DISCUSSION: Our findings suggest that the use of SAL prior to moderate-intensity exercise when breathing high levels of DE, does not reduce respiratory function or exercise ventilatory responses for up to 60 min following exercise.

Effects of the Turbine™ on Ventilatory and Sensory Responses to Incremental Cycling.

INTRODUCTION: The Turbine™ is a nasal dilator marketed to athletes to increase airflow, which may serve to reduce dyspnea and improve exercise performance, presumably via reductions in the work of breathing (WOB). However, the unpublished data supporting these claims were collected in individuals at rest that were exclusively nasal breathing. These data are not indicative of how the device influences breathing during exercise at higher ventilations when a larger proportion of breathing is through the mouth. Accordingly, the purpose of this study was to empirically test the efficacy of the Turbine™ during exercise. We hypothesized that the Turbine™ would modestly reduce the WOB at rest and very low exercise intensities but would have no effect on the WOB at moderate to high exercise intensities. METHODS: We conducted a randomized crossover study in young, healthy individuals (7M:1F; age = 27 ± 5 yr) with normal lung function. Each participant performed two incremental cycle exercise tests to exhaustion with the Turbine™ device or under a sham control condition. For the sham control condition, participants were told they were breathing a low-density gas to reduce the WOB, but they were actually breathing room air. The WOB was determined through the integration of ensemble averaged esophageal pressure-volume loops. Standard cardiorespiratory measures were recorded using a commercially available metabolic cart. Dyspnea was assessed throughout exercise using the 0-10 Borg scale. RESULTS: Peak V˙O2 and work rate were not different between conditions (P = 0.70 and P = 0.35, respectively). In addition, there was no interaction or main effect of condition on dyspnea, ventilation, or WOB throughout the exercise (all P > 0.05). CONCLUSION: These findings suggest that the Turbine™ does not reduce the WOB and has no effect on dyspnea or exercise capacity.

Reliability of diaphragm voluntary activation measurements in healthy adults.

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.

Near-infrared spectroscopy measures of sternocleidomastoid blood flow during exercise and hyperpnoea.

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.

Short-term effects of Lumacaftor/Ivacaftor (Orkambi™) on exertional symptoms, exercise performance, and ventilatory responses in adults with cystic fibrosis.

RATIONALE: Lumacaftor/ivacaftor (LUM/IVA) modestly improves lung function following 1 month of treatment but it is unknown if this translates into improvements in exercise endurance and exertional symptoms. METHODS: Adult CF participants completed a symptom-limited constant load cycling test with simultaneous assessments of dyspnea and leg discomfort ratings pre- and 1 month post-initiation of LUM/IVA. RESULTS: Endurance time, exertional dyspnea and leg discomfort ratings at submaximal exercise did not change significantly. There was a significant inverse correlation between changes in leg discomfort and endurance time (r = - 0.88; p = 0.009) following 1-month of LUM/IVA. CONCLUSIONS: Overall, 1-month of LUM/IVA did not increase endurance time or modify exertional dyspnea or leg discomfort ratings. However, individuals who experienced a reduction in leg discomfort following LUM/IVA had an improvement in endurance time. Future studies with a larger sample size are needed to verify these findings and to assess the long-term effects of LUM/IVA on exercise outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02821130. Registered July 1, 2016.

The effect of diaphragm fatigue on the multidimensional components of dyspnoea and diaphragm electromyography during exercise in healthy males.

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, V̇O2max  = 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 < 0.05) Borg 0-10 units during the 2nd, 3rd and 4th minutes of exercise, respectively. There was a significant correlation between the change in breathing unpleasantness ratings at HESET and the change in time-to-exhaustion (r = 0.66, P = 0.006). The immediate perception domain, a combination of peak unpleasantness and specific dyspnoea descriptor intensity ratings, was the only component of the MDP that was significantly increased with pre-DF (4.3 ± 1.9 vs. 3.6 ± 1.8, P = 0.04). There were no significant differences in EMGdi . In conclusion, diaphragm fatigue has negative effects on multiple domains of dyspnoea, which may partially explain why exercise performance decreases with it.

Prevalence and Risk Factors for Osteoporosis in Individuals With COPD: A Systematic Review and Meta-analysis.

BACKGROUND: Osteoporosis is prevalent in individuals with COPD. Updated evidence is required to complement the previous systematic review on this topic to provide best practice. The aim of this systematic review and meta-analysis was to quantitatively synthesize data from studies with respect to the prevalence and risk factors for osteoporosis among individuals with COPD. METHODS: EMBASE, CINAHL, MEDLINE, and PubMed databases were searched for articles containing the key words "COPD," "osteoporosis," "prevalence," and "risk factor." Eligibility screening, data extraction, and quality assessment of the retrieved articles were conducted independently by two reviewers. Meta-analyses were performed to determine osteoporosis prevalence and risk factors in individuals with COPD. Meta-regression analyses were conducted to explore the sources of heterogeneity. RESULTS: The pooled global prevalence from 58 studies was 38% (95% CI, 34-43). The presence of COPD increased the likelihood of having osteoporosis (OR, 2.83). Other significant risk factors for osteoporosis in COPD patients were BMI < 18.5 kg/m2 (OR, 4.26) and the presence of sarcopenia (OR, 3.65). CONCLUSIONS: Osteoporosis is prevalent in individuals with COPD, and the prevalence seems to be high and similar in many countries. Patients with COPD should be screened for osteoporosis and contributing risk factors.

Qualitative dimensions of exertional dyspnea in fibrotic interstitial lung disease.

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 Impact of Cycling Cadence on Respiratory and Hemodynamic Responses to Exercise.

PURPOSE: The physiological consequences of freely chosen cadence during cycling remains poorly understood. We sought to determine the effect of cadence on the respiratory and hemodynamic response to cycling exercise. METHODS: Eleven cyclists (10 males, 1 female; age, 27 ± 6 yr; V˙O2max = 60.8 ± 3.7 mL·kg·min) completed four, 6-min constant-load cycling trials at 10% below their previously determined gas exchange threshold (i.e., 63% ± 5% peak power) while pedaling at 60, 90, and 120 rpm, and a freely chosen cadence (94.3 ± 6.9 rpm) in randomized order. Standard cardiorespiratory parameters were measured and an esophageal electrode balloon catheter was used to assess electromyography of the diaphragm (EMGdi) and the work of breathing (Wb). Leg blood flow index (BFI) was determined on four muscles using near-infrared spectroscopy with indocyanine green dye injections. RESULTS: Oxygen uptake (V˙O2) increased as a function of increasing cadence (all pairwise comparisons, P < 0.05). The EMGdi and Wb were significantly greater at 120 rpm compared with all other conditions (all P < 0.01). Vastus medialis and semitendinosus BFI were significantly greater at 120 rpm compared with 60 and 90 rpm (all P < 0.05). Gastrocnemius BFI was higher at 120 rpm compared with all other cadences (all P < 0.01). No difference in BFI was found in the vastus lateralis (P = 0.06). Blood flow index was significantly correlated with the increase in V˙O2 with increasing cadence in the medial gastrocnemius (P < 0.001) and approached significance in the vastus lateralis (P = 0.09), vastus medialis (P = 0.06), and semitendinosus (P = 0.09). There was no effect of cadence on Borg 0-10 breathing or leg discomfort ratings (P > 0.05). CONCLUSIONS: High cadence cycling at submaximal exercise intensities is metabolically inefficient and increases EMGdi, Wb, and leg muscle blood flow relative to slower cadences.

Ventilatory and sensory responses to incremental exercise in adults with a Fontan circulation.

Many adults with single-ventricle congenital heart disease who have undergone a Fontan procedure have abnormal pulmonary function resembling restrictive lung disease. Whether this contributes to ventilatory limitations and increased dyspnea has not been comprehensively studied. We recruited 17 Fontan participants and 17 healthy age- and sex-matched sedentary controls. All participants underwent complete pulmonary function testing followed by a symptom-limited incremental cardiopulmonary cycle exercise test with detailed assessments of dyspnea and operating lung volumes. Fontan participants and controls were well matched for age, sex, body mass index, height, and self-reported physical activity levels (all P > 0.05), although Fontan participants had markedly reduced cardiorespiratory fitness and peak work rates ( P < 0.001). Fontan participants had lower values for most pulmonary function measurements relative to controls with 65% of Fontan participants showing evidence of a restrictive ventilatory defect. Relative to controls, Fontan participants had significantly higher breathing frequency, end-inspiratory lung volume (% total lung capacity), ventilatory inefficiency (high ventilatory equivalent for CO2), and dyspnea intensity ratings at standardized absolute submaximal work rates. There were no between-group differences in qualitative descriptors of dyspnea. The restrictive ventilatory defect in Fontan participants likely contributes to their increased breathing frequency and end-inspiratory lung volume during exercise. This abnormal ventilatory response coupled with greater ventilatory inefficiency may explain the increased dyspnea intensity ratings in those with a Fontan circulation. Interventions that enhance the ventilatory response to exercise in Fontan patients may help optimize exercise rehabilitation interventions, resulting in improved exercise tolerance and exertional symptoms. NEW & NOTEWORTHY This is the first study to comprehensively characterize both ventilatory and sensory responses to exercise in adults that have undergone the Fontan procedure. The majority of Fontan participants had a restrictive ventilatory defect. Compared with well-matched controls, Fontan participants had increased breathing frequency, end-inspiratory lung volume, and ventilatory inefficiency. These abnormal ventilatory responses likely form the mechanistic basis for the increased dyspnea intensity ratings observed in our Fontan participants during exercise.