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.

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.

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.

A multidimensional assessment of dyspnoea in healthy adults during exercise.

PURPOSE: (1) To determine whether healthy humans can distinguish between the intensity and unpleasantness of exertional dyspnoea; (2) to evaluate the reliability of qualitative dyspnoea descriptors during exercise; and (3) to assess the reliability of the Multidimensional Dyspnoea Profile (MDP) METHODS: Forty-four healthy participants (24M:20F, 25 ± 5 years) completed maximal incremental cycling tests on three visits. During visit 1, participants rated the intensity and unpleasantness of dyspnoea simultaneously throughout exercise using the modified 0-10 category-ratio Borg scale. On visits 2 and 3, participants rated either the intensity or unpleasantness of dyspnoea alone at the same measurement times as visit 1. On all visits, participants selected qualitative descriptors throughout all exercise intensities from a list of 4, selected relevant qualitative descriptors from a list of 15 at peak exercise, and completed the MDP. RESULTS: Participants rated their dyspnoea intensity significantly higher for a given minute ventilation ([Formula: see text]) compared to dyspnoea unpleasantness (dyspnoea-[Formula: see text] slope: 0.08 ± 0.02 vs. 0.07 ± 0.03 Borg 0-10/L min-1, p < 0.001) during visit 1. The onset of intensity ratings occurred at a significantly lower work rate compared to unpleasantness ratings measured on the same exercise test (52 ± 41 vs. 91 ± 53 watts, p < 0.001). Dyspnoea intensity and unpleasantness remained significantly different for a given ventilation even when measured independently on separate exercise tests (p < 0.05). There was good-to-excellent reliability (ICC > 0.60) for the use of qualitative dyspnoea descriptors and the MDP to measure dyspnoea at peak exercise. CONCLUSION: Exercise-induced dyspnoea in healthy adults can differ in the sensory and affective dimensions, and can be measured reliably using qualitative descriptors and the MDP.

Neurophysiological mechanisms of exertional dyspnoea in fibrotic interstitial lung disease.

Our understanding of the mechanisms of dyspnoea in fibrotic interstitial lung disease (ILD) is incomplete. The aims of this study were two-fold: 1) to determine whether dyspnoea intensity is better predicted by neural respiratory drive (NRD) or neuromechanical uncoupling (NMU) of the respiratory system in fibrotic ILD, and 2) to examine the effect of breathing 60% oxygen on NRD, NMU and dyspnoea ratings.Fourteen patients with fibrotic ILD were included. Visit 1 comprised a familiarisation incremental cycle exercise test, Visit 2 comprised a normoxic incremental cycling test to address Aim 1, and Visits 3 and 4 consisted of constant-load cycling while breathing room air or 60% oxygen to address Aim 2. Diaphragmatic electromyography (EMGdi) was used as a surrogate of NRD. NMU was calculated as the ratio between EMGdi (%max) and tidal volume (%vital capacity).On adjusted analysis, NMU and its constituents were all significantly associated with dyspnoea ratings during incremental cycling, with EMGdi having the strongest correlation. The between-treatment change in dyspnoea ratings during constant load cycling was only correlated with change in exercise endurance time and NMU.Dyspnoea more strongly reflected the level of EMGdi than NMU in fibrotic ILD. However, the improvement in dyspnoea with 60% oxygen was better predicted by improvements in NMU.

Effects of respiratory muscle work on respiratory and locomotor blood flow during exercise.

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

Sex-differences in COPD: from biological mechanisms to therapeutic considerations.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous respiratory condition characterized by symptoms of dyspnea, cough, and sputum production. We review sex-differences in disease mechanisms, structure-function-symptom relationships, responses to therapies, and clinical outcomes in COPD with a specific focus on dyspnea. Females with COPD experience greater dyspnea and higher morbidity compared to males. Imaging studies using chest computed tomography scans have demonstrated that females with COPD tend to have smaller airways than males as well as a lower burden of emphysema. Sex-differences in lung and airway structure lead to critical respiratory mechanical constraints during exercise at a lower absolute ventilation in females compared to males, which is largely explained by sex differences in maximum ventilatory capacity. Females experience similar benefit with respect to inhaled COPD therapies, pulmonary rehabilitation, and smoking cessation compared to males. Ongoing re-assessment of potential sex-differences in COPD may offer insights into the evolution of patterns of care and clinical outcomes in COPD patients over time.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

Sex differences in respiratory muscle activation patterns during high-intensity exercise in healthy humans.

Although women experience greater ventilatory constraints and have a higher work of breathing during exercise, they are less susceptible to diaphragm fatigue compared to men. The mechanisms for diaphragmatic fatigue resistance in women is unknown but may be related to sex differences in respiratory muscle recruitment. Accordingly, the purpose of this study was to determine if electromyography (EMG) of the diaphragm (EMGdi) and extra-diaphragmatic inspiratory muscles differ between sexes during exercise. Forty subjects (21M:19F) completed a constant load cycling test at 85% of maximum work rate until exhaustion, while instrumented with an oesophageal electrode catheter to measure EMGdi and surface electrodes to measure EMG of the sternocleidomastoid (EMGscm) and scalene (EMGsca) muscles. No sex difference in EMGdi was observed at any measurement time. However, EMGscm and EMGsca were higher throughout all submaximal exercise times in women (p<0.01). These results suggest greater reliance on the extra-diaphragmatic inspiratory muscles in women relative to men, which may serve as a strategy to minimize diaphragmatic fatigue.