Andrew H. Ramsook

Mechanisms of exertional dyspnoea in symptomatic smokers without COPD.

Dyspnoea and activity limitation can occur in smokers who do not meet spirometric criteria for chronic obstructive pulmonary disease (COPD) but the underlying mechanisms are unknown. Detailed pulmonary function tests and sensory–mechanical relationships during incremental exercise with respiratory pressure measurements and diaphragmatic electromyography (EMGdi) were compared in 20 smokers without spirometric COPD and 20 age-matched healthy controls. Smokers (mean±sd post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity 75±4%, mean±sd FEV1 104±14% predicted) had greater activity-related dyspnoea, poorer health status and lower physical activity than controls. Smokers had peripheral airway dysfunction: higher phase-III nitrogen slopes (3.8±1.8 versus 2.6±1.1%·L−1) and airway resistance (difference between airway resistance measured at 5 Hz and 20 Hz 19±11 versus 12±7% at 5 Hz) than controls (p<0.05). Smokers had significantly (p<0.05) lower peak oxygen uptake (78±40 versus 107±45% predicted) and ventilation (61±26 versus 97±29 L·min−1). Exercise ventilatory requirements, operating lung volumes and cardio-circulatory responses were similar. However, submaximal dyspnoea ratings, resistive and total work of breathing were increased in smokers compared with controls (p<0.05); diaphragmatic effort (transdiaphragmatic pressure/maximumal transdiaphragmatic pressure) and fractional inspiratory neural drive to the diaphragm (EMGdi/maximal EMGdi) were also increased (p<0.05) mainly reflecting the reduced denominator. Symptomatic smokers at risk for COPD had greater exertional dyspnoea and lower exercise tolerance compared with healthy controls in association with greater airways resistance, contractile diaphragmatic effort and fractional inspiratory neural drive to the diaphragm. Exertional dyspnoea in smokers without COPD is linked to higher inspiratory neural drive to the crural diaphragm http://ow.ly/e9Z7302uFM6

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

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.

Diaphragm Recruitment Increases during a Bout of Targeted Inspiratory Muscle Training.

PURPOSE The extent to which the diaphragm is targeted during a bout of inspiratory muscle training (IMT) is unknown. The purpose of this study was to characterize the relative activation patterns of the diaphragm and extradiaphragmatic inspiratory muscles during a bout of IMT and to determine whether diaphragmatic recruitment can be increased by giving subjects specific diaphragmatic breathing instructions (IMTdi). METHODS Ten healthy men were instrumented with surface EMG electrodes on the sternocleidomastoid (EMGscm), scalenes (EMGsca), parasternal intercostals (EMGpic), and seventh intercostal space (EMG7ic). A multipair esophageal electrode catheter measured crural diaphragmatic EMG (EMGdi) and transdiaphragmatic pressure (Pdi). Trial 1 of IMT involved 25 dynamic inspiratory maneuvers at 40% of maximal inspiratory mouth pressure using a variable flow resistive loading device where subjects were free to choose their own inspiratory muscle recruitment strategy. Trial 2 involved the same procedures, but subjects were given specific instructions to actively recruit their diaphragm. Cervical magnetic stimulation of the phrenic nerves verified the absence of diaphragmatic fatigue before commencing the second trial. RESULTS Compared with IMT, IMTdi resulted in a significant increase in EMGdi (56 ± 12 vs 73 ± 10%max, P = 0.002) and Pdi swings (39 ± 14 vs 64 ± 17 cm H2O, P < 0.0001) and a decrease in EMGsca (52 ± 21 vs 36 ± 22%max, P = 0.04). There was no difference in EMG7ic (26 ± 19 vs 33 ± 21%max, P = 0.36), EMGpic (31 ± 24 vs 25 ± 15%max, P = 0.22), and EMGscm (58 ± 21 vs 45 ± 24%max, P = 0.08) when comparing IMT versus IMTdi, respectively. CONCLUSIONS Simple diaphragmatic breathing instructions can significantly increase the recruitment of the diaphragm during IMT compared with a bout of IMT where individuals are free to choose their own inspiratory muscle recruitment strategy.

Effects of hyperoxia on dyspnoea and exercise endurance in fibrotic interstitial lung disease

Dyspnoea is a major source of distress and is the hallmark symptom of patients with interstitial lung disease (ILD). Supplemental oxygen may alleviate dyspnoea by attenuating arterial oxygen desaturation, increasing oxygen delivery and reducing the drive to breathe; however, previous studies show conflicting results on the effectiveness of supplemental oxygen on dyspnoea and exercise performance in ILD [1–6]. Methodological factors in these studies likely led to underestimation of the potential magnitude of improvement, including an insufficient fraction of inspired oxygen (FIO2) and/or the use of self-paced walking tests and incremental cycle tests rather than constant-load exercise protocols [3–8]. Dyspnoea was also either not evaluated or only evaluated at peak exercise [1, 3–6], which is insensitive to change compared to more clinically relevant submaximal exercise [8]. Finally, some studies were retrospective and did not include a blinded room-air exercise trial, making it difficult to rule out the potential placebo effect [4, 5]. The purpose of this study was to determine the effects of hyperoxia on exercise endurance as well as the intensity and qualitative dimensions of exertional dyspnoea in patients with fibrotic ILD. Hyperoxia significantly improves exertional dyspnoea and exercise tolerance in patients with fibrotic ILD http://ow.ly/WbHf309VwcM

Cardiorespiratory and sensory responses to exercise in adults with mild cystic fibrosis.

The purpose of this study was to evaluate cardiorespiratory fitness and reasons for exercise curtailment in a contemporary adult cystic fibrosis (CF) cohort with mild lung disease. Adults with mild CF (n = 19, forced expiratory volume in 1 s = 95 ± 17% predicted) were age-, sex-, ethnicity-, and body mass index-matched to healthy controls (n = 19) and underwent a detailed cardiopulmonary cycle exercise test. While CF subjects had a reduced peak oxygen uptake compared with controls, the values were normal when expressed as %predicted in 14/19 (74%) of subjects. Both groups demonstrated a normal cardiovascular limitation to exercise and stopped exercise primarily because of leg fatigue. Despite not being exercise-limited by respiratory factors, there was some evidence of ventilatory abnormalities as patients with mild CF had increased end-inspiratory lung volumes and reached an inflection/plateau in tidal volume relative to minute ventilation at lower exercise intensities compared with controls. Subjects with CF were not more likely to demonstrate expiratory flow limitation compared with controls and did not have evidence of dynamic hyperinflation during exercise. Despite increased end-inspiratory lung volumes and an earlier tidal volume inflection/plateau, CF subjects did not experience higher levels of dyspnea. In an exploratory analysis, a significant inverse correlation was observed between sweat chloride and peak work rate. Adult CF subjects with relatively well preserved spirometry have normal exercise performance relative to reference values and are primarily limited by nonrespiratory factors. However, ventilatory abnormalities were detected even in this mild CF cohort and should be evaluated in future therapeutic trials focused on disease-modifying therapies in mild CF.

Effects of inspiratory muscle training on respiratory muscle electromyography and dyspnea during exercise in healthy men

Inspiratory muscle training (IMT) has consistently been shown to reduce exertional dyspnea in health and disease; however, the physiological mechanisms remain poorly understood. A growing body of literature suggests that dyspnea intensity can be explained largely by an awareness of increased neural respiratory drive, as measured indirectly using diaphragmatic electromyography (EMGdi). Accordingly, we sought to determine whether improvements in dyspnea following IMT can be explained by decreases in inspiratory muscle electromyography (EMG) activity. Twenty-five young, healthy, recreationally active men completed a detailed familiarization visit followed by two maximal incremental cycle exercise tests separated by 5 wk of randomly assigned pressure threshold IMT or sham control (SC) training. The IMT group (n = 12) performed 30 inspiratory efforts twice daily against a 30-repetition maximum intensity. The SC group (n = 13) performed a daily bout of 60 inspiratory efforts against 10% maximal inspiratory pressure (MIP), with no weekly adjustments. Dyspnea intensity was measured throughout exercise using the modified 0-10 Borg scale. Sternocleidomastoid and scalene EMG was measured using surface electrodes, whereas EMGdi was measured using a multipair esophageal electrode catheter. IMT significantly improved MIP (pre: -138 ± 45 vs. post: -160 ± 43 cmH2O, P < 0.01), whereas the SC intervention did not. Dyspnea was significantly reduced at the highest equivalent work rate (pre: 7.6 ± 2.5 vs. post: 6.8 ± 2.9 Borg units, P < 0.05), but not in the SC group, with no between-group interaction effects. There were no significant differences in respiratory muscle EMG during exercise in either group. Improvements in dyspnea intensity ratings following IMT in healthy humans cannot be explained by changes in the electrical activity of the inspiratory muscles.NEW & NOTEWORTHY Exertional dyspnea intensity is thought to reflect an increased awareness of neural respiratory drive, which is measured indirectly using diaphragmatic electromyography (EMGdi). We examined the effects of inspiratory muscle training (IMT) on dyspnea, EMGdi, and EMG of accessory inspiratory muscles. IMT significantly reduced submaximal dyspnea intensity ratings but did not change EMG of any inspiratory muscles. Improvements in exertional dyspnea following IMT may be the result of nonphysiological factors or physiological adaptations unrelated to neural respiratory drive.

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.

Is parasternal intercostal EMG an accurate surrogate of respiratory neural drive and biomarker of dyspnea during cycle exercise testing

Recent evidence suggests that surface electromyography of the parasternal intercostals (EMGpara) can be a non-invasive alternative to diaphragmatic EMG (EMGdi) for estimating neural respiratory drive (NRD) during cardiopulmonary exercise testing (CPET). The purpose of this study was to determine if non-respiratory muscles influence EMGpara by having subjects place their hands on (Hon) and off (Hoff) the handlebars during cycling-based CPET. Ten healthy adults performed an incremental cycling test until volitional exhaustion. Participants were instrumented with an esophageal electrode catheter to measure EMGdi, and surface electrodes on the 2nd intercostal space to measure EMGpara. Subjects alternated between 30s of Hon and 30s Hoff during each exercise stage. There were no differences in EMGdi across all exercise intensities. However, EMGpara was significantly greater during the Hon vs. Hoff condition at all exercise intensities (p<0.05). These results suggest that EMGpara may not be an appropriate surrogate of NRD during cycle exercise testing due to co-activation of adjacent skeletal muscles.

Respiratory Mechanical and Cardiorespiratory Consequences of Cycling with Aerobars

Purpose Aerobars place a cyclist in a position where the trunk is flexed forward and the elbows are close to the midline of the body. This position is known to improve cycling aerodynamics and time trial race performance compared with upright cycling positions. However, the aggressive nature of this position may have important cardiorespiratory and metabolic consequences. The purpose of this investigation was to examine the respiratory mechanical, ventilatory, metabolic, and sensory consequences of cycling while using aerobars during laboratory-based cycling. Methods Eleven endurance-trained male cyclists (age, 26 ± 9 yr; V˙O2peak, 55 ± 5 mL·kg−1·min−1) were recruited. Visit 1 consisted of an incremental cycling test to determine peak power output. Visit 2 consisted of 6-min bouts of constant load cycling at 70% of peak incremental power output in the aerobar position, drop position, and upright position while grasping the brake hoods. Metabolic and ventilatory responses were measured using a commercially available metabolic cart, and respiratory pressures were measured using an esophageal catheter. Results Cycling in the aerobar position significantly increased the work of breathing (Wb), power of breathing (Pb), minute ventilation, ventilatory equivalent for oxygen and carbon dioxide, and transdiaphragmatic pressure compared with the upright position. Increases in the Wb and Pb in the aerobars relative to the upright position were strongly correlated with the degree of thoracic restriction, measured as the shoulder-to-aerobar width ratio (Wb: r = 0.80, P = 0.01; Pb: r = 0.69, P = 0.04). Conclusions Aerobars significantly increase the mechanical cost of breathing and leads to greater ventilatory inefficiency compared with upright cycling. Future work is needed to optimize aerobar width to minimize the respiratory mechanical consequences while optimizing aerodynamics.

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. Neural respiratory drive is a strong independent predictor of dyspnoea in patients with fibrotic ILD http://ow.ly/MXjd30hcabH