Paolo B. Dominelli

Mechanisms of exercise intolerance in Global Initiative for Chronic Obstructive Lung Disease grade 1 COPD

The purpose of this study was to determine if a dissociation existed between respiratory drive, as estimated by diaphragmatic electromyography (EMGdi), and its pressure-generating capacity during exercise in mild chronic obstructive pulmonary disease (COPD) and whether this, if present, had negative sensory consequences. Subjects meeting spirometric criteria for mild COPD (n=16) and age and sex-matched controls (n=16) underwent detailed pulmonary function testing and a symptom limited cycle test while detailed ventilatory, sensory and respiratory mechanical responses were measured. Compared with controls, subjects with mild COPD had greater ventilatory requirements throughout submaximal exercise. At the highest equivalent work rate of 60 W, they had a significantly higher: total work of breathing (32±17 versus 16±7 J·min−1; p<0.01); EMGdi (37.3±17.3 versus 17.9±11.7% of maximum; p<0.001); and EMGdi to transdiaphragmatic pressure ratio (0.87±0.38 versus 0.52±0.27; p<0.01). Dyspnoea–ventilation slopes were significantly higher in mild COPD than controls (0.17±0.12 versus 0.10±0.05; p<0.05). However, absolute dyspnoea ratings reached significant levels only at high levels of ventilation. Increased respiratory effort and work of breathing, and a wider dissociation between diaphragmatic activation and pressure-generating capacity were found at standardised work rates in subjects with mild COPD compared with controls. Despite these mechanical and neuromuscular abnormalities, significant dyspnoea was only experienced at higher work rates. Mild COPD patients experience respiratory mechanical abnormalities during exercise despite relatively preserved FEV1 http://ow.ly/yHukJ

Effect of thoracic gas compression and bronchodilation on the assessment of expiratory flow limitation during exercise in healthy humans

Expiratory flow limitation (EFL) during exercise may be overestimated or falsely detected when superimposing tidal breaths within a pre-exercise maximal expiratory flow volume (MEFV) curve due to thoracic gas compression (TGC) and bronchodilation. Accordingly, the purpose of this study was to determine the effects of TGC and bronchodilation on the assessment of EFL in 35 healthy subjects. A pre-exercise forced vital capacity (FVC) maneuver was performed that did not account for TGC (MEFV(pre)). Subjects then performed graded expirations from total lung capacity to residual volume at different efforts to account for TGC (MEFV(pre-TGC)). Post-exercise FVC (MEFV(post)) and post-exercise graded expirations (MEFV(post-TGC)) were performed to account for bronchodilation and TGC. EFL occurred in 29 subjects when using MEFV(pre). The magnitude of EFL in these subjects was 47+/-23% which was significantly higher than MEFV(pre-TGC) (28+/-28%), MEFV(post) (24+/-27%) and MEFV(post-TGC) (19+/-24%) (P<0.00001). Using the traditional MEFV(pre) curve overestimates and falsely detects EFL since it does not account for TGC and bronchodilation.

Oxygen cost of exercise hyperpnoea is greater in women compared with men

The oxygen cost of breathing represents a significant fraction of total oxygen uptake during intense exercise. At a given ventilation, women have a greater work of breathing compared with men, and because work is linearly related to oxygen uptake we hypothesized that their oxygen cost of breathing would also be greater. For a given ventilation, women had a greater absolute oxygen cost of breathing, and this represented a greater fraction of total oxygen uptake. Regardless of sex, those who developed expiratory flow limitation had a greater oxygen cost of breathing at maximal exercise. The greater oxygen cost of breathing in women indicates that a greater fraction of total oxygen uptake (and possibly cardiac output) is directed to the respiratory muscles, which may influence blood flow distribution during exercise.

Exercise‐induced arterial hypoxaemia and the mechanics of breathing in healthy young women

•  By virtue of their smaller lung volumes and airway diameters, women develop more mechanical ventilatory constraints during exercise, which may result in increased vulnerability to hypoxaemia during exercise. •  Hypoxaemia developed at all exercise intensities with varying patterns and was more common in aerobically trained subjects; however, some untrained women also developed hypoxaemia. •  Mechanical respiratory constraints directly lead to hypoxaemia in some women and prevent adequate reversal of hypoxaemia in most women. •  Experimentally reversing mechanical constraints with heliox gas partially reversed the hypoxaemia in subjects who developed expiratory flow limitation. •  Due in part to increased mechanical ventilatory constraints, the respiratory systems response to exercise is less than ideal in most women.

Experimental approaches to the study of the mechanics of breathing during exercise

This review describes the methodology and analysis of respiratory mechanics as it pertains to dynamic exercise. Underlying physical principles governing respiratory mechanics and commonly used measuring instruments will be discussed. We explain the physiological basis behind respiration, along with the dynamics of pulmonary ventilation. This review will outline the theoretical framework behind several forms of analysis along with their specific pitfalls, advantages and assumptions. Particular attention will be given to the techniques used to estimate the mechanical work of breathing. Specifically, we detail the different styles of work of breathing analysis and their inherent limitations as well as common sources of error often encountered. Finally, recent technological advancements that contribute to the understanding of respiratory mechanics are explained.

Revisiting dysanapsis: sex‐based differences in airways and the mechanics of breathing during exercise

What is the topic of this review? This review focuses on sex‐based differences in the anatomy of the respiratory system, which manifest in mechanical ventilatory contraints and potentially alter the integrative response to exercise. What advances does it highlight? Recent evidence indicates that women have smaller conducting airways than men, even when matched for lung size. Consequently, women are more likely to experience mechanical ventilatory constraints to exercise hyperpnoea. Furthermore, at a given ventilation, women have a higher work and oxygen cost of breathing, both of which may lead to differences in the whole‐body integrative response to dynamic exercise.

Hypoxia, not pulmonary vascular pressure, induces blood flow through intrapulmonary arteriovenous anastomoses

Blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) is increased by acute hypoxia during rest by unknown mechanisms. Oral administration of acetazolamide blunts the pulmonary vascular pressure response to acute hypoxia, thus permitting the observation of IPAVA blood flow with minimal pulmonary pressure change. Hypoxic pulmonary vasoconstriction was attenuated in humans following acetazolamide administration and partially restored with bicarbonate infusion, indicating that the effects of acetazolamide on hypoxic pulmonary vasoconstriction may involve an interaction between arterial pH and PCO2 . We observed that IPAVA blood flow during hypoxia was similar before and after acetazolamide administration, even after acid–base status correction, indicating that pulmonary pressure, pH and PCO2 are unlikely regulators of IPAVA blood flow.

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.

Dysanapsis and the resistive work of breathing during exercise in healthy men and women

We asked if the higher work of breathing (Wb) during exercise in women compared with men is explained by biological sex. We created a statistical model that accounts for both the viscoelastic and the resistive components of the total Wb and independently compares the effects of biological sex. We applied the model to esophageal pressure-derived Wb values obtained during an incremental cycle test to exhaustion. Subjects were healthy men (n = 17) and women (n = 18) with a range of maximal aerobic capacities (V̇o2 max range: men = 40-68 and women = 39-60 ml·kg(-1)·min(-1)). We also calculated the dysanapsis ratio using measures of lung recoil and forced expiratory flow as index of airway caliber. By applying the model we found that the differences in the total Wb during exercise in women are due to a higher resistive Wb rather than viscoelastic Wb. We also found that the higher resistive Wb is independently explained by biological sex. To account for the known effect of lung volumes on the dysanapsis ratio we compared the sexes with an analysis of covariance procedures and found that when vital capacity was accounted for the adjusted mean dysanapsis ratio is statistically lower in women (0.17 vs. 0.25 arbitrary units; P < 0.05). Our collective findings suggest that innate sex-based differences may exist in human airways, which result in significant male-female differences in the Wb during exercise in healthy subjects.

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.