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 (n516) and age and sex-matched controls (n516) 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. @ERSpublications Mild COPD patients experience respiratory mechanical abnormalities during exercise despite relatively preserved FEV1

To minimize transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus responsible for coronavirus disease (COVID-19), the U.S. Centers for Disease Control and Prevention and the World Health Organization recommend wearing face masks in public. Some have expressed concern that these may affect the cardiopulmonary system by increasing the work of breathing, altering pulmonary gas exchange and increasing dyspnea, especially during physical activity. These concerns have been derived largely from studies evaluating devices intentionally designed to severely affect respiratory mechanics and gas exchange. We review the literature on the effects of various face masks and respirators on the respiratory system during physical activity using data from several models: cloth face coverings and surgical masks, N95 respirators, industrial respirators, and applied highly resistive or high–dead space respiratory loads. Overall, the available data suggest that although dyspnea may be increased and alter perceived effort with activity, the effects on work of breathing, blood gases, and other physiological parameters imposed by face masks during physical activity are small, often too small to be detected, even during very heavy exercise. There is no current evidence to support sex-based or age-based differences in the physiological responses to exercise while wearing a face mask. Although the available data suggest that negative effects of using cloth or surgical face masks during physical activity in healthy individuals are negligible and unlikely to impact exercise tolerance significantly, for some individuals with severe cardiopulmonary disease, any added resistance and/or minor changes in blood gases may evoke considerably more dyspnea and, thus, affect exercise capacity.

Key pointsr The oxygen cost of breathing represents a significant fraction of total oxygen uptake during intense exercise.r 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.r For a given ventilation, women had a greater absolute oxygen cost of breathing, and this represented a greater fraction of total oxygen uptake.r Regardless of sex, those who developed expiratory flow limitation had a greater oxygen cost of breathing at maximal exercise.r 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.Abstract We compared the oxygen cost of breathing (V O 2 RM ) in healthy men and women over a wide range of exercise ventilations (V E ). Eighteen subjects (nine women) completed 4 days of testing. First, a step-wise maximal cycle exercise test was completed for the assessment of spontaneous breathing patterns. Next, subjects were familiarized with the voluntary hyperpnoea protocol used to estimateV O 2 RM . During the final two visits, subjects mimicked multiple times (four to six) the breathing patterns associated with five or six different exercise stages. Each trial lasted 5 min, and on-line pressure-volume and flow-volume loops were superimposed on target loops obtained during exercise to replicate the work of breathing accurately. At ß55 l min −1 V E ,V O 2 RM was significantly greater in women. At maximal ventilation, the absoluteV O 2 RM was not different (P > 0.05) between the sexes, but represented a significantly greater fraction of whole-bodyV O 2 in women (13.8 ± 1.5 vs. 9.4 ± 1.1%V O 2 ). During heavy exercise at 92 and 100% V O 2 max , the unit cost ofV E was +0.7 and +1.1 ml O 2 l −1 greater in women (P < 0.05). AtV O 2 max , men and women who developed expiratory flow limitation had a significantly greaterV O 2 RM than those who did not (435 ± 44 vs. 331 ± 30 ml O 2 min −1 ). In conclusion, women have a greateṙ V O 2 RM for a givenV E , and this represents a greater fraction of whole-bodyV O 2 . The greaterV O 2 RM in women may have implications for the integrated physiological response to exercise. Abbreviations EFL, expiratory flow limitation; MEFV, maximal expiratory flow-volume;V E , expired minute ventilation;V Emax , maximal expired minute ventilation;V O2 , oxygen uptake;V O2 max , maximal oxygen uptake;V O2RM , oxygen uptake of the respiratory muscles; WOB, work of breathing.

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Key points• 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 system's response to exercise is less than ideal in most women. AbstractThe purpose of this study was to characterize exercise-induced arterial hypoxaemia (EIAH), pulmonary gas exchange and respiratory mechanics during exercise, in young healthy women. We defined EIAH as a >10 mmHg decrease in arterial oxygen tension (P aO 2 ) during exercise compared to rest. We used a heliox inspirate to test the hypothesis that mechanical constraints contribute to EIAH. Subjects with a spectrum of aerobic capacities (n = 30; maximal oxygen consumption (V O 2 max ) = 49 ± 1, range 28-62 ml kg −1 min −1 ) completed a stepwise treadmill test and a subset (n = 18 with EIAH) completed a constant load test (∼85%V O 2 max ) with heliox gas. Throughout exercise arterial blood gases, oxyhaemoglobin saturation (S aO 2 ), the work of breathing (WOB) and expiratory flow limitation (EFL) were assessed. Twenty of the 30 women developed EIAH with a nadir P aO 2 and S aO 2 ranging from 58 to 88 mmHg and 87 to 96%, respectively. At maximal exercise, P aO 2 was inversely related toV O 2 max (r = -0.57, P < 0.05) with notable exceptions where some subjects with low aerobic fitness levels demonstrated EIAH. Subjects with EIAH had a greaterV O 2 max (51 ± 1 vs. 43 ± 2 ml kg −1 min −1 ), lower end-exercise S aO 2 (93.2 ± 0.5 vs. 96.1 ± 0.3%) and a greater maximal energetic WOB (324 ± 19 vs. 247 ± 23 J min −1 ), but had similar resting pulmonary function compared to those without EIAH. Most subjects developed EIAH at submaximal exercise intensities, with distinct patterns of hypoxaemia. In some subjects with varying aerobic fitness levels, mechanical ventilatory constraints (i.e. EFL) were the primary mechanism associated with the hypoxaemia during the maximal test. Mechanical ventilatory constraints also prevented adequate compensatory alveolar hyperventilation in most EIAH subjects. Minimizing mechanical ventilatory constraints with heliox inspiration partially reversed EIAH in subjects who developed EFL. In conclusion, healthy women of all aerobic fitness levels can develop EIAH and begin to do so at submaximal intensities. Mechanical ventilatory constraints are a primary mechanism for EIAH in some healthy women and prevent reversal of hypoxaemia in women for whom it is not the primary mech...

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.

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 , P > 0.05), but was lower on the proportional assist ventilator trial (3.4 ± 0.7 l min , 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.

Airway luminal area is the major determinant of resistance to airflow in the tracheobronchial tree. Women may have smaller central conducting airways than men; however, previous evidence is confounded by an indirect assessment of airway geometry and by subjects with prior smoking history. The purpose of this study was to examine the effect of sex on airway size in healthy nonsmokers. Using low-dose high-resolution computed tomography, we retrospectively assessed airway luminal area in healthy men ( n = 51) and women ( n = 73) of varying ages (19-86 yr). Subjects with a positive smoking history, cardiopulmonary disease, or a body mass index > 40 kg/m were excluded. Luminal areas of the trachea, right and left main bronchus, bronchus intermediate, left and right upper lobes, and the left lower lobe were analyzed at three discrete points. The luminal areas of the conducting airways were ~26%-35% smaller in women. The trachea had the largest differences in luminal area between men and women (298 ± 47 vs. 195 ± 28 mm or 35% smaller for men and women, respectively), whereas the left lower lobe had the smallest differences (57 ± 15 vs. 42 ± 9 mm or 26% smaller for men and women, respectively). When a subset of subjects was matched for height, the sex differences in airway luminal area persisted, with women being ~20%-30% smaller. With all subjects, there were modest relationships between height and airway luminal area ( r = 0.73-0.53, P < 0.05). Although there was considerable overlap between sexes, the luminal areas of the large conducting airways were smaller in healthy women than in men. NEW & NOTEWORTHY Previous evidence for sex differences in airway size has been confounded by indirect measures and/or cohorts with significant smoking histories or pathologies. We found that central airways in healthy women were significantly smaller (~26%-35%) than men. The significant sex-difference in airway size was attenuated (20%-30% smaller) but preserved in a subset of subjects matched for height. Over a range of ages, healthy women have smaller central airways than men.