Effects of Obesity and Sex on Ventilatory Constraints during a Cardiopulmonary Exercise Test in Children.

PURPOSE: Ventilatory constraints are common during exercise in children, but the effects of obesity and sex are unclear. The purpose of this study was to investigate the effects of obesity and sex on ventilatory constraints (i.e., expiratory flow limitation (EFL) and dynamic hyperinflation) during a maximal exercise test in children. METHODS: Thirty-four 8-12-year-old children without obesity (18 females) and 54 with obesity (23 females) completed pulmonary function testing and maximal cardiopulmonary exercise tests. EFL was calculated as the overlap between tidal flow-volume loops during exercise and maximal expiratory flow-volume loops. Dynamic hyperinflation was calculated as the change in inspiratory capacity from rest to exercise. RESULTS: Maximal minute ventilation was not different between children with and without obesity. Average end-inspiratory lung volumes (EILV) and end-expiratory lung volumes (EELV) were significantly lower during exercise in children with obesity (EILV: 68.8 ± 0.7%TLC; EELV: 41.2 ± 0.5%TLC) compared with children without obesity (EILV: 73.7 ± 0.8%TLC; EELV: 44.8 ± 0.6%TLC; P < 0.001). Throughout exercise, children with obesity experienced more EFL and dynamic hyperinflation compared with those without obesity (P < 0.001). Also, males experienced more EFL and dynamic hyperinflation throughout exercise compared with females (P < 0.001). At maximal exercise, the prevalence of EFL was similar in males with and without obesity, however the prevalence of EFL in females was significantly different with 57% of females with obesity experiencing EFL compared with 17% of females without obesity (P < 0.05). At maximal exercise, 44% of children with obesity experienced dynamic hyperinflation compared with 12% of children without obesity (P = 0.002). CONCLUSIONS: Obesity in children increases the risk of developing mechanical ventilatory constraints such as dynamic hyperinflation and EFL. Sex differences were apparent with males experiencing more ventilatory constraints compared with females.

Respiratory symptom perception during exercise in patients with heart failure with preserved ejection fraction.

We investigated whether central or peripheral limitations to oxygen uptake elicit different respiratory sensations and whether dyspnea on exertion (DOE) provokes unpleasantness and negative emotions in patients with heart failure with preserved ejection fraction (HFpEF). 48 patients were categorized based on their cardiac output (Q̇c)/oxygen uptake (V̇O2) slope and stroke volume (SV) reserve during an incremental cycling test. 15 were classified as centrally limited and 33 were classified as peripherally limited. Ratings of perceived breathlessness (RPB) and unpleasantness (RPU) were assessed (Borg 0-10 scale) during a 20 W cycling test. 15 respiratory sensations statements (1-10 scale) and 5 negative emotions statements (1-10) were subsequently rated. RPB (Central: 3.5±2.0 vs. Peripheral: 3.4±2.0, p=0.86), respiratory sensations, or negative emotions were not different between groups (p>0.05). RPB correlated (p<0.05) with RPU (r=0.925), "anxious" (r=0.610), and "afraid" (r=0.383). While DOE provokes elevated levels of negative emotions, DOE and respiratory sensations seem more related to a common mechanism rather than central and/or peripheral limitations in HFpEF.

Body composition in early pubescent children with obesity: effects following 1 year of nonintervention.

Little is known about whether body composition changes differently between children with and without obesity following 1 year of nonintervention. Therefore, we investigated body composition in early pubescent children (8-12 yr) with and without obesity before and after a period of 1 year of nonintervention. Early pubescent children (8-12 yr; Tanner stage ≤ 3) with (body mass index, BMI ≥ 95th percentile) and without obesity (15th < BMI < 85th percentile) were recruited. At baseline, 88 children (n = 25 without obesity) completed dual-energy X-ray absorptiometry imaging (DXA) for body composition measurements [%body fat, fat mass, fat-free mass (FFM)]. One year later, 47 participants (n = 15 without obesity) returned for repeat testing. The children without obesity were older (11.0 ± 1.0 vs. 10.0 ± 1.2 yr; means ± SD) (P = 0.013). There was no group difference in height, and both groups increased in height similarly after 1 year (147.7 ± 8.9 to 154.5 ± 9.2 cm without vs. 145.6 ± 5.8 to 152.5 ± 5.9 cm with obesity) (P < 0.001). Weight was greater (P < 0.001) in children with obesity at baseline as was the increase in weight after 1 yr (9.25 vs. 5.82 kg) (interaction, P = 0.005). Fat mass increased by 4.4 kg in children with obesity and by 1.1 kg in children without obesity (interaction, P < 0.001). However, there was no difference in fat-free mass between those with and without obesity at baseline (29.9 ± 5.9 vs. 31.6 ± 4.8 kg) (P = 0.206) with both groups increasing similarly over 1 year (gain of 4.87 vs. 4.85 kg with and without obesity, respectively). Without intervention, the increase in fat mass is four times greater in children with obesity after 1 year as compared with children without obesity.NEW & NOTEWORTHY Little is known about changes in body composition in children with and without obesity following 1 year of nonintervention. We report that without intervention, fat mass gain is significantly greater in children with obesity after 1 year compared with those without obesity. Body mass index (BMI) and %body fat measurements after 1 year yielded no significant increase suggesting that BMI and %fat alone are not suitable measures for tracking changes in adiposity among children.

Pediatric patients diagnosed as overweight and obese have an elevated risk of dyspnea.

We investigated whether pediatric patients with overweight and obesity are more likely to have dyspnea compared with those who are non-overweight. We collected de-identified data from TriNetX, a global federated multicenter research database, using both the UT Southwestern Medical Center and multinational Research Networks. Our analysis focused on patients aged 8-12 years. We identified overweight and obesity using ICD-10-CM codes E66 and dyspnea using code R06.0. Patients with overweight and obesity had a significantly higher risk of dyspnea compared with those who were non-overweight. This association was observed in both the UT Southwestern Network (risk ratio: 1.81, p < 0.001) and the Research Network (risk ratio: 2.70, p < 0.001). Furthermore, within the UT Southwestern Network, the risk was found to be higher in females compared with males (risk ratio: 2.17 vs. 1.67). These results have significant clinical implications, suggesting that clinicians should consider overweight and obesity as independent risk factors for dyspnea in pediatric patients after excluding other possible contributing factors.

Impact of maternal obesity on resting muscle sympathetic nerve activity during uncomplicated pregnancy: a longitudinal assessment.

Maternal obesity increases the risk of adverse pregnancy outcomes. The mechanisms that contribute to this elevated risk are unclear but may be related to greater activity of the sympathetic nervous system, which is associated with hypertensive disorders of pregnancy. We hypothesized that resting muscle sympathetic nerve activity (MSNA) would be greater in women with obesity during pregnancy when compared with normal-weight women. Blood pressure, heart rate, and MSNA were recorded during 5 min of supine rest in 14 normal-weight women [body mass index (BMI) 22.1 ± 2.1 (SD) kg/m2] and 14 women with obesity (BMI 33.9 ± 3.5 kg/m2) during (early and late) pregnancy and postpartum. All women had uncomplicated pregnancies. Resting MSNA burst frequency was not different between groups during early (normal weight 17 ± 10 vs. obesity 22 ± 15 bursts/min, P = 0.35) but was significantly greater in the obesity group during late pregnancy (23 ± 13 vs. 35 ± 15 bursts/min, P = 0.031) and not different postpartum (10 ± 6 vs. 9 ± 7 bursts/min, P = 0.74). These findings were also apparent when comparing burst incidence and total activity. Although still within the normotensive range, systolic blood pressure was greater in the obesity group across all time points (P = 0.002). Diastolic blood pressure was lower during pregnancy compared with postpartum (P < 0.001) and not different between groups (P = 0.488). Heart rate increased throughout pregnancy in both groups (P < 0.001). Our findings suggest that maternal obesity is associated with greater increases in sympathetic activity even during uncomplicated pregnancy. Future research is needed to determine if this is linked with an increased risk of adverse outcomes or is required to maintain homeostasis in pregnancy.NEW & NOTEWORTHY The impact of maternal obesity on resting muscle sympathetic nerve activity was examined during (early and late) and after uncomplicated pregnancy. Resting muscle sympathetic nerve activity is not different during early pregnancy or postpartum but is significantly elevated in women with obesity during late pregnancy when compared with normal-weight women. Future research is needed to determine if this is linked with an increased risk of adverse outcomes or is required to maintain homeostasis in pregnancy.

Static respiratory mechanics are unaltered in males and females with obesity.

We tested the hypothesis that independent of the obesity-related shift in lung volume subdivisions, obesity would not reduce the interrelationships of expiratory flow, lung volume, and static lung elastic recoil pressure in males and females. Simultaneous measurements of expiratory flow, volume, and transpulmonary pressure were continuously recorded while flow-volume loops of varying expiratory efforts were performed in a pressure-corrected, volume-displacement body plethysmograph in males and females with obesity. Static compliance curves were collected using the occlusion technique. Flow-volume, static pressure-volume, and static pressure-flow relationships were examined. Isovolume pressure-flow curves were constructed for the determination of the critical pressure for maximal flow. Data were compared with that collected in lean males and females. Individuals with obesity displayed a notable decrease in functional residual capacity. The interrelationships of flow, lung volume, static elastic recoil pressure, and the minimum pressure required for maximal expiratory flow in males and females with obesity were not different from that in lean males and females (all P > 0.05). Obesity does not alter the interrelationships of flow-volume-pressure of the lung in adult males and females (all P > 0.05). We further explored potential sex differences in static mechanics independent of obesity and observed that females have lower maximal expiratory flow due to a combination of smaller lungs and greater upstream flow resistance compared with males (all P ≤ 0.05).NEW & NOTEWORTHY The potential influence of obesity on the interrelationships between maximal expiratory flow, lung volume, and static lung elastic recoil pressure is unclear. These data show that the presence of obesity does not alter the relationship of flow and pressure across the mid-expiratory range in males and females. In addition, independent of obesity, females have smaller lungs and greater upstream flow resistance, which contributes to reduced maximal flow, when compared with males.

Ventilatory limitations in patients with HFpEF and obesity.

Heart failure with preserved ejection fraction (HFpEF) patients have an increased ventilatory demand. Whether their ventilatory capacity can meet this increased demand is unknown, especially in those with obesity. Body composition (DXA) and pulmonary function were measured in 20 patients with HFpEF (69 ± 6 yr;9 M/11 W). Cardiorespiratory responses, breathing mechanics, and ratings of perceived breathlessness (RPB, 0-10) were measured at rest, 20 W, and peak exercise. FVC correlated with %body fat (R2 =0.51,P = 0.0006), V̇O2peak (%predicted,R2 =0.32,P = 0.001), and RPB (R2 =0.58,P = 0.0004). %Body fat correlated with end-expiratory lung volume at rest (R2 =0.76,P < 0.001), 20 W (R2 =0.72,P < 0.001), and peak exercise (R2 =0.74,P < 0.001). Patients were then divided into two groups: those with lower ventilatory reserve (FVC<3 L,2 M/10 W) and those with higher ventilatory reserve (FVC>3.8 L,7 M/1 W). V̇O2peak was ∼22% less (p < 0.05) and RPB was twice as high at 20 W (p < 0.01) in patients with lower ventilatory reserve. Ventilatory reserves are limited in patients with HFpEF and obesity; indeed, the margin between ventilatory demand and capacity is so narrow that exercise capacity could be ventilatory limited in many patients.

Elevated risk of dyspnea in adults with obesity.

We investigated whether older adults (OA) with obesity are more likely to have dyspnea compared with OA without obesity, and whether OA with obesity are at a greater risk of having dyspnea compared with middle-aged (MA) and younger adults (YA) with obesity. We obtained de-identified data from the TriNetX UT Southwestern Medical Center database. We identified obesity and dyspnea using ICD-10-CM codes E66 and R06.0, respectively. Patients were separated into three age groups: OA, (65-75 y.o.), MA (45-55 y.o.), and YA (25-35 y.o). Within these groups, those with and without obesity or dyspnea were identified for analysis. The risk of dyspnea was greater in OA (risk ratio: 3.64), MA (risk ratio: 3.52), and YA (risk ratio: 2.76) with obesity compared with age-matched patients without obesity (all p < 0.01). The risk of dyspnea was greater in OA and MA with obesity compared with YA with obesity (both p < 0.001 vs. YA). These findings suggest that clinicians should consider obesity as an independent risk factor for dyspnea.

Effects of posture changes on dynamic cerebral autoregulation during early pregnancy in women with obesity and/or sleep apnea.

The incidence of syncope during orthostasis increases in early human pregnancy, which may be associated with cerebral blood flow (CBF) dysregulation in the upright posture. In addition, obesity and/or sleep apnea per se may influence CBF regulation due to their detrimental impacts on cerebrovascular function. However, it is unknown whether early pregnant women with obesity and/or sleep apnea could have impaired CBF regulation in the supine position and whether this impairment would be further exacerbated in the upright posture. Dynamic cerebral autoregulation (CA) was evaluated using transfer function analysis in 33 women during early pregnancy (13 with obesity, 8 with sleep apnea, 12 with normal weight) and 15 age-matched nonpregnant women during supine rest. Pregnant women also underwent a graded head-up tilt (30° and 60° for 6 min each). We found that pregnant women with obesity or sleep apnea had a higher transfer function low-frequency gain compared with nonpregnant women in the supine position (P = 0.026 and 0.009, respectively) but not normal-weight pregnant women (P = 0.945). Conversely, the transfer function low-frequency phase in all pregnancy groups decreased during head-up tilt (P = 0.001), but the phase was not different among pregnant groups (P = 0.180). These results suggest that both obesity and sleep apnea may have a detrimental effect on dynamic CA in the supine position during early pregnancy. CBF may be more vulnerable to spontaneous blood pressure fluctuations in early pregnant women during orthostatic stress compared with supine rest due to less efficient dynamic CA, regardless of obesity and/or sleep apnea.

Reducing Pulmonary Capillary Wedge Pressure During Exercise Exacerbates Exertional Dyspnea in Patients With Heart Failure With Preserved Ejection Fraction: Implications for V˙/Q˙ Mismatch.

BACKGROUND: The primary cause of dyspnea on exertion in heart failure with preserved ejection fraction (HFpEF) is presumed to be the marked rise in pulmonary capillary wedge pressure during exercise; however, this hypothesis has never been tested directly. Therefore, we evaluated invasive exercise hemodynamics and dyspnea on exertion in patients with HFpEF before and after acute nitroglycerin (NTG) treatment to lower pulmonary capillary wedge pressure. RESEARCH QUESTION: Does reducing pulmonary capillary wedge pressure during exercise with NTG improve dyspnea on exertion in HFpEF? STUDY DESIGN AND METHODS: Thirty patients with HFpEF performed two invasive 6-min constant-load cycling tests (20 W): one with placebo (PLC) and one with NTG. Ratings of perceived breathlessness (0-10 scale), pulmonary capillary wedge pressure (right side of heart catheter), and arterial blood gases (radial artery catheter) were measured. Measurements of V˙/Q˙ matching, including alveolar dead space (Vdalv; Enghoff modification of the Bohr equation) and the alveolar-arterial Po2 difference (A-aDO2; alveolar gas equation), were also derived. The ventilation (V˙e)/CO2 elimination (V˙co2) slope was also calculated as the slope of the V˙e and V˙co2 relationship, which reflects ventilatory efficiency. RESULTS: Ratings of perceived breathlessness increased (PLC: 3.43 ± 1.94 vs NTG: 4.03 ± 2.18; P = .009) despite a clear decrease in pulmonary capillary wedge pressure at 20 W (PLC: 19.7 ± 8.2 vs NTG: 15.9 ± 7.4 mm Hg; P < .001). Moreover, Vdalv (PLC: 0.28 ± 0.07 vs NTG: 0.31 ± 0.08 L/breath; P = .01), A-aDO2 (PLC: 19.6 ± 6.7 vs NTG: 21.1 ± 6.7; P = .04), and V˙e/V˙co2 slope (PLC: 37.6 ± 5.7 vs NTG: 40.2 ± 6.5; P < .001) all increased at 20 W after a decrease in pulmonary capillary wedge pressure. INTERPRETATION: These findings have important clinical implications and indicate that lowering pulmonary capillary wedge pressure does not decrease dyspnea on exertion in patients with HFpEF; rather, lowering pulmonary capillary wedge pressure exacerbates dyspnea on exertion, increases V˙/Q˙ mismatch, and worsens ventilatory efficiency during exercise in these patients. This study provides compelling evidence that high pulmonary capillary wedge pressure is likely a secondary phenomenon rather than a primary cause of dyspnea on exertion in patients with HFpEF, and a new therapeutic paradigm is needed to improve symptoms of dyspnea on exertion in these patients.

Inhibiting regional sweat evaporation modifies the ventilatory response to exercise: interactions between core and skin temperature.

In humans, elevated body temperatures can markedly increase the ventilatory response to exercise. However, the impact of changing the effective body surface area (BSA) for sweat evaporation (BSAeff) on such responses is unclear. Ten healthy adults (9 males, 1 female) performed eight exercise trials cycling at 6 W/kg of metabolic heat production for 60 min. Four conditions were used where BSAeff corresponded to 100%, 80%, 60%, and 40% of BSA using vapor-impermeable material. Four trials (one at each BSAeff) were performed at 25°C air temperature, and four trials (one at each BSAeff) at 40°C air temperature, each with 20% humidity. The slope of the relation between minute ventilation and carbon dioxide elimination (V̇E/V̇co2 slope) assessed the ventilatory response. At 25°C, the V̇E/V̇co2 slope was elevated by 1.9 and 2.6 units when decreasing BSAeff from 100 to 80 and to 40% (P = 0.033 and 0.004, respectively). At 40°C, V̇E/V̇co2 slope was elevated by 3.3 and 4.7 units, when decreasing BSAeff from 100 to 60 and to 40% (P = 0.016 and P < 0.001, respectively). Linear regression analyses using group average data from each condition demonstrated that end-exercise mean body temperature (integration of core and mean skin temperature) was better associated with the end-exercise ventilatory response, compared with core temperature alone. Overall, we show that impeding regional sweat evaporation increases the ventilatory response to exercise in temperate and hot environmental conditions, and the effect is mediated primarily by increases in mean body temperature.NEW & NOTEWORTHY Exercise in the heat increases the slope of the relation between minute ventilation and carbon dioxide elimination (V̇E/V̇co2 slope) in young healthy adults. An indispensable role for skin temperature in modulating the ventilatory response to exercise is noted, contradicting common belief that internal/core temperature acts independently as a controller of ventilation during hyperthermia.

Six Months of Exercise Training Improves Ventilatory Responses during Exercise in Adults with Well-Healed Burn Injuries.

INTRODUCTION: Pulmonary function is lower after a severe burn injury, which could influence ventilatory responses during exercise. It is unclear whether exercise training improves pulmonary function or ventilatory responses during exercise in adults with well-healed burn injuries. Therefore, we tested the hypothesis that exercise training improves pulmonary function and ventilatory responses during exercise in adults with well-healed burn injuries. METHODS: Thirty-nine adults (28 with well-healed burn injuries and 11 non-burn-injured controls) completed 6 months of unsupervised, progressive exercise training including endurance, resistance, and high-intensity interval components. Before and after exercise training, we performed comprehensive pulmonary function testing and measured ventilatory responses during cycling exercise. We compared variables using two-way ANOVA (group-time; i.e., preexercise/postexercise training (repeated factor)). RESULTS: Exercise training did not increase percent predicted spirometry, lung diffusing capacity, or airway resistance measures (time: P ≥ 0.14 for all variables). However, exercise training reduced minute ventilation ( V̇E ; time: P ≤ 0.05 for 50 and 75 W) and the ventilatory equivalent for oxygen ( V̇E /V̇O 2 ; time: P < 0.001 for 75 W) during fixed-load exercise for both groups. The ventilatory equivalent for carbon dioxide ( V̇E /V̇CO 2 ) during exercise at 75 W was reduced after exercise training (time: P = 0.04). The percentage of age-predicted maximum heart rate at the ventilatory threshold was lower in adults with well-healed burn injuries before ( P = 0.002), but not after ( P = 0.22), exercise training. Lastly, exercise training increased V̇E and reduced V̇E /V̇O 2 during maximal exercise (time: P = 0.005 for both variables). CONCLUSIONS: These novel findings demonstrate that exercise training can improve ventilatory responses during exercise in adults with well-healed burn injuries.

Respiratory psychophysiology and COVID-19: A research agenda.

After multiple waves of the COVID-19 pandemic, it has become clear that the impact of SARS-CoV-2 will carry on for years to come. Acutely infected patients show a broad range of disease severity, depending on virus variant, vaccination status, age and the presence of underlying medical and physical conditions, including obesity. Additionally, a large number of patients who have been infected with the virus present with post-COVID syndrome. In September 2020, the International Society for the Advancement of Respiratory Psychophysiology organized a virtual interest meeting on 'Respiratory research in the age of COVID-19', which aimed to discuss how research in respiratory psychophysiology could contribute to a better understanding of psychophysiological interactions in COVID-19. In the resulting current paper, we propose an interdisciplinary research agenda discussing selected research questions on acute and long-term neurobiological, physiological and psychological outcomes and mechanisms related to respiration and the airways in COVID-19, as well as research questions on comorbidity and potential treatment options, such as physical rehabilitation.

Challenging the Hemodynamic Hypothesis in Heart Failure With Preserved Ejection Fraction: Is Exercise Capacity Limited by Elevated Pulmonary Capillary Wedge Pressure?

BACKGROUND: Exercise intolerance is a defining characteristic of heart failure with preserved ejection fraction (HFpEF). A marked rise in pulmonary capillary wedge pressure (PCWP) during exertion is pathognomonic for HFpEF and is thought to be a key cause of exercise intolerance. If true, acutely lowering PCWP should improve exercise capacity. To test this hypothesis, we evaluated peak exercise capacity with and without nitroglycerin to acutely lower PCWP during exercise in patients with HFpEF. METHODS: Thirty patients with HFpEF (70±6 years of age; 63% female) underwent 2 bouts of upright, seated cycle exercise dosed with sublingual nitroglycerin or placebo control every 15 minutes in a single-blind, randomized, crossover design. PCWP (right heart catheterization), oxygen uptake (breath × breath gas exchange), and cardiac output (direct Fick) were assessed at rest, 20 Watts (W), and peak exercise during both placebo and nitroglycerin conditions. RESULTS: PCWP increased from 8±4 to 35±9 mm Hg from rest to peak exercise with placebo. With nitroglycerin, there was a graded decrease in PCWP compared with placebo at rest (-1±2 mm Hg), 20W (-5±5 mm Hg), and peak exercise (-7±6 mm Hg; drug × exercise stage P=0.004). Nitroglycerin did not affect oxygen uptake at rest, 20W, or peak (placebo, 1.34±0.48 versus nitroglycerin, 1.32±0.46 L/min; drug × exercise P=0.984). Compared with placebo, nitroglycerin lowered stroke volume at rest (-8±13 mL) and 20W (-7±11 mL), but not peak exercise (0±10 mL). CONCLUSIONS: Sublingual nitroglycerin lowered PCWP during submaximal and maximal exercise. Despite reduction in PCWP, peak oxygen uptake was not changed. These results suggest that acute reductions in PCWP are insufficient to improve exercise capacity, and further argue that high PCWP during exercise is not by itself a limiting factor for exercise performance in patients with HFpEF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04068844.

Mechanical effects of obesity on central and peripheral airway resistance in nonasthmatic early pubescent children.

BACKGROUND: In children, obesity typically reduces functional residual capacity (FRC), which reduces airway caliber and increases airway resistance. Whether these obesity-related changes in respiratory function can alter bronchodilator responsiveness is unknown. OBJECTIVE: To investigate bronchodilator responsiveness in nonasthmatic children with and without obesity. METHODS: Seventy nonasthmatic children, 8-12 years old, without (n = 19) and with (n = 51) obesity, completed spirometry, impulse oscillometry, and airway resistance measurements through plethysmography pre/post 360 µg of inhaled albuterol. FRC was assessed pre albuterol. A two-way analysis of variance determined the effects of obesity (group) and inhaled albuterol (pre-post) on outcome measures. RESULTS: FRC (%total lung capacity) was 16% lower in children with obesity compared with those without obesity. There was no significant group by pre-post albuterol interaction on any outcome variables. Albuterol inhalation reduced total, central and peripheral airway resistance and increased airway reactance (i.e., less negative) to a similar degree in children with and without obesity. In children with obesity, airway resistance was increased whether measured by impulse oscillometry or plethysmography. However, once airway resistance was adjusted for lung volumes (i.e., specific airway resistance or sRaw ), there were no differences between children with and without obesity. In addition, significant but moderate associations were detected between chest mass and FRC (r = -0.566; p < 0.001), FRC and total airway resistance (i.e., Raw ; r = -0.445; p < 0.001). CONCLUSIONS: In nonasthmatic early pubescent children, obesity increases total, central, and peripheral respiratory system resistance. However, the added respiratory system resistance and low lung volume breathing with obesity are not sufficient to reduce bronchodilator responsiveness.

Sex differences in the ventilatory responses to exercise in mild to moderate obesity.

NEW FINDINGS: What is the central question of the study? What are the sex differences in ventilatory responses during exercise in adults with obesity? What is the main finding and its importance? Tidal volume and expiratory flows are lower in females when compared with males at higher levels of ventilation despite small increases in end-expiratory lung volumes. Since dyspnoea on exertion is a frequent complaint, particularly in females with obesity, careful attention should be paid to unpleasant respiratory symptoms and mechanical ventilatory constraints while prescribing exercise. ABSTRACT: Obesity is associated with altered ventilatory responses, which may be exacerbated in females due to the functional consequences of sex-related morphological differences in the respiratory system. This study examined sex differences in ventilatory responses during exercise in adults with obesity. Healthy adults with obesity (n = 73; 48 females) underwent pulmonary function testing, underwater weighing, magnetic resonance imaging (MRI), a graded exercise test to exhaustion, and two constant work rate exercise tests; one at a fixed work rate (60 W for females and 105 W for males) and one at a relative intensity (50% of peak oxygen uptake, V ̇ O 2 peak ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ ). Metabolic, respiratory and perceptual responses were assessed during exercise. Compared with males, females used a smaller proportion of their ventilatory capacity at peak exercise (69.13 ± 14.49 vs. 77.41 ± 17.06% maximum voluntary ventilation, P = 0.0374). Females also utilized a smaller proportion of their forced vital capacity (FVC) at peak exercise (tidal volume: 48.51 ± 9.29 vs. 54.12 ± 10.43%FVC, P = 0.0218). End-expiratory lung volumes were 2-4% higher in females compared with males during exercise (P < 0.05), while end-inspiratory lung volumes were similar. Since the males were initiating inspiration from a lower lung volume, they experienced greater expiratory flow limitation during exercise. Ratings of perceived breathlessness during exercise were similar between females and males at comparable levels of ventilation. In summary, sex differences in the manifestations of obesity-related mechanical ventilatory constraints were observed. Since dyspnoea on exertion is a common complaint in patients with obesity, particularly in females, exercise prescriptions should be tailored with the goal of minimizing unpleasant respiratory sensations.

Alveolar Dead Space Is Augmented During Exercise in Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) exhibit many cardiopulmonary abnormalities that could result in V˙/Q˙ mismatch, manifesting as an increase in alveolar dead space (VDalveolar) during exercise. Therefore, we tested the hypothesis that VDalveolar would increase during exercise to a greater extent in patients with HFpEF compared with control participants. RESEARCH QUESTION: Do patients with HFpEF develop VDalveolar during exercise? STUDY DESIGN AND METHODS: Twenty-three patients with HFpEF and 12 control participants were studied. Gas exchange (ventilation [V˙E], oxygen uptake [V˙o2], and CO2 elimination [V˙co2]) and arterial blood gases were analyzed at rest, twenty watts (20W), and peak exercise. Ventilatory efficiency (evaluated as the V˙E/V˙co2 slope) also was measured from rest to 20W in patients with HFpEF. The physiologic dead space (VDphysiologic) to tidal volume (VT) ratio (VD/VT) was calculated using the Enghoff modification of the Bohr equation. VDalveolar was calculated as: (VD / VT × VT) - anatomic dead space. Data were analyzed between groups (patients with HFpEF vs control participants) across conditions (rest, 20W, and peak exercise) using a two-way repeated measures analysis of variance and relationships were analyzed using Pearson correlation coefficient. RESULTS: VDalveolar increased from rest (0.12 ± 0.07 L/breath) to 20W (0.22 ± 0.08 L/breath) in patients with HFpEF (P < .01), whereas VDalveolar did not change from rest (0.01 ± 0.06 L/breath) to 20W (0.06 ± 0.13 L/breath) in control participants (P = .19). Thereafter, VDalveolar increased from 20W to peak exercise in patients with HFpEF (0.37 ± 0.16 L/breath; P < .01 vs 20W) and control participants (0.19 ± 0.17 L/breath; P = .03 vs 20W). VDalveolar was greater in patients with HFpEF compared with control participants at rest, 20W, and peak exercise (main effect for group, P < .01). Moreover, the increase in VDalveolar correlated with the V˙E/V˙co2 slope (r = 0.69; P < .01), which was correlated with peak V˙o2peak (r = 0.46; P < .01) in patients with HFpEF. INTERPRETATION: These data suggest that the increase in V˙/Q˙ mismatch may be explained by increases in VDalveolar and that increases in VDalveolar worsens ventilatory efficiency, which seems to be a key contributor to exercise intolerance in patients with HFpEF.

Adults with well-healed burn injuries have lower pulmonary function values decades after injury.

Sub-acute (e.g., inhalation injury) and/or acute insults sustained during a severe burn injury impairs pulmonary function. However, previous work has not fully characterized pulmonary function in adults with well-healed burn injuries decades after an injury. Therefore, we tested the hypothesis that adults with well-healed burn injuries have lower pulmonary function years after recovery. Our cohort of adults with well-healed burn-injuries (n = 41) had a lower forced expiratory volume in one second (Burn: 93 ± 16 vs. Control: 103 ± 10%predicted, mean ± SD; d = 0.60, p = 0.04), lower maximal voluntary ventilation (Burn: 84 [71-97] vs. Control: 105 [94-122] %predicted, median [IQR]; d = 0.84, p < 0.01), and a higher specific airway resistance (Burn: 235 ± 80 vs. Control: 179 ± 40%predicted, mean ± SD; d = 0.66, p = 0.02) than non-burned control participants (n = 12). No variables were meaningfully influenced by having a previous inhalation injury (d ≤ 0.44, p ≥ 0.19; 13 of 41 had an inhalation injury), the size of the body surface area burned (R2  ≤ 0.06, p ≥ 0.15; range of 15%-88% body surface area burned), or the time since the burn injury (R2  ≤ 0.04, p ≥ 0.22; range of 2-50 years post-injury). These data suggest that adults with well-healed burn injuries have lower pulmonary function decades after injury. Therefore, future research should examine rehabilitation strategies that could improve pulmonary function among adults with well-healed burn injuries.

Physiological dead space during exercise in patients with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is associated with cardiopulmonary abnormalities that may increase physiological dead space to tidal volume (VD/VT) during exercise. However, studies have not corrected VD/VT for apparatus mechanical dead space (VDM), which may confound the accurate calculation of VD/VT. We evaluated whether calculating physiological dead space with (VD/VTVDM) and without (VD/VT) correcting for VDM impacts the interpretation of gas exchange efficiency during exercise in HFpEF. Fifteen HFpEF (age: 69 ± 6 yr; V̇o2peak: 1.34 ± 0.45 L/min) and 12 controls (70 ± 3 yr; V̇o2peak: 1.70 ± 0.51 L/min) were studied. Pulmonary gas exchange and arterial blood gases were analyzed at rest, submaximal (20 W for HFpEF and 40 W for controls), and peak exercise. VD/VT was calculated as [Formula: see text] - [Formula: see text]/[Formula: see text]. VD/VTVDM was calculated as [Formula: see text] - [Formula: see text]/[Formula: see text] - VDM/VT. VD/VT decreased from rest (HFpEF: 0.54 ± 0.07; controls: 0.32 ± 0.07) to submaximal exercise (HFpEF: 0.46 ± 0.07; controls: 0.25 ± 0.06) in both groups (P < 0.05), but remained stable (P > 0.05) thereafter to peak exercise (HFpEF: 0.46 ± 0.09; controls: 0.22 ± 0.05). In HFpEF, VD/VTVDM did not change (P = 0.58) from rest (0.29 ± 0.07) to submaximal exercise (0.29 ± 0.06), but increased (P = 0.02) thereafter to peak exercise (0.33 ± 0.06). In controls, VD/VTVDM remained stable such that no change was observed (P > 0.05) from rest (0.17 ± 0.06) to submaximal exercise (0.14 ± 0.06), or thereafter to peak exercise (0.14 ± 0.05). Calculating physiological dead space with and without a VDM correction yields quantitively and qualitatively different results, which could have impact on the interpretation of gas exchange efficiency in HFpEF. Further investigation is required to uncover the clinical consequences and the mechanism(s) explaining the increase in VD/VTVDM during exercise in HFpEF.NEW & NOTEWORTHY Calculating VD/VT with and without correcting for VDM yields quantitively and qualitatively different results, which could have an important impact on the interpretation of V/Q mismatch in HFpEF. The finding that V/Q mismatch and gas exchange efficiency worsened, as reflected by an increase in VD/VTVDM during exercise, has not been previously demonstrated in HFpEF. Thus, further studies are needed to investigate the mechanisms explaining the increase in VD/VTVDM during exercise in patients with HFpEF.