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.

Ventilatory Responses to Exercise by Age, Sex, and Health Status.

ABSTRACT: An understanding of the normal pulmonary responses to incremental exercise is requisite for appropriate interpretation of findings from clinical exercise testing. The purpose of this review is to provide concrete information to aid the interpretation of the exercise ventilatory response in both healthy and diseased populations. We begin with an overview of the normal exercise ventilatory response to incremental exercise in the healthy, normally trained young-to-middle aged adult male. The exercise ventilatory responses in two nonpatient populations (females, elderly) are then juxtaposed with the responses in healthy males. The review concludes with overviews of the exercise ventilatory responses in four patient populations (obesity, chronic obstructive pulmonary disease, asthma, congestive heart failure). Again, we use the normal response in healthy adults as the framework for interpreting the responses in the clinical groups. For each healthy and clinical population, recent, impactful research findings will be presented.

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.

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.

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.

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.

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.

Estimating exercise PaCO2 in patients with heart failure with preserved ejection fraction.

Patients with heart failure with preserved ejection fraction (HFpEF) exhibit cardiopulmonary abnormalities that could affect the predictability of exercise [Formula: see text] from the Jones corrected partial pressure of end-tidal CO2 (PJCO2) equation (PJCO2 = 5.5 + 0.9 × [Formula: see text] - 2.1 × VT). Since the dead space to tidal volume (VD/VT) calculation also includes [Formula: see text] measurements, estimates of VD/VT from PJCO2 may also be affected. Because using noninvasive estimates of [Formula: see text] and VD/VT could save patient discomfort, time, and cost, we examined whether partial pressure of end-tidal CO2 ([Formula: see text]) and PJCO2 can be used to estimate [Formula: see text] and VD/VT in 13 patients with HFpEF. [Formula: see text] was measured from expired gases measured simultaneously with radial arterial blood gases at rest, constant-load (20 W), and peak exercise. VD/VT[art] was calculated using the Enghoff modification of the Bohr equation, and estimates of VD/VT were calculated using [Formula: see text] (VD/VT[ET]) and PJCO2 (VD/VT[J]) in place of [Formula: see text]. [Formula: see text] was similar to [Formula: see text] at rest (-1.46 ± 2.63, P = 0.112) and peak exercise (0.66 ± 2.56, P = 0.392), but overestimated [Formula: see text] at 20 W (-2.09 ± 2.55, P = 0.020). PJCO2 was similar to [Formula: see text] at rest (-1.29 ± 2.57, P = 0.119) and 20 W (-1.06 ± 2.29, P = 0.154), but underestimated [Formula: see text] at peak exercise (1.90 ± 2.13, P = 0.009). VD/VT[ET] was similar to VD/VT[art] at rest (-0.01 ± 0.03, P = 0.127) and peak exercise (0.01 ± 0.04, P = 0.210), but overestimated VD/VT[art] at 20 W (-0.02 ± 0.03, P = 0.025). Although VD/VT[J] was similar to VD/VT[art] at rest (-0.01 ± 0.03, P = 0.156) and 20 W (-0.01 ± 0.03, P = 0.133), VD/VT[J] underestimated VD/VT[art] at peak exercise (0.03 ± 0.04, P = 0.013). Exercise [Formula: see text] and VD/VT[ET] provides better estimates of [Formula: see text] and VD/VT[art] than PJCO2 and VD/VT[J] does at peak exercise. Thus, estimates of [Formula: see text] and VD/VT should only be used if sampling arterial blood during CPET is not feasible.NEW & NOTEWORTHY [Formula: see text] provides a better estimate of [Formula: see text] than PJCO2 at peak exercise, and VD/VT[ET] provides a better estimate of VD/VT[art] than VD/VT[J] at peak exercise. Although we reported significant correlations, we did not find an identity between [Formula: see text] and estimates of [Formula: see text], nor did we find an identity between VD/VT[art] and estimates of VD/VT[art]. Thus, caution should be taken and estimates of [Formula: see text] and VD/VT should only be used if sampling arterial blood during CPET is not feasible.

Repeatability of dyspnea measurements during exercise in women with obesity.

While the 0-10 Borg scale to rate perceived breathlessness (RPB) is widely used to assess dyspnea on exertion, the repeatability of RPB in women with obesity is unknown. We examined the repeatability of RPB in women with obesity during submaximal constant-load cycling following at least 10 weeks of normal daily life. Seventeen women (37 ± 7 yr; 34.6 ± 4.5 kg/m2) who rated their breathlessness as 3 on the Borg scale (i.e., "moderate") during 60 W submaximal cycling repeated the same test following 19 ± 9 weeks of normal living. Mean body weight (93.8 ± 16.1 vs. 93.6 ± 116.8 kg, p = 0.94) and RPB (3.0 ± 0.0 vs. 3.1 ± 1.4, p = 0.80) did not differ between pre- and post-normal living periods. We demonstrate that subjective ratings of breathlessness are repeatable for the majority of subjects and can be used to accurately assess DOE during submaximal constant-load cycling in women with obesity.

Dysanapsis in men and women with obesity.

Obesity alters chest wall mechanics, reduces lung volumes, and increases airway resistance. In addition, the luminal area of the larger conducting airways is smaller in women than in men when matched for lung size. We examined whether differences in pulmonary mechanics with obesity and sex were associated with the dysanapsis ratio (DR), an estimate of airway size when the expiratory flow is maximal, in men and women with and without obesity. In addition, we examined the ability to estimate DR using predicted versus measured static recoil pressure at 50% forced vital capacity (FVC; Pst50FVC). Participants completed pulmonary function testing and measurements of pulmonary mechanics. Flow, volume, and transpulmonary pressure were recorded while completing forced vital capacity (FVC) maneuvers in a body plethysmograph. Static compliance curves were collected using the occlusion technique. DR was calculated using measured values of forced midexpiratory flow and Pst50FVC. DR was also calculated using Pst predicted from previously reported data. There was no significant group (lean vs. obese) by sex interaction or main effect of group on DR. However, women displayed significantly larger DR compared with men. Predicted Pst50FVC was significantly greater than measured Pst50FVC. DR calculated from measured Pst was significantly greater than when using predicted Pst. In conclusion, although obesity does not appear to alter airway size, women may have larger airways compared with men when midexpiratory flow is maximal. In addition, DR estimated using predicted Pst should be used with caution.NEW & NOTEWORTHY It is unclear whether obesity in combination with sex influences the dysanapsis ratio (DR). These data indicate that DR is unaltered in adults with obesity and is greater in women than in men but similar between sexes when matched for lung volume. We also report a significant difference between predicted and measured static recoil pressure. Thus, we caution against predicting static recoil pressure in the calculation of DR.

Dyspnea during exercise and voluntary hyperpnea in women with obesity.

Temporal responses of ratings of perceived breathlessness (RBP) during constant-load and incremental exercise, and during voluntary hyperpnea (EVH) were examined in women with obesity. Following 6 min of constant-load (60W) cycling, 34 women rated RPB≥4 (+DOE) and 22 women rated RPB≤2 (-DOE). Both groups completed an incremental cycling test and an EVH test at 40 and 60L/min; RPB was assessed each minute of incremental cycling and at the end of each EVH trial. RPB increased with ventilation during constant-load (+DOE: R2=0.86; -DOE: R2=0.82) and incremental (+DOE: R2=0.91; -DOE: R2=0.92) exercise, but + DOE had a greater y-intercept than -DOE (60W: -0.16±1.53 vs. -0.73±0.55; incremental: -0.50±1.40 vs. -1.71±0.84). Despite matching ventilation, RPB was greater in + DOE at baseline (0.97±1.14 vs. 0.14±0.28), 40L/min (2.50±1.43 vs. 0.98±0.91), and 60L/min (3.94±2.19 vs. 2.07±1.32) during EVH. These findings show that despite linear associations between RPB and ventilation during exercise and voluntary hyperpnea, breathlessness perception at a given ventilatory demand is heightened in +DOE compared with -DOE.

Obesity Blunts the Ventilatory Response to Exercise in Men and Women.

Rationale: Obesity presents a mechanical load to the thorax, which could perturb the generation of minute ventilation (V̇e) during exercise. Because the respiratory effects of obesity are not homogenous among all individuals with obesity and obesity-related effects could vary depending on the magnitude of obesity, we hypothesized that the exercise ventilatory response (slope of the V̇e and carbon dioxide elimination [V̇co2] relationship) would manifest itself differently as the magnitude of obesity increases.Objectives: To investigate the V̇e/V̇co2 slope in an obese population that spanned across a wide body mass index (BMI) range.Methods: A total of 533 patients who presented to a surgical weight loss center for pre-bariatric surgery testing performed an incremental maximal cycling test and were studied retrospectively. The V̇e/V̇co2 slope was calculated up to the ventilatory threshold. Patients were examined in groups based on BMI (category 1: 30-39.9 kg/m2, category 2: 40-49.9 kg/m2, and category 3: ≥50 kg/m2). Because the respiratory effects of obesity could be sex and/or age specific, we further examined patients in groups by sex and age (younger: <50 yr and older: ≥50 yr). Differences in the V̇e/V̇co2 slope were then compared between BMI category, age, and sex using a three-way ANOVA.Results: No significant BMI category by sex by age interactions was detected (P = 0.75). The V̇e/V̇co2 slope decreased with increases in BMI (category 1, 29.1 ± 4.0; category 2, 28.4 ± 4.1; and category 3, 27.1 ± 3.3) and was elevated in women (28.9 ± 4.1) compared with men (26.7 ± 3.2) (BMI category by sex interaction, P < 0.05). No age-related differences were observed (BMI category by age interaction, P = 0.55). The partial pressure for end-tidal CO2 was elevated at the ventilatory threshold in BMI category 3 compared with BMI categories 1 and 2 (both P < 0.01).Conclusions: These findings suggest that obesity presents a unique challenge to augmenting ventilatory output relative to CO2 elimination, such that the increase in the exercise ventilatory response becomes blunted as the magnitude of obesity increases. Further studies are required to investigate the clinical consequences and the mechanisms that may explain the attenuation of exercise ventilatory response with increasing BMI in men and women with obesity.

Autonomic regulation of the heart and arrhythmogenesis in trained breath-hold divers.

AbstractBreath-hold divers are known to develop cardiac autonomic changes and brady-arrthymias during prolonged breath-holding (BH). The effects of BH-induced hypoxemia were investigated upon both cardiac autonomic status and arrhythmogenesis by comparing breath-hold divers (BHDs) to non-divers (NDs). Eighteen participants (9 BHDs, 9 NDs) performed a maximal voluntary BH with face immersion. BHDs were asked to perform an additional BH at water surface to increase the degree of hypoxemia. Beat-to-beat changes in heart rate (HR), short-term fractal scaling exponent (DFAα1), the number of arrhythmic events [premature ventricular contractions (PVCs), premature atrial contractions (PACs)] and peripheral oxygen saturation (SpO2) were recorded during and immediately following BH. The corrected QT-intervals (QTc) were analyzed pre- and post-acute BH. A regression-based model was used to split BH into a normoxic (NX) and a hypoxemic phase (HX). During the HX phase of BH, BHDs showed a progressive decrease in DFAα1 during BH with face immersion (p < 0.01) and BH with whole-body immersion (p < 0.01) whereas NDs did not (p > 0.05). In addition, BHDs had more arrhythmic events during the HX of BH with whole-body immersion when compared to the corresponding NX phase (5.9 ± 6.7 vs 0.4 ± 1.3; p < 0.05; respectively). The number of PVCs was negatively correlated with SpO2 during BH with whole-body immersion (r = -0.72; p < 0.05). The hypoxemic stage of voluntary BH is concomitant with significant cardiac autonomic changes toward a synergistic sympathetic and parasympathetic stimulation. Co-activation led ultimately to increased bradycardic response and cardiac electrophysiological disturbances.