Inspiratory Capacity Maneuvers Research Articles

Tidal expiratory flow limitation during exercise is unrelated to peripheral hypercapnic chemosensitivity

We sought to determine if peripheral hypercapnic chemosensitivity is related to expiratory flow limitation (EFL) during exercise. Twenty participants completed one testing day which consisted of peripheral hypercapnic chemosensitivity testing and a maximal exercise test to exhaustion. The chemosensitivity testing consisting of two breaths of 10% CO2 (O2∼21%) repeated 5 times during seated rest and the first 2 exercise intensities during the maximal exercise test. Following chemosensitivity testing, participants continued cycling with the intensity increasing 20 W every 1.5 minutes till exhaustion. Maximal expiratory flow-volume curves were derived from forced expiratory capacity maneuvers performed before and after exercise at varying efforts. Inspiratory capacity maneuvers were performed during each exercise stage to determine EFL. There was no difference between the EFL and non-EFL hypercapnic chemoresponse (mean response during exercise 0.96 ± 0.46 and 0.91 ± 0.33 l min−1 mmHg−1, p=0.783). Peripheral hypercapnic chemosensitivity during mild exercise does not appear to be related to the development of EFL during exercise.

Reduced tidal volume-inflection point and elevated operating lung volumes during exercise in females with well-controlled asthma

IntroductionIndividuals with asthma breathe at higher operating lung volumes during exercise compared with healthy individuals, which contributes to increased exertional dyspnoea. In health, females are more likely to develop exertional...

Lower-limb resistance training reduces exertional dyspnea and intrinsic neuromuscular fatigability in individuals with chronic obstructive pulmonary disease.

Skeletal muscle atrophy, dysfunction, and fatigue are important complications of chronic obstructive pulmonary disease (COPD). Greater reliance on glycolytic metabolism and increased type III/IV muscle afferent activity increase ventilatory drive, promote ventilatory constraint, amplify exertional dyspnea, and limit exercise tolerance. To investigate whether muscular adaptation with resistance training (RT) could improve exertional dyspnea, exercise tolerance, and intrinsic neuromuscular fatigability in individuals with COPD (n = 14, FEV1 = 62 ± 21% predicted), we performed a proof-of-concept single-arm efficacy study utilizing 4 wk of individualized lower-limb RT (3 times/wk). At baseline, dyspnea (Borg scale), ventilatory parameters, lung volumes (inspiratory capacity maneuvers), and exercise time were measured during a constant-load test (CLT) at 75% maximal workload to symptom limitation. On a separate day, fatigability was assessed using 3 min of intermittent stimulation of the quadriceps (initial output of ∼25% maximal voluntary force). Following RT, the CLT and fatigue protocols were repeated. Compared with baseline, isotime dyspnea was reduced (5.9 ± 2.4 vs. 4.5 ± 2.4 Borg units, P = 0.02) and exercise time increased (437 ± 405 s vs. 606 ± 447 s, P < 0.01) following RT. Isotime tidal volume increased (P = 0.01), whereas end-expiratory lung volumes (P = 0.02) and heart rate (P = 0.03) decreased. Quadriceps force, relative to initial force, was higher at the end of the stimulation protocol posttraining (53.2 ± 9.1 vs. 46.8 ± 11.9%, P = 0.04). This study provides evidence that 4 wk of RT attenuates exertional dyspnea and improves exercise tolerance in individuals with COPD, which in part, is likely due to delayed ventilatory constraint and reduced intrinsic fatigability. A pulmonary rehabilitation program beginning with individualized lower-limb RT may help mitigate dyspnea before performing aerobic training in individuals with COPD.NEW & NOTEWORTHY This study presents the novel finding that 4-wk resistance training (RT) focused specifically on the lower limbs can reduce exertional dyspnea during constant-load cycling, improve exercise tolerance, and reduce intrinsic fatigability of the quadriceps in individuals with COPD.

Cardiovascular effects of exercise induced dynamic hyperinflation in COPD patients-Dynamically hyperinflated and non-hyperinflated subgroups.

An increase in respiratory rate and expiratory flow limitation can facilitate dynamic hyperinflation (DH), which may cause an element of the intrathoracic pressure in connection with the worsening of venous return, with negative effect on stroke volume (SV) and cardiac output (CO). It has been unclassified, whether poor circulatory adaptation to exercise can be attributed to DH or poor cardio-vascular performance itself in COPD. Only a subset of COPD patients exhibit dynamic hyperinflation during exercise. We designed a study to show how lung mechanical and cardiovascular parameters change in hyperinflated and non-hyperinflated COPD patients during exercise with a new experimental set-up. Thirty-three COPD patients with similar severity of COPD and left ventricular performance (20 men, 13 women, mean±SD age: 65,36±6,95 years) participated. We measured the cardiovascular parameters with a non-invasive device (Finometer-pro) including the left ventricular ejection time index (LVETi) and estimated the change of DH with inspiratory capacity (IC) manoeuvres during exercise. Twenty-one subjects exhibited DH (DH group) and 12 did not (non-DH group). The measurement results were given in mean ± SD and difference between the values measured during maximal load and rest also (ΔX = Xmax.load-Xrest). ΔSV and ΔCO were significantly higher in non-DH vs. DH patients (ΔSV: non-DH 9,7 ± 13,22 ml vs. DH -3,6 ± 14,34 ml, p = 0.0142; ΔCO: non-DH 2,26 ± 1,46 l/min vs. DH 0,88 ± 1,35 l/min, p = 0.0024). LVETi was not different between the two groups. Calculated oxygen delivery (DO2) during maximal load was significantly higher in non-DH group. We concluded that worse cardiovascular adaptation to exercise of COPD patients can be associated with exercise-induced DH in a similar cardiovascular aged COPD group.

Convolutional Neural Network Analysis to Predict Expiratory Flow Limitation During Exercise in Adults with Asthma

OBJECTIVE and HYPOTHESISThe objective of this study was to assess the potential for using well‐known convolutional neural network (CNN) designs to accurately identify the presence of expiratory flow‐limitation (EFL) during exercise in adult asthmatics. We hypothesized that a CNN model would accurately identify spontaneous exercise tidal flow‐volume loops (eFVL) that exceed maximal airflow from the maximal forced expiration (i.e., EFL).METHODS and RESULTSThe expiratory portion of spontaneous eFVLs were placed within the pre‐exercise maximal volitional flow‐volume envelope. Inspiratory capacity maneuvers were performed to determine the correct lung volume for placement of the eFVLs. We assembled a collection of spontaneous eFVLs from one asthmatic subject consisting of an equal number of eFVLs that were flow‐limited and non‐flow‐limited. Subsequently, our overall approach followed standard deep learning practices. The eFVLs were manually labelled as EFL and non‐EFL. The sci‐kit learn train_test_split() method was used to split the eFVLs randomly into training and testing sets using a 67%/33% split. We trained both a one‐ (expired airflow only) and a two‐channel (expired volume and airflow) CNN model to predict the presence or absence of EFL as a response to an eFVL. The models were instantiated as sequential models using the TensorFlow 2.6.0 python API. After 100 training epochs on the training cases, the 1‐channel model was challenged to predict the labels of the previously unseen testing cases. The 1‐channel model achieved 93.3% accuracy at predicting the EFL/non‐EFL labels as a response to the eFVLs despite having not been trained on these data. Additionally, the 2‐channel model was 100% accurate on the unseen test cases. We then challenged the 2‐channel model on 45 unseen eFVLs from a different asthmatic subject; the eFVLs consisted of a balance of EFL and non‐EFL. The model performed poorly, accurately identifying only 57% of the eFVLs as EFL or non‐EFL. We then trained an additional 2‐channel model on a random sample of the combined data from the two subjects and challenged the model on the unseen eFVLs from the same two subjects. At 25 epochs and 100 epochs, the CNN was challenged with unseen testing subjects and achieved 88 and 92% accuracy, respectively, at distinguishing between EFL and non‐EFL.CONCLUSIONSThese proof‐of‐concept findings provide strong evidence that neural network analyses hold promise as a novel method for identifying either the presence or absence of EFL. Given the current, tedious and nuanced methods for determining EFL, such artificial intelligence analyses hold promise for automating the analysis and identification of exercise ventilatory constraints.

Pitfalls in Expiratory Flow Limitation Assessment at Peak Exercise in Children: Role of Thoracic Gas Compression.

Thoracic gas compression and exercise-induced bronchodilation can influence the assessment of expiratory flow limitation (EFL) during cardiopulmonary exercise tests. The purpose of this study was to examine the effect of thoracic gas compression and exercise-induced bronchodilation on the assessment of EFL in children with and without obesity. Forty children (10.7 ± 1.0 yr; 27 obese; 15 with EFL) completed pulmonary function tests and incremental exercise tests. Inspiratory capacity maneuvers were performed during the incremental exercise test for the placement of tidal flow volume loops within the maximal expiratory flow volume (MEFV) loops, and EFL was calculated as the overlap between the tidal and the MEFV loops. MEFV loops were plotted with volume measured at the lung using plethysmography (MEFVp), with volume measured at the mouth using spirometry concurrent with measurements in the plethysmograph (MEFVm), and from spirometry before (MEFVpre) and after (MEFVpost) the incremental exercise test. Only the MEFVp loops were corrected for thoracic gas compression. Not correcting for thoracic gas compression resulted in incorrect diagnosis of EFL in 23% of children at peak exercise. EFL was 26% ± 15% VT higher for MEFVm compared with MEFVp (P < 0.001), with no differences between children with and without obesity (P = 0.833). The difference in EFL estimation using MEFVpre (37% ± 30% VT) and MEFVpost (31% ± 26% VT) did not reach statistical significance (P = 0.346). Not correcting the MEFV loops for thoracic gas compression leads to the overdiagnosis and overestimation of EFL. Because most commercially available metabolic measurement systems do not correct for thoracic gas compression during spirometry, there may be a significant overdiagnosis of EFL in cardiopulmonary exercise testing. Therefore, clinicians must exercise caution while interpreting EFL when the MEFV loop is derived through spirometry.

ENSIFENTRINE ADDED ON TO TIOTROPIUM SIGNIFICANTLY IMPROVES INSPIRATORY CAPACITY IN PATIENTS WITH SYMPTOMATIC COPD

SESSION TITLE: Obstructive Lung Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Ensifentrine (RPL554) is an investigational, first-in-class, inhaled dual inhibitor of PDE3 and PDE4 that combines bronchodilator and anti-inflammatory actions in a single compound. In a previously completed dose-ranging study in patients with COPD, nebulized ensifentrine delivered clinically meaningful and significant improvements versus placebo in lung function and symptoms (Singh et al. 2020). In a second dose-ranging study, nebulized ensifentrine (0.375, 0.75, 1.5 or 3 mg) or placebo was given in addition to tiotropium for 4 weeks in symptomatic COPD patients following a 14-day run-in on tiotropium. All ensifentrine doses produced significant bronchodilation on top of tiotropium with a dose-dependent increase from baseline to peak FEV1 (primary endpoint) at week 4 of 78 to 124 mL (placebo-corrected; all p<0.05). This abstract reports on the pre-specified exploratory investigation of the effect of twice-daily nebulized ensifentrine versus placebo on inspiratory capacity (IC) in the same study. METHODS: Analysis was performed on all randomized patients with sufficient data collected after intake of study treatment to compute the pharmacodynamic parameters based on FEV1 on at least one occasion. The analysis comprised 413 patients with 83, 83, 81, 82 in the 0.375, 0.75, 1.5, 3.0 mg ensifentrine + tiotropium groups and 84 in the placebo + tiotropium treatment group. IC maneuvers were conducted according to ATS/ERS guidelines (Miller et al, 2005) prior to the forced maneuvers 30 minutes pre-dose and 2 hours post-dose following randomization (Day 1) and at the last dose at Week 4. The change from baseline was calculated. RESULTS: Mean age was 64.3 years, with 52.2% under 65 years of age. Patients were primarily female (57.5%), caucasian (90.1%) and current smokers (55.3%) with chronic bronchitis (59%). Day 1 baseline IC was similar between treatment groups. Placebo-corrected change from baseline in IC on Day 1 (2h post-dose) was 76, 62, 115 and 108 mL for the 0.375, 0.75, 1.5, 3.0 mg ensifentrine + tiotropium groups, respectively. The 1.5 and 3 mg doses showed statistically significant improvements (p<0.01). After 4 weeks of twice-daily ensifentrine added to once daily tiotropium, there was a statistically significant improvement of 110.2 mL in IC (2 h post-dose) compared with placebo (tiotropium alone, p=0.0290) with the 3 mg ensifentrine dose + tiotropium treatment group. CONCLUSIONS: This study demonstrates a clinically meaningful response in IC after treatment with 4 weeks of ensifentrine in COPD patients who remain symptomatic and with impaired lung function despite the use of tiotropium. CLINICAL IMPLICATIONS: Measurement of IC as a marker of dynamic lung hyperinflation has been shown to correlate with dyspnea and exercise performance in stable COPD. Results suggest a physiological mechanism by which ensifentrine improved symptoms and health-related quality of life. DISCLOSURES: Consultant relationship with Verona Pharma Please note: $5001 - $20000 Added 06/01/2020 by Thomas Bengtsson, source=Web Response, value=Consulting fee Employee relationship with Verona pharma Please note: >$100000 by Tara Rheault, source=Admin input, value=Stock Employee relationship with Verona Pharma Please note: >$100000 Added 05/20/2020 by Kathleen Rickard, source=Web Response, value=Salary

The Prevalence of Expiratory Flow Limitation in Youth Elite Male Cyclists.

Twelve ET youth male cyclists (16.3 ± 1.0 yr (13-18 yr), 176.5 ± 6.2 cm, 64.2 ± 5.9 kg) and 12 CON subjects (17.6 ± 2.2 yr (13-18 yr), 177.9 ± 7.1 cm, 74.8 ± 11.2 kg) completed an incremental exercise test to determine peak oxygen consumption (V˙O2peak) on a cycle ergometer. Maximal flow volume loops (MFVL), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, forced expiratory flow between 25% and 75% of FVC, and peak expiratory flow were assessed before and after exercise, with inspiratory capacity maneuvers and dyspnea ratings measured in the last 20 s of each stage. EFL was quantified as the percentage of the expiratory tidal volume that overlapped with the maximal flow volume loop. V˙O2peak, dyspnea ratings at peak, and ventilation were higher in the ET compared with CON group (P < 0.05). The ET group experienced greater EFL prevalence at V˙O2peak, with 11 of 12 subjects exhibiting EFL compared with 5 of 12 subjects in the CON group (P = 0.014). When matched for absolute ventilation of 20, 40, 60, 80, and 100 L·min, there were no differences in EFL severity between the ET and CON groups (P = 0.473). Elite youth male cyclists have a greater prevalence of EFL at maximal exercise than do CON subjects who are similar in age, height, and lung size. Future research should determine whether EFL in youth ET male cyclists may limit their exercise performance.

The Effect of Carotid Chemoreceptor Inhibition on Exercise Tolerance in Chronic Heart Failure.

PurposeChronic heart failure (CHF) is characterized by heightened sympathetic nervous activity, carotid chemoreceptor (CC) sensitivity, marked exercise intolerance and an exaggerated ventilatory response to exercise. The purpose of this study was to determine the effect of CC inhibition on exercise cardiovascular and ventilatory function, and exercise tolerance in health and CHF.MethodsTwelve clinically stable, optimally treated patients with CHF (mean ejection fraction: 43 ± 2.5%) and 12 age- and sex-matched healthy controls were recruited. Participants completed two time-to-symptom-limitation (TLIM) constant load cycling exercise tests at 75% peak power output with either intravenous saline or low-dose dopamine (2 μg⋅kg–1⋅min–1; order randomized). Ventilation was measured using expired gas data and operating lung volume data were determined during exercise by inspiratory capacity maneuvers. Cardiac output was estimated using impedance cardiography, and vascular conductance was calculated as cardiac output/mean arterial pressure.ResultsThere was no change in TLIM in either group with dopamine (CHF: saline 13.1 ± 2.4 vs. dopamine 13.5 ± 1.6 min, p = 0.78; Control: saline 10.3 ± 1.2 vs. dopamine 11.5 ± 1.3 min, p = 0.16). In CHF patients, dopamine increased cardiac output (p = 0.03), vascular conductance (p = 0.01) and oxygen delivery (p = 0.04) at TLIM, while ventilatory parameters were unaffected (p = 0.76). In controls, dopamine improved vascular conductance at TLIM (p = 0.03), but no other effects were observed.ConclusionOur findings suggest that the CC contributes to cardiovascular regulation during full-body exercise in patients with CHF, however, CC inhibition does not improve exercise tolerance.

Absence of dynamic hyperinflation during exhaustive exercise in severe COPD reflects submaximal IC maneuvers rather than a nonhyperinflator phenotype.

Approximately 20% of chronic obstructive pulmonary disease (COPD) patients have been considered to have a "nonhyperinflator phenotype." However, this judgment depends on patients making a fully maximal inspiratory capacity (IC) maneuver at rest, since the IC during exercise is compared with this baseline measurement. We hypothesized that IC maneuvers at rest are sometimes submaximal and tested this hypothesis by measuring IC and associated neural respiratory drive at rest and during inhalation of CO2 and exercise in patients with COPD. Twenty-six COPD patients [age 66 ± 6 yr, mean forced expiratory volume in 1 s (FEV1) 40 ± 11% predicted] and 39 healthy subjects (age 39 ± 14 yr, FEV1 98 ± 12% predicted) were studied. IC and the diaphragm electromyogram (EMGdi) associated with it (EMGdi-IC) and forced inspiratory vital capacity (FIVC) and its corresponding EMGdi (EMGdi-FIVC) were measured during inhalation of 8% CO2 (8% CO2-92% O2) and room air. Incremental exhaustive cycle ergometer exercise was also performed in both patients with COPD and healthy subjects. IC, EMGdi-IC, FIVC, and EMGdi-FIVC during breathing 8% CO2 were significantly greater than those during breathing room air in both patients with COPD and healthy subjects (all P < 0.001). EMGdi-IC in patients with COPD constantly increased during exercise from 145 ± 40 µV at rest to 185 ± 52 µV at the end of exercise but change in IC was variable. Neural respiratory drive and its relevant IC increased during hypercapnia. Exercise-related hypercapnia in patients with COPD raises neural respiratory drives, which compensate for IC reduction, leading to underestimation of dynamic hyperinflation measured by IC at rest breathing room air.NEW & NOTEWORTHY Inspiratory capacity measured during hypercapnia is higher than that during eucapnia. Thus total lung capacity is not always be achieved by a standard inspiratory capacity maneuver, leading to risk of underestimation of dynamic hyperinflation in patients with severe chronic obstructive pulmonary disease after exhaustive exercise.

The effect of carotid chemoreceptor inhibition on exercise tolerance in chronic obstructive pulmonary disease: A randomized-controlled crossover trial.

Patients with chronic obstructive pulmonary disease (COPD) have an exaggerated ventilatory response to exercise, contributing to exertional dyspnea and exercise intolerance. We recently demonstrated enhanced activity and sensitivity of the carotid chemoreceptor (CC) in COPD which may alter ventilatory and cardiovascular regulation and negatively affect exercise tolerance. We sought to determine whether CC inhibition improves ventilatory and cardiovascular regulation, dyspnea and exercise tolerance in COPD. Twelve mild-moderate COPD patients (FEV1 83 ± 15 %predicted) and twelve age- and sex-matched healthy controls completed two time-to-symptom limitation (TLIM) constant load exercise tests at 75% peak power output with either intravenous saline or low-dose dopamine (2 μg·kg-1·min-1, order randomized) to inhibit the CC. Ventilatory responses were evaluated using expired gas data and dyspnea was evaluated using a modified Borg scale. Inspiratory capacity maneuvers were performed to determine operating lung volumes. Cardiac output was estimated using impedance cardiography and vascular conductance was calculated as cardiac output/mean arterial pressure (MAP). At a standardized exercise time of 4-min and at TLIM; ventilation, operating volumes and dyspnea were unaffected by dopamine in COPD patients and controls. In COPD, dopamine decreased MAP and increased vascular conductance at all time points. In controls, dopamine increased vascular conductance at TLIM, while MAP was unaffected. There was no change in time to exhaustion in either group with dopamine. These data suggest that the CC plays a role in cardiovascular regulation during exercise in COPD; however, ventilation, dyspnea and exercise tolerance were unaffected by CC inhibition in COPD patients.

Tidal Flow-Volume Loop Enveloping at Rest in Advanced COPD.

Expiratory flow limitation (EFL) is a key physiological abnormality in COPD. Comparing tidal-to-maximum flow-volume (F-V) loops is a simple and widely available method to assess EFL in patients with COPD. We aimed to investigate whether subjects with COPD showing significant resting tidal F-V enveloping (ie, > 50% tidal volume) would present with higher exertional operating lung volumes, which would lead to greater burden of dyspnea and poorer exercise tolerance compared to their counterparts. 37 subjects with COPD (21 males; 63.1 ± 9.2 years old; FEV1 = 37 ± 12% predicted) and 9 paired controls (3 males; 55.9 ± 11.7 y old) performed an incremental cardiopulmonary exercise testing on a cycle ergometer. Dyspnea perception, inspiratory capacity maneuvers after 3-4 sequential tidal F-V loops, and esophageal and gastric pressures were measured during exercise. Most subjects (31 of 37, 84%) presented with significant tidal F-V enveloping. Critical inspiratory constraints and upward dyspnea inflection points (as a function of both work rate and ventilation) were reached earlier in these subjects, thereby leading to poorer exercise tolerance compared to their counterparts (P = .01). Abdominal muscle recruitment (ie, increase in gastric pressure ≥ 15%) during tidal expiration was significantly higher in the EFL+ group. However, this did not bear an influence on the operating lung volumes, inspiratory constraints, dyspnea, cardiocirculatory responses, or exercise tolerance (P > .05). Tidal F-V loop enveloping at rest should be valued as it is related to relevant clinical outcomes, such as dyspnea burden and exercise tolerance in subjects with COPD.

Impaired central hemodynamics in chronic obstructive pulmonary disease during submaximal exercise.

It is unknown whether central hemodynamics are impaired during exercise in chronic obstructive pulmonary disease (COPD) patients. We hypothesized that, at a similar absolute V̇o2 during exercise, COPD patients would have a lower stroke volume and cardiac output compared with healthy controls. Furthermore, we hypothesized that greater static hyperinflation [ratio of inspiratory capacity to total lung capacity (IC/TLC)] and expiratory intrathoracic pressure would be significantly related to the lower cardiac output and stroke volume responses in COPD patients. Clinically stable COPD (n = 13; FEV1/FVC: 52 ± 13%) and controls (n = 10) performed constant workload submaximal exercise at an absolute V̇o2 of ~1.3 L/min. During exercise, inspiratory capacity maneuvers were performed to determine operating lung volumes and cardiac output (via open-circuit acetylene rebreathe technique) and esophageal pressure were measured. At similar absolute V̇o2 during exercise (P = 0.81), COPD had lower cardiac output than controls (COPD: 11.0 ± 1.6 vs. control: 12.2 ± 1.2 L/min, P = 0.03) due to a lower stroke volume (COPD: 107 ± 13 vs. control: 119 ± 19 mL, P = 0.04). The heart rate response during exercise was not different between groups (P = 0.66). FEV1 (%predicted) and IC/TLC were positively related to stroke volume (r = 0.68, P = 0.01 and r = 0.77, P < 0.01). Last, esophageal pressure-time integral during inspiration was positively related to cardiac output (r = 0.56, P = 0.047). These data demonstrate that COPD patients have attenuated cardiac output and stroke volume responses during exercise compared with control. Furthermore, these data suggest that the COPD patients with the most severe hyperinflation and more negative inspiratory intrathoracic pressures have the most impaired central hemodynamic responses.NEW & NOTEWORTHY Chronic obstructive pulmonary disease leads to cardiac structural changes and pulmonary derangements that impact the integrative response to exercise. However, it is unknown whether these pathophysiological alterations influence the cardiac response during exercise. Herein, we demonstrate that COPD patients exhibit impaired central hemodynamics during exercise that are worsened with greater hyperinflation.

Mechanical Unloading of the Respiratory System during 5km Cycling Time Trials in Hypoxia

In trained endurance athletes, the ability to defend arterial oxy-hemoglobin saturation (SaO2) during high intensity constant-workload exercise in moderate hypoxia depends in part on the ability to increase minute ventilation (V̇E). Previous data have shown, however, that despite the existence of a substantial amount of ventilatory reserve (V̇Eres) in some cyclists, V̇E surprisingly does not increase during 5km time trials (5kTT) in hypoxia, despite a significant decrease in both SaO2 and mean power output (PTT) from normoxia. PURPOSE: To determine the effect of reducing the work of breathing (Wb) on V̇E, breathlessness (RPB), and PTT during a 5kTT in hypoxia in highly trained cyclists. We hypothesized no change in RPB, while V̇E would increase with an attenuated decrement in SaO2 and PTT from normoxia. METHODS: Fourteen trained male cyclists (V̇O2max = 58.7 ± 4.7 ml·kg-1·min-1) performed a 5kTT under 3 conditions at sea level: ‘CON’ (FiO2 = 0.21), ‘HYP’ (FiO2 = 0.16), and ‘HYP+He’ (FiO2 = 0.16, with balance helium). Esophageal balloons were used to assess Wb in each condition. Inspiratory capacity maneuvers were performed at each km, and flow-volume loop analyses were used to assess the %EFL and V̇Eres. The modified Borg scale (0-10) was used to assess RPB at each km. RESULTS: Wb decreased from HYP to HYP+He by 30 ± 18% (p < 0.01). Despite a substantial V̇Eres throughout CON (52 ± 44 L·min-1), V̇E was not different between CON (117.4 ± 17.9 L·min-1) and HYP (124.8 ± 17.9 L·min-1) but increased during HYP+He (139.5 ± 22.0 L·min-1; p < 0.05). While SaO2 decreased from CON to HYP by 10 ± 1% (p < 0.01), SaO2 increased by 4 ± 1% from HYP to HYP+He (p < 0.01). PTT decreased from CON to HYP (-14.2%; p < 0.01) and increased from HYP to HYP+He (+5.5%; p < 0.01). When comparing HYP to HYP+He, a significant correlation was observed between ΔSaO2 and ΔPTT (r = 0.69; p < 0.05). RPB increased from CON (6.0 ± 2.0) to HYP (7.0 ± 2.0; p < 0.05) and was unchanged from HYP to HYP+He (6.6 ± 2.0). CONCLUSIONS: In moderate hypoxia, a low ventilatory reserve does not limit 5km time trial performance, where by design, individuals are free to adjust power output. The ability to utilize ventilatory reserve while remaining below a critical threshold of perceived breathlessness appears conducive to maintaining aerobic exercise performance in moderate hypoxia.

Dysanapsis Ratio as a Predictor of Expiratory Flow Limitation in Endurance Trained Athletes

PURPOSE: To investigate whether the dysanapsis ratio (DR) predicts expiratory flow limitation in highly trained athletes, as has been shown in healthy, active men and women. METHODS: Data from 124 highly trained men (age 21.9 ± 3.6 yrs) who performed maximal incremental tests to exhaustion were analyzed. The maximum expiratory flow-volume curve, along with inspiratory capacity maneuvers, were used to determine lung volumes, determine expiratory flows, and to quantify flow limitation. The subjects were partitioned into ‘flow-limited’ (EFL) and ‘non flow-limited’ (NEFL) groups, where tidal vs. maximal flow-volume overlap >5% qualifies as EFL. Group differences were evaluated using independent T-tests, while logistic regression was used to assess the predictive ability of DR, forced vital capacity (FVC), and V̇O2max on EFL. RESULTS: 63% of subjects (n = 78) displayed EFL with an average severity of 43.3 ± 21.0 %. EFL showed significantly lower FEV1 (4.5 ± 0.6 vs. 4.9 ± 0.6 L, p < .001), FEV1/FVC (86.3 ± 7.8 vs. 91.3 ± 5.7 %, p < .001), and FEF50 (6.1 ± 2.0 vs.7.6 ± 1.4 L·s-1, p < .001). However, no significant differences were found in FVC (5.2 ± 0.7 vs. 5.3 ± 0.8 L, p = .191) between groups. EFL showed a significantly smaller DR (0.2 ± 0.1 vs. 0.3 ± 0.1, p = .001) compared to NEFL. There were no differences between EFL and NEFL at peak exercise with respect to VO2max (67.1 ± 8.1 vs. 65.4 ± 4.5 ml·min-1·kg-1, p = .246), VE (155.9 ± 26.0 vs. 158.6 ± 26.6 L·min-1, p = .59), or frequency of breathing (56.8 ± 8.6 vs. 55.4 ± 10.3 br·min-1, p = .42). A significant predictive relationship was observed between DR on EFL (Odds Ratio (OR): 0.55, 95% CI 0.36 to 0.81, p < .01). A multivariate analysis indicated that DR (OR 0.35, 95% CI 0.21 to 0.58, p < .001), FVC (OR 0.49, 95% CI 0.31 to 0.78, p = .003), and V̇O2max (OR 1.63, 95% CI 1.05 to 2.53, p = .028) were significant predictors of EFL. CONCLUSIONS: Consistent with previous findings in active subjects, an increase in DR or FVC significantly decreases the likelihood of EFL in highly trained athletes. However, results from this analysis show that when controlling for DR and FVC, an increase in V̇O2max significantly increases the likelihood of EFL. This relationship was previously found to be non-significant in healthy active individuals and may highlight potential differences that exist within endurance trained populations.

Ventilatory responses in males and females during graded exercise with and without thoracic load carriage.

To compare the effects of thoracic load carriage on the ventilatory and perceptual responses to graded exercise, 14 pairs of height-matched, physically active males and females completed randomly ordered modified Balke treadmill exercise tests with and without a correctly sized and fitted 20.4kg backpack and work clothing. Subjects walked at 1.56m.s- 1 while grade was increased by 2% every 2min until exhaustion. Ventilatory responses were measured with open circuit spirometry and perceptual responses were evaluated using the modified Borg scale. Inspiratory capacity maneuvers were performed to calculate operating lung volumes. Despite height matching, males had significantly greater lung volumes and peak oxygen uptake ([Formula: see text]O2peak). Peak [Formula: see text]O2 and ventilation ([Formula: see text]E) were lower (p < 0.05) for all subjects under load. Throughout exercise, the ventilatory equivalents for [Formula: see text]O2 and carbon dioxide production were significantly higher in females, independent of condition. At similar relative submaximal intensities (%[Formula: see text]O2peak), there was no difference in [Formula: see text]E between conditions in either group, however, all subjects adopted a rapid and shallow breathing pattern under load with decreased tidal volume secondary to lower end-inspiratory lung volume. The relative changes in breathing pattern and operating lung volume between unloaded and loaded conditions were similar between males and females. Females reported significantly higher dyspnea ratings for a given [Formula: see text]E compared to males; however, the relationship between dyspnea and [Formula: see text]E was unaffected by load carriage. The relative response patterns for ventilatory and perceptual responses to graded exercise with thoracic loading were similar in males and females.

Low exertional inspiratory capacity is not related to dynamic inspiratory muscle weakness in heart failure

Reduction in inspiratory capacity (IC) during exercise has been reported in chronic heart failure (CHF). Since inspiratory muscle dysfunction may be present to a variable degree, the assumption that IC reduction during exercise represents an increase in end-expiratory lung volume must be made with caution. This interpretation is flawed if patients develop dynamic inspiratory muscle strength reduction, i.e., progressively lower esophageal (Pes) pressures as the IC maneuvers are repeated. Sixteen CHF patients and 9 age-matched controls performed an incremental exercise test with serial IC and respiratory pressure measurements. Regardless whether IC decreased or not with exercise (N = 4 and N = 12, respectively), Pes,IC remained stable. This was confirmed by similar Pes,sniff immediately upon exercise cessation (p > .05). No association was found between changes in IC and related Pes from rest to peak exercise. Owing to the lack of dynamic inspiratory muscle weakness, non-invasive indexes of lung mechanics can be reliably obtained from exercise IC in CHF.

How do the Carotid Chemoreceptors Modulate Ventilatory Control and Cardiovascular Regulation at Rest and During Exercise in COPD?

RATIONALEWe have recently demonstrated elevated activity and sensitivity of the carotid chemoreceptor (CC) in COPD, which may alter ventilatory and cardiovascular regulation at rest and during exercise. Accordingly, we sought to examine whether CC inhibition modifies ventilation and cardiovascular regulation at rest and during exercise in COPD.METHODSIn a randomized double blind crossover study, thirteen COPD patients (FEV1 predicted ± SD: 82 ± 19%) and thirteen healthy controls completed resting cardiovascular function measurements while receiving either intravenous (I.V.) saline or I.V. dopamine (2 mg/kg/min) while inspiring either room air or 100% O2 (order randomized). Participants then completed two time to symptom limitation constant load exercise tests at 75% peak power output, on separate days, while receiving either I.V. saline or dopamine (order randomized). At rest, arterial stiffness was determined by pulse‐wave velocity (PWV) and muscle sympathetic nerve activity (MSNA) was measured by microneurography. Ventilatory responses were evaluated using expired gas data and cardiac output (impedance cardiography) was collected to calculate vascular conductance (cardiac output/mean arterial pressure (MAP)). Exertional dyspnea was evaluated using a modified Borg scale and inspiratory capacity maneuvers were performed to determine operating lung volumes.RESULTSAt rest, CC inhibition with dopamine decreased central and peripheral PWV, ventilation and MAP (p&lt;0.05) while increasing vascular conductance in COPD. No change in CV function was observed with dopamine in controls. CC inhibition with hyperoxia decreased peripheral PWV and MSNA (p&lt;0.05) in COPD, while no change was observed in controls. At a standardized exercise time (isotime) of 4 minutes and at symptom limitation, minute ventilation was not different between saline and dopamine conditions in COPD or controls. Operating lung volumes and exertional dyspnea were not different between conditions within either group. Vascular conductance was increased (p&lt;0.05) during exercise with dopamine in COPD, secondary to reduced MAP, while no change was observed in controls. There was no change in time‐to‐exhaustion in either group with dopamine.CONCLUSIONResults from the current study suggest that the CC plays a role in cardiovascular regulation at rest and during exercise in COPD; however, exercise ventilation, dyspnea and exercise tolerance were unaffected by CC inhibition in COPD patients. Interventions aimed at chronically reducing CC activity may be beneficial to reduce cardiovascular risk in COPD.Support or Funding InformationLung Association of Alberta/NWTCanadian Institute of Health ResearchThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Imposed expiratory resistance, hyperinflation, and dyspnea are dissociated from locomotor fatigue during moderate exercise

Expiratory flow resistance (e.g. asthma, chronic obstructive pulmonary disease) results in dyspnea, dynamic hyperinflation, and premature exercise intolerance during heavy intensity exercise. This cascade seems to be primarily precipitated by abnormal lung mechanics that result in exacerbated symptoms and reduced maximal evocable limb motor activity. We do not know whether this cascade behaves in the same way during moderate exercise where only modest locomotor fatigue is expected to develop.We hypothesized that expiratory flow resistance would result in dynamic hyperinflation, dyspnea, and exacerbated locomotor fatigue during moderate intensity exercise in a similar manner to that during heavy intensity exercise.Volunteers (N=10, 27±6 yr) completed constant power moderate exercise (50% peak ramp power) with 3 levels of imposed expiratory flow resistance (7, 9, 11 cm H2O·L·s−1) or control (no imposed flow resistance). We measured operating lung volumes during exercise with inspiratory capacity maneuvers. Participants reported dyspnea and leg effort using a Borg 10‐point scale. At the termination of exercise we used a rapid switch from hyperbolic to isokinetic cycling to measure the decline in peak isokinetic power (Piso).Decline in Piso was not different when expiratory flow resistance was imposed (p&gt;0.05). Inspiratory capacity was smaller at the end of exercise in the most severe resistance (11 cm H2O·L·s−1) as compared to control (2.31±1.52 vs. 3.15±0.71 L; p&lt;0.05). Similarly, inspiratory reserve volume was smaller at the end of exercise in the most severe resistance as compared to control (−0.07±1.28 vs. 0.82±0.43 L; p&lt;0.05). Dyspnea was greater at the end of exercise in both mild and severe resistance (7 and 11 cm H2O·L·s−1) as compared to control (5.7±2.5 and 5.2±1.9 vs. 3.7±1.6; p&lt;0.05). Piso was not related to inspiratory reserve volume, inspiratory capacity, or dyspnea (p&gt;0.05).Imposed severe expiratory flow resistance results in hyperinflation and exacerbated dyspnea in healthy volunteers. Unlike what we have found during heavy exercise, however, abnormal lung mechanics and dyspnea were not related to maximal locomotor power during moderate exercise.

Effect of pulmonary rehabilitation on tidal expiratory flow limitation at rest and during exercise in COPD patients

We hypothesized that severe COPD patients who present with the disadvantageous phenomenon of Expiratory Flow Limitation (EFL) may benefit as COPD patients without EFL do after implementation of a Pulmonary Rehabilitation (PR) program. Forty-two stable COPD patients were studied at rest and during exercise. EFL and dynamic hyperinflation (DH) were documented using the negative expiratory pressure (NEP) technique and inspiratory capacity (IC) maneuvers, respectively. Patient centered outcomes were evaluated by the Saint-George’s Respiratory Questionnaire (SGRQ) and the mMRC dyspnea scale. Before PR, 16 patients presented with EFL at rest and/or during exercise. After PR, EFL was abolished in 15 out of those 16 EFL patients who exhibited a significant increase in IC values. These were mainly accomplished through a modification of the breathing pattern. In the 26 NFL patients no increase was noted in their IC or a modification of their breathing pattern. However, both NFL and EFL COPD patients improved exercise capacity and patients centered outcomes undergoing the same PR program.