Cycling Efficiency Is Not Compromised for Moderate Exercise in Moderately Severe COPD

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease caused by inhalation of noxious particles, most commonly cigarette smoking. The consequent changes in airways, lung parenchyma and pulmonary vasculature lead to increased resistive, elastic and threshold loads and impaired capacity of the respiratory muscle pump. COPD is characterized by progressive expiratory flow limitation. During exercise, increases in respiratory rate lead to shortening of expiratory time with consequent gas trapping. The resultant increase in end-expiratory lung volume is referred to as dynamic hyperinflation. Dynamic hyperinflation leads to further load-capacity imbalance with consequent increased neural respiratory drive to maintain ventilatory homeostasis, which is closely related to exertional breathlessness intensity. Neuromechanical dissociation, resulting in uncoupling of increased neural respiratory drive from ventilatory output, develops due to mechanical limitations on tidal volume expansion and reduced force-generating capacity of the diaphragm as dynamic hyperinflation progresses during exercise. This review provides an overview of methods of measuring dynamic hyperinflation in COPD and clinical interventions that aim to alleviate lung hyperinflation and improve exercise tolerance.

Patients with severe chronic obstructive pulmonary disease (COPD) develop dynamic lung hyperinflation (DH) during symptom-limited incremental and constant work exercise with cycle ergometer and treadmill. The increase in end-expiratory lung volume seems to be the best predictor of dyspnea. Quantification of DH is based on the relatively complex use of on-line measurement of inspiratory capacity (IC) from flow volume loops. We reasoned that DH could occur during daily activities such as walking, and that it could be simply measured using the spirometrically determined IC. We studied 72 men with COPD (FEV(1) = 45 +/- 13.3% predicted). IC was measured at rest and after a 6-min walk test. Exertional dyspnea was evaluated using the Borg scale and dyspnea during daily activities with the modified Medical Research Council (MRC) scale. IC decreased significantly from 28.9 +/- 6.7% TLC at rest to 24.1 +/- 6.8% TLC after exercise (p < 0.001). Exertional dyspnea correlated with DeltaIC (r = -0.49, p < 0.00001) and baseline MRC (r = 0.59, p < 0.00001). In many patients with COPD, walking leads to DH that can be easily determined with simple spirometric testing. DH helps explain exercise capacity limitation and breathlessness during simple daily activities.

<b>Background:</b> At the end of maximal exertion, the heart rate recovery (HRR) delay is a marker of the cardiac autonomic dysfunction and has been proposed as a powerful predictor of mortality. However, little is known about determinants of HRR delay in chronic obstructive pulmonary disease (COPD) patients. <b>Objective:</b> To assess HRR delay and its determinants in a cohort of COPD patients. <b>Methods:</b> We prospectively enrolled COPD outpatients. Anthropometric characteristics, lung function and cardiopulmonary exercise test data were recorded. A cut-off of HRR ≤ 12 beats was used to define HRR delay. <b>Results:</b> Of 195 patients enrolled, 105 (52%) showed HRR delay. As compared to patients without HRR delay, patients with delay were older, with a greater degree of dyspnoea (modified Medical Research Council score) and lower values of forced expiratory volume at the 1st second-FEV1 % pred., diffusion capacity for carbon monoxide-TLCO, inspiratory capacity (IC) % pred., and IC/TLC (total lung capacity) ratio. Moreover, patients with HRR delay had lower values of peak oxygen uptake, peak workload, energy expenditure (METs), oxygen uptake efficiency slope-OUES and higher value of the change of IC from rest to peak of exercise (Δ rest-to-peak IC, in L). In the multivariate regression model adjusted for age, sex, FEV1, body mass, peak oxygen uptake and use of β-blockers, we found that Δ rest-to-peak IC (Odds Ratio-OR 5.35; 95% CI 1.35 to 21.29; p=0.017) and IC % pred. (OR 0.967; 95% CI 0.938 to 0.997; p=0.032) predict the risk to have a HRR delay. <b>Conclusions:</b> In COPD outpatients, variables related to static (IC % pred.) and dynamic hyperinflation (Δ rest-to-peak IC) are determinant factors of HRR delay after maximal exercise.

Inspiratory capacity (IC) is widely used to assess dynamic hyperinflation in patients with chronic obstructive pulmonary disease (COPD) based on the assumption that this maneuver maximally activates inspiratory muscle and thus reliably achieves total lung capacity (TLC). However, inspiration during inflation is partially or wholly controlled by involuntary drive from brainstem and whereas the IC is derived from voluntary drive from the motor cortex. We hypothesized that voluntary IC maneuvers initiated from the motor cortex may be increased if there is additional chemical stimulation to the brainstem by hypercapnia. Nineteen healthy subjects (Age 43±15 years, 13 men/6 women) were studied. Diaphragm EMG (EMGdi) from multipair esophageal electrode and ventilation were recorded during inhalation 8%CO 2 (8%CO 2 +92%O 2 ) and room air. The order of inhalation of gases was random and was blind to subjects. Forced inspiratory vital capacity (FIVC) from residual volume and IC were performed. The EMGdi and FIVC elicited by a FIVC maneuver breathing 8%CO 2 were 169±61 µV and 4.92±1.00 l and were significantly greater than those breathing room air (143±47 µV, 4.3±0.89 l, p 2 were 172±55 µV and 3.28±0.66 L and were significantly greater than those during breathing room air (148±42 µV, 2.83±0.72 l, p We concluded that IC and diaphragm EMG generated by IC maneuver is submaximal at normacapnia. Therefore dynamic hyperinflation assessed by IC maneuver could have been underestimated in patients with COPD if they became hypercapnic. This study was supported by NSFC (No.81120108001).

Hyperoxia and normoxic helium independently reduce dynamic hyperinflation and improve the exercise tolerance of patients with chronic obstructive pulmonary disease (COPD). Combining these gases could have an additive effect on dynamic hyperinflation and a greater impact on respiratory mechanics and exercise tolerance. To investigate whether helium-hyperoxia improves the exercise tolerance and respiratory mechanics of patients with COPD. Ten males with COPD (FEV(1) = 47 +/- 17%pred [mean +/- SD]) performed randomized constant-load cycling at 60% of maximal work rate breathing air, hyperoxia (40% O(2), 60% N(2)), normoxic helium (21% O(2), 79% He), or helium-hyperoxia (40% O(2), 60% He). Exercise time, inspiratory capacity (IC), work of breathing, and exertional symptoms were measured with each gas. Compared with air (9.4 +/- 5.2 min), exercise time was increased with hyperoxia (17.8 +/- 5.8 min) and normoxic helium (16.7 +/- 9.1 min) but the improvement with helium-hyperoxia (26.3 +/- 10.6 min) was greater than both these gases (p = 0.019 and p = 0.007, respectively). At an isotime during exercise, all three gases reduced dyspnea and both helium mixtures increased IC and tidal volume. Only helium-hyperoxia significantly reduced the resistive work of breathing (15.8 +/- 4.2 vs. 10.1 +/- 4.1 L . cm H(2)O(-1)) and the work to overcome intrinsic positive end-expiratory pressure (7.7 +/- 1.9 vs. 3.6 +/- 2.1 L . cm H(2)O(-1)). At symptom limitation, tidal volume remained augmented with both helium mixtures, but IC and the work of breathing were unchanged compared with air. Combining helium and hyperoxia delays dynamic hyperinflation and improves respiratory mechanics, which translates into added improvements in exercise tolerance for patients with COPD.

ABSTRACTBackgroundAirflow limitation frequently leads to the interruption of activities of dailyliving (ADL) in patients with Chronic Obstructive Pulmonary Disease (COPD). Thesepatients commonly show absence of ventilatory reserve, reduced inspiratory reservevolume, and dynamic hyperinflation (DH).ObjectiveTo investigate ventilatory response and DH induced by three ADL-based protocols inCOPD patients and compare them to healthy subjects.MethodCross-sectional study. COPD group: 23 patients (65±6 years, FEV137.2±15.4%pred); control group: 14 healthy subjects (64±4 years) matched for age,sex, and body mass index. Both groups performed all three tests: Glittre-ADL test;an activity test that involved moving objects on a shelf (TSHELF); anda modified shelf protocol isolating activity with upper limbs(TSHELF-M). Ventilatory response and inspiratory capacity wereevaluated.ResultsBaseline ventilatory variables were similar between groups (p>0.05). Theventilatory demand increased and the inspiratory capacity decreased significantlyat the end of the tests in the COPD group. Ventilatory demand and DH were higher(p<0.05) in the TSHELF than in the TSHELF–M in the COPDgroup (p<0.05). There were no differences in DH between the three tests in thecontrol group (p>0.05) and ventilatory demand increased at the end of the tests(p<0.05) but to a lower extent than the COPD group.ConclusionThe TSHELF induces similar ventilatory responses to the Glittre-ADLtest in COPD patients with higher ventilatory demand and DH. In contrast, theventilatory response was attenuated in the TSHELF-M, suggesting thatsquatting and bending down during the Glittre-ADL test could trigger significantventilatory overload.

Dynamic pulmonary hyperinflation and abnormal air exchange are the primary causes of the exercise limitation of chronic obstructive pulmonary disease (COPD) patients. During exercise, COPD sufferers' lungs are dynamically hyperinflated. Increased inefficient ventilation reduces ventilation efficiency and causes a mismatch between ventilation volume and blood flow. The ventilatory equivalent for CO2 (VeqCO2) is a physiological parameter that can be measured using cardiopulmonary exercise testing. Therefore, the aim of this exploratory study was to perform cardiopulmonary exercise testing on people with COPD, investigate the impact of static pulmonary function on ventilation efficiency under the exercise state, and screen the predictive indicators of ventilation efficiency. Subject. The aim of this study was to look at the factors that influence the exercise ventilation efficiency of people with COPD. Method. A total of 76 people with COPD were recruited during the stable period. Age, gender, body height, body mass, and other basic information were recorded. The body mass index (BMI) was determined, and forced vital capacity (FVC), forced expiratory volume in one second (FEV1), residual volume/total lung capacity (RV/TLC), diffusing capacity of the lung for carbon monoxide (DLCO), and DLCO divided by the alveolar volume (DLCO/VA) were measured. The ventilatory equivalent for carbon dioxide (VE/VCO2) under the rest state (EqCO2rest), anaerobic threshold (EqCO2at), and maximum exercise state (EqCO2 max) were calculated to investigate the influencing factors for ventilation efficiency of people with COPD. Results. FEV1% was negatively correlated with EqCO2rest (r = −0.277, P value <0.05); FEV1/FVC % was negatively correlated with EqCO2rest and EqCO2at (r = −0.311, −0.287, P value <0.05); DLCO% was negatively correlated with EqCO2rest, EqCO2at, and EqCO2max (r = −0.408, −0.462, and −0.285, P value <0.05); DLCO/VA% was negatively correlated with EqCO2rest, EqCO2at, and EqCO2max (r = −0.390, −0.392, and −0.245, P value <0.05); RV/TLC was positively correlated with EqCO2rest and EqCO2at (r = 0.289, 0.258, P-value <0.05). The prediction equation from the multivariable regression analysis equation was Y = 40.04–0.075X (Y = EqCO2, X = DLCO/VA%). Conclusions. As the degree of ventilatory obstruction increased, the ventilation efficiency of the stable people with COPD under the exercise state showed a progressive decrease; the ventilation efficiency of the people with COPD decreased significantly under the maximum exercise state, and the ventilation capacity and diffusion capacity were the significant factors that affected the exercise ventilation efficiency. The diffusion function may predict the maximum ventilation efficiency and enable primary hospitals without exercise test equipment in developing countries to predict and screen patients at risk for current exercise based on limited information.

Introductionβ Blockers are important treatment for ischaemic heart disease and heart failure; however, there has long been concern about their use in people with chronic obstructive pulmonary disease (COPD) due...

Determining the Role of Dynamic Hyperinflation in Patients with Severe Chronic Obstructive Pulmonary Disease

Dynamic hyperinflation has important clinical consequences in patients with chronic obstructive pulmonary disease (COPD). Given that most of these patients have respiratory and peripheral muscle weakness, dyspnea and functional exercise capacity may improve as a result of inspiratory muscle training (IMT). The aim of the study was to analyze the effects of IMT on exercise capacity, dyspnea, and inspiratory fraction (IF) during exercise in patients with COPD. Daily inspiratory muscle strength and endurance training was performed for 8 weeks in 10 patients with COPD GOLD II and III. Ten patients with COPD II and III served as a control group. Maximal inspiratory pressure (Pimax) and endurance time during resistive breathing maneuvers (tlim) served as parameter for inspiratory muscle capacity. Before and after training, the patients performed an incremental symptom limited exercise test to maximum and a constant load test on a cycle ergometer at 75% of the peak work rate obtained in the pretraining incremental test. ET was defined as the duration of loaded pedaling. Following IMT, there was a statistically significant increase in inspiratory muscle performance of the Pimax from 7.75 ± 0.47 to 9.15 ± 0.73 kPa (P < 0.01) and of tlim from 348 ± 54 to 467 ± 58 seconds (P < 0.01). A significant increase in IF, indicating decreased dynamic hyperinflation, was observed during both exercise tests. Further, the ratio of breathing frequency to minute ventilation (bf/V′E) decreased significantly, indicating an improved breathing pattern. A significant decrease in perception of dyspnea was also measured. Peak work rate during the incremental cycle ergometer test remained constant, while ET during the constant load test increased significantly from 597.1 ± 80.8 seconds at baseline to 733.6 ± 74.3 seconds (P < 0.01). No significant changes during either exercise tests were measured in the control group. The present study found that in patients with COPD, IMT results in improvement in performance, exercise capacity, sensation of dyspnea, and improvement in the IF prognostic factor.

Is the Metronome-Paced Tachypnea Test (MPT) Ready for Clinical Use? Accuracy of the MPT in a Prospective and Clinical Study

Chronic obstructive pulmonary disease (COPD) is a severe respiratory disorder responsible for a significant morbidity and mortality in western societies. In the vast majority of patients, COPD is caused by tobacco smoke. Contributing factors leading to airway obstruction and lung hyperinflation in COPD differ from those observed in asthma, with a major role of hypersecretion and peripheral airway obstruction due to increased cholinergic airway smooth muscle tone. Therefore, anticholinergics are considered the firstline therapy to improve airway obstruction in COPD. In addition to effects on lung function, anticholinergics may also improve exercise tolerance, quality of life and sleep quality in these patients. When compared with other classes of bronchodilators, anticholinergics show an equal potency of bronchodilation, with a favorable safety profile. Due to their unique mechanism of action, anticholinergics can also be combined with different types of bronchodilators. Novel, long-acting anticholinergics may hold a future potential for further improvement of therapy in COPD, particularly in terms of user friendliness and compliance.

IntroductionLung hyperinflation in chronic obstructive pulmonary disease (COPD) is associated with activity limitation, impaired cardiac output, and mortality. Several studies have demonstrated that long-acting muscarinic antagonists (LAMAs) delivered by dry powder inhalers can promote lung deflation; however, the potential of nebulized LAMAs on improving hyperinflation in COPD is currently unknown.MethodsThis single-center, randomized, double-blind, two-way crossover study (NCT04155047) evaluated the efficacy of a single dose of nebulized LAMA [glycopyrrolate (GLY) 25 µg] versus placebo in patients with COPD and lung hyperinflation. Patients with moderate-to-severe COPD and a residual volume (RV) ≥ 130% of predicted normal were included. The primary endpoint was changed from baseline in RV at 6 h post-treatment. Other endpoints included changes from baseline in spirometric and plethysmographic measures up to 6 h post-treatment.ResultsA total of 22 patients (mean pre-bronchodilator RV, 153.7% of predicted normal) were included. The primary objective of the study was not met; the placebo-adjusted least squares (LS) mean [95% confidence interval (CI) change from baseline in RV with GLY at 6 h post-treatment was − 0.323 l (− 0.711 to 0.066); p = 0.0987]. A post hoc evaluation of the primary analysis was conducted after excluding a single statistical outlier; substantial improvements in RV with GLY compared with placebo was observed after exclusion of this outlier [placebo-adjusted LS mean change from baseline (95% CI) in RV was − 0.446 l (− 0.741 to − 0.150)]. Improvements from baseline were also observed with GLY compared with placebo in spirometric and plethysmographic measures up to 6 h post-treatment. GLY was generally safe, and no new safety signals were detected.ConclusionsThis is the first study to evaluate the effect of nebulized GLY on lung deflation. Nebulized GLY resulted in marked improvements in RV up to 6 h post-treatment, compared with placebo. Improvements were also observed with GLY in spirometric and plethysmographic parameters of lung function.Trial RegistrationClinicalTrials.gov identifier, NCT04155047.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41030-021-00166-5.

Dynamic hyperinflation and tolerance to interval exercise in patients with advanced COPD.

Fractionation of the serum proteins by filter-paper electrophoresis in 14 coal-miners who had the characteristic radiological opacities of rheumatoid pneumoconiosis but no evidence of rheumatoid arthritis showed a reduction in the mean level of albumin and increases in the alpha-2 and gamma-globulins compared with the values in non-arthritic miners with simple coal-workers' pneumoconiosis and in normal subjects. The changes were smaller than those found in miners with both rheumatoid arthritis and the radiological appearances of rheumatoid pneumoconiosis (Caplan's syndrome) and the mean levels did not differ significantly from those found in non-arthritic miners with progressive massive fibrosis. It is concluded that estimation of the serum protein fractions, unlike tests for rheumatoid factors, is unlikely to help in the differential diagnosis of unusual opacities seen on chest radiographs of miners without arthritis.