Exercise-induced dynamic hyperinflation in chronic obstructive pulmonary disease.

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.

Relationship Between Expiratory Muscle Dysfunction and Dynamic Hyperinflation in Advanced Chronic Obstructive Pulmonary Disease

The effects of training on dynamic hyperinflation in stable chronic obstructive pulmonary disease (COPD) were investigated by using a controlled study of 28 subjects with FEV(1) = 42.5 (8.3 SD)%pred and 20 matched controls [FEV(1) = 44.9 (10.4)%pred]. Training consisted of spending 45 min/day, 4 days/week on a cycle-ergometer for six weeks. Maximal inspiratory and expiratory pressures (MIP and MEP), lung volumes, and two constant-work-rate (CWR) exercise tests (low- and high-intensity) were performed. Significant (p < 0.0l) improvements in the training group were observed in MIP [+8 (12) cmH(2)O], MEP [+18 (20) cmH(2)O], and endurance to high-intensity CWR [+7(5) min], and there were significant decreases in respiratory rate and end-expiratory lung volume (EELV) during both exercise tests. At 5 min, EELV decreased 0.1(0.08) L and 0.31(0.13) L and at end of exercise, EELV decreased by 0.09(0.07) L and 0.15(0.11) L respectively, for the moderate- and high-intensity tests. Dyspnea also decreased significantly at both exercise intensities. No changes were observed in the control group. Increased endurance showed independent significant (p < 0.05) correlation with changes in EELV, leg fatigue, and MEP. EELV changes showed a significant negative correlation with resting inspiratory capacity. We conclude that exercise training has beneficial effects on respiratory pattern and dynamic hyperinflation that may partially explain the reduction in dyspnea and the improvement in exercise tolerance.

Dynamic hyperinflation loads the inspiratory muscles by increasing end-expiratory lung volume (EELV) and imposing intrinsic positive end-expiratory pressure (PEEPi), the latter behaving as an inspiratory threshold load (ITL). The major purpose of this study was to describe the independent effects of the imposed ITL and changes in operating lung volume on the perception of inspiratory difficulty. In eight healthy subjects, independent increases in EELV and ITL were induced by continuous positive airway pressure (CPAP) and external ITL applications, respectively; increase in both EELV and PEEPi (thus the imposed ITL) was induced by application of positive end-expiratory pressure (PEEP). The perceived inspiratory difficulty increased significantly when either EELV or ITL was increased, and was always greater during combined increase in EELV and the imposed ITL (during PEEP) than when either factor was increased independently, suggesting that the imposed ITL and EELV each contribute independently to inspiratory difficulty. Inspiratory difficulty of each subject under all conditions was then fitted into a step-forward multiple regression model. The imposed ITL was a significant contributor to inspiratory difficulty in all subjects and was the first parameter to be selected in six of the eight subjects. When the results of all the subjects were pooled, the imposed ITL alone explained 40% of variations in inspiratory difficulty. Adding the change in end-inspiratory lung volume (DeltaEILV) to the model explained an additional 24% of variations in inspiratory difficulty. The coefficients (slopes) of the imposed ITL and DeltaEILV were 0.21 +/- 0.02 cm H2O-1 and 0.051 +/- 0.006 %IC-1, respectively. It is concluded that under our experimental conditions, the imposed ITL is a better predictor for explaining the variability of the perceived inspiratory difficulty than the operating lung volume.

Hyperpnea and hyperinflation have been proposed as contributors to exaggerated energy demands in chronic obstructive pulmonary disease (COPD), yet there are incomplete data on exercise requirements. This study compared total-body energy demands of the internal (unloaded) and external work of cycling and delta mechanical efficiency in 40 patients (FEV1: 36+/-14% predicted) with COPD and 28 healthy age-matched controls while characterizing dynamic hyperinflation. Steady-state V O2 was obtained at rest, during unloaded and 20-W cycling, and at 20, 50, and 65% peak cycling power. Delta mechanical efficiency was calculated between constant-load cycling at 65 and 20% peak power. Dynamic hyperinflation was assessed from inspiratory capacity maneuvers. Oxygen demands (L.min) at rest, for internal work (0.47+/-0.14 vs 0.45+/-0.11) or external work at 20 W (0.62+/-0.20 vs 0.57+/-0.13), were not different between patients and controls, although ventilation was elevated in COPD. Cycling at 65% of peak power induced dynamic hyperinflation in COPD, which indices were not related to cycling efficiency. Delta efficiency (%) was not different between patients (26.3+/-8.1) and controls (24.8+/-4.0). Findings suggest that bioenergetics of submaximal cycling is not compromised in moderately severe COPD despite tachypnea and dynamic hyperinflation.

There are no reports concerning the regulation of end-expiratory lung volume (EELV) and flow-volume relationships during upper limb exercise in health and disease. We studied EELV during such exercise in 22 adults with cystic fibrosis (CF) and nine age-matched healthy control subjects. Subjects with CF were grouped according to the severity of their lung disease, as follows: mild = FEV1 > 80% predicted; moderate = FEV1 40 to 80% predicted, and severe = FEV1 < 40% predicted. EELV was calculated from measurements of inspiratory capacity (IC) made at each workload during an incremental arm and leg ergometer test to peak work capacity. In the control group, the decrease in EELV was significantly smaller for arm than for leg exercise at peak work (-0.13 L versus -0.53 L, p < 0.001) and for arm than for leg exercise at an equivalent submaximal ventilation (-0.13 L versus -0.46 L, p < 0.01). In the groups with moderate and severe CF, arm exercise resulted in an increase in EELV from resting levels (dynamic hyperinflation) that was not significantly different from the increase observed for leg exercise. For CF subjects there was a significant inverse relationship between FEV1 and changes in EELV from rest to peak arm exercise (r = -0.46, p < 0.05). In normal subjects, there was a difference in the EELV response for arm versus leg exercise. In CF subjects with airflow limitation, dynamic hyperinflation occurred with both forms of exercise.

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.

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.

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.

To examine the circulatory and respiratory effects of breathing pattern in patients with chronic obstructive pulmonary disease (COPD) and dynamic hyperinflation (DH) during controlled mechanical ventilation. Prospective, controlled, randomized, non-blinded study. Respiratory intensive care unit of a university hospital. Nine patients with acute respiratory failure and DH due to acute exacerbations of COPD. Keeping tidal volume and total breath duration (TTOT) constant, patients were ventilated at six different values of expiratory time (TE). TE changes were randomly induced by alterations of constant inspiratory flow (VI) and/or end-inspiratory pause (EIP). Patients were studied at three levels of VI(0.93 +/- 0.08, 0.72 +/- 0.06 and 0.55 +/- 0.04 l/s, mean +/- SE), with and without EIP (10% of TTOT). Lung volumes, airflows, airways pressures, oxygenation indices and dead space were measured. Alveolar pressure and airway resistance (Rmin), as well as the additional resistance (delta R) due to viscoelastic pressure dissipation and time-constant inequalities, were estimated by rapid airway occlusion during inflation. In seven out of nine patients, right-heart catheterization was performed and hemodynamic parameters were obtained at each value of TE. A significant decrease of intrinsic positive end-expiratory pressure (PEEPi), end-inspiratory static and mean (mPaw) airway pressures, end-expiratory lung volume above passive FRC (Vtrap), delta R and venous admixture and a significant increase of peak airway pressure, Rmin, stroke volume index and mixed venous PO2 (PvO2) were observed when VI increased. At each VI, the addition of EIP significantly decreased iso-volume expiratory flows and PvO2 and increased Vtrap and mPaw. We conclude that in mechanically ventilated patients with COPD, the pattern of lung inflation and TE alteration have a significant impact on respiratory system mechanics, gas exchange and hemodynamics. Addition of EIP in patients with COPD may be detrimental.

We hypothesized that patients with Cheyne-Stokes respiration exhibit periodic increases in end-expiratory lung volume, mediated by changes in breath components, postinspiratory inspiratory muscle activity, or both. Calibrated inductive plethysmography revealed that 12 of 12 patients with Cheyne-Stokes respiration experienced increases in end-expiratory volume during hyperpnea: maximum 412 +/- 112 (SE) ml (range 75-1,543 ml). Compared with quiet breathing, the breath with largest increase in end-expiratory volume had larger tidal volume (867 +/- 107 vs. 567 +/- 38 ml, p < 0.01) and shorter expiratory time (1.25 +/- 0.11 vs. 1.66 +/- 0.15 seconds, p < 0.05). During decrescendo, the breath with largest decrease in end-expiratory volume had smaller tidal volume (p < 0.01) and longer expiratory time (p < 0.01). Cross-correlation of time series revealed that end-expiratory volume was related to both breath components (p < 0.0001). Bipolar needle electrodes revealed that scalene muscle activity at end-expiration was 50.7 +/- 14.0% higher at highest increase in lung volume than during preceding apnea (p < 0.05). Time series for scalene activity and end-expiratory volume were cross-correlated (p < 0.008). Increase in tonic scalene activity at end-expiration, however, was equivalent during crescendo and decrescendo phases: 50.6 +/- 22.1 versus 42.0 +/- 12.9% (p = 0.48). In conclusion, patients with Cheyne-Stokes respiration exhibit fluctuations in end-expiratory lung volume, primarily because of alterations in tidal volume and expiratory time rather than postinspiratory inspiratory muscle activity.

The classification of chronic pulmonary obstructive disease (COPD) into clinical and pathophysiological subsets is not new, but increasing data is available on the relation of these different phenotypes to clinically meaningful outcomes. This review focuses on the “emphysema-hyperinflation” (EH) phenotype, which is characterised by a prominent loss of lung elastic recoil and hyperinflation burden that translates into marked exercise intolerance and a heightened sense of dyspnoea. Although no single genetic profile has been associated with the EH phenotype, recent data have shown that certain single nucleotide polymorphisms, such as DNAH5, appear to have an effect on the preferential development of hyperinflation in smokers. Static and dynamic hyperinflation are hallmarks of the EH phenotype, and abnormal increases in resting lung function indices such as total lung capacity (TLC), functional residual capacity (FRC) and inspiratory to TLC ratio (IC/TLC) seem more associated with the clinical EH phenotype than others markers of gas trapping. An increased level of dyspnoea on exertion and exercise intolerance are also characteristic of the EH presentation and are likely related in part to critical mechanical constraints imposed on tidal volume expansion in situations where ventilatory demands are increased, but also possibly on cardiac and hemodynamic anomalies related to emphysema and hyperinflation. Importantly, the clinical relevance of the EH phenotype is underlined by the finding that indices of hyperinflation such as IC/TLC and residual volume (RV) can be used as independent predictors of mortality in patients with COPD. Treatment of patients with the EH phenotype should primarily focus on smoking cessation and maximal bronchodilator therapy. New long-acting combined bronchodilators options provide clinicians with safe and effective ways to address the hyperinflation issue in this population. Pulmonary rehabilitation also has a positive impact on exercise tolerance, quality of life and hyperinflation, and should be routinely considered in patients with EH presentation that remain symptomatic despite optimal treatment, whereas as lung volume reduction techniques should be reserved for highly selected patients.

Introduction Chronic obstructive pulmonary disease (COPD) is a common worldwide problem associated with morbidity and mortality that, unlike other diseases, is increasing. Recently, COPD has become the third leading cause of death in the United States, an event that was not predicted to occur until the year 2020. Therapy for COPD focuses on smoking cessation, bronchodilators, oxygen therapy, pulmonary rehabilitation, lung volume reduction surgery (LVRS), transplantation and treatment of comorbidities. While many of these interventions may improve dyspnea and quality of life, only oxygen supplementation in those with hypoxemia at rest, smoking cessation and LVRS have been associated with improved mortality in COPD. This chapter will review the role of LVRS in the treatment of patients with advanced COPD, and also examine the current status of minimally invasive bronchoscopic techniques for lung reduction that are approved overseas but are currently under study in the United States. Rationale for lung reduction in COPD COPD is an inflammatory disease that leads to airflow obstruction secondary to a combination of airway disease and emphysema, primarily in the distal small airways of the lung. The small airways become narrowed due to airway inflammation, smooth muscle hypertrophy, peribronchial fibrosis and mucus plugging. In emphysema, the destruction of alveolar walls leads to a loss of tethering of distal small airways, predisposing the airway to expiratory collapse. Most individuals with COPD will have a mixture of small airways obstruction and emphysema, but some will have a predominance of one abnormality or the other. Lung emptying is determined by the expiratory time constant, which is the product of airway resistance and lung compliance. Because subjects with emphysema have both increased lung compliance and airways resistance, they have impaired lung emptying and are prone to hyperinflation. As emphysema progresses, total lung capacity (TLC) and residual volume (RV) both increase as a result of decreased lung compliance and unopposed chest wall recoil causing hyperinflation and gas trapping, respectively. During exertion, the respiratory rate increases, reducing the time available for lung emptying, and the end-expiratory lung volume (EELV) rises even further, leading to dynamic hyperinflation. Figure 8.1 demonstrates the rise in lung volumes that occurs during exercise in severe COPD. EELV rises during exercise, thereby limiting the normal increase in tidal volume that occurs during exercise.

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...

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.