Analysis of Influencing Factors for Exercise Ventilation Efficiency of COPD Patients.

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.

Anticholinergics aggravate the imbalance of the autonomic nervous system in stable chronic obstructive pulmonary disease.

BACKGROUND: Inhaled anticholinergics, recommended as first-line maintenance treatment for patients with moderate-to-severe chronic obstructive pulmonary disease (COPD), has been demonstrated to be associated with an increased risk of cardiovascular diseases. Nevertheless, why COPD patients using inhaled anticholinergics have this higher risk remains unknown. One of mechanisms may be an autonomic imbalance because anticholinergics yield reduced vagal nervous activity. To test our hypothesis, we studied heart rate recovery (HRR) after exercise, recognized as a marker of cardiac autonomic function, in COPD patients using and not using inhaled anticholinergics. METHODS: Sixty patients with COPD were involved in this study (mean FEV1 = 1.57 ± 0.42 L), including 24 patients who had received tiotropium for more than 1 year and 36 patients not using tiotropium as a control group. A maximal cardiopulmonary exercise test was performed. HRR was defined as the difference between peak exercise and at 1-min recovery heart rate. RESULTS: HRR was significantly lower in patients using tiotropium than in the controls (16 ± 6 vs 22 ± 8 beats/min, respectively, p < 0.05). Multivariate regression analysis revealed that tiotropium use and peak VCO2 were independent predictors of HRR in these COPD patients. CONCLUSIONS: These findings suggest that anticholinergics bronchodilators reduce HRR after exercise in COPD patients. This has the potential to aggravate autonomic nervous imbalance. Therefore, we recommend that COPD patients taking anticholinergic bronchodilators should be considered for monitoring of cardiac function and prescribers should be alert for cardiovascular events that may arise from autonomic nervous imbalance.

Cardiac Magnetic Resonance Imaging for Diagnosis of Cardiac Sarcoidosis: A Meta-Analysis.

Background: Cardiac magnetic resonance imaging (CMR) is an effective technique for the diagnosis of cardiac sarcoidosis (CS). The efficacy of CMR versus the Japanese Ministry of Health and Welfare (JMHW) guidelines considered as standard criterion for the diagnosis of CS remains to be elucidated. Methods: In this systematic review and meta-analysis, we aimed at assessing the diagnostic accuracy of CMR in cardiac sarcoidosis. We searched on PubMed from January 1, 1980, to March 28, 2018, on Embase from January 1, 1980, to March 29, 2018, and on the Cochrane Library from January 1, 1980, to April 1, 2018, using a strategy based on the search terms (sarcoidosis and magnetic resonance imaging) independently. We analyzed the data obtained with Revman 5.3 and Stata 14.0 software. Results: Eight studies with a total of 649 participants met the inclusion criteria, and data were extracted. CMR had an overall sensitivity of 0.93 (95% confidence interval (CI), 0.87-0.97) and specificity of 0.85 (95% CI, 0.68-0.94) for the diagnosis of cardiac sarcoidosis. The area under the summary receiver operating characteristic (SROC) curve was 0.95 (95% CI, 0.93-0.97). The subgroup analysis via public year showed that studies between 2011 and 2017 had an overall sensitivity of 0.95 (95% CI, 0.88-0.98) and specificity of 0.92 (95% CI, 0.49-0.99), with an area under the SROC curve being 0.96. Conclusions: The results of this meta-analysis suggest that CMR could be used for the diagnosis of cardiac sarcoidosis and screening of patients suspected of CS. With the improvement of the technique, the diagnostic accuracy of MRI has improved.

Translation of Exercise Test Response to Training Intensity Using the Count Scale.

BACKGROUND: Exercise testing is recommended before prescribing individualized exercise intensity. However, there are few data demonstrating how exercise test responses are translated into individualized training intensity using a simple method. We previously developed a simple method to rate dyspnea called the count scale, including the count scale number (CSN) and count scale time. The purpose of this study was to assess the CSN for translation of exercise test response to training intensity. METHODS: Twenty-eight subjects (22 men and 6 women) with COPD age 66.6 ± 8.22 y participated in 2 exercise sessions. During the first session, in which exercise was guided by the heart rate, the CSN and heart rate were obtained (ie, CSN1 and HR1) while the heart rate was increased by 20% compared with the resting heart rate. During the second session, exercise was guided by the CSN. When the CSN was close to the CSN1, the CSN and corresponding heart rate were recorded as CSN2 and HR2. Differences between CSN1 and CSN2 and between HR1 and HR2 were compared. The relationship between HR1 and HR2 was analyzed. Agreement between HR1 and HR2 was evaluated by Bland-Altman plots. RESULTS: No significant differences were seen between HR1 and HR2 (96 ± 11 and 97 ± 11, respectively; P = .14). A high correlation between HR1 and HR2 was found (r = 0.932, P < .001). The 95% CI for the difference between HR1 and HR2 was -1.2 to 8.5 beats/min. CONCLUSIONS: Exercise guided by the CSN alone could result in a given heart rate response, suggesting that the CSN is a simple and practical tool in translating exercise test results into individualized training intensity. With the CSN as the intensity indicator, patients can exercise safely and effectively.

14,15-epoxyeicosatrienoic Acid suppresses cigarette smoke extract-induced apoptosis in lung epithelial cells by inhibiting endoplasmic reticulum stress.

BACKGROUND/AIMS: Epoxyeicosatrienoic acids (EETs), a type of lipid mediators produced by cytochrome P450 epoxygenases, exert anti-inflammatory, angiogenic, anti-oxidative and anti-apoptotic effects. However, the role of EETs in cigarette smoke-induced lung injury and the underlying mechanisms are not fully known. The aim of this study was to explore the effects of CYP2J2-EETs on cigarette smoke extracts (CSE)-induced apoptosis in human bronchial epithelial cell line (Beas-2B) and the possible mechanisms involved. METHODS: Cytochrome P450 epoxygenase 2J2 (CYP2J2) and its metabolites EETs were assessed by western blotting or LC-MS-MS. Cell viability and apoptosis were determined by MTT assay and AnnexinV-PI staining. Reactive oxygen species (ROS) were assessed by measuring H2DCFDA. Caspase-3, HO-1, MAPK and endoplasmic reticulum (ER) stress-related markers GRP78, p-elF2a, and CHOP were evaluated by western blotting. RESULTS: CSE suppressed expression of both CYP2J2 and EET by Beas-2B cells. CSE also induced apoptosis, the generation of ROS and the ER stress in Beas-2B cells. These changes were abolished by pretreatment with exogenous 14,15-EET while pretreatment with 14,15-EEZE, a selective EET antagonist, abolished the protective effects of 14,15-EET. In addition, EETs increased the expression of antioxidant enzyme HO-1. Furthermore, 14,15-EET reduced CSE-induced activation of p38 and JNK. CONCLUSION: The data suggest that CYP2J2-derived EETs protect against CSE-induced lung injury possibly through attenuating ER stress.

Increased difference between slow and forced vital capacity is associated with reduced exercise tolerance in COPD patients.

BACKGROUND: A higher slow vital capacity (VC) compared with forced vital capacity (FVC) indicates small airway collapse and air trapping. We hypothesized that a larger difference between VC and FVC (VC-FVC) would predict impaired exercise capacity in patients with chronic obstructive pulmonary disease (COPD). METHODS: Pulmonary function and incremental cardiopulmonary exercise responses were assessed in 97 COPD patients. Patients were then divided into two groups: one in which VC > FVC (n = 77) and the other in which VC ≤ FVC (n = 20). RESULTS: Patients with VC > FVC had lower FEV1 and peak oxygen uptake (VO2/kg) compared with patients with VC ≤ FVC. There was a significant inverse correlation for the entire group between VC-FVC and peak VO2/kg (r = -0.404; p < 0.001). There was also a direct correlation between FEV1% pred and peak VO2/kg (r = 0.418; p < 0.001). The results of the multivariate regression analysis with peak VO2/kg as the dependent variable showed that VC-FVC, FEV1(% pred) and age were all significant independent predictors of peak VO2/kg. The model explained 35.9% of the peak VO2/kg variance. CONCLUSIONS: The difference between VC and FVC, easily measured by spirometry, can be used not only as an index of severity of airflow limitation, but also to predict exercise performance in COPD patients.

A new method for rating dyspnea during exercise in patients with chronic obstructive pulmonary disease.

BACKGROUND: The Borg scale is most commonly used to measure dyspnea in China. However, many patients that find it is difficult to distinguish the labeled numbers corresponding to different dyspnea scores. We developed a new method to rate dyspnea, which we call the count scale (CS). It includes the count scale number (CSN) and count scale time (CST). The aims of the present study were to determine the reproducibility and sensitivity of the CS during exercise in patients with chronic obstructive pulmonary disease (COPD). METHODS: Fourteen male patients with COPD (aged 58.00 ± 7.72 years) participated in this study. A progressive incremental exercise and a 6-minute constant work exercise test were performed every 2 to 3 days for a total of 3 times. The CS results were evaluated at rest and at 30% and 70% of maximal workload (Wmax) and Wmax. The Borg scales were obtained during exercise. RESULTS: No significant differences occurred across the three trials during exercise for the CS and Borg scores. The CSN and CST were more varied at Wmax (coefficient of variation (CV) = (22.28 ± 16.96)% for CSN, CV = (23.08 ± 19.11)% for CST) compared to 30% of Wmax (CV = (11.92 ± 8.78)% for CSN, CV = (11.16 ± 9.96)% for CST) and 70% of Wmax (CV = (9.08 ± 7.09)% for CSN, CV = (12.19 ± 12.32)% for CST). Dyspnea ratings with either CSN or CST tended to decrease at the higher workload compared to the lower workload. CSN and CST scores were highly correlated (r = 0.861, P < 0.001). CSN was negatively correlated with Borg scores (r = -0.363, P = 0.001). Similar results were obtained for the relationship between CST and Borg scores (r = -0.345, P = 0.003). CONCLUSION: We concluded that the CS is simple and reproducible when measuring dyspnea during exercise in patients with COPD.

Cardiac response and N-terminal-pro-brain natriuretic peptide kinetics during exercise in patients with COPD.

BACKGROUND: COPD increases the risk of cardiovascular problems. Dyspnea on exertion can be associated with COPD or heart failure or both. N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) is a marker of cardiac dysfunction, and exercise testing can identify subtle heart abnormalities. OBJECTIVE: To determine whether cardiac dysfunction adds to the mechanism of dyspnea caused primarily by impaired lung function in patients with mild to moderate COPD. METHODS: With 19 COPD patients and 10 healthy control subjects we measured physiologic variables and collected venous blood samples before and during incremental and constant-work-rate exercise, and measured NT-pro-BNP. RESULTS: Peak oxygen uptake and constant-work exercise time were significantly lower in the COPD group than in the control group (16 ± 4 mL/min/kg vs 19 ± 6 mL/min/kg, P = .04, and 7.8 ± 6.5 min vs 14.8 ± 7.3 min, P = .02). Between the groups there were no significant differences in anaerobic threshold, oxygen pulse (oxygen uptake divided by heart rate), or heart-rate reserve (difference between predicted and measured maximum heart rate). Both at rest and during constant-work exercise, NT-pro-BNP was not significantly higher in the COPD group than in the control group. In the COPD patients there was no significant correlation between constant-work exercise time and NT-pro-BNP at rest or during exercise. CONCLUSIONS: Heart failure did not contribute to exercise intolerance in patients with mild to moderate COPD.

[Ventilatory response at maximal exercise in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To compare the difference in the ventilatory equivalent for carbon dioxide (EqCO(2)) between the patients with chronic obstructive pulmonary disease (COPD) and normal adults at maximal exercise, and to identify the factors inducing the abnormal change of EqCO(2) in COPD patients. METHODS: Forty male COPD patients and fifteen normal males underwent symptom-limited cardiopulmonary exercise testing. Oxygen uptake and carbon dioxide output were measured breath-by-breath. Arterial blood samples were collected at maximal exercise to undergo gas analysis so as to calculate the dead space/tidal volume ratios (V(D)/V(T)) and alveolar-arterial PO(2) difference [P((A-a))O(2)]. RESULTS: The maximal oxygen uptake, maximal carbon dioxide output, and arterial partial pressure of carbon dioxide (PaCO(2)) of the COPD patients were (14.8 +/- 3.6) ml x kg(-1) x min(-1), (19.4 +/- 5.9) ml x kg(-1) x min(-1), and (87.6 +/- 13.9) mm Hg respectively, all significantly lower than those of the normal controls [(18.9 +/- 4.2) ml x kg(-1) x min(-1), (25.3 +/- 7.1) ml x kg(-1) x min(-1), and (113.9 +/- 13.6) mm Hg respectively, all P < 0.01]; and the EqCO(2), PaCO(2), P((A-a))O(2), and V(D)/V(T) of the COPD patients at maximal exercise were 33.0 +/- 5.1, (43.5 +/- 3.1) mm Hg, (43.5 +/- 3.1) mm Hg, 0.33 +/- 0.12 respectively, all significantly higher than those of the normal controls [28.5 +/- 2.6, (39.6 +/- 4.9) mm Hg, (12.6 +/- 6.3) mm Hg, and 0.26 +/- 0.07 respectively, P < 0.01, P < 0.01, P < 0.01, P < 0.05]. Multiple regression analysis showed that EqCO(2) was significantly positively correlated with V(D)/V(T) at maximal exercise in the COPD patients (r = 0.57, P < 0.01). CONCLUSION: Increased V(D)/V(T) may play an important role causing increase in EqCO(2) during exercise in patients with COPD.

[Effect of gas exchange at maximal intensity on exercise capacity in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the effect of gas exchange at maximal intensity on exercise capacity in patients with chronic obstructive pulmonary disease (COPD). METHODS: Forty-two male patients with COPD and 26 normal subjects performed incremental exercise test on cycle ergometer. Oxygen uptake and carbon dioxide output were measured continuously on the breath-by-breath mode. Arterial blood samples were drawn at maximal exercise. PaO2, PaCO2, the actual dead space/tidal volume ratios (V(D)/V(T)) and the alveolar-arterial PaO2 difference [ P(A-a) O2 ] were measured and calculated. Comparisons between the two groups were performed using independent samples t test. Linear regression analyses were made between maximal oxygen uptake (VO2max) and blood gas variables. RESULTS: VO2max in patients with COPD [(16 +/- 4) ml kg(-1) min(-1)] was significantly lower than in normal subjects [(19 +/- 6) ml kg(-1) min(-1)]. P(A-a)O2, V(D)/V(T) and PaCO2 were greater in patients [(43 +/- 3) mm Hg, 1 mm Hg =0.133 kPa, 0.35 +/- 0.11, (33 +/- 11) mm Hg] than in normal subjects at peak exercise [(40 +/- 5) mm Hg, 0.27 +/- 0.08, (15 +/- 7) mm Hg]. VO2max correlated strongly with V(D)/V(T) at peak exercise in patients (r = -0.734, P < 0.01). CONCLUSION: The increase in V(D)/V(T) inducing ventilatory inefficiency during exercise is one of the important causes for decreased exercise capacity in patients with COPD.

Effectiveness and safety of noninvasive positive-pressure ventilation for severe hypercapnic encephalopathy due to acute exacerbation of chronic obstructive pulmonary disease: a prospective case-control study.

BACKGROUND: Although severe encephalopathy has been proposed as a possible contraindication to the use of noninvasive positive-pressure ventilation (NPPV), increasing clinical reports showed it was effective in patients with impaired consciousness and even coma secondary to acute respiratory failure, especially hypercapnic acute respiratory failure (HARF). To further evaluate the effectiveness and safety of NPPV for severe hypercapnic encephalopathy, a prospective case-control study was conducted at a university respiratory intensive care unit (RICU) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) during the past 3 years. METHODS: Forty-three of 68 consecutive AECOPD patients requiring ventilatory support for HARF were divided into 2 groups, which were carefully matched for age, sex, COPD course, tobacco use and previous hospitalization history, according to the severity of encephalopathy, 22 patients with Glasgow coma scale (GCS) < 10 served as group A and 21 with GCS = 10 as group B. RESULTS: Compared with group B, group A had a higher level of baseline arterial partial CO2 pressure ((102 +/- 27) mmHg vs (74 +/- 17) mmHg, P < 0.01), lower levels of GCS (7.5 +/- 1.9 vs 12.2 +/- 1.8, P < 0.01), arterial pH value (7.18 +/- 0.06 vs 7.28 +/- 0.07, P < 0.01) and partial O(2) pressure/fraction of inspired O(2) ratio (168 +/- 39 vs 189 +/- 33, P < 0.05). The NPPV success rate and hospital mortality were 73% (16/22) and 14% (3/22) respectively in group A, which were comparable to those in group B (68% (15/21) and 14% (3/21) respectively, all P > 0.05), but group A needed an average of 7 cm H2O higher of maximal pressure support during NPPV, and 4, 4 and 7 days longer of NPPV time, RICU stay and hospital stay respectively than group B (P < 0.05 or P < 0.01). NPPV therapy failed in 12 patients (6 in each group) because of excessive airway secretions (7 patients), hemodynamic instability (2), worsening of dyspnea and deterioration of gas exchange (2), and gastric content aspiration (1). CONCLUSIONS: Selected patients with severe hypercapnic encephalopathy secondary to HARF can be treated as effectively and safely with NPPV as awake patients with HARF due to AECOPD; a trial of NPPV should be instituted to reduce the need of endotracheal intubation in patients with severe hypercapnic encephalopathy who are otherwise good candidates for NPPV due to AECOPD.

[Measurement of alveolar-arterial partial pressure of oxygen difference in patients with chronic obstructive pulmonary disease both at rest and during maximal exercise].

OBJECTIVE: To investigate the change of alveolar-arterial partial pressure of oxygen (PO2) difference [P (A-a) O2)] at rest and during exercise in patients with chronic obstructive pulmonary disease (COPD). METHODS: Cardiopulmonary exercise testing was performed in 47 COPD male patients aged (66 +/- 8) at stable stage to measure the oxygen uptake (VO2) and carbon dioxide output (VCO2) continuously in a breath-by-breath mode. Arterial blood samples were drawn both at rest and during maximal exercise. P(A-a) O2 is computed by the equation: PAO2-PaO2. RESULTS: The PaO2 level during exercise was (89 +/- 14) mm Hg, a little bit, however, not significantly, lower than that at rest [(92 +/- 9) mm Hg, P = 0.506]. The PaCO2 during exercise was 43 +/- 3 mm Hg, significantly higher than that at rest (41 +/- 4 mm Hg, P = 0.003). The patients were divided into two groups according to lung diffusing capacity for carbon monoxide (DLco). There was a significant increase in P(A-a) O2 from (16 +/- 8) mm Hg at rest to (42 +/- 9) mm Hg during maximal exercise in the DLco < 80% group (P = 0.005); however, in the DLco >80% group the P(A-a) O2 level during maximal exercise was (26 +/- 6) mm Hg, not significantly different from that at rest [(20 +/- 6) mm Hg, P = 0.106]. The P(A-a)O2 level of the DLco <80% group during maximal exercise was (42 +/- 9) mm Hg, significantly higher than that at rest [(16 +/- 8) mm Hg, P = 0.005]. The P(A-a)O2 was significantly negatively correlated with the forced vital capacity (r= -0.581, P = 0.037) and DLco (r = -0.671, P = 0.012). CONCLUSION: The increase in P (A-a) O2 during exercise in the COPD patients is mainly due to the limited diffusing capacity of the lung.