Autonomic dysfunction in patients with chronic obstructive pulmonary disease (COPD)

Key Words: It has been recognized that chronic obstructive pulmonary disease (COPD) is a systemic disease which has been shown to negatively affect the cardiovascular and autonomic nerve system. The complexity of the physiologic basis by which autonomic dysfunction occurs in patients with COPD is considerable and the knowledge in this field remains elementary. The purpose of this review is to provide an overview of important potential mechanisms which might affect the autonomic nervous system in patients with COPD. This review aims to summarize the basic research in the field of autonomic dysfunction in patients with COPD. In COPD patients the activity of sympathetic nerves may be affected by recurrent hypoxemia, hypercapnia, increased intrathoracic pressure swings due to airway obstruction, increased respiratory effort, systemic inflammation and the use of betasympathomimetics. Furthermore, experimental findings suggest that autonomic dysfunction characterized by a predominance of sympathetic activity can significantly modulate further inflammatory reactions. The exact relationship between autonomic dysfunction and health status in COPD remains to be elucidated. Treatment aimed to restore the sympathovagal balance towards a reduction of resting sympathetic activity may modulate the inflammatory state, and possibly contributes to improved health status in COPD

Cardiopulmonary and gas-exchange responses during the six-minute walk test in patients with Chronic Obstructive Pulmonary Disease

Background: The 6-min walk test (6MWT) is representative of daily life activities and reflects the functional capacity of patients with chronic obstructive pulmonary disease (COPD). Information on the cardiopulmonary and gas exchange responses to the 6MWT is limited. Objectives: We aimed to analyze the breath-by-breath cardiopulmonary and gas exchange responses of patients with COPD during the 6MWT. We also investigated the extent to which parameters reflecting cardiopulmonary and gas exchange function are associated with exercise capacity. Methods: The oxygen uptake (VO2) kinetics of patients were obtained using mobile telemetric cardiopulmonary monitoring during a 6MWT. A new mean response time (MRT) index was developed to quantify VO2 on-kinetics by correcting MRT for work rate (wMRT). Multiple linear regression analysis was performed to assess the association between variables reflecting cardiopulmonary and gas exchange function and exercise capacity [6-min walking distance (6MWD) and VO2 at steady state (VO2SS)]. Results: In 72 COPD patients (29 females) with a mean (SD) age of 65 (10) years, FEV1 44 (14) % predicted exercise capacity as assessed by VO2SS (p = 0.003) was significantly reduced across the stages of COPD. The criteria for maximal effort during the 6MWT were fulfilled by 82% of the patients. After adjustment for covariates, wMRT was independently associated with 6MWD (p = 9.7 × 10-5) and VO2SS (p = 5.5 × 10-10). Conclusions: As wMRT mostly depends on the rate of increase of pulmonary blood flow, our results underline the fact that cardiocirculatory function may play a significant role in exercise tolerance in patients with COPD. Our findings imply that modification of cardiocirculatory function may be beneficial in the treatment of COPD patients and improve their outcome more than anticipated previously

Modeling the oxygen uptake kinetics during exercise testing of patients with chronic obstructive pulmonary diseases using nonlinear mixed models

Abstract Background The six-minute walk test (6MWT) is commonly used to quantify exercise capacity in patients with several cardio-pulmonary diseases. Oxygen uptake ( V ̇ $\dot {\mathrm {V}}$ O2) kinetics during 6MWT typically follow 3 distinct phases (rest, exercise, recovery) that can be modeled by nonlinear regression. Simultaneous modeling of multiple kinetics requires nonlinear mixed models methodology. To the best of our knowledge, no such curve-fitting approach has been used to analyze multiple V ̇ $\dot {\mathrm {V}}$ O2 kinetics in both research and clinical practice so far. Methods In the present study, we describe functionality of the R package medrc that extends the framework of the commonly used packages drc and nlme and allows fitting nonlinear mixed effects models for automated nonlinear regression modeling. The methodology was applied to a data set including 6MWT V ̇ $\dot {\mathrm {V}}$ O2 kinetics from 61 patients with chronic obstructive pulmonary disease (disease severity stage II to IV). The mixed effects approach was compared to a traditional curve-by-curve approach. Results A six-parameter nonlinear regression model was jointly fitted to the set of V ̇ $\dot {\mathrm {V}}$ O2 kinetics. Significant differences between disease stages were found regarding steady state V ̇ $\dot {\mathrm {V}}$ O2 during exercise, V ̇ $\dot {\mathrm {V}}$ O2 level after recovery and V ̇ $\dot {\mathrm {V}}$ O2 inflection point in the recovery phase. Estimates obtained by the mixed effects approach showed standard errors that were consistently lower as compared to the curve-by-curve approach. Conclusions Hereby we demonstrate the novelty and usefulness of this methodology in the context of physiological exercise testing

Cardiopulmonary and gas-exchange responses during the six-minute walk test in patients with chronic obstructive pulmonary disease

Background: The 6-min walk test (6MWT) is representative of daily life activities and reflects the functional capacity of patients with chronic obstructive pulmonary disease (COPD). Information on the cardiopulmonary and gas exchange responses to the 6MWT is limited. Objectives: We aimed to analyze the breath-by-breath cardiopulmonary and gas exchange responses of patients with COPD during the 6MWT. We also investigated the extent to which parameters reflecting cardiopulmonary and gas exchange function are associated with exercise capacity. Methods: The oxygen uptake (VO2) kinetics of patients were obtained using mobile telemetric cardiopulmonary monitoring during a 6MWT. A new mean response time (MRT) index was developed to quantify VO2 on-kinetics by correcting MRT for work rate (wMRT). Multiple linear regression analysis was performed to assess the association between variables reflecting cardiopulmonary and gas exchange function and exercise capacity [6-min walking distance (6MWD) and VO2 at steady state (VO2SS)]. Results: In 72 COPD patients (29 females) with a mean (SD) age of 65 (10) years, FEV1 44 (14) % predicted exercise capacity as assessed by VO2SS (p = 0.003) was significantly reduced across the stages of COPD. The criteria for maximal effort during the 6MWT were fulfilled by 82% of the patients. After adjustment for covariates, wMRT was independently associated with 6MWD (p = 9.7 × 10-5) and VO2SS (p = 5.5 × 10-10). Conclusions: As wMRT mostly depends on the rate of increase of pulmonary blood flow, our results underline the fact that cardiocirculatory function may play a significant role in exercise tolerance in patients with COPD. Our findings imply that modification of cardiocirculatory function may be beneficial in the treatment of COPD patients and improve their outcome more than anticipated previously

Association between peripheral muscle strength, exercise performance, and physical activity in daily life in patients with Chronic Obstructive Pulmonary Disease

BACKGROUND: Resistance training of peripheral muscles has been recommended in order to increase muscle strength in patients with Chronic Obstructive Pulmonary Disease (COPD). However, whether peripheral muscle strength is associated with exercise performance (EP) and physical activity in daily life (PADL) in these patients needs to be investigated. The aim of this study is to evaluate whether strength of the quadriceps muscle (QS) is associated with EP and daily PADL in patients with COPD. METHODS: We studied patients with COPD (GOLD A-D) and measured maximal isometric strength of the left QS. PADL was measured for 7 days with a SenseWear-Pro® accelerometer. EP was quantified by the 6-minute walk distance (6MWD), the number of stands in the Sit-to-Stand Test (STST), and the handgrip-strength. Univariate and multivariate analyses were used to examine possible associations between QS, PADL and EP. RESULTS: In 27 patients with COPD with a mean (SD) FEV1 of 37.6 (17.6)% predicted, QS was associated with 6MWD, STST, and handgrip-strength but not with PADL. Multiple linear regression analyses showed that QS was independently associated with the 6MWD (β = 0.42, 95% CI 0.09 to 0.84, p = 0.019), STST (β = 0.50, 95% CI 0.11 to 0.86, p = 0.014) and with handgrip-strength (β = 0.45, 95% CI 0.05 to 0.84, p = 0.038). CONCLUSIONS: Peripheral muscle strength may be associated with exercise performance but not with physical activity in daily life. This may be due to the fact that EP tests evaluate patients' true abilities while PADL accelerometers may not

Additional file 2 of Modeling the oxygen uptake kinetics during exercise testing of patients with chronic obstructive pulmonary diseases using nonlinear mixed models

Sample R code. (R 388 kb