Analysis of nocturnal actigraphic sleep measures in patients with COPD and their association with daytime physical activity.

BACKGROUND: Sleep disturbances are common in patients with chronic obstructive pulmonary disease (COPD) with a considerable negative impact on their quality of life. However, factors associated with measures of sleep in daily life have not been investigated before nor has the association between sleep and the ability to engage in physical activity on a day-to-day basis been studied. AIMS: To provide insight into the relationship between actigraphic sleep measures and disease severity, exertional dyspnoea, gender and parts of the week; and to investigate the association between sleep measures and next day physical activity. METHODS: Data were analysed from 932 patients with COPD (66% male, 66.4±8.3 years, FEV1% predicted=50.8±20.5). Participants had sleep and physical activity continuously monitored using a multisensor activity monitor for a median of 6 days. Linear mixed effects models were applied to investigate the factors associated with sleep impairment and the association between nocturnal sleep and patients' subsequent daytime physical activity. RESULTS: Actigraphic estimates of sleep impairment were greater in patients with worse airflow limitation and worse exertional dyspnoea. Patients with better sleep measures (ie, non-fragmented sleep, sleeping bouts ≥225 min, sleep efficiency ≥91% and time spent awake after sleep onset <57 min) spent significantly more time in light (p<0.01) and moderate-to-vigorous physical activity (p<0.01). CONCLUSIONS: There is a relationship between measures of sleep in patients with COPD and the amount of activity they undertake during the waking day. Identifying groups with specific sleep characteristics may be useful information when designing physical activity-enhancing interventions.

Oxygen Uptake Recovery Kinetics after the 6-Minute Walk Test in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: There is a growing interest in exercise parameters capable of objectively evaluating the functional capacity of patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES: The purpose of the present study was to analyze breath-by-breath cardiopulmonary and gas exchange recovery responses of patients with COPD after a 6-minute walk test (6MWT). METHODS: Oxygen uptake (VO2) kinetics of patients were obtained using mobile telemetric cardiopulmonary monitoring during and after a 6MWT. Recovery kinetics were modelled using a 4-parameter nonlinear logistic model. Multiple linear regression was performed to assess the association between the half-time of recovery of oxygen consumption (T1/2 VO2) and exercise capacity (6-minute walking distance, 6MWD). RESULTS: Sixty-nine patients with COPD (28 females) with a mean age of 65 ± 10 years took part in the study. After adjustment for covariates (body mass index, forced expiratory volume in 1 s, forced vital capacity, and age), T1/2 VO2 was significantly associated with 6MWD (p = 0.002). CONCLUSIONS: T1/2 VO2 can be used to reflect exercise capacity in patients with COPD. As T1/2 VO2 mostly depends on the rate of increase in pulmonary blood flow, the results of the present study underline the importance of cardiocirculatory impairment for exercise intolerance in patients with 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 (VO(2SS))]. 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 VO(2SS) (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 VO(2SS) (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.

High prevalence of altered cardiac repolarization in patients with COPD.

BACKGROUND: Altered cardiac repolarization and increased dispersion of repolarization have been identified as risk factors for sudden cardiac death (SCD). The prevalence of and the mechanisms contributing to altered cardiac repolarization are currently unknown in COPD. METHODS: In 91 COPD patients, 32 controls matched for age, cardiovascular risk and medication, and 41 healthy subjects, measures of cardiac repolarization and dispersion of repolarization (QTc interval, QT dispersion) were derived from 12-lead electrocardiography (ECG). Prevalence rates of heart rate corrected QT (QTc) >450ms and QT dispersion >60ms were determined to assess the number of subjects at risk for SCD. Univariate and multivariate analyses were used to identify possible factors contributing to altered cardiac repolarization. RESULTS: QTc was found to be prolonged in 31.9% and QT dispersion in 24.2% of the COPD patients compared to 12.5% in matched controls and 0% in healthy subjects. The QTc interval was longer in COPD patients compared to matched and healthy controls respectively (437.9 ± 29.5 vs. 420.1 ± 25.3 ms, p = 0.001 and vs. 413.4 ± 18.2 ms, p < 0.001). QT dispersion was significantly increased in COPD patients compared to healthy subjects (45.4 (34.8 , 59.5) vs. 39.7 (29.3 , 54.8) ms, p = 0.049). Only oxygen saturation was independently associated with QTc duration in multivariate analysis (ß = -0.29, p = 0.015). CONCLUSION: One third of a typical COPD population has altered cardiac repolarization and increased dispersion of repolarization, which may be related to hypoxia. Altered cardiac repolarization may expose these patients to an increased risk for malignant ventricular arrhythmias and SCD.

The speed of blood pressure fluctuations in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been associated with increased risk for cardiovascular disease but mechanisms underlying this association are incompletely understood. The speed of beat-to-beat changes in systolic blood pressure (vSBP) was found to be pronounced in patients with elevated cardiovascular risk. Although increased vSBP may thus be a contributing mechanism to cardiovascular morbidity, no data exist on vSBP in patients with COPD. Therefore, the purpose of this study was to evaluate whether there is an association between severity of COPD and vSBP. METHODS: Resting beat-to-beat blood pressure was recorded during 5 min. vSBP was assessed by calculating the slopes of oscillatory fluctuations in SBP for different inter-beat intervals (IBI). Univariate and multivariate analyses were performed to evaluate the association between forced expiratory volume in 1 s (FEV1) and vSBP. RESULTS: This study comprised 60 patients with COPD (24 females) with a mean [SD] FEV1 of 45.4 [22.7] %predicted and 34 healthy controls. Short-term fluctuations in SBP were more pronounced in patients with COPD compared to healthy controls. There was a significant inverse correlation between FEV1 and vSBP (r=-0.41, p=0.001). Even after adjustment for covariates in multivariate analysis, FEV1 was found to be independently associated with vSBP. CONCLUSIONS: Patients with COPD are characterised by steeper blood pressure changes than healthy controls. The speed of fluctuations in SBP is associated with the severity of airflow limitation. Increased vSBP may be a mechanism underpinning the association between COPD and cardiovascular disease.

Determinants of endothelial function in patients with COPD.

Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular mortality. Endothelial dysfunction may underpin this association. This cross-sectional study aimed to determine the impact of airflow obstruction, systemic inflammation, oxidative stress, sympathetic activation, hypoxaemia and physical activity on endothelial function in COPD. In stable COPD patients, assessments of endothelial function by flow-mediated dilatation (FMD), cardiovascular risk (Pocock score), airflow obstruction (forced expiratory volume in 1 s (FEV1)), systemic inflammation (high-sensitivity C-reactive protein and interleukin-6), oxidative stress (malondialdehyde), sympathetic activation (baroreflex sensitivity), hypoxaemia (arterial oxygen tension), hypercapnia (arterial carbon dioxide tension (PaCO2)), physical activity (steps per day) and exercise capacity (6-min walking distance) were performed. Associations between FMD and potential determinants were assessed in univariate and multivariate analyses. 106 patients (Global Initiative for Chronic Obstructive Lung Disease stage I/II 35%, stage III 25% and stage IV 40%) were included. In multivariate analysis FEV1 was positively associated with FMD, independent of other significant FMD determinants from univariate analysis (sex, smoking, combined inhaled long-acting ß-adrenergic and steroid medication, heart rate, baroreflex sensitivity and PaCO2) and adjusted for potential confounders (cardiovascular risk and age). In addition, the FMD and FEV1 association was modified by physical activity. The findings of this study demonstrate that the severity of airflow obstruction is a significant determinant of endothelial function in patients with COPD. A high level of physical activity seems to have a favourable effect on this association.

The effects of controlled breathing during pulmonary rehabilitation in patients with COPD.

BACKGROUND: Conventional pulmonary rehabilitation programs improve exercise tolerance but have no effect on pulmonary function in patients with chronic obstructive pulmonary disease (COPD). The role of controlled breathing using respiratory biofeedback during rehabilitation of patients with COPD remains unclear. OBJECTIVES: To compare the effects of a conventional 4-week pulmonary rehabilitation program with those of rehabilitation plus controlled breathing interventions. METHODS: A randomized controlled trial was performed. Pulmonary function (FEV1), exercise capacity (6-min walking distance, 6 MWD), health-related quality of life (chronic respiratory questionnaire, CRQ) and cardiac autonomic function (rMSSD) were evaluated. RESULTS: Forty COPD patients (mean±SD age 66.1±6.4, FEV1 45.9±17.4% predicted) were randomized to rehabilitation (n=20) or rehabilitation plus controlled breathing (n=20). There were no statistically significant differences between the two groups regarding the change in FEV1 (mean difference -0.8% predicted, 95% CI -4.4 to 2.9% predicted, p=0.33), 6 MWD (mean difference 12.2 m, 95% CI -37.4 to 12.2 m, p=0.16), CRQ (mean difference in total score 0.2, 95% CI -0.1 to 0.4, p=0.11) and rMSSD (mean difference 2.2 ms, 95% CI -20.8 to 25.1 ms, p=0.51). CONCLUSIONS: In patients with COPD undergoing a pulmonary rehabilitation program, controlled breathing using respiratory biofeedback has no effect on exercise capacity, pulmonary function, quality of life or cardiac autonomic function.

Cardiac autonomic function and cardiovascular response to exercise in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with impaired exercise tolerance, but it has not been established to what extent cardiac autonomic function impacts on exercise capacity. OBJECTIVE: To evaluate whether there is an association between airflow limitation and cardiac autonomic function and whether cardiac autonomic function plays a role in exercise intolerance and daily physical activity (PA) in patients with COPD. METHODS: Univariate and multivariate analyses were performed to evaluate the association between both 6-minute walking test (6MWT) and PA (steps per day) and pulmonary function, cardiac autonomic function (HR at rest, HRR and heart rate variability, HRV) in patients with COPD. RESULTS: In 154 COPD patients (87 females, mean [SD]: age 62.5 [10.7] years, FEV(1) %predicted (43.0 [19.2]%), mean HR at rest was elevated (86.4 [16.4] beats/min) and HRV was reduced (33.69 [28.96] ms) compared to published control data. There was a significant correlation between FEV(1) and HR at rest (r = -0.32, p < 0.001), between HR at rest and 6MWD (r = -0.26, p = 0.001) and between HR at rest and PA (r = -0.29, p = 0.010). No correlation was found between HRV and 6MWD (r = 0.089, p = 0.262) and PA (r = 0.075, p = 0.322). In multivariate analysis both HR and FEV(1) were independent predictors of exercise capacity in patients with COPD. CONCLUSIONS: In patients with COPD the degree of airflow limitation is associated with HR at rest. The degree of airflow limitation and cardiac autonomic function, as quantified by HR at rest, are independently associated with exercise capacity in patients with COPD.

Cardiac autonomic dysfunction and health-related quality of life in patients with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: COPD is associated with impaired health-related quality of life (HRQL) and cardiac autonomic dysfunction. Data describing the association between these factors in patients with COPD are mostly lacking. The objective of this study was to evaluate whether there is an association between cardiac autonomic dysfunction and HRQL in COPD. METHODS: We studied 60 patients with COPD (37 women, mean (SD) age 65.20 (7.73) years, FEV(1) % pred. 46.58 (18.53) %) and measured HRQL, as assessed by the Chronic Respiratory Disease Questionnaire, and cardiac autonomic dysfunction, as assessed by heart rate variability (HRV). Analysis of HRV was performed using a Holter-ECG device during a recording period of 5 min. To evaluate a possible association between these factors, univariate and multivariate analyses were used. RESULTS: There was a significant correlation between Chronic Respiratory Disease Questionnaire total score and both variables of HRV reflecting parasympathetic tone; root mean square successive difference of RR intervals (rMSSD) (r = 0.34, P = 0.012) and the density of the beat-to-beat oscillation in the N-N interval of HRV in the high-frequency band (HF power) (r = 0.35, P = 0.01). In a multivariate analysis rMSSD was found to be independently associated with HRQL after correcting for FEV(1), carbon monoxide transfer coefficient (DL(CO)), 6MWD and CRP. CONCLUSIONS: Resting parasympathetic tone, as measured by HRV, is independently associated with HRQL, which emphasizes the role of cardiac autonomic dysfunction on HRQL in patients with COPD.

Identifying Physical Activity Profiles in COPD Patients Using Topic Models.

With the growing amount of physical activity (PA) measures, the need for methods and algorithms that automatically analyze and interpret unannotated data increases. In this paper, PA is seen as a combination of multimodal constructs that can cooccur in different ways and proportions during the day. The design of a methodology able to integrate and analyze them is discussed, and its operation is illustrated by applying it to a dataset comprising data from COPD patients and healthy subjects acquired in daily life. The method encompasses different stages. The first stage is a completely automated method of labeling low-level multimodal PA measures. The information contained in the PA labels are further structured using topic modeling techniques, a machine learning method from the text processing community. The topic modeling discovers the main themes that pervade a large set of data. In our case, topic models discover PA routines that are active in the assessed days of the subjects under study. Applying the designed algorithm to our data provides new learnings and insights. As expected, the algorithm discovers that PA routines for COPD patients and healthy subjects are substantially different regarding their composition and moments in time in which transitions occur. Furthermore, it shows consistent trends relating to disease severity as measured by standard clinical practice.

Association between peripheral muscle strength and daily physical activity in patients with COPD: a systematic literature review and meta-analysis.

BACKGROUND: Patients with chronic obstructive pulmonary disease have skeletal muscle dysfunction and reduced daily physical activity (PA). Whether the reduction in quadriceps strength (QS) is directly linked to physical inactivity remains to be elucidated. METHODS: A systematic review and a meta-analysis were conducted to determine the potential relationship between QS and the level of PA. The overall estimate of the correlation coefficient (r*) was calculated, and a subgroup analysis was conducted to analyze the association between QS and indices of PA separately. RESULTS: A total of 8 studies were included in the meta-analysis. The overall association between QS and PA was low but highly significant (r * = 0.288, 95% CI = 0.180-0.389; P < .001). In the subgroup analysis, the association between QS and the number of steps per day was low (r = 0.260; 95% CI = 0.060-0.440) and the association between QS and the time spent walking was moderate (r = 0.418; 95% CI = 0.229-0.576). CONCLUSIONS: Peripheral muscle strength is associated with PA as assessed by the number of steps per day and the time spent walking in patients with chronic obstructive pulmonary disease. The overall association between QS and PA was low to moderate and highly significant.

Quantifying the speed of fluctuations in systolic blood pressure.

Increased blood pressure variability (BPV), even in the absence of hypertension, has been identified as an important independent cardiovascular risk factor (CVRF). However, the role of the speed of changes in systolic blood pressure (SBP; vSBP) on cardiovascular risk needs to be investigated. The objective of this study was to investigate whether subjects with a high cardiovascular risk profile have an increased degree and speed of changes in SBP compared with subjects with low or no risk. Resting beat-to-beat blood pressure (BP) was recorded for 5 min. Standard BPV measures in both time and frequency domains were conducted. The s.d. of SBP (s.d.-SBP) values was used to quantify the degree of BPV. vSBP was assessed by calculating the slopes of oscillatory fluctuations in SBP for different interbeat intervals (IBI). Subjects were allocated to one of four groups according to the number of CVRFs (0, 1, 2, ≥ 3 CVRF). Of 122 subjects, 19.7% had 0 CVRF, 27.0% had 1, 32.0% had 2 and 21.3% had ≥ 3 CVRFs. There was an increase in vSBP across the four risk groups. The vSBP in patients without CVRF was 3.12 (1.09), 1 CVRF 3.23 (1.07), 2 CVRF 4.16 (2.26) and ≥ 3 CVRF 4.22 (1.66; P = 0.015). The s.d.-SBP was not significantly different between the cardiovascular risk groups. The speed of fluctuations in SBP rather than the degree of BPV is pronounced in patients with elevated cardiovascular risk. Increased speed of BP fluctuations may thus be a contributing mechanism to cardiovascular morbidity.

Sympathetic overactivity and cardiovascular disease in patients with chronic obstructive pulmonary disease (COPD).

Cardiovascular disease plays an important role regarding the morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). Sympathetic overactivity has been suggested to underpin the association between COPD and the development of cardiovascular disease. However, the pathophysiological basis by which sustained sympathetic overactivity affects cardiovascular function in patients with COPD is complex and incompletely understood. Different simple and more sophisticated measures of sympathetic activity, such as assessment of heart rate, blood pressure variability, and baroreflex sensitivity, provide information on the potential dysregulation of the autonomous nervous system. This review summarizes the findings from studies in animal models and humans on the potential relationship between COPD, sympathetic overactivity, and cardiovascular disease. There is preliminary evidence of sympathetic overactivity in COPD. However, direct evidence of a cause-effect relationship between sympathetic overactivity and cardiovascular disease from studies in COPD patients is lacking. Data from large cohorts of COPD patients and well-designed interventional studies looking at the relationship between COPD and autonomic nervous system function are urgently needed, hopefully leading to novel therapeutic and preventive approaches in the care of patients with COPD.

Comparison of photoplethysmographic and arterial tonometry-derived indices of arterial stiffness.

Arterial tonometry is a method to assess arterial stiffness and has become a valuable tool in the stratification of cardiovascular risk. The arterial tonometry-derived augmentation index (AIx) is a marker of arterial stiffness and an independent predictor of mortality. As the AIx is relatively cumbersome to obtain, simpler methods such as analysis of pulse waves obtained by digital photoplethysmography have been proposed to estimate arterial stiffness. The objective of this study is to compare the usefulness of the stiffness index (SI) derived from digital photoplethysmography and the AIx derived from radial tonometry for stratification of cardiovascular risk. We studied 83 subjects with a heterogeneous cardiovascular risk profile and determined the ability of the two devices to differentiate subjects with low from subjects with high cardiovascular risk estimated by the Europe (EU)-heart score. Failure rate in both devices was similar (3.6%). AIx and SI were modestly correlated (r=0.48, P<0.001) and both indexes correlated with the EU-score (r=0.54, P<0.001) and (r=0.56, P<0.001), respectively. Both devices discriminated accurately between subjects with high cardiovascular risk (upper tertile of the EU-score) and low cardiovascular risk (lower tertile). However, only the SI differentiated significantly between subjects with intermediate risk (middle tertile) and high risk (upper tertile). Compared with the AIx, assessment of the SI derived by digital photoplethysmography is simple and possibly yields an advantage in risk stratification of subjects with intermediate and high cardiovascular risk. Therefore, digital pulse wave analysis may be a valuable tool to estimate arterial stiffness in large clinical studies.

Predicting daily physical activity in patients with chronic obstructive pulmonary disease.

BACKGROUND: Objectively measuring daily physical activity (PA) using an accelerometer is a relatively expensive and time-consuming undertaking. In routine clinical practice it would be useful to estimate PA in patients with chronic obstructive pulmonary disease (COPD) with more simple methods. OBJECTIVES: To evaluate whether PA can be estimated by simple tests commonly used in clinical practice in patients with COPD. METHODS: The average number of steps per day was measured for 7 days with a SenseWear Pro™ accelerometer and used as gold standard for PA. A physical activity level (PAL) of <1.4 was considered very inactive. Univariate and multivariate analyses were used to examine the relationship between the 6-minute walking distance (6MWD), the number of stands in the Sit-to-Stand Test (STST), hand-grip strength and the total energy expenditure as assessed by the Zutphen Physical Activity Questionnaire (TEE(ZPAQ)). ROC curve analysis was used to identify patients with an extremely inactive lifestyle (PAL<1.4). RESULTS: In 70 patients with COPD (21 females) with a mean [SD] FEV(1) of 43.0 [22.0] %predicted, PA was found to be significantly and independently associated with the 6MWD (r = 0.69, 95% CI 0.54 to 0.80, p<0.001), STST (r = 0.51, 95% CI 0.31 to 0.66, p = 0.001) and TEEZPAQ (r = 0.50, 95% CI 0.30 to 0.66, p<0.001) but not with hand-grip strength. However, ROC curve analysis demonstrated that these tests cannot be used to reliably identify patients with an extremely inactive lifestyle. CONCLUSIONS: In patients with COPD simple tests such as the 6-Minute Walk Test, the Sit-to-Stand Test and the Zutphen Physical Activity Questionnaire cannot be used to reliably predict physical inactivity.

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

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.