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Background: Encorafenib-cetuximab has been approved for pretreated BRAF V600E -mutated metastatic colorectal cancer (mCRC) patients based on efficacy demonstrated in the randomized phase III BEACON trial. The aim of this real-world effectiveness study is to improve knowledge on the generalizability of trial results., Methods: This population-based real-world study includes all mCRC patients in the Netherlands treated with encorafenib-cetuximab since approval. Individual patient data and pathology reports were collected. Overall survival (OS) was compared to BEACON and subgroup analyses were conducted for patients who would have been eligible and ineligible for BEACON., Results: 166 patients were included with a median follow-up time of 14.5 months. Median OS was 6.7 months (95% CI:6.0-8.3) and differed from BEACON (9.3 months; 95% CI:8.0-11.3, p-value 0.002). Thirty-six percent of real-world patients would have been ineligible for the BEACON trial. Trial ineligible subgroups with symptomatic brain metastases and WHO performance status ≥2 had the poorest median OS of 5.0 months (95% CI:4.0-NR) and 3.9 months (95% CI:2.4-NR)., Conclusion: This real-world cohort of mCRC patients treated with encorafenib-cetuximab showed a clinically relevant efficacy-effectiveness gap for OS. The chance of survival benefit from encorafenib-cetuximab in patients with brain metastases and/or WHO performance status ≥2 is negligible as neither efficacy nor effectiveness has been demonstrated., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.) more...

Background: The head and neck cancers (HNCs) incidence differs between Europe and East Asia. Our objective was to determine whether survival of HNC also differs between European and Asian countries., Methods: We used population-based cancer registry data to calculate 5-year relative survival (RS) for the oral cavity, hypopharynx, larynx, nasal cavity, and major salivary gland in Europe, Taiwan, and Japan. We modeled RS with a generalized linear model adjusting for time since diagnosis, sex, age, subsite, and histological grouping. Analyses were performed using federated learning, which enables analyses without sharing sensitive data., Findings: Five-year RS for HNC varied between geographical areas. For each HNC site, Europe had a lower RS than both Japan and Taiwan. HNC subsites and histologies distribution and survival differed between the three areas. Differences between Europe and both Asian countries persisted even after adjustments for all HNC sites but nasal cavity and paranasal sinuses, when comparing Europe and Taiwan., Interpretation: Survival differences can be attributed to different factors including different period of diagnosis, more advanced stage at diagnosis, or different availability/access of treatment. Cancer registries did not have stage and treatment information to further explore the reasons of the observed survival differences. Our analyses have confirmed federated learning as a feasible approach for data analyses that addresses the challenges of data sharing and urge for further collaborative studies including relevant prognostic factors., Competing Interests: LL declares research funds to the institute for clinical studies from Astrazeneca, BMS, Boehringer Ingelheim, Celgene International, Eisai, Exelixis, Debiopharm International SA, Hoffmann-La Roche ltd, IRX Therapeutics, Medpace, Merck-Serono, MSD, Novartis, Pfizer, Roche, Buran, Alentis; occasional fees for participation as a speaker at conferences/congresses or as a scientific consultant for advisory boards from Astrazeneca, Bayer, MSD, Merck-Serono, AccMed, Neutron Therapeutics, Inc. GGe received grants or contracts from Astra-Zeneca, Janssen, Roche, Health~Holland TKI; KWF Dutch Cancer Society and European Commission. AG received grants or contracts from KWF Dutch Cancer Society and European Commission. AG and GGe have patents assigned to Royal Philips. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Botta, Matsuda, Charvat, Chiang, Lee, van Gestel, Martin, Geleijnse, Cellamare, Bonfarnuzzo, Marcos-Gragera, Guevara, Mousavi, Craig, Rodrigues, Rubió-Casadevall, Licitra, Cavalieri, Resteghini, Gatta, Trama and the RARECAREnet working group.) more...

Objective: Lymph node metastases (pN+) in presumed early-stage cervical cancer negatively impact prognosis. Using federated learning, we aimed to develop a tool to identify a group of women at low risk of pN+, to guide the shared decision-making process concerning the extent of lymph node dissection., Methods: Women with cervical cancer between 2005 and 2020 were identified retrospectively from population-based registries: the Danish Gynaecological Cancer Database, Swedish Quality Registry for Gynaecologic Cancer and Netherlands Cancer Registry. Inclusion criteria were: squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma; The International Federation of Gynecology and Obstetrics 2009 IA2, IB1 and IIA1; treatment with radical hysterectomy and pelvic lymph node assessment. We applied privacy-preserving federated logistic regression to identify risk factors of pN+. Significant factors were used to stratify the risk of pN+., Results: We included 3606 women (pN+ 11%). The most important risk factors of pN+ were lymphovascular space invasion (LVSI) (odds ratio [OR] 5.16, 95% confidence interval [CI], 4.59-5.79), tumour size 21-40 mm (OR 2.14, 95% CI, 1.89-2.43) and depth of invasion>10 mm (OR 1.81, 95% CI, 1.59-2.08). A group of 1469 women (41%)-with tumours without LVSI, tumour size ≤20 mm, and depth of invasion ≤10 mm-had a very low risk of pN+ (2.4%, 95% CI, 1.7-3.3%)., Conclusion: Early-stage cervical cancer without LVSI, a tumour size ≤20 mm and depth of invasion ≤10 mm, confers a low risk of pN+. Based on an international privacy-preserving analysis, we developed a useful tool to guide the shared decision-making process regarding lymph node dissection., (Copyright © 2023 Elsevier Ltd. All rights reserved.) more...

We described physical activity measures and hourly patterns in patients with chronic obstructive pulmonary disease (COPD) after stratification for generic and COPD-specific characteristics and, based on multiple physical activity measures, we identified clusters of patients. In total, 1001 patients with COPD (65% men; age, 67 years; forced expiratory volume in the first second [FEV 1 ], 49% predicted) were studied cross-sectionally. Demographics, anthropometrics, lung function and clinical data were assessed. Daily physical activity measures and hourly patterns were analysed based on data from a multisensor armband. Principal component analysis (PCA) and cluster analysis were applied to physical activity measures to identify clusters. Age, body mass index (BMI), dyspnoea grade and ADO index (including age, dyspnoea and airflow obstruction) were associated with physical activity measures and hourly patterns. Five clusters were identified based on three PCA components, which accounted for 60% of variance of the data. Importantly, couch potatoes (i.e. the most inactive cluster) were characterised by higher BMI, lower FEV 1 , worse dyspnoea and higher ADO index compared to other clusters ( p < 0.05 for all). Daily physical activity measures and hourly patterns are heterogeneous in COPD. Clusters of patients were identified solely based on physical activity data. These findings may be useful to develop interventions aiming to promote physical activity in COPD. more...

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., (© 2016 S. Karger AG, Basel.) more...

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. more...

Background: The 6-Minute Walk Test (6MWT) is representative of daily-life activities and reflects the functional capacity of patients. The change of oxygen uptake (VO2) in the initial phase of low-intensity exercise (VO2 kinetics) can be used to assess submaximal exercise performance of patients.The objective of the following study was to analyse VO2 kinetics in patients with different pulmonary and cardiovascular diseases. In addition, we investigated the extent to which VO2 kinetics at the onset of the 6MWT were associated with exercise capacity, morbidity and mortality., Methods: VO2 kinetics of 204 patients and 16 healthy controls were obtained using mobile telemetric cardiopulmonary monitoring during a 6MWT. A new mean response time (MRT) index (wMRT) was developed to quantify VO2 kinetics by correcting MRT for work rate. The differences in wMRT between disease categories as well as the association between wMRT and patients' exercise capacity and outcome - time to hospitalization/death- were tested., Results: The assessment of a robust wMRT was feasible in 86% (244/284) patients. wMRT was increased in patients compared to healthy controls (p <0.001). wMRT was largest in patients with pulmonary arterial hypertension (PAH). There were significant associations between wMRT and exercise capacity in all patients. High wMRT was found to be associated with a high rate of death and re-hospitalization in patients with CHF (p = 0.024). In patients with pulmonary diseases and pulmonary hypertension wMRT was not associated with outcome (p = 0.952)., Conclusions: Submaximal exercise performance of patients is reduced. O2 kinetics at the onset of exercise are associated with exercise capacity in all patients. wMRT was found to be an important prognostic factor in patients with congestive heart failure (CHF), but not with pulmonary diseases. more...

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. more...

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 (β = -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. more...

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., (Copyright © 2013 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.) more...

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. more...

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. more...

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. more...

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 β-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. more...

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. more...

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. more...

Both in today's scientific research and in clinical practice, there exists a need to address the uncertainty concerning the effectiveness and safety of cardiopulmonary exercise training (CPET) in patients with pulmonary arterial hypertension (PAH). It is commonly believed that CPET may be dangerous for patients with PAH, because increasing pressure on the pulmonary arteries may worsen right-sided heart failure. Recently, the first clinical trials on exercise training in patients with pulmonary hypertension reported promising results. Extension of the walking distance at the 6-minute walk test improved quality of life, endurance capacity and a reduction in symptoms were observed after CPET. Furthermore, CPET was well tolerated by the patients in five clinical trials. In conclusion, it may be postulated that CPET is an effective therapy in patients with PAH and was tendentially well tolerated by the patients. more...

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. more...

Background: Previous studies with small sample sizes reported contradicting findings as to whether pulmonary function tests can predict exercise-induced oxygen desaturation (EID)., Objective: To evaluate whether forced expiratory volume in one second (FEV(1)), resting oxygen saturation (SpO(2)) and diffusion capacity for carbon monoxide (DLCO) are predictors of EID in chronic obstructive pulmonary disease (COPD)., Methods: We measured FEV(1), DLCO, SpO(2) at rest and during a 6-min walking test as well as physical activity by an accelerometer. A drop in SpO(2) of >4 to <90% was defined as EID. To evaluate associations between measures of lung function and EID univariate and multivariate analyses were used and positive/negative predictive values were calculated. Receiver operating characteristic curve analysis was performed to determine the most useful threshold in order to predict/exclude EID., Results: We included 154 patients with COPD (87 females). The mean FEV(1) was 43.0% (19.2) predicted and the prevalence of EID was 61.7%. The only independent predictor of EID was FEV(1) and the optimal cutoff value of FEV(1) was at 50% predicted (area under ROC curve, 0.85; p < 0.001). The positive predictive value of a threshold of FEV(1) <50% was 0.83 with a likelihood ratio of 3.03 and the negative predicting value of a threshold of FEV(1) ≥80% was 1.0. The severity of EID was correlated with daily physical activity (r = -0.31, p = 0.008)., Conclusions: EID is highly prevalent among patients with COPD and can be predicted by FEV(1). EID seems to be associated with impaired daily physical activity which supports its clinical importance., (Copyright © 2012 S. Karger AG, Basel.) more...

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., (Copyright © 2011 S. Karger AG, Basel.) more...

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. more...

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., (© 2011 The Authors. Respirology © 2011 Asian Pacific Society of Respirology.) more...

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. more...