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Physical activity is reduced in severe asthma; impulse oscillometry was a better predictor than spirometry http://ow.ly/6WdN305D9aV

Background: Little is known about the consequences of idiopathic pulmonary fibrosis (IPF) for physical activity (PA). Objectives: We aimed to investigate levels of PA in IPF and to study associations of PA with lung function, exercise capacity, symptoms, and quality of life. Methods: In stable patients with IPF we measured PA (steps per day, SPD; physical activity level, PAL; minutes of moderate activity, MMA) by accelerometry (SenseWear Armband) for 1 week. We also assessed lung function (forced vital capacity, FVC; diffusing capacity for carbon monoxide, DLCO); exercise capacity (6-minute walking distance, 6MWD); dyspnea (modified Medical Research Council, mMRC); fatigue (Multidimensional Fatigue Inventory, MFI-20), and generic (12-Item Short Form Survey, SF-12) and health-related quality of life (St. George's Respiratory Questionnaire) as further clinical variables. Results: We investigated 48 patients with IPF in two centers (mean age, 67 years; 75% male; 23% on long-term oxygen therapy; mean FVC 75%pred.; mean DLCO 43%pred.; mean 6MWD 355 ± 140 m; mean SPD 5,017 ± 3,360). On a bivariate level, all clinical variables were significantly associated with SPD (p < 0.05). The associations of mMRC, MFI-20, SF-12 (physical health), and 6MWD with SPD were independent of impaired lung function (p < 0.05). At multivariate analyses, either 6MWD (total explained variance of the model, total R2: 42%) or MFI-20 (total R2: 39%) were the strongest independent predictors of SPD. Conclusion: Fatigue and exercise capacity are strong and independent predictors of PA in patients with IPF, which suggests that both measures should be assessed when the consequences of IPF for PA in daily life are studied.

Handgrip strength is a simple measure of upper limb muscle function that is associated with mortality in the general population and in patients with COPD.1 ,2 Recently, normative values for handgrip strength have been proposed based on centile scores in >224 000 healthy adults between 39 and 73 years of age, adjusted for age, sex, height and measurement side.3 As an illustration, in a typical 65-year-old male patient 5th and 10th centile of right handgrip strength range 18–28 kg and 20–30 kg, respectively, depending on the patient's height. It is unclear whether the identification of handgrip weakness based on these centiles has prognostic value in addition to known prognostic parameters like FEV1, age, dyspnoea symptoms (combined in the validated ADO index4) and body mass index (BMI). Therefore, we performed an a posteriori analysis of prospectively collected multicentre data in patients with stable COPD, followed for a median of 3.9 years.2 ,5–7 Handgrip strength was assessed using …

Summary Background Little is known about COPD patients' compliance with physical activity monitoring and how activity relates to disease characteristics in a multi-center setting. Methods In a prospective study at three Northern European sites physical activity and clinical disease characteristics were measured in 134 COPD patients (GOLD-stage II–IV; BODE index 0–9) and 46 controls. Wearing time, steps per day, and the physical activity level (PAL) were measured by a multisensory armband over a period of 6 consecutive days (in total, 144h). A valid measurement period was defined as ≥22 h wearing time a day on at least 5 days. Results The median wearing time was 142 h:17 min (99%), 141 h:1min (98%), and 142 h:24 min (99%), respectively in the three centres. A valid measurement period was reached in 94%, 97%, and 94% of the patients and did not differ across sites ( P = 0.53). The amount of physical activity did not differ across sites (mean steps per day, 4725 ± 3212, P = 0.58; mean PAL, 1.45 ± 0.20, P = 0.48). Multivariate linear regression analyses revealed significant associations of FEV 1 , 6-min walk distance, quadriceps strength, fibrinogen, health status, and dyspnoea with both steps per day and PAL. Previously unrecognized correlates of activity were grade of fatigue, degree of emphysema, and exacerbation rate. Conclusions The excellent compliance with wearing a physical activity monitor irrespective of study site and consistent associations with relevant disease characteristics support the use of activity monitoring as a valid outcome in multi-center studies.

Background Systemic effects of COPD are incompletely reflected by established prognostic assessments. We determined the prognostic value of objectively measured physical activity in comparison with established predictors of mortality and evaluated the prognostic value of noninvasive assessments of cardiovascular status, biomarkers of systemic inflammation, and adipokines. Methods In a prospective cohort study of 170 outpatients with stable COPD (mean FEV1, 56% predicted), we assessed lung function by spirometry and body plethysmography; physical activity level (PAL) by a multisensory armband; exercise capacity by 6-min walk distance test; cardiovascular status by echocardiography, vascular Doppler sonography (ankle-brachial index [ABI]), and N-terminal pro-B-type natriuretic peptide level; nutritional and muscular status by BMI and fat-free mass index; biomarkers by levels of high-sensitivity C-reactive protein, IL-6, fibrinogen, adiponectin, and leptin; and health status, dyspnea, and depressive symptoms by questionnaire. Established prognostic indices were calculated. The median follow-up was 48 months (range, 10-53 months). Results All-cause mortality was 15.4%. After adjustments, each 0.14 increase in PAL was associated with a lower risk of death (hazard ratio [HR], 0.46; 95% CI, 0.33-0.64; P Conclusions We found that objectively measured physical activity is the strongest predictor of all-cause mortality in patients with COPD. In addition, adiponectin level and vascular status provide independent prognostic information in our cohort.

Purpose The aim of this retrospective study was to compare patient characteristics, treatment patterns and treatment results in two groups of patients with limited disease (LD) and extensive disease (ED) small-cell lung cancer (SCLC) in 2004 - 2005 vs. 2007 - 2008. Patients and methods We included all patients with LD or ED SCLC in this retrospective analysis who were diagnosed in our department in the periods 2004 - 2005 and 2007 - 2008. We collected data on patient characteristics, chemotherapy, radiotherapy, treatment response and median survival. Statistical analyses were separately performed for patients in LD and ED SCLC. Results 109 patients had LD SCLC. The response rate on first-line therapy was 74 %. More than half of the cases had recurrent disease. Second-line treatment was given to about two thirds of these patients. Third-line therapy was administered in around 15 % of all cases. Prophylactic cranial irradiation was performed more frequently from 2007 - 2008. The median survival was 17 months. There were no statistically significant differences regarding patient characteristics and treatment results. ED SCLC was present in 188 patients. The response rate was around 68 %. All patients relapsed, second-line therapy was administered in half of these cases; third-line therapy in 10 % of all cases. No statistically significant differences were detected between the two time frames. Median survival was 10 months. Conclusion Overall, no statistically significant differences were present for patients with LD and ED SCLC in 2004 - 2005 vs. 2007 - 2008. Prophylactic cranial irradiation was employed more frequently in LD SCLC from 2007.

Background Little is known about the role of abnormal lung function in heart size and heart dysfunction in patients with COPD. We studied the relationship of lung function with heart size and heart dysfunction and associated consequences for 6-min walk distance (6MWD) in patients with COPD of different severitites. Methods In 138 patients with COPD (Global Initiative for Obstructive Lung Disease [GOLD] I-IV), we measured the size of all cardiac chambers, left ventricular diastolic dysfunction (relaxation and filling), and global right ventricular dysfunction (Tei-index) by echocardiography. We also measured lung function (spirometry, body plethysmography, and diffusion capacity) and 6MWD. Results The size of all cardiac chambers decreased with increasing GOLD stage. Overall, moderate relationships existed between variables of lung function and cardiac chamber sizes. Static hyperinflation (inspiratory-to-total lung capacity ratio [IC/TLC], functional residual capacity, and residual volume) showed stronger associations with cardiac chamber sizes than airway obstruction or diffusion capacity. IC/TLC correlated best with cardiac chamber sizes and was an independent predictor of cardiac chamber sizes after adjustment for body surface area. Patients with an IC/TLC ≤ 0.25 had a significantly impaired left ventricular diastolic filling pattern and a significantly impaired Tei-index compared with patients with an IC/TLC > 0.25. An impaired left ventricular diastolic filling pattern was independently associated with a reduced 6MWD. Conclusions An increasing rate of COPD severity is associated with a decreasing heart size. Hyperinflation could play an important role regarding heart size and heart dysfunction in patients with COPD.

CXCR2 might have a crucial role in neutrophil extracellular trap formation in COPD neutrophilshttp://ow.ly/LRst30iE1Bw

Background The metabolic syndrome is a condition frequently found among individuals > 60 years of age. It predisposes affected individuals to systemic inflammation and physical inactivity. Systemic inflammation and physical inactivity are relevant extrapulmonary markers of morbidity and mortality in patients with COPD. Here, we studied the following: (1) the frequency of the coexisting metabolic syndrome in patients with chronic bronchitis (CB) and COPD of different severities; and (2) its association with systemic inflammation and physical inactivity. Methods In 30 patients with CB (normal spirometry finding) and in 170 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages I to IV), we measured the characteristics of the metabolic syndrome, systemic inflammation (high-sensitivity C-reactive protein [hs-CRP], interleukin-6, fibrinogen), and the physical activity level. Results The frequencies of the metabolic syndrome in patients with CB, GOLD stages I, II, III, and IV, were 53%, 50%, 53%, 37%, and 44%, respectively (average, 47.5%). The levels of hs-CRP and interleukin-6 were significantly increased in patients with the metabolic syndrome, while the physical activity level was significantly decreased. Multivariate linear regression analyses revealed metabolic syndrome, physical activity level, and CB/GOLD stages to be independent predictors of hs-CRP and interleukin-6 levels, and physical activity level to be a predictor of fibrinogen levels. Conclusions In our study, almost one-half of the patients with CB/COPD had coexisting metabolic syndrome, with a slightly lower frequency in patients with severe COPD. The coexisting metabolic syndrome is associated with an increase in the levels of some systemic inflammatory markers and physical inactivity, independent of lung function impairment.

Physical activity is an important parameter related to morbidity and mortality in cardiovascular disease, metabolic syndrome/diabetes, mental disorders, cancer, and chronic obstructive pulmonary disease (COPD). In COPD, lower levels of physical activity as reported by the patients are associated with a faster annual lung function decline, increased number of hospitalizations, and higher risk of mortality. Self-reported physical activity, however, correlates only poorly with objectively quantified physical activity in patients with COPD. Recent data show that physical activity can reliably be measured in a substantial number of patients with COPD. Extrapulmonary effects of COPD are associated with reduced physical activity. Clinical characteristics commonly used to assess disease severity like the forced expiratory volume in 1 s or the 6-min walk distance only incompletely reflect the physical activity of patients with COPD.

The present study aimed to measure physical activity in patients with chronic obstructive pulmonary disease (COPD) to: 1) identify the disease stage at which physical activity becomes limited; 2) investigate the relationship of clinical characteristics with physical activity; 3) evaluate the predictive power of clinical characteristics identifying very inactive patients; and 4) analyse the reliability of physical activity measurements. In total, 163 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I-IV; BODE (body mass index, airway obstruction, dyspnoea, exercise capacity) index score 0-10) and 29 patients with chronic bronchitis (normal spirometry; former GOLD stage 0) wore activity monitors that recorded steps per day, minutes of at least moderate activity, and physical activity levels for 5 days (3 weekdays plus Saturday and Sunday). Compared with patients with chronic bronchitis, steps per day, minutes of at least moderate activity and physical activity levels were reduced from GOLD stage II/BODE score 1, GOLD stage III/BODE score 3/4 and from GOLD stage III/BODE score 1, respectively. Reliability of physical activity measurements improved with the number of measured days and with higher GOLD stages. Moderate relationships were observed between clinical characteristics and physical activity. GOLD stages III and IV best predicted very inactive patients. Physical activity is reduced in patients with chronic obstructive pulmonary disease from Global Initiative for Chronic Obstructive Lung Disease stage II/ body mass index, airway obstruction, dyspnoea, exercise capacity score 1. Clinical characteristics of patients with chronic obstructive pulmonary disease only incompletely reflect their physical activity.

Physical activity is reduced in patients with chronic obstructive pulmonary disease (COPD). COPD has a systemic component that includes significant extrapulmonary effects that may contribute to its severity in individual patients.To investigate the association of extrapulmonary effects of the disease and its comorbidities with reduced physical activity in patients with COPD.In a cross-sectional study, 170 outpatients with COPD (GOLD [Global Initiative for Chronic Obstructive Lung Disease] stages I-IV; BODE [body mass index, airway obstruction, dyspnea, and exercise capacity] score 0-10) underwent a series of tests. Physical activity was assessed over 5 to 6 consecutive days by using a multisensor accelerometer armband that records steps per day and the physical activity level (total daily energy expenditure divided by whole-night sleeping energy expenditure). Cardiovascular status was assessed by echocardiography, vascular Doppler sonography, and levels of N-terminal pro-B-type natriuretic peptide. Mental status, metabolic/muscular status, systemic inflammation, and anemia were assessed by Beck Depression Inventory, bioelectrical impedance analysis, handgrip strength, high-sensitivity C-reactive protein/fibrinogen, and hemoglobin, respectively.In a multivariate linear regression analysis using either steps per day or physical activity level as a dependent variable, the extrapulmonary parameters that were associated with reduced physical activity in patients with COPD independently of GOLD stages or BODE score were N-terminal pro-B-type natriuretic peptide levels, echocardiographically measured left ventricular diastolic function, and systemic inflammation.Higher values of systemic inflammation and left cardiac dysfunction are associated with reduced physical activity in patients with COPD.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is characterized by neutrophilic airway inflammation. Neutrophil extracellular trap (NET) formation - a meshwork of neutrophil DNA components and neutrophil enzymes are involved in innate immunity and inflammation. Little is known about the presence of these structures in induced sputum from stable COPD patients. METHODS: Induced sputum samples of 23 COPD patients and 10 healthy controls were collected. Sputum cells were harvested, cultivated and stained for NET components. Extracellular DNA was quantified using a NanoDrop 2000 spectrophotometer. RESULTS: NET formation was markedly upregulated in COPD sputum compared with healthy controls, irrespective of sputum purulence or smoking status. NET formation was associated with significantly higher concentration of extracellular DNA in sputum supernatant (484 ng/mul in COPD versus 268 ng/mul in controls, p = 0.013). Log-transformed extracellular DNA correlated with log-transformed absolute neutrophil numbers in sputum (r = 0.60; p < 0.001) and airway obstruction (r = -0.43; p = 0.013). CONCLUSION: NET formation associated with higher concentrations of extracellular DNA may be a pathobiological feature of COPD-derived sputum neutrophils.

Rationale: Little is known about the role of physical activity in the course of chronic obstructive pulmonary disease (COPD). Objectives: To assess changes in physical activity in COPD in relation to severity stages and changes in other disease components, and to evaluate the longitudinal association between sustained physical inactivity and disease progression. Methods: In this prospective cohort study, we measured physical activity (multisensory armband), airflow obstruction (FEV1), health status (St. George's Respiratory Questionnaire), exercise capacity (6-min-walk distance [6MWD]), muscle mass (fat-free mass [FFM]), and systemic inflammation (fibrinogen and high-sensitivity C-reactive protein) over a 3-year period in 137 patients with COPD and 26 with chronic bronchitis (normal spirometry). Measurements and Main Results: Independent of baseline disease severity, steps per day, total daily energy expenditure, and (daily) physical activity level (PAL) decreased by 393, 76 kcal, and 0.04 per year, respectively. The decline in PAL was significantly associated with a decline in FEV1 and an increase in St. George's Respiratory Questionnaire total score. Changes in 6MWD, FFM, and inflammatory markers were not associated with changes in PAL. Independent of FEV1, sustained physical inactivity (i.e. PAL(T0andT1) < 1.40) was related to a greater decline in 6MWD and FFM compared with that in patients with some level of activity (i.e., PAL(T0and/orT1) >= 1.40; difference, 17 m/yr and 0.87 kg/yr, respectively). Conclusions: Over time, physical activity substantially decreases across all severity stages of COPD, and this decline is paralleled by a worsening of lung function and health status. Sustained physical inactivity is associated with a progression of exercise intolerance and muscle depletion.

Background: COPD is characterized by exercise intolerance, muscle depletion, and physical inactivity. The aim of this study was to analyze the role of sustained physical inactivity for changes in exercise capacity and skeletal muscle mass in the course of COPD. Methods: In this cohort study, we measured physical activity level (PAL; total daily energy expenditure / resting metabolic rate) via multisensory armband, FEV 1 , 6-minute walk distance (6MWD), and fat-free mass (FFM; bioelectrical impedance) at baseline and after 3 years in 170 patients with COPD (GOLD stage I–IV) and 30 with chronic bronchitis. Patients were longitudinally classified into ”sustained physical inactivity” (i.e. PAL T0+T1 T0orT1 >1.40). Results: During follow-up, we found a significant decrease in PAL, FEV 1 , 6MWD, and FFM (p 1 , sustained physical inactivity was related to a greater decline in 6MWD and FFM compared to that in patients with some level of activity (difference, 21 m/yr and 0.81 kg/yr). Sustained physical inactivity was not related to an accelerated decline in FEV 1 . Conclusions: Sustained physical inactivity over time promotes a progression of exercise intolerance and muscle depletion in patients with COPD.

Rationale Sporadic lymphangioleiomyomatosis (LAM) is an orphan lung disease for which daily physical activity has not been studied so far and it is unclear whether a disease-specific impact beyond airflow limitation exists. Clinical correlates indicating reduced physical activity in addition to established parameters like airflow limitation and hypoxaemia are largely undetermined. Method We measured physical activity (steps per day, SPD; physical activity level, PAL; minutes of moderate activity, MMA) in 34 women with LAM, 32 FEV 1 -matched female patients with COPD and 15 age-matched healthy women for 1 week using an accelerometer. In addition, we assessed lung function measurements, questionnaires for generic and respiratory health status (12-Item Short Form Survey, SF-12; St. George9s Respiratory Questionnaire, SGRQ), dyspnoea (modified Medical Research Council dyspnoea scale, mMRC) and fatigue (Multidimensional Fatigue Inventory, MFI-20). Results Patients with LAM (mean age 52.7 years, mean FEV 1 62.7% predicted) showed reduced SPD, PAL and MMA (p 1 62.6% predicted). In multivariate regression analyses, adjusting for FEV 1 and long-term oxygen therapy, either generic health status (SF-12 physical health) or fatigue (MFI-20) were the strongest independent predictors for SPD in patients with LAM (p=0.006 and p=0.004, respectively). Conclusions Physical activity in daily life is substatially reduced in LAM, when compared with healthy controls and COPD - indicating a disease specific impact. The regular assessment of fatigue and generic health status may improve disease management in LAM by taking daily physical activity of patients with LAM more adequately into account.

This European Respiratory Society (ERS) statement provides a comprehensive overview on physical activity in patients with chronic obstructive pulmonary disease (COPD). A multidisciplinary Task Force of experts representing the ERS Scientific Group 01.02 “Rehabilitation and Chronic Care” determined the overall scope of this statement through consensus. Focused literature reviews were conducted in key topic areas and the final content of this Statement was agreed upon by all members. The current knowledge regarding physical activity in COPD is presented, including the definition of physical activity, the consequences of physical inactivity on lung function decline and COPD incidence, physical activity assessment, prevalence of physical inactivity in COPD, clinical correlates of physical activity, effects of physical inactivity on hospitalisations and mortality, and treatment strategies to improve physical activity in patients with COPD. This Task Force identified multiple major areas of research that need to be addressed further in the coming years. These include, but are not limited to, the disease-modifying potential of increased physical activity, and to further understand how improvements in exercise capacity, dyspnoea and self-efficacy following interventions may translate into increased physical activity. The Task Force recommends that this ERS statement should be reviewed periodically (e.g. every 5–8 years). Michael Polkey's contribution to this work was part funded by the NIHR Respiratory Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London, UK, who part fund his salary. Thierry Trooster's contribution was partly funded by the Flemish Research Foundation (#G.0871.13). Anouk Vaes' contribution to this work was partially funded by "Stichting de Weijerhorst" and Point-One funding from AgentschapNL, Dutch Ministry of Economic affairs, the Netherlands. Martijn A. Spruit's contribution to this work was partially funded by Point-One funding from AgentschapNL, Dutch Ministry of Economic affairs, the Netherlands. Benjamin Waschki's contribution to this work was partially funded by the German Center for Lung Research, Germany. The Task Force co-chairs are grateful to the ERS for funding this ERS statement.

Chronic obstructive pulmonary disease (COPD) has significant extrapulmonary effects, among others, on cardiovascular disease. Heart failure can frequently be found in patients with COPD. Etiology of heart failure in COPD is only poorly understood but may be related to the high frequency of ischemic heart disease in this population. Furthermore, recent data suggest that diastolic left ventricular dysfunction may have a role for heart failure in COPD.

INTRODUCTION: The coexistence of chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) is frequent and might be inter-related through inflammation-related processes reflected by specific markers. Here, we studied angiopoietin-like protein 4 (ANGPTL4), an upcoming cardiovascular marker, in stable COPD, and its relationship to cardiovascular function with respect to well-known CVD risk factors. METHODS: In a prospective COPD cohort study, we investigated serum ANGPTL4 levels, vascular status (ankle-brachial index (ABI)) and cardiac function (N-terminal pro-B-type natriuretic peptide (NT-proBNP)) as well as airflow limitation, objectively measured physical activity, the metabolic syndrome, high-sensitive C reactive protein (hs-CRP) and other CVD risk factors at 2 time points. We initially studied 74 stable COPD patients and 18 controls. For internal validation, we additionally studied 160 COPD patients of a former visit. RESULTS: ANGPTL4 was significantly elevated in COPD patients compared with controls (p=0.026). After correction for traditional CVD risk factors, including hs-CRP, higher levels of ANGPTL4 were independently associated with lower ABI (p=0.023) and higher NT-proBNP (p

The identification and validation of biomarkers to support the assessment of novel therapeutics for COPD continues to be an important area of research. The aim of the current study was to identify systemic protein biomarkers correlated with measures of COPD severity, as well as specific protein signatures associated with comorbidities such as metabolic syndrome. 142 protein analytes were measured in serum of 140 patients with stable COPD, 15 smokers without COPD and 30 non-smoking controls. Seven analytes (sRAGE, EN-RAGE, NGAL, Fibrinogen, MPO, TGF-α and HB-EGF) showed significant differences between severe/very severe COPD, mild/moderate COPD, smoking and non-smoking control groups. Within the COPD subjects, univariate and multivariate analyses identified analytes significantly associated with FEV(1), FEV(1)/FVC and DLCO. Most notably, a set of 5 analytes (HB-EGF, Fibrinogen, MCP-4, sRAGE and Sortilin) predicted 21% of the variability in DLCO values. To determine common functions/pathways, analytes were clustered in a correlation network by similarity of expression profile. While analytes related to neutrophil function (EN-RAGE, NGAL, MPO) grouped together to form a cluster associated with FEV(1) related parameters, analytes related to the EGFR pathway (HB-EGF, TGF-α) formed another cluster associated with both DLCO and FEV(1) related parameters. Associations of Fibrinogen with DLCO and MPO with FEV(1)/FVC were stronger in patients without metabolic syndrome (r = -0.52, p = 0.005 and r = -0.61, p = 0.023, respectively) compared to patients with coexisting metabolic syndrome (r = -0.25, p = 0.47 and r = -0.15, p = 0.96, respectively), and may be driving overall associations in the general cohort. In summary, our study has identified known and novel serum protein biomarkers and has demonstrated specific associations with COPD disease severity, FEV(1), FEV(1)/FVC and DLCO. These data highlight systemic inflammatory pathways, neutrophil activation and epithelial tissue injury/repair processes as key pathways associated with COPD.

Systemic effects of COPD are incompletely reflected by established prognostic assessments. We determined the prognostic value of objectively measured physical activity in comparison with established predictors of mortality and evaluated the prognostic value of noninvasive assessments of cardiovascular status, biomarkers of systemic inflammation, and adipokines.In a prospective cohort study of 170 outpatients with stable COPD (mean FEV(1), 56% predicted), we assessed lung function by spirometry and body plethysmography; physical activity level (PAL) by a multisensory armband; exercise capacity by 6-min walk distance test; cardiovascular status by echocardiography, vascular Doppler sonography (ankle-brachial index [ABI]), and N-terminal pro-B-type natriuretic peptide level; nutritional and muscular status by BMI and fat-free mass index; biomarkers by levels of high-sensitivity C-reactive protein, IL-6, fibrinogen, adiponectin, and leptin; and health status, dyspnea, and depressive symptoms by questionnaire. Established prognostic indices were calculated. The median follow-up was 48 months (range, 10-53 months).All-cause mortality was 15.4%. After adjustments, each 0.14 increase in PAL was associated with a lower risk of death (hazard ratio [HR], 0.46; 95% CI, 0.33-0.64; P.001). Compared with established predictors, PAL showed the best discriminative properties for 4-year survival (C statistic, 0.81) and was associated with the highest relative risk of death per standardized decrease. Novel predictors of mortality were adiponectin level (HR, 1.34; 95% CI, 1.06-1.71; P = .017), leptin level (HR, 0.81; 95% CI, 0.65-0.99; P = .042), right ventricular function (Tei-index) (HR, 1.26; 95% CI, 1.04-1.54; P = .020), and ABI1.00 (HR, 3.87; 95% CI, 1.44-10.40; P = .007). A stepwise Cox regression revealed that the best model of independent predictors was PAL, adiponectin level, and ABI. The composite of these factors further improved the discriminative properties (C statistic, 0.85).We found that objectively measured physical activity is the strongest predictor of all-cause mortality in patients with COPD. In addition, adiponectin level and vascular status provide independent prognostic information in our cohort.

SummaryPurposeThe aim of this retrospective study is to present data on clinical significance of lactate dehydrogenase (LDH) serum levels in an unselected contemporary patient population with small cell lung cancer (SCLC) in limited disease (LD) and extensive disease stage (ED).Patients and methodsFrom June 2004 to June 2008, our electronic database including all in-patient and out-patient contacts was searched for patients with newly diagnosed LD and ED SCLC. 397 cases were identified. We collected data on patient characteristics including clinical performance status and LDH serum levels, metastatic sites, efficacy of first line chemotherapy and survival.ResultsIn both limited and extensive disease SCLC, elevated LDH serum levels resulted in significantly shorter median survival. The effect was most pronounced if levels were 300 U/l or higher. In patients with limited disease and normal LDH levels, median survival was 18.0 months. If LDH was higher than 300 U/l, overall survival was reduced to 12 months. In cases with extensive disease, overall survival was significantly lower in patients with elevated LDH serum levels with an additional reduction in overall survival in patients with LDH levels above 300 U/l. (7.0 vs. 12.0 months, p =

Little is known about the role of abnormal lung function in heart size and heart dysfunction in patients with COPD. We studied the relationship of lung function with heart size and heart dysfunction and associated consequences for 6-min walk distance (6MWD) in patients with COPD of different severitites.In 138 patients with COPD (Global Initiative for Obstructive Lung Disease [GOLD] I-IV), we measured the size of all cardiac chambers, left ventricular diastolic dysfunction (relaxation and filling), and global right ventricular dysfunction (Tei-index) by echocardiography. We also measured lung function (spirometry, body plethysmography, and diffusion capacity) and 6MWD.The size of all cardiac chambers decreased with increasing GOLD stage. Overall, moderate relationships existed between variables of lung function and cardiac chamber sizes. Static hyperinflation (inspiratory-to-total lung capacity ratio [IC/TLC], functional residual capacity, and residual volume) showed stronger associations with cardiac chamber sizes than airway obstruction or diffusion capacity. IC/TLC correlated best with cardiac chamber sizes and was an independent predictor of cardiac chamber sizes after adjustment for body surface area. Patients with an IC/TLCor = 0.25 had a significantly impaired left ventricular diastolic filling pattern and a significantly impaired Tei-index compared with patients with an IC/TLC0.25. An impaired left ventricular diastolic filling pattern was independently associated with a reduced 6MWD.An increasing rate of COPD severity is associated with a decreasing heart size. Hyperinflation could play an important role regarding heart size and heart dysfunction in patients with COPD.

Purpose The aim of this retrospective study is to present data on patient characteristics, treatment patterns, and treatment results in an unselected contemporary patient population with small cell lung cancer (SCLC) in limited disease (LD) and extensive disease stage (ED). Patients and methods From June 2004 to December 2008, our electronic database including all in-patient and out-patient contacts was searched for patients with newly diagnosed lung cancer. 397 patients were found having SCLC. We collected data on patient characteristics, chemotherapy, side effects, response on treatment and survival. Results 39% of all patients had LD SCLC. Median age was 63 years. The response rate (RR) reached 76%. Stable disease was the result of first line therapy in 16%. Consecutive thoracic radiotherapy was given in 72%. Additional prophylactic cranial irradiation (PCI) was administered to 33%. 43% received second line therapy. Median survival was 18.8 months. In 61% of cases, ED SCLC was diagnosed. Median age was 61 years. Main metastatic sites were liver, bone, brain and adrenal glands. RR was 69%. Stable disease and progressive disease were the result of first line chemotherapy both in 12%. 15% received palliative cranial irradiation, 3% PCI. 51% were treated with second line therapy. Median survival reached 10.6 months. Conclusion We provide a comprehensive analysis of a contemporary patient population. Treatment patterns and survival data fit well in the context of current international trials on more selected patients. Multivariate analyses confirmed extend of disease, performance status and LDH serum levels as independent prognostic factors for survival. Age and gender reached no statistical significance.

The metabolic syndrome is a condition frequently found among individuals60 years of age. It predisposes affected individuals to systemic inflammation and physical inactivity. Systemic inflammation and physical inactivity are relevant extrapulmonary markers of morbidity and mortality in patients with COPD. Here, we studied the following: (1) the frequency of the coexisting metabolic syndrome in patients with chronic bronchitis (CB) and COPD of different severities; and (2) its association with systemic inflammation and physical inactivity.In 30 patients with CB (normal spirometry finding) and in 170 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages I to IV), we measured the characteristics of the metabolic syndrome, systemic inflammation (high-sensitivity C-reactive protein [hs-CRP], interleukin-6, fibrinogen), and the physical activity level.The frequencies of the metabolic syndrome in patients with CB, GOLD stages I, II, III, and IV, were 53%, 50%, 53%, 37%, and 44%, respectively (average, 47.5%). The levels of hs-CRP and interleukin-6 were significantly increased in patients with the metabolic syndrome, while the physical activity level was significantly decreased. Multivariate linear regression analyses revealed metabolic syndrome, physical activity level, and CB/GOLD stages to be independent predictors of hs-CRP and interleukin-6 levels, and physical activity level to be a predictor of fibrinogen levels.In our study, almost one-half of the patients with CB/COPD had coexisting metabolic syndrome, with a slightly lower frequency in patients with severe COPD. The coexisting metabolic syndrome is associated with an increase in the levels of some systemic inflammatory markers and physical inactivity, independent of lung function impairment.

Physical activity is an important parameter related to morbidity and mortality in cardiovascular disease, metabolic syndrome/diabetes, mental disorders, cancer, and chronic obstructive pulmonary disease (COPD). In COPD, lower levels of physical activity as reported by the patients are associated with a faster annual lung function decline, increased number of hospitalizations, and higher risk of mortality. Self-reported physical activity, however, correlates only poorly with objectively quantified physical activity in patients with COPD. Recent data show that physical activity can reliably be measured in a substantial number of patients with COPD. Extrapulmonary effects of COPD are associated with reduced physical activity. Clinical characteristics commonly used to assess disease severity like the forced expiratory volume in 1 s or the 6-min walk distance only incompletely reflect the physical activity of patients with COPD.

SummaryPurposeThe aim of this retrospective study is to present data on clinical significance of hyponatremia in an unselected contemporary patient population with small cell lung cancer (SCLC) with limited disease (LD) and extensive disease (ED).Patients and methodsOur electronic database was searched for patients with newly diagnosed SCLC from June 2004 to December 2008. 395 cases were identified. We collected data on patient characteristics including clinical performance status, serum sodium values, serum LDH values, metastatic sites, chemotherapy regimens and response, radiotherapy and survival.ResultsHyponatremia (sodium

Background The aim of this study was to test whether repeatable biomarkers collected from serum, bronchoalveolar lavage (BAL) and sputum of healthy smokers and smokers with COPD would have a prognostic value with respect to the decline in lung function over a 5 year period. Methods In 2006/2007 we had repeatedly collected serum, BAL and sputum of 23 healthy smokers and 24 smokers with COPD (GOLD II) and analysed a panel of more than 100 different parameters. In 2012 we reinvited these subjects to assess the change in lung function to enable the investigation of the potential prognostic value of the 2006/2007 markers and to determine the long-term repeatability of selected blood and serum markers. In this follow-up study we performed body-plethysmography, a blood gas analysis and collected blood and urine samples. The change in lung function was compared with 67 markers from BAL, sputum, serum and whole blood that were shown in the 2006/2007 assessment to be repeatable over a 6 week period. Results We were able to recruit 13 (54%) smokers with COPD and 11 (48%) former healthy smokers that participated in the 2006/2007 study. The decline in lung function was larger in COPD smokers; five of them changed to GOLD III, one to GOLD IV. Two healthy smokers changed to GOLD I. Blood cells, serum von Willebrand factor and alpha-1-antitrypsin showed a good repeatability over 5 years. In COPD smokers a weak correlation between 2006/2007 sputum markers of neutrophilic inflammation and the 5 year change in FEV1/FVC was found. Conclusions Our data suggests that inter-individual and group differences are maintained over a five year period. Despite the large panel of markers available for this analysis, a potential prognostic value appears to exist only for some sputum inflammatory markers. If these data can be confirmed in larger COPD cohorts, it would emphasize the value of sputum markers in clinical trials and support the assumption that an anti-inflammatory treatment can have long term benefits in COPD.