Comorbid conditions as predictors of mortality in severe COPD - an eight-year follow-up cohort study.

Purpose: Co-morbidities are common in chronic obstructive pulmonary disease (COPD) and are associated with increased morbidity and mortality. The aim of the present study was to explore the prevalence of several comorbid conditions in severe COPD, and to investigate and compare their associations with long-term mortality. Methods: In May 2011 to March 2012, 241 patients with COPD stage 3 or 4 were included in the study. Information was collected on sex, age, smoking history, weight and height, current pharmacological treatment, number of exacerbations the recent year and comorbid conditions. At December 31st, 2019, mortality data (all-cause and cause specific) were collected from the National Cause of Death Register. Data were analyzed using Cox-regression analysis with gender, age, previously established predictors of mortality and comorbid conditions as independent variables, and all-cause mortality and cardiac and respiratory mortality, respectively, as dependent variables. Results: Out of 241 patients, 155 (64%) were deceased at the end of the study period; 103 patients (66%) died of respiratory disease and 25 (16%) of cardiovascular disease. Impaired kidney function was the only comorbid condition independently associated with increased all-cause mortality (HR (95% CI) 3.41 (1.47-7.93) p=0.004) and respiratory mortality (HR (95%CI) 4.63 (1.61 to 13.4), p = 0.005). In addition, age ≥70, BMI <22 and lower FEV1 expressed as %predicted were significantly associated with increased all-cause and respiratory mortality. Conclusion: In addition to the risk factors high age, low BMI and poor lung function; impaired kidney function appears to be an important risk factor for mortality in the long term, which should be taken into account in the medical care of patients with severe COPD.

Expansion of Phenotypically Altered Dendritic Cell Populations in the Small Airways and Alveolar Parenchyma in Patients with Chronic Obstructive Pulmonary Disease.

Contrasting the antigen-presenting dendritic cells (DCs) in the conducting airways, the alveolar DC populations in human lungs have remained poorly investigated. Consequently, little is known about how alveolar DCs are altered in diseases such as chronic obstructive pulmonary disease (COPD). This study maps multiple tissue DC categories in the distal lung across COPD severities. Specifically, single-multiplex immunohistochemistry was applied to quantify langerin/CD207+, CD1a+, BDCA2+, and CD11c+ subsets in distal lung compartments from patients with COPD (GOLD stage I-IV) and never-smoking and smoking controls. In the alveolar parenchyma, increased numbers of CD1a+langerin- (p < 0.05) and BDCA-2+ DCs (p < 0.001) were observed in advanced COPD compared with controls. Alveolar CD11c+ DCs also increased in advanced COPD (p < 0.01). In small airways, langerin+ and BDCA-2+ DCs were also significantly increased. Contrasting the small airway DCs, most alveolar DC subsets frequently extended luminal protrusions. Importantly, alveolar and small airway langerin+ DCs in COPD lungs displayed site-specific marker profiles. Further, multiplex immunohistochemistry with single-cell quantification was used to specifically profile langerin DCs and reveal site-specific expression patterns of the maturation and activation markers S100, fascin, MHC2, and B7. Taken together, our results show that clinically advanced COPD is associated with increased levels of multiple alveolar DC populations exhibiting features of both adaptive and innate immunity phenotypes. This expansion is likely to contribute to the distal lung immunopathology in COPD patients.

Benefits, for patients with late stage chronic obstructive pulmonary disease, of being cared for in specialized palliative care compared to hospital. A nationwide register study.

BACKGROUND: In early stage chronic obstructive pulmonary disease (COPD), dyspnea has been reported as the main symptom; but at the end of life, patients dying from COPD have a heavy symptom burden. Still, specialist palliative care is seldom offered to patients with COPD; they more often receive end of life care in hospitals. Furthermore, symptoms, symptom relief and care activities in the last week of life for COPD patients are rarely studied. The aim of this study was to compare patient and care characteristics in late stage COPD patients treated in specialized palliative care (SPC) versus hospital. METHODS: Two nationwide registers were merged, the Swedish National Airway Register (SNAR) and the Swedish Register of Palliative Care (SRPC). Patients with COPD and < 50% of predicted forced expiratory volume in 1 s (FEV1), who had died in inpatient or outpatient SPC (n = 159) or in hospital (n = 439), were identified. Clinical COPD characteristics were extracted from the SNAR, and end of life (EOL) care characteristics from the SRPC. Descriptive statistics were used to describe the sample and the registered care and treatments. Independent samples t-test, Mantel-Haenszel chi-square test and Fisher's exact test was used to compare variables. To examine predictors of place of death, bivariate and multivariate logistic regression analyses were performed with a dependent variable with demographic and clinical variables used as independent variables. RESULTS: The patients in hospitals were older and more likely to have heart failure or hypertension. Pain was more frequently reported and relieved in SPC than in hospitals (p = 0.001). Rattle, anxiety, delirium and nausea were reported at similar frequencies between the settings; but rattle, anxiety, delirium, and dyspnea were more frequently relieved in SPC (all p < 0.001). Compared to hospital, SPC was more often the preferred place of care (p < 0.001). In SPC, EOL discussions with patients and families were more frequently held than in hospital (p < 0.001). Heart failure increased the probability of dying in hospital while lung cancer increased the probability of dying in SPC. CONCLUSION: This study provides evidence for referring more COPD patients to SPC, which is more focused on symptom management and psychosocial and existential support.

Early Predictors of Mortality in Patients with COPD, in Relation to Respiratory and Non-Respiratory Causes of Death - A National Register Study.

Background: Both single factors and composite measures have been suggested to predict mortality in patients with chronic obstructive pulmonary disease (COPD) and there is a need to analyze the relative importance of each variable. Objective: To explore the predictors of mortality for patients with COPD in relation to respiratory, cardiac, and malignant causes, as well as all causes of death. Methods: After merging the Swedish Respiratory Tract Register (SRTR) and the Swedish Cause of Death Register, patients with respiratory, cardiac, and other causes of death were identified. Demographic and clinical variables from the deceased patients' first registration with the SRTR were compared. Three univariable and multivariable Cox proportional hazards regression analyses were conducted for different causes of death, with time from first registration to either death or a fixed end date as dependent variable, and variables regarding demographics, respiration, and comorbidities as independent variables. Results: In the multivariable Cox models, mortality for patients with all causes of death was predicted by older age 1.79 (CI 1.41, 2.27), lower percentage of predicted forced expiratory volume in 1 second (FEV1 %) 0.99 (CI 0.98, 0.99), lower saturation 0.92 (CI 0.86, 0.97), worse dyspnea 1.48 (CI 1.26, 1.74) (p<0.002 to p<0.001), less exercise 0.91 (CI 0.85, 0.98), and heart disease 1.53 (CI 1.06, 2.19) (both p<0.05). Mortality for patients with respiratory causes was predicted by higher age 1.67 (CI 1.05, 2.65) (p<0.05), lower FEV1% 0.98 (CI 0.97, 0.99), worse dyspnea 2.05 (CI 1.45, 2.90), and a higher number of exacerbations 1.27 (CI 1.11, 1.45) (p<0.001 in all comparisons). For patients with cardiac causes of death, mortality was predicted by lower FEV1% 0.99 (CI 0.98, 0.99) (p=0.001) and lower saturation 0.82 (CI 0.76, 0.89) (p<0.001), older age 1.46 (CI 1.02, 2.09) (p<0.05), and presence of heart disease at first registration 2.06 (CI 1.13, 3.73) (p<0.05). Conclusion: Obstruction predicted mortality in all models and dyspnea in two models and needs to be addressed. Comorbidity with heart disease could further worsen the COPD patient's prognosis and should be treated by a multidisciplinary team of professional specialists.

Equal palliative care for patients with COPD? A nationwide register study.

Background: Although chronic obstructive pulmonary disease (COPD) is a life-limiting disease with a significant symptom burden, the patients are more often referred to nursing homes (NH), than to specialist palliative care (SPC) at the end of life (EOL). This study aimed to compare patients with COPD in SPC with those in NH and to compare the care provided. Methods: A national register study was carried out where the Swedish National Airway Register and the Swedish Register of Palliative Care were merged. COPD patients who died in NHs or short-term facilities were included in the NH group (n = 415) and those who died in SPC were included in the SPC group (n = 355). Demographic and clinical variables were included from the Swedish National Airway Register and variables concerning EOL care from the Swedish Register of Palliative Care. Results: Symptom prevalence was similar in NHs and SPC, but symptom assessment (32% vs 20%), symptom relief medication (93-98% in SPC vs 74-90% in NH), EOL discussions (88% vs 66%), and bereavement support (94% vs 67%) were more likely in SPC (in all comparisons p < 0.001). Younger age and co-habiting increased the probability of dying in SPC (p < 0.001). Conclusion: Despite similar symptom prevalence, older persons are more likely to be referred to NHs. If applying a palliative care philosophy in NHs, routine symptom assessment and prescription of rescue medication for frequent symptoms, would be more likely. Promoting advance care planning and EOL discussions at an earlier stage would result in more prepared patients and families.

Influences of patient education on exacerbations and hospital admissions in patients with COPD - a longitudinal national register study.

Introduction: Chronic obstructive pulmonary disease (COPD) contributes to impaired health-related quality of life (HRQoL). Patient education and smoking cessation programs are recommended to reduce the number of exacerbations and hospitalizations, but the effects of such programs have yet to be explored in larger samples. Objective: The aim was to explore the longitudinal effects of patient education and smoking cessation programs on exacerbations and hospital admissions in patients with COPD. Design: This is a register study where data from the Swedish National Airway Register, including 20,666 patients with COPD, were used. Baseline measures of demographic, disease-related, and patient-reported variables were compared with a follow-up, 10-30 months after baseline. Descriptive statistics and changes between baseline and follow-up were calculated. Results: Comparing those not participating in education programs to those who did, HRQoL deteriorated significantly between baseline and follow-up in non-participants; there was no change in either exacerbations or hospitalizations in either group; there was a significant difference in baseline HRQoL between the two, and, when controlling for this, there was no significant change (p = 0.73). Patients who participated in smoking cessation programs were younger than the non-participants; mean 66.0 (standard deviations (SD) 7.8) vs. mean 68.1 (SD 8.8), p = 0.006. Among participants in smoking cessation programs, the proportion with continued smoking decreased significantly, from 76% to 66%, p < 0.001. Exacerbations at follow-up were predicted by FEV1% of predicted value and exacerbations at baseline. Hospital admissions at follow-up were predicted by baseline FEV1% of predicted value and exacerbations at baseline. Conclusions: To prevent exacerbations and hospital admissions, treatment and prevention must be prioritized in COPD care. Patient education and smoking cessation programs are beneficial, but there is a need to combine them with other interventions.

Brain natriuretic peptide levels in middle aged subjects with normal left ventricular function in relation to mild-moderate COPD.

BACKGROUND: Levels of plasma brain natriuretic peptide (BNP) have been shown to be elevated in chronic obstructive pulmonary disease (COPD) especially in connection with cor pulmonale (CP) and the late stages of the disease. BNP is also raised in left sided heart failure which sometimes coincides with COPD. Whether BNP is elevated in subjects with mild-moderate stable COPD and normal left ventricular function is not clear. OBJECTIVE: To investigate BNP levels in subjects with mild-moderate COPD and normal left ventricular function. METHODS: This was a cross sectional study of 450 subjects from a population-based respiratory questionnaire survey. All subjects were examined with echocardiography and spirometry and blood samples were drawn for BNP measurements. Subjects with left sided heart disease (n = 26) or echocardiographic signs of elevated filling pressure (n = 75), COPD stages III and IV (n = 5) or missing data (n = 13) were excluded. RESULTS: In the final study population (n = 331) spirometry identified 86 subjects with COPD (GOLD stage I, n = 65 and GOLD stage II, n = 21). In comparison with the rest of the study population subjects with COPD were significantly older, longer and with a male predominance. In a multivariate linear regression analysis with log-normalized (lnBNP) as the dependent variable a significant correlation was found with age, left atrial volume, body surface area and haemoglobin, but not with any pulmonary variables. Even when comparing groups no significant difference could be found between the plasma levels of lnBNP in normal subjects (1.8 ± 0.7 mean ± SD, pmol/L) subjects and in COPD subjects (1.9 ± 0.7, P = 0.47). CONCLUSIONS: In a population with normal left ventricular function no significant differences in BNP levels between stable mild-moderate COPD subjects and normal individuals could be found.

VEGF synthesis is induced by prostacyclin and TGF-ß in distal lung fibroblasts from COPD patients and control subjects: Implications for pulmonary vascular remodelling.

BACKGROUND AND OBJECTIVE: Involvement of pulmonary vascular remodelling is a characteristic sign in COPD. Vascular mediators such as vascular endothelial growth factor (VEGF) and prostacyclin may regulate fibroblast activity. The objective was to study the synthesis of VEGF and interactions with prostacyclin and transforming growth factor (TGF)-ß1 in lung fibroblasts from patients with COPD and healthy control subjects. To further explore the autocrine role of synthesized VEGF on fibroblast activity, studies were performed in human lung fibroblasts (HFL-1). METHODS: Primary distal lung fibroblast cultures were established from healthy individuals and from COPD patients (GOLD stage IV). Lung fibroblasts were stimulated with the prostacyclin analogue iloprost and the profibrotic stimuli TGF-ß1 . VEGF synthesis was measured in the cell culture medium. Changes in proliferation rate, migration and synthesis of the extracellular matrix (ECM) proteins proteoglycans were analysed after stimulations with VEGF-A isoform 165 (VEGF165 ; 1-10 000 pg/mL) in HFL-1. RESULTS: Iloprost and TGF-ß1 significantly increased VEGF synthesis in both fibroblasts from COPD patients and control subjects. TGF-ß1 -induced VEGF synthesis was significantly reduced by the cyclooxygenase inhibitor indomethacin in fibroblasts from COPD patients. VEGF significantly increased proliferation rate and migration capacity in HFL-1. VEGF also significantly increased synthesis of the ECM proteins biglycan and perlecan. The VEGF receptors (VEGFR), VEGFR1, VEGFR2 and VEGFR3, were all expressed in primary lung fibroblasts and HFL-1. CONCLUSION: VEGF is synthesized in high amounts by distal lung fibroblasts and may have a crucial role in ongoing vascular remodelling processes in the distal lung compartments.

Characterization of secondary care for COPD in Sweden.

Introduction: Only a selected proportion of chronic obstructive pulmonary disease (COPD) patients are managed in secondary care. The aim of this study was to characterize disease severity, treatment and structure of secondary care for COPD in Sweden. Methods: Information was collected from 29 of 33 existing secondary care units of respiratory medicine in Sweden, using both individual data from 373 consecutively enrolled COPD patients with Global initiative on Obstructive Lung Disease (GOLD) stage III-IV and a structural questionnaire about available resources at the units. Patient data included exacerbations, health status assessed by COPD Assessment Test (CAT), lung function, comorbid conditions, pharmacological treatment and vaccinations. Structural data included available smoking cessation support, multidisciplinary rehabilitation, physical training, patient education and routine follow-up after exacerbations at the respective unit. All patients were reclassified according to the GOLD 2014 group A-D classification. Multiple linear regression investigated associations of available resources with number of exacerbations and CAT score. Results: According to GOLD 2014, 87% of the population were GOLD D and 13% were GOLD C. Triple inhaled therapy were prescribed in 88% of the patients. Over 75% of the units had resources for smoking cessation, multidisciplinary rehabilitation, physical training and patient education. Routine follow-up after exacerbations was available in 35% of the units. Being managed at units with access to structured patient education was associated with statistically significantly fewer exacerbations (adjusted regression coefficient (95% confidence interval) -0.79 (-1.39 to -0.19), p = 0.010). Conclusion: Most stage III-IV COPD patients managed at secondary care respiratory units in Sweden have maximized inhaled therapy and high risk disease even when reclassified according to GOLD 2014. Most units have access to smoking cessation, rehabilitation and patient education. Patients managed at units with structured patient education have a lower exacerbation risk.

Fixed ratio or lower limit of normal for the FEV1 /VC ratio: relation to symptoms and extended lung function tests.

There is no general agreement on the spirometric definition of chronic obstructive pulmonary disease (COPD). The global initiative for obstructive lung disease recommends a fixed ratio between forced expiratory volume in one-second (FEV1 ) and forced vital capacity (FVC) of <0·7 (FR) for the diagnosis of COPD. European Respiratory Society and American Thoracic Society favour the use of the fifth percentile of the age-related FEV1 /FVC ratio (the lower limit of normal, LLN). The purpose of this study was to analyse extensive lung function tests in groups of subjects fulfilling none, either or both of the spirometric criteria for COPD. From a previous population-based study, 450 subjects were examined with spirometry, body pletysmography diffusing capacity for CO (DL,CO ), Impulse Oscillometry System (IOS) and answered a questionnaire on respiratory symptoms and diseases. Seventy subjects fulfilled both spirometric COPD criteria (FR+LLN+), 62 subjects the fixed ratio criterion (FR+) only. Of the remaining 318 subjects, 236 were ever smokers (N-ES). Significant differences between all groups were seen for FEV1 and DL,CO . Significant differences between groups were also seen for residual volume (RV) and RV/total lung capacity. For IOS, variables and symptoms increasingly abnormal values were seen from never smokers to FR+LLN+. This study shows that subjects meeting both spirometric COPD criteria frequently have symptoms and findings at extended lung function tests compatible with the diagnosis. Also subjects meeting the fixed ratio criterion only tend to have more symptoms and lung function findings compatible with COPD than ever-smoking subjects with FEV1 /VC > 0·7.

Echocardiographic consequences of smoking status in middle-aged subjects.

BACKGROUND: Smoking is known to have many short- and long-term cardiovascular effects. Cardiac index (CI), which is cardiac output indexed to body surface area, is considered to be a valid measure of cardiac performance. We investigated whether there were any differences in CI or other echocardiographic variables between never smokers, ex-smokers, and current smokers in a cardiopulmonary healthy population. METHODS: Subjects (n=355) from a previous population-based respiratory questionnaire survey (never smokers, ex-smokers, and current smokers without significant chronic obstructive lung disease) were examined with echocardiography, and CI (L/min/m2 ) was calculated. RESULTS: Current smokers had a higher CI than never smokers 2.61±0.52 L/min/m2 vs. 2.42±0.49 L/min/m2 (P<.01). Ex-smokers had a nonsignificant, numerically higher value for CI than never smokers 2.54±0.54 L/min/m2 vs. 2.42±0.49 L/min/m2 (P>.05). Smoking status had no significant effect on other echocardiographic variables. CONCLUSION: We conclude that currents smokers without known cardiac disease or significant chronic obstructive lung disease show signs of slightly altered hemodynamics.

Management of COPD, equal treatment across age, gender, and social situation? A register study.

Chronic obstructive pulmonary disease (COPD) is a progressive chronic disease where treatment decisions should be based on disease severity and also should be equally distributed across age, gender, and social situation. The aim of this study was to determine to what extent patients with COPD are offered evidence-based interventions and how the interventions are distributed across demographic and clinical factors in the sample. Baseline registrations of demographic, disease-related, and management-related variables of 7,810 patients in the Swedish National Airway Register are presented. One-third of the patients were current smokers. Patient-reported dyspnea and health-related quality of life were more deteriorated in elderly patients and patients living alone. Only 34% of currently smoking patients participated in the smoking cessation programs, and 22% of all patients were enrolled in any patient education program, with women taking part in them more than men. Less than 20% of the patients had any contact with physiotherapists or dieticians, with women having more contact than men. Men had more comorbidities than women, except for depression and osteoporosis. Women were more often given pharmacological treatments. With increasing severity of dyspnea, participation in patient education programs was more common. Dietician contact was more common in those with lower body mass index and more severe COPD stage. Both dietician contact and physiotherapist contact increased with deteriorated health-related quality of life, dyspnea, and increased exacerbation frequency. The present study showed that COPD management is mostly equally distributed across demographic characteristics. Only a minority of the patients in the present study had interdisciplinary team contacts. Thus, this data shows that the practical implementation of structured guidelines for treatment of COPD varies, to some extent, with regard to age and gender. Also, disease characteristics influence guideline implementation for each individual patient. Quality registers have the strength to follow-up on compliance with guidelines and show whether an intervention needs to be adapted prior to implementation in health care practice.

Individualized prediction of lung-function decline in chronic obstructive pulmonary disease.

BACKGROUND: The rate of lung-function decline in chronic obstructive pulmonary disease (COPD) varies substantially among individuals. We sought to develop and validate an individualized prediction model for forced expiratory volume at 1 second (FEV1) in current smokers with mild-to-moderate COPD. METHODS: Using data from a large long-term clinical trial (the Lung Health Study), we derived mixed-effects regression models to predict future FEV1 values over 11 years according to clinical traits. We modelled heterogeneity by allowing regression coefficients to vary across individuals. Two independent cohorts with COPD were used for validating the equations. RESULTS: We used data from 5594 patients (mean age 48.4 yr, 63% men, mean baseline FEV1 2.75 L) to create the individualized prediction equations. There was significant between-individual variability in the rate of FEV1 decline, with the interval for the annual rate of decline that contained 95% of individuals being -124 to -15 mL/yr for smokers and -83 to 15 mL/yr for sustained quitters. Clinical variables in the final model explained 88% of variation around follow-up FEV1. The C statistic for predicting severity grades was 0.90. Prediction equations performed robustly in the 2 external data sets. INTERPRETATION: A substantial part of individual variation in FEV1 decline can be explained by easily measured clinical variables. The model developed in this work can be used for prediction of future lung health in patients with mild-to-moderate COPD. TRIAL REGISTRATION: Lung Health Study - ClinicalTrials.gov, no. NCT00000568; Pan-Canadian Early Detection of Lung Cancer Study - ClinicalTrials.gov, no. NCT00751660.

Health-related quality of life in a nationwide cohort of patients with COPD related to other characteristics.

BACKGROUND: In chronic obstructive pulmonary disease (COPD), various factors, such as dyspnoea, obstruction, exacerbations, smoking, exercise capacity, and body mass index, have been found to influence mortality and health-related quality of life (HRQOL). In order to identify subgroups of patients needing special attention, the aim of the present study was to explore the relationships between disease progression factors and HRQOL across COPD stages. METHODS: Baseline registrations from the Swedish COPD register of demographic, clinical, and patient-reported variables of 7,810 patients are presented. Dyspnoea was measured by the modified Medical Research Council (mMRC) dyspnoea scale and HRQOL by the Clinical COPD Questionnaire (CCQ). RESULTS: This study shows as expected that patients with spirometrically more severe COPD had a significantly higher number of exacerbations and hospitalisations, significantly increasing dyspnoea, significantly decreasing body mass index and exercise capacity, and significantly worsening HRQOL. When adjusting for spirometric stage of COPD, deteriorated HRQOL was predicted by increasing dyspnoea, depression/anxiety, increasing number of exacerbations, and decreased exercise capacity. Further, these data show that an mMRC value of 2 corresponds to a CCQ value of 1.9. CONCLUSION: The COPD patients suffered from a significant symptom burden, influencing HRQOL. A surprisingly great proportion of patients in spirometric stages II-IV showed marked changes of CCQ, indicating a need for an improved collaboration between clinical pulmonary medicine and palliative care.

The Relationship Between 24-Hour Symptoms and COPD Exacerbations and Healthcare Resource Use: Results from an Observational Study (ASSESS).

This observational study assessed the relationship between nighttime, early-morning and daytime chronic obstructive pulmonary disease (COPD) symptoms and exacerbations and healthcare resource use. COPD symptoms were assessed at baseline in patients with stable COPD using a standardised questionnaire during routine clinical visits. Information was recorded on exacerbations and healthcare resource use during the year before baseline and during a 6-month follow-up period. The main objective of the analysis was to determine the predictive nature of current symptoms for future exacerbations and healthcare resource use. 727 patients were eligible (65.8% male, mean age: 67.2 years, % predicted forced expiratory volume in 1 second: 52.8%); 698 patients (96.0%) provided information after 6 months. Symptoms in any part of the day were associated with a prior history of exacerbations (all p < 0.05) and nighttime and early-morning symptoms were associated with the frequency of primary care visits in the year before baseline (both p < 0.01). During follow-up, patients with baseline symptoms during any part of the 24-hour day had more exacerbations than patients with no symptoms in each period (all p < 0.05); there was also an association between 24-hour symptoms and the frequency of primary care visits (all p ≤ 0.01). Although there was a significant association between early-morning and daytime symptoms and exacerbations during follow-up (both p < 0.01), significance was not maintained when adjusted for potential confounders. Prior exacerbations were most strongly associated with future risk of exacerbation. The results suggest 24-hour COPD symptoms do not independently predict future exacerbation risk.

The phenotype of concurrent chronic bronchitis and frequent exacerbations in patients with severe COPD attending Swedish secondary care units.

BACKGROUND: Chronic bronchitis and previous exacerbations are both well-known risk factors for new exacerbations, impaired health-related quality of life, and increased mortality in COPD. The aim of the study was to characterize the phenotype of concurrent chronic bronchitis and frequent exacerbation in severe COPD. METHODS: Information on patient characteristics, comorbidity, and exacerbations from the previous year (total number and number requiring hospitalization) was collected from 373 patients with stage III and IV COPD attending 27 secondary care respiratory units in Sweden. Logistic regression used chronic bronchitis and frequent exacerbations (≥2 exacerbations or ≥1 hospitalized exacerbations in the previous year) as response variables. Stratification and interaction analyses examined effect modification by sex. RESULTS: Chronic bronchitis was associated with current smoking (adjusted odds ratio [OR] [95% CI], 2.75 [1.54-4.91]; P=0.001), frequent exacerbations (OR [95% CI], 1.93 [1.24-3.01]; P=0.004), and musculoskeletal symptoms (OR [95% CI], 1.74 [1.05-2.86]; P=0.031), while frequent exacerbations were associated with lung function (forced expiratory volume in 1 second as a percentage of predicted value [FEV1% pred]) (OR [95% CI] 0.96 [0.94-0.98]; P=0.001) and chronic bronchitis (OR [95% CI] 1.73 [1.11-2.68]; P=0.015). The phenotype with both chronic bronchitis and frequent exacerbations was associated with FEV1% pred (OR [95% CI] 0.95 [0.92-0.98]; P=0.002) and musculoskeletal symptoms (OR [95% CI] 2.55 [1.31-4.99]; P=0.006). The association of smoking with the phenotype of chronic bronchitis and exacerbations was stronger in women than in men (interaction, P=0.040). CONCLUSION: Musculoskeletal symptoms and low lung function are associated with the phenotype of combined chronic bronchitis and frequent exacerbations in severe COPD. In women, current smoking is of specific importance for this phenotype. This should be considered in clinical COPD care.

Comorbidity and health-related quality of life in patients with severe chronic obstructive pulmonary disease attending Swedish secondary care units.

INTRODUCTION: Our understanding of how comorbid diseases influence health-related quality of life (HRQL) in patients with chronic obstructive pulmonary disease (COPD) is limited and in need of improvement. The aim of this study was to examine the associations between comorbidities and HRQL as measured by the instruments EuroQol-5 dimension (EQ-5D) and the COPD Assessment Test (CAT). METHODS: Information on patient characteristics, chronic bronchitis, cardiovascular disease, diabetes, renal impairment, musculoskeletal symptoms, osteoporosis, depression, and EQ-5D and CAT questionnaire results was collected from 373 patients with Forced Expiratory Volume in one second (FEV1) <50% of predicted value from 27 secondary care respiratory units in Sweden. Correlation analyses and multiple linear regression models were performed using EQ-5D index, EQ-5D visual analog scale (VAS), and CAT scores as response variables. RESULTS: Having more comorbid conditions was associated with a worse HRQL as assessed by all instruments. Chronic bronchitis was significantly associated with a worse HRQL as assessed by EQ-5D index (adjusted regression coefficient [95% confidence interval] -0.07 [-0.13 to -0.02]), EQ-5D VAS (-5.17 [-9.42 to -0.92]), and CAT (3.78 [2.35 to 5.20]). Musculoskeletal symptoms were significantly associated with worse EQ-5D index (-0.08 [-0.14 to -0.02]), osteoporosis with worse EQ-5D VAS (-4.65 [-9.27 to -0.03]), and depression with worse EQ-5D index (-0.10 [-0.17 to -0.04]). In stratification analyses, the associations of musculoskeletal symptoms, osteoporosis, and depression with HRQL were limited to female patients. CONCLUSION: The instruments EQ-5D and CAT complement each other and emerge as useful for assessing HRQL in patients with COPD. Chronic bronchitis, musculoskeletal symptoms, osteoporosis, and depression were associated with worse HRQL. We conclude that comorbid conditions, in particular chronic bronchitis, depression, osteoporosis, and musculoskeletal symptoms, should be taken into account in the clinical management of patients with severe COPD.

Observational study to characterise 24-hour COPD symptoms and their relationship with patient-reported outcomes: results from the ASSESS study.

BACKGROUND: Few studies have investigated the 24-hour symptom profile in patients with COPD or how symptoms during the 24-hour day are inter-related. This observational study assessed the prevalence, severity and relationship between night-time, early morning and daytime COPD symptoms and explored the relationship between 24-hour symptoms and other patient-reported outcomes. METHODS: The study enrolled patients with stable COPD in clinical practice. Baseline night-time, early morning and daytime symptoms (symptom questionnaire), severity of airflow obstruction (FEV1), dyspnoea (modified Medical Research Council Dyspnoea Scale), health status (COPD Assessment Test), anxiety and depression levels (Hospital Anxiety and Depression Scale), sleep quality (COPD and Asthma Sleep Impact Scale) and physical activity level (sedentary, moderately active or active) were recorded. RESULTS: The full analysis set included 727 patients: 65.8% male, mean ± standard deviation age 67.2 ± 8.8 years, % predicted FEV1 52.8 ± 20.5%. In each part of the 24-hour day, >60% of patients reported experiencing ≥1 symptom in the week before baseline. Symptoms were more common in the early morning and daytime versus night-time (81.4%, 82.7% and 63.0%, respectively). Symptom severity was comparable for each period assessed. Overall, in the week before baseline, 56.7% of patients had symptoms throughout the whole 24-hour day (3 parts of the day); 79.9% had symptoms in ≥2 parts of the 24-hour day. Symptoms during each part of the day were inter-related, irrespective of disease severity (all p < 0.001). Early morning and daytime symptoms were associated with the severity of airflow obstruction (p < 0.05 for both). Night-time, early morning and daytime symptoms were all associated with worse dyspnoea, health status and sleep quality, and higher anxiety and depression levels (all p < 0.001 versus patients without symptoms in each corresponding period). In each part of the 24-hour day, there was also an association between symptoms and a patient's physical activity level (p < 0.05 for each period). CONCLUSIONS: More than half of patients experienced COPD symptoms throughout the whole 24-hour day. There was a significant relationship between night-time, early morning and daytime symptoms. In each period, symptoms were associated with worse patient-reported outcomes, suggesting that improving 24-hour symptoms should be an important consideration in the management of COPD.

Increased incidence of invasive bacterial disease in chronic obstructive pulmonary disease compared to the general population--a population based cohort study.

BACKGROUND: Innate defence mechanisms of the airways are impaired in chronic obstructive pulmonary disease (COPD), predisposing patients to lower respiratory tract infections, but less is known about the association with other infections. In this population-based cohort study, we investigated the associations between COPD and invasive bacterial disease by comparing incidence rates of bacteraemia in COPD patients and randomly selected reference individuals from the general population. METHODS: In this population based cohort study all patients with COPD, ≥40 years of age, who were discharged from hospitals in southern Sweden between 1990 and 2003 were identified in the Swedish Inpatient Register (n = 15,403). Age and gender matched reference individuals were randomly selected from the general population. Records were cross-referenced to the microbiological databases covering the region, 1990-2010. The hazard ratios (HR) of bloodstream infections and hospitalisations for infections were estimated by Cox proportional hazards regression. RESULTS: We found that individuals with COPD had a 2.5-fold increased incidence of bacteraemia compared to the reference individuals from the general population adjusted for other co-morbidity and socio-economic status (hazard ratio: 2.5, 95% confidence interval: 2.2-2.7). The increased incidence of bacteraemia was paralleled by an increased incidence of hospitalisation for non-respiratory infections, i.e., skin infections, pyelonephritis, or septic arthritis. Despite higher absolute rates of bloodstream infections among COPD patients than among the general population, the distribution of different pathogens was similar. CONCLUSIONS: In summary this population-based study shows COPD is associated with an increased incidence of invasive bacterial infections compared to the general population, indicating a general frailty of acquiring severe infections in addition to the specific susceptibility to infections of respiratory origin. The underlying contributory factors (e.g. smoking, corticosteroid use, co-morbid diseases or a frailty inherent to COPD itself) need to be disentangled in further studies.

Use of inhaled corticosteroids in patients with COPD and the risk of TB and influenza: A systematic review and meta-analysis of randomized controlled trials. a systematic review and meta-analysis of randomized controlled trials.

Background: The use of inhaled corticosteroids (ICSs) is associated with an increased risk of pneumonia in patients with COPD. However, the risks of other respiratory infections, such as TB and influenza, remain unclear.Methods: Through a comprehensive literature search of MEDLINE, EMBASE, CINAHL, Cochrane Library, and ClinicalTrials.gov from inception to July 2013, we identified randomized controlled trials of ICS therapy lasting at least 6 months. We conducted meta-analyses by the Peto, Mantel-Haenszel, and Bayesian approaches to generate summary estimates comparing ICS with non-ICS treatment on the risk of TB and influenza.Results: Twenty-fi ve trials (22,898 subjects) for TB and 26 trials (23,616 subjects) for influenza were included. Compared with non-ICS treatment, ICS treatment was associated with a significantly higher risk of TB (Peto OR, 2.29; 95% CI, 1.04-5.03) but not influenza (Peto OR, 1.24;95% CI, 0.94-1.63). Results were similar with each meta-analytic approach. Furthermore, the number needed to harm to cause one additional TB event was lower for patients with COPD treated with ICSs in endemic areas than for those in nonendemic areas (909 vs 1,667, respectively).Conclusions: This study raises safety concerns about the risk of TB and influenza associated with ICS use in patients with COPD, which deserve further investigation.