Impact of comorbidities in COPD clinical control criteria. The CLAVE study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) frequently coexists with other chronic diseases, namely comorbidities. They negatively impact prognosis, exacerbations and quality of life in COPD patients. However, no studies have been performed to explore the impact of these comorbidities on COPD clinical control criteria. RESEARCH QUESTION: Determine the relationship between individualized comorbidities and COPD clinical control criteria. STUDY DESIGN AND METHODS: Observational, multicenter, cross-sectional study performed in Spain involving 4801 patients with severe COPD (< 50 predicted forced expiratory volume in the first second [FEV1%]). Clinical control criteria were defined by the combination of COPD assessment test (CAT) scores (≤16 vs ≥17) and exacerbations in the previous three months (none vs ≥1). Binary logistic regression adjusted by age and FEV1% was performed to identify comorbidities potentially associated with the lack of control of COPD. Secondary endpoints were the relationship between individualized comorbidities with COPD assessment test and exacerbations within the last three months. RESULTS: Most frequent comorbidities were arterial hypertension (51.2%), dyslipidemia (36.0%), diabetes (24.9%), obstructive sleep apnea-hypopnea syndrome (14.9%), anxiety (14.1%), heart failure (11.6%), depression (11.8%), atrial fibrillation (11.5%), peripheral arterial vascular disease (10.4%) and ischemic heart disease (10.1%). After age and FEV1% adjustment, comorbidities related to lack of clinical control were cardiovascular diseases (heart failure, peripheral vascular disease and atrial fibrillation; p < 0.0001), psychologic disorders (anxiety and depression; all p < 0.0001), metabolic diseases (diabetes, arterial hypertension and abdominal obesity; all p < 0.001), sleep disorders (p < 0.0001), anemia (p = 0.015) and gastroesophageal reflux (p < 0.0001). These comorbidities were also related to previous exacerbations and COPD assessment test scores. INTERPRETATION: Comorbidities are frequent in patients with severe COPD, negatively impacting COPD clinical control criteria. They are related to health-related quality of life measured by the COPD assessment test. Our results suggest that comorbidities should be investigated and treated in these patients to improve their clinical control. TAKE-HOME POINTS: Study question: What is the impact of comorbidities on COPD clinical control criteria? RESULTS: Among 4801 patients with severe COPD (27.5% controlled and 72.5% uncontrolled), after adjustment by age and FEV1%, comorbidities related to lack of clinical control were cardiovascular diseases (heart failure, peripheral vascular disease and atrial fibrillation; p < 0.0001), psychologic disorders (anxiety and depression; p < 0.0001), metabolic diseases (diabetes, arterial hypertension and abdominal obesity; p < 0.001), obstructive sleep apnea-hypopnea syndrome (p < 0.0001), anaemia (p = 0.015) and gastroesophageal reflux (p < 0.0001), which were related to previous exacerbations and COPD assessment test scores. INTERPRETATION: Comorbidities are related to health-related quality of life measured by the COPD assessment test scores and history of exacerbations in the previous three months.

Determinants of blood eosinophil levels in the general population and patients with COPD: a population-based, epidemiological study.

BACKGROUND: Blood eosinophils are considered a biomarker for the treatment of chronic obstructive pulmonary disease (COPD). Population-based studies are needed to better understand the determinants of the blood eosinophil count (BEC) in individuals with and without COPD. METHODS: EPISCAN II is a multicentre, cross-sectional, population-based epidemiological study aimed at investigating the prevalence and determinants of COPD in Spain. Study subjects were randomly selected from the general population, and COPD was defined by a post-bronchodilator FEV1/FVC < 0.7. For the pre-specified outcomes related to BEC, the first 35 COPD and 35 non-COPD subjects were consecutively recruited in 12 of the participating centres with the objective of analysing 400 individuals in each group. Baseline BEC and its association with demographic, clinical and functional variables were analysed. RESULTS: A total of 326 COPD and 399 non-COPD subjects were included in the analysis. The mean age (standard deviation [SD]) was 63.2 years (11.0), 46.3% were male, and 27.6% were active smokers. BEC was significantly higher in individuals with COPD [192 cells/µL (SD: 125) vs. 160 cells/µL (SD: 114); p = 0.0003]. In a stepwise multivariate model, being male, active smoker and having a previous diagnosis of asthma were independently associated with having a higher BEC. CONCLUSIONS: This population-based study estimated the distribution of eosinophils in the healthy adult population and concluded that COPD patients have a significantly higher BEC. Male sex, active smoking and concomitant asthma were significantly associated with a higher BEC.

Bronchial Infection and Temporal Evolution of Bronchiectasis in Patients With Chronic Obstructive Pulmonary Disease.

BACKGROUND: Bronchiectasis (BE) impact the clinical course and prognosis of patients with chronic obstructive pulmonary disease (COPD). Yet, the temporal evolution of BE in these patients is unknown. This study seeks to assess the temporal evolution of BE in persons with COPD. METHODS: 201 moderate-to-severe patients were recruited between 2004 and 2007 and followed up at least every 6 monts (median of 102 months). To investigate the temporal evolution of BE, in 2015 a second high-resolution computed tomography scan (HRCT) was obtained in survivors and compared with the one obtained at recruitment. RESULTS: 99 (49.3%) died during follow-up. The second HRCT could be obtained in 77 patients and showed that (1) in 27.3% of patients BE never developed, in 36.4% they remained stable, in 16.9% they increased in size and/or extension, and in 19.5% new BE emerged; and that (2) the presence of chronic purulent sputum (hazard ratio [HR], 2.8 [95% confidence interval {CI}, 1.3-5.8]), number of hospitalizations due to exacerbatons (HR, 1.2 [95% CI, 1.1-1.5]), and number of pathogenic microorganism (PPM) isolations (HR, 1.1 [95% CI, 1.02-1.3]) were independent risk factors for the progression or development of BE. CONCLUSIONS: The presence of chronic purulent sputum production, number of PPMs isolated in sputum, and number of hospitalizations due to exacerbations of COPD are independent risk factors of BE progression in patients with COPD.

Chronic bronchial infection and incident cardiovascular events in chronic obstructive pulmonary disease patients: A long-term observational study.

BACKGROUND AND OBJECTIVE: Cardiovascular (CV) diseases are frequent in patients with chronic obstructive pulmonary disease (COPD). Likewise, chronic bronchial infection (CBI) is also frequent in COPD and it is associated with systemic inflammation, a well-known CV risk factor. The objective of this study was to investigate the relationship between CBI, systemic inflammation and incident CV events. METHODS: A post hoc analysis of prospectively collected cohort of 201 COPD patients [Global Initiative for Chronic Obstructive Lung Disease (GOLD) II-IV] followed up every 3-6 months for 84 months was conducted. CBI was defined as ≥3 positive pathogenic microorganisms sputum cultures over 1 year, separated by ≥3 months. Systemic inflammation was assessed by circulating levels of C-reactive protein and fibrinogen. Fatal and non-fatal CV events, including coronary and cerebrovascular events as well as arrhythmia episodes, were prospectively recorded. For analysis, they were analysed separately and combined in a composite variable. RESULTS: As hypothesized, CBI was associated with persistent systemic inflammation and a significantly higher incidence of CV events (HR: 3.88; 95% CI: 1.83-8.22), mainly of coronary origin independent of age, number and severity of exacerbations, comorbidities, other CV risk factors, lung function, BMI, smoking status and treatments. These associations were particularly significant in patients with CBI by Pseudomonas aeruginosa (PA). CONCLUSION: CBI, particularly by PA, is associated with sustained and enhanced systemic inflammation and a higher incidence of CV events (especially coronary events). The possibility that treating CBI may decrease systemic inflammation and CV events in COPD deserves prospective, interventional studies.

Inhaled Steroids, Circulating Eosinophils, Chronic Airway Infection, and Pneumonia Risk in Chronic Obstructive Pulmonary Disease. A Network Analysis.

Rationale: Treatment of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroids (ICS) is controversial, because it can reduce the risk of future exacerbations of the disease at the expense of increasing the risk of pneumonia.Objectives: To assess the relationship between the presence of chronic bronchial infection (CBI), reduced number of circulating eosinophils, ICS treatment, and the risk of pneumonia in patients with COPD.Methods: This was a post hoc long-term observational study of an historical cohort of 201 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease II-IV) who were carefully characterized (including airway microbiology) and followed for a median of 84 months. Results were analyzed by multivariate Cox regression and network analysis.Measurements and Main Results: Mean age was 70.3 years, 90.5% of patients were male, mean FEV1 was 49%, 71.6% of patients were treated with ICS, 57.2% of them had bronchiectasis, and 20.9% had <100 blood eosinophils/µl. Pathogenic microorganisms were isolated in 42.3% of patients, and 22.4% of patients fulfilled the definition of CBI. During follow-up, 38.8% of patients suffered one or more episodes of pneumonia, with CBI (hazard ratio [HR], 1.635) and <100 eosinophils/µl (HR, 1.975) being independently associated with the risk of pneumonia, particularly when both coexist (HR, 3.126). ICS treatment increased the risk of pneumonia in those patients with <100 eosinophils/µl and CBI (HR, 2.925).Conclusions: Less than 100 circulating eosinophils/µl combined with the presence of CBI increase the risk of pneumonia in patients with COPD treated with ICS.

A modified Delphi consensus study to identify improvement proposals for COPD management amongst clinicians and administrators in Spain.

AIMS: To identify the obstacles hindering the appropriate management of chronic obstructive pulmonary disease (COPD) in Spain based on consensus amongst clinicians and administrators. METHODS: A two-round modified Delphi questionnaire was sent to clinicians (pulmonologists and GPs) and administrators, all experts in COPD. The scientific committee developed the statements and selected the participating experts. Four areas were explored: diagnosis, training, treatment, and clinical management. Panellists' agreement was assessed using a 9-point Likert scale, with scores of 1 to 3 indicating disagreement and 7 to 9, agreement. Consensus was considered to exist when 70% of the participants agreed or disagreed with the statement. RESULTS: Respective response rates for the first and second round were 68% and 91% for clinicians, and 60% and 100% for administrators. The statements attracting the highest degree of consensus were: "Not enough nursing resources (time, staff, duties) are allocated for performing spirometry" (85.3% clinicians; 75% administrators); "Nurses need specific training in COPD" (84.8% clinicians; 100% administrators); "Rehabilitation programs are necessary for treating patients with COPD" (94.1% clinicians; 91.7% administrators); and "Integrated care processes facilitate the deployment of educational programs on COPD" (79.4% clinicians; 83.3% administrators). CONCLUSIONS: This document can inform the development and implementation of specific initiatives addressing the existing obstacles in COPD management. WHAT'S KNOWN: COPD is a prevalent and underdiagnosed disease that causes substantial morbidity and mortality. The National COPD Strategy established objectives and work programmes to apply in Spain. There are barriers impeding the application of interventions contemplated in the COPD strategy. WHAT'S NEW: Different agents involved in COPD management agree that the main challenges to improve COPD management are resource shortages in primary care nursing and lack of training in the use of COPD clinical guidelines. Clinicians and administrators involved in COPD management support the implementation of urgent measures to tackle the underdiagnosis of COPD, especially in primary care, along with the routine inclusion of respiratory rehabilitation programmes for COPD.

Risk Factors and Relation with Mortality of a New Acquisition and Persistence of Pseudomonas aeruginosa in COPD Patients.

The isolation of Pseudomonas aeruginosa (PA) in patients with chronic obstructive pulmonary disease (COPD) is associated with increased mortality. Yet, factors associated with first PA sputum isolation, and PA persistence have not been investigated before. The objective of the present study was to investigate risk factors for new acquisition and persistence of PA infection and their relationship with all-cause mortality in patients with COPD. Post-hoc analysis of prospectively collected cohort of 170 COPD patients (GOLD II-IV) who were free of previous PA isolation and followed up every 3-6 months for 85 [50.25-110.25] months. PA was isolated for the first time in 41 patients (24.1%) after 36 [12-60] months of follow-up. Risk factor for first PA isolation were high cumulative smoking exposure, severe airflow limitation, previous severe exacerbations, high fibrinogen levels and previous isolation of Haemophilus Influenzae. PA was isolated again one or more times during follow-up in 58.5% of these patients. This was significantly associated with the presence of CT bronchiectasis and persistence of severe exacerbations, whereas the use of inhaled antibiotic treatment after the first PA isolation (at the discretion of the attending physician) reduced PA persistence. During follow-up, 79 patients (46.4%) died. A single PA isolation did not increase mortality, but PA persistence did (HR 3.06 [1.8-5.2], p = 0.001). We conclude that PA occurs frequently in clinically stable COPD patients, risk factors for a first PA isolation and PA persistence are different, and the latter (but not the former) is associated with increased all-cause mortality.

COPD clinical control as a predictor of future exacerbations: concept validation in the SPARK study population.

The concept of chronic obstructive pulmonary disease (COPD) control has been proposed to guide treatment decisions in COPD. In this study, we aimed to validate the prospective value of this concept in the SPARK study population. Control was assessed based on COPD stability and impact. Patients with low impact and stability during weeks 1-12 were classified as controlled, and exacerbations were measured during a 52-week follow-up. Of the 2044 patients included a majority were non-controlled (80%), frequently due to high impact. During the follow-up, the rate of moderate/severe exacerbations was significantly lower in controlled patients (rate ratio, 0.56, 95% CI 0.48 to 0.65 p<0.0001) and time-to-first moderate/severe exacerbation was significantly delayed. This study demonstrated an association between control status and risk of exacerbations.

Predictive value of control of COPD for risk of exacerbations: An international, prospective study.

BACKGROUND AND OBJECTIVE: The concept of clinical control in COPD has been developed to help in treatment decisions, but it requires validation in prospective studies. METHODS: This international, multicentre, prospective study aimed to validate the concept of control in COPD. Patients with COPD were classified as controlled/uncontrolled by clinical criteria or CAT scores at baseline and followed up for 18 months. The main outcome was the difference in rate of a composite endpoint of moderate and severe exacerbations or death over the 18-month follow-up period. RESULTS: A total of 307 patients were analysed (mean age = 68.6 years and mean FEV1 % = 52.5%). Up to 65% and 37.9% of patients were classified as controlled by clinical criteria or CAT, respectively. Controlled patients had significantly less exacerbations during follow-up (by clinical criteria: 1.1 vs 2.6, P < 0.001; by CAT: 1.1 vs 1.9, P = 0.014). Time to first exacerbation was significantly prolonged for patients controlled by clinical criteria only (median: 93 days, IQR: 63; 242 vs 274 days, IQR: 221; 497 days; P < 0.001). Control status by clinical criteria was a better predictor of exacerbations compared to CAT criteria (AUC: 0.67 vs 0.57). CONCLUSION: Control status, defined by easy-to-obtain clinical criteria, is predictive of future exacerbation risk and time to the next exacerbation. The concept of control can be used in clinical practice at each clinical visit as a complement to the current recommendations of initial treatment proposed by guidelines.

Increased Incidence of Stroke, but Not Coronary Heart Disease, in Elderly Patients With Sleep Apnea.

Background and Purpose- The influence of age on the relationship between obstructive sleep apnea (OSA) and the incidence of hard cardiovascular events remains controversial. We sought to analyze the relationship between OSA and the incidence of stroke and coronary heart disease in a large cohort of elderly patients, as well as to investigate the role of continuous positive airway pressure (CPAP) treatment in these associations. Methods- Post hoc analysis of a prospective observational study of consecutive patients ≥65 years studied for OSA suspicion at 2 Spanish University Hospitals. Patients with an apnea-hypopnea index (AHI) <15 were the reference group. OSA was defined by an AHI ≥15 and classified as untreated (CPAP not prescribed or compliance <4 hours/day), mild-moderate (AHI 15-29), untreated severe (AHI ≥30), and CPAP-treated (AHI ≥15 and CPAP compliance ≥4 hours/day). Results- 859 and 794 elderly patients were included in the stroke and coronary heart disease analyses, respectively. The median (interquartile range) follow-up was 72 (50-88.5) and 71 (51.5-89) months, respectively. Compared with the reference group, the fully adjusted hazard ratios for the incidence of stroke were 3.42 (95% CI, 1.37-8.52), 1.02 (95% CI, 0.41-2.56), and 1.76 (95% CI, 0.62-4.97) for the untreated severe OSA group, CPAP-treated group, and untreated mild-moderate OSA group, respectively. No associations were shown between any of the different OSA groups and coronary heart disease incidence. Conclusions- The incidence of stroke, but not coronary heart disease, is increased in elderly patients with untreated severe OSA. Adequate CPAP treatment may reduce this risk.

Factors affecting the selection of an inhaler device for COPD and the ideal device for different patient profiles. Results of EPOCA Delphi consensus.

BACKGROUND: This study aimed to identify the relevant factors for the choice of an inhaler device by physicians and the selection of the most important characteristics of a device according to different characteristics of patients with COPD. METHOD: In this two-round Delphi survey, 96 Spanish COPD-expert pulmonologists completed an internet-based, self-administered questionnaire, which consisted of a first part with 19 items related to the prioritization of the drug or the device, the experience, ability and preference of the patient, and the experience and preferences of the healthcare professional. For each item, responses were grouped into three categories based on a 9-point Likert-type scale, calculating the response frequency and the degree of consensus. The second part included 18 items related to the inhalation devices with the aim to identify the main characteristics of a device for 8 different profiles of patients with COPD. RESULTS: Experts considered that the selection of a device was relevant when choosing the treatment for COPD patients, although 62.5% of them prioritised the selection of the drug over the device. The experience of the patient (89.6%) and his/her ability to handle the device (97.9%), together with coordination (96.9%), ability to learn (87.5%) and adherence to therapy (84.4%) were the main aspects considered in the selection of inhalation device. The panel identified Respimat® as the most adequate device for patients with either low inspiratory flow or severely impaired lung function and Spiromax® for patients with either impaired fine motor skills or older than 70 years. CONCLUSIONS: Selection of the inhalation device is recognized by specialists as a strategic therapeutic decision and should be based on the characteristics of the individual patient. Some devices may be more adequate for different patient profiles.

Validating the Concept of COPD Control: A Real-world Cohort Study from the United Kingdom.

The concept of Chronic Obstructive Pulmonary Disease (COPD) control has been developed to inform therapeutic decision-making. We explored the validity of a definition of COPD control in a representative population of patients with COPD in the United Kingdom. Electronic medical records and linked COPD questionnaire data from the Optimum Patient Care Research Database were used to characterize control status. Patients were aged ≥40 years, with spirometry-confirmed COPD, current or ex-smokers, and continuous records throughout the study period. Control was evaluated based on COPD stability and patients' (i) clinical features or (ii) COPD Assessment Test (CAT) score over a three-month baseline period and linked to time to first exacerbation. Of 2788 eligible patients, 2511 (90%) had mild/moderate COPD and 277 (10%) had severe/very severe COPD based on Body Mass Index, Obstruction, Dyspnoea, Exacerbations (BODEx) cut-off of 4. Within the mild/moderate cohort, 4.5% of patients were controlled at baseline according to clinical features and 21.5% according to CAT threshold of 10. Within the severe/very severe cohort, no patients were controlled at baseline according to the proposed clinical features and 8.3% were controlled according to CAT threshold of 20. Compared with uncontrolled patients, time to first exacerbation was longer for controlled patients with mild/moderate COPD but not for those with severe/very severe COPD. Lowering the BODEx threshold for severity classification to 2 increased the number of patients achieving control. CAT scores were not good predictors of the risk of future exacerbation. With the proposed definition, very few patients were defined as controlled.

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.

Assessment of the internal structure of GOLD 2011 system.

BACKGROUND: Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 introduced a new multidimensional system (symptom/risk) for assessment chronic obstructive pulmonary disease (COPD). The aim of this study was to explore the construct validity of the GOLD 2011 classification strategy; specifically, we evaluated its internal structure in terms of reliability and exploratory factor analysis (EFA). METHODS: Reliability (Cronbach alpha coefficient), correlations between variables and two successive EFA were performed to assess the internal structure of GOLD 2011. Symptoms (mMRC dyspnea score) and risk (number of previous year exacerbations and forced expiratory volume in the first second % of predicted) were selected as variables. RESULTS: The analysis included 679 COPD patients from two Spanish cohorts (71.4 ± 11.7 years). Alpha coefficient of the 3 items was 0.52 for the whole sample. Variables presented statistically significant correlations, but of low to moderate magnitude. A first EFA extracted only one factor accounting 52% of the total variance. A second EFA including four items (the three GOLD 2011 variables plus comorbidities as Charlson index score), extracted two-factors accounting for 65% of the total variance. The first factor included the three items of GOLD 2011, and the second contained only one variable (comorbidities). This solution was stable in patients with different levels of COPD severity. CONCLUSIONS: The available evidence suggests that GOLD 2011 strategy presented a low reliability, and its theorized multidimensionality was not confirm by EFA. Comorbidities appears as a separate and independent domain.

New GOLD classification: longitudinal data on group assignment.

RATIONALE: Little is known about the longitudinal changes associated with using the 2013 update of the multidimensional GOLD strategy for chronic obstructive pulmonary disease (COPD). OBJECTIVE: To determine the COPD patient distribution of the new GOLD proposal and evaluate how this classification changes over one year compared with the previous GOLD staging based on spirometry only. METHODS: We analyzed data from the CHAIN study, a multicenter observational Spanish cohort of COPD patients who are monitored annually. Categories were defined according to the proposed GOLD: FEV1%, mMRC dyspnea, COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ), and exacerbations-hospitalizations. One-year follow-up information was available for all variables except CCQ data. RESULTS: At baseline, 828 stable COPD patients were evaluated. On the basis of mMRC dyspnea versus CAT, the patients were distributed as follows: 38.2% vs. 27.2% in group A, 17.6% vs. 28.3% in group B, 15.8% vs. 12.9% in group C, and 28.4% vs. 31.6% in group D. Information was available for 526 patients at one year: 64.2% of patients remained in the same group but groups C and D show different degrees of variability. The annual progression by group was mainly associated with one-year changes in CAT scores (RR, 1.138; 95%CI: 1.074-1.206) and BODE index values (RR, 2.012; 95%CI: 1.487-2.722). CONCLUSIONS: In the new GOLD grading classification, the type of tool used to determine the level of symptoms can substantially alter the group assignment. A change in category after one year was associated with longitudinal changes in the CAT and BODE index.

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.

Prognostic value of bronchiectasis in patients with moderate-to-severe chronic obstructive pulmonary disease.

RATIONALE: The prevalence of bronchiectasis is high in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) and it has been associated with exacerbations and bacterial colonization. These have demonstrated some degree of prognostic value in patients with COPD but no information about the relationship between bronchiectasis and mortality in patients with COPD is currently available. OBJECTIVES: To assess the prognostic value of bronchiectasis in patients with moderate-to-severe COPD. METHODS: Multicenter prospective observational study in consecutive patients with moderate-to-severe COPD. Bronchiectasis was diagnosed by high-resolution computed tomography scan. A complete standardized protocol was used in all patients covering general, anthrophometric, functional, clinical, and microbiologic data. After follow-up, the vital status was recorded in all patients. Multivariate Cox analysis was used to determine the independent adjusted prognostic value of bronchiectasis. MEASUREMENTS AND MAIN RESULTS: Ninety-nine patients in Global Initiative for Chronic Obstructive Lung Disease (GOLD) II, 85 in GOLD III, and 17 in GOLD IV stages were included. Bronchiectasis was present in 115 (57.2%) patients. During the follow-up (median, 48 mo [interquartile range, 35-53]) there were 51 deaths (43 deaths in the bronchiectasic group). Bronchiectasis was associated with an increased risk of fully adjusted mortality (hazard ratio, 2.54; 95% confidence interval, 1.16-5.56; P = 0.02). CONCLUSIONS: Bronchiectasis was associated with an independent increased risk of all-cause mortality in patients with moderate-to-severe COPD.

Association between occupational exposure and chronic obstructive pulmonary disease and respiratory symptoms in the Spanish population.

INTRODUCTION: The aim of this study was to analyze the impact of occupational exposure on chronic obstructive pulmonary disease (COPD) and respiratory symptoms in the general Spanish population. METHODS: This was a study nested in the Spanish EPISCAN II cross-sectional epidemiological study that included participants who had completed a structured questionnaire on their occupational history, a questionnaire on respiratory symptoms, and forced spirometry. The data were analyzed using Chi-square and Student's t tests and adjusted models of multiple linear regression and logistic regression. RESULTS: We studied 7502 subjects, 51.1% women, with a mean age of 60±11 years. Overall, 53.2% reported some respiratory symptoms, 7.9% had respiratory symptoms during their work activity, 54.2% were or had been smokers, and 11.3% (851 subjects) met COPD criteria on spirometry. A total of 3056 subjects (40.7%) reported exposure to vapors, gases, dust or fumes (VGDF); occupational exposure to VGDF was independently associated with the presence of COPD (OR 1.22, 95% CI: 1.03-1.44), respiratory symptoms (OR 1.45, 95%: CI 1.30-1.61), and respiratory symptoms at work (OR 4.69, 95% CI: 3.82-5.77), with a population attributable fraction for COPD of 8.2%. CONCLUSIONS: Occupational exposure is associated with a higher risk of COPD and respiratory symptoms in the Spanish population. These results highlight the need to follow strict prevention measures to protect the respiratory health of workers.

Multidisciplinary Management of Patients With Chronic Obstructive Pulmonary Disease and Cardiovascular Disease.

Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) frequently coexist, increasing the prevalence of both entities and impacting on symptoms and prognosis. CVD should be suspected in patients with COPD who have high/very high risk scores on validated scales, frequent exacerbations, precordial pain, disproportionate dyspnea, or palpitations. They should be referred to cardiology if they have palpitations of unknown cause or angina pain. COPD should be suspected in patients with CVD if they have recurrent bronchitis, cough and expectoration, or disproportionate dyspnea. They should be referred to a pulmonologist if they have rhonchi or wheezing, air trapping, emphysema, or signs of chronic bronchitis. Treatment of COPD in cardiovascular patients should include long-acting muscarinic receptor antagonists (LAMA) or long-acting beta-agonists (LABA) in low-risk or high-risk non-exacerbators, and LAMA/LABA/inhaled corticosteroids in exacerbators who are not controlled with bronchodilators. Cardioselective beta-blockers should be favored in patients with CVD, the long-term need for amiodarone should be assessed, and antiplatelet drugs should be maintained if indicated.