The Association of Depressive Symptoms With Rates of Acute Exacerbations in Patients With COPD: Results From a 3-year Longitudinal Follow-up of the ECLIPSE Cohort.

BACKGROUND: Depression increases disability and health care utilization in older patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES: To determine contribution of depressive symptoms to the incidence of moderate-severe and severe acute exacerbations of COPD (AECOPD) over 3 years. DESIGN: We analyzed data collected from a prospective cohort of patients with COPD (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; ECLIPSE). SETTING: Multicentered outpatient. PARTICIPANTS: A total of 2059 patients with COPD with complete data (63.7% men, mean age 63.4 + 7.1 years). MEASUREMENTS: Depression was assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Moderate-severe AECOPDs were collected; a subset of very severe AECOPD was defined as requiring hospital admission. RESULTS: A total of 540 (26%) patients with COPD reported high depressive symptoms (CES-D ≥16). High depressive symptoms at baseline related to an increased risk of moderate-severe and severe AECOPD during the follow-up (odds ratio [OR] 1.18; 95% confidence interval [CI] 1.07-1.30; for moderate-severe and OR 1.36; 95% CI 1.09-1.69 for severe events risk of hospitalizations) independent of key covariates of an AECOPD history before recruitment in the study, history of gastroesophageal reflux, baseline severity of airflow limitation, and white blood cell count that were also associated with an increased risk of moderate to severe exacerbations (all P < .001). CONCLUSION: Presence of high depressive symptoms at baseline were associated with subsequent moderate-severe exacerbations and hospital admissions in patients with COPD over 3 years, independent of a history of exacerbations and other demographic and clinical factors. Targeted personalized medicine that focuses both on AECOPD risk and depression may be a step forward to improving prognosis of patients with COPD.

Coronary artery calcification is increased in patients with COPD and associated with increased morbidity and mortality.

BACKGROUND: Coronary artery calcification is pathognomonic of coronary artery disease (CAD). Whether CAD in patients with COPD is linked to lung function, functional capacity and/or clinically relevant outcomes is unknown. The objective was to assess the association between CAD and disease severity, functional capacity and outcomes in patients with COPD. METHODS: Coronary artery calcium score (CACS; Agatston score) was measured using chest CT in patients with COPD, smokers with normal spirometry and non-smokers from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. RESULTS: CACS was measured in 942 subjects: 672 with COPD (mean age±SD, 63±7 years; FEV1 49±16% predicted), 199 smokers with normal spirometry (54±9 years; FEV1 110±12% predicted) and 71 non-smokers (55±9 years; FEV1 114±14% predicted). CACS was higher in patients with COPD than smokers or non-smokers (median (IQR), 128 (492) vs 0 (75) vs 0 (3) Agatston units (AU), p<0.001). In patients with COPD, CACS correlated with age, pack-years, 6 min walking distance, modified Medical Research Council Dyspnoea score and circulating levels of interleukin (IL)-6, IL-8, Clara Cell protein 16, surfactant protein D and peripheral blood neutrophil count, but not with emphysema, exacerbation frequency, % predicted FEV1 or decline in FEV1. CACS was higher in patients with COPD who died than in those who survived until 3-year follow-up (CACS 406 vs 103 AU, p<0.001), and was associated with mortality in a Cox proportional hazards model (p=0.036). CONCLUSIONS: Patients with COPD have more CAD than controls and this is associated with increased dyspnoea, reduced exercise capacity and increased mortality. These data indicate that the presence of CAD in patients with COPD is associated with poor clinical outcomes.

Characteristics, stability and outcomes of the 2011 GOLD COPD groups in the ECLIPSE cohort.

The 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifies patients with chronic obstructive pulmonary disease (COPD) into four groups (A to D). We explored the characteristics, stability and relationship to outcomes of these groups within the ECLIPSE study (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points) (n = 2101). Main results showed that: 1) these groups differed in several clinical, functional, imaging and biological characteristics in addition to those used for their own definition; 2) A and D groups were relatively stable over time, whereas groups B and C showed more temporal variability; 3) the risk of exacerbation over 3 years increased progressively from A to D, whereas that of hospitalisation and mortality were lowest in A, highest in D and intermediate and similar in B and C, despite the former having milder airflow limitation. The prevalence of comorbidities and persistent systemic inflammation were highest in group B. The different longitudinal behaviour of group A versus B and C versus D (each pair with similar forced expiratory volume in1 s (FEV1) values supports the 2011 GOLD proposal of assessing COPD patients by more than FEV1 only. However the assumption that symptoms do not equate to risk appears to be naïve, as groups B and C carry equally poor clinical outcomes, though for different reasons.

Comorbidity, systemic inflammation and outcomes in the ECLIPSE cohort.

Comorbidities, are common in COPD, have been associated with poor outcomes and are thought to relate to systemic inflammation. To investigate comorbidities in relation to systemic inflammation and outcomes we recorded comorbidities in a well characterized cohort (ECLIPSE study) for 2164 clinically stable COPD subjects, 337 smokers and 245 non-smokers with normal lung function. COPD patients had a higher prevalence of osteoporosis, anxiety/panic attacks, heart trouble, heart attack, and heart failure, than smokers or nonsmokers. Heart failure (Hazard Ratio [HR] 1.9, 95% Confidence Interval [CI] 1.3-2.9), ischemic heart disease (HR 1.5, 95% CI 1.1-2.0), heart disease (HR 1.5, 95% CI 1.2-2.0), and diabetes (HR 1.7, 95% CI 1.2-2.4) had increased odds of mortality when coexistent with COPD. Multiple comorbidities had accumulative effect on mortality. COPD and cardiovascular disease was associated with poorer quality of life, higher MRC dyspnea scores, reduced 6MWD, higher BODE index scores. Osteoporosis, hypertension and diabetes were associated with higher MRC dyspnea scores and reduced 6MWD. Higher blood concentrations of fibrinogen, IL-6 and IL-8 levels occurred in those with heart disease. Comorbidity is associated with poor clinical outcomes in COPD. The comorbidities of heart disease, hypertension and diabetes are associated with increased systemic inflammation.

Characterisation of COPD heterogeneity in the ECLIPSE cohort.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations. This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE). METHODS: We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers. In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography. RESULTS: COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function. Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage. The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study. The distribution of these variables within each GOLD stage was wide. Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation. The amount of emphysema increased with GOLD severity. The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage. Some gender differences were also identified. CONCLUSIONS: The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease.