Fibrinogen, chronic obstructive pulmonary disease (COPD) and outcomes in two United States cohorts

BACKGROUND: Fibrinogen is a marker of systemic inflammation and may be important in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD). METHODS: We used baseline data from Atherosclerosis Risk in Communities and Cardiovascular Health Studies to determine the relation between fibrinogen levels and COPD and to examine how fibrinogen levels at baseline affected outcomes of death, development of COPD, lung function decline, and COPD-hospitalizations. RESULTS: Our study sample included 20,192 subjects, of whom 2995 died during the follow-up period. The mean fibrinogen level was 307.6 mg/dL and 10% of the sample had levels \u3e393.0 mg/dL. Subjects with Stage 3 or 4 COPD were more likely to have a fibrinogen level \u3e393.0 mg/dL (odds ratio 2.28, 95% confidence interval [CI]: 1.79-2.95). In the longitudinal adjusted models, fibrinogen levels \u3e393 mg/dL predicted mortality (hazards ratio 1.54, 95% CI: 1.39-1.70), COPD-related hospitalization (hazards ratio 1.45, 95% CI: 1.27-1.67), and incident Stage 2 COPD (odds ratio 1.36, 95% CI: 1.07-1.74). Similar findings were seen with continuous fibrinogen levels. CONCLUSION: In the Atherosclerosis Risk in Communities/Cardiovascular Health Studies cohort data, higher fibrinogen levels are predictors of mortality, COPD-related hospitalizations, and incident Stage 2 COPD

Validation of chronic obstructive pulmonary disease recording in the Clinical Practice Research Datalink (CPRD-GOLD).

OBJECTIVES: The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known. We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database. SETTING: 951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012. Individuals were selected for ≥1 of 8 algorithms to identify people with COPD. General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested. All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard. PRIMARY OUTCOME MEASURE: The primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed. RESULTS: 951 questionnaires were sent and 738 (78%) returned. After quality control, 696 (73.2%) patients were included in the final analysis. All four algorithms including a specific COPD diagnostic code performed well. Using a diagnostic code alone, the PPV was 86.5% (77.5-92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7-94.5%) but reduced case numbers by 10%. Algorithms without specific diagnostic codes had low PPVs (range 12.2-44.4%). CONCLUSIONS: Patients with COPD can be accurately identified from UK primary care records using specific diagnostic codes. Requiring spirometry or COPD medications only marginally improved accuracy. The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004

Inflammatory and Repair Serum Biomarker Pattern. Association to Clinical Outcomes in COPD

Background: The relationship between serum biomarkers and clinical expressions of COPD is limited. We planned to further describe this association using markers of inflammation and injury and repair. Methods: We studied lung function, comorbidities, exercise tolerance, BODE index, and quality of life in 253 COPD patients and recorded mortality over three years. Serum levels of Interleukins 6,8 and16, tumor necrosis factor alpha (TNF α) [inflammatory panel], vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) [injury and repair panel] and pulmonary and activation-regulated chemokine (PARC/CCL-18) and monocyte chemotactic protein 1 (MCP-1/CCL2) [chemoattractant panel] were measured. We related the pattern of the biomarker levels to minimal clinically important differences (MCID) using a novel visualization method [ObServed Clinical Association Results (OSCAR) plot]. Results: Levels of the inflammatory markers IL-6, TNF α were higher and those of injury and repair lower (p < 0.01) with more advanced disease (GOLD 1 vs. 4). Using the OSCAR plot, we found that patients in the highest quartile of inflammatory and lowest quartile of injury and repair biomarkers level were more clinically compromised and had higher mortality (p < 0.05). Conclusions: In COPD, serum biomarkers of inflammation and repair are distinctly associated with important clinical parameters and survival

Risk assessment for hospital admission in patients with COPD; a multi-centre UK prospective observational study.

In chronic obstructive pulmonary disease (COPD), acute exacerbation of COPD requiring hospital admission is associated with mortality and healthcare costs. The ERICA study assessed multiple clinical measures in people with COPD, including the short physical performance battery (SPPB), a simple test of physical function with 3 components (gait speed, balance and sit-to-stand). We tested the hypothesis that SPPB score would relate to risk of hospital admissions and length of hospital stay. Data were analysed from 714 of the total 729 participants (434 men and 280 women) with COPD. Data from this prospective observational longitudinal study were obtained from 4 secondary and 1 tertiary centres from England, Scotland, and Wales. The main outcome measures were to estimate the risk of hospitalisation with acute exacerbation of COPD (AECOPD and length of hospital stay derived from hospital episode statistics (HES). In total, 291 of 714 individuals experienced 762 hospitalised AECOPD during five-year follow up. Poorer performance of SPPB was associated with both higher rate (IRR 1.08 per 1 point decrease, 95% CI 1.01 to 1.14) and increased length of stay (IRR 1.18 per 1 point decrease, 95% CI 1.10 to 1.27) for hospitalised AECOPD. For the individual sit-to-stand component of the SPPB, the association was even stronger (IRR 1.14, 95% CI 1.02 to 1.26 for rate and IRR 1.32, 95% CI 1.16 to 1.49 for length of stay for hospitalised AECOPD). The SPPB, and in particular the sit-to-stand component can both evaluate the risk of H-AECOPD and length of hospital stay in COPD. The SPPB can aid in clinical decision making and when prioritising healthcare resources

Cardiovascular risk prediction using physical performance measures in COPD: results from a multicentre observational study

Funder: National Institute for Health Research; FundRef: http://dx.doi.org/10.13039/501100000272Funder: Health Data Research UKFunder: NIHR Cambridge Comprehensive Biomedical Research CentreFunder: NIHR Nottingham BRC respiratory themeObjectives: Although cardiovascular disease (CVD) is a common comorbidity associated with chronic obstructive pulmonary disease (COPD), it is unknown how to improve prediction of cardiovascular (CV) risk in individuals with COPD. Traditional CV risk scores have been tested in different populations but not uniquely in COPD. The potential of alternative markers to improve CV risk prediction in individuals with COPD is unknown. We aimed to determine the predictive value of conventional CVD risk factors in COPD and to determine if additional markers improve prediction beyond conventional factors. Design: Data from the Evaluation of the Role of Inflammation in Chronic Airways disease cohort, which enrolled 729 individuals with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II–IV COPD were used. Linked hospital episode statistics and survival data were prospectively collected for a median 4.6 years of follow-up. Setting: Five UK centres interested in COPD. Participants: Population-based sample including 714 individuals with spirometry-defined COPD, smoked at least 10 pack years and who were clinically stable for >4 weeks. Interventions: Baseline measurements included aortic pulse wave velocity (aPWV), carotid intima–media thickness (CIMT), C reactive protein (CRP), fibrinogen, spirometry and Body mass index, airflow Obstruction, Dyspnoea and Exercise capacity (BODE) Index, 6 min walk test (6MWT) and 4 m gait speed (4MGS) test. Primary and secondary outcome measures: New occurrence (first event) of fatal or non-fatal hospitalised CVD, and all-cause and cause-specific mortality. Results: Out of 714 participants, 192 (27%) had CV hospitalisation and 6 died due to CVD. The overall CV risk model C-statistic was 0.689 (95% CI 0.688 to 0.691). aPWV and CIMT neither had an association with study outcome nor improved model prediction. CRP, fibrinogen, GOLD stage, BODE Index, 4MGS and 6MWT were associated with the outcome, independently of conventional risk factors (p<0.05 for all). However, only 6MWT improved model discrimination (C=0.727, 95% CI 0.726 to 0.728). Conclusion: Poor physical performance defined by the 6MWT improves prediction of CV hospitalisation in individuals with COPD. Trial registration number: ID 11101

One-year change in health status and subsequent outcomes in COPD

BACKGROUND: Poor health status has been associated with morbidity and mortality in patients with COPD. To date, the impact of changes in health status on these outcomes remains unknown. AIMS: To explore the relationship of clinically relevant changes in health status with exacerbation, hospitalisation or death in patients with COPD. METHODS: Characteristics and health status (St George's Respiratory Questionnaire, SGRQ) were assessed over a period of 3 years in 2138 patients with COPD enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study: a longitudinal, prospective, observational study. Associations between change in health status (=4 units in SGRQ score) during year 1 and time to first exacerbation, hospitalisation and death during 2-year follow-up were assessed using Kaplan-Meier plots and log-rank test. RESULTS: 1832 (85.7%) patients (age 63.4±7.0 years, 65.4% male, FEV1 48.7±15.6% predicted) underwent assessment at baseline and 1 year. Compared with those who deteriorated, patients with improved or stable health status in year 1 have a lower likelihood of exacerbation (HR 0.78 (95% CI 0.67 to 0.89), p<0.001 and 0.84 (0.73 to 0.97), p=0.016, respectively), hospitalisation (0.72 (0.58 to 0.90), p=0.004 and 0.77 (0.62 to 0.96), p=0.023, respectively) or dying (0.61 (0.39 to 0.95), p=0.027 and 0.58 (0.37 to 0.92), p=0.019, respectively) during 2-year follow-up. This effect persisted after stratification for age and the number of exacerbations and hospitalisations during the first year of the study. CONCLUSIONS: Patients with stable or improved health status during year 1 of ECLIPSE had a lower likelihood of exacerbation, hospitalisation or dying during 2-year follow-up. Interventions that stabilise and improve health status may also improve outcomes in patients with COPD

Hospitalized exacerbations of COPD: risk factors and outcomes in the ECLIPSE cohort

Exacerbations of COPD requiring hospital admission have important clinical and societal implications. We sought to investigate the incidence, recurrence, risk factors, and mortality of patients with COPD exacerbations requiring hospital admission compared with those without hospital admission during 3-year follow-up. Patients with COPD (N = 2,138) were identified from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) observational cohort. An analysis of time to first event of hospital admission was performed using Kaplan-Meier curves and Cox proportional hazard regression adjusting for possible confounders. Of the 2,138 patients, 670 (31%) reported a total of 1,452 COPD exacerbations requiring hospital admission during the study period; 313 patients (15%) reported multiple events. A prior history of exacerbation of COPD requiring hospital admission was the factor associated with the highest risk of a new hospitalization for exacerbation (hazard ratio, 2.71; 95% CI, 2.24-3.29; P < .001). Other risk factors included more severe airflow limitation, poorer health status, older age, radiologic evidence of emphysema, and higher WBC count. Having been hospitalized for exacerbation significantly increased the risk of mortality (P < .001). Exacerbations of COPD requiring hospital admission occur across all stages of airflow limitation and are a significant prognostic factor of reduced survival across all COPD stages. Patients with COPD at a high risk for hospitalization can be identified by their past history for similar events, and other factors, including the severity of airflow limitation, poor health status, age, presence of emphysema, and leukocytosis. ClinicalTrials.gov; No.: NCT00292552; URL: www.clinicaltrials.gov