Conclusions: We found genome-wide significant associations with CB COPD on 4q22.1 (FAM13A) and 11p15.5 (EFCAB4A, CHID1 and AP2A2), and a locus associated with CB within COPD subjects on 1q23.3 (RPL31P11 and ATF6). This study provides further evidence that genetic variants may contribute to phenotypic heterogeneity of COPD.Trial registrationClinicalTrials.gov NCT00608764, NCT00292552 (Source: Respiratory Research)

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Depression and heart failure associated with clinical COPD questionnaire outcome in primary care COPD patients: a cross-sectional study.

NPJ Prim Care Respir Med. 2014;24:14066

Authors: Urff M, van den Berg JW, Uil SM, Chavannes NH, Damoiseaux RA

Abstract
BACKGROUND: Improvement in health-related quality of life (HRQoL) is one of the main goals in treating chronic obstructive pulmonary disease (COPD). Impaired HRQoL in COPD is associated with increased morbidity and mortality, hospitalisations and burden on our health-care system. The Clinical COPD Questionnaire (CCQ) is a validated, reliable, short questionnaire for the evaluation of disease-specific HRQoL in patients with COPD in primary care.
AIMS: To investigate factors that might be associated with CCQ outcome in COPD in a primary care setting.
METHODS: In a population of COPD patients in primary care, multiple regression analyses were used to assess associations between CCQ outcome and depression, heart failure, FEV1% predicted, FEV1/FVC, age, sex, body mass index and current smoking.
RESULTS: Data from 341 patients (mean age 68.1±10.3, COPD GOLD class I-III) were used for analyses. Together, heart failure and depression explained 23% of the variance in CCQ total score (P<0.001, N=93). Heart failure was most strongly associated with CCQ functional score (27% explained variance, P<0.001, N=100), whereas depression was most strongly associated with CCQ mental score (22% explained variance, P<0.001, N=93).
CONCLUSIONS: CCQ outcomes are higher in COPD patients with heart failure and depression. These findings might imply that heart failure and depression affect HRQoL of patients with COPD, and thus emphasise the importance of a holistic approach of this complex disease, leading to a correct diagnosis of COPD and its comorbidities, to achieve better tailored treatment of chronic patients.

PMID: 25230736 [PubMed - in process]

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Prediction of Disease Progression, Treatment Response and Dropout in Chronic Obstructive Pulmonary Disease (COPD).

Pharm Res. 2014 Sep 18;

Authors: Musuamba FT, Teutonico D, Maas HJ, Facius A, Yang S, Danhof M, Della Pasqua O

Abstract
PURPOSE: Drug development in chronic obstructive pulmonary disease (COPD) has been characterised by unacceptably high failure rates. In addition to the poor sensitivity in forced expiratory volume in one second (FEV1), numerous causes are known to contribute to this phenomenon, which can be clustered into drug-, disease- and design-related factors. Here we present a model-based approach to describe disease progression, treatment response and dropout in clinical trials with COPD patients.
METHODS: Data from six phase II trials lasting up to 6 months were used. Disease progression (trough FEV1 measurements) was modelled by a time-varying function, whilst the treatment effect was described by an indirect response model. A time-to-event model was used for dropout RESULTS: All relevant parameters were characterised with acceptable precision. Two parameters were necessary to model the dropout patterns, which was found to be partly linked to the treatment failure. Disease severity at baseline, previous use of corticosteroids, gender and height were significant covariates on disease baseline whereas disease severity and reversibility to salbutamol/salmeterol were significant covariates on Emax for salmeterol active arm.
CONCLUSION: Incorporation of the various interacting factors into a single model will offer the basis for patient enrichment and improved dose rationale in COPD.

PMID: 25231008 [PubMed - as supplied by publisher]

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D-dimer as a Prognostic Biomarker for Mortality in Chronic Obstructive Pulmonary Disease Exacerbation.

Am J Med Sci. 2014 Sep 17;

Authors: Fruchter O, Yigla M, Kramer MR

Abstract
BACKGROUND:: A major barrier to chronic obstructive pulmonary disease (COPD) research and management is lack of easily obtained biomarkers that are predictive of clinically important outcome measures.
OBJECTIVES:: We sought to investigate in patients admitted for acute exacerbation of COPD (AECOPD) the association of D-dimer (fibrin degradation product) obtained upon admission with in-hospital mortality and postdischarge prognosis.
METHODS:: Clinical and laboratory data were evaluated in 61 patients admitted for AECOPD in whom D-dimer levels were obtained and in whom venous thromboembolism/pulmonary embolism was excluded. Receiver operating characteristics curve was used to determine the optimal cutoff level for D-dimer that discriminated survivors versus nonsurvivors during index hospitalization, and during follow-up that extended to a median observation period of 62.6 months.
RESULTS:: Mean (±SD) age of the study cohort was 71.2 ± 10.5 years. Mean D-dimer level in nonsurvivors (n = 12) was significantly higher than in survivors (n = 49): 3.18 ± 0.97 mg/L versus 1.45 ± 1.18 mg/L, respectively, P = 0.0006. D-dimer level >1.52 mg/L predicted in-hospital mortality with a sensitivity and specificity of 100% and 63.6%, respectively. After discharge, median survival of patients with D-dimer above and below 1.52 mg/L were 9.6 and 62.6 months, respectively (hazard ratio = 2.636; 95% confidence interval = 1.271-6.426, P = 0.0111).
CONCLUSIONS:: Elevated D-dimer is a reliable prognostic marker for both short-term and long-term survival in patients admitted for AECOPD. Prospective studies are required to further establish the appropriate role of D-dimer as a prognostic biomarker in patients with COPD.

PMID: 25233043 [PubMed - as supplied by publisher]