Inflammatory Biomarkers and Comorbidities in Chronic Obstructive Pulmonary Disease

Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 13). 09/2012; 186(10). DOI: 10.1164/rccm.201206-1113OC
Source: PubMed


RATIONALE: Patients with chronic obstructive pulmonary disease (COPD) have evidence of systemic inflammation that may be implicated in the development of comorbidities. OBJECTIVES: To test the hypothesis that elevated levels of three inflammatory biomarkers are associated with increased risk of comorbidities in COPD. METHODS: We examined 8656 COPD patients from two large Danish population studies and during a median five years follow-up recorded hospital admissions due to major comorbidities as endpoints. MEASUREMENTS AND MAIN RESULTS: We measured baseline C-reactive protein (CRP), fibrinogen, and leukocyte count, and recorded admissions due to ischemic heart disease, myocardial infarction, heart failure, type II diabetes, lung cancer, pneumonia, pulmonary embolism, hip fracture, and depression for all participants. Multifactorially adjusted risk of ischemic heart disease was increased by a factor of 2.19(95%confidence interval:1.48-3.23) in individuals with three biomarkers elevated (CRP above 3 mg per liter, fibrinogen above 14 μmol per liter, and leukocyte count above 9 x109 per liter) versus individuals with all three biomarkers at or below these limits. Corresponding hazard ratios were 2.32(1.34-4.04) for myocardial infarction, 2.63(1.71-4.04) for heart failure, 3.54(2.03-6.19) for diabetes, 4.00(2.12-7.54) for lung cancer, and 2.71(2.03-3.63) for pneumonia. There were no consistent differences in risk of pulmonary embolism, hip fracture, or depression as a function of these three biomarkers. CONCLUSIONS: Simultaneously elevated levels of CRP, fibrinogen, and leukocyte count are associated with a 2 to 4-fold increased risk of major comorbidities in COPD. These biomarkers may be an additional tool for clinicians to conduct stratified management of comorbidities in COPD.

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    • "The differences found in our study did not appreciably change after adjusting for potential confounders, including body mass index, age, gender, FEV1 and the Charlson index. Although these variables have been associated with the systemic inflammatory load [34,35], few data are available on their relationships with local inflammatory biomarkers in respiratory tissues. In the present study, we failed to identify such an association. "
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    ABSTRACT: Background Chronic systemic inflammatory syndrome has been implicated in the pathobiology of extrapulmonary manifestations of chronic obstructive pulmonary disease (COPD). We aimed to investigate which cell types within lung tissue are responsible for expressing major acute-phase reactants in COPD patients and disease-free (“resistant”) smokers. Methods An observational case–control study was performed to investigate three different cell types in surgical lung samples of COPD patients and resistant smokers via expression of the C-reactive protein (CRP) and serum amyloid A (SAA1, SAA2 and SAA4) genes. Epithelial cells, macrophages and fibroblasts from the lung parenchyma were separated by magnetic microbeads (CD326, CD14 and anti-fibroblast), and gene expression was evaluated by RT-PCR. Results The sample consisted of 74 subjects, including 40 COPD patients and 34 smokers without disease. All three cell types were capable of synthesizing these biomarkers to some extent. In fibroblasts, gene expression analysis of the studied biomarkers demonstrated increased SAA2 and decreased SAA1 in patients with COPD. In epithelial cells, there was a marked increase in CRP, which was not observed in fibroblasts or macrophages. In macrophages, however, gene expression of these markers was decreased in COPD patients compared to controls. Conclusions These results provide novel information regarding the gene expression of CRP and SAA in different cell types in the lung parenchyma. This study revealed differences in the expression of these markers according to cell type and disease status and contributes to the identification of cell types that are responsible for the secretion of these molecules.
    BMC Pulmonary Medicine 05/2014; 14(1):95. DOI:10.1186/1471-2466-14-95 · 2.40 Impact Factor
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    • "Several biomarkers have been investigated in search of a better tool to predict clinically relevant outcomes such as mortality, hospitalisation, and exacerbations [2]. Biomarkers such as C-reactive protein (CRP) and leukocytes represent low-grade systemic inflammation and increased levels have been found in patients with COPD [3] and have been associated with a poor prognosis [4] and comorbidity [5]. Vitamin D on the other hand has anti-inflammatory properties and vitamin D deficiency has been associated with all-cause mortality in the general population [6] and mortality specifically linked to diseases of the respiratory system [7]. "
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    ABSTRACT: Inflammatory biomarkers predict mortality and hospitalisation in chronic obstructive pulmonary disease (COPD). Yet, it remains uncertain if biomarkers in addition to reflecting disease severity add new prognostic information on severe COPD. We investigated if leukocytes, C-reactive protein (CRP), and vitamin D were independent predictors of mortality and hospitalisation after adjusting for disease severity with an integrative index, the i-BODE index. In total, 423 patients participating in a pulmonary rehabilitation programme, with a mean value of FEV1 of 38% of predicted, were included. Mean followup was 45 months. During the follow-up period, 149 deaths (35%) were observed and 330 patients (78.0%) had at least one acute hospitalisation; 244 patients (57.7%) had at least one hospitalisation due to an exacerbation of COPD. In the analysis (Cox proportional hazards model) fully adjusted for age, sex, and i-BODE index, the hazard ratio for 1 mg/L increase in CRP was 1.02 (P = 0.003) and for 1 × 10(9)/L increase in leukocytes was 1.43 (P = 0.03). Only leukocyte count was significantly associated with hospitalisation. Vitamin D was neither associated with mortality nor hospitalisation. Leukocytes and CRP add little information on prognosis and vitamin D does not seem to be a useful biomarker in severe COPD in a clinical setting.
    The Scientific World Journal 01/2014; 2014(12):140736. DOI:10.1155/2014/140736 · 1.73 Impact Factor
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    • "Many systems including endocrine system are affected in COPD. Extrapulmonary effects of COPD and comorbidities diminish quality of life, aggravate symptoms and increase mortality [2-4]. "
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    ABSTRACT: Frequent exacerbations of chronic obstructive pulmonary disease (COPD) have negative effects on quality of life and survival. Thus, factors related to exacerbations should be determined. We aimed to evaluate the effects of thyroid function on quality of life and exacerbation frequency in COPD patients. The study population (n = 128) was divided into 3 groups (Group 1: COPD patients with hypothyroidism (n = 44); Group 2: COPD patients with normal thyroid function tests (n = 44); Group 3: Healthy subjects (n = 40)). Pulmonary function tests, maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) measurements were performed. Quality of life questionnaire (Short Form 36, SF-36) was carried out. Patients were followed up for one year and number of exacerbations was recorded. FVC, FEV1/FVC, and FEF 25--75% measurements were statistically different between group 1 and 2 (p = 0.041, p = 0.001, p = 0.009 respectively). Although MEP values were significantly different between group 1 and 2 (p = 0.006), there was no significant difference in MIP values between groups (p = 0.77). Quality of life scores in group 1 and 2 were significantly lower than control group. Exacerbation frequency was significantly higher in group 1 than in group 2 (p = 0.017). TSH values and exacerbation frequency had positive correlation (p < 0.0001; r = 0.82). The results of the present study suggest that thyroid function has an effect in exacerbation frequency of COPD. Decrease in exacerbation numbers with early detection of impairment in thyroid function will have positive contribution on quality of life in COPD patients.
    Multidisciplinary respiratory medicine 10/2013; 8(1):64. DOI:10.1186/2049-6958-8-64 · 0.15 Impact Factor
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