C-reactive protein and N-terminal prohormone brain natriuretic peptide as biomarkers in acute exacerbations of COPD leading to hospitalizations

Chen, Yu-wei Roy; Chen, Virginia; Hollander, Zsuzsanna; Leipsic, Jonathon; Hague, Cameron; DeMarco, Mari L.; FitzGerald, J. Mark; McManus, Bruce M.; Ng, Raymond T.; Sin, Don D.

doi:10.1371/journal.pone.0174063

Cited by 17 publications

(17 citation statements)

References 38 publications

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“…Previous studies have shown that CRP could be used as an independent in uencing factor to evaluate the control level of COPD chronic in ammation in patients, [12][13][14] while ALB is a prognostic marker of infection-related disease. 15 Our study observed that high CRP and PCT levels as well as low ALB level were associated with death in AECOPD patients with HF.…”

Section: Discussionmentioning

confidence: 99%

Optimized Combination of Circulating Biomarkers as Predictors of Prognosis in AECOPD Patients Complicated with Heart Failure

Yao

Wang

Shi

et al. 2020

Preprint

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BackgroundSystematic inflammation, nutritional status, and cardiovascular function have been associated with the outcomes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients with heart failure (HF). However, the value of their relevant biomarkers in predicting mortality has not been well defined yet. We aimed to investigate the prognostic value of circulating biomarkers including C-reaction protein (CRP) /albumin (ALB), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), and N-terminal pro-brain natriuretic peptide (NT-proBNP) for AECOPD patients with HF.Methods A total of 146 cases of AECOPD complicated with HF were enrolled and classified into survivor group (n=94) and non-survivor group (n=52). The baseline characteristics and blood-based biomarkers were collected. The predictors for prognosis were analyzed by multivariate logistic regression, and the ability to predict 28-day mortality was evaluated by receiver operating characteristics curve (ROC) and the area under the curve (AUC).ResultsThe patients in non-survivors had significantly higher levels of CRP, CRP/ALB, NLR, PCT and NT-proBNP, but lower ALB levels compared to the survivors [145.8±110.1 VS. 66.6±70.2mg/L, 5.9±4.9 VS. 2.3±2.6, 22.2 (11.1, 40.1) VS. 12.0 (6.2, 24.8), 2.6 (0.2, 10.3) VS. 0.08 (0.1, 0.5)ng/ml, 17912.5 (9344.0, 34344.5) VS. 9809.0 (4415.9, 16387.2)ng/ml, 26.8±6.4 VS. 31.0±4.6g/L; P < 0.001, <0.001, 0.001, <0.001, <0.001, and < 0.001, respectively]. No significant difference in PLR was found between the two groups (P=0.413). The logistic analysis revealed that CRP/ALB (OR=1.303, 95%CI: 1.145-1.483, P<0.001), NT-proBNP (OR=1.041, 95%CI: 1.010-1.073, P=0.009) and NLR (OR=1.010, 95%CI: 0.999-1.022, P<0.001) are independent risk factors for predicting the 28-day mortality. The AUC of the ROC curves were 0.768, 0.767, 0.757, 0.723, 0.716, and 0.668 for CRP/ALB, PCT, CRP, NT-proBNP, ALB, and NLR, respectively. The combination of CRP/ALB, NLR and NT-proBNP as biomarkers was shown to have better accuracy for predicting prognosis (AUC=0.830, 95%CI: 0.761-0.899, P<0.001), with a higher specificity of 80.8% and specificity of 77.7% as compared with each single biomarkers.ConclusionsHigh levels of NLR, CRP/ALB and NT-proBNP may be clinical usefully predictors for death in AECOPD patients with HF. Combination of NLR with CRP/ALB and NT-proBNP can provide a higher accuracy for predicting 28-day mortality in these patients.

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Section: Discussionmentioning

confidence: 99%

Optimized Combination of Circulating Biomarkers as Predictors of Prognosis in AECOPD Patients Complicated with Heart Failure

Yao

Wang

Shi

et al. 2020

Preprint

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“…The Rapid Transition Program (RTP) study details have been described previously. 13 For this sub-study, we assessed subjects who were enrolled between July 2012 and October 2015. All subjects included in this study had a confirmed primary diagnosis of AECOPD as deemed by board-certified general internists or pulmonologists who cared for these subjects.…”

Section: Methodsmentioning

confidence: 99%

“…In a systematic review for AECOPD biomarkers, 12 CRP was one of the most commonly studied biomarkers in AECOPD, and elevated concentrations have been found in AECOPD state compared to convalescence state. We have previously demonstrated that both NT-proBNP and CRP concentrations measured in blood are elevated in AECOPD compared to convalescence, and together they can reasonably discriminate between AECOPD requiring hospitalization compared to clinical stability with a cross-validated area under the curve (AUC) of 0.80, but their concentrations were only weakly related to each other, 13 which may indicate that they might represent different phenotypes of AECOPD.…”

Section: Introductionmentioning

confidence: 99%

Phenotyping COPD exacerbations using imaging and blood-based biomarkers

Alotaibi¹,

Chen²,

Hollander³

et al. 2018

COPD

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RationaleAcute exacerbations of chronic obstructive pulmonary disease (AECOPD) are caused by a variety of different etiologic agents. Our aim was to phenotype COPD exacerbations using imaging (chest X-ray [CXR] and computed tomography [CT]) and to determine the possible role of the blood tests (C-reactive protein [CRP], the N-terminal prohormone brain natriuretic peptide [NT-proBNP]) as diagnostic biomarkers.Materials and methodsSubjects who were hospitalized with a primary diagnosis of AECOPD and who had had CXRs, CT scans, and blood collection for CRP and NT-proBNP were assessed in this study. Radiologist blinded to the clinical and laboratory characteristics of the subjects interpreted their CXRs and CT images. ANOVA and Spearman’s correlation were performed to test for associations between these imaging parameters and the blood-based biomarkers NT-proBNP and CRP; logistic regression models were used to assess the performance of these biomarkers in predicting the radiological parameters.ResultsA total of 309 subjects were examined for this study. Subjects had a mean age of 65.6±11.1 years, 66.7% of them were males, and 62.4% were current smokers, with a mean FEV1 54.4%±21.5% of predicted. Blood NT-proBNP concentrations were associated with cardiac enlargement (area under the curve [AUC] =0.72, P<0.001), pulmonary edema (AUC =0.63, P=0.009), and pleural effusion on CXR (AUC =0.64, P=0.01); whereas on CT images, NT-proBNP concentrations were associated with pleural effusion (AUC =0.71, P=0.002). Serum CRP concentrations, on the other hand, were associated with consolidation on CT images (AUC =0.75, P<0.001), ground glass opacities (AUC =0.64, P=0.028), and pleural effusion (AUC =0.72, P<0.001) on CT images. A serum CRP sensitivity-oriented cutoff point of 11.5 mg/L was selected for the presence of consolidation on CT images in subjects admitted as cases of AECOPD, which has a sensitivity of 91% and a specificity of 53% (P<0.001).ConclusionElevated CRP may indicate the presence of pneumonia, while elevated NT-proBNP may indicate cardiac dysfunction. These readily available blood-based biomarkers may provide more accurate phenotyping of AECOPD and enable the discovery of more precise therapies.

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“…Studies show that BNP plays an important role in the diagnosis of heart failure, hypertension, and cardiopulmonary diseases [ 5 , 6 ]. For example, Chen et al [ 7 ] showed that N-terminal hormone BNP (NT-proBNP) has a certain value in the rapid diagnosis of patients requiring hospitalization for AECOPD. At present, many single nucleotide polymorphism (SNP) loci of the BNP gene are associated with hypertension and chronic heart failure.…”

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confidence: 99%

Association of brain natriuretic peptide gene polymorphisms with chronic obstructive pulmonary disease complicated with pulmonary hypertension and its mechanism

et al. 2018

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Objective: To examine the association between brain natriuretic peptide (BNP) gene single nucleotide polymorphisms (SNPs) and chronic obstructive pulmonary disease (COPD) and COPD with pulmonary hypertension (PH) and to analyze its mechanism. Methods: The genotypes of BNP at the rs198389, rs6668352, and rs198388 loci in 339 patients with COPD (205 in the COPD/PH− group and 134 in the COPD/PH+ group) and 125 healthy subjects were detected by PCR/Sanger sequencing. The serum levels of BNP, fibrinogen (Fbg), and Apelin were measured in all subjects by ELISA. Results: The BNP rs198389 locus G allele, rs6668352 locus A allele, and 198388 locus T allele were high risk factors for COPD (P<0.001). Logistics regression analysis showed that BNP rs198389 locus G allele, rs6668352 locus A allele, and rs198388 locus T allele were high risk factors for PH in COPD patients (all P<0.001). The levels of the serum BNP and Fbg protein in the control group, COPD/PH− group, and COPD/PH+ group increased successively, and the expression levels of Apelin protein decreased successively (all P<0.001). The BNP and Fbg protein levels in the wild-type, heterozygote, and mutant homozygote in BNP rs198389, rs6668352, and rs198388 loci increased successively, and the serum Apelin protein levels decreased successively (all P<0.001). Conclusion: The polymorphisms of BNP at the rs198389, rs6668352, and rs198388 loci are associated with the occurrence of COPD and COPD with PH, and the occurrence may be related to the abnormal expression level of BNP, Fbg, and Apelin protein in the serum.

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C-reactive protein and N-terminal prohormone brain natriuretic peptide as biomarkers in acute exacerbations of COPD leading to hospitalizations

Cited by 17 publications

References 38 publications

Optimized Combination of Circulating Biomarkers as Predictors of Prognosis in AECOPD Patients Complicated with Heart Failure

Optimized Combination of Circulating Biomarkers as Predictors of Prognosis in AECOPD Patients Complicated with Heart Failure

Phenotyping COPD exacerbations using imaging and blood-based biomarkers

Association of brain natriuretic peptide gene polymorphisms with chronic obstructive pulmonary disease complicated with pulmonary hypertension and its mechanism

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