NT-pro BNP in AECOPD-PH: Old Biomarker, New Insights-Based on a Large Retrospective Case-Controlled Study

doi:10.21203/rs.3.rs-686373/v1

Download PDF

Research

NT-pro BNP in AECOPD-PH: Old Biomarker, New Insights-Based on a Large Retrospective Case-Controlled Study

https://doi.org/10.21203/rs.3.rs-686373/v1

This work is licensed under a CC BY 4.0 License

Journal Publication

published 01 Dec, 2021

Read the published version in Respiratory Research →

You are reading this latest preprint version

Pulmonary hypertension (PH) is one of the common complications in chronic obstructive pulmonary disease (COPD). The study aimed to evaluate the predicting ability of N-terminal pro brain natriuretic peptide (NT-pro BNP) in patients with AECOPD-PH and its relationship with the severity of PH. A large retrospective case-controlled study (n=1072) was performed in the First Affiliated Hospital of Xinjiang Medical University from January 2018 to December 2020, and patients were divided into stable COPD (n=178), AECOPD (n=688) and AECOPD-PH group (n=206). In unadjusted analysis and PSM (model 1, 2, 3), red cell distribution width (RDW), total bilirubin (TBIL), and NT-pro BNP were higher in patients with AECOPD-PH than those in AECOPD group. Logistic regression analysis showed that RDW had no statistic difference. When the range of NT-proBNP was 271-1165 pg/mL (OR: 0.293; 95%CI: 0.184-0.467; P<0.001) and NT-proBNP > 1165pg/mL (OR: 0.559; 95%CI: 0.338-0.926; P=0.024), the morbidity risk of PH in AECOPD patients was increased, so did TBIL. In receiver operating characteristic (ROC) curves, at the cut-off value of NT-proBNP was 175.14 pg/mL, AUC was 0.651 (P<0.001), which was better than TBIL (AUC: 0.590, P<0.001). As for the results of rank correlation analysis, TBIL had no significant difference, and NT-proBNP had a weak correlation with severity of PH with AECOPD (r=0.299, P=0.001).Our findings suggest that NT-proBNP has a diagnostic efficacy in AECOPD-PH and NT-proBNP has a weak correlation with severity of PH with AECOPD.

Pulmonology

Acute exacerbations of chronic obstructive pulmonary disease

Pulmonary hypertension

NT-proBNP

Pulmonary hypertension(PH)may occur in patients with chronic obstructive pulmonary disease (COPD) due to inadequate alveolar ventilation, hypoxia, and pulmonary vascular remodeling (1, 2). A recently study found that approximately 1% of the world’s population has PH and that the prevalence among people over 65 years old increases to 10% (1). One third of deaths in COPD patients relate to cardiovascular disease, equaling or exceeding pulmonary related disease mortality (3). However, it may be early diagnosis can be difficult to distinguish between COPD patients with acute exac erbations alone or acute exacerbations with PH. As PH symptoms such as dyspnea on exertion, shortness of breath, and fatigue are non-specific (4).

N-terminal pro brain natriuretic peptide (NT-proBNP) is secreted by cardiomyocytes in response to ventricular stretch and is a noninvasive marker of right ventricular dysfunction (5). NT-proBNP levels correlate with functional capacity, right ventricular function, echocardiographic and hemodynamic variables. It plays an important role in maintaining cardiopulmonary homeostasis. Serum concentrations of NT-proBNP are elevated in clinical conditions that affect not only left (LV) but also right ventricle (RV), both markers can be used as prognostic parameters for PH and have been recommended in the current guidelines (6, 7). Management and treatment of cardiovascular disease in patients with COPD is critical to reduce morbidity and mortality (8). A recently study showed that the low, medium, and high NT-proBNP categories as part of the multiparametric risk assessment approach included in the PH patient management scope (6). The level of NT-proBNP is highly prognostic of PH progression, and patients with persistently high NT-proBNP may have the highest risk of disease progression (5, 9). NT-proBNP is powerful independent predictors of death and adverse events in heart failure, a broad range of cardiovascular conditions even in asymptomatic individuals.

Current research suggested that timely intensive management of those with a raised NT-proBNP detected may be useful in identifying cardiovascular disease, stratifying risk, and guiding the treatment of COPD (6). These cardiovascular treatments could reduce the incidence of heart failure and left ventricular dysfunction in patients(8). However, chest tightness, shortness of breath, cough and sputum may only be acute exacerbation of COPD (AECOPD), or may be caused by PH,which for patients with COPD. We therefore undertook retrospective analysis study to direct future research and provided evidence. The study aims to define the associations and diagnostic accuracy of NT-proBNP elevation patients in AECOPD with PH.

Patients

A single center cross-sectional study was performed at First Affiliated Hospital of Xinjiang Medical University from January 2018 to December 2020, patients were divided into stable COPD, AECOPD and AECOPD patients with PH (AECOPD-PH). The research was approved by Xinjiang Medical University Ethical Committees and all patients provided written informed consent. The enrolled patients were diagnosed as regarding GOLD criteria (10). The patients seemed to have PH if PASP > 30 mmHg, and were classified into three subgroups, mild (30–50 mmHg), moderate (50–70 mmHg), and severe (> 70 mmHg) degrees (2).

Data collection

All data was obtained. Patients’ blood pressure and pulse rate measured on admission; BMI, smoking status, complications, biomarkers: white blood cell (WBC), red blood cell (RBC), red cell distribution width (RDW), mean volume (MPV), fibrinogen degrdtion products (FDP), D-Dimer (DD), albumin globulin ratio (A/G), total bilirubin (TBIL), NT-proBNP and so on. The echocardiography reports of patients were collected.

Exclusion criteria

Patients underwent thorough pulmonary and cardiologic preinclusion screening, and those with pulmonary disease other than COPD, as well as arrhythmia, valvular disease were excluded. This study included the number of 1072 patients; 676 patients were excluded (details shown in Fig. 1). Patients were divided into three groups, group 1 - COPD group (n = 178); Group 2 - AECOPD group (n = 688); Group 3 - AECOPD-PH group (n = 206).

Biochemical measurement and echocardiography

WBC, RBC, RDW, and MPV (XN-2000, SYSMEX, Japan). ALB, TG, TC, HDL, LDL and TBIL (Cobas8000, Roche, Germany). FDP and DD (ACL- TOP-750, Werfen, Spain). NT-ProBNP (VITROS 5600,Ortho Clinical Diagnostics༌American). CRP (VITROS 5600༌Ortho Clinical Diagnostics, American), IL-6 and PCT (Cobas701, Roche, Germany). Echocardiography was performed in all AECOPD patients (EPIQ-7C, Philips, Netherlands).

Statistical analysis

All analyses were performed by SPSS 25 (IBM, American). Quantitative variables were described as median (interquartile range, IQR) and the Wilcoxon rank-sum test was used to compare between groups, expressed as mean ± standard deviation, and t test was used to compared between groups. Qualitative variables were described as frequency (number, percentages) and compared between two groups by the Fisher exact test or the Chi-square test as appropriate. To reduce selection bias for treatment and any other related potential confounding factor, we performed a baseline characteristic adjustment for patients by propensity matching score (PSM). PSM details showed in Table 2 (model 1, 2 and 3, matched 1:1, calipers value = 0.05). Then the markers were layered, stepwise multivariate Logistic regression was used to calculate the adjusted OR and its 95%CI. The diagnostic performance of biomarkers was statistically significant in the above statistical analysis by means of receiver operating characteristic (ROC) curves, the optimal threshold on the curve was considered to predict AECOPD-PH. Finally, rank correlation analysis was used to analyze the correlation between NT-ProBNP and the severity of AECOPD-PH. P value < 0.05 was significant for statistical analyses.

Demographics and clinical presentations

Overall, among 1748 patients included, finally 1702 patients were enrolled into this study (Fig. 1). Median age was 73 years old (IQR 65–80), 440 patients (25.85%) were female. The pulse rate of AECOPD patients was higher than that of COPD group. Among the patients, there were 134 (12.50%) of patients still smoking, and 242 (22.57%) were ex-smoker. There were 235 (21.92%) patients complied with diabetes mellitus, 637 (59.14%) patients complied with coronary atherosclerotic heart disease, it was almost as many patients as complied with hypertension (n = 634, 59.14%). 20.43% (n = 219) of patients had history of cerebral infarction. Most patients with AECOPD-PH have mild / moderate pulmonary hypertension (n = 156, 75.73%) (Table 1).

Blood biomarkers

PCT, CRP and IL-6 had significant difference in three groups (P < 0.001), however there was no difference between AECOPD-PH group and AECOPD group, so did WBC, Hb, MPV, DD, FDP, ALB, A/G, TG, TC and HDL. Among the three groups, RDW in AECOPD-PH group (13.9, 13.2–15.5 %) was higher than that in AECOPD group (13.5, 12.9–14.6 %) and COPD group (13.2, 12.7–13.8 %), but there was no difference between COPD and AECOPD-PH group (P = 0.164). The serum TBIL level of AECOPD-PH group (13.2, 9.5–18.8µmol/L) was not only higher than that of AECOPD group (11.8, 8.8–15.5µmol/L), but also higher than COPD group (11.2, 8.4–14.7µmol/L). However, there was no significant difference between COPD and AECOPD groups (P = 0.473). The level of NT-proBNP in AECOPD-PH group (273.53, 83.31-1023.70 pg/mL) was significantly higher than that of AECOPD group (93.4, 3.59-316.69 pg/mL, P < 0.001). Since most COPD patients were admitted to the hospital for other diseases, there were few patients who need to complete the NT-proBNP examination,so statistical analysis is not done here (Table 1 and Fig. 2).

Propensity score matching

Many variables were statistically different. The matched variables showed no difference between AECOPD and AECOPD-PH group after PSM. 206 patients in each cohort were compared (Table 2 and Fig. 3). After three PSM models, WBC, RDW, TBIL and NT-proBNP still had statistical difference. However, the increased WBC was non-specific, so no further analysis was performed.

Logistic regression analysis

RDW, TBIL and NT-proBNP were stratified, and then multivariate logistic regression was performed to investigate associations between biomarkers levels and the prediction of AECOPD-PH. The results supported elevated NT-proBNP and TBIL might be significantly associated with AECOPD-PH, excepted for RDW (Table 3). Significant predictive ability was found for AECOPD-PH with TBIL < 13.8µmol/L (OR = 0.598, 95%CI: 0.413–0.864), TBIL at the range of 13.8–16.5µmol/L (OR = 0.485, 95%CI: 0.280–0.841) and NT-proBNP>1165pg/mL (OR = 0.559, 95%CI: 0.338–0.926), NT-proBNP at the range of 271-1165pg/mL (OR = 0.293, 95%CI: 0.184–0.467). In the analysis of logistic, there was no association in the elevated RDW with low/moderately elevated RDW value (OR = 0.806, 95%CI: 0.547–1.186 vs OR = 0.933, 95%CI: 0.587–1.481). The analysis showed that the elevated RDW might not be associated with AECOPD-PH.

ROC analysis of blood biomarkers

We calculated the ROC curve generated by significant indicators from previous analysis. The variables showed predictive ability for AECOPD-PH. The validity of NT-ProBNP in predicting AECOPD-PH was significant (P < 0.001). The AUC of NT-proBNP (0.651) was higher than TBIL(0.590). The optimal threshold of NT-proBNP (175.14 pg/mL) corresponded to predict whether AECOPD patients complied with PH. The cut-off value of NT-proBNP was 175.14 pg/mL (sensitivity: 0.617, specificity: 0.638) in predicting AECOPD-PH (P < 0.001). The cut-off value of TBIL was 15.07µmol/L (sensitivity: 0.437, specificity: 0.732), the AUC was 0.590 (P < 0.001) (Table 4 and Fig. 4).

Rank correlation analysis

Rank correlation was performed to explore whether there was a correlation between high levels of NT-ProBNP (≥ 175.14pg/ml) / TBIL (≥ 15.07µmol/L) and PASP value. Detecting the correlation between PH severity (based on PASP value) and NT-ProBNP / TBIL, a weak correlation of NT-ProBNP was reported in AECOPD-PH group (r = 0.299, P = 0.001). However, the correlation between TBIL and PASP was no significantly different (r = 0.173, P = 0.105) (Table 5).

This analysis is a large retrospective case-controlled study to examine the role of NT-proBNP in AECOPD-PH. Our findings suggest that NT-proBNP has a diagnostic efficacy to predict morbidity in patients with AECOPD-PH and 175.14 pg/mL is a predictive NT-proBNP threshold. And NT-proBNP has a weak correlation with severity of PH with AECOPD.

COPD is a common chronic disease, and its incidence has gradually increased recently (11). PH is a common complication of COPD, which seriously affects the prognosis and quality of life of patients (12). AECOPD-PH can cause death in severe cases (13). The prevalence of PH in AECOPD depends on the severity of the disease and the definition of PH.

In our research, we conducted a preliminary statistical analysis of demographic data and some biomarkers, and found that age, gender, complications, smoking and other indicators were statistically significant, in order to eliminate the influence of these confounding factors, PSM (caliper value = 0.05, 1:1 matched) was used to analyze data, NT-proBNP, TBIL and RDW were significantly different in the three groups (P<0.05), and these models did indicate that the results were stable and reliable. Then NT-proBNP, TBIL and RDW were performed by multivariate logistic regression analysis to test the predicting AECOPD-PH relevance, NT-proBNP and TBIL had statistical significance (P<0.05). Then ROC curve was used to examined the diagnostic efficacy of NT-proBNP and TBIL, and found that NT-proBNP was the most suitable biomarker for diagnosing AECOPD-PH (AUC = 0.651). Finally, NT-proBNP had a weak correlation with severity of AECOPD-PH.

PH increases natriuretic peptide secretion in the right-sided heart chambers. Gene expression of NT-proBNP is up-regulated in the right atria with increased pressures, disruption of the natriuretic peptide receptor NPR-A worsens hypoxia-induced PH (14). NT-proBNP is typically influenced by age, gender, and obesity in addition to renal function (15), in our research, first, we excluded the patients with renal insufficiency, then data analysis indicated age and gender indeed had a significant difference between COPD group and AECOD-PH group, however, BMI had no significant difference (P>0.05), it might be associated with low distribution of obesity in China. We and other studies revealed low NT-proBNP levels in stable COPD patients (16).

In the absence of a significant left heart disease, NT-proBNP serves as a biomarker of an increased workload of the right heart originating from pulmonary arterial hypertension (17, 18). We did not have the opportunity to assess the NT-proBNP levels during periods of stable COPD, since data have shown these values to be significantly lower than during AECOPD group or AECOPD-PH group. The results showed that elevated NT-proBNP levels predicted morbidity rather than severity of AECOPD-PH. First, we excluded chronic cardiac insufficiency in all enroll patients, NT-proBNP elevation was a result of AECOPD-PH, different statistical models were performed to draw a reliable and stable conclusion of the demographic data and different biomarkers in AECOPD and AECOPD-PH groups, we supported that NT-proBNP could predict the morbidity of AECOPD-PH, accordingly, in our study, elevated NT-proBNP levels (≥ 175.14 pg/mL) had a more significant predictive value than TBIL (AUC = 0.651 VS AUC = 0.590), which was diagnosed with sensitivity (61.7%) and specificity (63.8%). Based on the PASP values of echocardiography (it allows an estimation of the pulmonary artery pressure and gives an overall impression of the right and left heart deformities and function), the AECOPD-PH group was further divided into several subgroups (mild, moderate and severe). However, elevated NT-proBNP had a weak correlation with severity of AECOPD-PH (r = 0.299, P = 0.001). Macchia et al. supported that the assessment of NT-proBNP was useful for the detection of ventricular dysfunction in patients with COPD. A cut-off value of 160 pg/mL increased>10-fold the probability of finding ventricular dysfunction with echocardiography, it is basically consistent with our ROC results. For AECOPD patients, NT-proBNP measurement may help identify patients with PH. In multiple studies, NT-proBNP did not correlate with typical parameters used to evaluate severity of exacerbation such as hypoxia, hypercapnia type of exacerbation, or forced expiratory volume in the first second of expiration, our study also agreed with it. A few studies have demonstrated elevated BNP correlating with increasing mortality, either in hospital or long-term (19). This association has not been replicated in other studies with larger COPD populations, making the prior observation a potential consequence of a smaller sample size (20, 21). We were unable to assess the association of NT-proBNP independently in a multivariate analysis due to the low in-hospital mortality rate in our population.

For many years, RDW was almost exclusively used for the differential diagnosis of anemia. Recently it was increasingly investigated as a negative prognostic factor in variety of acute and chronic medical conditions, such as cardiovascular disease, community-acquired pneumonia (22). Several studies showed that increased RDW is associated with disease severity and long-term mortality in COPD patients (23–25). Ozgul et al. showed increased RDW values in COPD patients compared to controls as well as in smokers compared to nonsmokers (24, 26). In our study, unadjusted data and PSM models (calipers value = 0.05) all showed RDW indeed had a significant difference in AECOPD-PH group(P<0.05). However, in logistic regression analysis, elevated RDW had no statistic difference compared with low/moderately elevated RDW value (P>0.05). The results supported elevated RDW might not be associated with AECOPD-PH.

Total bilirubin (TBIL) has been considered as a powerful endogenous antioxidant in recent years. Liu et al. supported a different conclusion that the association between TBIL and diabetic retinopathy risk was not a simple linear association but a U-shaped curve (27), a cohort study based on 7685 middle-aged British men firstly revealed that there was a U-shaped relationship between TBIL and risk of ischemic heart disease (28). Our data analysis was similar to it, compared with TBIL < 13.8µmol/L, TBIL13.8-16.5µmol/L had a lower protective trend than TBIL > 16.5µmol/L (OR = 0.485, 95%CI: 0.280–0.841 and OR = 0.598, 95%CI: 0.413–0.864, respectively). And the actual U-shaped association might be the combination of antioxidation and liver toxicity effects (27). In our study, TBIL had a lower predictive value than NT-proBNP, and it had no significant difference in correlation with AECOPD-PH severity (P>0.05).

In conclusion, we suggest that NT-proBNP has strongly diagnostic efficacy to predict morbidity in patients with AECOPD-PH and 175.14 pg/ mL is a predictive NT-proBNP threshold. And NT-proBNP has a weak correlation with severity of PH with COPD. COPD complied with PH was not a common disease; we have tried our best to collect as much sample size as possible.

Our study also has several limitations, such as a retrospective, single‑center design and the lack of a healthy control group. In our population and the mixture of patients with chronic COPD may also have biased this observation (29). Most regretfully, since this is a large retrospective case-controlled study, too few patients were eventually included in the log-rank, and we cannot make statistics on the prognosis of NT-proBNP in predicting AECOPD-PH.

NT-proBNP has a diagnostic efficacy in AECOPD complicated with PH and NT-proBNP has a weak correlation with severity of PH with AECOPD.

Chronic obstructive pulmonary disease (COPD); Acute exacerbation of chronic obstructive pulmonary disease (AECOPD); Pulmonary arterial hypertension (PH); Normal chronic drug (N-proBNP); Total bilirubin (TBIL); Width of Erythrocyte volume distribution (RDW).

Acknowledgments

The author thanks Xin Hu help for the guidance of professional knowledge in respiration

Authors’ contributions

WS, FMT and LW analyzed the literature and wrote the manuscript. QZ, NF, and JHF collected the patient data. JL and YW disposed the data. JW and XMM read and approved the final manuscript.

Funding

This work was supported by the National Natural Science Foundation of China (81760005).

Availability of data and materials

Not applicable.

Ethics approval and consent to participate

The study was approved by the Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University. All participants have signed informed consent forms.

Competing interests

The authors declare that he has no competing interests.

Liu J, Yang J, Xu S, Zhu Y, Xu S, Wei L, et al. Prognostic impact of red blood cell distribution width in pulmonary hypertension patients: A systematic review and meta-analysis. Medicine (Baltimore). 2020;99(16):e19089.
Hoeper MM, Ghofrani HA, Grunig E, Klose H, Olschewski H, Rosenkranz S. Pulmonary Hypertension. Dtsch Arztebl Int. 2017;114(5):73-84.
McGarvey LP, John M, Anderson JA, Zvarich M, Wise RA, Committee TCE. Ascertainment of cause-specific mortality in COPD: operations of the TORCH Clinical Endpoint Committee. Thorax. 2007;62(5):411-5.
Petrauskas LA, Saketkoo LA, Kazecki T, Saito S, Jaligam V, deBoisblanc BP, et al. Use of red cell distribution width in a population at high risk for pulmonary hypertension. Respir Med. 2019;150:131-5.
Chin KM, Rubin LJ, Channick R, Di Scala L, Gaine S, Galie N, et al. Association of N-Terminal Pro Brain Natriuretic Peptide and Long-Term Outcome in Patients With Pulmonary Arterial Hypertension. Circulation. 2019;139(21):2440-50.
Hawkins NM, Khosla A, Virani SA, McMurray JJ, FitzGerald JM. B-type natriuretic peptides in chronic obstructive pulmonary disease: a systematic review. BMC Pulm Med. 2017;17(1):11.
Frantz RP, Farber HW, Badesch DB, Elliott CG, Frost AE, McGoon MD, et al. Baseline and Serial Brain Natriuretic Peptide Level Predicts 5-Year Overall Survival in Patients With Pulmonary Arterial Hypertension: Data From the REVEAL Registry. Chest. 2018;154(1):126-35.
Mascarenhas J, Azevedo A, Bettencourt P. Coexisting chronic obstructive pulmonary disease and heart failure: implications for treatment, course and mortality. Curr Opin Pulm Med. 2010;16(2):106-11.
Adrish M, Nannaka VB, Cano EJ, Bajantri B, Diaz-Fuentes G. Significance of NT-pro-BNP in acute exacerbation of COPD patients without underlying left ventricular dysfunction. Int J Chron Obstruct Pulmon Dis. 2017;12:1183-9.
Mirza S, Clay RD, Koslow MA, Scanlon PD. COPD Guidelines: A Review of the 2018 GOLD Report. Mayo Clinic proceedings. 2018;93(10):1488-502.
Lopez-Campos JL, Tan W, Soriano JB. Global burden of COPD. Respirology. 2016;21(1):14-23.
Samareh Fekri M, Torabi M, Azizi Shoul S, Mirzaee M. Prevalence and predictors associated with severe pulmonary hypertension in COPD. Am J Emerg Med. 2018;36(2):277-80.
Kurashima K, Takaku Y, Hoshi T, Kanauchi T, Nakamoto K, Takayanagi N, et al. Lobe-based computed tomography assessment of airway diameter, airway or vessel number, and emphysema extent in relation to the clinical outcomes of COPD. Int J Chron Obstruct Pulmon Dis. 2015;10:1027-33.
Phua J, Lim TK, Lee KH. B-type natriuretic peptide: issues for the intensivist and pulmonologist. Crit Care Med. 2005;33(9):2094-13.
Stienen S, Salah K, Eurlings LW, Bettencourt P, Pimenta JM, Metra M, et al. Targeting N-Terminal Pro-Brain Natriuretic Peptide in Older Versus Younger Acute Decompensated Heart Failure Patients. JACC Heart Fail. 2016;4(9):736-45.
Bhatti H, Ramdass A, Cury JD, Jones LM, Shujaat A, Louis M, et al. Operator dependent factors implicated in failure of non-invasive positive pressure ventilation (NIPPV) for respiratory failure. Clin Respir J. 2017;11(6):901-5.
Leuchte HH, Baumgartner RA, Nounou ME, Vogeser M, Neurohr C, Trautnitz M, et al. Brain natriuretic peptide is a prognostic parameter in chronic lung disease. Am J Respir Crit Care Med. 2006;173(7):744-50.
Leuchte HH, Holzapfel M, Baumgartner RA, Ding I, Neurohr C, Vogeser M, et al. Clinical significance of brain natriuretic peptide in primary pulmonary hypertension. J Am Coll Cardiol. 2004;43(5):764-70.
Vallabhajosyula S, Sundaragiri PR, Kanmanthareddy A, Ahmed AA, Mahfood Haddad T, Rayes HA, et al. Influence of Left Ventricular Hypertrophy on In-Hospital Outcomes in Acute Exacerbation of Chronic Obstructive Pulmonary Disease. COPD. 2016;13(6):712-7.
Inoue Y, Kawayama T, Iwanaga T, Aizawa H. High plasma brain natriuretic peptide levels in stable COPD without pulmonary hypertension or cor pulmonale. Intern Med. 2009;48(7):503-12.
Stolz D, Breidthardt T, Christ-Crain M, Bingisser R, Miedinger D, Leuppi J, et al. Use of B-type natriuretic peptide in the risk stratification of acute exacerbations of COPD. Chest. 2008;133(5):1088-94.
Salvagno GL, Sanchis-Gomar F, Picanza A, Lippi G. Red blood cell distribution width: A simple parameter with multiple clinical applications. Crit Rev Clin Lab Sci. 2015;52(2):86-105.
Tertemiz KC, Ozgen Alpaydin A, Sevinc C, Ellidokuz H, Acara AC, Cimrin A. Could "red cell distribution width" predict COPD severity? Rev Port Pneumol (2006). 2016;22(4):196-201.
Epstein D, Nasser R, Mashiach T, Azzam ZS, Berger G. Increased red cell distribution width: A novel predictor of adverse outcome in patients hospitalized due to acute exacerbation of chronic obstructive pulmonary disease. Respir Med. 2018;136:1-7.
Kalemci S, Akin F, Sarihan A, Sahin C, Zeybek A, N Y. Relationship between hematological parameters and severity of chronic obstructive pulmonary disease. Pol Arch Intern Med. 2018;31(128(3)):171-7.
Ozgul G, Seyhan EC, Ozgul MA, Gunluoglu MZ. Red Blood Cell Distribution Width in Patients With Chronic Obstructive Pulmonary Disease and Healthy Subjects. Arch Bronconeumol. 2017;53(3):107-13.
Liu M, Wang J, He Y. The U-Shaped Association between Bilirubin and Diabetic Retinopathy Risk: A Five-Year Cohort Based on 5323 Male Diabetic Patients. J Diabetes Res. 2018;2018:4603087.
Breimer LH, Wannamethee G, Ebrahim S, Shaper AG. Serum bilirubin and risk of ischemic heart disease in middle-aged British men. Clinical chemistry. 1995;41(10):1504-8.
Macchia A, Rodriguez Moncalvo JJ, Kleinert M, Comignani PD, Gimeno G, Arakaki D, et al. Unrecognised ventricular dysfunction in COPD. Eur Respir J. 2012;39(1):51-8.

Due to technical limitations, tables are only available as a download in the Supplemental Files section.

PHtable.xlsx

Download PDF

Journal Publication

published 01 Dec, 2021

Read the published version in Respiratory Research →

Editorial decision: Major revision
16 Sep, 2021
Review #2 received at journal
08 Aug, 2021
Review #1 received at journal
30 Jul, 2021
Reviewer #2 agreed at journal
26 Jul, 2021
Reviews received at journal
19 Jul, 2021
Reviewers invited by journal
19 Jul, 2021
Reviewer #1 agreed at journal
18 Jul, 2021
First submitted to journal
04 Jul, 2021
Editor assigned by journal
03 Jul, 2021
Submission checks completed at journal
03 Jul, 2021
Editor invited by journal
03 Jul, 2021

You are reading this latest preprint version

NT-pro BNP in AECOPD-PH: Old Biomarker, New Insights-Based on a Large Retrospective Case-Controlled Study

Status:

Journal Publication

Version 1

Abstract

Figures

Background

Methods

Patients

Data collection

Exclusion criteria

Biochemical measurement and echocardiography

Statistical analysis

Results

Demographics and clinical presentations

Blood biomarkers

Propensity score matching

Logistic regression analysis

ROC analysis of blood biomarkers

Rank correlation analysis

Discussion

Conclusions

Abbreviations

Declarations

References

Tables

Supplementary Files

Status:

Journal Publication

Version 1