Association of Blood Inflammatory Biomarkers with Clinical Outcomes in Patients with AECOPD: An 8-Year Retrospective Study in Beijing

Abstract

Purpose

To discover potential inflammatory biomarkers, which can compare favorably with traditional biomarkers, and their best cut-offs at first admission to predict clinical outcomes (short-term and long-term) and the risk of readmission among acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients.

Patients and Methods

Novel inflammatory biomarkers (such as the neutrophil–lymphocyte ratio [NLR], platelet–lymphocyte ratio [PLR], etc.) were compared with traditional biomarkers by Pearson’s correlation test. Logistic regression analysis and receiver operating characteristic (ROC) curves were applied to judge the accuracy of these novel biomarkers to predict in-hospital mortality.

Results

Surviving AECOPD patients had lower NLR, PLR, and lymphocyte-to-monocyte ratios than non-survival patients (all P < 0.001). According to Pearson’s correlation test, there was a linear correlation between novel and traditional biomarkers (all P < 0.05). In terms of a single biomarker, the AUC value of NLR was the largest, which was not inferior to C-reactive protein (Z-P = 0.064), and superior to erythrocyte sedimentation rate (Z-P = 0.002) and other novel single inflammatory biomarkers (all Z-P < 0.05). The mortality of patients with NLR ≥ 4.43 was 2.308-fold higher than that of patients with NLR < 4.43. After dividing patients into a higher or lower NLR group, pooled results showed that patients with NLR ≥ 4.43 had a higher rate of treatment failure, intensive care unit admission, longer hospital length of stay, one-year mortality after the index hospitalization, and overall mortality than patients with NLR < 4.43 (all P < 0.001). Patients with NLR ≥ 4.43 were associated with higher and earlier first readmission due to AECOPD than patients with lower NLR.

Conclusion

NLR was the best to forecast the clinical prognosis and readmission risk among AECOPD patients, which was not inferior to CRP, and the best cut-off value of NLR was 4.43.

Keywords:

• acute exacerbations of chronic obstructive pulmonary disease
• neutrophil–lymphocyte ratio
• mortality
• inflammatory biomarkers
• readmission rate
• treatment failure rate

Abbreviations

AECOPD, Acute exacerbation of chronic obstructive pulmonary disease; NLR, Neutrophil–lymphocyte ratio; PLR, Platelet–lymphocyte ratio; LMR, Lymphocyte-to-monocyte ratio; ENR, Eosinophil-to-neutrophil ratio; ELR, Eosinophil-to-lymphocyte ratio; CRP, C-reactive protein; ESR, Erythrocyte sedimentation rate; PMR, Platelet to mean platelet volume ratio; ROC, Receiver-operating characteristic; KM, Kaplan–Meier; WHO, World Health Organization; PCT, Procalcitonin; CRP, C-reactive protein; ESR, Erythrocyte sedimentation rate; NIPPV, Non-invasive positive pressure ventilation; CAP, Community acquired pneumonia; CBC, Complete blood count; EMRD, Electronic medical record database; NIMV Non-invasive mechanical ventilation; IMV, Invasive mechanical ventilation; LOS, Length of stay; ICU, Intensive care unit; IQR, Interquartile range; ROC, Receiver-operating characteristic; OR, Odds ratios; CIs, Confidence intervals; K–M, Kaplan–Meier; BMI, Body mass index; RDW, Red blood cell distribution width; MPV, Mean platelet volume; BUN, Blood urea nitrogen; SGOT, Serum glutamic-oxaloacetic transaminase; NT-proBNP, N-terminal pro-B-type natriuretic peptide; LDL, Low-density lipoprotein; SGPT, Serum glutamic pyruvic transaminase; MCV, Mean corpuscular volume; PLT, Platelet; PaCO₂, Pressure of carbon dioxide; HCO₃, Bicarbonate; ALB, Albumin; RR, Rate ratio; GOLD, Global initiative for chronic obstructive lung disease; AUC, Area under curve; COVID-19, Corona Virus Disease 2019; C-index, Concordance index.

Data Sharing Statement

Data about individual deidentified participants of this trial will be available from the corresponding author Zhaohui Tong (Email: [email protected]) on reasonable request after the main results of the study have been published.

Ethics Statement

This study was approved by the Research Ethics Board of Beijing Chao-Yang Hospital (project approval number: 2020-ke-544). This study complies with the declaration of Helsinki.

Informed Consent Statement

Informed consent was waived due to the anonymous and mandatory nature of the data.

Author Contributions

Shuai Shao developed the initial idea of this study. Shuai Shao, Zhijing Zhang made their contributions to study design, execution, acquisition of data, analysis, interpretation and writing of this article. Zhaohui Tong, Lin Feng and Lirong Liang also made significantly contributed to this work in study execution, acquisition of data, interpretation of this article. Lirong Liang and Lin Feng critically reviewed the article. Zhaohui Tong substantially revised this article and provided revision suggestions for it to make it better. All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that there are no conflicts of interest in this work.

Additional information

Funding

This work was supported by grants from the Beijing Municipal Science & Technology Commission (No. Z201100005520028) and the Beijing Municipal Administration of Hospitals Incubating Program (PX2020014). The funders had no role in the study design, data collection, data analysis and interpretation, writing of the report, or the decision to submit the article for publication.