Predictive Role of White Blood Cell Differential Count for the Development of Acute Exacerbation in Korean Chronic Obstructive Pulmonary Disease

Abstract

Purpose

Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by chronic inflammation. Acute exacerbation of COPD (AECOPD) manifests as acute worsening of respiratory symptoms and is associated with high morbidity and mortality. The aim of the present study was to evaluate the predictive value of white blood count (WBC) and its derived inflammatory biomarkers for AECOPD.

Methods

From the Korean COPD Subgroup Study cohort, a prospective and multicenter observational study, 826 patients who had baseline complete blood count (CBC) and 3-year AECOPD data were included. Follow-up CBC data at 1 (n = 385), 2 (n = 294), and 3 (n = 231) years were collected for available patients. The primary outcome was the occurrence of AECOPD at 3 years. The risk of AECOPD was evaluated using a binary logistic analysis.

Results

The cumulative incidences of 12-, 24-, and 36-month AECOPD were 47.6%, 60.5%, and 67.6%, respectively. Patients with AECOPD at 3 years had higher baseline WBC counts, neutrophil counts, neutrophil/lymphocyte ratio (NLR), and neutrophil/monocyte ratio than those without AECOPD. Higher WBC count, neutrophil count, and NLR were associated with the 3-year occurrence of AECOPD in the univariate analysis, but only the higher neutrophil count was a significant risk factor (odds ratio [OR] = 1.468; 95% confidence interval [CI]: 1.024–2.104) in the covariates-adjusted analysis. In the analysis of changes in inflammatory parameters, a decrease in the platelet count (OR = 0.502; 95% CI: 0.280–0.902) and NLR (OR = 0.535; 95% CI: 0.294–0.974) at 2 years and an increase in the eosinophil count (OR = 2.130; 95% CI: 1.027–4.416) at 3 years were significantly associated with AECOPD in the adjusted analysis.

Conclusion

Our data suggest that a high baseline WBC count, particularly neutrophil count, was associated with a higher incidence of long-term AECOPD.

Keywords:

• blood cell count
• blood platelets
• eosinophils
• lymphocytes
• neutrophils
• pulmonary disease
• chronic obstructive

Abbreviations

COPD, chronic obstructive pulmonary disease; AECOPD, acute exacerbation of chronic obstructive pulmonary disease; AE, acute exacerbation; BMI, body mass index; GERD, gastroesophageal reflux disease; IQR, interquartile range; TB, tuberculosis; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; FEF25-75, forced expiratory flow between 25–75% of vital capacity; DLco, diffusing capacity for carbon monoxide; DL/VA, diffusing capacity for carbon monoxide/alveolar volume; Hb, hemoglobin; TLC, total lung capacity; VC, vital capacity; IC, inspiratory capacity; FRC, functional residual capacity; RV, residual volume; mMRC, modified Medical Research Council; CAT, COPD Assessment Test; SGRQ, St. George’s Respiratory Questionnaire; SpO2, oxygen saturation; ICS, inhaled corticosteroid; LABA, long-acting beta agonist; LAMA, a long-acting muscarinic antagonist; PDE4 inhibitor, phosphodiesterase-4 inhibitor; LTRA, leukotriene receptor antagonist; CBC, complete blood count; OR, odds ratio; CI, confidence interval; WBC, white blood cell; NLR, neutrophil/lymphocyte ratio; dNLR, derived neutrophil/lymphocyte ratio; MLR, monocyte/lymphocyte ratio; EBR, eosinophil/basophil ratio; KOCOSS, Korean COPD Subtype Study.

Data Sharing Statement

Data generated and/or analyzed during the study are available from the corresponding author on reasonable request.

Ethics Approval and Consent to Participate

All patients signed an informed consent form for the use of clinical data, and ethics approval was obtained from all medical institutions, including the Institutional Review Board of the Soonchunhyang University Seoul Hospital (2022-03-019).

Author Contributions

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 they have no conflicts of interests.

Additional information

Funding

This work was supported by the Soonchunhyang University Research Fund and the Research Program funded Korea National Institute of Health (Fund CODE 2016ER670100, 2016ER670101, 2016ER670102, 2018ER67100, 2018ER67101, 2018ER67102, 2021ER120500, 2021ER120501, and 2021ER120502).