Inflammatory discordance phenotype in COPD: Dissociation between neutrophil-to-lymphocyte ratio and conventional markers

Abstract

Background Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder with diverse inflammatory profiles. Long-term oxygen therapy (LTOT) identifies a subgroup of patients with advanced disease; however, the systemic inflammatory characteristics of this population remain incompletely defined. Objective To investigate systemic inflammatory markers in clinically stable COPD patients according to LTOT status and to examine whether elevated NLR reflects conventional inflammatory activation or a distinct immune profile. Methods This study represents a secondary, exploratory subgroup analysis of a prospectively collected COPD cohort. Patients were stratified according to LTOT status and compared in terms of pulmonary function, gas exchange parameters, and inflammatory markers. NLR was analyzed in relation to total leukocyte count (WBC), C-reactive protein (CRP), eosinophil count, and oxygenation parameters. Between-group comparisons were performed using non-parametric tests, and correlation and multivariable regression analyses were conducted to identify independent associations with NLR. Results A total of 127 clinically stable COPD patients were included, of whom 31 (24.4%) were receiving LTOT. LTOT-treated patients had significantly higher NLR values compared with non-LTOT patients (6.32 ± 4.87 vs 3.68 ± 2.41, p = 0.001), accompanied by lower lymphocyte and eosinophil counts. In contrast, total leukocyte count and CRP levels were similar between groups. In multivariable analysis, WBC, eosinophil count, and CRP remained independently associated with NLR, whereas oxygenation parameters and pulmonary function measures were not. Conclusions This study suggests that NLR elevation in advanced COPD may not necessarily reflect overt systemic inflammation, but rather a distinct immune phenotype. Context-specific interpretation of NLR may therefore be required in advanced disease.