Baseline Neutrophil-to-Lymphocyte Ratio and Longitudinal Lung Function Decline in Chronic Obstructive Pulmonary Disease: A Retrospective Cohort Study
Abstract
Background Systemic inflammation may contribute to heterogeneous lung function trajectories in chronic obstructive pulmonary disease (COPD), but evidence linking the neutrophil-to-lymphocyte ratio (NLR) to longitudinal forced expiratory volume in one second (FEV1) change is limited. Methods We analyzed repeated spirometry from a single-center retrospective cohort. Eligibility required clinically stable chronic obstructive pulmonary disease, baseline blood counts, at least two qualified spirometry assessments, and at least 12 months of recorded follow-up. Linear mixed-effects models estimated the association between baseline log2-transformed neutrophil-to-lymphocyte ratio and annual forced expiratory volume in one second (FEV1) change. Sequential models added demographic and exposure variables, then baseline disease severity. Post hoc analyses examined common visit windows and sensitivity to covariate selection. Results Of 819 patients, 667 met longitudinal cohort criteria; 640 patients with 2525 qualified observations entered the complete-case model. Median recorded follow-up was 22 months, with a median of four qualified assessments per patient. Additional FEV1 decline per ratio doubling increased from 4.05 mL/year unadjusted (95% confidence interval −1.95 to 10.04) to 8.26 mL/year after severity adjustment (2.29 to 14.23; P=0.0068). Comparisons within the same 640 patients also showed model dependence. Restriction to baseline, 6-month and 12-month visit windows yielded 12.78 mL/year (2.72 to 22.84; 269 patients). The corresponding baseline, 12-month and 24-month estimate was imprecise (13.57 mL/year; −0.04 to 27.17; 116 patients). Conclusion Higher baseline neutrophil-to-lymphocyte ratio was associated with modestly faster lung function decline after adjustment for disease severity. The association depended on the adjustment model and does not establish causality or individual predictive value. Prospective studies with standardized follow-up are needed.