Peripheral Blood Neutrophil-Monocyte-to-Lymphocyte Ratio and Long-Term All-Cause Mortality in Patients with Chronic Obstructive Pulmonary Disease: A Population-Based Primary Care Cohort Study.

Background/Objectives: Chronic obstructive pulmonary disease (COPD) is a heterogeneous syndrome with substantial variability in clinical progression and survival. Although neutrophil-to-lymphocyte ratio has been widely studied, evidence regarding neutrophil-to-monocyte plus lymphocyte ratio (NMLR) remains limited. This study evaluated whether baseline peripheral blood neutrophil-to-monocyte plus lymphocyte ratio (NMLR), a composite marker of systemic inflammation, was independently associated with long-term all-cause mortality in patients with COPD managed in primary care. Methods: We conducted a retrospective population-based cohort study using electronic health records from the Lleida Health Region (Spain) between 1 January 2014 and 31 December 2023. Patients with spirometry-confirmed COPD and available baseline complete blood counts were included. Baseline NMLR was calculated as (absolute neutrophil count + absolute monocyte count)/absolute lymphocyte count using the first valid blood sample obtained after cohort entry. Patients were categorized into NMLR quartiles. Associations with all-cause mortality were assessed using multivariable Cox proportional hazards regression models adjusted for age, sex, smoking status, lung function, and baseline comorbidity burden. Results: A total of 2644 patients were included, contributing 19,231 person-years of follow-up. During a median follow-up of 8.8 years, 1085 deaths occurred. Mortality increased progressively across NMLR quartiles, from 28.3% in the lowest quartile to 60.2% in the highest quartile. In fully adjusted analyses, patients in the highest quartile had higher all-cause mortality than those in the lowest quartile (hazard ratio [HR] 2.00; 95% confidence interval [CI] 1.66-2.40; p < 0.001). When modeled continuously, each doubling of baseline NMLR was associated with a 34% increase in mortality risk (HR 1.34; 95% CI 1.26-1.42). Conclusions: Elevated baseline NMLR was independently associated with increased long-term mortality in COPD. As an inexpensive and routinely available inflammatory biomarker, NMLR may improve mortality risk stratification and support future evaluation of risk-stratified follow-up strategies in primary care. External validation is required before implementation in routine clinical practice.