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

Abstract

Highlights What are the main findings?1. Among 2644 patients with spirometry-confirmed COPD and available baseline neutrophil-to-monocyte plus lymphocyte ratio (NMLR), 1085 deaths occurred during 19,231 person-years of follow-up. 2. Elevated baseline NMLR was independently associated with increased long-term all-cause mortality, with patients in the highest quartile showing an approximately twofold-higher adjusted risk compared with those in the lowest quartile. What are the implications of the main findings?1. Higher baseline NMLR was independently associated with increased long-term all-cause mortality in patients with COPD. 2. Baseline NMLR may improve mortality risk stratification and contribute to precision follow-up approaches in primary care, although external validation is required before clinical implementation. Abstract 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.