Neutrophil-to-Lymphocyte Ratio (NLR) as a Biomarker in Clinically Stable Chronic Obstructive Pulmonary Disease: SPIROMICS cohort

Rationale: Inflammation is central to chronic obstructive pulmonary disease (COPD) pathogenesis but incompletely represented in COPD prognostic models. Neutrophil to lymphocyte ratio (NLR) is a readily available inflammatory biomarker. Objectives: To explore the associations of NLR with smoking status, clinical features of COPD, and future adverse outcomes. Methods: We analyzed NLR calculated from the complete blood count of participants who currently or formerly smoked (n = 2,624) and tobacco-naïve controls (n = 187) in the SPIROMICS multicenter observational cohort study. We assessed the stability of NLR at 6 weeks and 1 year, the association with select blood biomarkers, and the impact of smoking on NLR and cell counts. We stratified participants by NLR quartiles to compare cross-sectional clinical features at enrollment, prospectively observed exacerbations at 1 year, and mortality during longitudinal follow-up. Results: Higher NLR quartiles were broadly associated with more severe clinical features of COPD. NLR values were repeatable at 6 weeks (ICC=0.74) and 1 year (ICC=0.62). The impact of smoking on NLR varied with the severity of airflow limitation, mediated by an interaction between smoking, FEV1 % predicted, and neutrophil counts but not lymphocyte counts. The highest NLR quartile (>3.11) was associated with an increased risk of exacerbation over 1-year (adjusted OR=1.51 95%CI 1.18, 1.92) and increased risk of mortality (adjusted HR=1.41, 95%CI 1.20, 1.66) compared to quartiles 1-3. Conclusions: Elevated NLR in stable COPD is a widely available biomarker associated with increased risk for exacerbation and death. The impact of cigarette smoking on NLR varies with disease severity.