Nonlinear associations of the neutrophil-to-lymphocyte ratio and derived neutrophil-to-lymphocyte ratio with asthma-COPD overlap prevalence: a cross-sectional study.

Background: Asthma-chronic obstructive pulmonary disease overlap (ACO) is associated with persistent airflow limitation and adverse clinical outcomes. Whether the neutrophil-to-lymphocyte ratio (NLR) and derived NLR (dNLR) show nonlinear associations with ACO prevalence among patients with asthma is uncertain. Methods: We conducted a retrospective cross-sectional analysis of 505 patients with asthma. ACO was defined by coexisting physician-documented diagnoses of asthma and COPD. The usual diagnostic framework is based on Global Initiative for Asthma guidance for asthma and Global Initiative for Chronic Obstructive Lung Disease criteria for COPD; the latter include compatible clinical features and persistent post-bronchodilator airflow limitation (FEV1/FVC <0.70). NLR and dNLR were evaluated as continuous, standardized, and quartile-based exposures. Multivariable logistic regression, restricted cubic splines, and two-piecewise logistic regression were used to assess associations and potential inflection points. Medication-stratified analyses were exploratory. Results: Of 680 patients screened, 505 were included, including 190 (37.6%) with ACO and 315 (62.4%) with asthma without COPD. In the fully adjusted model, the highest vs. lowest quartiles of NLR [odds ratio [OR], 4.97; 95% confidence interval [CI], 2.50-9.87; Conclusion: Higher NLR and dNLR were independently associated with greater ACO prevalence in this single-center asthma cohort. These inexpensive blood-derived indices may help identify patients who warrant further diagnostic assessment, but the proposed inflection points and medication interactions require external and prospective validation.