A101-12 Type 1 Immunity Predominates in Chronic Bronchitis Patients With Chronic Obstructive Pulmonary Disease

Rationale Chronic Bronchitis (CB) represents a clinical phenotype of chronic obstructive pulmonary disease (COPD) characterized by chronic inflammatory airway disease. The role of Type 1 immunity, reflected in Th1 cell distribution and Th1-driving cytokines, and the relationship between Th1 and Th2 cell responses remain somewhat controversial. This study assesses the immune responses in COPD patients with traditionally defined CB and hypothesizes that CB is characterized by a predominant Type 1 immune response. Methods We performed a single-center, prospective, observational cohort study of participants between 40-80 years of age with clinically diagnosed COPD. CB was defined based on reported symptoms as per Medical Research Council (MRC) criteria1. Besides routine spirometric and clinical assessments, all subjects underwent extensive bioprofiling, which included peripheral blood flow-cytometric analysis and serum cytokine analysis using Luminex Discovery Assay (R&D Systems, Inc, MN). T-cell subsets were analyzed by flow cytometry using a panel of lineage-specific surface and intracellular markers distinguishing Th1, Th2, Th17 and T-reg cells (CD3+CD4+CXCR3+CCR6-CD161-, CD3+CD4+CXCR3-CCR4+CRTH2+, CD3+CD4+CXCR3-CCR6+CD161+, and CD3+CD4+CD25+FOXP3+, respectively). Data was analyzed using the Wilcoxon rank-sum test and Chi-square tests for continuous and categorical variables, respectively, while correlations were assessed using Spearman’s Rho or logistic regression models adjusted for relevant covariates. Results Of 83 active and former smokers with predominantly moderate symptomatic COPD, CB was present in 22.9% of the cohort. Compared to COPD patients without CB, multivariate analysis adjusted for age, sex, race, smoking status, leukocytes, sedimentation rate, and baseline exacerbations demonstrated that COPD patients with CB had a higher percentage of Th1 cells (27.2±8.1 vs. 20.0±5.9%, P < 0.01) and higher Th1/Th2 ratios (5.7±3.6 vs. 2.7±1.6, P < 0.01) in peripheral blood. CB was also associated with lower percentages of Th17 cells and Th17/Treg ratios. Despite predominance of Type 1 immune responses in CB, elevated blood eosinophil counts over >300cells/ µL were equally prevalent in both groups, and average baseline eosinophil counts remained similar among both groups (177±116 vs. 175±143, P = 0.47). Conclusion Clinically diagnosed chronic bronchitis in stable COPD is associated with increased Type 1 immune responses. Despite this association, eosinophil counts and eosinophilic phenotype prevalence were similar to non-CB patients. An increased understanding of inflammatory responses will allow for more informed diagnostic measures and targeted therapeutics. REFERENCE 1. Fletcher CM, Elmes PC, Fairbairn AS, Wood CH. The significance of respiratory symptoms and the diagnosis of chronic bronchitis in a working population. Br Med J. 1959;2(5147):257-266.