Relationships of Serum CC16 Levels with Smoking Status and Lung Function in COPD

Background: The club cell secretory protein (CC16) has anti-inflammatory and antioxidant effects, and low CC16 serum levels have been associated with both risk and progression of COPD, yet the interaction between smoking and CC16 on lung function outcomes remains unknown. Methods: Utilizing cross-sectional data on United States veterans, CC16 serum concentrations were measured by ELISA and log transformed for analyses. Spirometry was conducted and COPD status was defined by post-bronchodilator FEV1/FVC ratio \u3c 0.7. Smoking measures were self-reported on questionnaire. Multivariable logistic and linear regression were employed to examine associations between CC16 levels and COPD, and lung function with adjustment for covariates. Unadjusted Pearson correlations described relationships between CC16 level and lung function measures, pack-years smoked, and years since smoking cessation. Results: The study population (N = 351) was mostly male, white, with an average age over 60 years. An interaction between CC16 and smoking status on FEV1/FVC ratio was demonstrated among subjects with COPD (N = 245, p = 0.01). There was a positive correlation among former smokers and negative correlation among current or never smokers with COPD. Among former smokers with COPD, CC16 levels were also positively correlated with years since smoking cessation, and inversely related with pack-years smoked. Increasing CC16 levels were associated with lower odds of COPD (ORadj = 0.36, 95% CI 0.22-0.57, Padj \u3c 0.0001). Conclusions: Smoking status is an important effect modifier of CC16 relationships with lung function. Increasing serum CC16 corresponded to increases in FEV1/FVC ratio in former smokers with COPD versus opposite relationships in current or never smokers. Additional longitudinal studies may be warranted to assess relationship of CC16 with smoking cessation on lung function among subjects with COPD

Investigation of Cumulative Genetic Risk and CC16 in Adult Asthma and COPD Populations

INVESTIGATION OF CUMULATIVE GENETIC RISK AND CC16 IN ADULT ASTHMA AND COPD POPULATIONS Kelli C. Gribben, Ph.D. University of Nebraska Medical Center, 2022 Supervisors: Paraskevi A. Farazi and Tricia D. LeVan, Ph.D. Asthma and Chronic Obstructive Pulmonary Disease (COPD) have complex etiologies and lack biological predictors that can be used for primary prevention, early detection, progression, or monitoring. Genetic risk scores (GRS) aggregate genetic effects from GWAS-identified susceptibility variants associated with a trait. GRS may provide opportunities to improve disease prediction to inform public health and clinical interventions. Asthma GRS studies utilizing multi-ethnic populations are scarce and there is a need for GRS to be evaluated in independent study populations. The Club Cell Secretory Protein (CC16) is a promising biomarker for asthma and COPD. Several gaps exist in the literature regarding CC16’s role in asthma and COPD. This dissertation addressed several key gaps in the literature by utilizing three different study populations: National Health and Nutrition Examination Survey (NHANES), Agricultural Lung Health Study (ALHS), and a Midwest United States Veteran population. The aims addressed the questions: 1) Is a GRS, based on external asthma GWAS, associated with asthma in an independent study population, NHANES, and does smoke exposure (i.e. cotinine) affect associations between GRS and asthma?, 2) Are CC16 polymorphisms associated with adult asthma, subtypes and asthma control in adults from ALHS?, 3) Are CC16 protein levels associated with lung function, smoking status or smoking history among a Veteran COPD population? Results of these studies will add new knowledge of the potential utility of an asthma GRS and CC16 biomarker to ultimately reduce burden and improve clinical management of asthma and COPD