Current Smoking With or Without Chronic Bronchitis is Independently Associated With Goblet Cell Hyperplasia in Healthy Smokers and COPD Subjects: an Analysis of the SPIROMICS Cohort

Abstract

Background: COPD, chronic bronchitis (CB) and active smoking have all been associated with large airway goblet cell hyperplasia (GCH) in small studies. Active smoking is strongly associated with CB, but there is a disconnect between CB clinical symptoms and pathology. Chronic cough and sputum production poorly correlate with the presence of GCH or COPD. We hypothesized that the primary determinant of GCH in ever smokers with or without airflow obstruction is active smoking. Methods: Goblet Cell Density (GCD) was measured in 71 current or former smokers [32 subjects without COPD and 39 COPD subjects] in which endobronchial mucosal biopsies were obtained during the SPIROMICS bronchoscopy substudy. Biopsies were stained with Periodic Acid Schiff-Alcian Blue, and GCD was measured as number of goblet cells/mm basement membrane by two independent observers in a blinded fashion. GCD was divided into tertiles (1=low, 2=medium, 3=high) based on log10 transformed values. Multivariable logistic and linear regressions were performed with CB and current smoking as the independent variables of interest and demographics and FEV1% predicted smoking as covariates.Results: Log10 GCD was greater in current smokers compared to former smokers (1.16±0.28 [n=31] vs. 0.85±0.42 [n=40], p=0.001). Those with classically defined CB had a greater log10 GCD compared to those without CB (1.21±0.31 [n=13] vs. 0.94±0.39 [n=58], p=0.024). Similarly, those with CB by the SGRQ definition had a greater log10 GCD compared to those without CB (1.13±0.39 [n=25] vs. 0.91±0.39 [n=43], p=0.028). Tertiles 2 and 3 had a greater percent of current smokers compared to tertile 1 (16.7, 50.0 and 63.6% in tertiles 1, 2 and 3, respectively, p=0.004). Current smoking was independently associated with tertile 3 (high GCD) (OR 4.15, 95% CI 1.17, 14.71) whereas CB was not in multivariable logistic regression. Similar results were found with multivariable linear regression for log10 GCD.Conclusions: GCD is higher in current smokers with and without airflow obstruction and in CB. However, current smoking, but not CB, is independently associated with GCD. These results suggest that GCH is induced by active smoke exposure and does not necessarily correlate with the clinical symptoms of CB.