Chronic bronchitis and current smoking are associated with more goblet cells in moderate to severe COPD and smokers without airflow obstruction

Abstract

Background: Goblet cell hyperplasia is a classic but variable pathologic finding in COPD. Current literature shows that smoking is a risk factor for chronic bronchitis but the relationship of these clinical features to the presence and magnitude of large airway goblet cell hyperplasia has not been well described. We hypothesized that current smokers and chronic bronchitics would have more goblet cells than nonsmokers or those without chronic bronchitis (CB), independent of airflow obstruction.

Methods: We recruited 15 subjects with moderate to severe COPD, 12 healthy smokers, and 11 healthy nonsmokers. Six endobronchial mucosal biopsies per subject were obtained by bronchoscopy and stained with periodic acid Schiff-Alcian Blue. Goblet cell density (GCD) was quantified as goblet cell number per millimeter of basement membrane. Mucin volume density (MVD) was quantified as volume of mucin per unit area of basement membrane.

Results: Healthy smokers had a greater GCD and MVD than nonsmokers and COPD subjects. COPD subjects had a greater GCD than nonsmokers. When current smokers (healthy smokers and COPD current smokers, n = 19) were compared with all nonsmokers (nonsmoking controls and COPD ex-smokers, n = 19), current smokers had a greater GCD and MVD. When those with CB (n = 12) were compared to those without CB (n = 26), the CB group had greater GCD. This finding was also seen in those with CB in the COPD group alone. In multivariate analysis, current smoking and CB were significant predictors of GCD using demographics, lung function, and smoking pack years as covariates. All other covariates were not significant predictors of GCD or MVD.

Conclusions: Current smoking is associated with a more goblet cell hyperplasia and number, and CB is associated with more goblet cells, independent of the presence of airflow obstruction. This provides clinical and pathologic correlation for smokers with and without COPD.

Fig 1. Examples of mucosal biopsies from A) a healthy nonsmoker, B) a healthy smoker, C) a COPD subject without chronic bronchitis, and D) a COPD subject with chronic bronchitis, taken at 40x.

Specimens stained with periodic acid Schiff-Alcian Blue, staining goblet cells blue/purple. Basement membrane measured is outlined in red.

Fig 2. Goblet cell density in healthy nonsmokers, smokers without airflow obstruction, and COPD subjects.

A. Data expressed as goblet cells per millimeter of basement membrane. Mucin volume density in the same three groups, B. Data expressed as mean±SE. Normal = healthy nonsmoking group, Healthsmoke = healthy smoker group, COPD = chronic obstructive pulmonary disease group, GC/MM = goblet cells per millimeter basement membrane, MVD = mucin volume density.

Fig 3. Goblet cell density in all smokers (smokers without airflow obstruction and COPD subjects that currently smoke) compared with all nonsmokers (healthy nonsmokers and COPD subjects who quit smoking).

A. Data expressed as goblet cells per millimeter of basement membrane. Mucin volume density in all smokers compared with all nonsmokers, B. Data expressed as mean±SE. GC/MM = goblet cells per millimeter basement membrane, MVD = mucin volume density.

Fig 4. Goblet cell density between those with chronic bronchitis and those without chronic bronchitis in the entire cohort (left) and in the COPD subjects alone (right).

Data expressed as goblet cells per millimeter of basement membrane. GC/MM = goblet cells per millimeter basement membrane, CB+ = chronic bronchitis, CB- = no chronic bronchitis, COPD CB+ = COPD subjects with chronic bronchitis, COPD CB- = COPD subjects without chronic bronchitis.