Relationships between Airway Remodeling and Clinical Characteristics in COPD Patients

Abstract

Background: Airway remodeling is a cardinal feature of chronic obstructive pulmonary disease (COPD) pathology. However, inconsistent findings have been reported regarding the nature of proximal airway remodeling in COPD. This is likely due to the heterogeneity of COPD. This study investigated the histopathological features of airway remodeling in bronchial biopsies of COPD patients compared to smoking controls (S). We tested the hypothesis that histopathological features in bronchial biopsies relate to clinical characteristics in COPD patients, focusing on smoking status, symptom burden, lung function, exacerbation risk and inhaled corticosteroid (ICS) use. Methods: We recruited 24 COPD patients and 10 S. We focused on reticular basement membrane thickness (RBM), surface immunoglobulin A (IgA) expression, goblet cell numbers (periodic acid-Schiff [PAS]+), sub-mucosal remodeling markers including collagen 4, 6 and laminin expression, and inflammatory cell counts (CD45+). Results: RBM thickness was increased in frequent exacerbators, IgA expression was reduced in COPD patients with worse lung function, and goblet cell numbers were increased in COPD patients compared to S but with no difference between the COPD subgroups. Collagen 4 expression was associated with higher symptom burden and worse quality of life. Sub-mucosal inflammatory cell counts were increased in COPD non-inhaled corticosteroid (ICS) users compared to ICS users and S. Conclusion: We observed relationships between the histopathological features of airway remodeling and clinical characteristics in COPD patients. Our data highlight the influence of clinical heterogeneity on diverse patterns of airway remodeling in COPD patients.

Keywords: IgA; basement membrane; collagen; goblet cells; histology; immune cells.

Figure 1

Quantification of reticular basement membrane thickness and goblet cells. The reticular basement membrane (RBM) thickness (A–D) and goblet cells (E–I) were compared between (A,E) COPD patients and smoking controls (S), with further detailed clinical phenotyping in COPD patients based upon (B,F) exacerbations, (C,G) airflow limitation, (D,H) smoking status, and (I) chronic bronchitis. Data presented as mean + SEM. Comparisons between groups were made by one-way ANOVA followed by Tukey’s test.

Figure 2

Quantification of IgA expression. IgA expression was compared between (A) COPD patients and smoking controls (S), with further detailed clinical phenotyping in COPD patients based upon (B) exacerbations, (C) airflow limitation, and (D) smoking status. Data presented as median ± range. Comparisons between groups were made by one-way Kruskal–Wallis followed by Dunn’s multiple comparison tests.

Figure 3

Quantification of collagen 4 and 6 expression. Collagen 4 (A–D) and 6 expression (E–H) were compared between (A,E) COPD patients and smoking controls (S), with further detailed clinical phenotyping in COPD patients based upon (B,F) exacerbations, (C,G) airflow limitation, and (D,H) smoking status. Data presented as median ± range. Comparisons between groups were made by Kruskal–Wallis followed by Dunn’s tests.

Figure 4

Quantification of laminin expression. Laminin expression was compared between (A) COPD patients and smoking controls (S), with further detailed clinical phenotyping in COPD patients based upon (B) exacerbations, (C) airflow limitation, and (D) smoking status. Data presented as median ± range. Comparisons between groups were made by one-way Kruskal–Wallis followed by Dunn’s tests.

Figure 5

Quantification of airway immune cell counts in ICS users and non-users. Intra-epithelial (A) and sub-mucosal (B) CD45⁺ immune cells numbers were compared between ICS users (ICS yes), ICS non-users (ICS no), and smoking controls (S). Data presented as mean + SEM. Comparisons between groups were made by one-way ANOVA followed by Tukey’s multiple comparison test.