Abstract

Rationale: Little knowledge exists on structural changes and plugging in small airways in cystic fibrosis.

Objective: To characterise the extent of plugging and contribution of secreted mucins to the plugs.

Methods: Small airways in patients with cystic fibrosis at transplantation (n = 18) were compared with control non-smokers (n = 10). Tissue sections were stained with Alcian blue (AB)/periodic acid-Schiff (PAS), for mucins MUC5B and MUC5AC, and for neutrophils and its chemoattractant interleukin (IL) 8. Epidermal growth factor receptor (EGFR) and its ligand pro-transforming growth factor α were also identified using immunohistochemical staining. Epithelial and luminal contents were assessed morphometrically.

Results: Plugs occupying >50% of total luminal volume were found in 147 of 231 (63.6%) airways in patients with cystic fibrosis, but only in 1 of 39 (2.6%) airways in controls. In the epithelium of patients with cystic fibrosis, AB/PAS, MUC5B, and MUC5AC-stained volume densities were increased 10-fold (p<0.01), indicating increased mucin production. In airway lumens, staining for mucins was also increased in cystic fibrosis, indicating increased mucin secretion. In the epithelium of patients with cystic fibrosis, neutrophil numbers were markedly increased and were inversely correlated with volume densities of mucous glycoconjugates (r = −0.66, p<0.005). IL8 staining was increased in the epithelium of patients with cystic fibrosis and colocalised with mucins. Staining for EGFR and for pro-transforming growth factor α were increased in the epithelium of patients with cystic fibrosis; positive correlations were found between EGFR-stained volume density and both AB/PAS and IL8-stained volume densities.

Conclusions: Most of the small airways are plugged in cystic fibrosis at the time of transplantation. Mucins contribute to airway plugging. Recruited neutrophils may be involved in mucin secretion in the plugs. Increased expression of EGFR and its ligand suggests roles in mucin synthesis and neutrophil recruitment.