Search

Increased mucin expression is a feature of nasal polyposis. Corticosteroids reduce polyp size and symptoms, but their effect on mucin production remains unknown. In this study, the effects of intranasal corticosteroids on MUC5AC mucin expression, nasal resistance, eosinophil and neutrophil infiltration, epidermal growth factor receptor (EGFR), interleukin (IL)-8, and tumour necrosis factor (TNF)-alpha expression was assessed in nasal polyps. In nine subjects, one nasal polyp was removed surgically before treatment and another was removed after 8 weeks of intranasal fluticasone (400 microg.day(-1)). Tissues were processed for in situ hybridisation and immunohistochemical staining. Described effects of fluticasone on nasal polyps (reduction in nasal resistance and in eosinophil infiltration) were evaluated. Morphometric analysis was performed to assess the effect of fluticasone on epithelial-, MUC5AC-, EGFR- and IL-8-stained areas, TNF-alpha-stained cells, and neutrophil numbers. Treatment with fluticasone decreased nasal resistance and intra-epithelial eosinophils. The MUC5AC-stained area in the epithelium was unchanged by treatment; MUC5AC mRNA expression was unaffected by treatment. EGFR-stained area, intra-epithelial neutrophil numbers, IL-8 and TNF-alpha expression were also unchanged by therapy. Intranasal fluticasone was effective in decreasing nasal airflow resistance and intra-epithelial eosinophils but had no effect on mucin or epidermal growth factor receptor expression or on neutrophil recruitment.

Pituitary adenylate cyclase-activating peptide (PACAP) 38 displays several biological activities relevant to obstructive airway disease. In this study, the occurrence of PACAP 38 in human small bronchi and corresponding pulmonary arteries was analysed immunocytochemically. The dilatory effects of this peptide on the same structures were also studied in vitro. A moderate number of PACAP-like immunoreactive nerve fibres was seen in association with bronchial and vascular smooth muscle and around seromucous glands. PACAP 38 caused a concentration-dependent relaxation of precontracted bronchial and pulmonary arterial segments. The maximal relaxation was more pronounced in the airways than in the arteries, whereas the potency in both was identical. PACAP 38 caused relaxation of all segments tested (nine patients), whereas vasoactive intestinal polypeptide (VIP) failed to cause relaxation of bronchial segments from six of nine patients. Both PACAP and VIP dilated all pulmonary arterial segments tested. In conclusion, pituitary adenylate cyclase-activating peptide 38 is a potent dilator of human bronchi and is present in the human lung. Pituitary adenylate cyclase-activating peptide 38 may, therefore, play a role in the endogenous regulation of airway tone. The inhibitory effects of pituitary adenylate cyclase-activating peptide 38 are more consistent than those of the related neuropeptide vasoactive intestinal polypeptide, perhaps reflecting a difference in susceptibility to degrading enzymes.