mometasone-furoate and Metaplasia

Allergic rhinitis is associated with specific histopathologic changes in the nasal mucosa including squamous metaplasia and local eosinophilia. Previous studies have shown that mometasone furoate aqueous nasal spray is effective and well tolerated in reducing perennial rhinitis and seasonal allergic rhinitis symptoms. We undertook a multicenter, open-label study to evaluate, by nasal biopsy, the tissue changes associated with mometasone furoate use (200 microg/day) during a 12-month treatment period in patients with perennial rhinitis. Of the 69 patients enrolled in the study, 52 completed all 12 months of treatment. Nasal biopsy specimens obtained from patients at baseline and after treatment were evaluated in a blinded fashion by computerized image analysis, qualitative histologic examination, and immunocytochemistry. Morphologic examination of nasal biopsy specimens showed a decrease in focal metaplasia, no change in epithelial thickness, and no sign of atrophy after treatment with mometasone furoate. Immunocytochemical analyses of nasal biopsy specimens obtained before and after treatment revealed a significant decrease in major basic protein-positive eosinophils and tryptase-positive mast cells in the epithelium and lamina propria after treatment. Mometasone furoate appeared to attenuate the inflammatory process by reducing the extent of inflammatory cell infiltration, particularly of eosinophils. This study demonstrated that long-term administration of mometasone furoate is not associated with adverse tissue changes in the nasal mucosa of patients with perennial rhinitis.

Topics: Administration, Intranasal; Adolescent; Adult; Angiogenesis Inducing Agents; Anti-Inflammatory Agents; Atrophy; Biopsy; Blood Proteins; Chymases; Eosinophil Granule Proteins; Eosinophilia; Eosinophils; Epithelium; Female; Follow-Up Studies; Glucocorticoids; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Inflammation Mediators; Male; Mast Cells; Metaplasia; Middle Aged; Mometasone Furoate; Nasal Mucosa; Pregnadienediols; Rhinitis, Allergic, Perennial; Ribonucleases; Serine Endopeptidases; Single-Blind Method; Tryptases

The aim of this study was to assess protein and mRNA expression of epithelial membrane protein 1 (EMP1) in the nasal mucosa of patients with nasal polyps (NP), and to determine what changes occur in response to glucocorticosteroid (GC) treatment.. NP tissue was obtained from 55 patients, 18 of whom were treated with nasal GCs (i.e. these 18 patients had NP biopsies taken before and after treatment). Biopsies of inferior turbinate mucosa from 30 healthy subjects were used as controls. Quantitative PCR and immunohistochemistry were performed to determine the expression levels of EMP1. EMP1 mRNA expression was significantly lower (2.77-fold) in tissues from NP patients before GC treatment when compared to controls, but was increased in these patients after GC treatment. EMP1 staining in nasal epithelium co-localized with both basal (p63(+)) and differentiated (CK18(+)) epithelial cells. Their immunoreactivity was significantly greater in controls than NP patients. EMP1 mRNA levels were lower in the epithelium with severe hyperplasia (1.79-fold) or with metaplasia (1.85-fold) as compared to those with mild to moderate hyperplasia or non-metaplastic epithelium, respectively. Positive correlations between EMP1 and other epithelial cell-related gene (e.g. JUN, PTGS2, AREG etc.) mRNAs were observed.. EMP1 could be a biomarker for aberrant epithelial remodelling and metaplasia in chronic inflammatory upper airway mucosa (e.g. NP).

Topics: Adult; Anti-Inflammatory Agents; Down-Regulation; Epithelium; Female; Humans; Hyperplasia; Male; Metaplasia; Middle Aged; Mometasone Furoate; Nasal Mucosa; Nasal Polyps; Neoplasm Proteins; Pregnadienediols; Receptors, Cell Surface