Nasal inflammation and its response to local glucocorticoid regular treatment in patients with persistent non-allergic rhinitis: a pilot study

Abstract

BackgroundThe pathogenesis of non-allergic rhinitis (NAR) is still largely unknown. Furthermore, it is unclear whether there is a correlation between the effect of nasal glucocorticoids on nasal inflammation and on nasal symptoms and quality of life.MethodsIn this pilot study we recruited 12 healthy subjects and 24 patients with recently diagnosed persistent NAR [12 untreated and 12 under regular treatment with nasal fluticasone furoate (two sprays of 27.5 μg each in each nostril once daily, total daily dose = 110 μg) for at least 20 days]. Each subject filled a mini rhinoconjunctivitis quality of life questionnaire (mini RQLQ). Nasal scrapings were obtained from each subject and used to prepare slides for Diff-Quik and immunocytochemical staining for inflammatory and epithelial cells count, MUC5AC expression and the general pro-inflammatory transcription factor nuclear factor kB (NF-kB) activation.ResultsThe nasal score of the mini RQLQ, the number of nasal inflammatory cells (neutrophils, eosinophils) and the number of goblet cells are significantly higher in untreated patients with persistent NAR compared with control subjects and treated NAR patients. The percentage of MUC5AC+ nasal epithelial cells is significantly increased in untreated patients with persistent NAR compared with the control subjects (41.8 ± 6.4 vs 22.3 ± 4.8, respectively; p = 0.0403) without significant differences between control subjects and patients with persistent NAR on regular fluticasone furoate treatment (33.9 ± 5.0 %; p = 0.0604) nor between the 2 groups of persistent NAR subjects (p = 0.3260). The number of cytosolic and/or nuclear p65+ nasal epithelial and inflammatory cells was not significantly different between the three groups.ConclusionsPatients with persistent untreated NAR, compared with normal control subjects and patients with persistent NAR under regular treatment with nasal fluticasone furoate by at least 20 days, have more nasal symptoms, worst quality of life and an increased number of nasal inflammatory cells (neutrophils, eosinophils), goblet cells and MUC5AC+ nasal epithelial cells. This nasal inflammation seems unrelated to NF-kB activation.

Protective effects of inhalation of essential oils from Mentha piperita leaf on tight junctions and inflammation in allergic rhinitis

“…The activation of the MAPK signaling pathway, including ERK, JNK, and p38 phosphorylation, is mediated by claudin-1 and occludin ( 42 ), which have several phosphorylation sites on the carboxy-terminal tail, related to the regulation of MAPK ( 43 ). Downstream of MAPK, such as the NF-κB signaling pathway, is a major protein complex involved in the regulation of various immune response, including the inducement of allergic rhinitis ( 44 ). Based on those reports, inhibitors targeting MAPKs have been developed to reduce inflammation and the disruption of tight junctions ( 45 ).…”

Corticosteroids

“…At sites of acute and/or chronic mucosal inflammation, there is often an increased secretion of the major secretory mucins (MUC5AC and MUC5B). The effect of the glucocorticoids on the expression of these mucins is still quite controversial and may be cell-and tissue-type dependent [50].…”

Role of the mucins in pathogenesis of COPD: implications for therapy

“…Many genes associated with mucin-secreting cell differentiation such as ErbB4, runt-related transcription factor 2 (RUNX2), as well as janus kinases (JAK)/ signal transducer and activator of transcription proteins (STAT) and PI3K/AKT signaling pathways, were upregulated in response to budesonide. In contrast, a small pilot study evaluated patients with persistent untreated non-allergic rhinitis (NAR, n=12, mean age 39.5±4 years, all non-smokers) compared with patients with persistent NAR (n=12, mean age 48±4 years, all non-smokers) under regular treatment with nasal fluticasone furoate for at least 20 days and compared to normal control subjects (n=12, mean age 32.5±3 years, all non-smokers)[96]. No patients or control subjects had been treated in the previous 60 days with systemic and/or nasal glucocorticoids, antihistamine 1 receptor drugs, anti-leukotrienes, methylxanthines, or any kind of immunosuppressive drugs, mucolytics/antioxidants drugs by systemic or local routes.…”

“…Each subject went underwent a single nasal scraping performed under direct visual inspection and defined the ratio between ciliated and mucin-secreting cells, usually in favour of ciliated cells[97]. Immunocytochemical staining for MUC5AC was performed[96] Nasal scrapes obtained from patients with untreated NAR showed different total numbers of nasal epithelial cells compared with scrapes from both normal subjects and NAR patients treated with nasal fluticasone furoate (92.3±17.2 vs 413.8±2.8A c c e p t e d M a n u s c r i p t vs 407.8±62.6, respectively). Total nasal epithelial cell numbers were similar between NAR patients treated with nasal fluticasone furoate and normal subjects.…”