Immunological mechanisms underlying chronic rhinosinusitis with nasal polyps

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and quality-of-life impacting disorder, with an underlying immunological mechanism similar to other conditions such as eosinophilic asthma or atopic eczema.

Areas covered: This review article summarizes the most recent evidence on the main immunological mechanisms involved in the pathogenesis and the perpetuation of CRSwNP, with a particular focus on the key role of epithelium-derived inflammation as a consequence of the interaction with the airborne environment.

Expert commentary: The increase in knowledge of the immunology of CRSwNP leads to the development of therapeutical strategies based upon the use of biologic agents that, according to a personalized and precision medicine approach, will provide each single patient with the most suitable immunological treatment.     

Fluticasone propionate aqueous nasal spray does not influence the recurrence rate of chronic rhinosinusitis and nasal polyps 1 year after functional endoscopic sinus surgery

BACKGROUND: Local corticosteroids are widely used in the treatment of nasal polyps and chronic rhinosinusitis both before and after nasal surgery. Their efficacy after functional endoscopic sinus surgery (FESS) has not been fully established by placebo-controlled trials. OBJECTIVE: This double-blind placebo-controlled randomized study was performed in order to investigate whether fluticasone propionate aqueous nasal spray (FPANS) reduces the recurrence rate of nasal polyps and chronic rhinosinusitis during the first year after FESS. PATIENTS AND METHODS: The trial looked at 162 patients aged 18 years and older requiring FESS for chronic rhinosinusitis or nasal polyps. After FESS combined with peri-operative systemic corticosteroids, patients were randomized and given FPANS 400 microg b.i.d., FPANS 800 microg b.i.d. or placebo b.i.d. for the duration of 1 year. Patients were withdrawn from the trial (but still included in the study for statistical purposes) if there were recurrent or persistent diseases, defined as progressive regrowth of nasal polyps, recurrent signs and symptoms of chronic sinusitis combined with abnormalities on computed tomography scan and persistent complaints for at least 2 months after FESS. RESULTS: A significant reduction of symptoms was seen after FESS. After 1 year, 46 patients had been withdrawn from the trial because of recurrent diseases and 32 patients because of persistent symptoms. No differences in the number of patients withdrawn because of recurrent or persistent diseases were found between the patients treated with FPANS and patients treated with placebo. We were also unable to find a positive effect of FPANS compared with placebo in several subgroups such as patients with nasal polyps, high score at FESS or no previous sinus surgery. CONCLUSION: This placebo-controlled study does not show that treatment with FPANS up to 1 year after FESS had a positive effect compared with placebo.     

The epithelium-derived inflammatory mediators of chronic rhinosinusitis with nasal polyps

ABSTRACT

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory airway disease characterized as tight junction loosening, inflammation, and mucosal remodeling. Epithelial cells form a barrier against allergens, bacteria, and proteases, and can also trigger or enhance the immune response by releasing various inflammatory mediators including cytokines, chemokines, and secreted proteins to promote the pathogenesis of CRSwNP.

Areas covered: We review the epithelium-derived cytokine and secreted protein networks driving CRSwNP, and discuss these mediators in a cellular context. We illustrate their roles as potential mediators-biomarkers in clinical practice, which may help to understand the mechanisms underlying the pathologies of different endotypes of CRSwNP and to improve treatment outcomes in patients with CRSwNP based on the development of novel predictors for CRSwNP management.

Expert opinion: The understanding of the role of epithelium-derived inflammatory mediators helps to investigate the pathophysiological mechanisms of CRSwNP endotypes. An increasing number of studies show that these mediators target immune cells and promote the recruitment, activation or regulation of the proliferation or apoptosis of these cells. Based on this achievement, further investigations are necessary to explore the multi-dimensional role of epithelium-derived inflammatory mediators in CRSwNP.     

Predictors of bronchial hyperresponsiveness in chronic rhinosinusitis with nasal polyp

Background:  Chronic rhinosinusitis with nasal polyposis (CRSNP) and asthma are inflammatory lesions of the respiratory epithelium. This study was conducted to evaluate predictive factors of bronchial hyperresponsiveness (BHR) in patients with CRSNP.
Methods:  BHR was evaluated using a methacholine bronchoprovocation test (MBPT) in 122 consecutive patients newly diagnosed with CRSNP at Seoul National University Hospital from January 2004 to June 2006. The following parameters were analyzed and compared between the BHR and non-BHR groups: symptoms, atopic status, current smoking, disease severity of CRSNP based on the Lund–Mackay scoring system of sinus CT, and counts of eosinophils in the serum and nasal tissues.
Results:  Thirty-five percent of the patients were found to have BHR, and BHR was found to occur more frequently in patients that were currently suffering from sneezing ( P  = 0.007). In addition, the mean eosinophil counts of the serum and nasal tissues were higher in the BHR group than in the non-BHR group ( P  = 0.001 for the serum, P  = 0.045 for the nasal tissues), and the eosinophil counts of the serum correlated to those of the nasal tissues ( r  = 0.334, P  = 0.013). The disease severity, as determined by the Lund–Mackay scoring system, was not different between the two groups ( P  > 0.05). The best cutoff serum eosinophil count for predicting BHR in CRSNP patients was determined to be 300 cells/μl (sensitivity 70%, specificity 70%).
Conclusion:  Taken together, these results indicate that moderate to severe sneezing and a serum eosinophil count ≥ 300 cells/μl may be predictive factors for BHR in patients with CRSNP.     

Regulation of glucocorticoid receptor in nasal polyps by systemic and intranasal glucocorticoids

Background: Poor response of nasal polyps to glucocorticoids (GCs) may be because of abnormal expression of GC receptors (GR) α and β or to downregulation of GRα. We aimed to evaluate the in vivo regulation of GR isoforms in GC‐treated nasal polyps and to assess the relationship between clinical response to GCs and GR levels. Methods: Patients with nasal polyps were randomly (3:1) treated (n = 51) or not (n = 14) with oral prednisone and intranasal budesonide for 2 weeks, plus intranasal budesonide for 10 additional weeks. Nasal symptoms were evaluated. Biopsies were obtained before (w0) and after 2 (w2) and 12 (w12) weeks of treatment, and analysed for their inflammatory content and GR mRNA (10² cDNA copies/μg total RNA) and protein (% immunoreactive inflammatory cells) expression. Healthy nasal mucosa (n = 11) was also investigated. Data are presented as median and 25–75th percentile. Results: At w0, nasal polyps expressed less GRα mRNA (1343;683–2263; P < 0.05) and GR protein (41;29–54; P < 0.05) than nasal mucosa (2474;1346–2933; 60;51–72, respectively). GRβ immunoreactivity was higher in nasal polyps (11;4–19; P < 0.05) than in nasal mucosa (5;2–5). At w2, increased GRα mRNA (2010;1037–2732; P < 0.01) and GR protein (56;27–71; P = 0.056) were found compared with w0 (1177;759–2058; 37;29–55, respectively). At w12, GRα mRNA and GR protein were similar to w0. GRβ expression was unaltered by treatment. Neither GRα nor GRβ correlated with nasal symptoms. GR immunoreactivity negatively correlated with eosinophils (r = ?0.478; P < 0.001). Conclusions: GRα is downregulated in nasal polyps and upregulated by GC treatment. Neither GRα nor GRβ appear to determine the sensitivity to GCs in nasal polyposis.