Experimental Study On Differential Expression Of Periostin In Different Phenotypes Of Chronic Rhinosinusitis

Background and objective: According to EPOS2012, rhinosinusitis is defined as the inflammation of the nasal cavity and nasal sinuses with two or more symptomatic characteristics. One of the essential conditions is stuffiness/ nasal obstruction or rhinorrhea (anterior and posterior nasal drip) with or without facial pain/sense of pressure and hyposmia/anosmia. An endoscopy examination showed the presence of nasal polyps, accompanied by mucopurulent secretions mainly from the middle nasal meatus, and/or mucosal edema or congestion primarily located at middle nasal meatus;A computed tomograph scan(CT) revealed mucosal changes in the ostiomeatal complex and/or nasal sinus 1. The duration of symptoms of chronic rhinosinusitis was not less than 12 weeks, and the symptoms did not disappear completely. In clinical practice,chronic rhinosinusitis (CRS) can be classified as chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP).Some scholars classified CRSwNP into eosinophil(EOS), neutrophil (NEU), and non-EOS and non-NEU according to the types and number of infiltrating cells in nasal polyps2. There were different internal pathophysiological mechanism among the different phenotypes of chronic rhinosinusitis, this differences may indicate different pathogenesis.Identifying different pathogenesis may be achieved through a specific biomarker. Multiple biomarkers of different endotypes of chronic rhinosinusitis have been identified,such as specific IgE and the endotoxin IgE of Staphylococcus aureus,that can be used as a biomarker of different endotype of chronic rhinosinusitis3.Individualized therapies can be selected based on specific biomarkers of different endotypes 4,5.Periostin has been regarded as a systemic biomarker of eosinophilic respiratorytract inflammation in patients with asthma 6,7. . which benefits tissue fibrosis underthe mucosal epithelium of the respiratory tract and structure reconstruction 8,9 Inflammation has been simultaneously presented in both upper and lower respiratory tracts 10. Moreover,histopathological studies have found that structural remodelling is also present in the nasal cavity and sinus tissues of chronic rhinosinusitis patients,which is consistent with structure remodeling of lo0wer respiratory tract in patients diagnosed with asthma11 Therefore, We speculate that the expression of periostin may exist in the tissues of nasal mucosa in patients with chronic rhinosinusitis.This expression may have differences in different phenotypes of chronic rhinosinusitis,such differences may have important significance for understanding the endotypes of chronic rhinosinusitis,there is a certain relationship with the pathogenesis of chronic rhinosinusitis.Elevated periostin concentrations in serum were correlated with a specific phenotype of eosinophilic asthma, and often complicated by obstructive pulmonary dysfunction and nasal disorders 12. Serum periostin appears to be a more sensitive tool for detection of airflow limitation in asthmatic patients with a Th2(with higher IL-5 and IL-13) high eosinophilic phenotype when compared to absolute eosinophil countsand sputum eosinophils13., serum periostin has two characteristics as a biomarker for bronchial asthma: it is both a surrogate biomarker of type 2 immune responses and abiomarker reflecting tissue remodeling or fibrosis14 . Other study found that eosinophil infiltration in nasal polyps and nasal mucosa occupes 59.6% of CRSwNP,and eosinophil infiltration plays a central role in the pathophysiological process of chronic rhinosinusitis15. In eosinophilic chronic rhinosinusitis with nasal polyps,the expression of periostin may be related with eosinophils and the pathogenesis of eosinophilic chronic rhinosinusitis with nasal polyps.Objective: In this study, the distribution and expression of periostin in nasal tissues from different phenotypes of chronic rhinosinusitis were detected to evaluate the effect of periostin in the pathophysiological process of chronic rhinosinusitis and to offer evidence for endotypes of chronic rhinosinusitis.Method: Selected patients in hospital are divided into the following groups:individuals with chronic rhinosinusitis without nasal polyps (CRSsNP, 19 cases),individuals with chronic rhinosinusitis with nasal polyps (CRSwNP, 36 cases), and individuals with a deviation of nasal septum (DNS, 15 cases). The mucosal tissues of the ethmoid sinus of patients with chronic rhinosinusitis without nasal polyps ,mucosal tissues of the ethmoid sinus and nasal polyps of chronic rhinosinusitis with nasal polyps and inferior turbinate tissues of patients with a deviation of nasal septum were collected. Based on the infiltration of eosinophils,the chronic rhinosinusitis with nasal polyps were divided into eosinophilic chronic rhinosinusitis with nasal polyps(ECRSwNP,10 cases) and Non-eosinophilc chronic rhinosinusitis with nasal polyps (NonECRSwNP,26 cases).Immunohistochemical(IHC) staining was performed to assess the distribution of periostin,quantitative reverse transcription-polymerase chain reaction( RT-PCR) was conducted to detect the expression of periostin mRNA in nasal tissue specimens and the expression of periostin mRNA was observed. The serum concentration of periostin was measured using enzyme-linked immunosorbent assay( ELISA) in all specimens. Correlation analysis of each index is performed among immunohistochemical staining score of periostin,periostin mRNA in the nasal mucosa, the infiltration of eosinophils in nasal mucosa and the serum concentration of periostin, the proportion of blood eosinophils.Result: The periostin in the four groups was primarily distributed at the basal membrane of the nasal mucosal epithelium and the fiber tissues beneath the nasal mucosal epithelium. The staining score for the CRSsNP (the mucosal tissues of the ethmoid sinus) , ECRSwNP(mucosal tissues of the ethmoid sinus,nasal polyps),NonECRSwNP(mucosal tissues of the ethmoid sinus,nasal polyps) and DNS(mucosal tissues of inferior turbinate) groups was 3.19±0.98, 3.90±0.42/4.17±0.52, 3.20±0.86/3.32±0.84 and 2.44±0.86 respectively.Iimmunohistochemical staining score in patients of CRSsNP , ECRSwNP and NonECRSwNP groups is significantly higher than that in patients in the DNS group, and the difference is statistically significant(P<0.05,P<0.01,P<0.01). Iimmunohistochemical staining score in patients of ECRSwNP is higher than other three groups, the difference is statistically significant(P<0.01). The difference between CRSsNP and NonECRSwNP groups is not statistically significant (P>0.05).The serum levels of periostin among the four groups were detected using ELISA. The serum concentrations of periostin in patients with CRSsNP, ECRSwNP,NonECRSwNP and DNS were 47962.77 ± 14307.30,72138.91 ±21722.43,43012.45 ± 10314.95 and 31337.81±8181.02pg/mL. The serum concentrations of periostin in patients with ECRSwNP were significantly higher compared with those in the CRSsNP, NonECRSwNP and DNS groups( P<0.01). The serum concentrations of periostin in patients with DNS were significantly lower than those in other three groups, the difference is statistically significant (P<0.01) . The serum concentrations of periostin in patients with CRSsNP were same as those in NonECRSwNP group, the difference is not statistically significant (P>0.05) .Periostin mRNA was presented in the nasal mucosal tissue of the four groups .The values of periostin mRNA in the nasal mucosal tissues of the CRSsNP,ECRSwNP,NonECRSwNP and DNS groups were 0.351156 ±0.250896,0.477044 ± 0.505552,0.326074 ± 0.412194 and 0.340352 ± 0.304540 respectively. Compared with that in the patients of the DNS group, the periostin mRNA in the nasal mucosal tissue of the CRSsNP , ECRSwNP and NonECRSwNP groups increased, but the difference was not statistically significant (P>0.05).In ECRSwNP group, there was a positive correlation between the expression of Periostin in nasal polyps and the infiltration of eosinophils in the ethmoid mucosa and nasal polyps (P < 0.01, P < 0.05), The serum periostin concentration and blood eosinophil proportion have a certain correlation (P < 0.01) .serum Periostin concentration and blood eosinophil proportion has certain correlation (P < 0.01). In the four groups, there was no significant correlation between the expression of periostin in local tissues and the proportion of eosinophils in the blood (P>0.05).There was no significant correlation between the expression of periostin mRNA and the infiltration of eosinophils in the local tissue, the proportion of eosinophils in the blood (P> 0.05).Conclusion: 1 As one of the inflammatory mediators, periostin is involved in the process of chronic inflammation of chronic rhinosinusitis.2 The involvement of periostin in the pathogenesis of eosinophilic chronic rhinosinusitis with nasal polyps is positively associated with the infiltration of eosinophils.3 Periostin is involved in the process of tissue remodeling in the different types of chronic rhinosinusitis.