Eosinophilic Chronic Rhinosinusitis With Nasal Polyps Patients Research Articles

Comparison of Long-Term Postoperative Outcomes of the Subtypes of Chronic Rhinosinusitis with Nasal Polyps.

(1) Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory condition that significantly impacts the health-related quality of life (HRQOL) of patients. This study aims to investigate the disparities in preoperative examination findings, postoperative HRQOL, and disease control status based on CRSwNP subtypes. (2) Methods: A retrospective analysis was conducted on 202 patients who underwent endoscopic sinus surgery for CRSwNP. The study assessed clinical characteristics, blood eosinophil and immunoglobulin E (IgE) levels, modified Lund-Kennedy and Lund-Mackay scores, and Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) scores. HRQOL was evaluated using the Sino-nasal Outcome Test (SNOT-22) scores, and disease control status was assessed based on the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 guidelines. (3) Results: Of the 202 patients, Eosinophilic CRSwNP patients exhibited significantly higher preoperative peripheral blood eosinophil ratios and IgE levels, and JESREC scores (p < 0.05). Two years postoperatively, patients in the non-eosinophilic group showed significantly improved SNOT-22 scores compared to preoperative scores (p = 0.007). Notably, the proportion of patients with uncontrolled disease was significantly higher in the eosinophilic group (p = 0.035). Logistic regression analyses identified preoperative SNOT-22 scores and eosinophilic CRSwNP subtype as influential factors on disease control status (p < 0.05). (4) Conclusions: Patients with more severe preoperative symptoms and eosinophilic CRSwNP demonstrated poorer long-term treatment outcomes.

Risk factors for postoperative recurrence in eosinophilic chronic rhinosinusitis with nasal polyps: development of a prediction model.

To identify risk factors for postoperative recurrence in patients with eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) and develop a nomogram prediction model for identifying patients at high risk of recurrence. A cohort study involving 200 ECRSwNP patients analyzed clinical data for recurrence predictors using univariate and multivariate logistic regression analyses. A nomogram model was developed and validated using Receiver Operating Characteristic (ROC) curves. Mean absolute error (MAE) calculations evaluated the model's predictive accuracy. At six-month follow-up, 39 patients (19.5%) experienced recurrence. Factors such as preoperative tissue eosinophil percentage, eosinophil cationic protein (ECP), serum-specific immunoglobulin E (IgE), interleukin-5 (IL-5), and postoperative nasal environment were identified as risk factors for recurrence. The nomogram incorporating these factors demonstrated high predictive accuracy (AUC = 0.989, MAE = 0.026). This study underscores the significance of individualized risk assessment in managing ECRSwNP recurrence. The developed nomogram provides a robust tool for clinical prognostication, aiding personalized treatment strategies and improving patient outcomes.

Integrative analysis of immune-related signature profiles in eosinophilic chronic rhinosinusitis with nasal polyposis.

Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is a subtype of chronic rhinosinusitis (CRS) that is associated with the nasal cavity and sinus polyps, elevated levels of eosinophils, and dysregulated immune responses to environmental triggers. The underlying cause of ECRSwNP is not well understood, and few studies have focused on the unique features of this subtype of CRS. Our study integrated proteomic and transcriptomic data with multi-omic bioinformatics analyses. We collected nasal polyps from three ECRSwNP patients and three control patients and identified 360 differentially expressed (DE) proteins, including 119 upregulated and 241 downregulated proteins. Functional analyses revealed several significant associations with ECRSwNP, including focal adhesion, hypertrophic cardiomyopathy, and extracellular matrix (ECM)-receptor interactions. Additionally, a protein-protein interaction (PPI) network revealed seven hub proteins that may play crucial roles in the development of ECRSwNP. We also compared the proteomic data with publicly available transcriptomic data and identified a total of 1077 DE genes. Pathways enriched by the DE genes involved angiogenesis, positive regulation of cell motility, and immune responses. Furthermore, we investigated immune cell infiltration and identified biomarkers associated with eosinophil and M2 macrophage infiltration using CIBERSORT and Weighted Gene Correlation Network Analysis (WGCNA). Our results provide a more complete picture of the immune-related mechanisms underlying ECRSwNP, which could contribute to the development of more precise treatment strategies for this condition.

MiR-200a-3p regulates epithelial-mesenchymal transition and inflammation in chronic rhinosinusitis with nasal polyps by targeting ZEB1 via ERK/p38 pathway.

Several biological processes are regulated by miR-200a-3p, including cell proliferation, migration, and epithelial-mesenchymal transition (EMT). In this study we aimed to uncover the diagnostic value and molecular mechanisms of miR-200a-3p in chronic rhinosinusitis with nasal polyps (CRSwNP). The expressions of miR-200a-3p were detected by quantitative real-time polymerase chain reaction (qRT-PCR), Zinc finger E-box binding homeobox 1 (ZEB1) levels were examined by qRT-PCR and immunofluorescence staining. The interaction between miR-200a-3p and ZEB1 was predicted by TargetScan Human 8.0 and confirmed by dual-luciferase reporter assays. In addition, the effect of miR-200a-3p and ZEB1 on EMT-related makers and inflammation cytokines was assessed by qRT-PCR and Western blotting in human nasal epithelial cells (hNEpCs) and primary human nasal mucosal epithelial cells (hNECs). We found that miR-200a-3p was downregulated in non-eosinophilic and eosinophilic CRSwNP patients when compared with controls. The diagnostic value of miR-200a-3p in serum is reflected by the receiver operating characteristic curve and the 22-item Sino-Nasal Outcome Test. Bioinformatic analysis and luciferase reporter assay identified ZEB1 as a target of miR-200a-3p. ZEB1 was more highly expressed in CRSwNP than in controls. Furthermore, miR-200a-3p inhibitor or ZEB1 overexpression significantly suppressed the epithelial marker E-cadherin; promoted the activation of vimentin, α-spinal muscle atrophy, and N-cadherin; and aggravated inflammation in hNEpCs. Knockdown of ZEB1 significantly alleviated the cellular remodeling caused by miR-200a-3p inhibitor via the extracellular signal-regulated kinase (ERK)/p38 pathway in hNECs. miR-200a-3p suppresses EMT and inflammation by regulating the expression of ZEB1 via the ERK/p38 pathway. Our study presents new ideas for protecting nasal epithelial cells from tissue remodeling and finding a possible target for disease.

Predictive diagnostic value of serum 25-hydroxyvitamin D3 in eosinophilic chronic rhinosinusitis with nasal polyps

Objective: To compare the value of 25-hydroxyvitamin D3 (25-(OH)D3) with other clinical parameters in the prediction and diagnosis of eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). Methods: Eligible chronic rhinosinusitis with nasal polyps (CRSwNP) patients and healthy subjects in the Affiliated Hospital of Guizhou Medical University from January to April of 2021 were included for this study. The age, gender, past history and other basic characteristics of all subjects were recorded. The CRSwNP patients were classified into ECRSwNP and non-eosinophilic chronic rhinosinusitis with nasal polyps (nECRSwNP) endotypes by the percentage of tissue eosinophils. Serum 25-(OH)D3 levels measurements were performed in all subjects. Paranasal sinus CT scans, blood eosinophil counts, and determination of total immunoglobulin E (total IgE), Th1/Th2 plasma cytokines and nasal nitric oxide (nNO) levels were performed before surgery. Logistic regression analysis was used to evaluate the related factors of ECRSwNP. Receiver operating characteristic (ROC) curves was used to evaluate the predictive potential of the clinical parameters. Results: One hundred and twenty-seven CRSwNP patients and 40 healthy subjects were recruited, including 74 males and 93 females of the patients, with the age of (38.73±13.05) years. In patients with ECRSwNP, serum 25-(OH)D3 levels were significantly lower than those in nECRSwNP patients ((26.14±4.58) ng/ml vs (35.71±7.86) ng/ml, t=-8.564, P<0.01). The prevalence of asthma, prevalence of allergic rhinitis, peripheral blood eosinophil counts, total IgE levels, nNO levels and CT scores ratio for ethmoid sinus and maxillary sinus (E/M ratio) of ECRSwNP patients were significantly higher than those in nECRSwNP patients (all P<0.05). However, there was no significant difference in Th1/Th2 cytokines levels between the histological types of CRSwNP (all P>0.05). Among the predictive indicators, 25-(OH)D3 had the highest predictive value, with ROC area under curve (AUC) value of 0.882. The best cut-off point of 28.5 ng/ml for 25-(OH)D3 demonstrated a sensitivity of 0.871 and a specificity of 0.762 for ECRSwNP. Conclusion: Measurement of serum 25-(OH)D3 level may be used as an effective method to distinguish between ECRSwNP and nECRSwNP.

Predictive value of clinical characteristics in eosinophilic chronic rhinosinusitis with nasal polyps: A cross-sectional study in the Chinese population.

Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is a refractory subtype of chronic rhinosinusitis with nasal polyps (CRSwNP), with clinical characteristics differing from those of non-ECRSwNP. We aimed to explore the predictive value of clinical characteristics, including medical history, symptoms, and signs, prior to ECRSwNP diagnosis, and to develop a nomogram for use in clinical practice. A total of 502 patients with CRSwNP were enrolled. Based on the degree of eosinophilic infiltration in nasal polyps (NPs), patients were classified as ECRSwNP or non-ECRSwNP group. Participants' demographic characteristics, asthma history, severity of nasal symptoms (nasal obstruction, rhinorrhea, hyposmia, and facial pain/headache) according to the visual analog scale, and nasal polyp scores based on polyp scoring system were recorded. Logistic regression analysis was performed to screen for independent risk factors, and a model nomogram was constructed. The percentage of asthmatic patients and the hyposmia, rhinorrhea, and total nasal symptom scores were significantly higher in ECRSwNP patients than that in non-ECRSwNP patients. The nasal polyp score was lower in the eosinophilic group than that in the non-eosinophilic group. Logistic regression analysis revealed that asthma history and hyposmia, rhinorrhea and nasal polyp scores were independent predictors of ECRSwNP. A nomogram consisting of these four independent risk factors was constructed, and its C-index was 0.808 (95% CI, 0.771 to 0.846). The nomogram based on asthma history and olfactory, rhinorrhea, and nasal polyp scores could help predict ECRSwNP, providing a simple, fast, and practical way to distinguish ECRSwNP from non-ECRSwNP cases in clinical practice.

The expression of Notch pathway in nasal polyps and its correlation with the decreased Treg percentage and eosinophil infiltration

Objective: To investigate the correlation between Notch pathway expression in nasal polyps and Treg percentage and Eos infiltration. Methods: Patients with chronic sinusitis and simple nasal septum deviation who received nasal endoscopic surgery in the Third Affiliated Hospital of Sun Yat-Sen University between November 2012 and August 2018 were selected and enrolled in CRS group and control group respectively. Nasal mucosa tissues were collected from 30 CRSsNP patients (14 males and 16 females aged from 18 to 63), 58 CRSwNP patients (38 males and 20 females aged from 18 to 65) and 29 patients (19 males and 10 females aged from 20 to 57), who underwent nasal endoscopic surgery for correction of simple nasal septum deviation. Hematoxylin-eosin(HE) staining was used to observe the infiltration of eosinophilic granulocytes in the tissues and to classify chronic sinusitis with polyps (CRSwNP) into eosinophilic chronic rhinosinusitis with nasal polyps (Eos-CRSwNP)and non-eosinophilic chronic rhinosinusitis with nasal polyps (Eos-CRSwNP). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of Notch pathway receptors (Notch-l, 2, 3, 4) and their ligands (Jagded-l, Jagded-2, Delta-l, Delta-3and Delta-4) in the nasal mucosa of each group, as well as the expression of Th2 cytokines (IL-4, IL-5, IL-13), eosinophilic cationic protein (ECP)and the key transcription factor Foxp3 in Treg cells. Finally, flow cytometry was used to detect CD4+CD25+Foxp3+ Treg cells in nasal mucosa of each group. Results: Compared with controls, the expression of Th2 cytokines (IL-4, IL-5, IL-13) in CRSsNP and non-Eos-CRSwNP patients was the highest in Eos-CRSwNP (F=16.930,9.197,9.116, all P<0.05). Foxp3 had the lowest expression in Eos-CRSwNP patients and was lower than non-Eos-CRSwNP patients (F=2.780,P<0.05), and was negatively correlated with ECP (r=-0.326,P<0.05). Compared with controls, Eos-CRSwNP patients in CRSsNP patients and non-Eos-CRSwNP patients exhibited a significantly lower frequency of CD4+CD25+Foxp3+Treg cells (F=13.140, all P<0.01). The expression of Notch-l and Jagged-l in Eos-CRSwNP was significantly higher than that of the controls, CRSsNP patients and non-Eos-CRSwNP patients (F=5.953/F=6.380, P<0.05). In the nasal polyp group, the expression of Notch-l and Jagged-l showed significantly negative correlation with Foxp3 (r=-0.611/-0.346, all P<0.05), and positive correlation with Th2 cytokines (IL-4, IL-5, IL-13) and ECP, respectively (r=0.781/0.459,0.621/0.601,0.605/0.490,0.464/0.668, all P<0.05). There was no significant difference in the expression of receptor and ligand of the other Notch pathway among the groups. Conclusion: Abnormal activation of Notch-l/Jagged-l pathway may be involved in decreasing Treg ratio in Eos-CRSwNP, thereby promoting Th2 inflammatory response and Eosinophil infiltration.

Distinct expression of SARS-CoV-2 receptor ACE2 correlates with endotypes of chronic rhinosinusitis with nasal polyps.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) entry factors, ACE2 and TMPRSS2, are highly expressed in nasal epithelial cells. However, the association between SARS‐CoV‐2 and nasal inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been investigated. We thus investigated the expression of SARS‐CoV‐2 entry factors in nasal tissues of CRSwNP patients, and their associations with inflammatory endotypes of CRSwNP.MethodsThe expression of ACE2 and TMPRSS2 was assessed in nasal tissues of control subjects and eosinophilic CRSwNP (ECRSwNP) and nonECRSwNP patients. The correlations between ACE2/TMPRSS2 expression and inflammatory indices of CRSwNP endotypes were evaluated. Regulation of ACE2/TMPRSS2 expression by inflammatory cytokines and glucocorticoids was investigated.ResultsACE2 expression was significantly increased in nasal tissues of nonECRSwNP patients compared to ECRSwNP patients and control subjects, and positively correlated with the expression of IFN‐γ, but negatively correlated with tissue infiltrated eosinophils, and expression of IL5 and IL13. IFN‐γ up‐regulated ACE2 expression while glucocorticoid attenuated this increase in cultured nasal epithelial cells. Genes co‐expressed with ACE2 were enriched in pathways relating to defence response to virus in nasal tissue. TMPRSS2 expression was decreased in nasal tissues of CRSwNP patients compared to control subjects and not correlated with the inflammatory endotypes of CRSwNP. Glucocorticoid treatment decreased ACE2 expression in nasal tissues of nonECRSwNP patients, but not in ECRSwNP patients, whereas TMPRSS2 expression was not affected.ConclusionThese findings indicate that ACE2 expression, regulated by IFN‐γ, is increased in nasal tissues of nonECRSwNP patients and positively correlates with type 1 inflammation.

Association between the sinus microbiota with eosinophilic inflammation and prognosis in chronic rhinosinusitis with nasal polyps

Dysbiosis of the sinus microbiome affects the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNPs). We investigated whether the sinus microbiota in CRSwNPs is associated with eosinophilic inflammation, especially in relation to innate lymphoid cells (ILCs), prognosis, and serum extracellular vesicles (EVs). Middle meatal swabs and serum from 31 CRSwNPs patients and six healthy controls were analyzed by 16S ribosomal RNA sequencing. ILC2s and cytokines from sinonasal tissues were measured by flow cytometry and ELISA, respectively. The relative abundances (RAs) of bacteria were compared based on eosinophilic inflammation and surgical outcome. The correlations between sinus bacteria and ILC2s, cytokines, and serum EVs were analyzed. The compositions of sinus bacteria were different between groups at the genus level. In eosinophilic CRSwNPs patients, the RA of Anaerococcus was significantly decreased (P = 0.010), whereas that of Lachnoclostridium was significantly increased (P = 0.038) compared with that in controls. The RA of Lachnoclostridium showed a significant positive correlation with interleukin (IL)-5-producing ILC2 populations (R = 0.340, P = 0.049), whereas the RA of Anaerococcus showed a negative correlation with IL-5-producing ILC2 populations (R = −0.332, P = 0.055). The RAs of Corynebacterium, Anaerococcus, and Tepidimonas were significantly decreased in patients with suboptimal outcomes compared with those in patients with optimal outcomes and control subjects. Some sinus bacteria and serum EVs showed positive correlations. CRSwNPs patients showed distinct microbiota compositions based on eosinophilic inflammation in relation to ILC2s and surgical outcome. These findings support a relationship between the microbiota and the host immune response in CRSwNPs.

Impact of sinus surgery on type 2 airway and systemic inflammation in asthma

Objective: Asthma is frequently associated with chronic rhinosinusitis with nasal polyps (CRSwNP). Although endoscopic sinus surgery (ESS) improves asthma control in CRSwNP patients with asthma, the mechanism that underlies the response to surgical treatment is still unclear. We evaluated the relevance of changes in asthma control and changes in airway/systemic inflammation in eosinophilic CRSwNP patients with not well controlled asthma who underwent ESS.Methods: We prospectively assessed changes in the asthma control questionnaire (ACQ) score, blood eosinophil counts (B-Eos), forced expiratory volume in 1 s (FEV1), and fraction of exhaled nitric oxide (FeNO) levels at 1-week before and 8 and 52 weeks after ESS.Results: Twenty-five subjects were analyzed. The ACQ score, B-Eos, and FeNO decreased, and FEV1 increased significantly after ESS. In the period from baseline to 52 weeks after ESS, changes in ACQ were significantly correlated with the changes in blood eosinophil counts (r = 0.58, p<.01) and FeNO (r = 0.45, p<.05). Ten subjects (40%) showed consistently improved asthma control at 52-weeks after ESS. In the remaining subjects, although the ACQ score temporarily improved at 8-weeks after ESS, but eventually deteriorated at 52-weeks. Higher levels of total immunoglobulin E were associated with long-term improved asthma control after ESS.Conclusions: In eosinophilic CRSwNP patients with asthma, sinus surgery impacts asthma control through the suppression of airway/systemic type 2 inflammation. The present study reinforced the common pathophysiology of type 2 inflammation between the upper and lower airways.

Changes in the clinical and histological characteristics of Chinese chronic rhinosinusitis with nasal polyps over 11 years.

Traditionally, it was believed that chronic rhinosinusitis with nasal polyps (CRSwNP) demonstrated less eosinophilic and more neutrophilic inflammation in China compared to North America and Europe. However, inflammatory patterns may change over time. The study aimed to analyze the changing trends in the clinical and histological characteristics of CRSwNP over time in China. A total of 115 consecutive CRSwNP patients from 2003 to 2005 and 114 consecutive CRSwNP patients from 2014 to 2016 were enrolled in this retrospective study. The clinical and histological data were compared between patients from the 2 time periods. The percentage of eosinophils in nasal polyp tissue increased, and the percentage of neutrophils and total inflammatory cell count decreased, over 11 years. The proportion of eosinophilic CRSwNP significantly increased from 59.1% to 73.7% over 11 years. The proportion of neutrophils and the total inflammatory cell count in nasal polyps decreased, and the proportion of eosinophilic CRSwNP patients using intranasal corticosteroids 1 month before surgery increased remarkably over 11 years. Moreover, eosinophilic CRSwNP patients had better compliance with intranasal corticosteroid use than non-eosinophilic CRSwNP patients, and patients with comorbid allergic rhinitis and asthma had better compliance with intranasal corticosteroid use than patients without those conditions. Eosinophilic CRSwNP, which was previously a minor subtype in East Asians, has increased remarkably in incidence to become the predominant CRSwNP subtype in Beijing, China, indicating that rhinologists should place greater emphasis on its diagnosis and treatment.

Inhibition of arachidonate 15-lipoxygenase reduces the epithelial-mesenchymal transition in eosinophilic chronic rhinosinusitis with nasal polyps.

The epithelial-mesenchymal transition (EMT) is a distinguishing characteristic of chronic rhinosinusitis with nasal polyps (CRSwNP). The underlying mechanism remains largely unknown. Arachidonate 15-lipoxygenase (ALOX15), an enzyme involved in arachidonic acid metabolism, has been reported to cause airway epithelial injury and thus may further promote the EMT. The aim of this study was to evaluate the role of ALOX15 during the EMT process in CRSwNP. A total of 54 samples were obtained, including 10 from healthy control, 16 from non-eosinophilic CRSwNP, and 28 from eosinophilic CRSwNP. Hematoxylin and eosin staining was performed to determine the basement membrane (BM) thickness. The concentration of molecules mediating remodeling was assayed by Luminex. The messenger RNA (mRNA) and protein levels of target genes were measured by quantitative real-time polymerase chain reaction (PCR) and Western blotting. EMT was enhanced in eosinophilic CRSwNP compared with the healthy controls and non-eosinophilic CRSwNP infiltrated with lymphocytes and/or plasma cells. The expression pattern of molecules related to remodeling, including matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), and transforming growth factor β (TGF-β) family members, differed between the subtypes of CRSwNP. The mRNA level of ALOX15 was correlated with the BM thickness and MMP-1 and TGF-β3 expression. The inhibition of ALOX15 by PD146176 could induce claudin-1, claudin-4, claudin-7, zonula occludens (ZO)-1, ZO-2, E-Cadherin, TIMP-1, and TIMP-3 expressions and reduce the levels of MMP-1 and N-Cadherin in epithelial cells acquired from eosinophilic CRSwNP patients. The specific inhibition of ALOX15 could attenuate the EMT, which may provide an alternative method for the treatment of CRSwNP.

The prognostic role of serum eosinophil and basophil levels in sinonasal polyposis.

Predicting which patients are at a higher risk for recurrent chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most challenging problems in clinical rhinology. A direct association between CRSwNP recurrence rates and serum eosinophil and basophil counts was reported. This study aimed to identify best-fitting cutoffs for binarizing preoperative serum eosinophils and basophils (counts/percentages) for prognostic purposes in cases of CRSwNP recurrence after surgery. A secondary endpoint was to distinguish said cutoffs for prognosticating recurrence in subcohorts of patients with histologically diagnosed eosinophilic/non-eosinophilic CRSwNP. A retrospective study was performed on 280 patients (127 eosinophilic and 153 non-eosinophilic CRSwNP) examining the prognostic role of serum eosinophil and basophil levels. For all patients examined, mean preoperative serum eosinophil and basophil levels were significantly higher in patients whose CRSwNP recurred. Patients with eosinophil counts ≥0.24 cells × 109 /L and percentages ≥3.7% had odds ratios (ORs) of 2.57 and 2.19 for recurrence; patients with basophil counts ≥0.03 cells × 109 /L and percentages ≥0.5% had ORs of 2.19 and 2.24, respectively. Among histologically eosinophilic CRSwNP patients, mean eosinophils and basophils (counts/percentages) were significantly higher in cases that recurred. Serum eosinophil and basophil values were directly correlated. The recurrence odds were OR 2.52 for high eosinophils (≥5.9%), and OR 2.52 and 2.69 for high basophils (≥0.04 cells × 109 /L and ≥0.5%, respectively). High serum eosinophil and basophil values should be further investigated because they could pinpoint patients at higher risk of eosinophilic-type CRSwNP recurrence. These preliminary results support the increasing interest in the role of basophils in CRSwNP.

Genetic polymorphism of antioxidant enzymes in eosinophilic and non-eosinophilic nasal polyposis.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the paranasal sinuses, and its pathophysiology is not yet precisely known. It is suggested that oxygen free radicals play an important role in the pathogenesis of nasal polyposis. This study aimed to identify genetic polymorphisms of superoxide dismutase (SOD 2), catalase (CAT), and inducible nitric oxide synthase (iNOS) enzymes in eosinophilic CRSwNP and non-eosinophilic CRSwNP patients; the study also aimed to evaluate the effect of genetic polymorphism of antioxidant enzymes on CRSwNP etiopathogenesis. One hundred thirty patients, who received endoscopic sinus surgery due to CRSwNP, and 188 control individuals were included in this study. Nasal polyp tissues were divided into two groups histopathologically as eosinophilic CRSwNP and non-eosinophilic CRSwNP. Venous blood samples were taken from the patient and control groups. Polymorphisms in the Ala16Va1 gene, which is the most common variation of SOD-2 gene, and 21 A/T polymorphisms in catalase gene were evaluated with the restriction fragment length polymorphism method and -277 C/T polymorphism in the iNOS gene was evaluated with the DNA sequencing method. The GG genotype distribution for the (-277) A/G polymorphism in the iNOS gene was a statistically significant difference between eosinophilic CRSwNP and control groups (p<0.05). The CC genotype distribution for the SOD2 A16V (C/T) polymorphism was not statistically significant in all groups (p>0.05). The TT genotype distribution for the A/T polymorphism in catalase gene at position -21 was statistically significant differences in eosinophilic CRSwNP and control groups (p<0.05). Increased free oxygen radical levels, which are considered effective factors in the pathogenesis of CRSwNP, can occur due to genetic polymorphism of enzymes in the antioxidant system and genetic polymorphism of antioxidant enzymes in eosinophilic CRSwNP patients might contribute to the pathophysiology.

Interleukin-13 Inhibits Lipopolysaccharide-Induced BPIFA1 Expression in Nasal Epithelial Cells.

Short palate, lung, and nasal epithelium clone 1 (SPLUNC1) protein is expressed in human nasopharyngeal and respiratory epithelium and has demonstrated antimicrobial activity. SPLUNC1 is now referred to as bactericidal/permeability-increasing fold containing family A, member 1 (BPIFA1). Reduced BPIFA1 expression is associated with bacterial colonization in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Interleukin 13 (IL-13), predominately secreted by T helper 2 (TH2) cells, has been found to contribute to airway allergies and suppress BPIFA1 expression in nasal epithelial cells. However, the molecular mechanism of IL-13 perturbation of bacterial infection and BPIFA1 expression in host airways remains unclear. In this study, we found that lipopolysaccharide (LPS)-induced BPIFA1 expression in nasal epithelial cells was mediated through the JNK/c-Jun signaling pathway and AP-1 activation. We further demonstrated that IL-13 downregulated the LPS-induced activation of phosphorylated JNK and c-Jun, followed by attenuation of BPIFA1 expression. Moreover, the immunohistochemical analysis showed that IL-13 prominently suppressed BPIFA1 expression in eosinophilic CRSwNP patients with bacterial infection. Taken together, these results suggest that IL-13 plays a critical role in attenuation of bacteria-induced BPIFA1 expression that may result in eosinophilic CRSwNP.