Chronic Sinusitis With Nasal Polyps Research Articles

Ganglioside GD3 Regulates Inflammation and Epithelial-to-Mesenchymal Transition in Human Nasal Epithelial Cells.

Chronic sinusitis with nasal polyps (CRSwNP) is one of the most common chronic inflammatory diseases, and involves tissue remodeling. One of the key mechanisms of tissue remodeling is the epithelial-mesenchymal transition (EMT), which also represents one of the pathophysiological processes of CRS observed in CRSwNP tissues. To date, many transcription factors and forms of extracellular stimulation have been found to regulate the EMT process. However, it is not known whether gangliosides, which are the central molecules of plasma membranes, involved in regulating signal transmission pathways, are involved in the EMT process. Therefore, we aimed to determine the role of gangliosides in the EMT process. First, we confirmed that N-cadherin, which is a known mesenchymal marker, and ganglioside GD3 were specifically expressed in CRSwNP_NP tissues. Subsequently, we investigated whether the administration of TNF-α to human nasal epithelial cells (hNECs) resulted in the upregulation of ganglioside GD3 and its synthesizing enzyme, ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialytransferase 1 (ST8Sia1), and the consequently promoted inflammatory processes. Additionally, the expression of N-cadherin, Zinc finger protein SNAI2 (SLUG), and matrix metallopeptidase 9 (MMP-9) were elevated, but that of E-cadherin, which is known to be epithelial, was reduced. Moreover, the inhibition of ganglioside GD3 expression by the siRNA or exogenous treatment of neuraminidase 3 (NEU 3) led to the suppression of inflammation and EMT. These results suggest that gangliosides may play an important role in prevention and therapy for inflammation and EMT.

Comparison of the General Characteristics of Patients with Severe Asthma Who Switched from Omalizumab to Mepolizumab versus Patients Who Responded to Omalizumab Treatment: A Real-Life Study

Introduction: Severe asthma is characterized by frequent recurrent airway symptoms and exacerbations, and these affect the quality of life. Biological agents can be used in the treatment of patients with severe asthma if the disease cannot be controlled with standard controller treatment. The aim of this study was to compare the clinical characteristics and laboratory data of patients with severe asthma who were switched from omalizumab to mepolizumab and patients with severe asthma who responded to omalizumab. Methods: The clinical characteristics and laboratory data of patients with severe asthma who responded to omalizumab and switched from omalizumab to mepolizumab were compared retrospectively. Results: Evaluation was made of a total of 79 patients, including 64 omalizumab responders and 15 who switched to mepolizumab from omalizumab. After omalizumab and mepolizumab treatment, the annual number of asthma attacks, the use of oral corticosteroid (OCS), the annual number of hospitalizations, and the eosinophil count significantly decreased (omalizumab: p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively; mepolizumab: p = 0.001, p = 0.001, p = 0.002, p = 0.001, respectively). After omalizumab treatment, the increase in forced expiratory volume in 1 s (FEV1) (%) and asthma control test (ACT) score were determined to be statistically significant (p < 0.001, p < 0.001, respectively). After mepolizumab treatment, the increase in ACT score was significant (p = 0.003). Drug allergy, chronic sinusitis with nasal polyps (CRSwNP), regular use of OCS, and high baseline eosinophil count (cells/µL) were associated with poor response to omalizumab treatment (odds ratio [OR] = 7.86, p = 0.003; OR = 52.92, p < 0.001; OR = 10.16, p = 0.004; OR = 0.99, p = 0.004, respectively). House dust mite sensitivity and high baseline FEV1 (%) were associated with good response to omalizumab treatment (OR = 0.29, p = 0.041; OR = 1.06, p = 0.03, respectively). The blood eosinophil count had diagnostic value in predicting the nonresponsiveness to omalizumab treatment (area under the curve [AUC]: 0.967, p < 0.001, cut-off: 510). Conclusion: A high pretreatment eosinophil count, concomitant CRSwNP, a history of drug allergy, and regular OCS use may be associated with poor response to omalizumab treatment in patients with severe asthma. Depending on the treatment response, treatment switching can be applied between biological agents. The results of the current study should be supported by multicenter studies.

Systemic inflammation response index predicts the postoperative recurrence of chronic rhinosinusitis with nasal polyps: a retrospective study in the Chinese population.

Endoscopic sinus surgery (ESS) is now frequently used to treat chronic sinusitis with nasal polyps (CRSwNP), but postoperative recurrence plagues many patients. We aimed to assess the value of the systemic inflammation response index (SIRI) and the systemic immune-inflammatory index (SII) for the prediction of postoperative recurrence in patients with CRSwNP. A total of 143 patients with CRSwNP and 76 age- and sex-matched healthy subjects were enrolled. Patients were divided into the recurrence group and the non-recurrence group according to the recurrence of CRSwNP. Univariate and multivariate analyses showed independent risk factors for the recurrence. A receiver operating characteristic curve analysis was conducted to assess the predictive accuracy of the variables and determine the optimal cut-off values. Finally, a survival analysis was conducted. Univariate analysis revealed that age, sex, CRP, EOS, SIRI, SII, NLR, ELR, and Lund-Mackay CT scores were significant predictors of the recurrence of CRSwNP. Multivariate analysis confirmed that SIRI (OR = 1.310, p < 0.001) and Lund-Mackay CT scores (OR = 1.396, p < 0.001) were independent predictors. SIRI (AUC = 0.761, 95% CI: 0.685-0.836) had a certain value in predicting the recurrence of CRSwNP. SIRI is a potential predictive marker of the postoperative recurrence of CRSwNP.

Evaluation of the efficacy of endoscopic posterior nasal neurectomy with pharyngeal neurectomy of allergic rhinitis combined with chronic rhinosinusitis with nasal polyps

Objective:To investigate the effect of posterior nasal neurectomy（PNN） with pharyngeal neurectomy （PN） on chronic sinusitis with nasal polyps （CRSwNP）complicated with perennial allergic rhinitis （PAR）. Methods:83 patients with perennial allergic rhinitis combined with chronic group-wide sinusitis with nasal polyps who attended our hospital from July 2020 to July 2021 were selected. All patients underwent conventional functional endoscopic sinusitis surgery（FESS）+ nasal polypectomy. Patients were divided according to whether they underwent PNN+PN. 38 cases in the experimental group underwent FESS combined with PNN+PN; 44 cases in the control group underwent conventional FESS alone. All patients underwent the VAS, RQLQ, and MLK before treatment, and at 6 months and 1 year after surgery. Meanwhile, other relevant data were collected and the preoperative and postoperative follow-up data were collected and analyzed to assess the differences between the two groups. Results:The total postoperative follow-up period was 1 year. The recurrence rate of nasal polyps at 1 year postoperatively and the nasal congestion VAS score at 6 months postoperatively were not statistically significant in the two groups（P>0.05）. However, the patients in the experimental group had statistically significantly lower effusion and sneezing VAS scores, MLK endoscopy scores and RQLQ scores at 6 months and 1 year postoperatively, and nasal congestion VAS scores at 1 year postoperatively compared to the control group（P<0.05）. Conclusion:For patients with perennial AR complicated with CRSwNP, the combination of the PNN+PN in FESS can significantly improve the short-term curative effect, and PNN+PN is a safe and effective surgical treatment.

Some Macrophages With High Expression of CHOP Undergo Necroptosis in Chronic Rhinosinusitis.

Endoplasmic reticulum stress (ER stress) is activated in chronic sinusitis with nasal polyps (CRSwNP) and leads to increased expression of C/EBP homologous protein (CHOP). However, the role of CHOP in the pathogenesis of CRSwNP remains unclear. CHOP expression was detected by immunohistochemistry staining in nasal mucosa of control and CRSwNP patients. Co-localization of CHOP and cleaved caspase3, p-MLKL, and CD68 was detected by immunofluorescence staining in CRSwNP patients. TNFα, IFNγ, IL1β, LPS, and tunicamycin were added to primary dispersed nasal polyp cells (DNPCs) to explore their roles in cell death. Western blot, CCK8 assay, and flow cytometry were employed to detect cell death. CHOP was specifically activated in CRSwNP compared to controls. It was mainly macrophages that highly expressed CHOP, some of which underwent apoptosis and the other underwent necroptosis. IL1β induced increased CHOP and apoptosis, and a slight p-MLKL. In addition, ER stress could also promote p-MLKL expression. Whereas classical TNFα plus IFNγ and LPS did not induce increased necroptosis in DNPCs. IL1β induced the apoptotic pathway and minor necroptosis. And ER stress also plays a role in the occurrence of necroptosis in CRSwNP.

The Nasal Bacteria Microbiome Comparison Among Fungal Ball Sinusitis, Chronic Sinusitis with Polyps.

To evaluate the composition of the microbial community of the middle nasal in paranasal sinus fungus ball (FB), chronic sinusitis with nasal polyps (CRSwNP) and healthy controls, providing new insights into the pathogenesis of FB and CRSwNP. Through 16s rRNA gene high-throughput sequencing to determine the microbial characterization from patients with FB (n = 29) and CRSwNP (n = 10), and healthy controls (n = 4). The FB group had significantly lower αdiversity and significantly different β diversity compared to the other groups. All three groups mainly consisted of four bacterial phyla (Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria). In the FB group, the highest relative abundance was found in Proteobacteria (47.04%). However, pairwise comparisons resulted in statistically significant differences only for Firmicutes (CRSwNP, p = 0.003, Control, p = 0.008). The CRSwNP group was statistically different from the control group in TM7(p = 0.010), Chloroflexi(p = 0.018) and Bacteroidete(p = 0.027). At the genus level, the FB group had the highest relative abundance of Haemophilus (11.53%), followed by Neisseria (7.39%), and Neisseria abundance (p < 0.001) was significantly different from the remaining two groups. Ruminococcacea abundance (p < 0.001) and Comamonadaceae abundance (p < 0.001) were increased in the CRSwNP group. The relative abundance of Lactobacillus (p < 0.001), Bacteroides S24_7 (p < 0.001), and Desulfovibrio (p < 0.001) was significantly decreased in the FB and CRSwNP groups compared to the control group. The imbalance of the microbial community is related to the pathogenesis of sinusitis.

SMARCB1 (INI-1)-Deficient Sinonasal Carcinoma: A Case Report and Literature Review.

Background: SWItch/Sucrose Non-Fermentable related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1)-deficient sinonasal carcinoma (SDSC) is a malignant tumor classified as sinonasal undifferentiated carcinoma (SNUC). Purpose: Owing to the high aggressiveness and poor prognosis reported in recent literature, patients diagnosed with SNUC should consider further immunohistochemical examination to screen for SDSC. Timely diagnosis is critical and will contribute to follow-up targeted therapy and improved patient prognosis. Research Design: Case report. Study Sample: A case of SDSC with a history of chronic sinusitis with nasal polyps (CRSwNP). Data Collection: We collected all the clinical data of this patient. Results: The patient underwent planned functional endoscopic sinus surgery (FESS) and received chemotherapy combined with immunotherapy postoperatively. There was no evidence of recurrence or metastasis at the 3-month follow-up. Conclusions: The patient in this case presented with right intermittent epistaxis, and surgical histopathological examination confirmed a diagnosis of right SDSC and left CRSwNP. No related research has been reported.

S100A11 regulates nasal epithelial cell remodeling and inflammation in CRSwNPs via the RAGE-mediated AMPK-STAT3 pathway

Abnormal remodeling of the nasal mucosal epithelium and persistent chronic inflammation are important pathological features of chronic sinusitis with nasal polyps (CRSwNPs). In order to explore the molecular regulation mechanism of CRSwNPs, we performed iTRAQ protein profile analysis on 18 clinical samples collected (9 patients with nasal polyps and 9 healthy patients) and found that S100A11, a Ca2+-binding protein, was significantly higher in CRSwNPs. Subsequently, we demonstrated that S100A11 was mainly located in nasal mucosal epithelial cells and is up-regulated in human nasal epithelial stem/progenitor cells (hNESPCs) from CRSwNPs patients and CRSwNPs epithelial cell model established with S. aureus. To determine the functional role of S100A11 and the signal pathways in epithelial cells, we constructed S100A11 overexpression vector, small interfering RNA, recombinant protein-S100A11 (rh-S100A11) and RAGE inhibitor (sRAGE). Results showed that upregulation of S100A11 inhibited epithelial cell viability and promoted apoptosis and inflammation, in addition, S100A11 can regulate the signal homeostasis of AMPK-STAT3 via RAGE mediation in epithelial cells. Our findings suggest that S100A11 is involved in CRSwNPs epithelial tissue remodeling and inflammatory response regulation and may be a useful target for CRSwNPs therapy.

Study on the correlation between eosinophils and chronic rhinosinusitis with nasal polyps in Xinjiang region of China

Objective: To explore the correlation between eosinophils (Eos) and the incidence of chronic sinusitis with nasal polyps (CRSwNP) in Xinjiang region of China by comparing the proportion of inflammatory cells in the pathological tissues and peripheral blood. Methods: Retrospective analysis was performed on 582 patients with CRSwNP who underwent endoscopic nasal surgery in the First Affiliated Hospital of Xinjiang Medical University from January 2012 to March 2018, including 367 males and 215 females, aged (45.5±13.4) years (x¯±s). Patients were divided into groups according to demographic characteristics, recurrence and complication of allergic rhinitis (AR). Preoperative blood routine and postoperative pathological section data of nasal polyps were collected to compare the ratio of inflammatory cells in pathological tissue and the ratio of peripheral blood Eos in each group. The correlation between the proportion of inflammatory cells in the pathological tissue of nasal polyps and the recurrence of CRSwNP was analyzed, as well as the distribution of (eosCRSwNP) in Uygur and Han CRSwNP patients in Xinjiang region. Statistical analysis was performed by SPSS 19.0 software. Results: Compared with non-recurrent CRSwNP patients, the ratio of Eos in nasal polyp tissue and peripheral blood was increased significantly, (Z value was -3.142 and -2.344, respectively, both P<0.05). Compared with CRSwNP patients without AR, the ratio of Eos in nasal polyps and peripheral blood was also increased significantly in patients with AR (Z value was -6.664 and -4.520, respectively, both P<0.05). There was a positive correlation between tissue Eos and CRSwNP recurrence (r=0.130, P=0.002). The majority of CRSwNP patients were both eosCRSwNP in Uygur and Han ethnic groups. Conclusions: Eos is associated with the recurrence of CRSwNP in Xinjiang region, and eosCRSwNP is the dominant factor in both Uygur and Han patients.

Correlation of tissue eosinophil count and modified CT olfactory cleft score and olfactory function in patients with nasal polyps

Objective:To investigate the effect of tissue eosinophil count on olfactory function in patients with chronic sinusitis with nasal polyps（CRSwNP）. Method:We prospectively selected 59 patients with CRSwNP. All the patients were not treated with oral or topical glucocorticoids for at least 1 month at the time of enrollment. All the nasal polyps were taken under local anesthesia in the outpatient department for eosinophil count and percentage calculation. The patients were divided into eosinophilic CRSwNP（ECRS group） and non-eosinophilic CRSwNP（non-ECRS group）. Baseline data was compared between the two groups. Spearman correlation analysis was performed on tissue eosinophil count and Lund-Mackay score, modified olfactory cleft scores, Sniffin' Sticks olfactory test, olfactory evoked potential peak latency and amplitude respectively. Result:Thirty-five of 59 patients with CRSwNP completed olfactory evoked potential test, from whom we collected stable waveforms. The ECRS group had a higher olfactory cleft area CT score, ethmoid sinus CT score and blood eosinophil count and percentage; there was a significant difference between the ECRS group and the non-ECRS group in single and bilateral odor test threshold（T value）（P=0.017）. There was no significant correlation between tissue eosinophil count and subjective olfactory VAS score（P>0.05）. Tissue eosinophil count was related to the bilateral T value in Sniffin' Sticks olfactory test（r=-0.322, P=0.013）, anterior and posterior olfactory cleft area scores（r=0.431 and 0.415, respectively, P=0.001） and olfactory evoked potential N1 latency（r=0.504, P=0.001） and P2 latency（r=0.374, P=0.020）, but not related to Lund-Mackay scores. In addition, there was a significant correlation between the unilateral T score in Sniffin' Sticks test and the unilateral olfactory evoked potential N1 latency（r=-0.505, P=0.002）. Conclusion:The increase of tissue eosinophilia was closely related to olfactory disfunctions in CRSwNP. It could be reflected by modified CT olfactory cleft score, Sniffin' Sticks olfactory test T value and oERP peak latency. In addition, T value was negatively consistent with latency of oERP N1 peak.

Expression of COX-1, COX-2, 5-LOX and hbox {CysLT}_2 in nasal polyps and bronchial tissue of patients with aspirin exacerbated airway disease

BackgroundAspirin exacerbated respiratory disease (AERD) is a disease of the upper and lower airways. It is characterized by severe asthma, chronic sinusitis with nasal polyps (CRSwNP) and intolerance towards nonsteroidal analgesics (NSAR). Arachidonic acid (AA) metabolites play an important role in the pathogenesis of AERD. It is still unknown, whether metabolism of AA is comparable between the upper and lower airways as well as between patients with and without NSAR intolerance.ObjectiveWe sought to analyze differences in the expression of cyclooxygenases type 1 and 2 (COX-1, COX-2), arachidonate 5-lipoxygenase (5-LOX) and cysteinyl leukotriene receptor type 2 (hbox {CysLT}_2) in nasal polyps and the bronchial mucosa of patients with aspirin intolerant asthma (AIA, n=23) as compared to patients with aspirin tolerant asthma (ATA, n=17) and a control group with nasal polyps, but without asthma (NPwA, n=15).MethodsTissue biopsies from nasal polyps and bronchial mucosa were obtained during surgical treatment of nasal polyps by endonasal functional endoscopic sinus surgery (FESS) under general anesthesia from intubated patients. Immunohistochemistry was used to analyze the expression of COX-1, COX-2, 5-LOX and hbox {CysLT}_2 in nasal and bronchial mucosa. Categorization into the different patient groups was performed according to the patient history, clinical and laboratory data, pulmonary function and provocation tests, as well as allergy testing.ResultsWe observed a stronger expression of 5-LOX and hbox {CysLT}_2 in submucosal glands of nasal and bronchial tissue compared to epithelial expression. The expression of COX-1 and COX-2 was stronger in epithelia compared to submucosal glands. There was a similar expression of the enzymes and hbox {CysLT}_2 between upper and lower airways in all patient groups. We did not detect any significant differences between the patient groups.ConclusionsThe AA-metabolizing enzymes and the hbox {CysLT}_2 were expressed in a very similar way in different microscopic structures in samples of the upper and lower airways of individual patients. We did not detect differences between the patient groups indicating the pathogenetic role of AA metabolism in these disorders is independent of the presence of NSAR-intolerance.

Analysis of virulence genes of Staphylococcus aureus in nasal secretionsof patients with chronic rhinosinusitis

Objective:To investigate the differences of virulence genes of Staphylococcus aureus in patients with chronic sinusitis with nasal polyps (CRSwNP) and chronic sinusitis without nasal polyps (CRSsNP), and to explore the relationship between different virulence factors and the incidence of sinusitis and nasal polyps.Method:The PCR method was used to detect 17 kinds of virulence genes of Staphylococcus aureus isolated from nasal secretions of 41 strains.Result:①The detection rate of SEB in the experimental group was significantly higher than that in the control group, the detection rate of SEB in the CRSwNP group was higher than that in the CRSsNP group, and the other 5 kinds of enterotoxin genes were not statistically significant between the experimental group and the control group;②Staphylococcus aureus adhesin in the experimental group and the control group were detected, and the detection rate was relative higher in both control and experimental goups. However, the detection rate were not statistically significant between the experimental group and the control group;③The detection rate of HLα and HLβ genes encoding hemolysin was higher in the experimental group and the control group, and there was no significant difference between the 2 groups in the experimental group and the control group.Conclusion:Staphylococcus aureus carrying enterotoxin gene was more likely to cause CRS. The greater the incidence of nasal polyps was found in patients infected by Staphylococcus aureus carrying more enterotoxin gene.

The role of local allergy in the nasal inflammation.

Local allergic inflammation (LAI) is recognized recently. 'entopy' was used to define LAI, which was positively correlated with allergen provocation testing, local sIgE up-regulation, inflammatory mediator secretion, and a lack of systemic allergy. The study of LAI is in its infancy and focuses mainly on the respiratory system. It is closely related to nasal inflammation and plays important roles in patients with nonallergic rhinitis (NAR), nonallergic chronic sinusitis with nasal polyps (CRSwNP), and nonallergic fungal rhinosinusitis (NAFRS). Based on studies using nasal allergen provocation testing, 40-57% of patients with NAR exhibited positive results and could be diagnosed as local allergic rhinitis. Total IgE and common airborne allergen-sIgE were up-regulated in eosinophilic CRSwNP patients compared to noneosinophilic CRSwNP patients and healthy controls, possibly due to local allergic inflammation. Some researchers also found that the level of local sIgE was increased in patients with NAFRS; they suggested that local allergic inflammation occurs in NAFRS. Studies of LAI will increase our understanding of nasal inflammation and help to establish novel treatments. However, the diagnosis of local allergic inflammation is complex due to the lack of convenient detection methods. The relationship between local allergic inflammation and systemic allergic inflammation is unclear, and an appropriate treatment for local allergic inflammation is required.

Predictive significance of tissue eosinophilia for nasal polyp recurrence

To evaluate the association between clinical parameters, especially tissue eosinophilia, and chronic sinusitis with nasal polyps (CRSwNP) recurrence. To identify optimal criteria of tissue eosinophilia as a predictor for recurrence. Two hundred and forty-eight CRSwNP patients were enrolled in this study. The demographic and clinical features were compared between recurrence and no recurrence groups. Mucosal specimens were assessed for the presence of tissue inflammatory cells. Factors associated with polyp recurrence were analyzed by Logistic regression analysis and optimal cutoff point of the predictor for nasal polyp recurrence was determined by receiver operating characteristic curve. SPSS 19.0 software was used to analyze the data. The recurrence rate was 55.6%(138/248 patients) in this cohort. Tissue and peripheral eosinophilia, comorbid asthma, olfactory score and Lund-Mackay score were significantly correlated with polyp recurrence(all P<0.01). As a predictor for recurrence, tissue eosinophil accumulation outweighed other parameters. A cutoff value of 27% for tissue eosinophil percentage was able to predict recurrence with 96.4% sensitivity and 92.7% specificity (AUC=0.971, P<0.001). Tissue eosinophilia provides valuable information regarding to polyp recurrence. Tissue eosinophil proportion equal to or over 27% may be regarded as the prognostic criterion for nasal polyp recurrence.

Chronic rhinosinusitis with nasal polyps and without nasal polyps is associated with increased expression of lysophosphatidic acid-related molecules.

Chronic sinusitis with nasal polyps (CRSwNPs) or CRS without NPs (CRSsNPs) is associated with expression of various cytokines. Lysophosphatidic acid (LPA) generated by autotaxin (ATX), LPA-producing enzyme, initiates signaling cascade involved in the inflammatory responses and participates in diverse biological processes through LPA receptors, including cytokine production. We analyzed the expression and distribution patterns of LPA-related molecules in nasal secretion and sinus mucosa of normal controls and patients with CRSwNPs and CRSsNPs, to evaluate the possible effects of the ATX-LPA receptor axis on the pathogenesis of CRS. LPA levels in nasal secretion and the expression and distribution patterns of ATX and LPA receptors 1-3 (LPA1-3) in sinus mucosa were investigated using ELISA, real-time polymerase chain reaction, Western blot, and immunohistochemistry. We elucidated the effect of CRS-relevant cytokines on the expression of ATX and LPA receptors, using cultured sinus epithelial cells, and investigated the effect of LPA on the expression of CRS-relevant cytokines, using sinus mucosa explant culture. LPA, ATX, and LPA1-3 levels are increased in CRSwNPs and CRSsNPs. ATX and LPA1-3 were localized to superficial epithelium, submucosal glands in normal and inflammatory mucosa, but in inflammatory mucosa, they were found in inflammatory cells. LPA1-3 were noted in endothelium. Sinus mucosa explant stimulated with LPA increasingly produced IL-4, IL-5, interferon gamma, and TNF-alpha, and in cultured epithelial cells stimulated with CRS-relevant cytokines, ATX, and LPA1-3 were differentially induced. LPA in human sinus mucosa may play important roles in the pathogenesis of CRS, contributing to produce CRS-related cytokines. LPA-related molecules were increased in CRS, which may attribute to CRS-related cytokines.

Cigarette smoke exposure is associated with vitamin D3 deficiencies in patients with chronic rhinosinusitis

Cigarette smoke (CS) plays a role in the exacerbation of chronic rhinosinusitis (CRS); however, the mechanism for this is unknown. We hypothesize that CS impairs human sinonasal epithelial cell (HSNEC) conversion of 25(OH)D3 (25VD3) to 1,25-dihydroxyvitamin D3 (1,25VD3) and, furthermore, that supplementation with 1,25VD3 will reverse smoke-induced inflammatory responses by HSNECs. We sought to determine the effect of CS on vitamin D3 (VD3) levels, conversion, and regulation of CS-induced inflammation in control subjects and patients with CRS. Blood and sinus tissue explants were collected at the time of surgery from control subjects, patients with chronic rhinosinusitis without nasal polyps, and patients with chronic sinusitis with nasal polyps (CRSwNP). Expression of VD3 metabolizing enzymes were measured by using RT-PCR. Primary HSNECs were cultured from tissue explants. 25VD3 with and without cigarette smoke extract (CSE) was used to examine conversion of 25VD3 to 1,25VD3, as well as HSNEC production of proinflammatory cytokines. CS exposure was associated with reduced circulating and sinonasal 25VD3 levels in all groups compared with those seen in CS-naive, disease-matched counterparts. CS exposure decreased expression of CYP27B1 and was especially pronounced in patients with CRSwNP. CSE impairs control HSNEC conversion of 25VD3. HSNECs from patients with CRSwNP also demonstrate an intrinsic reduction in conversion of 25VD3 to 1,25VD3. Exogenous 1,25VD3 reduces CSE-induced cytokine production by HSNECs. Exposure to CS is associated with reduced 25VD3 levels and an impaired ability of HSNECs to convert 25VD3 to 1,25VD3. Addition of 1,25VD3 reduces the proinflammatory effects of CS on HSNECs. Impaired VD3 conversion by CS exposure represents a novel mechanism through which CS induces its proinflammatory effects.

P‐glycoprotein promotes epithelial T helper 2–associated cytokine secretion in chronic sinusitis with nasal polyps

Sinonasal epithelial cells are recognized as drivers of inflammation in chronic sinusitis with nasal polyps (CRSwNP) through secretion of T helper 2 (Th2)-promoting cytokines. P-glycoprotein (P-gp) is overexpressed in nasal polyps and modulates epithelial cytokine secretion in healthy mucosa. The objective of this study is to determine whether P-gp overactivity promotes Th2-associated cytokine secretion in CRSwNP. Polyp explants (n = 4) and primary epithelial cell cultures (n = 5) were cultivated from patients with CRSwNP. Explant P-gp activity was determined using a calcein assay. In culture, P-gp was quantified by enzyme-linked immunosorbent assay (ELISA) and sensitivity to PSC-833 inhibition was determined using a calcein assay. Lipopolysaccharide (LPS)-stimulated cytokine secretion of interleukin 6 (IL-6), IL-8, IL-25, and granulocyte macrophage colony stimulating factor (GM-CSF) were quantified by ELISA and compared to secretion following P-gp inhibition. Differences in P-gp expression and cytokine secretion were compared using a Mann-Whitney U test. Secretion was correlated with P-gp expression using a Pearson correlation coefficient. Calcein retention is increased in P-gp inhibited vs uninhibited polyp explants (mean ± standard deviation [SD]; 5.17 ± 1.76 vs 2.55 ± 0.62; p < 0.05) but not in controls, indicating increased nasal polyp P-gp activity. P-gp is sensitive to dose-dependent P-gp inhibition with PSC-833 in vitro. LPS-stimulated secretion of normalized GM-CSF (45.21 ± 41.39) and IL-6 (63.16 ± 36.37) were significantly reduced following P-gp inhibition (8.47 ± 3.28; p < 0.01, and 39.94 ± 31.07; p < 0.05; respectively) and secretion was highly correlated with P-gp expression(r = 0.824, p < 0.05, and r = 0.833, p < 0.05; respectively). P-gp overactivity promotes Th2-associated epithelial cytokine secretion in nasal polyps, suggesting a novel mechanism for maintaining chronic inflammation in CRSwNP.

Detection of Staphylococcal Exotoxins in Antrochoanal Polyps and Chronic Rhinosinusitis with Nasal Polyps

Staphylococcal exotoxins have been reported in the pathogenesis of many chronic inflammatory diseases. Recent reports have hypothesized that staphylococcal exotoxins might be related to inflammatory mucosal changes seen in chronic sinusitis with nasal polyps (CRS-NPs). Staphylococcal exotoxins have the capacity to act as superantigens (SAgs), bypassing normal antigen processing and directly stimulating a massive inflammatory response. The objective of this study was to analyze polyp tissue samples from patients with antrochoanal polyps (ACPs) and CRS-NPs for the presence of staphylococcal exotoxins. Prospective cohort study. Tertiary medical center. Tissue samples were obtained from 29 patients and 16 controls. Thirteen of 29 patients had ACPs, and 16 had CRS-NPs. Specimens were analyzed for the presence of 5 staphylococcal exotoxins (SEA, SEB, SEC, SED, and toxic shock syndrome toxin-1) using enzyme-linked immunosorbent assay (ELISA). At least 1 toxin was detected in 7 of 13 patients with ACPs and in 13 of 16 patients with CRS-NPs, whereas it was detected in only 4 controls. There were no statistically significant differences between ACP and control groups (P = .063). Our results showed a statistically significant association between toxin detection and patients with CRS-NPs (P = .003). Inflammatory triggers in ACP remain a subject of debate, and this study does not support the hypothesis that staphylococcal exotoxins may play a role in ACP ethiopathogenesis. Our research is consistent with the possibility of SAgs as etiological agents in the development of bilateral nasal polyposis.

Assessment of Predictive Factors for Biofilms Presence in Chronic Rhinosinusitis with Polyps

Objective: Evaluate predictive factors for the presence of biofilms during sinus surgery for chronic sinusitis with nasal polyps (CRSwP). Method: Prospective study conducted in a tertiary care center in 2008 to 2009. Patients underwent sinus surgery for CRSwP, and mucosal samples were harvested for scanning electron microscopic. Preoperative data were recorded. Data were considered nonparametric. Mann-Whitney test and Spearman rank correlation were used. Results: Biofilms were present in 66.6 % (22/33) of the CRSwNP patients. Both groups had similar age median [Interquartile Range] = 45.0 [15.0] (38-56) vs 46.5 [27.0] (22-78) and the same sex distribution (male:female ratio = 1.75). Patients with biofilms had worst Lund-Kennedy score (6.0[3.0] (3-10) vs 8.0[3.0] (3-11), U = 69.5, P = .44). Although patients with biofilms had worst NOSE and Lund-Mackay scores and best SNOT-20 and SNOT-20(5+) scores, those were not statistically different between groups. There was a strong correlation between preoperative NOSE and SNOT-20 scores in both groups. Conclusion: This study showed that biofilms were present in most patients with CRSwNP. Despite the fact that NOSE and Lund-Mackay scores were worse in patients with biofilms, only Lund-Kennedy scores shown a significant predictive value to find biofilms intraoperatively.

Human sinonasal epithelial cells direct dendritic function and T‐cell T helper 1/T helper 2 skewing following Aspergillus exposure

In lower airway disease such as asthma, epithelial cells have been shown to be potent regulators of dendritic cell (DC) functions. However, it is unclear how human sinonasal epithelial cells (HSNECs) from patients with sinusitis regulate DC functions. Therefore, in these studies we investigated the ability of Aspergillus fumigatus exposed HSNECs to regulate DC antigen uptake, maturation, and direction of T-cell T helper 1 (Th1)/Th2 skewing. Primary HSNECs were cultured from control (n = 8), chronic sinusitis without nasal polyps (CRSsNP) (n = 9), and chronic sinusitis with nasal polyps (CRSwNP) (n = 7) patients and exposed to Aspergillus. Conditioned media was placed upon monocyte-derived DCs from healthy controls. DC antigen uptake was assessed by dextran-fluorescein isothiocyanate (FITC) uptake. DC differentiation and maturation was assessed by immunostaining for CD209, CD80, and CD86 followed by flow cytometric analysis. DC direction of T-cell Th1/Th2 skewing was evaluated by immunostaining followed by intracellular flow cytometric analysis for interferon (IFN)-γ and interleukin (IL)-5. Control and CRSsNP HSNECs have the capacity to stimulate DC antigen uptake, differentiation, and maturation following Aspergillus exposure. CRSwNP HSNECs stimulate DC activation independent of Aspergillus exposure. Furthermore, Aspergillus-exposed CRSwNP HSNECs skew T-cells toward a Th2 phenotype. CRSwNP-derived HSNECs stimulate DC maturation and Th2 skewing independent of Aspergillus exposure. However, control and CRSsNP HSNECs induce DC maturation and Th2 skewing after Aspergillus exposure. These in vitro studies demonstrate that HSNECs are key regulators of DC functions in the sinus microenvironment.