Chronic Rhinosinusitis Without Nasal Polyps Group Research Articles

Characterizing immune microenvironment cell composition of chronic rhinosinusitis with nasal polyps based on mass cytometry technology

Objective: To analyze the cellular composition characteristics of the nasal tissue immune microenvironment in patients with control, chronic rhinosinusitis without nasal polyps (CRSsNP), non-eosinophilic chronic rhinosinusitis with nasal polyps (neCRSwNP), and eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) using mass cytometry flow technology. Methods: Thirteen CRS patients who underwent endoscopic nasal surgery at the Department of Otorhinolaryngology Head and Neck Surgery of Peking Union Medical College Hospital from March to December 2022 were recruited, including 8 males and 5 females, aged 22.3 to 58.3 years. Three control mucosae were obtained from normal ethmoid or sphenoid sinuses of patients with benign tumors of the temporal fossa or non-functional pituitary adenomas who underwent endoscopic surgery, excluding allergic rhinitis and sinusitis. Sixteen clinical tissue samples (3 of control, 3 of CRSsNP, 4 of neCRSwNP, and 6 of eCRSwNP) were prepared into single-cell suspensions. Mass cytometry flow detection was performed using a combination of 42 molecular markers to analyze the differences in cell subpopulations among the groups. Data were analyzed using GraphPad Prism 9. Results: Based on the mass cytometry flow results, cells from control, CRSsNP, neCRSwNP, and eCRSwNP were divided into seven main cell subgroups, with detailed subgrouping of T/NK cells and myeloid cells. In T/NK cells, compared with the control group, the number of NK CD56bright cells increased in the CRSsNP group, while NK CD56dim cells decreased; compared with the CRSsNP group, the eCRSwNP group showed a decrease in NKT cells and CD4+Tem cells; compared with the CRSsNP group, the eCRSwNP group showed a significant increase in CD25 expression within Treg cells; compared with the CRSsNP group, the eCRSwNP group showed a significant decrease in Tbet expression in CD8+Teff cells and CD8+TRM cells; in eCRSwNP, the expression of CD103 in CD8+TRM cells was significantly lower than in CRSsNP. In myeloid cells, compared with the other three groups, the eCRSwNP group showed a significant increase in macrophages and a significant decrease in cDC1 and monocytes; compared with the control group and CRSsNP, the eCRSwNP group also showed a significant decrease in resting state macrophages; compared with the CRSsNP group, the eCRSwNP group showed a significant decrease in the level of CX3CR1 within cDC2 and monocytes; the expression levels of NLRP3 in cDC2 and macrophages in the eCRSwNP group were significantly higher than in the other three groups; compared with the control group, the expression levels of Gata3 in cDC2 and macrophages in the eCRSwNP group were also significantly increased; additionally, the expression of CCR2 within monocytes in the eCRSwNP group was lower than in the CRSsNP group. In ILC, compared with the control group, the expression of CCR6 decreased in the eCRSwNP group. Conclusions: Compared with the control group, CRSsNP, and neCRSwNP, eCRSwNP shows an increase in macrophage number, a decrease in cDC1 and resting state macrophages, and depletion of protective cells CD103+CD8+TRM. Additionally, the expression levels of CCR2 and CX3CR1 in monocytes of eCRSwNP are decreased.

Effects and clinical significance of NLRP3 inflammasome activated by IL-17A in CRSwNP

Objective: To investigate the effects and clinical significance of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activated by interleukin (IL)-17A in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: Patients underwent nasal endoscopic surgery in the Third Affiliated Hospital of Sun Yat-sen University from January 2020 to December 2021 were collected, including 28 CRSwNP (including 19 males and 9 females, aged 19 to 67 years), 22 chronic rhinosinusitis without nasal polyps (CRSsNP) and 22 controls. qRT-PCR was used to detect the expressions of IL-17A, NLRP3, IL-1β and IL-18 in the three groups, and their correlations were analyzed. The positions of IL-17A, NLRP3 and IL-18 in nasal polys were analyzed by immunofluorescence. Western Blotting and ELISA were employed to detect the expression of NLRP3, IL-1β and IL-18 in the human nasal epithelial cells after using IL-17A stimulation or IL-17A receptor inhibitor. Immunofluorescence was used to observe the NLRP3, IL-1β, and IL-18 protein expression after IL-17A stimulating human nasal epithelial cells, and after the use of IL-17A receptor inhibitor and NLRP3 inhibitor MCC950. The correlations between NLRP3, IL-1β, IL-18 and CT scores, nasal endoscopic scores, visual analogue scale (VAS) scores, and sino-nasal outcome test (SNOT) 22 scores of CRSwNP patients were analyzed. SPSS 20.0 software was used for statistical analysis. Results: The expressions of IL-17A, NLRP3, IL-1β and IL-18 in the tissues of CRSwNP patients were significantly higher than those in CRSsNP group(P=0.018,P<0.001,P=0.005, P=0.016) and the control group(all P<0.001). IL-17A was positively correlated with the expression of NLRP3, IL-1β, and IL-18(r ralue was 0.643,0.650,0.629,respectively, all P<0.05). IL-17A, NLRP3, and IL-18 were co-localized in the epithelial propria of polyp tissue. IL-17A stimulated the expressions of NLRP3, IL-1β, and IL-18 in human nasal epithelial cells. After the use of IL-17A receptor inhibitor, the expressions of NLRP3, IL-1β, and IL-18 were significantly down-regulated. After the use of NLRP3 inhibitor MCC950, IL-17A was significantly down-regulated to promote the expression of NLRP3, IL-1β, and IL-18. The expressions of NLRP3, IL-1β and IL-18 were positively correlated with CT, nasal endoscopy, VAS, and SNOT22 scores in patients with CRSwNP. Conclusions: IL-17A promotes the release of IL-1β and IL-18 by activating the NLRP3 inflammasome and aggravates the severity of the disease in CRSwNP.

Association between Social Determinants of Health and Allergic Fungal Rhinosinusitis: A Systematic Review and Meta-analysis.

Some previous studies have shown an increased prevalence of allergic fungal rhinosinusitis (AFRS) among young, black patients with poor access to health care; however, results have been mixed. The purpose of this study was to investigate the relationship between social determinants of health and AFRS. PubMed, Scopus, CINAHL. A systematic review was performed searching for articles published from date of inception to September 29, 2022. English language articles describing the relationship between social determinants of health (i.e., race, insurance status) and AFRS as compared to chronic rhinosinusitis (CRS) were selected for inclusion. A Meta-analysis of proportions with comparison (Δ) of weighted proportions was conducted. A total of 21 articles with 1605 patients were selected for inclusion. The proportion of black patients among AFRS, chronic rhinosinusitis with nasal polyps (CRSwNP), and chronic rhinosinusitis without nasal polyps (CRSsNP) groups was 58.0% [45.3%-70.1%], 23.8% [14.1%-35.2%], and 13.0% [5.1%-24.0%], respectively. This was significantly higher among the AFRS population compared to both the CRSwNP population (Δ34.2% [28.4%-39.6%], p < .0001) and the CRSsNP population (Δ44.9% [38.4%-50.6%], p < .0001). The proportion of patients who were either uninsured or covered by Medicaid among the AFRS, CRSwNP, and CRSsNP populations was 31.5% [25.4%-38.1%], 8.6% [0.7%-23.8%], and 5.0% [0.3%-14.8%], respectively. This was significantly higher among the AFRS group than the CRSwNP group (Δ22.9% [15.3%-31.1%], p < .0001) and the CRSsNP group (Δ26.5% [19.1%-33.4%], p < .0001). This study confirms that AFRS patients are more likely to be Black and either uninsured or on subsidized insurance than their CRS counterparts.

SNOT-22 Quality of Life Scores Improve After Endoscopic Endonasal Repair of Spontaneous Cerebrospinal Fluid Rhinorrhea.

Patients with spontaneous cerebrospinal fluid (CSF) rhinorrhea can experience significant sinonasal symptom burden, leading to poor quality of life (QOL). The objective of this study was to investigate sinonasal outcome test-22 (SNOT-22) scores in patients undergoing endoscopic endonasal surgery for spontaneous CSF rhinorrhea and compare them to patients undergoing endoscopic sinus surgery (ESS) for chronic rhinosinusitis without nasal polyps (CRSsNP). A multi-institutional retrospective review of patients with spontaneous CSF rhinorrhea and CRSsNP was performed. Pre-surgery and post-surgery SNOT-22 scores and domains were compared within each group. Improvements in SNOT-22 scores after surgery were compared between the groups. Ninety-one patients were in the CSF rhinorrhea group and 105 patients were in the CRSsNP group. Within each group, surgery significantly improved total SNOT-22 scores, domain scores, and most of the individual symptoms. Comparing the 2 groups revealed similar improvements in total SNOT-22 scores (P = .244). The CSF rhinorrhea group improved more in runny nose (P < .001), postnasal discharge (P < .001), wake up at night (P = .024), and embarrassed (P = .002). The CRSsNP group improved more in sneezing (P = .027), nasal blockage (P < .001), decreased sense of smell/taste (P = .011), thick nasal discharge (P < .001), facial pain/pressure (P = .008), and the ear/facial domain (P = .010). Patients with spontaneous CSF rhinorrhea experience significant symptom burden. Those who undergo CSF leak repair should experience significant improvement in QOL similar to patients who undergo ESS for CRSsNP as measured by SNOT-22.

Predictive value of S100A4 in eosinophilic chronic rhinosinusitis with nasal polyps.

S100A4 is a pro-inflammatory mediator which has been implicated in airway inflammatory diseases. However, its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. The purpose of this study is to determine the expression of S100A4 and evaluate its potential value in distinguishing its endotypes. Sixty CRSwNP patients, 30 chronic rhinosinusitis without nasal polyps (CRSsNP) patients, and 30 healthy controls (HC) were enrolled in this study, and serum and tissue samples were collected. Serum and tissue S100A4 levels were detected by enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, western blotting and immunofluorescence. Their clinical values in predicting postoperative recurrence of CRSwNP were evaluated by multivariate analysis and ROC curves. Serum levels of S100A4 were notably increased in the CRSwNP group than in the CRSsNP and HC groups (p < 0.05), and positively correlated with tissue and peripheral eosinophil count and percentage (p < 0.05). The serum S100A4 concentrations were significantly elevated in the Eos CRSwNP group in comparison with the non-Eos CRSwNP group (p < 0.05). Multivariate analysis and ROC curve presented that serum S100A4 levels were associated with CRSwNP endotypes. Additionally, tissue S100A4 mRNA and protein levels were significantly enhanced in the CRSwNP group than in the HC group and CRSsNP group, especially in the Eos CRSwNP group. Our results demonstrated that the S100A4 expression was increased in CRSwNP patients and associated with the endotypes. S100A4 could be a serologic biomarker for evaluating tissue eosinophilic inflammation and predicting endotypes in CRSwNP patients.

Individual SNOT-22 Items Aid in Differentiating Between Spontaneous Cerebrospinal Fluid Rhinorrhea and Chronic Rhinosinusitis Without Nasal Polyps.

Spontaneous cerebrospinal fluid (CSF) rhinorrhea is a diagnostic challenge due to its overlapping symptomatology with other sinonasal diseases. The objective of this study was to investigate whether items on the sinonasal outcome test (SNOT)-22 could suggest a diagnosis of spontaneous CSF rhinorrhea versus chronic rhinosinusitis without nasal polyps (CRSsNP). A multi-institutional retrospective chart review of patients with spontaneous CSF rhinorrhea and a control group of CRSsNP patients was performed. Individual SNOT-22 scores and domain scores were compared. One hundred fifteen patients were included in both cohorts. Of the patients in the CSF rhinorrhea group, 48% were misdiagnosed as chronic rhinosinusitis (CRS) prior to the correct identification of a CSF leak. On bivariate analysis, the CSF rhinorrhea group scored significantly higher on the SNOT-22 for runny nose (P < .001) and was more likely to designate this symptom as most important (P < .001). The CRSsNP group scored significantly higher in nasal blockage (P < .001), thick nasal discharge (P < .001), facial pain/pressure (P < .001), and in the ear/facial (P < .001) and rhinologic (P = .003) domains. Multivariable logistic regression revealed that runny nose (P < .001) was most predictive of spontaneous CSF rhinorrhea while nasal blockage (P < .001), thick nasal discharge (P < .001), and facial pain/pressure (P = .001) were predictive of CRSsNP after adjusting for relevant confounders. No significant difference was observed in total SNOT-22 scores between groups (P = .676). Spontaneous CSF rhinorrhea is commonly misdiagnosed as other sinonasal pathologies. However, individual SNOT-22 items can help aid in suggesting a CSF leak. Spontaneous CSF rhinorrhea should be suspected in patients who have high SNOT-22 scores for runny nose and report this symptom as most important, but have lower scores related to the other cardinal symptoms of CRS.

The role of serum macrophage migration inhibitory factor in preoperative prediction of chronic rhinosinusitis with nasal polyps endotypes

BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease and can be categorized into eosinophilic CRSwNP (eCRSwNP) and non-eosinophilic CRSwNP (neCRSwNP). Exploring effective biomarkers to distinguish endotypes is important for personalized therapies. The present study aims to evaluate the predictive value of serum MIF in CRSwNP endotypes. MethodsOne hundred and twenty CRSwNP patients, including 51 eCRSwNP and 69 neCRSwNP, 40 chronic rhinosinusitis without nasal polyps (CRSsNP) patients and 40 healthy controls (HC) were enrolled. Serum MIF levels were determined by enzyme-linked immunosorbent assay (ELISA). The patients’ clinical variables were analyzed for correlations with serum MIF. Receiver operating characteristic (ROC) curve and multivariate analysis were utilized to assess the predictive value of serum MIF in CRSwNP endotypes. ResultsThe serum MIF levels were significantly higher in CRSwNP group than CRSsNP group and HC group (P < 0.001), and the serum MIF levels were increased in eCRSwNP compared to neCRSwNP group (P = 0.006). Elevated serum MIF levels were significantly correlated with blood eosinophil (B-EOS) count (r = 0.411, P < 0.001), B-EOS percentage (r = 0.377, P < 0.001), visual analog scale score (r = 0.204, P = 0.025), tissue eosinophil (T-EOS) count (r = 0.705, P < 0.001) and T-EOS percentage (r = 0.671, P < 0.001) in CRSwNP patients. ROC curve demonstrated that serum MIF exhibited good preoperative prediction in CRSwNP endotypes (area under the curve = 0.925, P < 0.001). Multivariate regression analysis showed that serum MIF was an independent factor associated with CRSwNP endotypes. ConclusionsThis was the first study identifying serum MIF as a possible specific biomarker for preoperatively distinguishing CRSwNP endotypes. Furthermore, the serum MIF levels were found to be closely associated with the degree of mucosal eosinophil infiltration.

Long term outcomes of balloon sinuplasty for the treatment of chronic rhinosinusitis with and without nasal polyps

ObjectivesThe aim of this study was to evaluate the 4-year outcomes and effectiveness of balloon sinuplasty in the treatment of chronic rhinosinusitis (CRS). Material and methodsWe evaluated the long-term outcomes in terms of symptoms, nasal endoscopy and computed tomography of 110 patients with CRS submitted to balloon sinuplasty in Centro Hospitalar do Funchal retrospectively.Sinus symptoms were determined by the Sino-Nasal Outcome Test (SNOT-22), endoscopic examination determined by Modified Lund Kennedy score (MLK) and computerized tomography scan of paranasal sinuses (CT-PNS) was evaluated through Lund Mackay scores (LM).Data was collected from 82 patients with chronic rhinosinusitis without nasal polyps (CRSsNP) and from 28 patients with nasal polyps (CRSwNP). ResultsLocal anesthesia procedures were performed in 45.5% of the patients.First follow up was obtained at 2 years (median 22.45 ± 13.6 months) and at 4 years (median 44.45 ± 14 months) after balloon sinuplasty.The mean baseline SNOT-22 score was of 50.26 ± 15.33 for patients with CRSsNP and 52.25 ± 18.06 in CRSsNP patients. Both scores were reduced to 7.00 ± 13.5 and 10.00 ± 22.50 at 4 years follow-up respectively. Baseline MLK score was 4.90 ± 2.12 for patients in CRSsNP group and 10.00 ± 2.00 in the CRSwNP group Both scores were reduced to 1.65 ± 1.67 and 4.86 ± 2.16. The overall mean average LM CT-PNS score was 8.71 ± 4.728 preoperatively for the CRSsNP and 16.18 ± 3.9 in patients with CRSwNP and were reduced to 1.00 ± 1.75 and 8.69 ± 4.6 after BSP.SNOT 22, MLK and LM scores showed consistent improvement over baseline at all time points until the end of the study (median 44.45 ± 14 months).Significant improvements were recorded at all time points in the patient's symptom score, nasal endoscopy scores and imaging scores (P < 0.0001). ConclusionBalloon sinuplasty appears to be safe and effective for the treatment of CRS with great long-term outcomes.

Microbiology of chronic rhinosinusitis with different clinical phenotypes

Objective:To observe the microbiological characteristics and clinical correlation of chronic rhinosinusitis with different clinical phenotypes. Method:One hundred and ninety-six patients with chronic rhinosinusitis（CRS） underwent nasal endoscopic surgery, including 126 patients with Chronic rhinosinusitis with nasal polyps（CRSwNP） and 70 patients with chronic rhinosinusitis without nasal polyps（CRSsNP）; 78 patients with nasal septum deviation（control group） were enrolled. The nasal discharge samples were collected before operation, and the bacteria were isolated and identified by the traditional culture method. The bacteria were compared between the two groups by Pearson chi-square test or Fisher exact test, and the bacteria were compared between groups by Kruskal-Wallis rank sum test. Out statistically significant variables（P<0.05）. Result:The total bacterial detection rate was 73.0% in the three groups, 76.2% in the CRSwNP group, 68.6% in the CRSsNP group and 71.8% in the control group, respectively（P=0.579）. The detection rate of the bacteria was mainly Gram-positive bacteria. The higher detection rate included: Staphylococcus epidermidis, Pseudodiphtheria, Staphylococcus aureus, Haemophilus influenzaemola, Haemella influenzaemola. The detection rate of Haemophilus influenzae in the CRSwNP group and the control group（13.5% vs 2.6%, P=0.009）, but there were statistical differences CRSsNP.There was no statistically significant difference in the detection rate of the bacteria（8.6% vs 2.6%, P=0.15） between the CRSsNP group and the control group; The difference of staphylococcus aureus detection rate between NonECRSwNP group and ECRSwNP group was statistically significant （9.6% vs 28.1%,P=0.017）.There was no significant difference in staphylococcus aureus detection rate between NonECRSsNP group and ECRSsNP group （9.4% vs 16.7%, P=0.482）. Conclusion:Haemophilus influenzae may be a potential cause of CRSwNP; S. aureus may promote the eosinophilic granulocyte inflammatory response to CRSwNP.

Clinical Characteristics of Patients with Chronic Rhinosinusitis without Nasal Polyps in an Academic Setting

Although patients with chronic rhinosinusitis without nasal polyps (CRSsNP) represent a majority of the chronic rhinosinusitis (CRS) population, they have not been completely characterized phenotypically. To perform a comprehensive phenotypic characterization of subjects with CRSsNP, using CRS with nasal polyps (CRSwNP) as a comparator. Patients with a history of CRS with positive sinus computed tomography (>18 years old) evaluated in the allergy/immunology or otolaryngology clinics of an academic center between 2002 and 2012 were identified via International Classification of Diseases, Ninth Revision codes. A retrospective chart review was performed on a subset of 507 patients with CRSsNP and 874 with CRSwNP. Characteristics analyzed included demographics, comorbid conditions, and radiologic sinus severity. Of the total CRS population, approximately 82% had CRSsNP and 18% had CRSwNP. Of the 507 patients in the CRSsNP group, 319 (63%) were female compared with 393 of 847 (45%) in the CRSwNP group. The prevalence of atopy was 52% in CRSsNP versus 76% in CRSwNP (P < .0001). In CRSsNP, atopic patients had more severe radiographic disease compared with nonatopic patients (P < .005). The prevalence of asthma was 36% in CRSsNP versus 56% in CRSwNP (P < .0001). Comorbid asthma was not associated with radiographic sinus disease severity in CRSsNP but was associated with severity in CRSwNP (P < .0001). The relative prevalence of CRS phenotypes in the western population is approximately 80% CRSsNP and 20% CRSwNP. Patients with CRSsNP were predominantly female, whereas patients with CRSwNP were predominantly male. The prevalence of asthma was higher in our cohort of patients with CRSsNP than previously described. Atopy was associated with more severe radiographic sinonasal disease in CRSsNP, whereas asthma was not associated with radiographic sinonasal disease severity.

Role of vitamin D in chronic rhinosinusitis: a systematic review and meta-analysis study

BackgroundChronic rhinosinusitis (CRS) is one of the most common diseases with no specific long-term treatment. CRS can present in two phenotypes: chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP). Vitamin D (VD) is considered to have an immunomodulatory role, especially in allergic diseases. Recent studies have found that patients with CRS have VD level lower than normal, especially patients with CRSwNP.AimThe aim of this study was to systematically evaluate and find out whether there is a relationship between serum VD level and CRS and its phenotypes.Materials and methodsUsing Medline database, we conducted a systematic search to find all related articles published up to 31 August 2016 using the keywords Vitamin D, allergic rhinitis, CRSwNP, and CRSsNP and applying certain inclusion and exclusion criteria.ResultsSix articles were included with a total number of participants of 309 with serum VD level. Four comparisons were made. The first comparison showed no statistically significant difference in VD level between the CRSsNP and the control group. The second comparison showed a statistically significantly lower VD level in the CRSwNP group than in the control group. The third comparison showed a statistically significantly lower VD level in the CRSwNP than in the CRSsNP group. The last comparison showed no statistically significant difference in VD level between CRS with or without nasal polyps and controls.ConclusionVD level was significantly low in patients with CRSwNP, which might have a causative relationship. However, there was no relation between VD level and CRSsNP.

GSK-3β activation index is a potential indicator for recurrent inflammation of chronic rhinosinusitis without nasal polyps.

Chronic rhinosinusitis without nasal polyps (CRSsNP) is one of the most common otorhinolaryngologic diseases worldwide. However, the underlying mechanism remains unclear. In this study, the expression of glycogen synthase kinase 3 (GSK‐3) was quantitatively evaluated in patients with CRSsNP (n = 20) and healthy controls (n = 20). The mRNA levels of GSK‐3α and GSK‐3β were examined by qPCR, the immunoreactivities of GSK‐3β and nuclear factor‐κB (NF‐κB) were examined by immunohistochemistry (IHC) staining, and the protein levels of GSK‐3β, phospho‐GSK‐3β (p‐GSK‐3β, s9) and NF‐κB were examined using Western blot analysis. We found that GSK‐3 was highly expressed in both CRSsNP and control groups without significant difference in both GSK‐3β mRNA and protein levels. However, when compared with healthy control group, the GSK‐3β activation index, defined as the ratio of GSK‐3β over p‐GSK‐3β, was significantly decreased, whereas the NF‐κB protein abundance was significantly increased in CRSsNP group (P < 0.05). Strikingly, the GSK‐3β activation index, was highly correlated with NF‐κB protein level, as well as CT scores in CRSsNP group (P < 0.05). It was also highly correlated with the mRNA expressions of inflammation‐related genes, including T‐bet, IFN‐γ and IL‐4 in CRSsNP group (P < 0.05). Our findings suggest that GSK‐3β activation index, reflecting the inhibitory levels of GSK‐3β through phosphorylation, may be a potential indicator for recurrent inflammation of CRSsNP, and that the insufficient inhibitory phosphorylation of GSK‐3β may play a pivotal role in the pathogenesis of CRSsNP.

Relationship and significance among IL-6,PI3K/Akt and GSK 3β in chronic rhinosinusitis

Objective:To explore the relationship and significance among the expressions of cytokines IL-6，PI3K/Akt signaling transduction pathway, and GSK3β in chronic rhinosinusitis.Method:The proteins for IL-6,PI3K,Akt,GSK3β were assayed by Western blot, and mRNAs of cytokines IL-6,IL-6 receptor were measured by real-time quantitative polymerase chain reaction(qPCR) in nasal tissue from the patients with chronic rhinosinusitis with nasal polyps(CRSwNP),chronic rhinosinusitis without nasal polyps(CRSsNP) and control subjects. Result:IL-6,PI3K,Akt,GSK3β proteins in CRS were higher than those in the control subjects, the differences were statistically significant(P<0.05). There was no significant difference between the groups of CRSsNP and CRSwNP. There were significant differences of cytokines IL-6 mRNA expression between CRSsNP, CRSwNP and control group(P<0.05).IL-6 exists in two forms glycosylated(55 kd) and non-glycosylated(25 kd) in CRS. CRSsNP group mainly glycosylated (glycosylated and non-glycosylated protein expression ratio is about 2.4：1)，CRSwNP group mainly non-glycosylated(glycosylated and non-glycosylated protein expression ratio values about 0.4：1).There was a positive correlation trend among the expressions of IL-6,PI3K,Akt and GSK3β in CRS. Conclusion:The abnormal expressions of IL-6,PI3K,Akt and GSK3β in the nasal mucosa of CRS may play a pro-inflammatory role in the occurrence and development of CRS. The glycosylated IL-6 and the non-glycosylated IL-6 may be both involved in the inflammation of CRS.

Distinct mucosal immunopathologic profiles in atopic and nonatopic chronic rhinosinusitis without nasal polyps in Central China.

The role of atopy to aeroallergens in chronic rhinosinusitis without nasal polyps (CRSsNP) remains unclear. This study aimed to investigate the mucosal immunopathologic characteristics of CRSsNP with and without atopy to inhalant allergens. Thirteen nonatopic CRSsNP patients, 9 atopic CRSsNP patients, and 11 nonatopic control subjects were enrolled in this study. The expression of type 1, 2, and 17 cytokines, growth factors, and chemokines for T cell subsets and granulocytes in sinonasal mucosa was detected using Bio-Plex suspension chip technology or enzyme-linked immunosorbent assay (ELISA). Subjective symptoms were scored on a visual analogue scale (VAS), while disease severity on computed tomography (CT) was graded by the Lund-Mackay CT scoring system. There was no significant difference in VAS and CT scores between atopic and nonatopic CRSsNP. Compared with control, both atopic and nonatopic CRSsNP demonstrated increased interferon γ (IFN-γ) levels in sinonasal mucosa. In contrast, although no difference in interleukin 5 (IL-5), IL-13 and eotaxin-1 expression, or mucosal eosinophil infiltration, was found between the control and whole CRSsNP group, atopic CRSsNP manifested an increased expression of IL-5, IL-13 and eotaxin-1, as well as an enhanced infiltration of mucosal eosinophils in comparison with control and nonatopic CRSsNP. Mucosal eosinophil infiltration correlated with IL-5 and eotaxin-1 expression. No difference in IL-12, IL-4, IL-6, IL-17A, IL-8, myeloperoxidase, "regulated upon activation normal T cell expressed and presumably secreted" (RANTES), or chemokine (C-X-C motif) ligand 10 (CXCL10) protein expression was found among control, atopic CRSsNP, and nonatopic CRSsNP. Atopic and nonatopic CRSsNP have distinct mucosal immunopathologic profiles. CRSsNP is a heterogeneous disorder consisting of multiple groups of biological subtypes, or "endotypes," which may argue for different therapeutic strategies.

Surfactant proteins A and D are related to severity of the disease, pathogenic bacteria and comorbidity in patients with chronic rhinosinusitis with and without nasal polyps.

Surfactant proteins (SP) A and D play a critical role in the innate defence of respiratory mucosa. Although numerous studies have focused on the importance of surfactant in the lower airways, relatively little is known about its role in the upper respiratory system. The prospective study was conducted with 61 subjects divided into patients with chronic rhinosinusitis with nasal polyps (CRSwNP), with chronic rhinosinusitis without nasal polyps (CRSsNP) and healthy controls. SP-A and SP-D were detected in nasal lavage fluid (NALF) by ELISA and in nasal mucosa by immunohistochemical staining. Severity of the diseases assessed by preoperative CT score, presence of comorbidity (allergy and bronchial asthma) and bacterial culture from the middle nasal meatus was evaluated. In nasal mucosa, SPs were localised in ciliated cells of the surface epithelium and serous acini of the submucosal glands. Stronger expression of SPs in submucosal glands was observed in CRSwNP and CRSsNP groups in comparison with controls. In patients with CRSsNP and more severe form of the disease, higher levels of SP-A and SP-D in NALF and stronger immunoreactivity of these proteins in nasal mucosa were detected. Identification of pathogenic bacteria was associated with higher levels of SP-A and SP-D in NALF and nasal mucosa in patients with CRSsNP and control group. Presence of allergy was associated with stronger expression of SP-A in submucosal glands in all CRS patients and with decreased levels of both SPs in NALF in CRSsNP patients. Surfactant proteins A and D play an important role in innate host defence of upper respiratory tract. Different expression of these proteins in patients with chronic rhinosinusitis indicates possible novel target of therapy in these patients.