Chronic Rhinosinusitis Without Nasal Polyps Research Articles

Olfaction in COPD.

Olfaction is poorly characterized in COPD. To test the hypothesis that olfaction is reduced in COPD, we assessed olfaction with the "Sniffin' Sticks" test and a questionnaire addressing olfaction in COPD and a corresponding control group in respect to age and sex. We also explored whether there is an association between COPD, chronic rhinosinusitis without nasal polyps (CRSsNP), and other predefined covariates with olfactory function. Olfactory function was assessed by the score for threshold (T), discrimination (D) and identification (I), and the composite TDI score in the "Sniffin' Sticks" test and by self-reported evaluation of impaired olfaction and of "decreased sense of smell and taste" in the 22-item Sino-Nasal Outcome Test (SNOT-22) in 90 COPD patients and 93 controls. A clinical interview and ENT-examination with nasal endoscopy, skin prick test and spirometry with reversibility were performed. The TDI, D and I scores were significantly lower in the COPD group than in the control group. The T score was not significantly different between the two groups. Hyposmia and anosmia were present in up to 79% of patients with COPD. The prevalence of self-reported impaired olfactory function and for "decreased sense of smell and taste" - was more than two-fold greater in the COPD than in the control group. COPD, higher age, male sex and allergy were associated with a lower TDI score, while CRSsNP was not associated with the TDI score. COPD is associated with olfactory dysfunction and the underlying mechanisms for this dysfunction should be elucidated.

The expression and significance of TRPM8 among chronic rhinosinusitis with nasal polyps

Objective: To compare the expression and difference of melastatin-related transient receptor potential 8(TRPM8) among chronic rhinosinusitis, nasal polyps and normal mucosa tissues. And to explore the significant expression of TRPM8 among CRSwNP. Methods: Fifty-one patients underwent endoscopic sinus surgery in the Department of Otorhinolaryngology Head and Neck Surgery of Renmin Hospital of Wuhan University from February 2019 to January 2020 were recruited, including 33 males and 18 females, aged from 14 to 65 years old (34.55±1.689).Immunohistochemistry was used to detected the expression of TRPM8 protein among CRSsNP(17),CRSwNP (17) and control tissuses(17). In addition, the correlation between the expression of TRPM8 protein in CRSwNP patients and preoperative CT Lund-Mackay scores and preoperative VAS scores and sinonasal outcome test-20 scores was analyzed, respectively. The primary human nasal epithelial cells were cultured in vitro and the expression of TRPM8 was detected by quantitative real-time PCR and western blotting. The tissue in control group, chronic rhinosinusitis without nasal polyps (CRSsNP) group and the CRSwNP group were collected and grinded into tissue homogenized. The expression of TRPM8 protein was detected by western blotting after 24 h stimulation after homogenate was added into the medium of RPMI 2650 and primary nasal epithelial cells. Results: Compared with the control, the expression of TRPM8 was significantly up-regulated in nasal polyps (t=6.852, P<0.05). TRPM8 was mainly expressed in epithelial cells. The expression of TRPM8 in the epithelial cells of CRSsNP had no difference with the control group (t=1.980, P>0.05). In addition, the expression of TRPM8 in CRSwNP patients was positively correlated with the preoperative CT Lund-Mackay scores and VAS scores and SNOT-20 scores (r=0.512, P<0.05;r=0.853, P<0.01;r=0.814, P<0.01). After cultured primary epithelial cells in vitro, the expression level of TRPM8 in epithelial cells derived from nasal polyp was significantly higher than that in control group (t=8.845, P<0.05). By adding the homogenization of control and CRSsNP and CRSwNP tissues, the expression of TRPM8 in RPMI 2650 cells and primary nasal epithelial cells was changed and that was significantly increased after adding the homogenization of the group of CRSwNP. Conclusion: TRPM8 is highly expressed in nasal polyps epithelial cells, suggesting that TRPM8 may be involved in the pathogenesis of nasal polyps regulated by nasal epithelial cells.

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.

Eosinophils Correlate with Epithelial-Mesenchymal Transition in Chronic Rhinosinusitis with Nasal Polyps

Introduction: Chronic inflammation and tissue remodeling always occur together in chronic rhinosinusitis (CRS). Epithelial-mesenchymal transition (EMT) plays a critical role in airway remodeling. Objective: Changes of epithelial cells in sinus mucosa in different subtypes of CRS, especially in eosinophilic chronic rhinosinusitis with nasal polyps, and the role of EMT and eosinophils (EOS) in airway remodeling are still unknown. Methods: We included 85 patients in this study. They were divided into 4 groups: a normal control (NC) group, a chronic rhinosinusitis without nasal polyps (CRSsNP) group, an eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) group, and a noneosinophilic chronic rhinosinusitis with nasal polyps (non-ECRSwNP) group. Clinical data were all collected and analyzed. Standard hematoxylin and eosin staining, immunohistochemical staining, and 2-color immunofluorescence staining were performed. Biomarkers of EMT, epithelial cadherin, and vimentin were labeled. The immunohistochemistry results of each group were counted and statistically analyzed. Results and Conclusion: E-cadherin was downregulated, and vimentin was upregulated in epithelial tissue from the ECRSwNP group, compared with that from the control group and the other groups. The number of vimentin-expressing epithelial cells correlated with sinus CT imaging Lund-Mackay scores (r = 0.560, p < 0.001). Moreover, expression levels of vimentin in the epithelium were associated with numbers of infiltrating EOS in tissues (r = 0.710, p < 0.001) and the peripheral blood EOS ratio (r = 0.594, p < 0.001). EMT occurred in patients with CRSwNP, especially in those with ECRSwNP. Epithelial reprogramming correlates with eosinophil infiltration and disease severity. Eosinophils contributed to impairment of epithelial function and promoted EMT in CRSwNP.

Cytokine-Induced Modulation of SARS-CoV2 Receptor Expression in Primary Human Nasal Epithelial Cells.

Background: Viral entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) via the spike protein enables endocytosis into host cells using the ACE2 receptor and TMPRSS2. The frequent upper respiratory tract symptoms of COVID-19 and the localization of the virus to the nasopharynx, the most common site of swabbing, indicate that the sinonasal mucosa may play an important role in SARS-CoV2 infection and viral replication. Methods: This paper investigates the presence of ACE2 receptor and TMPRESS2 expression in the primary human nasal epithelial cells (HNECs) from the following: chronic rhinosinusitis without nasal polyps (CRSsNP), CRS with nasal polyps (CRSwNP) and control (non-CRS) patients, and maps the expression changes when exposed to Th1, Th2, Th17-associated cytokines. Results: We found that ACE2 and TMPRSS2 expression was higher in control HNECs than CRSwNP HNECs, and that both ACE2 and TMPRSS2 were downregulated further by Th2 cytokines in CRSwNP HNECs. Conclusions: This indicates an immune dysregulated state of CRSwNP mucosa, which normally contributes to a chronic inflammatory state, and might support an altered susceptibility to SARS-CoV2 infection and transmission.

Upregulation of Basonuclin1 Is Associated with p63-Involved Epithelial Barrier Impairment and Type-2 Helper T-cell Inflammation in Chronic Rhinosinusitis with Nasal Polyps

Background: Tumor protein p63 has been shown to be important for epithelial dysfunction, including epithelial barrier defects and mucosal inflammation, in the development of chronic rhinosinusitis with nasal polyps (CRSwNP). Basonuclin1 (BNC1), an epithelial-specific transcriptional factor, is a direct downstream target of p63 and thus might be involved in the pathogenesis of CRSwNP. Objective: We sought to investigate whether BNC1 was associated with p63-mediated epithelial barrier defects and nasal mucosal inflammation in CRSwNP. Methods: Nasal tissue biopsies were obtained from 91 patients to CRSwNP, 49 chronic rhinosinusitis without nasal polyps (CRSsNP) patients, and 28 control subjects. Immunohistochemistry and immunofluorescence staining were used to determine the distribution of BNC1 in tissues and localization in cells, respectively. Quantitative PCR was performed to detect the expression levels of BNC1, TP63, epithelial barrier proteins, and type-2 helper T-cell inflammation-related genes. Results: BNC1 mRNA expression was significantly elevated in the tissues in CRSwNP patients compared with CRSsNP (1.96-fold, p = 0.0003) and control groups (2.40-fold, p < 0.0001). BNC1 staining was strongly positive in the nasal epithelium and co-localized with p63-positive epithelial cells. The expression of BNC1 mRNA was strongly correlated with TP63 mRNA level both in tissue biopsies (r = 0.78, p < 0.0001) and epithelial scrapings (r = 0.97, p < 0.0001). BNC1 expression was also positively correlated with epithelial barrier protein genes (CDH1, CLDN1, CLDN4, TJP1, and TJP2) and epithelial genes involved in T_H2 inflammation (IL33, CCL26, CLC, and ALOX15). Conclusions: Overexpression of BNC1 may be associated with increased expression of TP63, and possibly contribute to the epithelial barrier defects and T_H2 inflammation in CRSwNP.

Short-term Oral Steroids Significantly Improves Chronic Rhinosinusitis Without Nasal Polyps.

The efficacy of short-term oral corticosteroids in chronic rhinosinusitis without nasal polyps (CRSsNP) is unknown. The aim of this controlled study was to assess the immediate and long-term outcomes from a short course of a commonly used oral corticosteroid, prednisolone, in well-defined CRSsNP patients. Prospective, observational controlled study. A prospective-controlled study of CRSsNP patients treated with prednisolone at 0.5 mg/kg tapered over 10 days and non-prednisolone treated CRSsNP patients (controls) and follow-up at 2, 6, and 12 months. Baseline and follow-up SinoNasal Outcome Test (SNOT)-22, nasal endoscopy (Lund-Kennedy), and sinus CT scan scores (Lund-Mackay) were compared. At 2 months, there was a significant improvement in the SNOT-22, nasal endoscopy, and sinus CT scan scores in the prednisolone group (P < .0001) compared with controls (p=ns, Mann-Whitney U test). 52.5% of prednisolone-treated CRSsNP patients had improved symptoms and did not require sinus surgery at 12 months compared with 14.3% of controls (P < .001). Side-effects were reported in 8.9% of prednisolone-treated patients. Patients who benefited from prednisolone had a median symptom duration of 7.25 (99% confidence, upper limit of 11) months compared with 18 months in those requiring surgery. Short-term oral prednisolone significantly improved all three clinical measures of disease in CRSsNP patients and avoided surgical intervention in 52.5% patients in the first 12 months. Patients with symptoms for less than 11 months were most likely to benefit. The side-effects of oral steroids require careful consideration and further studies are needed to ascertain appropriate dosage and treatment duration. 3 Laryngoscope, 131:E2618-E2626, 2021.

Mucin 5AC is significantly upregulated in exosomes from the nasal lavage fluid and may promote the expression of COX-2, VEGF and MMP-9: an implication in nasal polyp pathogenesis

BACKGROUND: Exosomes are critical mediators of intercellular communication and could be involved in many human diseases; however, little is known about the role of exosomes in nasal polyps (NP). METHODS: Exosomes in nasal lavage fluids (NLF) were isolated by ultracentrifugation. Exosome identity was validated by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and specific exosomal markers. The exosome proteome was revealed by LC-MS/MS, and the expression of the candidate exosomal protein, mucin 5AC, was confirmed by Western blot analysis and immunohistochemistry (IHC). Cellular uptake of the exosomes was monitored by fluorescence confocal microscopy and the ensuing effects on COX-2, VEGF and MMP-2/MMP-9 were determined by Western blotting, ELISA and gelatin zymography, respectively. RESULTS: Mass spectrometry analysis and subsequent verification by Western blotting identified that mucin 5AC was significantly upregulated in exosomes from NLFs of NP patients. Moreover, the expression of mucin 5AC was increased in the tissue specimens of the NP patients. Functional assays suggest that the mucin 5 AC-enriched exosomes could be effectively taken up by chronic rhinosinusitis without NP (CRSsNP)-derived fibroblasts, the control cells, resulting in a significant increase in the expression of COX-2, VEGF and MMP-9. CONCLUSIONS: Mucin 5AC, the major airway mucin, cannot only be carried and transferred by nasal exosomes, but may also promote tissue remodeling and angiogenesis and thus could be a potential therapeutic target of NP.

Liver X Receptor Expression and Pentraxin 3 Production in Chronic Rhinosinusitis and Sinonasal Mucosal Fibroblast Cells.

The long pentraxin 3 (PTX3) is a prototypic molecule for recognizing pathogens. Liver X receptors (LXRs), belonging to nuclear receptors (NRs) for cholesterol metabolism through heterodimerizing with other NRs, were recently reported to participate in inflammation. However, their roles in chronic rhinosinusitis without nasal polyps (CRSsNP) are unclear. Therefore, this study was sought to explore roles of LXRs in chronic rhinosinusitis (CRS) sinonasal tissues and derived fibroblasts. Immunohistochemistry indicated that LXRα and β expression and lipid/fat deposition were differentially expressed in the control and CRSsNP nasal mucosa. GW7647 (a peroxisome proliferator activated receptor α (PPARα) agonist) and GW3965 (a dual agonist for LXRα and β) significantly caused PTX3 induction in the fibroblast cells. GW3965 induced PTX3 mRNA and protein expression, and the induction substantially led to PTX3 secretion. Meanwhile, an endogenous agonist-cholesterol had a similar enhancing effect on the induction of PTX3 protein. LXR siRNA knockdown to lower LXRα or β expression significantly compromised PTX3 induction. Interestingly, GW3965 also induced phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) activation and its inhibition reduced PTX3 expression. Collectively, we demonstrated here for the first time that CRSsNP nasal mucosa differentially expresses LXRα and β and deposits lipids/fats that may contain cholesterol metabolites to activate LXRs. Activation of LXRs leads to PTX3 production in sinonasal mucosa-derived fibroblasts. Our previous study showed PTX3 overexpression in the nasal cavity of CRSsNP, whereas this study highlights that cholesterol metabolites and LXR activation regulate PTX3 production and may contribute to antimicrobial activity and tissue repair during CRSsNP progression.

Role of specific IgE on staphylococcal enterotoxin B in chronic rhinosinusitis severity.

To investigate the clinical significance of specific IgE-staphylococcal enterotoxin B (IgE-SEB) in CRS (chronic rhinosinusitis). Retrospective analysis of patients who were positive for specific IgE-staphylococcal enterotoxin B. Tertiary rhinology clinic. A total of 965 patients who were tested for specific IgE-staphylococcal enterotoxin B from December 2016 to December 2017. We retrospectively reviewed the records of 965 patients who were tested for specific IgE-staphylococcal enterotoxin B from December 2016 to December 2017. Patient demographics, titre-specific IgE to staphylococcal enterotoxin B levels, MAST, serologic test and medical records were reviewed. IgE-SEB (KU/L) was higher in CRS patients than non-CRS patients (0.13±0.37 vs 0.08±0.22, respectively; P-value: .044), and the IgE-SEB (+, ≥0.35) rate was also higher (10.06% vs 4.46%, respectively; P-value: .030). IgE-SEB(KU/L) was higher in the CRS group than in the fungal sinusitis group (0.13±0.37 vs 0.03±0.05, respectively; P-value: <.001), and the IgE-SEB (+, ≥0.35) rate was also higher (10.06% vs 0%, respectively; P-value: .015). Between the CRSsNP (chronic rhinosinusitis without nasal polyps) and CRSwNP (chronic rhinosinusitis with nasal polyps) groups, there were no differences in IgE-SEB (KU/L) or IgE-SEB (+) rates. IgE-SEB positivity was not associated with the presence of polyps, concomitant asthma or postoperative recurrence. As the values of IgE-SEB (KU/L) and the IgE-SEB (+, >0.1) rate increased, the CRS severity also increased. IgE-SEB showed a positive correlation with Lund-Mackay CT severity score, but not with postoperative recurrence or nasal polyps. Further studies are needed to obtain clear evidence that IgE-SEB can be considered as an independent CRS endotype.

Pre-treatment clinical study of rhinosinusitis impact on the quality of life among patients having both external nasal deformity and deviated nasal septum

&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Sino-nasal disease often gives an experience of impacting quality of life significantly, more so among chronic cases. Hence a self-perceived disease specific impact viz rhinosinusitis disability index (RSDI) which is a validated reliable measure of quality of life is being studied.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A prospective study conducted on patients, attending department of ENT on out and or in-patient basis who are diagnosed to have rhinosinusitis with external nasal deformity and deviated nasal septum (DNS) were selected on simple random basis for this study between July 2018 to November 2019. This study group subjected for answering standard questionnaire of RSDI proforma before treatment. Data statistically analyzed using IBM SPSS version 22.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among the statistically calculated ‘n' (40) patients of this study, 23 were male (57.5%) and 17 were female (42.5%) patients of the age between 15-45 years. In our study, majority of patients (n=23) had simple type DNS (57.5%), followed by obstructive type 37.5% (n=15) and impacted type 5% (n=2) and majority of patients showed type I (50%) external nasal deformity followed by type V (25%). In our study, 11 patients were diagnosed with acute rhinosinusitis, 15 patients with chronic rhinosinusitis without nasal polyps (CRSsNP) and 14 patients with chronic rhinosinusitis with nasal polyps (CRSwNP). The physical, functional and emotional domains showed no statistical significance with respect to external nasal deformity and DNS. However, disease factor had statistically significant impact (p&amp;lt;0.05) on the quality of life among rhinosinusitis patients with mean scores of 13.7, 19.42, and 10.80.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In rhinosinusitis patients, the disease affects the quality of life in terms of physical, functional and emotional domains, but not by the external nasal deformity and or DNS associated.&lt;/p&gt;

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.

P63+Krt5+ basal cells are increased in the squamous metaplastic epithelium of patients with radiation-induced chronic Rhinosinusitis

BackgroundSquamous metaplasia (SM) is an irreversible form of airway epithelial remodeling. Hyperproliferation of basal cells was observed in squamous metaplastic epithelium of chronically inflamed airway. However, the association of such aberrant proliferation of basal cells with SM in the nasal epithelium after radiation damage remains unclear. The aim of this study was to investigate SM and accompanying levels of p63+Krt5+ (basal cell markers) cells in the nasal epithelium of patients with radiation-induced chronic rhinosinusitis (CRSr) and patients with chronic rhinosinusitis without nasal polyps (CRSsNP) compared to healthy controls.MethodsWe assessed the prevalence of SM and the expression of p63+, Krt5+, p63+Krt5+, and Ki67+ cells through immunofluorescence(IF) staining of the inferior turbinate (IT) tissues from patients with CRSr (n = 36), CRSsNP (n = 33) and controls (n = 28).ResultsThe prevalence of SM and the number of p63+Krt5+ cells were both significantly increased in patients with CRSr compared to patients with CRSsNP and controls. The number of Ki67+ cells were both significantly increased in patients with CRSr and CRSsNP compared to controls, but the ratio of Ki67+ cells to p63+Krt5+ cells was significantly lower in patients with CRSr compared to patients with CRSsNP. In patients with CRSr, an increased number of p63+Krt5+ basal cells was observed in SM epithelium compared to non-SM epithelium.ConclusionSM is increased in the nasal epithelium of patients with CRSr, in which aberrant levels of p63+Krt5+ basal cells serves as an important pathologic feature in the squamous metaplastic epithelium.

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.

Type 2 inflammation in chronic rhinosinusitis without nasal polyps: Another relevant endotype

Chronic rhinosinusitis without nasal polyps (CRSsNP) is mainly considered a type 1 mediated disease. The role and clinical significance of type 2 immune responses in CRSsNP have not been addressed sufficiently; a recent cluster analysis for CRS described the existence of a subgroup of patients with CRSsNP with a type 2 inflammation. We aimed to characterize the underlying type 2 immune response and its clinical significance in patients with CRSsNP. A total of 240 patients with CRSsNP were endotyped and subdivided on the basis of expression of marker cytokines. Clinical data such as recurrence, comorbid asthma and allergy, and numbers of blood eosinophils and neutrophils were collected from all patients. Aselection of 15 patients was further characterized for the presence of eosinophils, neutrophils, Charcot-Leyden crystals, and eosinophil extracellular traps in the mucosae. A type 2 immune response with increased levels of IL-4, IL-5, eosinophil cationic protein, IgE, and Staphylococcus aureus enterotoxin-specific IgE was observed in 49% of patients with CRSsNP. Those patients showed increased numbers of blood and tissue eosinophils, and they displayed a considerable eosinophilic inflammation associated with eosinophil extracellular trap cell death and Charcot-Leyden crystals. Asignificantly increased prevalence of recurrence and asthma was observed in patients with type 2 CRSsNP compared with in patients with non-type 2 CRSsNP. However, only 4 of 117 patients with type 2 CRSsNP developed nasal polyps within 12 years. This study shows that type 2 immune responses in CRSsNP follow similar patterns but are less pronounced than in chronic rhinosinusitis with nasal polyps. Also CRSsNP with a moderate type 2 immune response showed a considerable eosinophilic inflammation with clinical impact.

Effectiveness of micronized nasal irrigations with hyaluronic acid/isotonic saline solution in non-polipoid chronic rhinosinusitis: A prospective, randomized, double-blind, controlled study.

Sodium hyaluronate has been proposed as a treatment for improving the symptoms of chronic rhinosinusitis. The present study evaluated the effect of the intranasal administration of hyaluronic acid in a group of patients affected by chronic rhinosinusitis without nasal polyps (CRSsNP). Thirty subjects aged 18-65years affected by CRSsNP were enrolled. The subjects were randomly administered hyaluronic acid or isotonic saline solution by nasal nebulizer twice per day for 30days. They were evaluated before (T0) and after the treatment (T1) with Sino-Nasal Outcome Test-22, visual analogue scale for rhinorrhea, nasal obstruction, facial pain and hyposmia/hypogeusia, nasal endoscopy, active anterior rhinomanometry, peak nasal inspiratory flow and nasal cytology. Comparing the study and the control group, at T1 no significant differences were observed in both objective and subjective parameters. Being included in the study group rather than in the control group did not have a significant effect on the variation of the considered parameters between T0 and T1. Considering the effects of the micronized douches independently from the type of solution used (either hyaluronic acid or isotonic saline solution), although no difference emerged between study and control group for any of the objective parameters, there was an improvement of Sino-Nasal Outcome Test-22 scores (p=.0005), visual analogue scale for nasal obstruction (p=.0006) and for hyposmia/hypogeusia (p=.04). The treatment with micronized nasal douches can improve the sino-nasal symptoms of CRSsNP, in particular nasal obstruction and olfactory ability. No advantage of the use of hyaluronic acid over isotonic saline solution emerged.

Expression of long pentraxin 3 in human nasal mucosa fibroblasts, tissues, and secretions of chronic rhinosinusitis without nasal polyps.

Numerous studies have shown that microbiomes play an important role in the pathogenesis of chronic rhinosinusitis (CRS). In addition to a known short pentraxin, C-reactive protein, long pentraxin 3 (PTX3) belongs to pentraxin family which detects conserved microbial pentraxin motifs and mobilizes early defense against foreign invaders, but its participation in CRS remains unclear. In the present study, through an intensive screening, peptidoglycan (PGN) was selected as a main material to investigate the action mechanism of a cell wall component on CRS without nasal polyps (CRSsNP) nasal mucosa-derived fibroblasts and the PTX3 expression in human nasal mucosa tissue and discharge. The PGN not only enhanced PTX3 mRNA and protein production in cells but also caused marked PTX3 secretion into extracellular space. The pharmacological interventions indicated that the PTX3 induction was mediated mainly through toll-like receptor 2 (TLR2), phosphoinositide-phospholipase C (PI-PLC), protein kinase C (PKC), NF-κB, and cAMP response element binding protein (CREB), which was further confirmed by the observations that a direct PKC activator (phorbol ester) had a similar inductory effect on PTX3 expression/production and the siRNA interference knockdown of PKCμ/δ, NF-κB, and CREB compromised PTX3 production. Meanwhile, PTX3 was found to be overexpressed/produced in nasal mucosa and discharge/secretion of the CRSsNP patients. Collectively, we first demonstrated here that PGN enhances PTX3 expression and release in nasal fibroblasts through TLR2, PI-PLC, PKCμ/δ, NF-κB, and CREB signaling pathways. The PTX3 is overexpressed in nasal mucosa and discharge/secretion of CRSsNP patients, revealing its possible importance in CRSsNP development and progression. KEY MESSAGES: Long pentraxin 3 (PTX3) is highly expressed in nasal mucosa and discharge/secretion of patients of chronic rhinosinusitis without nasal polyps (CRSsNP). The bacteria cell wall component-peptidoglycan (PGN) causes PTX3 expression in CRSsNP nasal mucosa-derived fibroblasts, contributing to the PTX3 increase in tissues. PGN induces PTX3 expression through a previously known IκB/NF-κB and a novel PKCμ/δ and CREB signaling pathway. The PTX3 may be used as a biomarker for CRS.

Local inflammatory marker production in Lithuanian patients with chronic rhinosinusitis with nasal polyps

There are two clinical subtypes of chronic rhinosinusitis (CRS): chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP). The aim of the study here was to determine the levels of invasive inflammatory markers in nasal mucosa samples taken from CRSwNP patients during the surgery and to identify markers that could serve as targets for potential clinical and therapeutic interventions. The study was carried out in 59 patients with proven CRSwNP and a control group consisting of 52 healthy individuals. Concentrations of the inflammatory markers of interest were determined using a LuminexR Assay multiplex kit. The data obtained indicated that levels of inflammatory cytokines interleukin (IL)-2, -4, -5, -7, -12, -17 and -22 were all significantly higher in the nasal polyps (NP) than those in the mucosa of control participants. No differences were seen between the study groups for IL -6, -10, -13, -21 and interferon (IFN)-γ. OR (Odds Ratio) analyses confirmed that elevations in mucosal levels of IL-2, -4, -5, -7, -12, -17, and -22 were likely immune markers of CRSwNP. In conclusion, the present study demonstrated that IL-2, -4, -12 and -22 may be important in the etiopathogenesis of CRSwNP; as markers, each show moderate sensitivity, but high specificity in the Lithuanian population. IL-17 had good sensitivity, but low specificity in the CRSwNP patients.

A 10-Year Follow-Up of a Randomized Prospective Study of 2 Treatments for Chronic Rhinosinusitis Without Nasal Polyps and Investigation of the Impact of Gastroeosophageal Reflux Disease in the Resistance to Treatment

To compare the 2 long-term medical strategies in chronic rhinosinusitis without nasal polyps (CRSnNP) and to identify the role of gastroesophageal reflux disease (GERD) and Helicobacter pylori as factors of treatment failure. Fifty-seven patients with CRSnNP were randomized into 2 therapeutic groups. The first group was treated with 4 weeks of amoxicillin/clavulanate and a short course of oral steroids. The second group received 8 weeks of clarithromycin. Sinonasal Outcome Test-20 (SNOT-20) and Lund and Mackay scores were assessed at baseline and after treatment, and GERD Health-Related Quality of Life (GERD-HRQL) questionnaire was evaluated in all patients. Patients with a GERD-HRQL score >8 received esogastroscopy and H pylori detection. Patients were followed during a 10-year period for clinical course and GERD evolution. The 10-year evolution of patients was described in terms of recurrence, medical, and surgical treatments. Thirty-seven patients completed the study; SNOT-20 and Lund and Mackay scores similarly improved in both groups. Amoxicillin/clavulanate group had significantly more adverse reactions than the clarithromycin group (P = .03). After the therapeutic course, 35% (amoxicillin/clavulanate) and 41% (clarithromycin) of patients needed functional endoscopic sinus surgery (FESS). During the long-term follow-up, 54% (amoxicillin/clavulanate) and 40% (clarithromycin) of patients had late CRSnNP recurrence; FESS was performed in less than 15% of cases of recurrence. Gastroesophageal reflux disease complaint's severity was associated with late recurrence of CRSnNP. Amoxicillin/clavulanate and clarithromycin would be competitive treatments for CRSnNP. Gastroesophageal reflux disease seems to be a negative factor for treatment response and recurrence.

γδT cells contribute to type 2 inflammatory profiles in eosinophilic chronic rhinosinusitis with nasal polyps.

Eosinophilic chronic rhinosinusitis with nasal polyps (ECRS) is a condition linked with type 2 inflammation, poor treatment outcomes, and high recurrence tendency. Although γδT cells have been reported to induce type 2 immune responses and eosinophilic infiltration in several diseases, their role in ECRS has not been fully explored. We aimed to evaluate the association of γδT cells with the type 2 inflammatory profiles in ECRS. Nasal tissue samples obtained from patients with chronic rhinosinusitis with nasal polyps (CRSwNP) (51 eosinophilic and 48 non-eosinophilic), 50 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 58 control subjects were examined for γδT cells, inflammatory markers and eosinophils using HE, RT-qPCR, ELISA, immunofluorescence, and flow cytometry. In parallel, studies were also conducted in an ECRS murine model induced by anti-γδT cells neutralizing antibody administration. γδT cells expression was significantly increased in tissues from patients with ECRS compared with non-ECRS, CRSsNP and control subjects. Moreover, inflammatory markers including type 2 proinflammatory cytokines (IL-4, IL-5, IL-13), GATA3, eosinophil cationic protein (ECP), and eotaxin levels were also increased in nasal tissues of patients with ECRS, and Vγ1+ γδT cells mRNA expression was positively correlated with type 2 cytokines, GATA3, and ECP. In the ECRS murine model, anti-Vγ1+ γδT antibody treatment reduced the infiltration of eosinophils and expression of type 2 cytokines, GATA3, and ECP in nasal mucosae. In conclusion, the results of the present study suggest that γδT cells play a crucial role in the type 2 inflammatory profiles and nasal tissue eosinophilic infiltration in patients with ECRS.