Osteomeatal Complex Obstruction is not Associated with Adjacent Sinus Disease in Chronic Rhinosinusitis with Polyps

Heterogeneous inflammatory patterns in chronic rhinosinusitis without nasal polyps in Chicago, Illinois

BackgroundChronic rhinosinusitis (CRS) current therapeutic approaches still fail in some patients with severe persistent symptoms and recurrences after surgery. We aimed to evaluate the master transcription factors gene expression levels of T cell subtypes in chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) that could represent new, up-stream targets for topical DNAzyme treatment.Patients and methodsTwenty-two newly diagnosed CRS patients (14 CRSwNP and 8 CRSsNP) were prospectively biopsied and examined histopathologically. Gene expression levels of T-box transcription factor (T-bet, TBX21), GATA binding protein 3 (GATA3), Retinoic acid-related orphan receptor C (RORC) and Forkhead box P3 (FOXP3) were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR).ResultsEosinophilic CRSwNP was characterized by higher level of GATA3 gene expression compared to noneosinophilic CRSwNP, whereas there was no difference in T-bet, RORC and FOXP3 between eosinophilic and noneosinophilic CRSwNP. In CRSsNP, we found simultaneous upregulation of T-bet, GATA3 and RORC gene expression levels in comparison to CRSwNP; meanwhile, there was no difference in FOXP3 gene expression between CRSwNP and CRSsNP.ConclusionsIn eosinophilic CRSwNP, we confirmed the type 2 inflammation by elevated GATA3 gene expression level. In CRSsNP, we unexpectedly found simultaneous upregulation of T-bet and GATA3 that is currently unexplained; however, it might originate from activated CD8+ cells, abundant in nasal mucosa of CRSsNP patients. The elevated RORC in CRSsNP could be part of homeostatic nasal immune response that might be better preserved in CRSsNP patients compared to CRSwNP patients. Further data on transcription factors expression rates in CRS phenotypes are needed.

The aim of this study was, firstly, to classify patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) into inflammatory endotypes and, secondly, to investigate the relationships between blood and tissue eosinophilia and clinical outcomes in CRSwNP, including disease severity, and recurrence. This cross-sectional, observational, nonrandomized study has been realized between January 2023-December 2024 enrolling a sample of 469 consecutive patients with chronic rhinosinusitis, of which 239 patients with CRSwNP and 230 patients with CRSsNP. The classification of CRSwNP and CRSsNP into inflammatory endotypes was performed by analyzing the levels of blood and tissue eosinophilia. The prevalence of asthma and allergy to nonsteroidal anti-inflammatory drugs (NSAIDs) in the two groups was also analyzed. In the group of patients with CRSwNP, the severity of the disease and the level of quality of life impairment were evaluated, depending on the degree of tissue eosinophilia. The importance of the association between blood vs. tissue eosinophilia and the relapse of CRSwNP was also assessed. The proportion of patients with elevated blood eosinophil levels was higher in CRSwNP than CRSsNP (17.4% vs. 4.35%). Tissue eosinophilia was identified in 163 of 235 (69.4%) patients with CRSwNP compared with 29 of 230 (12.6%) patients with CRSsNP. From an inflammatory perspective, revision surgery was strongly associated with tissue eosinophilia. In contrast, elevated blood eosinophil levels were only moderately associated with revision surgery.

Conclusion: Biofilms were more prevalent in patients with CRSwNP compared to both CRSsNP and controls, and also on the ethmoid bulla compared to the middle turbinate, supporting a biofilm-related pathogenesis of CRSwNP.Objective: To investigate the prevalence of biofilms in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) compared to patients with chronic rhinosinusitis without nasal polyps (CRSsNP) and controls. To examine the prevalence of biofilms in different anatomical localizations.Study design: Cross-sectional.Methods: This study comprised 27 patients with CRSsNP, 34 patients with CRSwNP, and 25 controls. Biopsies from the middle turbinate, the uncinate process, and the ethmoid bulla were harvested pre-operatively, snap frozen in isopentane, cooled, and stored at −80°C. Prepared with Invitrogens’ Baclight LiveDead kit and investigated with confocal scanning laser microscopy.Results: Biofilms were studied in 33/34 (97%) CRSwNP, 22/27 (82%) CRSsNP, and 14/25 (56%) controls. The difference in point prevalence between patients with CRSwNP vs CRSsNP (p = 0.042, χ2 = 4.12), CRSwNP vs Controls (p < 0.001, χ2 = 15.0), and CRSsNP vs controls (p = 0.047, χ2 = 3.96) were all significant. Biofilms were found in 43/54 (80%) ethmoid bulla, 39/55 (71%) uncinate process, and 31/50 (62%) middle turbinate. The difference between the ethmoid bulla and the middle turbinate locations (p = 0.047, χ2 = 3.93) was significant.

Background: As of today, chronic rhinosinusitis (CRS) characterized by inflammatory processes and tissue remodeling of the mucosal lining is classified into two phenotypes: chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP). Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent endopeptidases that play a crucial role in degrading basement membranes and extracellular matrix. MMP-7 and MMP-9 may play significant roles in CRS development. Objective: To determine the level of zinc-dependent endopeptidases in the tissues of patients with CRSwNP and CRSsNP. Materials and Methods: The study included 54 patients meeting the inclusion criteria, among them 12 patients in the control group, and 21 patients each in subgroup A (CRSwNP) and subgroup B (CRSsNP) of the main group. Patients underwent SNOT-22 questionnaire, endoscopic evaluation using the Lund-Kennedy scale, CT scans graded by the Lund-Mackay scale, and levels of MMP-9 and MMP-7 enzymes were determined in surgically removed fragments of pathological tissues. Results: It was found that CRSwNP is more commonly associated with olfactory dysfunction. However, obstruction of the olfactory cleft by polypoid elements, according to CT scans, was observed in only 19.04% of cases (4 out of 21 patients). The level of MMP-7 for the control group was 8.17±5.15 μg/ml, for subgroup A it was 23.67±11.89 μg/ml, and for subgroup B it was 17.93±9.88 μg/ml. Student's t-test revealed no significant difference between subgroups A and B of the main group, p&gt;0.05 (T-statistic: 1.7; p-value: 0.09). However, when compared individually with the control group, a statistical difference was observed in each case, p&lt;0.05. In contrast to MMP-7 data, statistically significant differences were observed when comparing the MMP-9 levels of each group using the t-test, p&lt;0.05. The distribution of mean MMP-9 levels for the groups was as follows: control group – 17.49±8.81 μg/ml, subgroup A – 36.04±16.03 μg/ml, and subgroup B – 26.06±11.04 μg/ml. Conclusions: MMP-9 and MMP-7 are key enzymes involved in the formation of polypoid tissue or pseudocysts in different phenotypes of CRS and influence the severity of the disease's clinical course. Therefore, these endopeptidases could potentially serve as biomarkers for CRS activity and as targets for new therapeutic agents that could inhibit them. Keywords: chronic rhinosinusitis, endoproteases, MMP-9, MMP-7, nasal cavity, nasal mucosa, nasal polyps, nasal cavity pseudocysts.

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common upper airway inflammatory disease with a high postoperative recurrence rate. This study is aimed at exploring the expression of B cell-activating factor (BAFF) in CRSwNP and its association with postoperative recurrence. Methods A total of 80 CRSwNP patients, including 40 primary CRSwNP patients and 40 recurrent CRSwNP patients, 40 chronic rhinosinusitis without nasal polyps (CRSsNP) patients, and 40 healthy controls (HC) were enrolled in this study, and the serum and tissue samples were collected. The circulating and tissue BAFF expressions were detected by enzyme-linked immunosorbent assay reverse transcription-polymerase chain reaction and immunohistochemistry. Their clinical values for predicting postoperative recurrence of CRSwNP were evaluated. Results We determined serum levels of BAFF were remarkably increased in the CRSwNP group than the CRSsNP and HC groups (P < 0.05), and higher concentrations of BAFF were associated with peripheral eosinophil percentage (r = 0.614, P < 0.001). The serum BAFF concentrations were significantly higher in the recurrent CRSwNP group in comparison with the primary group (P < 0.05). Multivariate analysis and receiver operating characteristic (ROC) curve presented that serum BAFF levels were associated with the postoperative recurrence in CRSwNP patients (P < 0.05). Moreover, tissue BAFF levels were significantly increased in the CRSwNP group than the HC group, especially in the recurrent CRSwNP group (P < 0.05), and enhanced BAFF RNA expressions were correlated with serum BAFF levels (r = 0.703, P < 0.001). Conclusion Our results elucidated that the BAFF expression was enhanced in CRSwNP patients and associated with postoperative recurrence. BAFF could be a serologic biomarker for predicting postoperative recurrence in CRSwNP patients.

Objective:To study the expression and role of interleukin-18 (IL-18) in different clinical phenotypes of chronic rhinosinusitis(CRS)and in different subtypes of CRS with nasal polyps (CRSwNP).Method:During nasal endoscopic surgery, inferior turbinates were obtained from 13 patients with nasal septum deviation (control group),uncinate processes were obtained from 10 patients with chronic rhinosinusitis without nasal polyps (CRSsNP) and nasal polyp tissues were obtained from 36 patients with CRSwNP, respectively. IL-5 expression in CRSwNP was detected by ELISA, and the expression of IL-18 mRNA and protein in different subtypes of CRS were assessed by real-time PCR, ELISA and immunohistochemistr.Result:CRSwNP was divided into 12 cases of IL-5 positive nasal polyps (IL-5+NP)group and 24 cases of IL-5 negative nasal polyps (IL-5-NP)group. The expression of IL-18 mRNA and protein in all CRSsNP,IL-5+NP and IL-5-NP groups were higher than that in control group (P<0.01 or P<0.05),but no significant difference existed between IL-5+NP and IL-5-NP (P>0.05) group. IL-18 also expresses in epithelial cells of normal nasal mucosa.Conclusion:CRSwNP can be divided into two main subtypes: IL-5+NP and IL-5-NP. The increasing expression of IL-18 in CRSsNP, IL-5+NP and IL-5-NP compared with control group indicates that IL-18 may play a key role in the pathogenesis of CRS, and IL-18 expression in nasal polyps is not affected by the type of inflammation. The possible presence of balance between IL-18 and IL-18 binding protein in normal nasal mucosa provides a new way for research and treatment of CRS.

The antimicrobial protein short palate, lung, and nasal epithelium clone 1 (SPLUNC1) is differentially modulated in eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyps

T-cell regulation in chronic paranasal sinus disease

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.

Chronic rhinosinusitis without nasal polyps (CRSsNP) and with nasal polyps (CRSwNP) is characterized by persistent inflammation of sinonasal mucosa. Glucocorticoid-induced leucine zipper (GILZ) is a recently described anti-inflammatory mediator. Here we analysed the expression of GILZ in CRSsNP and CRSwNP, its association with response to surgery, and its cytokine-driven expression regulation in the upper airways. Methods The messenger RNA (mRNA) and protein expression of GILZ in 33 CRSsNP, 32 CRSwNP, and 11 control samples was assessed by means of a quantitative RT-PCR and immunohistochemistry, respectively. Nasal explant culture was used to investigate the effect of IFN-gamma, IL-4, IL-13, IL-1beta, and TNF-alpha on GILZ mRNA expression in normal sinonasal mucosa. The GILZ mRNA and protein expression was significantly suppressed in both CRSsNP and CRSwNP patients compared with controls. No significant difference in GILZ expression was found between CRSsNP and CRSwNP patients. Comparing patients responsive and patients recalcitrant to surgery, a significant further decrease of GILZ expression was found in recalcitrant patients both in the CRSsNP and in the CRSwNP group. IL-1beta, TNF-alpha, IL-4, and IL-13 reduced, whereas IFN-gamma enhanced GILZ mRNA levels in the sinonasal mucosa. Down-regulated expression of GILZ may contribute to the pathogenesis of CRSsNP and CRSwNP and associate with response to surgery. GILZ expression in the upper airways can be regulated differentially by different cytokines.

Suppressor of cytokine signaling 3 expression is diminished in sinonasal tissues from patients with chronic rhinosinusitis with nasal polyps

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.

The European Position Paper on Rhinosinusitis and Nasal Polyps 2012 is the update of similar evidence based position papers published in 2005 and 2007. The document contains chapters on definitions and classification, we now also proposed definitions for difficult to treat rhinosinusitis, control of disease and better definitions for rhinosinusitis in children. More emphasis is placed on the diagnosis and treatment of acute rhinosinusitis. Throughout the document the terms chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP) are used to further point out differences in pathophysiology and treatment of these two entities. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. Last but not least all available evidence for management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is analyzed and presented and management schemes based on the evidence are proposed. This executive summary for otorhinolaryngologists focuses on the most important changes and issues for otorhinolaryngologists. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

Clinicians frequently encounter patients manifesting with sinonasal symptoms meeting diagnostic criteria for rhinosinusitis, yet demonstrating radiologically-negative sinus computed tomography (CT) findings. These patients typically exhibit poor response to conventional pharmacological therapies. Investigating the pathogenesis of these patients is critically important. This retrospective cohort study characterizes 53 cases of CT-negative symptomatic sinonasal disorders (CTN-SSD) compared with 132 chronic rhinosinusitis without nasal polyps (CRSsNP) controls, utilizing standardized metrics including the following: symptom visual analog scale, Lund-Kennedy endoscopic scores, 22-item Sino-Nasal Outcome Test (SNOT-22), and Lund-Mackay CT scoring. The CTN-SSD group demonstrated a greater proportion of female relative to the control group (73.58% vs 63.36%, P < .001). Of the patients with CTN-SSD in the study, 69.81% fulfilled the International Classification of Headache Disorders, third edition diagnostic criteria for migraine. The CTN-SSD cohort showed significantly-higher prevalence of posterior rhinorrhea (P = .028) and headache/facial pain (P < .001), whereas CRSsNP patients predominantly exhibited nasal obstruction, anterior rhinorrhea, and olfactory dysfunction (P < .001). While mucoid secretion rates were comparable between 2 groups (P = .153), purulent discharge exclusively occurred in CRSsNP cases (P < .001). In addition, mucosal swelling was significantly-more prevalent in CRSsNP patients than in patients with CTN-SSD (P < .001). There was no significant difference in SNOT-22 scores between the 2 groups. However, the CRSsNP group scored higher in the nasal subdomain, whereas the CTN-SSD group demonstrated elevated scores in the aural/facial and psychological subdomains (P < .001). Patients with symptoms of sinusitis but negative CT finding frequently meet the diagnostic criteria for migraine, and the possibility cannot be excluded that their symptoms are nasal presentations of migraine resembling those of rhinosinusitis, which may result in inappropriate therapies.