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Purpose: Endotype-driven treatment has been introduced in the management of chronic rhinosinusitis with nasal polyps (CRSwNP), and an understanding of the associations between phenotypes and endotypes of CRSwNP will be beneficial in identifying responders. We aimed to determine the correlations between clinical manifestations and type 2 inflammatory mediators of sinonasal tissues., Methods: Adult patients undergoing endoscopic sinus surgery for bilateral CRSwNP were prospectively enrolled. Tissue eosinophilia and type 2 mediator expression in tissue homogenates were assessed and correlated with clinical features, including symptoms, comorbidities, blood eosinophil counts, specific allergen immunoglobulin (IgE) testing, computed tomography (CT) scan findings, and Sino-Nasal Outcome Test-22 scores., Results: A total of 93 subjects were recruited in our study. Fifty-nine (63.4%) cases were identified as the eosinophilic endotype, demonstrating with higher rates of comorbidity of asthma, blood eosinophilia and a high ethmoid-maxillary ratio on CT images. To correlate of phenotypes with the inflammatory mediator profile, multivariate analyses revealed the associations of IgE expression in nasal polyp tissues with allergen sensitization (p = 0.042), CT ethmoid-maxillary ratio (p = 0.001) and tissue eosinophil counts (p = 0.022); the association of interleukin (IL-5) expression with the blood eosinophil percentage (p = 0.020); and the association of IL-13 expression with white blood cell count (p = 0.002) and central compartment-type inflammation (p < 0.001)., Conclusion: We demonstrated associations of IgE and IL-5 expression with clinical features of eosinophilic-type inflammation and a significantly elevated level of IL-13 in patients with central-compartment-type CRSwNP. These observations may be useful when considering the use of type 2 biologic treatment and require further validation studies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study aimed to elucidate the revision rate, time to revision, and factors associated with revision of endoscopic sinus surgery (ESS) in Taiwan., Design: Retrospective study., Setting: Population-based analysis., Participant: We identified all in-hospital patients, aged >20 years, who underwent ESS between 2000 and 2008 from the Taiwan National Health Insurance Research Database, and followed up with them until 2018., Main Outcome Measures: Factors associated with revision surgery were analyzed using multivariable Cox proportional hazard model., Results: Overall, 66 592 patients were identified (mean age, 46.3 years; 62% males). The revision rate was 14.5% (9644/66 592) and time to revision surgery was 5.9 years. Multivariable Cox proportional hazard model showed that young age, male gender (hazard ratio [HR] = 1.18; 95% confidence interval [CI], 1.13-1.23), having nasal polyposis (HR = 1.17; 95% CI, 1.12-1.22), having allergic rhinitis (HR = 1.08; 95% CI, 1.04-1.13), having asthma (HR = 1.26; 95% CI, 1.14-1.39), and surgical time of >4 h (HR = 1.11; 95% CI, 1.06-1.16) were associated with increased risk of revision surgery. Concurrent septal surgery (HR = 0.81; 95% CI, 0.76-0.87), turbinate surgery (HR = 0.91; 95% CI, 0.85-0.97), or septal and turbinate surgery (HR = 0.68; 95% CI, 0.64-0.73) were associated with decreased risks of revision surgery., Conclusion: In Taiwan, risk factors for revision ESS are young age, male gender, having nasal polyposis, having allergic rhinitis, having asthma, and long surgical times. Concurrent septal or turbinate surgery decreases the risk of revision., (© 2022 John Wiley & Sons Ltd.)

Background: The clinical characteristics of central-compartment-type chronic rhinosinusitis (CRS) in East Asian individuals are not clear. We sought to investigate the clinical features and the cytokine profiles of central-compartment-type CRS in our patient group., Methods: Adult patients diagnosed with bilateral CRS were recruited, and patients who had previously undergone sinus surgery and pansinusitis (Lund-Mackay scores >23) were excluded. Central-compartment-type CRS was defined by both endoscopic and radiological features. The symptoms, inhalant allergen sensitization status, endoscopic findings, and radiological assessments were recorded and compared between patients with central-compartment-type CRS and other types of CRS. We also examined the extent of tissue eosinophilia and specific cytokine protein levels (eosinophil cationic protein [ECP], myeloperoxidase [MPO], immunoglobulin E [IgE], interleukin [IL]-4, IL-5, and IL-13) in the sinonasal tissues., Results: Central-compartment-type CRS was found in 16 (23.9%) patients, and non-central-compartment-type CRS was found in 51 (76.1%) patients. Hyposmia or anosmia as the major symptom was more common in the central-compartment-type CRS group. The numbers of eosinophils in tissue and serum were significantly higher in the central-compartment-type CRS patients. The presence of allergen sensitization was not significantly different between groups. The levels of IL-5 and IL-13 were increased in middle turbinate tissues of patients with central-compartment-type CRS., Conclusion: Central-compartment-type CRS was associated with hyposmia or anosmia, eosinophilic subtypes, and elevated levels of IL-5 and IL-13 in middle turbinate tissues but not necessarily correlated with allergic disease in our patients., (© 2021 ARS-AAOA, LLC.)

Background: The role of allergy in the development of chronic rhinosinusitis (CRS) in East Asians is not clear., Aims/objectives: The aim was to investigate the impact of allergies in the clinical characteristics of chronic rhinosinusitis., Material and Methods: A total of 138 CRS patients who underwent endoscopic sinus surgery were included. A brief history of rhinosinusitis symptoms, blood eosinophil count, blood-specific allergen tests, computed tomography (CT) scan findings, Lund-Mackay (LM) CT scores, and Sino-Nasal Outcome Test (SNOT-22) Questionnaire scores, and sinoscopy findings at 3 and 6 months postoperatively., Results: The ImmunoCAP test was positive in 71(51%) patients and negative in 67(49%) patients. The mean age of those who received endoscopic sinus surgery was 7-years younger in the allergic group compared with the non-allergic group (p = .008). The peripheral eosinophil count in the allergic group was higher than that of the non-allergic group (p = .008). The LM scores and SNOT-22 scores were not significantly different between the two groups. The recurrence rate of nasal polyps in the allergic group was higher but without statistical significance., Conclusions and Significance: Allergy may accelerate the disease progression of CRS. The presence of the serum-specific IgE was correlated with peripheral eosinophil percentage, especially in the CRSwNP patients.

Objectives/hypothesis: Chronic rhinosinusitis colonized with Pseudomonas aruginosa is difficult to treat and is related to biofilm formation. Repeated sinus surgery is often required for these patients. Short palate, lung, and nasal epithelial clone 1 (SPLUNC1) is an epithelium-secreted protein that is involved in innate immunity and has anti-Pseudomonas and antibiofilm functions. This study examined if SPLUNC1 expression was related to sinusitis with bacterial culture positive for Pseudomonas and the possibility of using SPLUNC1 to predict treatment outcomes for sinusitis., Study Design: Nonrandomized retrospective study., Methods: This was a retrospective study of patients at a tertiary referral center. Pseudomonas aruginosa infection was compared to clinical variables such as SPLUNC1 mRNA expression levels, immunohistochemical (IHC) stain intensity, Lund-Mackay sinus computed tomography scores, rapid recurrent sinusitis, requirement for repeat sinus surgery, Phadiatop test results, age, gender, nasal polyp(s), and patients' presence/absence of diabetes mellitus. Comparisons between groups were performed using the χ(2) test or Fisher exact test when one confronter was <5. The statistical analyses were carried out with SPSS version 13., Results: P. aeruginosa sinus infections were associated with lower sinus mucosa SPLUNC1 expression (P = .0018), weaker SPLUNC1 IHC staining intensity (P = .011), and poor postoperative outcome (i.e., need repeated sinus surgery) (P < .001). Other factors were not associated with Pseudomonas sinus infection., Conclusions: Sinusitis with positive P. aeruginosa bacterial culture is associated with decreased SPLUNC1 sinus mucosa expression. Repeated sinus surgeries are more frequently needed for these patients., (Copyright © 2013 The American Laryngological, Rhinological, and Otological Society, Inc.)

Nasal mucosa is an immune responsive organ evidenced by eliciting both specific local secretory IgA and systemic IgG antibody responses with intra-nasal administration of antigens. Nevertheless, the role of nasal epithelial cells in modulating such responses is unclear. Human nasal epithelial cells (hNECs) obtained from sinus mucosa of patients with chronic rhinosinusitis were cultured in vitro and firstly were stimulated by Lactococcus lactis bacterium-like particles (BLPs) in order to examine their role on antibody production. Secondly, both antigens of immunodominant protein IDG60 from oral Streptococcus mutans and hemagglutinin (HA) from influenza virus were tested to evaluate the specific antibody response. Stimulated hNECs by BLPs exhibited a significant increase in the production of interleukin-6 (IL-6), and thymic stromal lymphopoietin (TSLP). Conditioned medium of stimulated hNECs has effects on enhancing the proliferation of CD4+ T cells together with interferon-γ and IL-5 production, increasing the costimulatory molecules on dendritic cells and augmenting the production of IDG60 specific IgA, HA specific IgG, IgA by human peripheral blood lymphocytes. Such production of antigen specific IgG and IgA is significantly counteracted in the presence of IL-6 and TSLP neutralizing antibodies. In conclusion, properly stimulated hNECs may impart immuno-modulatory effects on the antigen-specific antibody response at least through the production of IL-6 and TSLP.

Background: Short palate, lung, and nasal epithelium clone 1 (SPLUNC1) protein is an airway epithelial cell-derived molecule exerting host defense against pathogen. However, the function and regulation of SPLUNC1 in nasal epithelial cells are still unclear. Chronic rhinosinusitis with nasal polyps (CRSwNPs) is a disorder characterized by eosinophilic Th2 inflammation and frequent microbial colonization. The pathogenesis has been postulated as a disturbed mucosal immune response. This study investigates the SPLUNC1 expression of nasal polyp epithelial cells in air-liquid interface (ALI) culture and after treating with Th2 inflammatory cytokines IL-13., Methods: Human nasal polyp epithelial cells isolated from patients with CRSwNPs were put in different cell culture models at days 0 and 21 and were assessed for expression of SPLUNC1 by microarray. Cultured cells in ALI plus retinoic acid (ALI + RA) model were then incubated with 0, 1, 10, and 100 ng/mL human recombinant IL-13 for up to 5 days. The expression of SPLUNC1 was assessed by real-time quantitative polymerase chain reaction (RT-Q-PCR), reverse-transcriptase PCR (RT-PCR) and Western blot analysis., Results: ALI + RA culture model harvesting ciliary differentiated nasal epithelial cells constitutively expressed high levels of SPLUNC1. In contrast, SPLUNC1 is reduced under classic submerged single layer culture. SPLUNC1 is also dose-responsively down-regulated after incubation with IL-13., Conclusion: A microenvironmental milieu containing IL-13 may be detrimental to the host innate immunity response, at least in part, through the inhibition of SPLUNC1 production.

The coronavirus SARS-CoV-2 is the causative agent of the ongoing severe acute respiratory disease pandemic COVID-19. Tissue and cellular tropism is one key to understanding the pathogenesis of SARS-CoV-2. We investigate the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of human donors using a diverse panel of banked tissues. Here, we report our discovery that the ACE2 receptor protein robustly localizes within the motile cilia of airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during host respiratory transmission. We further determine whether ciliary ACE2 expression in the upper airway is influenced by patient demographics, clinical characteristics, comorbidities, or medication use, and show the first mechanistic evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) does not increase susceptibility to SARS-CoV-2 infection through enhancing the expression of ciliary ACE2 receptor. These findings are crucial to our understanding of the transmission of SARS-CoV-2 for prevention and control of this virulent pathogen.

Background: Isolated sphenoid sinus disease (ISSD) is a rare clinical entity with potentially serious complications. The etiological distribution of ISSD varies among different areas and ethnicities. We aimed to investigate the clinical features of patients with endoscopic treated ISSD.Methods: We retrospectively reviewed all patients with ISSD who had undergone endoscopic surgery between April 2013 and May 2019. The patient records were reviewed for demographic data, clinical presentations, endoscopic and imaging study findings, surgical outcomes and complications.Results: A total of 37 patients with ISSD who underwent surgery were recruited. We divided patients into three groups according to etiology, including inflammatory diseases (78.4%), neoplasms (13.5%) and spontaneous cerebrospinal fluid (CSF) leaks (8.1%); fungal ball (62.2%) constituted the major cause of ISSD. Overall, the most common presenting symptom was headache or facial pain (65.5%). The endoscopic findings of bloody discharge and tumor lesions were mainly from the neoplasm group. Bony defects were more obvious on computed tomography in the neoplasm and CSF leak groups. Magnetic resonance imaging revealed a higher rate of involvement of the cavernous sinus (40.0%) and intracranial extensions (40.0%) in the neoplasm group. To summarize the surgical outcomes, the success rate was 97.1%, and the major complication rate was 5.4%.Conclusion: ISSD represents a variety of etiologies, mostly comprising fungal ball in our area, while there is still a considerable proportion of ISSDs attributed to neoplasm and CSF leak. Untreated ISSD can result in serious complications. We recommend early surgical intervention for all patients with ISSD. [ABSTRACT FROM AUTHOR]