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This article discusses the role of nasal tissue-resident memory T (TRM) cells in chronic rhinosinusitis (CRS) with nasal polyps. The study found that non-eosinophilic CRS (NECRS) is characterized by an abundance of CD69+CD103+ TRM cells, which produce type 1 and type 17 cytokines. These TRM cells may contribute to NECRS pathogenesis and could indicate difficult-to-treat cases. The findings provide new insights into the role of nasal-resident T cells in CRS and suggest potential therapeutic targets. [Extracted from the article]

This article explores the associations between the extracellular matrix proteins tenascin C (TNC), fibronectin (FN), and periostin (PN) with edema formation and Th2 inflammation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). The study found that TNC, FN, and PN levels were significantly higher in NP tissue compared to controls, and they were positively correlated with edema score and disease severity. Additionally, TNC was predominantly correlated with Th2-related factors. The findings suggest that TNC, FN, and PN play a role in edema formation and disease severity in NP, providing potential targets for treatment. [Extracted from the article]

Tight junction (TJ) proteins establish a physical barrier between epithelial cells, playing a crucial role in maintaining tissue homeostasis by safeguarding host tissues against pathogens, allergens, antigens, irritants, etc. Recently, an increasing number of studies have demonstrated that abnormal expression of TJs plays an essential role in the development and progression of inflammatory airway diseases, including chronic obstructive pulmonary disease, asthma, allergic rhinitis, and chronic rhinosinusitis (CRS) with or without nasal polyps. Among them, CRS with nasal polyps is a prevalent chronic inflammatory disease that affects the nasal cavity and paranasal sinuses, leading to a poor prognosis and significantly impacting patients' quality of life. Its pathogenesis primarily involves dysfunction of the nasal epithelial barrier, impaired mucociliary clearance, disordered immune response, and excessive tissue remodeling. Numerous studies have elucidated the pivotal role of TJs in both the pathogenesis and response to traditional therapies in CRS. We therefore to review and discuss potential factors contributing to impair and repair of TJs in the nasal epithelium based on their structure, function, and formation process. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) is thought to result from complex interactions between the host immune system, microbiota, and environmental exposures. Currently, there is limited data regarding the impact of ambient particulate matter ≤2.5 μm in diameter (PM2.5) in the pathogenesis of CRS, despite evidence linking PM2.5 to other respiratory diseases. We hypothesized that PM2.5 may result in differential cytokine patterns that could inform our mechanistic understanding of the effect of environmental factors on CRS. Methods: We conducted an analysis of data prospectively collected from 308 CRS patients undergoing endoscopic sinus surgery. Cytokines were quantified in intraoperative mucus specimens using a multiplex flow cytometric bead assay. Clinical and demographic data including zip codes were extracted and used to obtain tract‐level income and rurality measures. A spatiotemporal machine learning model was used to estimate daily PM2.5 levels for the year prior to each patient's surgery date. Spearman correlations and regression analysis were performed to characterize the relationship between mucus cytokines and PM2.5. Results: Several inflammatory cytokines including IL‐2, IL‐5/IL‐13, IL‐12, and 21 were significantly correlated with estimated average 6, 9, and 12‐month preoperative PM2.5 levels. These relationships were maintained for most cytokines after adjusting for age, income, body mass index, rurality, polyps, asthma, and allergic rhinitis (AR) (p <.05). There were also higher odds of asthma (OR = 1.5, p =.01) and AR (OR = 1.48, p =.03) with increasing 12‐month PM2.5 exposure. Higher tissue eosinophil counts were associated with increasing PM2.5 levels across multiple timeframes (p <.05). Conclusions: Chronic PM2.5 exposure may be an independent risk factor for development of a mixed, type‐2 dominant CRS inflammatory response. [ABSTRACT FROM AUTHOR]

Following the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) treatment algorithm for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), patients suffering from severe uncontrolled CRSwNP are recommended to receive oral corticosteroids, (revision) sinus surgery, systemic biologicals and/or aspirin treatment after desensitization (ATAD). Given the major differences in indications, outcomes, practical considerations, risks and costs of these key pillars of treatment, there is a growing need to define criteria for each treatment option and list the clinically relevant and major considerations for them. This EUFOREA document therefore provides an expert panel overview of the expected outcomes, specific considerations and (contra)indications of the five major treatment arms of severe uncontrolled CRSwNP: oral corticosteroids, primary and revision sinus surgery, biological treatment and ATAD. This overview of treatment considerations is needed to allow physicians and patients to consider the different options in the context of providing optimal and personalized care for severe uncontrolled CRSwNP. In conclusion, the five major treatment options for severe uncontrolled CRSwNP have intrinsic advantages, specific indications and considerations that are of importance to the patient, the physician and the society. This EUFOREA statement supports the unmet need to define criteria for the indication of every treatment pillar of CRSwNP. [ABSTRACT FROM AUTHOR]

This article discusses the use of dupilumab, a monoclonal antibody, as a treatment option for chronic rhinosinusitis with nasal polyps (CRSwNP). The study aimed to identify predictive biomarkers for the response to dupilumab in CRSwNP patients. The researchers analyzed the populations of innate lymphoid cells (ILCs) in the blood of patients before treatment and categorized them into fast, normal, and slow responders based on clinical outcomes. They found that increased frequencies of conventional ILC2s were associated with fast responders, while increased frequencies of ILC3s were associated with slow responders. Additionally, they observed increased numbers of inflammatory ILC2s in fast responders. The study suggests that baseline frequencies of inflammatory ILC2s may be a predictor for patients' responses to dupilumab. However, the small sample size and selection bias of the study should be considered when interpreting the results. [Extracted from the article]

Background: Dupilumab, a monoclonal anti‐IL‐4Rα antibody, is approved for several type 2 mediated inflammatory diseases like asthma, atopic dermatitis, and diffuse type 2 chronic rhinosinusitis (CRS). Clinical studies had reported a transient increase in blood eosinophils during dupilumab therapy. This study aimed to assess the impact of elevated blood eosinophils on clinical outcome and to investigate the cause of high blood eosinophil levels under dupilumab therapy. Methods: Patients suffering from diffuse type 2 CRS treated with dupilumab were examined on days 0, 28, 90, and 180 after therapy start. Sino‐Nasal‐Outcome‐Test Score (SNOT‐22), Total Nasal Polyp Score (TNPS), and blood samples were collected. Cytokine measurements and proteomics analysis were conducted. Flow cytometry analysis measured receptor expression on eosinophils. Results: Sixty‐eighty patients were included. Baseline eosinophilia ≥0.3G/L was observed in 63.2% of patients, and in 30.9% of patients, eosinophils increased by ≥0.5G/L under dupilumab. Subjects with eosinophilia ≥0.3G/L at baseline had the best SNOT‐22 mean change compared to no eosinophilia. Eosinophil elevation during dupilumab therapy had no impact on clinical scores. The eosinophil adhesion molecule VCAM‐1 decreased significantly during therapy in all patients. The chemokine receptor CXCR4 was significantly down‐ and IL‐4 upregulated in subjects with eosinophil increase. Conclusion: Our findings suggest that increased eosinophils in type 2 CRS are associated with a good clinical response to dupilumab. Patients with elevated IL‐4 at baseline developed dupilumab‐induced transient eosinophilia. We identified the downregulation of VCAM‐1 and surface markers CD49d and CXCR4 on eosinophils as possible explanations of dupilumab‐induced eosinophilia. [ABSTRACT FROM AUTHOR]

Background: Viruses may drive immune mechanisms responsible for chronic rhinosinusitis with nasal polyposis (CRSwNP), but little is known about the underlying molecular mechanisms. Objectives: To identify epigenetic and transcriptional responses to a common upper respiratory pathogen, rhinovirus (RV), that are specific to patients with CRSwNP using a primary sinonasal epithelial cell culture model. Methods: Airway epithelial cells were collected at surgery from patients with CRSwNP (cases) and from controls without sinus disease, cultured, and then exposed to RV or vehicle for 48 h. Differential gene expression and DNA methylation (DNAm) between cases and controls in response to RV were determined using linear mixed models. Weighted gene co‐expression analysis (WGCNA) was used to identify (a) co‐regulated gene expression and DNAm signatures, and (b) genes, pathways, and regulatory mechanisms specific to CRSwNP. Results: We identified 5585 differential transcriptional and 261 DNAm responses (FDR <0.10) to RV between CRSwNP cases and controls. These differential responses formed three co‐expression/co‐methylation modules that were related to CRSwNP and three that were related to RV (Bonferroni corrected p <.01). Most (95%) of the differentially methylated CpGs (DMCs) were in modules related to CRSwNP, whereas the differentially expressed genes (DEGs) were more equally distributed between the CRSwNP‐ and RV‐related modules. Genes in the CRSwNP‐related modules were enriched in known CRS and/or viral response immune pathways. Conclusion: RV activates specific epigenetic programs and correlated transcriptional networks in the sinonasal epithelium of individuals with CRSwNP. These novel observations suggest epigenetic signatures specific to patients with CRSwNP modulate response to viral pathogens at the mucosal environmental interface. Determining how viral response pathways are involved in epithelial inflammation in CRSwNP could lead to therapeutic targets for this burdensome airway disorder. [ABSTRACT FROM AUTHOR]

Background: Dupilumab is an anti‐T2‐inflammatory biological registered for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), indicated by integrated CRS‐care pathways when optimal medico‐surgical treatment yields insufficient CRS control. This study aims to evaluate long‐term results with focus on established therapeutic efficacy while tapering dupilumab. Methods: Real‐life, prospective observational cohort study in single tertiary referral center with add‐on dupilumab as primary biological treatment in adult (≥18 years) biological‐naïve CRSwNP patients per the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS)2020‐indication with a 2‐year follow‐up. Tapering (increasing interdose interval) applied every 24 weeks, conditional to sufficient treatment response and CRS control. Results: Mean scores (s.d.) of all co‐primary outcomes improved significantly from baseline (228) to the 48 (214) and 96‐weeks (99) timepoints: Nasal Polyp Score (0–8) improved from 5,3 (1,9) to 1,4 (1,8) and 1,3 (1,7); SinoNasal Outcome Test (SNOT)‐22 (0–110) improved from 53,6 (19,6) to 20,2 (15,4) and 21,2 (15,6); Sniffin'Sticks‐12 identification test (0–12; 0–6 anosmia, 7–10 hyposmia, 11–12 normosmia) improved from 3,7 (2,4) to 7,7 (2,9) and 7,3 (3,04); Asthma Control Test (5–25; >19 indicating well‐controlled asthma) improved from 18,5 (4,8) to 21,8 (3,8) and 21,4 (3,9). Tapering was feasible in 79,5% of the patients at the 24‐weeks timepoint, and in 93,7% and 95,8% at the 48‐ and 96‐weeks timepoints, respectively. One‐way repeated‐measures ANOVA demonstrated no significant alterations of individual co‐primary outcome mean‐scores from 24 weeks onward. Conclusion: This first long‐term real‐life prospective observational cohort study shows high therapeutic efficacy of dupilumab for severe CRswNP in the first 2 years. Therapeutic efficacy is principally established within 24 weeks and endures while tapering dupilumab conditional to treatment response and CRS control. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) and asthma commonly co‐occur. No studies have leveraged large samples needed to formally address whether preexisting CRS is associated with new onset asthma over time. Methods: We evaluated whether prevalent CRS [identified in two ways: validated text algorithm applied to sinus computerized tomography (CT) scan or two diagnoses] was associated with new onset adult asthma in the following year. We used electronic health record data from Geisinger from 2008 to 2019. For each year we removed persons with any evidence of asthma through the end of the year, then identified those with new diagnosis of asthma in the following year. Complementary log–log regression was used to adjust for confounding variables (e.g., sociodemographic, contact with the health system, comorbidities), and hazard ratios (HRs) and 95% confidence intervals (CI) were calculated. Results: A total of 35,441 persons were diagnosed with new onset asthma and were compared to 890,956 persons who did not develop asthma. Persons with new onset asthma tended to be female (69.6%) and younger (mean [SD] age 45.9 [17.0] years). Both CRS definitions were associated (HR, 95% CI) with new onset asthma, with 2.21 (1.93, 2.54) and 1.48 (1.38, 1.59) for CRS based on sinus CT scan and two diagnoses, respectively. New onset asthma was uncommonly observed in persons with a history of sinus surgery. Conclusion: Prevalent CRS identified with two complementary approaches was associated with a diagnosis of new onset asthma in the following year. The findings may have clinical implications for the prevention of asthma. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health‐related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real‐world evidence is still limited. Methods: This Phase IV real‐life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow‐up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint. Results: We observed a significant decrease in NPS from a median value of 6 (IQR 5–6) at baseline to 1.0 (IQR 0.0–2.0) at 12 months (p <.001), and a significant decrease in Sino‐Nasal Outcomes Test‐22 (SNOT‐22) from a median score of 58 (IQR 49–70) at baseline to 11 (IQR 6–21; p <.001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p <.001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent‐moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria. Conclusions: Our findings from this large‐scale real‐life study support the effectiveness of dupilumab as an add‐on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis with a type 2 inflammatory pattern (T2CRS) is believed to be restricted to the nose and sinuses and associated with polyps, without clear serologic markers. Dupilumab is a promising new therapy in difficult to treat T2CRS. No factors are known to predict dupilumab treatment outcome. Methods: Patients undergoing dupilumab treatment were assessed clinically to report ultra‐short‐ and short‐term outcome up to 90 days. Serum samples were taken on day 0 and 30 days of treatment, and proteomic analyses were performed using Olink®. The results were compared with healthy controls (HC). The aim was to identify clinical and serological markers associated with a treatment response to dupilumab. Confirmation of predictive parameters was evaluated in a prospective cohort of 20 T2CRS patients. Results: Thirty patients were included, 80% of which were treatment responders. SinoNasalOutcomeTest‐20 (SNOT‐20) scores and the total nasal polyp score improved significantly (p <.05) on Day 7. An improvement of 2.5 points at the first visit was associated with a favorable outcome with a sensitivity of 86%. Proteomic analyses revealed significant changes compared with HC. Furthermore, we could identify OPG in the serum of dupilumab‐treated patients that may serve as a predictor of the clinical outcome of dupilumab treatment. The predictive value of OPG was confirmed in the second cohort. Conclusion: Clinical response after 1 week of treatment with dupilumab is highly associated with a favorable outcome. High sensitivity proteomic analyses can identify T2CRS‐specific dysregulated proteins in serum. Serum OPG may serve as a predictor for dupilumab treatment outcome before the initiation of any therapy. [ABSTRACT FROM AUTHOR]

Background: Patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) often require repeat sinus surgery. Mepolizumab reduced the need for sinus surgery in the SYNAPSE trial; this analysis sought to provide a more in‐depth assessment of surgery endpoints in SYNAPSE. Methods: SYNAPSE was a double‐blind Phase III trial (NCT03085797) in adults with recurrent, refractory, severe, CRSwNP eligible for repeat sinus surgery despite standard of care treatments and previous surgery. Patients were randomized (1:1) to mepolizumab 100 mg subcutaneously or placebo, plus standard of care, every 4 weeks for 52 weeks. Time to first inclusion on a waiting list for sinus surgery and time to first actual sinus surgery (both up to week 52) were assessed; the latter endpoint was also analyzed post hoc according to time since last sinus surgery before study screening and baseline blood eosinophil count. Results: Among 407 patients (mepolizumab: 206; placebo: 201), mepolizumab versus placebo reduced the risk of being included on a waiting list for sinus surgery (week 52 Kaplan–Meier probability estimate [95% confidence interval]: 13.9% [9.8%, 19.5%] vs. 28.5% [22.7%, 35.4%]). Mepolizumab versus placebo reduced the risk of sinus surgery irrespective of time (<3 vs ≥3 years) since patients' last sinus surgery prior to study screening (hazard ratios [95% confidence intervals] 0.28 [0.09, 0.84] and 0.50 [0.26, 0.98], respectively) and baseline blood eosinophil count. Conclusions: Mepolizumab reduced the risk of further sinus surgery in patients with recurrent, refractory, severe CRSwNP, irrespective of the patient baseline characteristics assessed. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis with nasal polyps (CRSwNP) associated with type 2 inflammation and non‐steroidal anti‐inflammatory drug (NSAID)‐exacerbated respiratory disease (N‐ERD) can be difficult to control with standard medical therapy and sinus surgery. In this group, biologicals are potentially promising treatment options. The phase III clinical trials for omalizumab, dupilumab, mepolizumab and benralizumab in CRSwNP have demonstrated favourable outcomes. Moving forward, direct comparisons among biologicals, refining patient selection criteria for specific biologicals, determining optimal treatment duration and monitoring long‐term outcomes are areas of emerging interest. This review summarizes the clinical evidence from the recent 2 years on the role of biologicals in severe CRSwNP and N‐ERD, and proposes an approach towards decision‐making in their use. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the nasal cavity characterized by excessive nasal mucus secretion and nasal congestion. The development of CRS is related to pathological mechanisms induced by hypoxia. Under hypoxic conditions, the stable expression of both Hypoxia inducible factor‐1 (HIF‐1) α and HIF‐2α are involved in the immune response and inflammatory pathways of CRS. The imbalance in the composition of nasal microbiota may affect the hypoxic state of CRS and perpetuate existing inflammation. Hypoxia affects the differentiation of nasal epithelial cells such as ciliated cells and goblet cells, induces fibroblast proliferation, and leads to epithelial‐mesenchymal transition (EMT) and tissue remodeling. Hypoxia also affects the proliferation and differentiation of macrophages, eosinophils, basophils, and mast cells in sinonasal mucosa, and thus influences the inflammatory state of CRS by regulating T cells and B cells. Given the multifactorial nature in which HIF is linked to CRS, this study aims to elucidate the effect of hypoxia on the pathogenic mechanisms of CRS. [ABSTRACT FROM AUTHOR]

In our cohort, AFRS patients had higher serum antifungal IgE and IgG titers than patients with eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) and healthy individuals (Figure S1A,B and Table S1). To address these questions, we generated monoclonal Abs (mAbs) from IgE-secreting plasmablasts (PBs) in the nasal polyps of patients with AFRS and characterized their antigen reactivity. Allergic fungal rhinosinusitis (AFRS) is a subset of chronic rhinosinusitis characterized by fungal allergy.1 Serum IgE of AFRS patients often exhibits broad reactivity to multiple fungi, including I Alternaria alternata i and I Aspergillus fumigatus i 2. [Extracted from the article]

Background: There are different levels of severity among patients who suffer from chronic rhinosinusitis with nasal polyps (CRSwNP). In this study, the epidemiology of CRSwNP and severe CRswNP was estimated. Methods: A retrospective claim data analysis was conducted on adult CRSwNP patients (ICD‐10: J33), and those classified as severe CRSwNP patients with inadequate disease control (based upon combinations of previous and current treatments) between 2015 and 2019. Prevalence and incidence figures were calculated and extrapolated to the German population. In addition, baseline characteristics and treatment outcomes were analysed. Results: Overall, the 5‐year prevalence of adult CRSwNP cases from 2015 to 2019 in Germany was 374,115 cases (about 5500 per million), with 12,989 (about 200 per million) patients being classified as severe CRSwNP with inadequate disease control, whereas 267,880 (about 3900 per million) patients were identified as having an incident CRSwNP diagnosis between 2016 and 2019. From the incident CRSwNP cohort, 80.55% had received at least one intranasal corticosteroid (INCS), 24.27% received at least 1 systemic corticosteroid (SCS), and 17.33% received at least one functional endoscopic sinus surgery (FESS) within 12 months after their incident diagnosis. Conclusion: Severe CRSwNP with inadequate disease control affects about 200 per million people in Germany. INCS is the first‐choice treatment for most CRSwNP patients; however, for patients with severe CRSwNP, SCS are prescribed more frequently and long‐term effects of these should be further investigated, especially if despite treatment, adequate disease control cannot be achieved. [ABSTRACT FROM AUTHOR]

This document is a reply to a correspondence regarding a study titled "Sinus inflammation and chronic rhinosinusitis are associated with a diagnosis of new onset asthma in the following year." The authors respond to concerns raised by Cheng et al. about potential confounding variables and the need for further research on sinus surgery and eosinophilic inflammation. They also address concerns about the methodology used in the study, including the potential for misclassification of patients and measurement error. The authors express gratitude for the feedback and acknowledge their conflicts of interest. [Extracted from the article]

This article is a correspondence discussing a study titled "Sinus inflammation and chronic rhinosinusitis are associated with a diagnosis of new onset asthma in the following year." The authors of the correspondence offer some suggestions and considerations regarding the study. They emphasize the importance of considering potential confounders that may influence the association between chronic rhinosinusitis (CRS) and asthma, such as environmental exposures and socio-economic status. They also highlight the need to investigate how CRS treatments affect asthma outcomes and address methodological limitations in future research. Overall, while the study highlights a link between CRS and new asthma cases, further exploration is needed to fully understand this association. [Extracted from the article]

Flow cytometry served to determine the frequencies of ILC subsets (A-C, G) and total ILCs expressing signature ILC-subset cytokines (D-E) in the CD45+ cells from control-UTs, CRSsNP-UTs, CRSwNP-UTs, and CRSwNP-NPs (A-E) or ECRS-NPs and NECRS-NPs (G, H). Similar transcriptome comparisons with NPs from ECRS and NECRS patients using our data and a public database (GSE72713)5 then showed that ECRS and NECRS clustered separately. There were 28 ECRS-NPs and eight NECRS-NPs in (G) and (H) and 39 control-UTs in (H). [Extracted from the article]

At present, clinicians are still short of curative treatment for CRSwNP, and more than 15-20% of patients are poorly controlled and undergo multiple revision surgeries.[1] It is generally accepted that endoscopic sinus surgery (ESS) cannot control the underlying inflammation. A phase III study of mepolizumab, an anti-interleukin-5 (IL-5) antibody (SYNAPSE[5]), exclusively enrolled patients with CRSwNP who had undergone at least one prior sinus surgery and were in need of revision surgery. [Extracted from the article]

Background: About one‐tenth of patients with difficult‐to‐treat chronic rhinosinusitis with nasal polyps (CRSwNP) have comorbid non‐steroidal anti‐inflammatory drug‐exacerbated respiratory disease (NSAID‐ERD). Dupilumab, a fully human monoclonal antibody that blocks the shared interleukin (IL)‐4/IL‐13 receptor component, is an approved add‐on treatment in severe CRSwNP. This post hoc analysis evaluated dupilumab efficacy and safety in patients with CRSwNP with/without NSAID‐ERD. Methods: Data were pooled from the phase 3 SINUS‐24 and SINUS‐52 studies in adults with uncontrolled severe CRSwNP who received dupilumab 300 mg or placebo every 2 weeks. CRSwNP, nasal airflow, lung function, and asthma control outcomes at Week 24 were evaluated, and treatment–subgroup interactions were assessed for patients with and without NSAID‐ERD. Results: Of 724 patients, 204 (28.2%) had a diagnosis of NSAID‐ERD. At Week 24, least squares mean treatment differences demonstrated significant improvements in nasal polyp score, nasal congestion (NC), Lund–Mackay computed tomography, 22‐item Sinonasal Outcome Test (SNOT‐22), Total Symptom Score (TSS), rhinosinusitis severity visual analog scale, peak nasal inspiratory flow (PNIF), six‐item Asthma Control Questionnaire score, and improvement in smell with dupilumab versus placebo (all p <.0001) in patients with NSAID‐ERD. Treatment comparisons demonstrated significantly greater improvements with dupilumab in patients with versus without NSAID‐ERD for NC (p =.0044), SNOT‐22 (p =.0313), TSS (p =.0425), and PNIF (p =.0123). Conclusions: In patients with uncontrolled severe CRSwNP, dupilumab significantly improved objective measures and patient‐reported symptoms to a greater extent in the presence of comorbid NSAID‐ERD than without. Dupilumab was well tolerated in patients with/without NSAID‐ERD. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis (CRS) is a common clinical syndrome that produces significant morbidity and costs to our health system. The study of CRS has progressed from an era focused on phenotype to include endotype‐based information. Phenotypic classification has identified clinical heterogeneity in CRS based on endoscopically observed features such as presence of nasal polyps, presence of comorbid or systemic diseases, and timing of disease onset. More recently, laboratory‐based findings have established CRS endotype based upon specific mechanisms or molecular biomarkers. Understanding the basis of widespread heterogeneity in the manifestations of CRS is advanced by findings that the three main endotypes, Type 1, 2, and 3, orchestrate the expression of three distinct large sets of genes. The development and use of improved methods of endotyping disease in the clinic are ushering in an expansion of the use of biological therapies targeting Type 2 inflammation now and perhaps other inflammatory endotypes in the near future. The purpose of this review is to discuss the phenotypic and endotypic heterogeneity of CRS from the perspective of advancing the understanding of the pathogenesis and improvement of treatment approaches and outcomes. [ABSTRACT FROM AUTHOR]

In this corrigendum to the original article, we have included a revised Fig 2 (I) with the right staining image as shown in this corrigendum (Figure 2), to address the error in the original article. Keywords: CRSwNP; epithelial remodeling; HIPPO; IL-13; YAP EN CRSwNP epithelial remodeling HIPPO IL-13 YAP 713 716 4 02/01/22 20220201 NES 220201 To Editor: In Feb 2021, we published a letter titled "Role of yes-associated protein in interleukin-13 induced nasal remodeling of chronic rhinosinusitis with nasal polyps" in Allergy (PMID: 33301614; 10.1111/all.14699). We would like to emphasize, however, that this error did not affect the results and conclusion of the article as the error stemmed from misplacing of the IF image at the wrong grouping column during the preparation of the manuscript revision. [Extracted from the article]

Studies showed that 15-lipoxygenase can oxidize polyunsaturated fatty acids and promote eosinophilic inflammation.5 Eosinophils metabolize linoleic acid through expression of 15-lipoxygenase-1, whose highest-affinity substrate is linoleic acid.6 Thus, linoleic acid is important in the development of eosinophilic inflammation in Eos NP. Furthermore, linoleic acid is an important differential metabolite that may be associated with polyp-derived eosinophils. Keywords: chronic rhinosinusitis; metabolomics; nasal polyps EN chronic rhinosinusitis metabolomics nasal polyps 653 656 4 02/01/22 20220201 NES 220201 ACKNOWLEDGEMENTS We would like to acknowledge Shasha Ma for her effective assistance in experiment technology and figures production. [Extracted from the article]

Background: Recent studies have revealed that the nasal microbiota in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is profoundly altered and is correlated with systemic inflammation. However, little is known regarding whether the microbiota can be utilized to predict nasal polyp recurrence. This study is aimed to determine whether altered nasal microbiota constituents could be used as biomarkers to predict CRSwNP recurrence. Methods: Nasal microbiota constituents were quantified and characterized using bacterial 16S ribosomal RNA gene sequencing. Selected features for least absolute shrinkage and selection operator regression‐based predictors were the nasal microbiota community composition and CRSwNP patient clinical characteristics. The primary outcome was recurrence, which was determined post‐admission. Results: By distinguishing recurrence‐associated nasal microbiota taxa and exploiting the distinct nasal microbiota abundance between patients with recurrent and non‐recurrent CRSwNP, we developed a predictive classifier for the diagnosis of nasal polyps' recurrence with 91.4% accuracy. Conclusions: Key taxonomical features of the nasal microbiome could predict recurrence in CRSwNP patients. The nasal microbiome is an understudied source of clinical variation in CRSwNP and represents a novel therapeutic target for future prevention and treatment. [ABSTRACT FROM AUTHOR]

Four patients ceased treatment, due to non-responsiveness (1); subjective insufficient control (1); persistent hypereosinophilia (1); and possible treatment emergent serious adverse event (1), that is, pericarditis (unverifiable treatment relation, see Supplement). Concluding, this first large, real-life, prospective observational cohort study verifies add-on dupilumab therapy as highly efficacious in the treatment of difficult-to-treat, type-2 inflammation-driven CRSwNP, concurrently validating the applied EPOS2020 indication criteria for biological treatment. Keywords: biological therapy; dupilumab; observational study; sinusitis; treatment outcome EN biological therapy dupilumab observational study sinusitis treatment outcome 670 674 5 02/01/22 20220201 NES 220201 ACKNOWLEDGEMENTS The authors would like to thank Y. te Winkel and I.M. Bruins for their assistance in organization and data collection CONFLICT OF INTEREST WF and SR are advisory board members of Sanofi and Novartis. [Extracted from the article]

Children without asthma symptoms, and any antiasthma treatment during last year, including fall-winter season 2020, were defined as I patients without asthma symptoms i (Figure 1C). In the fall-winter 2020 season, asthma symptoms and/or antiasthma therapy were reported in 31(27.9%) children (Figure 1C). [Extracted from the article]

Background: The human monoclonal antibody dupilumab blocks interleukin (IL)‐4 andIL‐13, key and central drivers of type 2 inflammation. Dupilumab, on background mometasone furoate nasal spray (MFNS), improved outcomes in the phase III SINUS‐52 study (NCT02898454) in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). This posthoc analysis of SINUS‐52 examined whether eosinophilic status of CRSwNP was a predictor of dupilumab efficacy. Methods: Patients were randomized 1:1:1 to dupilumab 300 mg every 2 weeks (q2w) until week 52; dupilumab 300 mg q2w until Week 24, then 300 mg every 4 weeks until week 52; or placebo (MFNS) until week 52. Coprimary endpoints were change from baseline in nasal polyps score (NPS), nasal congestion (NC), and Lund‐Mackay score assessed by CT (LMK‐CT) at week 24. Patients (n = 438) were stratified by eosinophilic chronic rhinosinusitis (ECRS) status according to the Japanese Epidemiological Survey of Refractory Eosinophilic Rhinosinusitis algorithm. Results: Dupilumab significantly improved NPS, NC, and LMK‐CT scores versus placebo at week 24 in all ECRS subgroups (p < 0.001), with improvements maintained or increased at week 52 (p < 0.001). There was no significant interaction between ECRS subgroup (non‐/mild or moderate/severe) and dupilumab treatment effect for all endpoints at weeks 24 and 52 (p > 0.05), except LMK‐CT at week 24 (p = 0.0275). Similar results were seen for the secondary endpoints. Dupilumab was well tolerated across all ECRS subgroups. Conclusion: Dupilumab produced consistent improvement in symptoms of severe CRSwNP irrespective of ECRS status. Therefore, blood eosinophil level may not be a suitable biomarker for dupilumab efficacy in CRSwNP. [ABSTRACT FROM AUTHOR]

Background: Clinically meaningful improvement in the Sino‐Nasal Outcome Test‐22 (SNOT‐22) was observed in patients with severe, eosinophilic asthma, and nasal polyposis (NP) treated with benralizumab in the ANDHI trial. A post hoc assessment of the effects of benralizumab on SNOT‐22 response and asthma efficacy measures in these patients was conducted for further characterization of the efficacy and safety of benralizumab for patients with severe asthma and NP. Methods: Adults with severe, eosinophilic asthma who had experienced ≥2 prior‐year exacerbations despite high‐dosage inhaled corticosteroid plus additional controller[s] were randomized to 24 weeks of benralizumab or placebo. Patients with physician‐diagnosed chronic rhinosinusitis with NP of any severity ongoing at baseline who consented to participate were included in the current ANDHI NP substudy population. Effect on NP symptoms was assessed by the SNOT‐22, with an improvement of at least 8.9 defined as clinically significant (responder). Effects on chronic asthma outcomes were assessed by means of annualized asthma exacerbation rate (AER), St. George's Respiratory Questionnaire (SGRQ) total score, forced expiratory volume in one second (FEV1), and Asthma Control Questionnaire‐6 (ACQ‐6). All p‐values were nominal. Results: Of the ANDHI population (n = 656), 23% (n = 153) participated in the NP substudy (n = 96 benralizumab; n = 57 placebo). Patients were 50% female, with mean age of 53 years, had prior‐year AER = 3.3; mean pre‐bronchodilator FEV1 = 55% predicted; and median blood eosinophil count ​= 510 cells/µl. For patients with high baseline SNOT‐22 scores (>30), benralizumab treatment improved symptoms of NP as measured by SNOT‐22 from baseline to Week 24 compared with placebo (Week 24: −10.44 [p =.0176]). Percentage of responders to SNOT‐22 was greater for benralizumab vs. placebo (71.3% vs. 45.5%; p =.0036), and effect was enhanced for patients with high baseline SNOT‐22 scores (>30). A 69% reduction vs. placebo in annualized AER (0.77 vs. 2.47; p <.0001) and greater clinically meaningful improvements from baseline in SGRQ total score (−16.7), FEV1 (+0.32 L), and ACQ‐6 (–0.88) were observed (p <.0001). Benralizumab was well‐tolerated. Frequency of adverse events (AEs) was similar for benralizumab (76.0%) and placebo (73.7%) groups. Most common AEs (frequency ≥5%) reported at a greater frequency in benralizumab vs. placebo included headache, sinusitis, pyrexia, and influenza. Conclusions: These substudy data from ANDHI demonstrated the efficacy profile of benralizumab for patients with severe, eosinophilic asthma and NP, with improvement in SNOT‐22 and asthma outcomes. [ABSTRACT FROM AUTHOR]

Keywords: clinical immunology; ENT (rhinitis sinusitis nasal polyps...); epidemiology; inflammation; quality-of-life; rhinitis; sinusitis EN clinical immunology ENT (rhinitis sinusitis nasal polyps...) epidemiology inflammation quality-of-life rhinitis sinusitis 3806 3809 4 12/01/21 20211201 NES 211201 ACKNOWLEDGMENTS The authors would like to thank the residents from the Department for Otorhinolaryngology (University Hospitals Leuven) for their help in including participants. Clinical immunology, ENT (rhinitis sinusitis nasal polyps...), epidemiology, inflammation, quality-of-life, rhinitis, sinusitis (C) Prevalence of sNHR in patients under medication for their (sino)nasal symptoms and patients not under medication for their (sino)nasal symptoms. [Extracted from the article]

Background: Chronic rhinosinusitis (CRS) is a common chronic respiratory condition, frequently associated with asthma and affecting the majority of cystic fibrosis (CF) patients. Pseudomonas aeruginosa infections and biofilms have been implicated in recalcitrant CRS. One of the mechanisms of action for bacteria in CRS and CF is mucosal barrier disruption by secreted products that contribute to the inflammation. However, the role of biofilm and planktonic forms of P. aeruginosa in this process is not known. The aim is to determine the effect of P. aeruginosa exoproteins isolated from CF and non‐CF CRS patients on the mucosal barrier. Methods: Exoproteins from 40 P. aeruginosa isolates were collected in planktonic and biofilm forms and applied to air‐liquid interface (ALI) cultures of primary human nasal epithelial cells (HNECs). Mucosal barrier integrity was evaluated by transepithelial electrical resistance (TEER), passage of FITC‐dextrans and immunofluorescence of tight junction proteins. Cytotoxicity assays were performed to measure cell viability, and IL‐6 ELISA was carried out to evaluate pro‐inflammatory effects. Results: Planktonic exoproteins from 20/40 (50%) clinical isolates had a significant detrimental effect on the barrier and significantly increased IL‐6 production. Barrier disruption was characterized by a reduced TEER, increased permeability of FITC‐dextrans and discontinuous immunolocalization of tight junction proteins and was significantly more prevalent in isolates harvested from patients with comorbid asthma (P <.05). Conclusion: Exoproteins from planktonic P. aeruginosa clinical isolates from asthmatic CRS patients have detrimental effects on the mucosal barrier and induce IL‐6 production potentially contributing to the mucosal inflammation in CRS patients. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis (CRS) is a complex upper airway inflammatory disease with a broad spectrum of clinical variants. As our understanding of the disease pathophysiology evolves, so too does our philosophy towards the approach and management of CRS. Endotyping is gaining favour over phenotype‐based classifications, owing to its potential in prognosticating disease severity and delivering precision treatment. Endotyping is especially useful in challenging CRS with nasal polyposis cases, for whom novel treatment options such as biologicals are now available. The latest European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2020) reflects these changes with updated rhinosinusitis classifications and new integrated care pathways. With the coronavirus disease 2019 (COVID‐19) pandemic, physicians and rhinologists have to balance the responsibility of managing their patients' upper airway while adequately protecting themselves from droplet and aerosol transmission. This review summarises the key updates from EPOS2020, endotype‐based classification and biomarkers. The role of biologicals in CRS and the lessons we can draw from their use in severe asthma will be examined. Finally, the principles of CRS management during COVID‐19 will also be discussed. [ABSTRACT FROM AUTHOR]

Keywords: ACE2; chronic rhinosinusitis; COVID-19; eosinophil; olfactory neuroepithelium; SARS-CoV-2; TMPRSS2 EN ACE2 chronic rhinosinusitis COVID-19 eosinophil olfactory neuroepithelium SARS-CoV-2 TMPRSS2 2904 2907 4 09/03/21 20210901 NES 210901 ACKNOWLEDGMENTS This study was partially sponsored by a research grant (FIS PI19/00806) from Instituto Carlos III, Ministerio de Ciencia, Innovación y Universidades, Spain. (G) mRNA expression levels, as revealed by RT-PCR, of genes encoding for SARS-CoV-2 entry protein (ACE2 and TMPRSS2) in olfactory mucosa from CRSwNP patients and control cases. However, ACE2/TMPRSS2 expressions in the ONE from CRSwNP patients, that may be a risk factor for SARS-CoV-2 infection of the olfactory bulbs and brain entry, remain to be investigated. [Extracted from the article]

Adequate nasal breathing is indispensable for athletes, and nasal symptoms have been shown to interfere with their subjective feeling of comfortable breathing and quality of life. Nasal symptoms are caused by either structural abnormalities or mucosal pathology. Structural pathologies are managed differently from mucosal disease, and therefore, adequate diagnosis is of utmost importance in athletes in order to choose the correct treatment option for the individual. Literature suggests that nasal symptoms are more prevalent in athletes compared to the general population and certain sports environments might even trigger the development of symptoms. Given the high demands of respiratory function in athletes, insight into triggering factors is of high importance for disease prevention. Also, it has been suggested that athletes are more neglectful to their symptoms and hence remain undertreated, meaning that special attention should be paid to education of athletes and their caregivers. This review aims at giving an overview of nasal physiology in exercise as well as the possible types of nasal pathology. Additionally, diagnostic and treatment options are discussed and we focus on unmet needs for the management and prevention of these symptoms in athletes within the concept of precision medicine. [ABSTRACT FROM AUTHOR]

This systematic review evaluates the efficacy and safety of biologicals for chronic rhinosinusitis with nasal polyps (CRSwNP) compared with the standard of care. PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CRSwNP‐related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. RCTs evaluated (dupilumab‐2, omalizumab‐4, mepolizumab‐2, and reslizumab‐1) included 1236 adults, with follow‐up of 20–64 weeks. Dupilumab reduces the need for surgery (NFS) or oral corticosteroid (OCS) use (RR 0.28; 95% CI 0.20–0.39, moderate certainty) and improves with high certainty smell evaluated with UPSIT score (mean difference (MD) +10.54; 95% CI +9.24 to +11.84) and quality of life (QoL) evaluated with SNOT‐22 (MD −19.14; 95% CI −22.80 to −15.47), with fewer treatment‐related adverse events (TAEs) (RR 0.95; 95% CI 0.89–1.02, moderate certainty). Omalizumab reduces NFS (RR 0.85; 95% CI 0.78–0.92, high certainty), decreases OCS use (RR 0.38; 95% CI 0.10–1.38, moderate certainty), and improves high certainty smell (MD +3.84; 95% CI +3.64 to +4.04) and QoL (MD −15.65; 95% CI −16.16 to −15.13), with increased TAE (RR 1.73; 95% CI 0.60–5.03, moderate certainty). There is low certainty for mepolizumab reducing NFS (RR 0.78; 95% CI 0.64–0.94) and improving QoL (MD −13.3; 95% CI −23.93 to −2.67) and smell (MD +0.7; 95% CI −0.48 to +1.88), with increased TAEs (RR 1.64; 95% CI 0.41–6.50). The evidence for reslizumab is very uncertain. [ABSTRACT FROM AUTHOR]

Mepolizumab for chronic rhinosinusitis with nasal polyps: treatment efficacy by comorbidity and blood eosinophil count. Knowledge gaps in using type 2 biologics for real-world treatment of chronic rhinosinusitis with nasal polyps By translating scientific results into an integrated care strategy, biologics targeting T2 inflammation have achieved major progress in treating severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) during the last decade. In RCTs, discontinuation of biologics caused a slow bounce of nasal polyp scores and nasal symptoms, indicating that continued treatment is necessary to sustain positive outcomes. [Extracted from the article]

Background: Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory disease, characterized by eosinophilic infiltration, T‐helper type 2 (Th2‐type) response, and olfactory dysfunction. A master regulator of Th2‐type inflammation, thymic stromal lymphopoietin (TSLP), is important for basophil activation. TSLP‐elicited basophils are a key factor in the pathogenesis of ECRS. Methods: In order to elucidate the mechanisms of ECRS in humans, we aimed to establish a murine model of ECRS based on TSLP production in response to the topical application of MC903 (a vitamin D3 analog) and the subsequent TSLP‐induced basophil activation. Histological analyses were performed to assess immune cell infiltration into the nasal mucosa and to explore the impact of eosinophilic inflammation on the olfactory epithelium. The status of Th2‐type inflammation was evaluated by quantitative real‐time PCR and enzyme‐linked immunosorbent assay (ELISA). Results: Eosinophils, basophils, and M2 macrophages increased significantly in the nasal mucosa of the mice treated with MC903 and ovalbumin (OVA), compared to those treated with OVA alone or the controls. Quantitative real‐time PCR and ELISA revealed elevated expression of interleukin (IL)‐4, IL‐5, IL‐13, TSLP, the chemokine CCL11, and CCL24 in the nasal mucosa of the ECRS mice. In parallel, thinned olfactory epithelium and decreased mature olfactory sensory neurons were observed in the ECRS mice. Conclusions: Our model of ECRS displayed Th2‐type inflammation in the sinonasal region, including both eosinophil infiltration and basophil infiltration. Additionally, olfactory epithelium turned out to be affected by eosinophilic inflammation. These features are consistent with the characteristics of the human ECRS. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) entry factors, ACE2 and TMPRSS2, are highly expressed in nasal epithelial cells. However, the association between SARS‐CoV‐2 and nasal inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been investigated. We thus investigated the expression of SARS‐CoV‐2 entry factors in nasal tissues of CRSwNP patients, and their associations with inflammatory endotypes of CRSwNP. Methods: The expression of ACE2 and TMPRSS2 was assessed in nasal tissues of control subjects and eosinophilic CRSwNP (ECRSwNP) and nonECRSwNP patients. The correlations between ACE2/TMPRSS2 expression and inflammatory indices of CRSwNP endotypes were evaluated. Regulation of ACE2/TMPRSS2 expression by inflammatory cytokines and glucocorticoids was investigated. Results: ACE2 expression was significantly increased in nasal tissues of nonECRSwNP patients compared to ECRSwNP patients and control subjects, and positively correlated with the expression of IFN‐γ, but negatively correlated with tissue infiltrated eosinophils, and expression of IL5 and IL13. IFN‐γ up‐regulated ACE2 expression while glucocorticoid attenuated this increase in cultured nasal epithelial cells. Genes co‐expressed with ACE2 were enriched in pathways relating to defence response to virus in nasal tissue. TMPRSS2 expression was decreased in nasal tissues of CRSwNP patients compared to control subjects and not correlated with the inflammatory endotypes of CRSwNP. Glucocorticoid treatment decreased ACE2 expression in nasal tissues of nonECRSwNP patients, but not in ECRSwNP patients, whereas TMPRSS2 expression was not affected. Conclusion: These findings indicate that ACE2 expression, regulated by IFN‐γ, is increased in nasal tissues of nonECRSwNP patients and positively correlates with type 1 inflammation. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis is regarded as a chronic airway disease. According to WHO recommendations, it may be a risk factor for COVID‐19 patients. In most CRSwNP cases, the inflammatory changes affecting the nasal and paranasal mucous membranes are type‐2 (T2) inflammation endotypes. Methods: The current knowledge on COVID‐19 and on treatment options for CRS was analyzed by a literature search in Medline, Pubmed, international guidelines, the Cochrane Library and the Internet. Results: Based on international literature, on current recommendations by WHO and other international organizations as well as on previous experience, a panel of experts from EAACI and ARIA provided recommendations for the treatment of CRS during the COVID‐19 pandemic. Conclusion: Intranasal corticosteroids remain the standard treatment for CRS in patients with SARS‐CoV‐2 infection. Surgical treatments should be reduced to a minimum and surgery preserved for patients with local complications and for those with no other treatment options. Systemic corticosteroids should be avoided. Treatment with biologics can be continued with careful monitoring in noninfected patients and should be temporarily interrupted during the course of the COVID‐19 infection. [ABSTRACT FROM AUTHOR]

Keywords: allergy treament; asthma; atopic dermatitis; ENT (rhinitis; sinusitis; nasal polyps...); immunotherapy clinical EN allergy treament asthma atopic dermatitis ENT (rhinitis sinusitis nasal polyps...) immunotherapy clinical 593 596 4 02/20/21 20210201 NES 210201 Allergic diseases such as asthma, chronic rhinosinusitis (CRS), atopic dermatitis (AD), allergic rhinitis, and eosinophilic esophagitis (EoE) affect more than 30% of the population,1 with a dramatic increase2 and a lack of effective treatments for recurrent or adverse effects of corticosteroids and immunosuppressants.3,4 Dupilumab is a monoclonal antibody that targets the IL-4 receptor alpha subunit and inhibits IL-4/IL-13 signaling, thus downregulating type-2 inflammatory responses.5 Currently, dupilumab has proven effectiveness in patients with serious allergic diseases.6-8 However, the evidence on safety of dupilumab is insufficient in allergic diseases. A pooled analysis showed that the incidence of any serious TEAE was 223 of 4923 (4.53%) patients receiving dupilumab treatment and 139 of 2401 (5.79%) patients receiving placebo. The risk of any leading to permanent treatment discontinuation in patients receiving dupilumab treatment was similar to that in patients receiving placebo (RR = 0.78; 95% CI, 0.53-1.16; I P i = .23; I2 = 32.37%; Figure 1D). What's more, our result showed that dupilumab is associated with a lower risk of developing other allergic diseases, such as asthma or sinusitis, indicated that dupilumab can effectively prevent the occurrence of other allergic diseases in patients with allergic disease and that it plays a defensive and protective role against allergic diseases. [Extracted from the article]

Keywords: CRSwNP; epithelial remodeling; HIPPO; IL-13; YAP EN CRSwNP epithelial remodeling HIPPO IL-13 YAP 600 604 5 02/20/21 20210201 NES 210201 Chronic rhinosinusitis (CRS) is a common otolaryngologic disease. IF results on day 2 (A-D) and day 24 (E-H), showed that IL-13+VP treatment resulted in a decreased basal cell percentage (D, H), decreased YAP activity in basal cells (B, F), and a decreased basal cell proliferation level (C, G). Generally, YAP inhibits epithelial differentiation.8 However, our results demonstrated that YAP can also promote goblet cell differentiation and YAP inhibitor reversed IL-13-induced goblet cell hyperplasia. [Extracted from the article]

Hypoxia-induced factor-1 induces NLRP3 expression by M1 macrophages in noneosinophilic chronic rhinosinusitis with nasal polyps Keywords: chronic rhinosinusitis with nasal polyps; hypoxia-induced factor-1 ; inflammation; macrophage; NOD-like receptor family; pyrin domain containing 3 EN chronic rhinosinusitis with nasal polyps hypoxia-induced factor-1 inflammation macrophage NOD-like receptor family pyrin domain containing 3 582 586 5 02/20/21 20210201 NES 210201 To the Editor, Chronic rhinosinusitis with nasal polyps (CRSwNP) is a widespread chronic inflammatory disease of the nasal mucosa and can manifest in different phenotypes. HIF-1 , hypoxia-induced factor-1 ; NLRP3, NOD-like receptor family, pyrin domain containing 3; eosCRSwNP, eosinophilic chronic rhinosinusitis with nasal polyps gl Additionally, we found that Arg-1-positive type II macrophage was mainly observed in eosCRSwNP, while the INOS-positive type I macrophage was observed mostly in non-eosCRSwNP. [Extracted from the article]

Background: Chronic rhinosinusitis (CRS) epidemiology has been largely studied using symptom‐based case definitions, without assessment of objective sinus findings. Objective: To describe radiologic sinus opacification and the prevalence of CRS, defined by the co‐occurrence of symptoms and sinus opacification, in a general population‐based sample. Methods: We collected questionnaires and sinus CT scans from 646 participants selected from a source population of 200 769 primary care patients. Symptom status (CRSS) was based on guideline criteria, and objective radiologic inflammation (CRSO) was based on the Lund‐Mackay (L‐M) score using multiple L‐M thresholds for positivity. Participants with symptoms and radiologic inflammation were classified as CRSS+O. We performed negative binomial regression to assess factors associated with L‐M score and logistic regression to evaluate factors associated with CRSS+O. Using weighted analysis, we calculated estimates for the source population. Results: The proportion of women with L‐M scores ≥ 3, 4, or 6 (CRSO) was 11.1%, 9.9%, and 5.7%, respectively, and 16.1%, 14.6%, and 8.7% among men. The respective proportion with CRSS+O was 1.7%, 1.6%, and 0.45% among women and 8.8%, 7.5%, and 3.6% among men. Men had higher odds of CRSS+O compared to women. A greater proportion of men (vs women) had any opacification in the frontal, anterior ethmoid, and sphenoid sinuses. Conclusion: In a general population‐based sample in Pennsylvania, sinus opacification was more common among men than in women and opacification occurred in different locations by sex. Male sex, migraine headache, and prior sinus surgery were associated with higher odds of CRSS+O. [ABSTRACT FROM AUTHOR]

Our understanding of the pathophysiology of chronic rhinosinusitis (CRS) is continuously evolving. The traditional description of CRS in terms of two phenotypes based on the presence or absence of nasal polyps belies the underlying intricate immunopathophysiological processes responsible for this condition. CRS is being increasingly recognized as a disease spectrum encompassing a range of inflammatory states in the sinonasal cavity, with non‐type 2 inflammatory disease on one end, type 2 inflammatory, eosinophil‐heavy disease on the other and an overlap of both in different proportions in between. Abundance in research on the immune mechanisms of CRS has revealed various new endotypes that hold promise as biomarkers for the development of targeted therapies in severe, uncontrolled CRS. The introduction of precision medicine to manage this chronic, complex condition is a step forward in providing individualized care for all patients with CRS. In this review, the latest research on the pathophysiology of CRS with a focus on potential novel biomarkers and treatment options over the last 2 years are summarized and integrated into a suggested model of precision medicine in CRS. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) negatively affects health‐related quality of life (HRQoL). In a previously reported randomized clinical trial (NCT01920893), addition of dupilumab to mometasone furoate in patients with CRSwNP refractory to intranasal corticosteroids (INCS) significantly improved endoscopic, radiographic, and clinical endpoints and patient‐reported outcomes. The objective of this analysis was to examine the impact of dupilumab treatment on HRQoL and productivity using secondary outcome data from this trial. Methods: Following a 4‐week mometasone furoate nasal spray run‐in, patients were randomized to commence subcutaneous dupilumab (600 mg loading dose, then 300 mg once weekly for 15 weeks [n = 30], or matched placebo [n = 30]). Outcomes included scores on the CRS disease severity visual analog scale (VAS), 22‐item Sino‐Nasal Outcome Test (SNOT‐22), 5‐dimension EuroQoL (EQ‐5D) general health status VAS, and 36‐item Short‐Form Health Survey (SF‐36) for HRQoL and nasal polyp‐related healthcare resource use questionnaires. Results: Following 16 weeks of treatment, the proportion of patients with moderate‐to‐severe CRSwNP (VAS > 3‐10) decreased from 86.2% to 21.4% with dupilumab and 88.0% to 84.2% with placebo. Dupilumab (vs placebo) resulted in significantly greater improvement in HRQoL, based on SNOT‐22, SF‐36, and EQ‐5D VAS scores. The dupilumab group had a significantly lower adjusted annualized mean number of sick leave days (0.09, vs 4.18 with placebo, P =.015) and significantly greater improvement (vs placebo) in the SNOT‐22 item "reduced productivity." Conclusions: In adults with CRSwNP refractory to treatment with INCS alone, the addition of dupilumab reduced disease severity, significantly improved HRQoL, and improved productivity. [ABSTRACT FROM AUTHOR]

For over 30 years, Bob has studied basophils and mast cells and published many important and impactful papers describing the regulation of their signaling, activation, and products especially in human allergic diseases. Allergic disease, basophil, sinusitis, eosinophils, mast cells, ENT (rhinitis, nasal polyps...) Bob first became interested in the role of basophils and mast cells, key effector cells in the allergic response. [Extracted from the article]