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Background Methods Results Conclusions Endoscopic sinus surgery (ESS) maximized for topical steroid irrigations is highly effective for polyp disease. As extent and completeness of ESS varies widely by situation and practitioner, it is important to understand when revision surgery is appropriate, particularly in the era of biologic treatments.A Completion of Surgery Index (CoSI) was developed to assess operative changes in polyp patients using pre‐ and postoperative computed tomography scans. The CoSI was then applied and tested in a cohort of consecutive chronic rhinosinusitis with nasal polyps (CRSwNP) patients, and examined within the context of quality‐of‐life improvements.The CoSI assesses surgical extent on a scale of 0–100, with 100 representing the highest possible degree of surgical completeness. Among 100 consecutive CRSwNP patients undergoing ESS in 2021 with postoperative topical steroid irrigations, including 75 revision surgeries, SNOT‐22 scores improved at 6 months postoperatively, with durable and consistent improvement at 24 months (p < 0.001). Preoperative CoSI scores in revision surgery patients were 49.4 ± 26.0, improving to 91.0 ± 8.1 postoperatively. SNOT‐22 scores for primary ESS patients and patients with a preoperative CoSI score of less than 70 improved by 26.4 and 28.1 points, respectively, in contrast to patients with a preoperative CoSI of 70 or greater (14.1 points, p = 0.029).It is important to define extent of surgery in CRSwNP to stratify postsurgical patients based on likelihood to benefit from revision surgery or alternative medications. The CoSI can be utilized to identify patients who are likely to improve significantly with revision surgical intervention. [ABSTRACT FROM AUTHOR]

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is associated with high levels of cysteinyl leukotrienes, prostaglandin D2, and low levels of prostaglandin E2. Further, 15-hydroxyeicosatetraenoic acid (15-HETE) levels may have predictive value in therapeutic outcomes of aspirin desensitization. Accumulation of nasal group 2 innate lymphoid cells (ILC2s) has been demonstrated during COX-1 inhibition in AERD, although the relationships between tissue ILC2 accumulation, reaction symptom severity, and novel lipid biomarkers are unknown. OBJECTIVE: We sought to determine whether novel lipid mediators are predictive of nasal ILC2 accumulation and symptom scores during COX-1 inhibitor challenge in patients with AERD. METHODS: Blood and nasal scraping samples from patients with AERD were collected at baseline and COX-1 inhibitor reaction and then processed for flow cytometry for nasal ILC2s and serum for lipidomic analysis. RESULTS: Eight patients with AERD who were undergoing aspirin desensitization were recruited. Of the 161 eicosanoids tested, 42 serum mediators were detected. Baseline levels of 15-HETE were negatively correlated with the change in numbers of airway ILC2s (r = -0.6667; P = .0428). Docosahexaenoic acid epoxygenase metabolite 19,20-dihydroxy-4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid (19,20-diHDPA) was positively correlated with both changes in airway ILC2s (r = 0.7143; P = .0305) and clinical symptom scores (r = 0.5000; P = .0081). CONCLUSION: Low levels of baseline 15-HETE predicted a greater accumulation of airway ILC2s in patients with AERD who were receiving COX-1 inhibition. Further, increases in the cytochrome P pathway metabolite 19,20-dihydroxy-4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid (19,20-diHDPA) were associated with increased symptoms and nasal ILC2 accumulation. Future studies to assess how these mediators might control ILC2s may improve the understanding of AERD pathogenesis.

Background: Our population‐based study has previously shown that being born in winter or spring was associated with adult‐onset asthma. The aim was to study if season of birth (SOB) is associated with airway allergy and related diseases: NSAID exacerbated respiratory disease (N‐ERD), asthma, allergic rhinitis (AR), nonallergic rhinitis (NAR), chronic rhinosinusitis with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP) in Finland. Methods: A randomly sampled retrospective registry‐based follow‐up data (n = 74,868) of patients visiting Hospital District of Helsinki and Uusimaa (HUS) in Finland was used. The birth date, sex, visit date and comorbidities were collected from electronic health record data during visits from 2005 to 2019. Results: The mean (SD, range) age of the sample was 34.53 (25.47, 0–102) years, with 48.7 % being men. We divided the whole population in four groups based on the season they were born (SOB‐groups). When observing these four SOB‐groups, the proportion of those having asthma was 43.1%, 42.1%, 41.1%, 42.7%, in winter, spring, summer, and autumn SOB‐groups, respectively. The proportion of those having AR was 12.6%, 12.0%, 10.7%, 12.1%, respectively. When having summer as a reference, being born in any other time of year was significantly associated with AR and, being born in autumn or winter was associated with asthma. No significant association was observed in CRS or N‐ERD or NAR groups in adjusted models. Conclusions: The study suggests that early life immunological events may have a role a role in pathogenesis of asthma and AR. As no association was observed between SOB and CRSsNP, CRSwNP, N‐ERD or NAR, further studies on this are warranted. [ABSTRACT FROM AUTHOR]

Significant advancements have been achieved in understanding the roles of different immune cells, as well as cytokines and chemokines, in the pathogenesis of eosinophilic airway conditions. This review examines the pathogenesis of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), marked by complex immune dysregulation, with major contributions from type 2 inflammation and dysfunctional airway epithelium. The presence of eosinophils and the role of T-cell subsets, particularly an imbalance between Treg and Th17 cells, are crucial to the disease's pathogenesis. The review also investigates the pathogenesis of eosinophilic asthma, a unique asthma subtype. It is characterized by inflammation and high eosinophil levels, with eosinophils playing a pivotal role in triggering type 2 inflammation. The immune response involves Th2 cells, eosinophils, and IgE, among others, all activated by genetic and environmental factors. The intricate interplay among these elements, chemokines, and innate lymphoid cells results in airway inflammation and hyper-responsiveness, contributing to the pathogenesis of eosinophilic asthma. Another scope of this review is the pathogenesis of Eosinophilic Granulomatosis with Polyangiitis (EGPA); a complex inflammatory disease that commonly affects the respiratory tract and small to medium-sized blood vessels. It is characterized by elevated eosinophil levels in blood and tissues. The pathogenesis involves the activation of adaptive immune responses by antigens leading to T and B cell activation and eosinophil stimulation, which causes tissue and vessel damage. On the other hand, Allergic Bronchopulmonary Aspergillosis (ABPA) is a hypersensitive response that occurs when the airways become colonized by aspergillus fungus, with the pathogenesis involving activation of Th2 immune responses, production of IgE antibodies, and eosinophilic action leading to bronchial inflammation and subsequent lung damage. This analysis scrutinizes how an imbalanced immune system contributes to these eosinophilic diseases. The understanding derived from this assessment can steer researchers toward designing new potential therapeutic targets for efficient control of these disorders. [ABSTRACT FROM AUTHOR]

Abstract Background Our population‐based study has previously shown that being born in winter or spring was associated with adult‐onset asthma. The aim was to study if season of birth (SOB) is associated with airway allergy and related diseases: NSAID exacerbated respiratory disease (N‐ERD), asthma, allergic rhinitis (AR), nonallergic rhinitis (NAR), chronic rhinosinusitis with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP) in Finland. Methods A randomly sampled retrospective registry‐based follow‐up data (n = 74,868) of patients visiting Hospital District of Helsinki and Uusimaa (HUS) in Finland was used. The birth date, sex, visit date and comorbidities were collected from electronic health record data during visits from 2005 to 2019. Results The mean (SD, range) age of the sample was 34.53 (25.47, 0–102) years, with 48.7 % being men. We divided the whole population in four groups based on the season they were born (SOB‐groups). When observing these four SOB‐groups, the proportion of those having asthma was 43.1%, 42.1%, 41.1%, 42.7%, in winter, spring, summer, and autumn SOB‐groups, respectively. The proportion of those having AR was 12.6%, 12.0%, 10.7%, 12.1%, respectively. When having summer as a reference, being born in any other time of year was significantly associated with AR and, being born in autumn or winter was associated with asthma. No significant association was observed in CRS or N‐ERD or NAR groups in adjusted models. Conclusions The study suggests that early life immunological events may have a role a role in pathogenesis of asthma and AR. As no association was observed between SOB and CRSsNP, CRSwNP, N‐ERD or NAR, further studies on this are warranted.

Chronic rhinosinusitis with nasal polyps (CRSwNP) causes nasal obstruction and olfactory dysfunction. Aspirin-exacerbated respiratory disease (AERD) is the triad of CRSwNP, asthma, and respiratory reactions to COX-1 inhibitors. Patients with AERD have elevated nasal IL-5 levels and high numbers of antibody-secreting cells (ASCs), including plasma cells and plasmablasts, in their polyp tissue; in addition, their nasal polyp (NP) IgE levels are correlated with disease severity and recurrence of nasal polyposis. We sought to explore differences in the transcriptomic profile, activation markers, and IL-5Rα expression and function of NP ASCs from patients with AERD and CRSwNP. NP tissue was collected from patients with AERD and CRSwNP and digested into single-cell suspensions. NP cells were analyzed for protein expression by mass cytometry. For IL-5Rα functional studies, plasma cells were purified and cultured in vitro with or without IL-5 and analyzed by bulk RNA sequencing. Compared with polyp tissue from patients with CRSwNP, polyp tissue from patients with AERD contained significantly more ASCs and had increased ASC expression of IL-5Rα. ASCs from patients with AERD expressed higher protein levels of B-cell activation and regulatory markers (CD40, CD19, CD32, and CD38) and the proliferation marker Ki-67. ASCs from patients with AERD also expressed more IL5RA , IGHE , and cell cycle– and proliferation-related transcripts (CCND2 , MKI67 , CDC25A, and CDC25B) than did ASCs from patients with CRSwNP. Stimulation of plasma cells from patients with AERD with IL-5 induced key cell cycle genes (CCND2 and PTP4A3), whereas IL-5 stimulation of ASCs from patients with CRSwNP induced few transcriptomic changes. NP tissue ASCs from patients with AERD express higher levels of functional IL-5Rα and markers associated with cell cycling and proliferation than do ASCs from patients with aspirin-tolerant CRSwNP. [ABSTRACT FROM AUTHOR]

Background: Previous studies have determined that up to 6% of patients with aspirin-exacerbated respiratory disease (AERD) have family history of AERD, indicating a possible link with genetic polymorphisms. However, whole exome sequencing (WES) studies of such associations are currently lacking. Objectives: We sought to examine whether WES can identify pathogenic variants associated with AERD. Methods: Diagnoses of AERD were confirmed in patients with nasal polyps and asthma. WES was performed using an Illumina sequencing platform. Human Phenotype Ontology terms were used to define the patients’ phenotypes. Exomiser was used to annotate, filter, and prioritize possible disease-causing genetic variants. Results: Of 39 patients with AERD, 41% reported a family history of asthma and 5% reported a family history of AERD. Pathogenic exome variants in the filaggrin gene (FLG) were found in 2 patients (5%). Other variants not known to be pathogenic were detected in an additional 16 patients (41%) in genes related to epithelial integrity and cellular interactions, including genes encoding desmoglein 3 (DSG3), dynein axonemal heavy chain 9 (DNAH9), collagen type VII alpha 1 chain (COL7A1), collagen type XVII alpha 1 chain (COL17A1), chromodomain helicase DNA binding protein-7 (CHD7), TSC complex subunit 2/tuberous sclerosis-2 protein (TSC2), P-selectin (SELP), and platelet-derived growth factor receptor-alpha (PDGFRA). Conclusion: WES identified a monogenic susceptibility to AERD in 5% of patients with FLG pathogenic variants. Other variants not previously identified as pathogenic were found in genes relevant to epithelial integrity and cellular interactions and may further reveal genetic factors that contribute to this condition.

Significant advancements have been achieved in understanding the roles of different immune cells, as well as cytokines and chemokines, in the pathogenesis of eosinophilic airway conditions. This review examines the pathogenesis of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), marked by complex immune dysregulation, with major contributions from type 2 inflammation and dysfunctional airway epithelium. The presence of eosinophils and the role of T-cell subsets, particularly an imbalance between Treg and Th17 cells, are crucial to the disease’s pathogenesis. The review also investigates the pathogenesis of eosinophilic asthma, a unique asthma subtype. It is characterized by inflammation and high eosinophil levels, with eosinophils playing a pivotal role in triggering type 2 inflammation. The immune response involves Th2 cells, eosinophils, and IgE, among others, all activated by genetic and environmental factors. The intricate interplay among these elements, chemokines, and innate lymphoid cells results in airway inflammation and hyper-responsiveness, contributing to the pathogenesis of eosinophilic asthma. Another scope of this review is the pathogenesis of Eosinophilic Granulomatosis with Polyangiitis (EGPA); a complex inflammatory disease that commonly affects the respiratory tract and small to medium-sized blood vessels. It is characterized by elevated eosinophil levels in blood and tissues. The pathogenesis involves the activation of adaptive immune responses by antigens leading to T and B cell activation and eosinophil stimulation, which causes tissue and vessel damage. On the other hand, Allergic Bronchopulmonary Aspergillosis (ABPA) is a hypersensitive response that occurs when the airways become colonized by aspergillus fungus, with the pathogenesis involving activation of Th2 immune responses, production of IgE antibodies, and eosinophilic action leading to bronchial inflammation and subsequent lung damage. This analysis scrutinizes how an imbalanced immune system contributes to these eosinophilic diseases. The understanding derived from this assessment can steer researchers toward designing new potential therapeutic targets for efficient control of these disorders.

Abstract Background Aspirin-exacerbated respiratory disease (AERD) and IgG4-related disease (IgG4RD) share a common pathway of Th2-mediated immune mechanism; there have been several cases of IgG4RD developed in patients with asthma, especially in those comorbid with chronic rhinosinusitis (CRS). IgG4RD has often been treated with systemic corticosteroids, rituximab, or immune-suppressive agents, but frequently failed with relapse. Case presentation Here, we present a case of a 64-year-old male patient with severe AERD with CRS complicated with IgG4RD, who has been successfully treated and maintained with anti-IL-4 receptor antibody, dupilumab after achieving unsatisfactory responses with previous treatments including steroids, rituximab, omalizumab, and reslizumab. The patient’s symptoms (periorbital swelling and asthmatic/nasal symptoms) were remarkably improved; serum levels of IgG4/IgE as well as plasmablast/eosinophil counts progressively decreased without any recurrence sign for over 2 years of dupilumab treatment. Conclusion These findings demonstrate that blocking the IL-4/IL-13 pathway with dupilumab can be an effective treatment with long-term safety in patients with severe AERD with CRS complicated by IgG4RD.

Background: The frontal sinus and its drainage pathway are difficult spaces to navigate surgically. The complexity of the frontal recess anatomy as well as inflammatory factors may influence outcomes of endoscopic frontal sinusotomy. It is not clear which factors are more important in determining post-operative frontal ostium patency. Objective: The objective is to investigate whether the distribution of fronto-ethmoidal cells, frontal recess dimensions and sinonasal inflammation predict frontal ostium patency at 1- and 2-years after endoscopic frontal sinusotomy. Methods: A retrospective review of 94 chronic rhinosinusitis patients (185 sides) who had undergone endoscopic frontal sinusotomies between 2015 and 2019 was conducted. Computed tomography was used to evaluate the type of fronto-ethmoidal cells present and determine the dimensions of the frontal recess. The International Classification of the Radiological Complexity of frontal recess and frontal sinus was used to grade the complexity of frontal recess anatomy. Mucosal inflammation was graded according to a structured histopathology report. Frontal ostium patency at 1- and 2-years post-operatively was recorded. Results: The frontal ostium patency rates were 80.9% and 73.4% at 1- and 2-years respectively. Eosinophilic predominance (adjusted OR 3.5, 95% CI 1.6–8.0, p = 0.003) and mucosal ulceration on histology (adjusted OR 4.5, 95% CI 1.1–17.9, p = 0.033) predicted ostial stenosis at 1 year. Smoking (adjusted OR 7.6, 95% CI 2.4–24.7, p = 0.001), aspirin exacerbated respiratory disease (AERD) (adjusted OR 7.6, 95% CI 1.9–30.1, p = 0.004) and histological findings of severe inflammation (adjusted OR 8.9, 95% CI 1.9–41.2, p = 0.005) were independent predictors of ostial stenosis at 2 years. Frontal cell patterns, frontal recess dimensions and frontal recess complexity did not predict frontal ostium stenosis at both 1- and 2-years post-operatively. Conclusion: Post-operative control of sinonasal inflammation is important in maintaining frontal ostium patency, regardless of frontal cell patterns or frontal recess dimensions. [ABSTRACT FROM AUTHOR]

KEY POINTS: Patients are increasingly turning to online education materials to aid with disease management.Patient education materials on aspirin‐exacerbated respiratory disease are of poor readability with significant room for improvement. [ABSTRACT FROM AUTHOR]

IntroductionAspirin desensitization (AD) and aspirin therapy after desensitization (ATAD) are therapeutic interventions for patients with aspirin-exacerbated respiratory disease (AERD). Our aim is to investigate whether its addition to endoscopic sinus surgery (ESS) improves the overall prognosis of the disease.MethodsA systematic review of the current literature including adult patients with a positive diagnosis of AERD undergoing endoscopic sinus surgery (ESS) in the context or in absence of upper airway comorbidity, prior to AD + ATAD.ConclusionThis review concludes that the surgical approach is beneficial in AERD, but its effects are short—lived. Surgery should be considered initially with subsequent AD + ATAD in AERD patients, due to the sustained improvement achieved compared to those receiving ESS alone.

Background: Aspirin-exacerbated respiratory disease (AERD) and IgG4-related disease (IgG4RD) share a common pathway of Th2-mediated immune mechanism; there have been several cases of IgG4RD developed in patients with asthma, especially in those comorbid with chronic rhinosinusitis (CRS). IgG4RD has often been treated with systemic corticosteroids, rituximab, or immune-suppressive agents, but frequently failed with relapse. Case presentation: Here, we present a case of a 64-year-old male patient with severe AERD with CRS complicated with IgG4RD, who has been successfully treated and maintained with anti-IL-4 receptor antibody, dupilumab after achieving unsatisfactory responses with previous treatments including steroids, rituximab, omalizumab, and reslizumab. The patient's symptoms (periorbital swelling and asthmatic/nasal symptoms) were remarkably improved; serum levels of IgG4/IgE as well as plasmablast/eosinophil counts progressively decreased without any recurrence sign for over 2 years of dupilumab treatment. Conclusion: These findings demonstrate that blocking the IL-4/IL-13 pathway with dupilumab can be an effective treatment with long-term safety in patients with severe AERD with CRS complicated by IgG4RD. [ABSTRACT FROM AUTHOR]

Background: Asthma with NSAID‐exacerbated respiratory disease (NERD) is associated with uncontrolled or severe asthma. NERD patients are more prone to severe allergic reactions and their asthma exacerbations lead to hospitalisations twice as often compared to patients with non‐NERD‐asthma. NERD patients are prone to recurrent nasal polyposis requiring frequent endoscopic sinus surgeries. However, the early risk factors of NERD are not fully understood. The aim was to identify risk factors of NERD among patients with adult‐onset asthma. Methods: We used data from 1350 population‐based adult asthmatics with adult‐onset asthma from Finnish national registers. NERD was defined as self‐reported wheeze or other typical respiratory symptoms after ingestion of NSAIDs. Thirty‐six covariates covering several domains (personal characteristics, life‐style, early life factors, asthma characteristics and multimorbidities) were selected based on literature and were studied in association with NERD using logistic regressions. Results: The study population included 153 (11.3%) asthmatics with NERD. Thirty‐six covariates were entered in univariate logistic regression analysis, in which 23 were associated with NERD (p < 0.05). These variables were entered in a multivariable logistic regression model in which allergic respiratory symptoms, female sex, osteoarthritis, difficult asthma, nasal polyps, second‐hand smoke exposure at home, having 3 or more older siblings and being overweight were significantly associated with asthma with NERD (p < 0.05). Overweight decreased the risk of NERD, other factors increased it. Conclusion: According to our study, risk factors of NERD in part are associated with female sex, BMI, exposure to tobacco smoke, allergy, orthopaedic disorders and infection history, and their early recognition might thus be important to manage the burden of NERD. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have suggested that patients with aspirin‐exacerbated respiratory disease (AERD) have a high likelihood of alcohol intolerance. The purpose of this systematic review is to identify if there is sufficient evidence to confirm this correlation and the impact of medical therapy on subsequent alcohol tolerance. Data Sources: PubMed, EMBASE, SCOPUS, EBSCO, Google Scholar, Cochrane Library, and Grey literature. We also performed snowballing on the identified observational studies (OS) for additional data. Review Methods: A systematic review was conducted from 1968 to 2022 to identify those studies describing AERD symptomatology triggered by alcohol intake. The primary outcome was to analyze the current literature for the association between alcohol intolerance and AERD symptoms. The secondary outcome looked for improvement in alcohol tolerance after aspirin desensitization or biological therapy. Results: A total of 775 studies were identified and 40 abstracts were evaluated. From these, 5 studies met the inclusion criteria. Of the 5 manuscripts, there was 1 case‐control, 2 cohort, and 2 cross‐sectional studies. A total of 522 participants with AERD and a history of alcohol consumption were included, with 52.8% reporting at least 1 sinopulmonary exacerbation after alcohol intake. One of 3 studies noted improvement in alcohol tolerance after medical therapy with aspirin desensitization. Conclusion: The current literature suggests that patients with AERD have a high risk of alcohol intolerance. Additionally, aspirin desensitization may improve alcohol tolerance in this patient population. [ABSTRACT FROM AUTHOR]

Aspirin-exacerbated respiratory disease (AERD) is characterized by eosinophilic asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and intolerance to cyclooxygenase-1 inhibitors. Interest is emerging in studying the role of circulating inflammatory cells in CRSwNP pathogenesis and its course, as well as their potential use for a patient-tailored approach. By releasing IL-4, basophils play a crucial role in activating the Th2-mediated response. The main aim of this study was to, first, investigate the level of the pre-operative blood basophils' values, blood basophil/lymphocyte ratio (bBLR) and blood eosinophil-to-basophil ratio (bEBR) as predictors of recurrent polyps after endoscopic sinus surgery (ESS) in AERD patients. The secondary aim was to compare the blood basophil-related variables of the AERD series (study group) with those of a control group of 95 consecutive cases of histologically non-eosinophilic CRSwNP. The AERD group showed a higher recurrence rate than the control group (p < 0.0001). The pre-operative blood basophil count and pre-operative bEBR were higher in AERD patients than in the control group (p = 0.0364 and p = 0.0006, respectively). The results of this study support the hypothesis that polyps removal may contribute to reducing the inflammation and activation of basophils. [ABSTRACT FROM AUTHOR]

Background: Epithelial barrier disturbances in CRSwNP patients play an important role in both the innate and adaptive immune responses, contributing to chronic inflammation, olfactory dysfunction, and impairments in quality of life. Objective: To evaluate the role of the sinonasal epithelium in disease and health, review the pathophysiology of epithelial barrier dysfunction in CRSwNP, and the immunologic targets for treatment. Methods: Literature review. Results: Blockade of cytokines such as thymic stromal lymphopoietin (TSLP), IL-4, and IL-13 have shown promise in barrier restoration and IL-13, specifically may be central to olfactory dysfunction. Conclusion: The sinonasal epithelium plays a crucial role in the health and function of the mucosa and immune response. Increased understanding of the local immunologic dysfunction has led to several therapeutics that can potentially restore epithelial barrier function and olfaction. Real world and comparative effectiveness studies are needed. [ABSTRACT FROM AUTHOR]

Background: Aspirin-exacerbated respiratory disease (AERD) is a chronic condition characterized by the presence of asthma, chronic rhinosinusitis with nasal polyposis, and sensitivity to aspirin and other non-steroidal anti-inflammatory drugs. Diagnosis is based on careful clinical history and physical examination, characteristic laboratory and radiographic findings, and, in unclear cases, aspirin challenge. Established treatment is founded on comprehensive endoscopic sinus surgery followed by topical steroids and aspirin desensitization. T2 biologics are now available for refractory cases. Objective: To summarize the historic literature on AERD, its diagnosis and treatment options, as well as to review the most current publications on the topic and explore areas for future research. Methods: A literature review utilizing the PubMed database was performed. Results: Seminal journal articles regarding the diagnosis and treatment of AERD were reviewed with close attention to evidence-based protocols and knowledge gaps in the field as areas for future research. Conclusion: AERD is a complex disease which requires careful diagnostic work-up and coordinated care between the allergist and rhinologist to facilitate optimal treatment outcomes. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti‐inflammatory drug (NSAID)–exacerbated respiratory disease (N‐ERD) has been considered an acquired condition. Positive first‐degree family history has been reported in 1% of cases. The geographic and genetic isolation of the Finnish population offers exceptional opportunities for inheritance studies. In this questionnaire study, we explored the familial aggregation of N‐ERD in 66 Finnish families of patients with N‐ERD. The majority of patients (67%) had a positive family history of NSAID intolerance, asthma, nasal polyposis, or N‐ERD. Furthermore, 55% had a positive first‐degree family history of asthma, 21% nasal polyposis, 20% NSAID intolerance, and 11% N‐ERD. The prevalence of asthma, nasal polyposis, NSAID intolerance, and N‐ERD among first‐degree relatives was 13%, 5%, 4%, and 2%, respectively. We present the pedigrees of the 44 affected families. According to our findings, Finnish patients with N‐ERD seem to have a genetic susceptibility to it. [ABSTRACT FROM AUTHOR]

Abstract Background Asthma with NSAID‐exacerbated respiratory disease (NERD) is associated with uncontrolled or severe asthma. NERD patients are more prone to severe allergic reactions and their asthma exacerbations lead to hospitalisations twice as often compared to patients with non‐NERD‐asthma. NERD patients are prone to recurrent nasal polyposis requiring frequent endoscopic sinus surgeries. However, the early risk factors of NERD are not fully understood. The aim was to identify risk factors of NERD among patients with adult‐onset asthma. Methods We used data from 1350 population‐based adult asthmatics with adult‐onset asthma from Finnish national registers. NERD was defined as self‐reported wheeze or other typical respiratory symptoms after ingestion of NSAIDs. Thirty‐six covariates covering several domains (personal characteristics, life‐style, early life factors, asthma characteristics and multimorbidities) were selected based on literature and were studied in association with NERD using logistic regressions. Results The study population included 153 (11.3%) asthmatics with NERD. Thirty‐six covariates were entered in univariate logistic regression analysis, in which 23 were associated with NERD (p

The recent discovery of innate lymphoid cells has revolutionized our understanding of the pathogenesis of immune diseases including allergy and asthma. Innate lymphoid cells (ILCs) are a heterogeneous collection of lymphocytes that lack antigen-specificity (non-T, non-B cells) and potently produce characteristic cytokines of T cell subsets (Th1, Th2, Th17). ILCs are divided into group 1 (ILC1s), group 2 (ILC2s), or group 3 (ILC3s). Similar to Th2 cells, ILC2s produce IL-4, IL-5, and IL-13, among others, and are present in increased numbers in samples from patients with many allergic disorders including asthma and chronic rhinosinusitis (CRS). Animal models have identified that ILC2s contribute to eosinophilic tissue infiltration, airway hyperresponsiveness, mucus production, as well as coordinate adaptive immune responses. Finally, recent studies support regulation of ILC2s by neuro-immune mechanisms as well as demonstrate a significant degree of plasticity between ILC subsets that may impact the immune responses in asthma and allergic airway diseases. Here, we review the current literature on ILC2s in human asthma and allergic airway diseases, as well as highlight some recent mechanistic insights into ILC2 function from in vitro studies and in vivo animal models.

Aspirin-exacerbated respiratory disease has fascinated and frustrated specialists in allergy/immunology, pulmonology, and otorhinolaryngology for decades. It generally develops in previously healthy young adults and is unremitting and challenging to treat. The classical triad of asthma, nasal polyposis, and pathognomonic respiratory reactions to aspirin and other cyclooxygenase-1 inhibitors is accompanied by high levels of mast cell activation, cysteinyl leukotriene production, platelet activation, and severe type 2 respiratory inflammation. The "unbraking" of mast cell activation and further cysteinyl leukotriene generation induced by cyclooxygenase-1 inhibition reflect an idiosyncratic dependency on cyclooxygenase-1–derived products, likely prostaglandin E 2 , to maintain a tenuous homeostasis. Although cysteinyl leukotrienes are clear disease effectors, little else was known about their cellular sources and targets, and the contributions from other mediators and type 2 respiratory inflammation effector cells to disease pathophysiology were unknown until recently. The applications of targeted biological therapies, single-cell genomics, and transgenic animal approaches have substantially advanced our understanding of aspirin-exacerbated respiratory disease pathogenesis and treatment and have also revealed disease heterogeneity. This review covers novel insights into the immunopathogenesis of aspirin-exacerbated respiratory disease from each of these lines of research, including the roles of lipid mediators, effector cell populations, and inflammatory cytokines, discusses unanswered questions regarding cause and pathogenesis, and considers potential future therapeutic options. [ABSTRACT FROM AUTHOR]

Abstract Background Complex airway disease such as Chronic Rhinosinusitis with Asthma or Aspirin Exacerbated Respiratory Disease requires a multidisciplinary approach to management and treatment. Many centers in the USA have created collaborative multidisciplinary clinics to support the management of these patients; however, similar structures do not appear to exist in Canada. Methods This mixed methods study used a combination of structured interviews and a cross-sectional national survey. Interviewees included members of the Canadian Rhinology Working Group and survey participants were a combination of academic and community Rhinologists, Respirologists and Allergists. All participation was voluntary and selection criteria was based on their involvement in treating complex airway disease. Our objective was to identify the current state of diagnosis and treatment of complex airway patients in Canada between Rhinology, Respirology and Allergy and understand the barriers, challenges and propose solutions to establishing a multidisciplinary airway clinic in Canada. Results Four Rhinologists participated in qualitative interviews and a convenience sample of 42 specialists through our known network responded to our quantitative survey. From our survey, 54.8% believed multidisciplinary clinics were necessary in the management of complex airway disease, providing better outcomes and cost-savings (69%, 45.2%). Most specialties agreed that history, physical, pulmonary function and skin prick testing was important for diagnosis (92.9%, 92.9%, 88.1%). If clinicians were to participate in a multidisciplinary clinic, they would be willing to forego an average of 14.2% of their mean daily income for that clinic. The ideal clinic location was split between a neutral shared location vs. a Rhinology clinic space (38.1%, 45.2%). Conclusions Complex airway diseases are currently managed in subspecialty silos resulting in fragmented care. Our study highlights gaps in management, areas for improvement and support for establishing multidisciplinary complex airway disease clinics in Canada to better treat this population.

Background: Pathophysiology-targeting treatments exist for aspirin-exacerbated respiratory disease (AERD) through aspirin desensitization and biologics, such as dupilumab. With increasing attention paid to these treatments, which may be associated with significant side effects and/or cost, there is little description of chronic rhinosinusitis with nasal polyps (CRSwNP) response to treatment with intranasal corticosteroids and saline irrigations in AERD. Objective: To determine the effect of intranasal budesonide irrigations for the treatment of CRSwNP in AERD. Methods: This is an observational study of 14 AERD patients presenting to a rhinology clinic for CRS who were treated with twice daily high volume, low pressure irrigations with 240 mL of saline to which a 0.5 mg/2 mL respule of budesonide was added. All participants completed a 22-item Sinonasal Outcome Test (SNOT-22) at enrollment and at follow up 1 to 6 months later. Polyp scores were also calculated at each time point. Results: SNOT-22 scores ranged from 26 to 98 (median: 40.5) at enrollment and 3 to 85 (median: 38.5) at follow-up. Polyp scores ranged from 2 to 6 (median: 4) at enrollment at 0 to 6 (median: 2) at follow-up. Over the treatment period, change in SNOT-22 score ranged from −38 to 16 (median: −18) and change in polyp score ranged from −2 to 0 (median: −0.5). Approximately 57% of participants experienced at least 1 minimal clinically important difference in SNOT-22 score and 21% of participants had a SNOT-22 score <20 at follow-up. Conclusion: Medical management with intranasal corticosteroids and saline irrigations alone leads to significant improvement in sinonasal symptomatology in a subset of AERD. [ABSTRACT FROM AUTHOR]

Biologic medications have dramatically altered the landscape for treatment of allergic conditions including aspirin-exacerbated respiratory disease (AERD) and allergic bronchopulmonary aspergillosis (ABPA). Biologics should be considered for patients who are refractory to first line therapies for ABPA. Biologics should be discussed with patients with AERD. Variable responses to different biologics indicate that there may be various endotypes of AERD and ABPA, similar to asthma. Alternative biologics may be considered in patients who fail to respond to initial treatment., Competing Interests: Disclosure J. Huang: nothing to disclose. A.A. White: Speaker Bureau for Regeneron/Sanofi, Optinose, AstraZeneca, Amgen, GSK, Blueprint; Advisory Board: Blueprint, Cogent, GSK, Regeneron; Research Support: Regeneron, United States, AstraZeneca, United Kingdom., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD) presents a significant challenge in clinical management owing to recalcitrant disease with accompanying profound impacts on patient quality of life. Although asthma represents a significant component of this disease, quality of life disruptions are driven primarily by recalcitrant sinonasal problems, olfactory dysfunction, and the associated psychosocial and dietary implications. This review delves into specific quality of life metrics used to assess NSAID-ERD and the associated health care burden and financial implications of this disease, offering insights into the comparative challenges in chronic rhinosinusitis with nasal polyps when available. The article reviews the associated costs and cost-effectiveness of NSAID-ERD-directed therapies, including endoscopic sinus surgery, aspirin desensitization, and biologic therapy. Although some of these emerging treatment approaches show promise, they also present numerous unanswered questions, reflecting the dynamic nature of this field. As the landscape of NSAID-ERD management continues to evolve, this review provides insights into the challenges faced by clinicians and underscores the need for further research to optimize patient care and quality of life outcomes., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Dupilumab, a mAb targeting IL-4Rα, improves upper and lower airway symptoms in patients with aspirin-exacerbated respiratory disease (AERD), but the mechanisms leading to clinical improvement are not fully elucidated. Our aim was to identify the mechanistic basis of clinical improvement in patients with AERD treated with dupilumab. A total of 22 patients with AERD were treated with dupilumab for 3 months for severe asthma and/or chronic rhinosinusitis with nasal polyps. Clinical outcomes were assessed at baseline and at 1 and 3 months after initiation of dupilumab. Nasal fluid, urine, blood, and inferior turbinate scrapings were collected at the 3 time points for determination of mediator levels, cellular assays, and RNA sequencing. Participants had rapid improvement in clinical measures, including sense of smell, sinonasal symptoms, and lung function after 1 month of treatment with dupilumab; the improvements were sustained after 3 months of dupilumab. Baseline severity of smell loss was correlated with lower nasal prostaglandin E 2 levels. Dupilumab increased nasal prostaglandin E 2 level and decreased levels of nasal albumin, nasal and urinary leukotriene E 4 , and serum and nasal IgE. Transcripts related to epithelial dysfunction and leukocyte activation and migration were downregulated in inferior turbinate tissue after treatment with dupilumab. There were no dupilumab-induced changes in nasal eosinophilia. Inhibition of IL-4Rα in AERD led to rapid improvement in respiratory symptoms and smell, with a concomitant improvement in epithelial barrier function, a decrease in inflammatory eicosanoid levels, and an increase in the anti-inflammatory eicosanoid prostaglandin E 2 level. The therapeutic effects of dupilumab are likely due to decreased IL-4Rα signaling on respiratory tissue granulocytes, epithelial cells, and B cells. [ABSTRACT FROM AUTHOR]

Background: Aspirin-exacerbated respiratory disease is characterized by asthma, chronic rhinosinusitis with nasal polyps, and sensitivity to aspirin and other cyclooxygenase-1 inhibitors. The use of medical identification by patients with aspirin-exacerbated respiratory disease can provide essential information to prevent accidental exposure to cyclooxygenase-1 inhibitor medications. There is no available literature on medical identification use in the aspirinexacerbated respiratory disease patient population. Methods: A cross-sectional survey study was designed to measure the perception of the need for a medical identification and its use by the patients diagnosed with aspirin-exacerbated respiratory disease at The Ottawa Hospital. Results: Six hundred eighty patients were identified in our registry with a documented sensitivity to nonsteroidal antiinflammatory drugs or aspirin; 12 additional patients were identified during a clinical visit. A total of 68 patients with aspirin-exacerbated respiratory disease met the inclusion criteria. Twenty-one patients were successfully enrolled. The majority (81%, n = 17) of the patients were not using any medical identification. The most common reason reported by patients for not using the medical identification was a lack of knowledge and awareness regarding its significance. Conclusion: In this survey of patients with aspirin-exacerbated respiratory disease, patients were found to have little knowledge regarding the benefits of medical identification use. Subsequently, medical identification use was very limited, supporting a clear need for further patient education and awareness. [ABSTRACT FROM AUTHOR]

Background: Identifying effective therapy for recalcitrant chronic rhinosinusitis with nasal polyposis (CRSwNP) is a major challenge; and subtypes such as aspirin-exacerbated respiratory disease (AERD) are even more difficult to treat. Evidence on topical antibiotics use in (CRSwNP) is lacking. Current consensus guidelines recommend against its routine use, but recent reviews show some benefit when managing recalcitrant disease after endoscopic sinus surgery (ESS). Objective: Evaluate the effect of culture-directed topical antibiotics on sinonasal outcomes in AERD patients with a positive perioperative sinonasal bacterial culture who have undergone ESS. Methods: A retrospective cohort study of AERD patients with positive sinonasal culture, who underwent ESS from 2016 to 2021 was performed. Forty-four patients were identified and stratified based on their postoperative medical treatment. Twenty-six underwent postoperative intranasal corticosteroids (INCS) alone, while eighteen underwent INCS plus a 4-weeks treatment with topical antibiotics. SNOT-22 and Lund-Kennedy score (LKS) were assessed preoperatively and at 4-weeks and 4-6 months after ESS. Results: A statistically significant improvement in the 4-weeks and 4-6 months postoperative SNOT-22 and LKS were noted within both groups (p<0.05). However, only a statistically significant difference was found in the 4-weeks postoperative LKS when comparing between treatment groups (p=0.01). Our linear regression model demonstrated a relationship between the use of combined therapy with INCS and topical antibiotics and the LKS 4-weeks post ESS (p=0.015). Conclusion: In AERD patients with a confirmed sinus infection, the combination of culture-directed topical antibiotics and intranasal corticosteroid irrigations in the postoperative period can provide a shortterm improvement in endoscopic scores. [ABSTRACT FROM AUTHOR]

Mast cells (MCs) contribute prominently to all allergic diseases, yet are still poorly understood owing to their exclusive residence in tissues. Recently, the use of RNA-sequencing, proteomics, and other technological advances have accelerated the acquisition of new knowledge. This includes an expanded definition of MC heterogeneity and developmental origins, previously unrecognized functions for MCs, discoveries of genetic causes of MC-related disorders, the introduction of new therapies for clonal MC disease, and the identification of new potential target for treatments. This issue of Advances addresses key studies from 2020 to 2021. [ABSTRACT FROM AUTHOR]

BackgroundIdentifying effective therapy for recalcitrant chronic rhinosinusitis with nasal polyposis (CRSwNP) is a major challenge; and subtypes such as aspirin-exacerbated respiratory disease (AERD) are even more difficult to treat. Evidence on topical antibiotics use in (CRSwNP) is lacking. Current consensus guidelines recommend against its routine use, but recent reviews show some benefit when managing recalcitrant disease after endoscopic sinus surgery (ESS).ObjectiveEvaluate the effect of culture-directed topical antibiotics on sinonasal outcomes in AERD patients with a positive perioperative sinonasal bacterial culture who have undergone ESS.MethodsA retrospective cohort study of AERD patients with positive sinonasal culture, who underwent ESS from 2016 to 2021 was performed. Forty-four patients were identified and stratified based on their postoperative medical treatment. Twenty-six underwent postoperative intranasal corticosteroids (INCS) alone, while eighteen underwent INCS plus a 4-weeks treatment with topical antibiotics. SNOT-22 and Lund-Kennedy score (LKS) were assessed preoperatively and at 4-weeks and 4-6 months after ESS.ResultsA statistically significant improvement in the 4-weeks and 4-6 months postoperative SNOT-22 and LKS were noted within both groups (p

Aspirin-exacerbated respiratory disease (AERD) is characterized by eosinophilic asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and intolerance to cyclooxygenase-1 inhibitors. Interest is emerging in studying the role of circulating inflammatory cells in CRSwNP pathogenesis and its course, as well as their potential use for a patient-tailored approach. By releasing IL-4, basophils play a crucial role in activating the Th2-mediated response. The main aim of this study was to, first, investigate the level of the pre-operative blood basophils’ values, blood basophil/lymphocyte ratio (bBLR) and blood eosinophil-to-basophil ratio (bEBR) as predictors of recurrent polyps after endoscopic sinus surgery (ESS) in AERD patients. The secondary aim was to compare the blood basophil-related variables of the AERD series (study group) with those of a control group of 95 consecutive cases of histologically non-eosinophilic CRSwNP. The AERD group showed a higher recurrence rate than the control group (p < 0.0001). The pre-operative blood basophil count and pre-operative bEBR were higher in AERD patients than in the control group (p = 0.0364 and p = 0.0006, respectively). The results of this study support the hypothesis that polyps removal may contribute to reducing the inflammation and activation of basophils.

[Display omitted] Aspirin-exacerbated respiratory disease (AERD) is a severe disease involving dysregulated type 2 inflammation. However, the role other inflammatory pathways play in AERD is poorly understood. We sought to broadly define the inflammatory milieu of the upper respiratory tract in AERD and to determine the effects of IL-4Rα inhibition on mediators of nasal inflammation. Twenty-two AERD patients treated with dupilumab for 3 months were followed over 3 visits and compared to 10 healthy controls. Nasal fluid was assessed for 45 cytokines and chemokines using Olink Target 48. Blood neutrophils and cultured human mast cells, monocytes/macrophages, and nasal fibroblasts were assessed for response to IL-4/13 stimulation in vitro. Of the nasal fluid cytokines measured, nearly one third were higher in AERD patients compared to healthy controls, including IL-6 and the IL-6 family–related cytokine oncostatin M (OSM), both of which correlated with nasal albumin levels, a marker of epithelial barrier dysregulation. Dupilumab significantly decreased many nasal mediators, including OSM and IL-6. IL-4 stimulation induced OSM production from mast cells and macrophages but not from neutrophils, and OSM and IL-13 stimulation induced IL-6 production from nasal fibroblasts. In addition to type 2 inflammation, innate and IL-6–related cytokines are also elevated in the respiratory tract in AERD. Both OSM and IL-6 are locally produced in nasal polyps and likely promote pathology by negatively affecting epithelial barrier function. IL-4Rα blockade, although seemingly directed at type 2 inflammation, also decreases mediators of innate inflammation and epithelial dysregulation, which may contribute to dupilumab's therapeutic efficacy in AERD. [ABSTRACT FROM AUTHOR]

Background: Complex airway disease such as Chronic Rhinosinusitis with Asthma or Aspirin Exacerbated Respiratory Disease requires a multidisciplinary approach to management and treatment. Many centers in the USA have created collaborative multidisciplinary clinics to support the management of these patients; however, similar structures do not appear to exist in Canada. Methods: This mixed methods study used a combination of structured interviews and a cross-sectional national survey. Interviewees included members of the Canadian Rhinology Working Group and survey participants were a combination of academic and community Rhinologists, Respirologists and Allergists. All participation was voluntary and selection criteria was based on their involvement in treating complex airway disease. Our objective was to identify the current state of diagnosis and treatment of complex airway patients in Canada between Rhinology, Respirology and Allergy and understand the barriers, challenges and propose solutions to establishing a multidisciplinary airway clinic in Canada. Results: Four Rhinologists participated in qualitative interviews and a convenience sample of 42 specialists through our known network responded to our quantitative survey. From our survey, 54.8% believed multidisciplinary clinics were necessary in the management of complex airway disease, providing better outcomes and cost-savings (69%, 45.2%). Most specialties agreed that history, physical, pulmonary function and skin prick testing was important for diagnosis (92.9%, 92.9%, 88.1%). If clinicians were to participate in a multidisciplinary clinic, they would be willing to forego an average of 14.2% of their mean daily income for that clinic. The ideal clinic location was split between a neutral shared location vs. a Rhinology clinic space (38.1%, 45.2%). Conclusions: Complex airway diseases are currently managed in subspecialty silos resulting in fragmented care. Our study highlights gaps in management, areas for improvement and support for establishing multidisciplinary complex airway disease clinics in Canada to better treat this population. [ABSTRACT FROM AUTHOR]

Patients with aspirin exacerbated respiratory disease (AERD) experience a severe and recalcitrant form of chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma, which are exacerbated by aspirin/NSAID ingestion. As compared with aspirin-tolerant CRSwNP, patients with AERD experience more severe olfactory dysfunction, which is one of the key contributors to the observed decrease in quality of life (QOL) in this disease. The objective of this paper is to review the published olfactory outcomes observed with various treatment modalities.

Objective: To review and evaluate outcomes of patients with aspirin-exacerbated respiratory disease (AERD) following endoscopic sinus surgery and subsequent aspirin desensitization. Methods: Electronic searches of OVID MEDLINE (1948 to September 10, 2019), EMBASE (1980 to September 10, 2019), and PubMed were performed on September 10, 2019. A systematic review of the literature was performed using the 2009 PRISMA guidelines. Studies with both preoperative and postoperative data for patients with AERD who underwent sinus surgery and aspirin desensitization were considered appropriate for inclusion. Publications were written in English and included patients aged 18 years or older. Results: Six studies met inclusion criteria for this systematic review. The primary outcome measure was change in symptom profile measured by patient-reported quality of life scores. The results demonstrate statistically significant improvement in symptoms following endoscopic sinus surgery, with sustained improvement following aspirin desensitization. Revision surgery rates were significantly lower in patients maintained on aspirin therapy. Conclusion: This review suggests that surgery followed by aspirin desensitization results in improvement in both subjective and objective outcome measures. The adjunctive use of aspirin desensitization allows for long-term stability in symptom scores. Recurrence of polyps and worsening symptoms requiring revision surgery occurs when aspirin maintenance therapy is interrupted.

Background: Aspirin-exacerbated respiratory disease (AERD) is an aggressive inflammatory disorder of the upper and lower respiratory tract. Corticosteroids, leukotriene modifiers, endoscopic sinus surgery (ESS), aspirin (ASA) desensitization, and biological immunomodulators are currently used to treat the disorder. Objective: The objective of this study was to determine the psychosocial impact of ESS and ASA desensitization on AERD patients. Methods: All AERD patients who underwent complete ESS were divided into two cohorts based on ASA desensitization status. The psychosocial metrics of the SNOT-22 were collected and analyzed at the following time points: pre-operative, 1-month, 3-month, 6-month, and 12-month after ESS. Results: One hundred and eighty-four AERD patients underwent ESS from November 2009 to November 2018. From this group, 130 patients underwent ASA desensitization (AD cohort) and 54 patients remained non-desensitized (ND cohort). AD patients showed a significantly greater reduction in total SNOT-22 scores over the study period compared to ND patients (p = 0.0446). Analysis of SNOT-22 psychosocial metrics showed a significantly greater improvement in patient productivity in the AD cohort when compared to the ND cohort (p = 0.0214). Further, a sub-group analysis accounting for subject attrition showed a significantly greater improvement in both productivity and concentration in AD patients when compared to the ND cohort (productivity: p = 0.0068; concentration: p = 0.0428). Conclusions: ESS followed by ASA desensitization decreases the overall psychosocial burden in AERD patients with a significant improvement in perceived productivity and concentration. This has significant implications given the psychosocial impact of chronic diseases.

Aspirin-exacerbated respiratory disease (AERD) patients with CRSwNP suffer from reduced quality of life, reduced economic productivity, and higher risk of depression and sleep dysfunction. These patients often require frequent medical and surgical therapy, including functional endoscopic sinus surgery for recalcitrant disease. Given this severity, anti-type 2 biologic treatments are being investigated for use in this subgroup of patients with CRSwNP, including Omalizumab and Dupilumab. Preliminary data suggests that SNOT-22 related quality of life improvements following treatment with biologics are comparable to the current standard of care in the short term, but there is a lack of long-term data and standardized regimen that makes direct comparison difficult. Biologic therapies additionally require continuous use to avoid recurrence, and currently cost many times more than existing medical or surgical therapies.

Objective: To provide a comprehensive state-of-the-art review of the emerging role of urine leukotriene E4 (uLTE4) as a biomarker in the diagnosis of chronic rhinosinusitis (CRS), aspirin-exacerbated respiratory disease (AERD), and asthma. Data Sources: Ovid MEDLINE(R), Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. Review Methods: A state-of-the-art review was performed investigating the role of uLTE4 as a diagnostic biomarker, predictor of disease severity, and potential marker of selected therapeutic efficacy. Conclusions: uLTE4 has been shown to be a reliable and clinically relevant biomarker for CRS, AERD, and asthma. uLTE4 is helpful in ongoing efforts to better endotype patients with CRS and to predict disease severity. Implications for Practice: Aside from being a diagnostic biomarker, uLTE4 is also able to differentiate aspirin-tolerant patients from patients with AERD and has been associated with objective disease severity in patients with CRS with nasal polyposis. uLTE4 levels have also been shown to predict response to medical therapy, particularly leukotriene-modifying agents. [ABSTRACT FROM AUTHOR]

Abstract Background Mepolizumab (MEP) is the first anti Interleukin (IL)-5 add-on therapy approved for the treatment of severe refractory eosinophilic asthma. Case presentation We describe here the case of a 49 years-old woman with Aspirin-exacerbated respiratory disease (AERD), chronic rhinosinusitis, nasal polyposis and eosinophilic gastroenteritis successfully treated with MEP. Several laboratory and clinical items improved during therapy; moreover MEP showed to be useful as steroid sparing agent. Conclusions This case supports that the use of mepolizumab can be effective also in other eosinophilic conditions different from asthma and this opens to new therapeutic perspectives.

Aspirin exacerbated respiratory disease (AERD) is known by the triad of chronic rhinosinusitis with nasal polyposis (CRSwNP), aspirin hypersensitivity, and asthma, but its etiology and physiopathogenesis are still unclear. This cross-sectional study was designed to investigate allergy and inflammatory cells (neutrophils vs. eosinophils) dominancy in nasal polyp tissue of patients with AERD compared to non-AERD patients. CRSwNP patients scheduled for endoscopic sinus surgery were recruited in this study. Nasal polyp tissue was analyzed for infiltrating cells, and Eosinophil dominant and neutrophil dominant polyps were determined. AERD was confirmed by oral aspirin challenge (OAC). Demographics data; history of asthma, exacerbation by using NSAIDs, routine use of aspirin, type of surgery (primary or revision), and results of skin prick test and spirometry were recorded. Pathology results and contributing factors compared between AERD and non-AERD patients. Sixty-five patients (39 women, 26 men) were enrolled in the study (mean age 38.83 ± 12.43 years). Thirty (46%) patients had positive OAC tests. Totally 41 patients (63.1%) had eosinophilic polyps. 80% of patients with eosinophilic polyp had positive OAC and were AERD (P < 0.05). There was no significant difference in demographics, revision surgery, and concomitant asthma between AERD and non-AERD groups (P > 0.05). The positive skin prick test was higher in AERD and also in eosinophilic polyp patients, but it was not statistically significant (P = 0.086 and P = 0.177). Eosinophilic polyps are more common in AERD. A positive skin prick test is associated with AERD and eosinophilic polyp. [ABSTRACT FROM AUTHOR]

Non-steroidal anti-inflammatory drug (NSAID)—exacerbated respiratory disease (NERD) is an adult-onset inflammatory condition of the upper and lower airways. It is characterized by the co-existence of asthma, nasal polyposis, and hypersensitivity to NSAIDs. Over one-fourth of patients also have symptoms of chronic middle-ear infection. The clinical course of NERD is often severe and generally requires multimodal treatment with recurrent surgical measures. Studies presenting the disease burden and subjective symptom control of NERD are limited. In this qualitative questionnaire study, we present the clinical characteristics of asthma, nasal polyposis, NSAID intolerance and possible recurrent or chronic middle-ear infection of 66 confirmed NERD patients treated at our tertiary referral center between January 2016 and May 2017. Additionally, we present the patient-reported disease control of asthma, nasal polyposis, and middle-ear symptoms on a four-category Likert scale. The proportion of NERD patients with recurrent or chronic middle-ear infection was 18%. The proportion of good or very good subjective disease control was 83% for asthma, 58% for nasal polyposis, and 33% for chronic middle-ear infection, if present. Chronic middle-ear infection is common among NERD patients and should more often be recognized as part of the entity. Together with nasal polyposis, chronic middle-ear infection seems to affect patients more than asthma. The patient's perspective of disease control should be considered when planning the interdisciplinary follow-up and treatment of NERD.

Background: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP), and aspirin‐exacerbated respiratory disease (AERD) have varying levels of inflammation and disease severity. Solitary chemosensory cells (SCCs) are enriched in nasal polyps, are the primary source of interleukin 25 (IL‐25) in upper airways, leading to type 2 inflammation, and are activated by bitter‐tasting denatonium benzoate (DB). Thus, we sought to evaluate DB taste perception at a range of concentrations in order to identify 1 that most differentiates CRS subgroups from controls. Methods: CRSsNP (n = 25), CRSwNP (n = 26), and AERD (n = 27) patients as well as controls (n = 25) tasted 6 DB concentrations in a fixed, random order, rating on a category scale of 0 (no intensity) to 12 (extremely intense). Sinonasal epithelial cultures were treated with and without denatonium and analyzed for IL‐25 via flow cytometry. Results: CRSsNP patients rated DB as significantly less intense than did controls at all concentrations: 5.62 × 10–9M, 1.00 × 10–8M, 1.78 × 10–8M, 3.16 × 10–8M, 5.62 × 10–8M, and 1.00 × 10–7M (all p < 0.0083). CRSwNP patients did not show significant differences from controls. AERD patients rated DB as significantly more intense than did controls at concentrations of 1.00 × 10–8M and 3.16 × 10–8M (p < 0.0083). In vitro data demonstrated significant increase in IL‐25–positive cells after denatonium stimulation (n = 5), compared to control (n = 5) (p = 0.012). Conclusion: Our findings link in vitro DB stimulation of sinonasal tissue with increased IL‐25 and show differential DB taste perception in CRS subgroups relative to the control group, with CRSsNP being hyposensitive and AERD being hypersensitive. We propose a concentration of 3.16 × 10–8M for future study of clinical utility. [ABSTRACT FROM AUTHOR]