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Purpose: This study evaluated whether stratified preoperative, pre- aspirin desensitization (AD) sinonasal symptom scores predict postoperative, post-AD outcomes in Aspirin exacerbated respiratory disease (AERD)., Materials and Methods: Retrospective chart review of patients with aspirin challenge-proven AERD who underwent endoscopic sinus surgery followed by AD was performed. Preoperative, postoperative/pre-AD, and postoperative/post-AD sinonasal symptom scores were collected (22-item Sino-Nasal Outcomes Test, SNOT-22). A longitudinal linear mixed-effects model was used for data analysis., Results: Forty-seven patients (59.6% female) aged 48.0 ± 13.2 were included. Average time from surgery to AD was 70.0 ± 52.8 days. Preoperative SNOT-22 scores (n = 47) were divided into tertiles (cutoffs of 36 and 54 indicating mild [22.5 ± 13.7], moderate [44.3 ± 12.2], and severe [72.9 ± 19.7] disease). This corresponded to 12 (25.5%), 18 (38.3%), and 17 (36.2%) subjects being categorized into mild, moderate, and severe tertiles, respectively. Postoperative, pre-AD SNOT-22 in all disease groups decreased and were not significantly different (12.3 ± 13.7, 11.1 ± 12.2, 22.7 ± 19.7; p = 0.074). At short-term post-AD, only the severe group worsened (35.0 ± 20.3, p < 0.001), whereas other groups demonstrated negligible change (9.3 ± 14.3 and 14.4 ± 12.2). At long-term post-AD, all groups redemonstrated convergence in symptom scores (23.7 ± 20.9, 19.4 ± 15.4, and 31.0 ± 27.6, p = 0.304)., Conclusion: Preoperative SNOT-22 scores may be used as a predictor of postoperative, post-AD patient-reported outcomes in AERD. Patients with mild and moderate disease may derive benefit from surgery and AD alone, while those with severe disease may require additional interventions (e.g., biologics)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aspirin-exacerbated respiratory disease (AERD) is characterized by the clinical triad of chronic rhinosinusitis with nasal polyps, asthma, and an intolerance to medications that inhibit the cycloxgenase-1 enzyme. Patients with AERD on average have more severe respiratory disease compared with patients with chronic rhinosinusitis with nasal polyps and/or asthma alone. Although patients with AERD traditionally develop significant upper and lower respiratory tract symptoms on ingestion of cycloxgenase-1 inhibitors, most of these same patients report clinical benefit when desensitized to aspirin and maintained on daily aspirin therapy. This Work Group Report provides a comprehensive review of aspirin challenges, aspirin desensitizations, and maintenance aspirin therapy in patients with AERD. Identification of appropriate candidates, indications and contraindications, medical and surgical optimization strategies, protocols, medical management during the desensitization, and recommendations for maintenance aspirin therapy following desensitization are reviewed. Also included is a summary of studies evaluating the clinical efficacy of aspirin therapy after desensitization as well as a discussion on the possible cellular and molecular mechanisms explaining how this therapy provides unique benefit to patients with AERD., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study is to explore the sinopulmonary outcomes of aspirin desensitization through a systematic review and meta-analysis., Data Sources: Embase and OVID Medline databases., Review Methods: A systematic review of published articles on outcomes following aspirin desensitization in any language for relevant articles was performed in February 2019. Outcomes included sinonasal quality-of-life assessment, sense-of-smell scores, FEV-1 (forced expiratory volume in 1 second), and medication/steroid use., Results: Thirteen studies met the inclusion criteria out of 6055 articles screened. Aspirin desensitization resulted in significant improvement in FEV-1 and reduction in asthma medication/steroid use ( P < .05). There was no significant improvement in the sinonasal quality of life of patients who underwent aspirin desensitization ( P = .098)., Conclusion: Aspirin desensitization appears to be effective in improving pulmonary outcomes and should be considered in the treatment of patients with aspirin-exacerbated respiratory disease. However, good-quality studies are still needed to determine the ideal protocol tailored to individual patients.

Aspirin-exacerbated respiratory disease (AERD) is characterized by eosinophilic chronic rhinosinusitis with nasal polyps, asthma, and upper-/lower-respiratory tract reactions to nonsteroidal antiinflammatory drugs. Persistent, severe disease, anosmia, and alcohol sensitivity is typical. AERD is mediated by multiple pathways, including aberrant arachidonic acid metabolism leading to elevated leukotriene E4 and decreased prostaglandin E2. Mast cell mediators (prostaglandin D2) and unique properties of eosinophils and type 2 innate lymphoid cells, along with receptor-mediated signaling, also contribute to AERD pathogenesis. Pharmacologic therapies are a cornerstone of AERD treatment and include leukotriene modifiers, corticosteroids, biologics, and aspirin., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose of Review: This review summarizes the latest information on the appropriate identification, evaluation, and treatment of patients with nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NSAID-ERD), also known as aspirin-exacerbated respiratory disease (AERD). Within the framework of our understanding of the underlying pathophysiology of NSAID-ERD, we also provide an update regarding new surgical techniques and newly available or upcoming medical therapies that may benefit these patients., Recent Findings: There have been considerable developments regarding recommendations for both the extent and timing of sinus surgery for NSAID-ERD. The last few years have also given us several new biologic medications that warrant consideration in the treatment of patients with recalcitrant NSAID-ERD. Further clinical trials are underway to investigate additional medications that may decrease the type 2 inflammation that dominates this disease. Despite the severe lower respiratory inflammation and recurrent nature of the nasal polyps in patients with NSAID-ERD, significant recent advances now afford much-improved quality of life for these patients. Careful collaboration between Allergy/Immunology and Rhinology specialists is imperative to ensure proper treatment of patients with NSAID-ERD.

Purpose: Aspirin-exacerbated respiratory disease (AERD) is a severe form of chronic rhinosinusitis with nasal polyps (CRSwNP) accompanied by asthma and an aspirin intolerance. The underlying pathomechanism of AERD still remains unclear, recent data suggest a complex inflammatory imbalance. In the present study, we investigated the cytokine patterns in AERD, CRSwNP and healthy control patients. Furthermore, we describe the change in cytokine level in the course of aspirin desensitization (AD) with continuous intake of aspirin., Methods: The study included a total of 104 participants, 48 healthy controls, 45 patients with nasal polyps and 11 patients with AERD undergoing AD. Nasal secretions were analyzed for IL-1β, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17, THF-α, IFN-γ, eotaxin and ECP using Bio-Plex Human Cytokine Assay and Uni-CAP FEIA. Baseline measurements of cytokine levels were performed in all 104 patients; in patients with AERD, follow-up was performed 1-6 and 6-24 months after the initiation of AD., Results: Our preliminary results show a T H 2 dominated, eosinophilic milieu in AERD patients, which decreased in the first weeks of AD. However, after 6 months of AD, proinflammatory cytokines show a tendency to increase again. Also, T H 1 as well as T reg associated cytokine seem to increase over time., Conclusions: For the first time, the present work shows the cytokine pattern in nasal secretions of AERD patients before and during AD. Further investigation of the complex interaction of inflammatory cytokines during AD might reveal important insights into the disease entity of AERD and open up new horizons for a targeted therapy.

Objectives: To assess the safety and efficacy of Aspirin desensitization combined with long-term Aspirin therapy in patients with Aspirinexacerbated respiratory disease (AERD)., Methods: We searched the PubMed, Ovid, Cochrane Library, and Google Scholar databases from inception to October 2018 for articles in English. We only included randomized controlled trials and parallel or cross-over studies in which adults with AERD were randomly assigned to undergo Aspirin desensitization and receive long-term Aspirin therapy or placebo., Results: A total of 869 citations were retrieved, and 6 studies met the criteria for analysis. All studies indicated that nasal symptoms, asthma symptoms, or both improved significantly after Aspirin desensitization. In addition, most studies reported a decline in corticosteroid dosage (oral and inhaled). The 4 studies that reported nasal polyps did not demonstrate a change in nasal polyps with Aspirin therapy compared with placebo. The dropout rates in all studies reviewed ranged from 5.8% to 55.7%, and the most common adverse events were gastrointestinal symptoms., Conclusions: Clearly, Aspirin desensitization and treatment are beneficial for AERD patients, with relief of nasal symptoms, improvement in asthma control, decrease in daily corticosteroid use, and no fatal adverse events. However, the long-term adverse effects of Aspirin desensitization and optimal dosage of Aspirin merit further investigation.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used throughout the world. They are frequently involved in hypersensitivity reactions, which range from local or mild reactions to systemic and severe reactions. Consequently, it is necessary to perform an exhaustive study of patients in order to make an accurate diagnosis, search for safe procedures in the case of severe reactions, and identify alternative treatment options. Various guidelines and protocols address the management of hypersensitivity to NSAIDs, although these vary widely from country to country. The Committees of Asthma, Rhinoconjunctivitis, and Drug Allergy of the Spanish Society of Allergy and Clinical Immunology (SEAIC) propose the present position statement on available options for provocation testing with aspirin/NSAIDs. This document is the fruit of an exhaustive review of current evidence and is based on recent publications addressing the diagnosis of patients with hypersensitivity to NSAIDs and on a consensus-oriented discussion among a group of experts from the SEAIC. The main objective was to draft an easy-toread, practical guideline for health care professionals in specialist areas who assess and manage patients with suspected hypersensitivity to NSAIDs. Furthermore, indications, contraindications, and procedures for oral, bronchial, and nasal provocation tests with aspirin/NSAIDs have been updated.

Background: Aspirin desensitization and treatment benefits most patients with aspirin-exacerbated respiratory disease (AERD), although some patients fail therapy. Our objective was to assess whether recent endoscopic sinus surgery (ESS) improved aspirin treatment outcomes in AERD patients who initially failed aspirin therapy., Methods: Outcomes of aspirin desensitization and treatment in AERD patients prospectively enrolled were assessed preoperatively and at 4, 12, and 24 weeks after ESS by determining changes in Asthma Control Test (ACT) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores and respiratory function. Biomarkers, including fractional excretion of nitric oxide (FeNO), spirometry, nasal inspiratory peak flow (NPF), immunoglobulin E (IgE), and eosinophil count, were measured., Results: Nineteen patients who benefited (responders) and 21 patients who failed (nonresponders) preoperative aspirin treatment with a distant history of ESS (mean, 48 months) were identified. Nonresponders were more likely to be African American (71%, p < 0.01) and have higher baseline IgE levels (252 kU/L vs 87 kU/L in responders, p < 0.01). 24 of the 40 patients (nine responders and 15 non-responders) required subsequent ESS and underwent another aspirin desensitization 3-4 weeks after ESS. All 24 patients tolerated a second round of aspirin desensitization and treatment. The primary aspirin therapy was associated with a significant increase in IgE in nonresponders, but there was no significant increase in IgE after the second aspirin desensitization and treatment., Conclusion: Antecedent ESS enhances aspirin treatment responses in AERD patients and may convert patients who failed aspirin treatment before surgery to a more responsive phenotype after ESS. Patients with higher baseline serum IgE levels may benefit from ESS performed shortly before aspirin desensitization and therapy., (© 2019 ARS-AAOA, LLC.)

Background: Aspirin desensitization is increasingly recommended for the treatment of aspirin-exacerbated respiratory disease (AERD). The objective of this study is to systematically review the efficacy and safety of aspirin desensitization in patients with AERD., Methods: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and World Health Organization (WHO) International Clinical Trials Registry Platform from inception to January 5, 2019. We included randomized trials and comparative observational studies in any language. Data extraction and risk of bias assessment were performed in duplicate independently., Results: Five randomized controlled trials (RCTs) enrolled 233 patients with AERD. Compared to placebo, aspirin desensitization (mean daily dose 800 mg) improved quality of life (risk ratio [RR] 2.00; 95% confidence interval [CI], 1.31 to 3.06; heterogeneity measure [I 2 ] = 0%; risk difference [RD] +24%; 22-item Sino-Nasal Outcome Test [SNOT-22] scale [0 to 110, higher worse]; mean difference [MD] -10.27 [95% CI, -6.39 to -14.15]; moderate-certainty); and respiratory symptoms (RR 2.20 [95% CI, 1.55 to 2.73], I 2 = 34%, RD +36%; American Academy of Otolaryngology (AAO) scale [0 to 20, higher worse]; MD -2.56 [95% CI,-1.12 to -3.92]; high-certainty). Aspirin desensitization increased adverse events severe enough to cause treatment discontinuation (major bleeding, gastritis, asthma exacerbation, or rash causing drug discontinuation, RR 4.39 [95% CI, 1.43 to 13.50], I 2 = 0%, RD +11%, moderate-certainty), and gastritis (RR 3.84 [95% CI, 1.12 to 13.19], I 2 = 0%, RD +9%, low-certainty). Findings were robust to sensitivity analyses. Two available observational studies were not informative because they lacked adjustment for confounders and/or contemporaneous controls., Conclusion: In patients with AERD, moderate-certainty and high-certainty evidence shows that aspirin desensitization meaningfully reduces symptoms of rhinosinusitis and improves quality of life, but results in a significant increase in adverse events., (© 2019 ARS-AAOA, LLC.)

Background: Aspirin challenge and desensitization remains the criterion standard in diagnosis and treatment for patients with aspirin-exacerbated respiratory disease (AERD), but the protocols can be time and resource intensive., Objective: To provide evidence that oral aspirin challenge and desensitization can be safely performed in an outpatient setting in 1 day., Methods: Forty-four patients with a confirmed diagnosis of AERD, stable asthma, and baseline FEV 1 value greater than or equal to 70% of predicted completed an oral aspirin challenge and desensitization protocol. The starting dose was 40.5 mg with escalating doses of aspirin (81, 162.5, 325 mg) at 90-minute intervals until symptoms were provoked. Desensitization was defined as tolerating a repeated administration of the provocative aspirin dose and at least 1 subsequent dose, bringing the total aspirin ingested during the in-clinic desensitization to 325 mg or more., Results: Ninety-three percent of patients completed the challenge and desensitization in 1 day, with an average protocol completion time of 9 hours and 29 minutes. Two patients (4.6%) chose to complete the protocol over 2 days. One patient (2.3%) was discontinued from the protocol because of ongoing abdominal discomfort and diarrhea. No patient required epinephrine, emergency department visit, or hospitalization., Conclusions: Patients with AERD on a stable asthma regimen and with a baseline FEV 1 value greater than or equal to 70% can be safely desensitized to aspirin using a 90-minute dose escalation protocol, starting at a dose of 40.5 mg, and defining desensitization as tolerance of the repeated provocation dose and at least 1 subsequent aspirin dose, bringing total cumulative daily dose to 325 mg or more. This protocol can routinely be completed in 1 day., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Clinical features of aspirin-exacerbated respiratory disease (AERD) are characterized by overproduction of cysteinyl leukotrienes (LT) and eosinophil activation, in which epithelial cells contribute to eosinophilic airway inflammation. Folliculin (FLCN) helps maintain the integrity of epithelial barrier, but little is known about FLCN in AERD., Objective: We investigated the role of FLCN in the pathogenic mechanisms of AERD., Methods: We recruited 178 subjects with AERD, 276 subjects with aspirin-tolerant asthma (ATA) and 71 normal healthy controls (NC) at Ajou Medical Center. Levels of FLCN and interleukin (IL)-8 in sera and supernatants were measured by ELISA. Peripheral blood eosinophils isolated from asthmatic patients were cocultured with human airway epithelial cells (HAECs) pretreated with LTE 4 , dexamethasone and montelukast. The intracellular expressions of FLCN, tight (TJ) (occludins, claudin-1) and adherens (AJ) junctions (E-cadherin) were analysed by Western blotting. shRNA was used to down-regulate FLCN (shFLCN) in HAECs., Results: Serum FLCN levels were significantly higher in AERD group than in ATA and NC groups (all P < 0.001). The cut-off value of 56.6 pg/mL was used to define the high FLCN phenotype (highFLCN). Asthmatic patients with highFLCN were associated with increased airway hyperresponsiveness to methacholine (P = 0.015). The serum FLCN level could discriminate AERD group from NC group with 82% sensitivity (AUC = 0.793, P < 0.001). When HAECs were exposed to LTE 4 , FLCN release was increased significantly (P < 0.05), which were amplified along with disruption of TJ and AJ expressions when HAECs were cocultured with eosinophils and LTE 4 (all P < 0.05); these effects were suppressed by dexamethasone and montelukast. FLCN knockdown reduced IL-8 release and occludin expression from shFLCN HAECs., Conclusions: Our findings suggest that high LT and airway eosinophilia increased FLCN release from HAECs, which enhance epithelial activation and disruption. Modulation of FLCN may be a potential target for AERD., (© 2018 John Wiley & Sons Ltd.)

Background: Aspirin-exacerbated respiratory disease (AERD) is a distinct eosinophilic phenotype of severe asthma with accompanying chronic rhinosinusitis, nasal polyposis, and hypersensitivity to aspirin. Urinary 3-bromotyrosine (uBrTyr) is a noninvasive marker of eosinophil-catalyzed protein oxidation. The lack of in vitro diagnostic test makes the diagnosis of AERD difficult. We aimed to determine uBrTyr levels in patients with AERD (n = 240) and aspirin-tolerant asthma (ATA) (n = 226) and to assess whether its addition to urinary leukotriene E 4 (uLTE 4 ) levels and blood eosinophilia can improve the prediction of AERD diagnosis., Methods: Clinical data, spirometry and blood eosinophilis were evaluated. UBrTyr and uLTE 4 levels were measured in urine by HPLC and ELISA, respectively., Results: Both groups of asthmatics (AERD, n = 240; ATA, n = 226) had significantly higher uBrTyr, uLTE 4 levels, and blood eosinophils than healthy controls (HC) (n = 71) (p < 0.05). ULTE 4 levels and blood eosinophils were significantly higher in AERD as compared to ATA (p = 0.004, p < 0.0001, respectively). whereas uBrTyr levels were not significantly different between both asthma phenotypes (p = 0.34). Asthmatics with high levels of uBrTyr (> 0.101 ng/mg Cr), uLTE 4 levels (> 800 pg/mg Cr) and blood eosinophils (> 300 cells/ul) were 7 times more likely to have AERD.. However, uBrTyr did not increase the benefit for predicting AERD when uLTE 4 and blood eosinophils were already taken into account (p = 0.57)., Conclusion: UBrTyr levels are elevated both in AERD and ATA as compared to HC, but they could not differentiate between these asthma phenotypes suggesting a similar eosinophilic activation. The addition of uBrTyr to elevated uLTE4 levels and blood eosinophils did not statistically enhance the prediction of AERD diagnosis.

Background: Aspirin-exacerbated respiratory disease (AERD) is characterized by chronic eosinophilic rhinosinusitis, nasal polyps, asthma, and respiratory sensitivity to aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). In addition to sensitivity to aspirin and NSAIDs, the majority of patients with AERD have been reported to have respiratory intolerance associated with the consumption of alcohol., Methods: A multicenter prospective cohort study was performed. Patients with AERD confirmed by aspirin challenge were eligible to participate. Those who described themselves as able to tolerate alcohol consumption were excluded. Patients underwent aspirin desensitization following endoscopic sinus surgery. A questionnaire was distributed to patients before and after desensitization to determine pre-desensitization and post-desensitization symptoms associated with alcohol ingestion., Results: Forty-five patients were enrolled and 37 patients completed the study. The most common pre-desensitization symptoms were nasal congestion (95.6%), rhinorrhea (46.7%), and wheezing (40%). Improvement in the ability to tolerate alcohol was noted in 86.5% of participants (95% confidence interval [CI], 75.5% to 97.5%) and 70.3% of participants (95% CI, 55.5% to 85.0%) described desensitization to be "very helpful" or "extremely helpful" for their ability to tolerate alcohol., Conclusion: The majority of patients with AERD who experience respiratory symptoms with alcohol consumption describe improvement in this domain following aspirin desensitization., (© 2018 ARS-AAOA, LLC.)

Background: Patients with aspirin-exacerbated respiratory disease (AERD) are distinguished from patients with aspirin-tolerant asthma (ATA) by significantly higher baseline concentrations of urinary leukotriene E 4 (uLTE 4 ). However, an overlap between the individual values of the groups exists., Objective: The objective of this study was to estimate the discriminative value of uLTE 4 concentration in differentiating between patients with AERD and patients with ATA and evaluate the diagnostic accuracy of uLTE 4 measurement alone and added to clinical parameters to predict AERD diagnosis in patients with asthma., Methods: Clinical data were collected from questionnaires. Spirometry, skin prick tests, total IgE, and blood eosinophilia were evaluated. ULTE 4 concentrations were measured in morning urine samples by enzyme-linked immune assay (ELISA)., Results: Patients with AERD (n = 247) had significantly higher uLTE 4 concentrations than those with ATA (n = 239). The uLTE 4 concentration of 800.0 pg/mg creatinine as measured by ELISA on a spot sample best discriminated the 2 groups (area under the curve 0.7; 95% confidence interval 0.66-0.74, sensitivity 49%, specificity 81%). The positive predictive value and negative predictive value (NPV), after considering the prevalence of AERD in the population of asthmatics, were 16% and 96%, respectively. Nasal polyps, upper airway symptoms, nasal corticosteroid treatment, asthma exacerbations, forced expiratory volume in the 1 second predicted, and age of asthma onset were independent predictors of AERD diagnosis. The addition of elevated uLTE 4 concentration to the set of clinical parameters enhanced slightly the prediction of AERD diagnosis beyond the level predicted by clinical parameters (P = .036)., Conclusions: A set of typical clinical parameters has a superior accuracy in prediction of AERD diagnosis than the measurement of uLTE 4 concentration alone. The addition of uLTE 4 concentration to clinical parameters slightly enhances the prediction of AERD diagnosis, especially due to a high NPV., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: We previously reported that the ILVBL gene on chromosome 19p13.1 was associated with the risk for aspirin-exacerbated respiratory disease (AERD) and the percent decline of forced expired volume in one second (FEV1) after an oral aspirin challenge test. In this study, we confirmed the association between polymorphisms and haplotypes of the ILVBL gene and the risk for AERD and its phenotype., Methods: We recruited 141 AERD and 995 aspirin-tolerant asthmatic (ATA) subjects. All study subjects underwent an oral aspirin challenge (OAC). Nine single nucleotide polymorphisms (SNPs) with minor allele frequencies above 0.05, which were present in the region from 2 kb upstream to 0.5 kb downstream of ILVBL in Asian populations, were selected and genotyped., Results: In an allelic association analysis, seven of nine SNPs were significantly associated with the risk for AERD after correction for multiple comparisons. In a codominant model, the five SNPs making up block2 (rs2240299, rs7507755, rs1468198, rs2074261, and rs13301) showed significant associations with the risk for AERD (corrected P = 0.001-0.004, OR = 0.59-0.64). Rs1468198 was also significantly associated with the percent decline in FEV1 in OAC tests after correction for multiple comparisons in the codominant model (corrected P = 0.033), but the other four SNPs in hapblock2 were not., Conclusion: To the best of our knowledge, this is the first report of an association between SNPs on ILVBL and AERD. SNPs on ILVBL could be promising genetic markers of this condition.

Aspirin hypersensitivity associated with chronic rhinosinusitis-with or without nasal polyposis-and asthma resistant to conventional therapy defines the aspirin-exacerbated respiratory disease (AERD). We describe the case of a 15-year-old female patient with adverse reaction to aspirin, chronic rhinosinusitis, and severe asthma. She also experienced chronic idiopathic urticaria worsened by non-steroidal anti-inflammatory drug administration. AERD was diagnosed based on clinical history and symptoms. Given the poor responsiveness to standard therapy for respiratory and cutaneous symptoms, omalizumab was administered for 24 weeks with control of respiratory symptoms and short term improvement of cutaneous symptoms. Pediatr Pulmonol. 2017;52:E26-E28. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are some of the most common culprits of drug-induced hypersensitivity reactions, and can lead to a wide array of adverse effects. The accurate and timely diagnosis of aspirin and NSAID-induced hypersensitivity reactions is important for both patient safety and for the initiation of appropriate disease-specific management and treatment. Because there are no reliably validated in vitro tests available, aspirin and NSAID challenges are considered to be the criterion standard for the diagnosis of these hypersensitivity reactions, though in some patients the diagnosis can be made on the basis of a clear clinical history., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction: Aspirin-exacerbated respiratory disease is defined by the clinical tetrad of aspirin sensitivity, nasal polyps, asthma, and chronic rhinosinusitis. Patients experience acute upper and lower airway reactions with exposure to aspirin and other cyclooxygenase-1 inhibiting medications. However, airway inflammation and disease progression occur even in the absence of exposure to these medications, often leading to aggressive polyp formation and need for systemic corticosteroids to treat exacerbations in asthma and rhinosinusitis. Areas covered: This review focuses on the direct and indirect complications of aspirin-exacerbated respiratory disease. Current and potential management strategies are discussed with emphasis on aspirin desensitization. Expert commentary: Aspirin desensitization remains the gold standard of treatment. Demonstrated benefits of desensitization include improved symptom scores, reduction in use of systemic corticosteroids, slowing of polyp regrowth, and tolerance of aspirin and other NSAIDs for various therapeutic purposes. Continued investigation into the pathogenic mechanisms of AERD is likely to yield new diagnostic and therapeutic approaches.

Aspirin-Exacerbated Respiratory Disease (AERD) and Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) are both characterized by the presence of chronic sinonasal inflammation and nasal polyps. Unlike in CRSwNP, AERD patients develop respiratory reactions following ingestion of COX-1 inhibitors. AERD patients also, on average, have worse upper respiratory disease with increased sinonasal symptoms, mucosal inflammation and requirements for revision sinus surgery when compared to CRSwNP patients. While no single genetic factor has been identified in either CRSwNP or AERD to date, differences in the metabolism of arachidonic acid as well as innate immune cell activation may uniquely contribute to AERD pathogenesis., Competing Interests: Whitney Stevens has no financial conflicts of interest. Robert Schleimer has served as a consultant with several pharmaceutical companies with interest in CRS, including Astra-Zeneca, Genentech, GSK, Intersect ENT, Merck, Regeneron and Sanofi. Dr. Schleimer is a founder, shareholder and advisor for Allakos., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aspirin-exacerbated respiratory disease (AERD) severity and its clinical phenotypes are characterized by genetic variation within pathways for arachidonic acid metabolism, inflammation, and immune responses. Epigenetic effects, including DNA methylation and histone protein modification, contribute to regulation of many genes that contribute to inflammatory states in AERD. The development of noninvasive, predictive clinical tests using data from genetic, epigenetic, pharmacogenetic, and biomarker studies will improve precision medicine efforts for AERD and asthma treatment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aspirin-exacerbated respiratory disease (AERD) is characterized by chronic rhinosinusitis with nasal polyps, asthma, and reactions to cyclooxygenase-1-inhibiting drugs. This condition is often refractory to standard medical treatments and results in aggressive nasal polyposis that often requires multiple sinus surgeries. Aspirin desensitization followed by daily aspirin therapy is an important treatment option, and its efficacy has been validated in multiple research studies. Aspirin desensitization is not without risk, but specific protocols and recommendations exist to mitigate the risk. Most patients with AERD can undergo aspirin desensitization in an outpatient setting under the supervision of an allergist., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Aspirin-exacerbated respiratory disease (AERD) represents a severe form of chronic rhinosinusitis (CRS) characterized by nasal polyposis, bronchial asthma, and aspirin intolerance. This syndrome, known as Samter's triad, is more difficult to manage than routine CRS and poses a challenge to the treating clinician. We performed a systematic review of the literature to determine the role of endoscopic sinus surgery in patients with AERD who are on adjuvant medical therapies., Data Sources: PubMed, Embase, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, Cochrane Technology Assessments, Cochrane Economic Evaluations, Cochrane Groups, and Clinicaltrials.gov., Review Methods: 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 were considered appropriate for inclusion. Publications were written in English, included patients aged 18 years or older, and had a minimum follow-up of 3 months., Results: Eighteen studies met criteria for inclusion in our review. The primary outcome was change in symptom profile as measured by sinonasal and asthma symptom scores. Most studies demonstrated improvement in sinus- and asthma-related symptoms and quality-of-life measures after endoscopic sinus surgery., Conclusion: This review, which did not exclude the use of concomitant medical therapy, suggests that surgery is beneficial in AERD management. Evidence demonstrates improvement in sinonasal and asthma symptom severity and frequency, radiographic and endoscopy scores, and quality of life after surgery., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.)

Aspirin-exacerbated respiratory disease (AERD) is a complex clinical syndrome characterised by severe asthmatic attack upon treatment with aspirin and/or non-steroidal anti-inflammatory drugs (NSAIDs). Genetic predisposition has been considered as a crucial determinant and candidate genes have concentrated especially on cysteinyl leukotrienes (LTs)-related genes as the inhibitory action of aspirin and NSAIDs on cyclooxygenase activity may cause overproduction of cysteinyl LTs. However, conflicting results have been reported, in parallel with replication studies in different ethnic groups. Thus, future areas of investigations need to focus on comprehensive approaches towards the discovery of other genetic biomarkers. Unfortunately, few papers have been reported about gene polymorphisms in Japanese patients with AERD. Here, we described on our recent genetic investigations on B2ADR, IL-13, IL-17A, CYP2C19, TBXA2R, CRTH2 and HSP70. This review indicates potential genetic biomarkers contributing to the early diagnosis of AERD, which may include CYP2C19 and HSP70 gene polymorphisms, and future validation studies in independent population are required to provide reassurance about our findings., (Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.)

Aspirin-exacerbated respiratory disease (AERD) is an asthma phenotype with a prevalence that ranges from 2% to 25% of the asthma population. The 2% prevalence applies to patients with mild and 25% to severe, persistent asthma. COX-1-inhibiting nonsteroidal anti-inflammatory drugs, including aspirin, aggravate the preexisting upper and lower respiratory disease, sometimes in a life-threatening manner. The upper airway disease is characterized by an eosinophilic, hyperplastic rhinosinusitis with polyps. Eosinophilia, both peripheral and in the airways with Th2 inflammation, characterizes this disease. The role of allergic sensitivity in AERD is unclear, even though more than 30% of affected patients produce specific IgE to environmental allergens. Clinically, the respiratory symptoms are not usually associated with allergen exposure. The mechanism responsible for this phenotype is likely related to leukotriene (LT) metabolism because patients who are affected compared with patients who were aspirin tolerant, produce greater amounts of cysteinyl LTs. The synthesis of cysteinyl LTs is further increased after aspirin challenge and symptom exacerbation. Eosinophilia as well as a variety of other biologic markers, for example, Th2 cytokines, peripheral blood periostin, and LT enzymes and receptors, are associated with AERD both in the blood and in respiratory mucosa. These markers may help identify patients with AERD, but aspirin or other nonsteroidal anti-inflammatory drugs challenge is the primary means to confirm the diagnosis. A variety of single nucleotide polymorphisms and genes are associated with AERD, but the studies to date are limited to select populations and have not conclusively demonstrated a uniform genetic pattern in subjects with this disease. Treatment of AERD can be challenging because the nasal symptoms, including polyposis, are often refractory to both surgery and medical treatment, and the asthma can be difficult to control. Aspirin desensitization, followed by daily aspirin administration, can improve both upper and lower respiratory tract symptoms in up to 60% of individuals., (Published by Elsevier Inc.)

Background: Aspirin-exacerbated respiratory disease (AERD) is distinguished from aspirin-tolerant asthma/chronic sinusitis in large part by an exuberant infiltration of eosinophils that are characterized by their overexpression of metabolic pathways that drive the constitutive and aspirin-induced secretion of cysteinyl leukotrienes (CysLTs)., Objective: We defined the inflammatory milieu that in part drives CysLT overproduction and, in particular, the role of IFN-γ in the differentiation of eosinophils., Methods: Quantitative real-time PCR was performed for TH1 and TH2 signature cytokines on tissue from control subjects, patients with chronic hyperplastic eosinophilic sinusitis, and patients with AERD, and their cellular source was determined. The influence of IFN-γ on maturation, differentiation, and functionality of eosinophils derived from hematopoietic stem cells was determined., Results: Gene expression analysis revealed that tissue from both aspirin-tolerant subjects and patients with AERD display a TH2 cytokine signature; however, AERD was distinguished from chronic hyperplastic eosinophilic sinusitis by the prominent expression of IFN-γ. Intracellular and immunohistochemical cytokine staining revealed that the major sources of these cytokines were the eosinophils themselves. IFN-γ promoted the maturation of eosinophil progenitors, as measured by increased mRNA and surface expression of CCR3 and sialic acid-binding immunoglobulin-like lectin 8 (Siglec-8). Additionally, IFN-γ increased the expression of genes involved in leukotriene synthesis that led to increased secretion of CysLTs. IFN-γ-matured eosinophil progenitors were also primed, as demonstrated by their enhanced degranulation., Conclusions: High IFN-γ levels distinguish AERD from aspirin-tolerant asthma and underlie the robust constitutive and aspirin-induced secretion of CysLTs that characterize this disorder., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

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: 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.

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]

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]

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]

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.

Introduction: NSAID-exacerbated respiratory disease (N-ERD) is mainly treated with topical and oral corticosteroids, as well as acetylsalicylic acid (ASA) treatment after desensitization (ATAD). During desensitization and ATAD, it is common to experience an exacerbation of respiratory symptoms and other side effects, which may lead to cessation of treatment. Objectives: The aim of this retrospective follow-up study was to evaluate the effect of ATAD on lung functions and respiratory symptoms, and to clarify the occurrence of adverse events. Methods: We analysed the patient data of 67 patients treated with ASA desensitization between 2006 and 2016 in three hospitals, concerning adverse events, respiratory symptoms, lung function tests, and reasons for discontinuation. Results: 26 patients discontinued AD or ATAD. The most common reasons for discontinuation were lack of response (9%) and side effects (18%). ATAD did not affect lung function values in the follow-up of up to 5 years. Upper respiratory symptoms improved in 31 (52%) and lower respiratory symptoms (LRS) in 7 (10%) cases. Side effects occurred in 42 (63%) cases, the most common being dyspepsia and lower respiratory symptoms. Conclusion: Our study suggests that ATAD has little effect on lower airway functions. Side effects were common, and discontinuation rates high.

This case report discusses the unusual finding of aural polyps as a manifestation of aspirin-exacerbated respiratory disease (AERD). A 55-year-old patient with a history of AERD, persistent otorrhea, and mixed hearing loss was found to have bilateral aural polyps and tympanic membrane perforations. He was treated with steroid and antibiotic otic drops and aspirin desensitization, with plans for future aural polypectomy and bone anchored hearing aid due to persistent hearing loss. Several prior cases of aural polyps have been reported in association with AERD, with treatment ranging from otic drops and oral steroids to surgical intervention and aspirin desensitization. Aural polyps may be a more common manifestation of AERD than previously thought and may require surgical intervention despite maximal medical therapy.

Background: We previously reported that the ILVBL gene on chromosome 19p13.1 was associated with the risk for aspirin-exacerbated respiratory disease (AERD) and the percent decline of forced expired volume in one second (FEV1) after an oral aspirin challenge test. In this study, we confirmed the association between polymorphisms and haplotypes of the ILVBL gene and the risk for AERD and its phenotype.Methods: We recruited 141 AERD and 995 aspirin-tolerant asthmatic (ATA) subjects. All study subjects underwent an oral aspirin challenge (OAC). Nine single nucleotide polymorphisms (SNPs) with minor allele frequencies above 0.05, which were present in the region from 2 kb upstream to 0.5 kb downstream of ILVBL in Asian populations, were selected and genotyped.Results: In an allelic association analysis, seven of nine SNPs were significantly associated with the risk for AERD after correction for multiple comparisons. In a codominant model, the five SNPs making up block2 (rs2240299, rs7507755, rs1468198, rs2074261, and rs13301) showed significant associations with the risk for AERD (corrected P = 0.001-0.004, OR = 0.59-0.64). Rs1468198 was also significantly associated with the percent decline in FEV1 in OAC tests after correction for multiple comparisons in the codominant model (corrected P = 0.033), but the other four SNPs in hapblock2 were not.Conclusion: To the best of our knowledge, this is the first report of an association between SNPs on ILVBL and AERD. SNPs on ILVBL could be promising genetic markers of this condition. [ABSTRACT FROM AUTHOR]

Background: Aspirin-exacerbated respiratory disease (AERD) is a chronic disease characterized by chronic rhinosinusitis, nasal polyposis, asthma, and intolerance to nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin challenge is considered the gold standard for diagnosing AERD. Many patients with AERD have reported clinical benefits when desensitized to aspirin and maintained on daily aspirin therapy. In this study, we have summarized aspirin challenges and aspirin desensitization in our division during the past ten years. Methods: We reviewed aspirin challenges and desensitization procedures performed in the Allergy and Immunology Division at the Hamad Medical Corporation, Doha, Qatar, between 2010 and 2020 from our procedures log registry and reported the results of the procedures. Results: The procedures were performed for patients with chronic rhinosinusitis, nasal polyposis, and bronchial asthma with a historical reaction to NSAIDs or those never exposed to NSAIDs. The challenge and desensitization procedure protocol is outlined in table.1. Of the 45 procedures performed, 36 (80%) patients reacted during aspirin desensitization; and their characteristics, historical reaction to NSAIDs, provoking dose, length of desensitization, and types of reactions were reviewed. Of the reactors, 32 (88%) patients completed aspirin desensitization successfully. The mean (± SD) age of patients was 46 (± 11.6) years, and 51% were women. The historical symptoms were asthma symptoms (56%) and naso-ocular (21%). The common (71%) reaction during the procedure was asthma symptoms, and 29% had naso-ocular symptoms. The provoking dose was 50–75 mg in most patients. The desensitization procedure was carried out over 2 days in most patients; however, 29% of the patients needed more than 2 days to complete the desensitization. None of the reactors needed emergency epinephrine use or hospital admission. Conclusion: In our review, desensitization was successful in all the patients who reacted to aspirin, and it was the only therapeutic choice for patients with AERD before the era of biologics. The procedure was well tolerated in most patients. Aspirin challenge was positive in 80% of our patients with suspected AERD, and this has an important diagnostic value that may help in choosing the proper biologic, such as dupilumab, for these patients. [ABSTRACT FROM AUTHOR]

Introduction: Aspirin-exacerbated respiratory disease (AERD) is a clinical entity characterized by hypersensitivity to aspirin leading to asthma and chronic rhinosinusitis with nasosinusal polyposis. The pathophysiology of the disease involves disruption at the level of arachidonic acid metabolism. Therefore, genetic association studies have been focused on the genes coding this pathway. As other mechanisms involved in the genesis of the disease were elucidated, the corresponding genes were also explored.Aim: To describe the association reported in the literature between gene polymorphisms involved in the pathophysiology or therapeutic processes of AERD.Results: There is a genetic association between polymorphisms of genes involved in the synthesis of proteins related to arachidonic acid metabolism (LTC4S, ALOX5), antigen presentation (HLA), inflammation (IL5, IL17), and aspirin metabolism (CYP2C19).Conclusions: Genetic association research in AERD has evaluated studies of SNPs in metabolic pathways related to arachidonic acid. Recently, whole genome analysis strategies have allowed the detection of new genetic variants that were previously not considered. Furthermore, these studies have identified SNPs that are associated with inflammatory processes, which could serve as diagnostic markers or predictors of the therapeutic response. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the efficacy and the underlining mechanism of aspirin desensitization among patients with Aspirin Exacerbated Respiratory Disease (AERD). Thirtyeight patients, who had undergone an aspirin challenge test and were diagnosed as having AERD, were engaged in a double-blind randomized clinical trial. They were divided into two groups--an active group of patients who went through aspirin desensitization, and the control group, receiving placebo. Clinical symptoms and the quality of life of the patients--in addition to the levels of interleukin 4 and 5 (IL4), (IL5)--were documented at the beginning of the study and again after six months of aspirin desensitization. The quality of life of the patients was significantly higher in the active group after six months (P = 0.001). Medication requirements and symptom score were manifested to be significantly lower in the active group after six months than at the beginning of the study (P = 0.005, 0.017 respectively). Forced expiratory volume in the second one (FEV1) was, also, significantly higher in the active group after six months of the study (P = 0.032). IL5 was found to be significantly lower in the active group after six months (P = 0.019). However, no significant difference was observed in the levels of IL4 between the two groups (P = 0.152). The study revealed that aspirin desensitization can improve the quality of life of patients with AERD, lessen their symptoms and medication requirements, lower their levels of IL5, and improve some pulmonary function tests such as FEV1. [ABSTRACT FROM AUTHOR]

Previously, we used a proteomic approach to demonstrate that the protein level of fatty acid-binding protein 1 (FABP1) is increased in nasal polyps in patients with aspirin-exacerbated respiratory disease (AERD). To reveal the genetic effect of FABP1 variants, we evaluated the association of FABP1 polymorphisms with the risk of AERD in 207 asthmatics with AERD and 1019 aspirin-tolerant asthmatics (ATA). Seven polymorphisms of FABP1 were selected from the National Center for Biotechnology Information (build 36) using minor allele frequency and linkage disequilibrium criteria. The genotype and haplotype distributions were not significantly different between the AERD and ATA groups in all of the genetic models. The percent decline of forced expiratory volume in 1 second (FEV1) after the oral aspirin challenge (OAC) test did not differ according to single-nucleotide polymorphism (SNP) genotypes. In haplotype analysis, asthmatic patients who were BL2ht2 homozygotes showed a greater decline in FEV1 after the OAC test than subjects who possessed 1 or no copy of BL2ht2 ( P = 0.035). However, these observations were not significant after correction for multiple comparisons (corrected P value = 1.00). Neither genotype nor haplotype was associated with the presence of nasal polyposis in the study subjects. Although we did not find a significant association between the FABP1 polymorphisms and AERD, our data suggest that the 7 SNPs are not associated with the increased expression of FABP1 in asthmatic patients with AERD. Further studies of epigenetic factors that may contribute to the increased expression of FABP1 in AERD should be performed. [ABSTRACT FROM AUTHOR]

Abstract: Aspirin exacerbated respiratory disease (AERD) is a distinct clinical entity characterized by eosinophilic rhinosinusitis, asthma and often nasal polyposis. Exposure to aspirin or other nonsteroid anti-inflammatory drugs (NSAIDs) exacerbates bronchospasms with asthma and rhinitis. Disease progression suggests a skewing towards TH2 type cellular response along with moderate to severe eosinophil and mast cell infiltration. Alterations in upper and lower airway cellular milieu with abnormalities in eicosanoid metabolism and altered eicosanoid receptor expression are the key features underlying AERD pathogenesis. Dysregulation of arachidonic acid (AA) metabolism, notably reduced prostaglandin E2 (PGE2) synthesis compared to their aspirin tolerant counterpart and relatively increased PGD2 production, a TH2/eosinophil chemoattractant are reported in AERD. Underproduced PGE2 is metabolized by overexpression of 15 prostaglandin dehydrogenase (15-PGDH) to inactive products further reducing PGE2 at real time. This relives the inhibitory effect of PGE2 on 5-lipoxygenase (5-LOX) resulting in overproduction of cysteinyl leukotrienes (CysLTs). Diminished formation of CysLT antagonists called lipoxins (LXs) also augments CysLTs responsiveness. Occasional intake of NSAIDs favors even more 5-LOX product formation, further narrowing the bronchoconstrictive bottle neck, resulting in acute asthmatic exacerbations along with increased mucus production. This review focuses on abnormalities in biochemical and molecular mechanisms in eicosanoid biosynthesis, eicosanoid receptor dysregulation and associated polymorphisms with special reference to arachidonic acid metabolism in AERD. [Copyright &y& Elsevier]

Anosmia with asthma and nasal polyposis raises suspicion for aspirin-exacerbated respiratory disease (AERD). Guidelines for desensitization of patients with AERD to prevent recurrent nasal polyposis and improve upper and lower respiratory symptoms are well established. We present a patient with an uncommon reaction to acetylsalicylic acid (ASA) and nonsteroidal anti-inflammatory drugs who required deviation from the standard ASA desensitization approach. [ABSTRACT FROM AUTHOR]