Aspirin Desensitization Research Articles

Rate of dupilumab use and symptom severity of patients with chronic rhinosinusitis with nasal polyposis after Draf 3 frontal sinusotomy.

The indications for endoscopic modified Lothrop procedure (Draf 3) in patients with refractory chronic rhinosinusitis with nasal polyposis (CRSwNP) remain unclear. This study evaluates the effectiveness of Draf 3 for refractory CRSwNP focusing on improvements in disease severity and need for subsequent dupilumab rescue therapy. Retrospective review of patients with CRSwNP undergoing Draf 3 surgery at a tertiary center between 2012 and 2022. Clinicodemographic variables were compared across those who did versus did not require rescue with postoperative dupilumab. Time to postoperative dupilumab rescue was analyzed and longitudinal disease-specific outcomes were measured using the sinonasal outcomes test (SNOT-22). Within 87 patients with CRSwNP, 24.1% had aspirin-exacerbated respiratory disease (AERD). Significant improvement in SNOT-22 score was found in CRSwNP with AERD (p<0.001) and without AERD (p=0.01) up to 24 months postoperative. 14.9% eventually required rescue with a dupilumab. More specifically, of 21 patients with AERD, 24.1% eventually required rescue with dupilumab. Dupilumab rescue was associated with a greater number of prior sinus surgeries (p=0.02), prior aspirin desensitization (p=0.02), and worse preoperative Lund-MacKay scores (p<0.001). No association between biologic rescue and frontal recess antero-posterior diameter was found (p=0.20). Draf 3 surgery in CRSwNP was associated with significant improvement in SNOT-22 score at 24 months. Furthermore, only 14.9% of patients required dupilumab rescue. Patients with AERD were more likely to require rescue with dupilumab even though 75.1% avoided treatment with the biologic over the study period.

The Burden of Nonsteroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease: Interplay Between Quality of Life and Economic Implications

NSAID-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. Though asthma represents a significant component of this disease, quality of life disruptions are driven primarily by recalcitrant sinonasal complaints, 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 healthcare burden and financial implications of this disease, offering insights into the comparative challenges in chronic rhinosinusitis with nasal polyps (CRSwNP) where available. The article reviews the associated costs and cost-effectiveness of NSAID-ERD-directed therapies, including endoscopic sinus surgery, aspirin desensitization, and biologic therapy. While 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.

Updates on the Natural History and Clinical Characteristics of NSAID-ERD

Nonsteroidal Anti-Inflammatory Drug Exacerbated Respiratory Disease (NSAID-ERD) is a distinct clinical syndrome characterized by NSAID hypersensitivity, asthma, and nasal polyposis. Its diagnosis is challenging due to variable presentations and a lack of simple tests, leading to diagnostic delays. Recent research has revealed its genetic predispositions, environmental triggers, and associations with atopy and second-hand tobacco smoke exposure or smoking cessation. Despite its severity, diagnostic awareness remains low, leading to the delay in effective management. Therapeutically, NSAID-ERD necessitates multidisciplinary approaches, often combining surgical interventions with medical management, including aspirin desensitization and biologic agents. However, predictive biomarkers for treatment response remain elusive. Understanding the underlying mechanisms driving NSAID-ERD pathogenesis and identifying reliable biomarkers are crucial for enhancing diagnostic accuracy and refining targeted therapeutic strategies for this debilitating condition. This review aims to provide a thorough understanding of NSAID-ERD, covering its history, clinical features, epidemiology, diagnosis, systemic and molecular biomarkers, available treatment options, and avenues for future research.

Biologics Reduce Symptoms of Alcohol Intolerance Better than Aspirin Desensitization in Patients with N-ERD and Nasal Polyps.

Non-steroidal anti-inflammatory drugs (NSAIDs) exacerbated respiratory disease (N-ERD) is associated with chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and NSAID hypersensitivity. An overproduction of leukotrienes characterizes the pathomechanism of the disease. N-ERD patients often report breathing difficulties after consuming alcohol. These symptoms have been observed in patients receiving either aspirin therapy after desensitization (ATAD), therapy with the biologics dupilumab (anti-IL-4Ra antibody) and omalizumab (anti-IgE antibody), or intranasal corticosteroid treatment (INCS). This retrospective, real-world study assessed the severity of alcohol-related and non-alcohol-related respiratory symptoms in CRSwNP/N-ERD patients 3-6 months after ATAD, biologic (dupilumab or omalizumab), or INCS therapy. A total of 171 patients (98 women and 73 men) were enrolled in the study. All groups received standard INCS therapy. Sixty-three patients were treated with ATAD; 48 received biologics (dupilumab n = 31; omalizumab n = 17); and 60 received INCS only and served as a control group. Alcohol-dependent symptoms and typical CRS symptoms (alcohol-independent) were quantified using visual analog scales (VAS). ATAD and biological therapy significantly reduced VAS scores for alcohol dependence and CRS symptoms. In the control group receiving INCS, only non-alcohol dependent CRS symptoms improved significantly (p < 0.05). The most significant differences in pre/post scores were observed in patients receiving dupilumab, with the most significant improvement in alcohol-dependent and CRS symptoms (dupilumab > omalizumab > ATAD). This real-world study shows that alcohol-related respiratory symptoms are a relevant parameter in CRSwNP/N-ERD patients. Patients benefit more from biologic therapy than from ATAD in terms of their alcohol-related symptoms and other CRS symptoms. Future studies should include placebo-controlled oral alcohol challenge.

Results of a survey on the current management of chronic rhinosinusitis with nasal polyps in Germany

With a prevalence of 0.55% to 4%, chronic rhinosinusitis with nasal polyps (CRSwNP) is a relevant part of the daily work of German otolaryngologists. The aim of the questionnaire-based data collection was to assess the current treatment status of CRSwNP in Germany. For this purpose, 24 questions within an anonymized online questionnaire were sent to all German ENT departments. Of 160 contacted ENT departments, 50 participated in the survey (31.3%). Among these, 76% performed more than 100 sinus surgeries annually and 38% treated more than 50 patients with biologics. Saline irrigations (80%) and intranasal glucocorticoids (GCS, 96%) were the most common conservative therapies. Systemic GCSs (52%) and intranasal GCS irrigation (20%) were less common. 80% of departments used biologics in the therapy of CRSwNP with an overall preference for dupilumab (70%). For therapy of aspirin intolerance, biologics (52%) were preferred to aspirin desensitization (26%). Prior to treatment with biologics clinical workup included the nasal polyp score (90%), the SNOT-22 questionnaire (84%), surrogate markers of type 2 inflammation (60%-72%), and computer tomography (50%). Final treatment success was assessed after 24 weeks (50%). Mostly, the responding departments followed German and European recommendations for diagnosis and therapy of CRSwNP. Therapy with biologics is widely used. The value of preoperative systemic GCS and the frequent performance of CT before initiation of therapy with a biologic should be debated in regard to its currently widespread use.

Progress in application of aspirin desensitization and maintenance therapy in aspirin-exacerbated respiratory disease

Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome characterized by chronic rhinosinusitis with nasal polyps, asthma and the development of significant airway symptoms following the ingestion of aspirin and other nonsteroid anti-inflammatory drugs (NSAIDs). At present, aspirin challenge is the gold standard for diagnosis. Aspirin desensitization and aspirin therapy after desensitization (ATAD) is one of the classical therapies. This paper described the application of aspirin desensitization and ATAD in AERD and provided the reference for the comprehensive treatment of AERD.

Biologic therapy in patients with severe NSAID-exacerbated respiratory disease and previous aspirin desensitization : Results of a multicentric study

Chronic rhinosinusitis with nasal polyps (CRSwNP) is atype‑2 inflammatory disease of the upper airways, with severe impairment of quality of life. Persons affected by NSAID-exacerbated respiratory disease (NERD) usually present with highly dynamic recurrence of polyps and disease despite prior treatment with sinus surgeries, oral corticosteroids, and aspirin desensitization (ATAD). Biologic therapy has fundamentally changed the choice of therapeutic concept; however, limited data exist on subgroups such as NERD patients. The aim of the current article is to report on amulticenter retrospective study on add-on therapy with dupilumab, omalizumab, and mepolizumab in patients with NERD. This is aretrospective cohort study of patients (NERD+, status after ATAD) in three reference centers in Germany (Munich, Mainz, Berlin). Subjective and objective parameters were collected at 4, 8, and 12months after biologic therapy initiation in accordance with current EPOS/EUFOREA (European Position Paper on Rhinosinusitis and Nasal Polyps/European Forum for Research and Education in Allergy and Airway Diseases) guidelines. Biologic agents were chosen depending on availability and patient characteristics. Treatment was commenced in 122patients meeting the criteria for CRSwNP and NERD. The endoscopic polyp score, SNOT-22 questionnaire score, visual analogue scoring of total symptoms/severity of disease, and sense of smell (psychophysical testing with Sniffin'Sticks/Brief Smell Identification Test, B‑SIT; Sensonics, Inc., Haddon Heights, NJ, USA) improved significantly after 4 and 12months of add-on therapy (p < 0.0001). All three biologic agents significantly improved one or more disease parameter. Adverse events were not life threatening but led to change of biologic agent in 4cases. Patients rated biologic therapy significantly better than ATAD, with improved long-term disease control. Add-on biologic therapy is effective, safe, and widely accepted among CRSwNP + NERD patients. Future studies might allow for personalized algorithms with sequential surgery, ATAD, and/or biologic therapy.

One- versus 2-day aspirin desensitization in aspirin exacerbated respiratory disease: Aquality improvement project.

Current aspirin desensitization protocols for aspirin-exacerbated respiratory disease (AERD) require from 1 to 3 days to complete. Our aim was to assess the implementation of a 1-day versus 2-day aspirin desensitization protocol in patients with aspirin-exacerbated respiratory disease. We used a preintervention-postintervention quality improvement design to compare the completion rates, reaction rates, and estimated costs of a 2-day versus 1-day aspirin desensitization. The cost for each desensitization was estimated on the basis of 2017-2020 US Medicare standards. We included the predesensitization variables for FEV1 value, urinary leukotriene E4 level, absolute eosinophil count (AEC), and total IgE level for each group. A total of 15 patients underwent a 2-day aspirin desensitization in the 4-year (2017-2020) preintervention period and were compared with 8 patients who underwent a 1-day aspirin desensitization in the 1-year (2021) postintervention period. The desensitization completion rate (93% vs 100% [P= 1]) and the mean number of reactions requiring intervention during the desensitization protocols (0.26 vs 0.8 [P= .14]) were similar between groups. The average time frame between last polypectomy and desensitization was longer in the 2-day group (1946 vs 39.2 days [P= .03]). The mean values for FEV1 level, urinary leukotriene E4 level, absolute eosinophil count, and total IgE level were 76% vs 83% (P= .6), 1084 vs 385 pg/mg (P= .2), 686 vs 306 cells/μL (P= .74), and 735 vs 278 kU/L (P= .5), respectively. The estimated direct cost reduction was $762 per aspirin desensitization for using 1-day vs 2-day aspirin desensitization. Compared with a 2-day protocol, the implementation of a 1-day aspirin desensitization was characterized by similar completion and reaction rates as well as lower costs.

Is endoscopic sinus surgery sufficient to modify the evolution of adult AERD? Aspirin desensitization as a maintenance factor: systematic review.

Aspirin 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. A 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. This 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.

Lower serum 15-HETE level predicts nasal ILC2 accumulation during COX-1 inhibition in AERD

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. 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. 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. 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). 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.

Association Between Aspirin-Exacerbated Respiratory Disease and Atherosclerotic Cardiovascular Disease: A Retrospective Review of US Claims Data

Aspirin-exacerbated respiratory disease (AERD) consists of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and hypersensitivity to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs). Asthma is associated with increased risk of atherosclerotic cardiovascular diseases (ASCVD). However, there is lack of data on association between AERD and ASCVD. To investigate the relationship between AERD and subsequent risk of ASCVD. An algorithm to find patients with AERD was generated and validated through chart review at our home institution. This algorithm was applied to a national insurance claims database to obtain data for a retrospective cohort study. Demographic and comorbidity data were obtained for propensity matching. Several methods of analysis were performed on the data. A total of 571 patients met criteria for AERD; 3909 met criteria for asthma, CRSwNP, and no allergy to aspirin or NSAIDs (group 1); and 75,050 met criteria for asthma, CRS without nasal polyps, and no allergy to aspirin or NSAIDs (group 2). After covariate adjustment, AERD was significantly associated with ASCVD, including severe ASCVD, over groups 1 and 2 regardless of asthma severity. Patients with AERD are at higher risk of ASCVD than patients with asthma and CRSwNP or CRS without nasal polyps, underscoring the need for early ASCVD screening and a consideration for aspirin desensitization or use of a nonaspirin antiplatelet agent in the setting of AERD and comorbid ASCVD.

Automated Identification of Aspirin-Exacerbated Respiratory Disease Using Natural Language Processing and Machine Learning: Algorithm Development and Evaluation Study.

Aspirin-exacerbated respiratory disease (AERD) is an acquired inflammatory condition characterized by the presence of asthma, chronic rhinosinusitis with nasal polyposis, and respiratory hypersensitivity reactions on ingestion of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). Despite AERD having a classic constellation of symptoms, the diagnosis is often overlooked, with an average of greater than 10 years between the onset of symptoms and diagnosis of AERD. Without a diagnosis, individuals will lack opportunities to receive effective treatments, such as aspirin desensitization or biologic medications. Our aim was to develop a combined algorithm that integrates both natural language processing (NLP) and machine learning (ML) techniques to identify patients with AERD from an electronic health record (EHR). A rule-based decision tree algorithm incorporating NLP-based features was developed using clinical documents from the EHR at Mayo Clinic. From clinical notes, using NLP techniques, 7 features were extracted that included the following: AERD, asthma, NSAID allergy, nasal polyps, chronic sinusitis, elevated urine leukotriene E4 level, and documented no-NSAID allergy. MedTagger was used to extract these 7 features from the unstructured clinical text given a set of keywords and patterns based on the chart review of 2 allergy and immunology experts for AERD. The status of each extracted feature was quantified by assigning the frequency of its occurrence in clinical documents per subject. We optimized the decision tree classifier's hyperparameters cutoff threshold on the training set to determine the representative feature combination to discriminate AERD. We then evaluated the resulting model on the test set. The AERD algorithm, which combines NLP and ML techniques, achieved an area under the receiver operating characteristic curve score, sensitivity, and specificity of 0.86 (95% CI 0.78-0.94), 80.00 (95% CI 70.82-87.33), and 88.00 (95% CI 79.98-93.64) for the test set, respectively. We developed a promising AERD algorithm that needs further refinement to improve AERD diagnosis. Continued development of NLP and ML technologies has the potential to reduce diagnostic delays for AERD and improve the health of our patients.

Monoclonal antibody or aspirin desensitization in NSAID-exacerbated respiratory disease (N-ERD)?

Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) is a clinical syndrome characterized by nasal polyposis, asthma, and intolerance to aspirin/NSAID. It affects approximately 15% cases of severe asthma, 10% of nasal polyps and 9% of rhinosinusitis. N-ERD results in associated asthma exacerbations, oral corticosteroids bursts, corticosteroid-dependent disease, and multiple endoscopic sinus surgeries. Unknown influences cause polyp epithelium to release alarmins, such as IL-33 and TSLP. These cytokines activate lymphoid cells, both Th2 and ILC2, to release cytokines such as IL5, IL4 and IL13, resulting in complex type 2 inflammation involving mast cells, eosinophils and platelets. Arachidonic acid released from such cells is metabolized into mediators. N-ERD is characterized by an imbalance in eicosanoid levels, especially CysLTs, PDG and PGE2. Patients with N-ERD present nasal symptoms (congestion, hyposmia/anosmia, nasal discharge) and lower airways symptoms (cough, sneezing, shortness of breath, chest tightness), anosmia, severe hyposmia as well as severe asthma which impacts the quality of life in this disease and leads to safety concerns in patients daily lives. Despite the variety of treatment strategies, the likelihood of recurrence of symptoms is high in patients with N-ERD. The most important strategies for treating N-ERD are listed as following: drug therapies, aspirin desensitization, monoclonal antibodies and other therapies associated. N-ERD treatment remains a major challenge in the current situation. Selecting the appropriate patient for aspirin desensitization, monoclonal antibodies or both is essential. This review provides an overview on aspirin desensitization and biologics in N-ERD and might help in decision making from both the perspective of the physician and patient. Patient characteristics, safety, efficacy, health care costs, but also patient preferences are all factors to take into account when it comes to a choice between biologics or aspirin desensitization.

Comparison of the clinical outcomes of patients with NSAID-exacerbated respiratory disease receiving aspirin or biologicals

Objective NSAID-exacerbated respiratory disease (NERD) is characterized by exacerbation of respiratory symptoms after NSAID intake. While research for specific treatment options continues in patients who cannot tolerate or are unresponsive to aspirin treatment after aspirin desensitization (ATAD), biologicals have emerged as a new therapeutic option in NERD patients. The aim of this study was to compare the quality of life, and the sinonasal and respiratory outcomes of NERD patients treated with ATAD or biologicals. Methods Patients who have been followed up at a tertiary care allergy center and who have been receiving at least one of ATAD, mepolizumab or omalizumab for at least six months were included. Evaluations were made using sinonasal outcome test (SNOT-22), asthma control test (ACT), short form-36 (SF-36), blood eosinophil counts, need for recurrent functional endoscopic sinus surgeries (FESS), and asthma or rhinitis exacerbations requiring oral corticosteroids (OCS). Results A total of 59 patients comprised of 35 (59%) females and 24 (41%) males with a mean age of 46.1 (min-max, 20–70) years were included. The baseline blood eosinophil count was higher, and a significant decrease in blood eosinophil counts was observed in the mepolizumab group compared to ATAD group (p = 0.001, p < 0.001, respectively). At follow-up, the rate of recurrent FESS was lower in the group that received mepolizumab (p = 0.02). Conclusions In NERD patients, mepolizumab significantly decreased blood eosinophil counts and recurrent FESS. There was no significant difference between the patients receiving ATAD or mepolizumab regarding other clinical parameters.

Abstract Number ‐ 136: Aspirin Desensitization in Cerebral Aneurysms and Management for the Neurointerventionalist

Introduction Aspirin (ASA) is the pillar of cerebrovascular and systemic vascular disease management. ASA allergy/hypersensitivity presents a challenge to the NeuroInterventionalist due to difficulties achieving optimum medical management prior to and after neurointerventional treatment. Currently there is vast cardiovascular literature describing successful ASA desensitization protocols, however the same cannot be said for neurointervention.The purpose of our study was to describe our experience with ASA hypersensitivity management in cerebrovascular disease and review of the relevant literature in patients with aneurysms. We present two cases of patients with cerebrovascular aneurysms requiring neurointervention with a pipeline embolization device who were successfully desensitized to their ASA hypersensitivity prior to treatment and the different variables encountered/approach for each patient. Methods N/A Results 37 yo F with history of pre‐eclampsia while pregnant with twins presented with complaints of a severe headache 22 days after delivery and on MRA head and neck had unruptured bilateral paraclinoid para‐ophthalmic internal carotid artery aneurysms. She was placed on Brilinta instead of Plavix due to subtherapeutic PruTest. She underwent successful endovascular coil embolization of the unruptured RIGHT paraclinoid para‐ophthalmic internal carotid artery aneurysm. Post coil embolization she underwent desensitization in the ICU for ASA under the care of the ICU physician and the allergist; 1mg, 5mg, 10mg, 20mg, 45mg ‐ each given 30 min apart. The protocol was followed by ASA 81mg the next morning and had successful endovascular flow diversion with Pipeline Flex Embolization Device for LEFT paraclinoid para‐ophthalmic internal carotid artery aneurysm. 71 yo F with history of uncontrolled HTN. During her hypertensive work‐up was found to have an approximately 6 mm unruptured right internal carotid artery aneurysm on CTA. She was successfully desensitized to ASA and optimized with Aspirin and Brilinta. She underwent successful endovascular flow diversion with Microvention FRED X Flow Diverter of the unruptured medially directed right paraclinoid ophthalmic segment internal carotid artery aneurysm. Conclusions There are few reports of ASA desensitization in patients with cerebral aneurysms ‐ due to this there are few established set protocols. We describe our protocol for high risk patients and post‐op management of patients undergoing neurointerventional procedures.We report these 2 case reports to help add to the current literature of ASA desensitization utilization in patients with CNS aneurysms and may help create more standardized protocols.

What's New in the Diagnosis and Treatment of Aspirin-Exacerbated Respiratory Disease: A Brief Review

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.

Aspirin desensitization in nonsteroidal anti-inflammatory exacerbated respiratory disease: The first prospective cohort in Chile.

Nonsteroidal anti-inflammatory exacerbated respiratory disease (N-ERD) is characterized by the Samter triad: chronic rhinosinusitis with nasal polyps, asthma, and nonallergic hypersensitivity to NSAIDs. Its diagnosis is based on a complete clinical history and an aspirin (ASA) challenge test. Medical treatments include biological drugs and ASA desensitization. This study aims to evaluate the clinical response of patients with N-ERD undergoing functional endoscopic surgery (FES), followed by ASA desensitization and maintenance treatment, being the first prospective cohort study carried out in Chile. We conducted 1-year follow-up of 12 patients with N-ERD treated with FES, desensitization, and maintenance with ASA. For each control, the medication score, sinonasal symptomatology (SNOT-22), PEF (peak expiratory flow), nasal polyposis (Lildholdt score), and the appearance of adverse effects were recorded. Computed tomography (CT) of the paranasal cavities was performed at baseline and at the 12-month follow-up to calculate the Lund-Mackay score. Patients presented a reduction of SNOT-22 after the FES, which was maintained at 12 months (p = 0.002); the symptoms that showed the greatest reduction were feeling embarrassed and nasal obstruction. The Lildholdt score was also significantly reduced (p = 0.001); in only three patients, the nasal polyps recurred, and all were small. The PEF showed a slight nonsignificant increase of 3.3%. In total, 75% of patients had an adverse effect, the most frequent being abdominal pain (66.7%), but none of the 12 patients required discontinuation of aspirin treatment in 1-year follow-up. The Lund-Mackay score had a significant reduction of 6.6 points (p < 0.001). ASA desensitization is safe and effective in reducing upper and lower respiratory symptoms in patients with N-ERD and delays the reappearance of nasal polyps, although it is not exempt from adverse effects, with the vast majority being mild.

Algorithmic Identification of Patients With Aspirin-Exacerbated Respiratory Disease Using an Electronic Health Record.

To determine whether an electronic health record (EHR) system can be used to identify cases of aspirin-exacerbated respiratory disease (AERD) in an area outside of a regional referral center with low rates of aspirin desensitization therapy. Retrospective chart review single academic tertiary care hospital. Single-site academic tertiary care hospital. Using Epic's SlicerDicer function, an algorithm was created and applied to all patient charts from 2013 to 2021. The algorithm was as follows: "Allergy/Contraindication to NSAIDs OR aspirin" AND "Diagnosis of Nasal polyp AND "Diagnosis of Asthma." Clinical data including demographics, NSAID reaction, and specialist involvement was collected. A total of 54 potential cases of AERD were identified. Thirty-twowere determined to have AERD after chart review, yet 12 of these patients (37.5%) had no mention of AERD within the chart. The 54 patients were stratified into 2 cohorts based on reaction to NSAIDs: respiratory (n = 29) or unspecified (n = 25). Of the patients in the respiratory reaction group, 26 were found to have clinical AERD, demonstrating a positive predictive values (PPV) of 89.7%. The overall PPV was 59.3%. Those with a respiratory reaction to NSAIDS listed in the EHR were more likely to have clinical AERD (odds ratio27.44; confidence interval6.08-123.85; p < 0.0001). Only 2 patients (6.3%) underwent aspirin desensitization. AERD remains under-diagnosed in the study population. The informatics algorithm presented here has a high positive predictive value for identifying clinical AERD patients in a geographical area with low rates of aspirin desensitization and may aid in identifying candidates for expanded treatment options.

The role of oxylipins in NSAID-exacerbated respiratory disease (N-ERD).

Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) is characterized by nasal polyp formation, adult-onset asthma, and hypersensitivity to all cyclooxygenase-1 (COX-1) inhibitors. Oxygenated lipids are collectively known as oxylipins and are polyunsaturated fatty acids (PUFA) oxidation products. The most extensively researched oxylipins being the eicosanoids formed from arachidonic acid (AA). There are four major classes of eicosanoids including leukotrienes, prostaglandins, thromboxanes, and lipoxins. In N-ERD, the underlying inflammatory process of the upper and lower respiratory systems begins and occurs independently of NSAID consumption and is due to the overproduction of cysteinyl leukotrienes. Leukotriene mediators all induce edema, bronchoconstriction, and airway mucous secretion. Thromboxane A2 is a potent bronchoconstrictor and induces endothelial adhesion molecule expression. Elevated Prostaglandin D2 metabolites lead to vasoconstriction, additionally impaired up-regulation of prostaglandin E2 leads to symptoms seen in N-ERD as it is essential for maintaining homeostasis of inflammatory responses in the airway and has bronchoprotective and anti-inflammatory effects. A characteristic feature of N-ERD is diminished lipoxin levels, this decreased capacity to form endogenous mediators with anti-inflammatory properties could facilitate local inflammatory response and expose bronchial smooth muscle to relatively unopposed actions of broncho-constricting substances. Treatment options, such as leukotriene modifying agents, aspirin desensitization, biologic agents and ESS, appear to influence eicosanoid pathways, however more studies need to be done to further understand the role of oxylipins. Besides AA-derived eicosanoids, other oxylipins may also pay a role but have not been sufficiently studied. Identifying pathogenic N-ERD mechanism is likely to define more effective treatment targets.

SNOT-22 scores after 6 months of aspirin therapy are predictive of long-term quality of life in AERD

Background: Aspirin exacerbated respiratory disease (AERD) is an inflammatory condition that consists of eosinophilic asthma, chronic rhinosinusitis with nasal polyps, and respiratory reactions to cyclooxygenase-1 inhibitors. Aspirin therapy after aspirin desensitization (ATAD) is the most extensively studied treatment paradigm for AERD. Objective: The objective was to identify which time point of ATAD was most predictive of long-term outcomes as measured by the 22-item Sino-Nasal Outcome Test (SNOT-22). Methods: A retrospective chart review was conducted of patients at a single institution who underwent endoscopic sinus surgery, followed by ATAD, and had remained on ATAD for 2 consecutive years. SNOT-22 scores were recorded at predesensitization as well as at the 3-, 6-, 12-, and 24-month postdesensitization time points. The patients were separated into two cohorts at each of the data collection time points based on whether their SNOT-22 scores were < 20 (responders) or ≥ 20 (nonresponders). Responder status was compared between each time point and at 24-month postdesensitization. The odds ratios (OR) were then calculated between the two groups at each of the following time points: postsurgery/predesensitization, and 3-, 6-, and 12-month postdesensitization. Results: There were 70 patients who met the inclusion criteria of having 24-month postdesensitization SNOT-22 scores available. Responder status at 6 months after surgery had the most predictive OR 16.5 (95% confidence interval, 3.71-73.44) for long-term outcomes at 24 months. Conclusion: The SNOT-22 scores after 6 months of ATAD showed the greatest predictive value for long-term quality-of-life outcomes and, therefore, poor 6-month SNOT-22 scores could serve as a basis for consideration of alternative therapies.