Management Of Aspirin-exacerbated Respiratory Disease Research Articles

Personalized management of aspirin-exacerbated respiratory disease: From clinical presentation to therapeutic strategies

Aspirin-exacerbated respiratory disease (AERD), defined as the triad of asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and development of upper- and/or lower-respiratory symptoms after exposure to aspirin or other cyclooxygenase-1 inhibitors, has a prevalence of up to 30% for adults with asthma and with CRSwNP. The pathogenesis is likely due to a combination of abnormal genetic variants and environmental exposures, which results in types 1, 2, and/or 3 inflammation and dysregulation of arachidonic acid metabolism. Patients with AERD often fail to respond to conservative medical treatment, including all topical corticosteroids, antileukotrienes, and saline solution irrigation; furthermore, short courses of SCS generally provide only temporary improvement. Advanced therapeutic options include endoscopic sinus surgery; aspirin treatment after aspirin desensitization; and biologics, e.g., dupilumab, omalizumab, and mepolizumab. A successful and long-lasting clinical response often requires combination or sequential treatments with more than one of these therapeutic approaches. After a review of the efficacy, safety, and logistical considerations of each of these therapeutic options, an algorithmic approach for patient management is presented.

GASTROINTESTINAL SYMPTOMS WITH ASPIRIN-EXACERBATED RESPIRATORY DISEASE MAY INCREASE RISK FOR FAILURE DURING RAPID ASPIRIN DESENSITIZATION

<h3>Introduction</h3> Aspirin-exacerbated respiratory disease (AERD) is a chronic condition with polyposis, asthma, and sensitivity to nonsteroidal anti-inflammatory drugs. Management of AERD is often through aspirin desensitization, which historically was a two-day or longer process. Few studies have examined specific phenotypes with the safety and efficacy of a one-day oral aspirin desensitization protocol. <h3>Methods</h3> We completed a single-center, retrospective chart review analyzing all patients with AERD who underwent a rapid, one-day aspirin desensitization from October 2018-April 2022. Descriptive statistics were used to analyze the data. <h3>Results</h3> Thirty-two of 36 (89%) subjects underwent successful aspirin desensitization. Sixty-six percent (21/32) of successful desensitization were completed in a single day (6.4 hours) and 34% (11/32) in two days (9.4 hours). The most common dose to illicit symptoms was 81 mg in the one-day group and 120 mg in the two-day group. Sinonasal symptoms during the reaction were the most common in both groups. Thirty-eight percent (8/21) of the one-day subjects discontinued aspirin maintenance therapy with 50% (4/8) initiating dupilumab. Similarly, 27% (3/11) of the two-day group discontinued aspirin with 33% (1/3) initiating dupilumab. Of the 4 subjects who failed desensitization, 3 had severe gastrointestinal symptoms with 1 requiring epinephrine at the clinic. <h3>Conclusion</h3> A single-day oral aspirin desensitization procedure appears safe and effective for AERD. Patients who failed desensitization more likely had gastrointestinal reactions to aspirin. Further research is necessary to explore the role of gastrointestinal reactions in AERD and the likelihood of failing aspirin desensitization.

New concepts for the pathogenesis and management of aspirin-exacerbated respiratory disease.

The purpose of this review is to provide a comprehensive summary of the current understanding of the pathogenesis of aspirin-exacerbated respiratory disease (AERD), and an update on its management. Elevated levels of 15-oxo-eicosatetraenoic acid (15-Oxo-ETE), a newly described metabolite of arachidonic acid, have been identified in nasal polyps of AERD patients. In nasal polyps, activated basophils, and interleukin-5 -receptor-α-positive IL-5Rα+ plasma cells are associated with more severe nasal polyposis in AERD. Alveolar monocyte-derived macrophages and their persistent proinflammatory activation were suggested as putative factors contributing to AERD. Although not AERD-specific, three biological agents are now available for the management of both nasal polyposis and asthma. A newly downstream product of 15-lipoxygenase, 15-Oxo-ETE, was recently found to be significantly elevated in nasal polyps from AERD patients. This eicosanoid metabolite likely originates from an interplay between epithelial cells and mast cells. Nasal polyp basophils, IL-5Rα+ plasma cells, and alveolar macrophages were identified as important contributors to inflammation in AERD. Besides traditional aspirin desensitization and treatment for AERD management, several biologics for treatment of asthma are available, including three that have been approved for nasal polyposis. These biologic agents show variable rates of success in controlling AERD symptoms.

Effectiveness of endoscopic sinus surgery and aspirin therapy in the management of aspirin-exacerbated respiratory disease.

Background: Aspirin therapy and/or type 2 (T2) biologics are used in the management of aspirin-exacerbated respiratory disease (AERD). Objective: To identify the number of patients with AERD who tolerated aspirin therapy, yet due to persistent symptoms, incorporated T2 biologic management. Methods: A retrospective review was performed between July 2016 and June 2019. Patients with AERD and who underwent endoscopic sinus surgery (ESS), aspirin desensitization (AD), and at least 6 months of aspirin therapy (ATAD) after AD, and who remained biologic-naive up through this timepoint were included in the study. Introduction of a T2 biologic while on ATAD was the primary outcome. The secondary outcome was a change in a validated patient-reported outcome measure for chronic rhinosinusitis score between the postoperative predesensitization timepoint, and the 6-month postdesensitization timepoint, presented as means and compared by using the Student's t-test. Results: A total of 103 patients met inclusion criteria. Two patients (1.9%) ultimately supplemented ATAD with a T2 biologic. The mean outcomes measure test score after 6 months of ATAD for patients who received biologics was 40.5 versus 15 in those who did not receive biologics (p = 0.02). The mean differences between the postoperative predesensitization test score and the 6-month postdesensitization test score for patients who went on to receive biologics was an increase of 13 versus a decrease of 10 for those patients who did not receive biologics (p = 0.12). Conclusion: ESS, coupled with AD and ATAD, was successful in the long-term management of the majority of the patients with AERD, which rarely required the incorporation of T2 biologics. Patient questionnaires, such as outcomes measure test score, may identify aspirin therapy failures and help guide the practitioner in deciding when to introduce T2 biologics into the patient's treatment regimen.

A multicenter approach to evaluate omalizumab effectiveness in Samter's triad.

Omalizumab proved to be very effective in improving control of severe atopic asthma. Many small-sized studies suggested a potential role for omalizumab in the management of aspirin-exacerbated respiratory disease. The aim of this study is to describe the effectiveness of omalizumab in a multicentre group of patients with Samter's triad. We retrospectively enrolled eight patients (5 females) with Samter's triad who underwent at least one year of omalizumab therapy. Clinical data, functional parameters and questionnaires for asthma and nasal polyposis control were collected at baseline and follow-up. We observed a significant reduction of moderate-to-severe asthma exacerbations, together with an increase of FEV1 and a reduction of steroids intake. An improvement in asthma control and nasal symptoms was also reported. This multicenter study confirms the effectiveness of omalizumab in patients affected by Samter's triad. Omalizumab may represent a potential therapeutic option for the management of this disease.

Aspirin Exacerbated Respiratory Disease: Epidemiology, Pathophysiology, and Management.

The correlation between aspirin sensitivity, asthma, and nasal polyposis was recognized in the early 20th century. Today, this classic triad of symptoms, eponymously named Samter’s Triad, is known as aspirin exacerbated respiratory disease (AERD). Aspirin exacerbated respiratory disease affects approximately 0.3–0.9% of the general population in the USA and approximately 7% of asthmatic patients. The management of AERD is challenging as no single modality has proven to have high rates of symptom control. Consequently, disease management typically involves a multimodality approach across both medical and surgical disciplines. This review describes the epidemiology of AERD and the current state-of-the-art as it relates to the underlying pathophysiologic mechanisms of this disease process. A significant proportion of the review is focused on the appropriate diagnostic workup for AERD patients including the utility of aspirin provocation testing. The spectrum of medical treatments, including aspirin desensitization and recently introduced immunotherapies, are discussed in detail. Furthermore, surgical approaches to disease control, including advanced endoscopic techniques, are reviewed and treatment outcomes presented.

Omalizumab can inhibit respiratory reaction during aspirin desensitization

BackgroundAspirin desensitization has been associated with benefit in management of aspirin-exacerbated respiratory disease (AERD). An intervention that would encourage aspirin desensitization to be performed more frequently has substantial potential for improving outcomes and quality of life in patients with AERD. ObjectiveWe investigated whether omalizumab administration would be associated with attenuation of aspirin-provoked bronchospasm in patients with AERD undergoing aspirin desensitization. MethodsWe carried out a randomized, double-blind, placebo-controlled study in which subjects with AERD who fulfilled label criteria for omalizumab received omalizumab or placebo for 16 weeks, and then underwent aspirin desensitization. ResultsEleven subjects completed aspirin desensitization. Of the 7 who were randomized to omalizumab, 5 had no respiratory reaction during aspirin desensitization. Compared with placebo, omalizumab was associated with a significantly greater likelihood for subjects with AERD to have no respiratory reaction during desensitization (P = .04, Fisher exact test). There was an overall difference in urinary leukotriene E4 (LTE4) levels in subjects who received omalizumab and did not have a respiratory reaction during desensitization compared with subjects randomized to placebo (P = .035, mixed model with interaction). Urinary LTE4 levels were significantly higher with respiratory reaction in placebo subjects compared with levels obtained after the 100-mg dose in AERD subjects who had no respiratory reaction (P < .001, mixed model with interaction). ConclusionIn atopic AERD subjects, omalizumab administration for 16 weeks was associated with “clinically silent” desensitization. Further studies to investigate the therapeutic utility of omalizumab in patients with AERD who are candidates for aspirin desensitization are warranted based on these findings. Trial RegistrationClinicalTrials.gov Identifier NCT00555971.

The role of aspirin desensitization in the management of aspirin-exacerbated respiratory disease.

Aspirin-exacerbated respiratory disease (AERD) is a progressive inflammatory disease of the upper and lower airways characterized by marked eosinophilic nasal polyposis, asthma, and respiratory reactions to medications that inhibit the cyclooxygenase pathway. Aspirin desensitization has proven to be an effective tool in the management of this disease when used in a multidisciplinary setting. The purpose of this article is to review the current literature regarding AERD, aspirin desensitization, and share our opinion regarding the most optimal multidisciplinary approach to these complex patients. Numerous studies, including randomized, double-blind, placebo-controlled trials, have demonstrated the therapeutic effectiveness of aspirin desensitization with significant improvement in number of sinus infections per year, olfactory scores, nasal symptom scores, asthma symptom scores, sinus operations, hospitalizations, emergency room visits, and oral steroid use. Furthermore, the role of surgery is becoming increasingly important for recalcitrant sinus disease with recent studies showing comprehensive surgery as more beneficial to disease management. Aspirin desensitization is an effective therapeutic tool in the management of AERD. A multidisciplinary approach is critical between the otorhinolaryngologist and allergist to provide the most optimal care for this complex patient population.

Aspirin Desensitization Treatment for the Management of Aspirin-Exacerbated Respiratory Disease

Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome characterized by nasal polyps, chronic hypertrophic eosinophilic sinusitis, asthma, and sensitivity to cyclooxygenase-1 (COX-1) inhibitors. The treatment of asthma and chronic rhinosinusitis in AERD is difficult, since those patients usually suffer from severe steroid dependent asthma and frequent recurrence of nasal polyps despite combined medical and surgical treatment. Aspirin desensitization (AD) can be considered as an additional treatment option in selected patients with AERD. Aspirin doses ranging from 100 to 1300 mg/day were reported to be effective for this purpose.

Update on the Management of Aspirin-Exacerbated Respiratory Disease.

Aspirin-exacerbated respiratory disease (AERD) is an adult-onset upper and lower airway disease consisting of eosinophilic nasal polyps, asthma, and respiratory reactions to cyclooxygenase 1 (COX-1) inhibitors. Management includes guideline-based treatment of asthma and sinus disease, avoidance of COX-1 inhibitors, and for some patients aspirin desensitization followed by high-dose aspirin therapy. Despite this, many patients have inadequately controlled symptoms and require multiple sinus surgeries. In this review, we discuss the current standard approaches to the management of AERD, and we introduce several therapeutics under development that may hold promise for the treatment of AERD.