Treatment Of Aspirin-exacerbated Respiratory Disease Research Articles

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-exacerbated respiratory disease treated with omalizumab: 3 cases report and literature review

Objective: To summarize the clinical data of aspirin-exacerbated respiratory disease (AERD) treated with omalizumab in Peking University First Hospital and reviewed the relative literatures. Methods: We analyzed retrospectively the clinical data of three cases of AERD treated with omalizumab in Peking University First Hospital from March 1, 2018 to December 31, 2021. The clinical researches on the treatment of AERD with omalizumab up to January 31, 2022 were retrieved in PubMed, China National Knowledge Infrastructure (CNKI) and Wanfang Data. Results: Our three patients of AERD treated with omalizumab for 32 to 68 weeks obtained relief of symptoms of upper and lower respiratory tract, improvement in lung function, and reduction in percentage of blood eosinophils. There were 14 clinical studies on treatment of AERD with omalizumab, including 3 randomized, double-blind and placebo-controlled studies and 11 self-controlled case series studies. The majority of studies showed that omalizumab contributed to improve the symptoms of AERD, decrease the frequency of asthma attacks and reduce systemic glucocorticoid use. Conclusion: Omalizumab can improve the disease control of AERD, but further studies are needed.

Major complications of aspirin desensitization and maintenance therapy in aspirin-exacerbated respiratory disease.

Treatment of aspirin-exacerbated respiratory disease (AERD) includes endoscopic sinus surgery (ESS) and aspirin desensitization (AD) with aspirin therapy after desensitization (ATAD). The objective of this study was to determine the rate of major complications associated with aspirin use that resulted in the discontinuation of aspirin therapy. This study was a retrospective chart review of patients with AERD who underwent ESS, AD, and ATAD at a single AERD tertiary center between July 2016 and February 2019. Complications associated with aspirin that resulted in the discontinuation of aspirin therapy were analyzed via analysis of variance and logistic regression. In total, 109 AERD patients underwent ESS with subsequent AD. Ten patients (9.2%) discontinued therapy after AD, before starting ATAD. Eight patients (7.3%) discontinued therapy after starting ATAD. There were 91 patients (83.5%) with no complications throughout ATAD. Reasons for discontinuation included gastritis, upper gastrointestinal (GI) bleed, anaphylaxis, persistent sinonasal symptoms, recurrent epistaxis, asthma exacerbation, and a nummular rash. There was no significant correlation between complication rate and (1) aspirin doses (analysis of variance [ANOVA] F: 0.69; p = 0.51), (2) gender (odds ratio [OR] 0.56; 95% confidence interval [CI], 0.19 to 1.65; p = 0.30), (3) age (OR 1.04; 95% CI, 0.96 to 1.09; p = 0.06), or (4) race/ethnicity (OR 1.12; 95% CI, 0.88 to 1.44; p = 0.36). AD with ATAD was associated with only a 0.92% incidence of a clinically significant GI bleed, and only a 0.92% incidence of anaphylaxis. A remaining 16 patients (14.7%) discontinued aspirin therapy due to minor clinical sequelae. These findings demonstrate that the majority of AERD patients tolerate AD with ATAD without any major complications.

In vitro safety of ketotifen as a topical nasal rinse.

Ketotifen is a second-generation noncompetitive H1-antihistamine and mast-cell stabilizer. It is commonly used to treat or prevent allergic conjunctivitis, asthma, chronic urticaria, anaphylaxis, mast-cell, and other allergic-type disorders. However, it has never been studied in aspirin-exacerbated respiratory disease (AERD), an aggressive phenotype of chronic rhinosinusitis with nasal polyps, where the mast cell plays a prominent role its pathogenesis. Human sinonasal epithelial cells were grown at an air-liquid interface (ALI). Ketotifen powder was dissolved in saline to make 4 test solutions at 1.04, 2.08, 10.4, and 20.8 µg/mL. Control (saline) or ketotifen solution was added apically to ALI cultures from tissue of 5 unique patients, and ciliary beat frequency (CBF) changes were recorded. Lactate dehydrogenase was measured at 24 and 48 hours to estimate long-term cellular toxicity. Apical application of ketotifen at all concentrations was neither ciliotoxic nor ciliostimulatory, with no change in CBF over a period of 15 minutes after application. Cellular toxicity for all concentrations at 24 and 48 hours after application was <3% and <7%, respectively, that of lysed cultures. Topical application of ketotifen to an in vitro model of sinonasal epithelium is safe, as evaluated by CBF and lactate dehydrogenase. Ketotifen is neither ciliotoxic nor ciliostimulatory, and no long-term cellular toxicity was observed. Ketotifen may have promise as a topical nasal rinse in the treatment of AERD.

Benefits and harms of aspirin desensitization for aspirin-exacerbated respiratory disease: a systematic review and meta-analysis.

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. 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. 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 [I2 ] = 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], I2 = 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], I2 = 0%, RD +11%, moderate-certainty), and gastritis (RR 3.84 [95% CI, 1.12 to 13.19], I2 = 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. 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.

Mepolizumab for the treatment of aspirin-exacerbated respiratory disease associated with coronary spasm

Mepolizumab for the treatment of aspirin-exacerbated respiratory disease associated with coronary spasm

Dietary Fatty Acid Modification for the Treatment of Aspirin-Exacerbated Respiratory Disease: A Prospective Pilot Trial

The high levels of eicosanoid production and the clinical efficacy of leukotriene-modifying pharmacotherapies for patients with aspirin-exacerbated respiratory disease (AERD) suggest that other interventions targeting arachidonic acid dysregulation may also improve disease control. To assess the utility of a high omega-3/low omega-6 diet for the treatment of AERD. Prospective, nonblinded dietary intervention in 10 adult patients with AERD at Brigham and Women's Hospital in Boston, MA. The primary objective was for subjects to reduce dietary omega-6 fatty acid consumption to less than 4 g/d and increase omega-3 intake to more than 3 g/d. The primary outcome was change in urinary leukotriene E4, with changes in other eicosanoids, platelet activation, lung function, and patient-reported questionnaires also assessed. Of the 10 subjects who screened for the study, all 10 completed the dietary intervention. Urinary leukotriene E4 decreased by 0.17 ng/mg (95% CI,-0.29 to-0.04; P= .02) and tetranor prostaglandin D-M decreased by 0.66 ng/mg creatinine (95% CI,-1.21 to-0.11; P= .02). There was a 15.1-point reduction in the 22-item Sino-Nasal Outcome Test score (95% CI,-24.3 to-6.0; P= .01), a 0.27-point reduction in the 7-item Asthma Control Questionnaire score (95% CI,-0.52 to-0.03; P= .03), and no change in FEV1 % predicted (P=.92) or forced vital capacity % predicted (P=.74). All patients lost some weight over the 2-week intervention period, and there were no diet-associated adverse events. A high omega-3/low omega-6 diet may be an appropriate adjunct treatment option for patients with AERD.

Aspirin-exacerbated respiratory disease: Prevalence, diagnosis, treatment, and considerations for the future.

Aspirin-exacerbated respiratory disease (AERD) is a late onset condition characterized by the Samter triad (aspirin sensitivity [as well as sensitivity to any nonselective cyclooxygenase inhibitor], nasal polyps, asthma) and additional features, including eosinophilic chronic rhinosinusitis, hypereosinophilia, anosmia, frequent absence of atopy, and, intolerance to ingestion of red wine and other alcoholic beverages. The diagnosis is rare, and, because of this, it is also often missed by physicians. However, it is highly overexpressed in patients with severe asthma (and severe chronic rhinosinusitis with nasal polyps), which makes its recognition essential. For this review, we considered mechanisms involved in the pathogenesis of this disease and discussed the clinical symptoms of AERD. We also discussed the role of aspirin desensitization in the treatment of AERD. Also, we considered medications (e.g, leukotriene modifiers) and surgical interventions that have a role in the treatment of AERD.

Omalizumab in the treatment of aspirin-exacerbated respiratory disease

Omalizumab in the treatment of aspirin-exacerbated respiratory disease

Aspirin or Other Nonsteroidal Inflammatory Agent Exacerbated Asthma

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.