Aspirin-exacerbated respiratory disease:Update on medical management

Aspirin-exacerbated respiratory disease(AERD)is frequently diagnosed in patients with severe type 2 airway inflammation presenting with nasal polyps and severe asthma.It has been associated with a recalcitrant course with high medical and surgical requirements.The advent of recent biological and other targeted treatments show promise in the medical management of patient with AERD.The goal of complete disease control where patients no longer require recurrent surgical procedures,systemic corticosteroid exposure and may live with a stable and relatively normal quality of life is now within reach.Further work is necessary to identify biomarkers predictive of treatment response.

Systematic review of outcomes for endoscopic sinus surgery and subsequent aspirin desensitization in aspirin-exacerbated respiratory disease

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

Endogenous cannabinoids may regulate chronic inflammation in aspirin-exacerbated respiratory disease

Aspirin-exacerbated respiratory disease(AERD)is characterized by the triad of chronic rhinosinusitis with nasal polyposis,adult-onset asthma and non-IgE mediated reactions to aspirin and other cyclooxygenase-1(COX-1)inhibitors.Patients with AERD are dependent on COX-1 activity to maintain production of prostaglandin(PG)species,such as PGE2,which maintain physiologic levels of inflammation and limit the production of pro-inflammatory cysteinyl leukotrienes.The endogenous cannabinoid system is a family of immunomodulatory lipids and their innate g-protein coupled receptors that are closely related to arachidonic acid and may modulate inflammation via several pathways,including the direct production of metabolically active prostaglandin glycerol-esters.A recent pilot study has identified the significant up-regulation of the peripherally expressed,type-2 cannabinoid receptor(CB2)in AERD nasal polyps versus control tissues from patients with either allergic fungal rhinosinusitis or no history of chronic sinonasal inflammation.These early findings suggest the involvement of increased endogenous cannabinoid activity in prostaglandin deficient states such as AERD.Future study is needed to explore the significance of these findings,with specific investigation of the impact of CB2 activation on markers of airway inflammation,as well as the potential to measure CB2 expression as a screening biomarker for the evaluation of unrecognized disease.

Pathogenesis of NSAID-induced reactions in aspirin-exacerbated respiratory disease

It is well-established that following ingestion of aspirin or any other inhibitor of cyclooxygenase-1, patients with Samter’s disease, or aspirin-exacerbated respiratory disease (AERD) develop the sudden onset of worsening respiratory clinical symptoms, which usually in-volves nasal congestion, rhinorrhea, wheezing and bronchospasm. Gastrointestinal distress, nausea, a pruritic rash and angioedema can also occasionally develop. However, the underlying pathologic mechanism that drives these clinical reactions remains elusive. Pretreatment with medications that inhibit the leukotriene pathway decreases the severity of clinical reactions, which points to the involvement of cysteinyl leukotrienes (cysLTs) in the pathogenesis of these aspirin-induced reactions. Furthermore, studies of aspirin challenges in carefully-phenotyped patients with AERD have confirmed that both proinflammatory lipid mediators, predominantly cysLTs and prostaglandin (PG) D 2, and the influx of effector cells to the respiratory tissue, contribute to symptom development during aspirin-induced reactions. Mast cells, which have been identified as the major cellular source of cysLTs and PGD 2, are likely to be major participants in the acute reactions, and are an attractive target for future pharmacotherapies in AERD. Although several recent studies support the role of platelets as inflammatory effector cells and as a source of cysLT overproduction in AERD, it is not yet clear whether platelet activation plays a direct role in the development of the aspirin-induced reactions. To further our understanding of the pathogenesis of aspirin-induced reactions in AERD, and to broaden the pharmacotherapeutic options available to these patients, additional investigations with targeted clinical trials will be required.

The importance of timely diagnosis of aspirin-exacerbated respiratory disease for patient health and safety

Backgroud:Aspirin-exacerbated respiratory disease(AERD)is a difficult-to-treat syndrome where timely diagnosis and initiation of disease-specific therapies are pertinent to improved patient outcomes.Objective:To characterize the most common timeline for development of the clinical triad[asthma,nasal polyposis,and reactions to nonsteroidal anti-inflammatory drugs(NSAIDs)],identify barriers to prompt diagnosis of AERD,and describe indications for an aspirin challenge to facilitate accurate diagnosis.Methods:Six hundred ninety-seven patients with diagnosed AERD and history of at least one sinus surgery to remove nasal polyps were identified in the Brigham and Women’s Hospital AERD registry.Patient reported age at disease onset of asthma,nasal polyposis,and age of first NSAID reaction were obtained from 2013 to 2019 at enrollment.Results:Of the 697 patients identified,diagnosis of asthma preceded diagnosis of nasal polyposis and first NSAID reaction,although there was considerable variability between patients.Conclusions:Prompt diagnosis of AERD is important for patient and provider education and improved care of this difficult-to-treat population of patients.Consider diagnostic aspirin challenge in patients without historical reactions to NSAIDs who have an otherwise compatible clinical history,specifically in patients who take daily low-dose aspirin,leukotriene modifiers,avoid NSAIDs,or who are severely symptomatic at baseline where it would be difficult to identify an acute worsening of symptoms.