Update on recent advances in the management of aspirin exacerbated respiratory disease

Abstract

Aspirin intolerant asthma (AIA) is frequently characterized as an aspirin (ASA)-exacerbated respiratory disease (AERD). It is a clinical syndrome associated with chronic severe inflammation in the upper and lower airways resulting in chronic rhinitis, sinusitis, recurrent polyposis, and asthma. AERD generally develops secondary to abnormalities in inflammatory mediators and arachidonic acid biosynthesis expression. Upper and lower airway eosinophil infiltration is a key feature of AERD; however, the exact mechanisms of such chronic eosinophilic inflammation are not fully understood. Cysteinyl leukotriene over-production may be a key factor in the induction of eosinophilic activation. Genetic studies have suggested a role for variability of genes in disease susceptibility and response to medication. Potential genetic biomarkers contributing to the AERD phenotype include HLA-DPB1*301, LTC4S, ALOX5, CYSLT, PGE2, TBXA2R, TBX21, MS4A2, IL10 -1082A > G, ACE -262A > T, and CRTH2 -466T > C; the four-locus SNP set was composed of B2ADR 46A > G, CCR3 -520T > G, CysLTR1 -634C > T, and FCER1B -109T > C. Management of AERD is an important issue. Aspirin ingestion may result in significant morbidity and mortality, and patients must be advised regarding aspirin risk. Leukotriene receptor antagonists (LTRA) that inhibit leukotriene pathways have an established role in long-term AERD management and rhinosinusitis. Aspirin desensitization may be required for the relief of upper and lower airway symptoms in AERD patients. Future research should focus on identification of biomarkers for a comprehensive diagnostic approach.

Keywords: Aspirin; asthma; eosinophil; genetic polymorphism; leukotriene.

Fig. 1

Schematic representation of the metabolism of arachidonic acid by the cyclooxygenase and the 5-and 15-LO pathways.

Fig. 2

Genetic markers of AERD. HLA, human leukocyte antigen; LTC4S, leukotriene C4 synthase; ALOX5, arachidonate 5-lipoxygenase; CYSLTR 1, cysteinyl leukotriene receptor 1; CYSLTR2, cysteinyl leukotriene receptor 2; TBXA2R, thromboxane A2 receptor; MS4A2, high affinity immunoglobulin epsilon receptor beta-subunit; FCER1AG,high affinity immunoglobulin epsilon receptor gamma-subunit; IL10, interleukin10; ACE, angiotensin converting enzyme-I.