Aspirin-Exacerbated Respiratory Disease: Evaluation and Management

The clinical syndrome of aspirin-exacerbated respiratory disease (AERD) is a condition where inhibition of cyclooxygenase-1 (COX-1) induces attacks of upper and lower airway reactions, including rhinorrhea and varying degrees of bronchospasm and laryngospasm. Although the reaction is not IgE-mediated, patients can also present with anaphylactic hypersensitivity reactions, including hypotension, after exposure to COX-1 inhibiting drugs. All patients with AERD have underlying nasal polyps and intractable sinus disease which may be difficult to treat with standard medical and surgical interventions. This review article focuses on the management of AERD patients with a particular emphasis on aspirin desensitization and continuous treatment with aspirin.

Role of Toll-like Receptor 3 Variants in Aspirin-Exacerbated Respiratory Disease

PURPOSE: Although the mechanism of virus-induced, aspirin-exacerbated respiratory disease (AERD) is not known fully, direct activation of viral components through Toll-like receptor 3 (TLR3) has been suggested. TLR3 recognizes double-stranded RNA (dsRNA), and activates nuclear factor-kappaB and increases interferon-gamma, which signals other cells to induce airway inflammation in asthma. Considering the association of TLR3 in viral infections and AERD, we investigated whether promoter and non-synonymous variants of TLR3 were associated with AERD. METHODS: The three study groups, 203 with AERD, 254 with aspirin-tolerant asthma (ATA), and 274 normal healthy controls (NC) were recruited from Ajou University Hospital, Korea. Two polymorphisms, -299698G>T and 293391G>A [Leu412Phe], were genotyped using primer extension methods. RESULTS: Genetic associations were examined between two genetic polymorphisms of TLR3 (-299698G>T and 293391G>A [Leu412Phe]) in the three study groups. AERD patients that carried the GG genotype of 293391G>A showed a significantly lower frequency compared with ATA in both co-dominant (P=0.025) and dominant models (P=0.036). Similarly, in the minor allele frequency, the A allele was significantly higher (P=0.023) in AERD compared with ATA for this polymorphism. AERD patients who carried HT2 [GA] showed a significantly higher frequency than other haplotypes in co-dominant (P=0.02) and recessive (P=0.026) models. CONCLUSIONS: Our findings suggest that the -299698G>T and 293391G>A [Leu412Phe] polymorphisms of the TLR3 gene are associated with the AERD phenotype.

Association of beta2-Adrenergic Receptor Polymorphism with the Phenotype of Aspirin-Intolerant Acute Urticaria

The genetic mechanism of aspirin intolerant acute urticaria (AIAU) is unknown. To demonstrate an association between the beta2 adrenergic receptor (ADRB2) polymorphism and the phenotype of AIAU, one hundred fourteen patients with AIAU, 110 patients with aspirin intolerant chronic urticaria (AICU), and 498 normal healthy controls (NC) based on a Korean population were enrolled. The genotype of ADRB2 at 46 A > G was analyzed using a direct sequencing method. The ADRB2 polymorphism at 46 A > G showed a significant difference between AIAU and NC; the frequency of the major genotype was significantly higher in the AIAU group (p= 0.017 in recessive model), while no differences were noted in allele and genotype frequencies between AICU and NC. In conclusion, the ADRB2 (46 A > G) gene polymorphism may contribute to the development of the phenotype of AIAU.

Analysis of Leukotriens Release and Fas/Fas Ligand Expression between Aspirin Sensitive and Non-Aspirin Sensitive Nasal Polyp Patients / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Fas and Fas ligand (Fas-L) interactions mediate apoptosis of eosinophils. It is possible that reduction of Fas/Fas-L or Fas-L expression on eosinophils could induce the eosinophilia seen in Samter's triad. The purpose of this study was to analyse the release of LT and Fas/Fas-L expression pattern following exposure to varying concentrations of aspirin in aspirin sensitive nasal polyp (ASP) and non-aspirin sensitive nasal polyp (NASP) patients. MATERIALS AND METHODS: Twenty NASP patients and 16 ASP patients were recruited. Nine healthy subjects served as normal controls. LT levels and Fas/Fas ligand expressions were analysed by ELISA and flow cytometry. RESULTS: Both NASP and ASP patients showed increased release of LT on aspirin exposure in blood and nasal polyps. But ASP patients showed an even greater release of LT on aspirin exposure in blood as compared to NASP patients (p<0.05). LT release from peripheral blood elements do not necessarily coincide with those results obtained from nasal polyps. Eosinophils in ASP patients have significantly decreased Fas expression when compared to NASP patients (p<0.0001). CONCLUSION: These results suggested the role of LT and eosinophils in aspirin intolerance mechanisms in both blood and nasal polyp tissues. The decreased expression of the Fas receptor or defect of Fas/Fas-L interaction could be an important role in pathogenesis of nasal polyp regardless of their association with aspirin sensitivity.