Cytological and mRNAs peripheral blood markers of aspirin intolerance in asthmatics

Background: Pathogenesis of aspirin-induced asthma is misunderstood and the responsibility of biochemical lipid mediators disturbances to induce overall upper and lower airways disease remains speculative. Aims: Aims of the study were to compare angiogenesis/inflammation on nasal polyps, between aspirin tolerant, intolerant asthmatics (ATA, AIA) and to analyze peripheral blood for inflammation, which has been few investigated. Methods: Using aspirin challenge, 26 ATA, 22 AIA were identified. Blood samples were collected before and 24h after aspirin challenge, then analyzed for cell counts and for expression of mRNAs coding for inflammatory and angiogenic proteins. In addition, 18 patients underwent surgery for nasal polyps. Tissue were collected for histological analysis and mRNA expressions, coding for angiogenic and inflammatory proteins. Results: Before aspirin challenge, blood eosinophils (E) and platelets were increased in AIA (p < 0.01 and p = 0.025 respectively). After aspirin challenge, in AIA solely, blood E decreased (p=0.006) and neutrophil increased (p=9.10-5). At baseline, in blood, mRNA expression for CX3CR1, PTGDR, VEGF, autotaxin, annexin-3 were similar between AIA and ATA. After oral aspirin challenge, galectin-10, VEGF, PTGDR and annexin-3 mRNA expressions were significantly increased in blood of AIA.Finally, histological, immunohistological and QT-PCR evaluations of nasal polyps were identical between AIA and ATA. Conclusions: Our results confirm that AIA is associated to a baseline blood eosinophilia. We report original results on peripheral blood samples following oral aspirin challenge in AIA, suggesting the impact of aspirin to modulate inflammation in AIA.