The utility of biomarkers in diagnosis of aspirin exacerbated respiratory disease

Background Aspirin-exacerbated respiratory disease (AERD) is a distinct eosinophilic phenotype of severe asthma with accompanying chronic rhinosinusitis, nasal polyposis, and hypersensitivity to aspirin. Urinary 3-bromotyrosine (uBrTyr) is a noninvasive marker of eosinophil-catalyzed protein oxidation. The lack of in vitro diagnostic test makes the diagnosis of AERD difficult. We aimed to determine uBrTyr levels in patients with AERD ( n = 240) and aspirin-tolerant asthma (ATA) ( n = 226) and to assess whether its addition to urinary leukotriene E 4 (uLTE 4 ) levels and blood eosinophilia can improve the prediction of AERD diagnosis. Methods Clinical data, spirometry and blood eosinophilis were evaluated. UBrTyr and uLTE 4 levels were measured in urine by HPLC and ELISA, respectively. Results Both groups of asthmatics (AERD, n = 240; ATA, n = 226) had significantly higher uBrTyr, uLTE 4 levels, and blood eosinophils than healthy controls (HC) ( n = 71) ( p < 0.05). ULTE 4 levels and blood eosinophils were significantly higher in AERD as compared to ATA ( p = 0.004, p < 0.0001, respectively). whereas uBrTyr levels were not significantly different between both asthma phenotypes ( p = 0.34). Asthmatics with high levels of uBrTyr (> 0.101 ng/mg Cr), uLTE 4 levels (> 800 pg/mg Cr) and blood eosinophils (> 300 cells/ul) were 7 times more likely to have AERD.. However, uBrTyr did not increase the benefit for predicting AERD when uLTE 4 and blood eosinophils were already taken into account ( p = 0.57). Conclusion UBrTyr levels are elevated both in AERD and ATA as compared to HC, but they could not differentiate between these asthma phenotypes suggesting a similar eosinophilic activation. The addition of uBrTyr to elevated uLTE4 levels and blood eosinophils did not statistically enhance the prediction of AERD diagnosis.