The utility of biomarkers in diagnosis of aspirin exacerbated respiratory disease

Abstract

BackgroundAspirin-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 E4 (uLTE4) levels and blood eosinophilia can improve the prediction of AERD diagnosis.MethodsClinical data, spirometry and blood eosinophilis were evaluated. UBrTyr and uLTE4 levels were measured in urine by HPLC and ELISA, respectively.ResultsBoth groups of asthmatics (AERD, n = 240; ATA, n = 226) had significantly higher uBrTyr, uLTE4 levels, and blood eosinophils than healthy controls (HC) (n = 71) (p < 0.05). ULTE4 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), uLTE4 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 uLTE4 and blood eosinophils were already taken into account (p = 0.57).ConclusionUBrTyr 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.

Adult‐onset eosinophilic airway diseases

“…[81][82][83] Peripheral blood eosinophilia is commonly observed in patients with N-ERD. 84 During aspirin provocation, the number of blood eosinophils decreases, 85 and activated eosinophils accumulate in the respiratory tract, 86 although the biomarkers of eosinophil activation such as 3-bromotyrosine and eosinophil-derived neurotoxin in urine do not increase. 87 Another unique inflammatory condition in N-ERD is the presence of eosinophils or other granulocytes in peripheral blood and airway tissues adhered to platelets, 88,89 which provide LTA4 to granulocytes and participate in CysLT overproduction.…”

“…Peripheral blood eosinophilia is commonly observed in patients with N‐ERD 84 . During aspirin provocation, the number of blood eosinophils decreases, 85 and activated eosinophils accumulate in the respiratory tract, 86 although the biomarkers of eosinophil activation such as 3‐bromotyrosine and eosinophil‐derived neurotoxin in urine do not increase 87 .…”

Clinical Characteristics, Urinary Leukotriene E4 Levels, and Aspirin Desensitization Results in Patients With NSAID-Induced Blended Reactions

“…However, these data are still controversial. 22 23 24 There have also been preliminary studies showing that uLTE4 levels might be increased in NECD. 25 26 Whether the measurement of basal uLTE4 levels could be a diagnostic marker for any phenotype of NSAID hypersensitivity is yet to be explored.…”

Elevated Urine LeukotrieneE4Is Associated With Worse Objective Markers in Nasal Polyposis Patients

“…This is a stable end product which can accumulate in plasma and urine. Urinary LTE4 has been demonstrated to be a reliable biomarker of several inflammatory disease conditions including AERD 11‐14 . Previous data have shown that a urine LTE4 (uLTE4) liquid chromatography–mass spectrometry (LC–MS) assay cutoff of 166 pg/mg Cr suggested the presence of aspirin sensitivity with 89% specificity among patients with a clinical history of aspirin sensitivity 12 …”