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.

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Background We hypothesized that S100A1 is regulated during human hypertrophy and heart failure (HF), and that it may be implicated in remodeling after left ventricular assist device (LVAD). S100A1 is decreased in animal and human HF and restoration produces functional recovery in animal models and in failing human myocytes. With the potential for gene therapy, it is important to carefully explore human cardiac S100A1 regulation and its role in remodeling. Methods and Results We measured S100A1, the sarcoplasmic endoplasmic reticulum Ca2+ATPase (SERCA), phospholamban (PLB) and ryanodine receptor (RYR) proteins as well as β-adrenergic receptor density (β-AR) in non-failing (NF), hypertrophied (LVH), failing (F) and failing LVAD-supported (F+LVAD) hearts. We determined functional consequences of protein alterations in isolated contracting muscles from the same hearts. S100A1, SERCA and PLB were normal in LVH, but decreased in F, while RYR was unchanged in either group. Baseline muscle contraction was not altered in LVH or F. β-AR and inotropic response were decreased in F. In F+LVAD, S100A1 and SERCA showed no recovery, while PLB, β-AR and the inotropic response fully recovered. Conclusions S100A1 and SERCA, both key Ca2+-regulatory proteins, are decreased in human HF and these changes are not reversed following LVAD. The clinical significance of these findings for cardiac recovery remains to be addressed.

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