Aspirin-exacerbated asthma: avoiding challenge is still challenging.

AERD is an organ-specific disease, characterized by abnormalities in the biosynthesis of eicosanoid mediators and eicosanoid receptor expression. The biochemical hallmark of AERD is enhanced cysteinyl leukotriene (CysLT) production both at baseline [9, 10] and following aspirin challenge [11, 12] . As AERD is not a systemic disease, it is not surprising that studies of different inflammatory cells in the blood have so far failed to produce consistent support for specific NSAID-induced ex vivo activation of cells from subjects with AERD. Higashi et al. [13] , in this issue, reason that acetylsalicylic acid intolerance might be maintained in sputum cells when they are recovered from the lower airways of patients with asthma, if these cells were challenged by aspirin ex vivo. They found that release of CysLTs by sputum cells from patients with AERD was neither induced by aspirin ex vivo when cells were collected at baseline nor in sputum cells recovered after lysine-aspirin-induced bronchoconstriction. On the other hand, they found that the release of CysLTs from sputum cells triggered by ionophores in both instances was higher in the AERD group, both at baseline and after the lysine-aspirin bronchoprovocation. Their results confirm that AERD is characterized by enhanced CysLTs production both at baseline and following aspirin challenge. The difference in the amounts of CysLT release between aspirin-sensitive and aspirin-tolerant asthmatic patients apThe term ‘aspirin-exacerbated respiratory disease’ (AERD), instead of the formerly used ‘aspirin-induced asthma’, highlights that the core issue for these patients is not drug hypersensitivity, but the underlying chronic inflammatory respiratory disease, occasionally exacerbated by aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) [1] . The gold standard for diagnosing AERD is aspirin challenge, which may be performed through three different routes of provocation challenges: oral, bronchial and nasal inhalation, the oral challenge being considered the test with the best sensitivity and specificity [2] . As well as being time-consuming, aspirin challenges are not without risk, and more than a third of patients have been reported to experience late reactions following bronchial aspirin challenge [3] . For these reasons, in vitro tests would be welcome, but unfortunately, till now, none could be recommended for routine diagnosis [4] . More recently, three in vitro tests measuring aspirin/NSAIDsspecific peripheral blood leukocyte activation have been proposed: measurement of sulfidoleukotriene release with inconsistent results [5, 6] , measurement of cell surface molecule CD63 expression upon in vitro challenge [7] with quite variable specificity and sensitivity and measurement of aspirin-triggered 15-HETE generation, which appears to be promising [8]. Its clinical usefulness has, however, not yet been confirmed by larger studies. Published online: March 1, 2012