Concurrent coxibs and anti-platelet therapy unmasks aspirin-exacerbated respiratory disease.

Characterization of occupational exposures to cleaning products used for common cleaning tasks – a pilot study of hospital cleaners. Concurrent coxibs and anti-platelet therapy unmasks aspirin-exacerbated respiratory disease To the Editor: Aspirin-exacerbated respiratory disease (AERD) is a clinical tetrad of chronic hypertrophic eosinophilic sinusitis, nasal polyps, asthma and sensitivity to any medication that inhibits cyclooxygenase (COX)-1, namely aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) [1]. The final metabolites of the degradation of arachidonic acid via COX-1 pathway are thromboxanes, prostacyclin and prostaglandins (PG); the most crucial ones are PGE 2 and PGD 2. According to the classical ''cyclooxygenase'' hypothesis, inhibition of COX-1, but not COX-2, triggers various mechanisms leading to asthmatic and/or nasal symptoms in AERD patients. The central mechanism was regarded as the deprivation of PGE 2 as a consequence of COX-1 inhibition, which would lead to an even more increased local and systemic generation of cysteinyl leukotrienes (LT). The overproduction of cysteinyl LT, due to upregulation of LTC 4 synthase and/or cysteinyl LT receptors in the airways, the hallmark of the disease, occurs at baseline as well, although at a much lower degree than after aspirin/NSAIDs intake [2]. After the introduction of the selective COX-2 inhibitors, casually referred to as coxibs, several well-designed studies reported the excellent safety profile of these new NSAIDs in patients with AERD [3, 4]. Nevertheless, shortly afterwards, as the use of coxibs extended, so did the number of case reports warning the clinicians that some AERD patients may not tolerate coxibs [5, 6]. In fact, all the position papers and updates on AERD evaluation and management recommend giving the first full dose of these drugs in the physician's office [7]. A recent study by DAHAM et al. [8] proposes a theory that might explain the underlying mechanism. These authors demonstrate that biosynthesis of PGD 2 (bronchoconstrictor and pro-inflammatory mediator) in patients with asthma (of which one-third had AERD), is increased at baseline, catalysed by constitutive COX-1 only, and is not inhibited by a short 3-day treatment with celecoxib. Meanwhile, whole body formation of PGE 2 (bronchodilator and anti-inflammatory) is predominantly COX-2 dependent and decreases progressively, with a reduction of .50% as compared to baseline, during coxib treatment. Although none of the AERD patients in this study experienced bronchoconstriction throughout the coxib treatment, COX-2 inhibition definitely had a much lesser impact on the decrease in bronchoconstrictory PGD 2 than on protective PGE 2 , …