Background: Prostaglandin E-2 (PGE(2)) is thought to play a role in the pathogenesis of aspirin-sensitive asthma (ASA).

Objective: We sought to extend our previous observations implicating impaired inflammatory cell responsiveness to PGE(2) as a pathogenetic mechanism in patients with aspirin-sensitive rhinosinusitis to the bronchial mucosa in patients with ASA.

Methods: Immunohistochemistry was used to enumerate inflammatory cells and their expression of cysteinyl leukotriene receptors 1 and 2 (CysLT(1) and CysLT(2)) and the PGE(2) receptors E-prostanoid 1 to 4 (EP1-EP4) in bronchial biopsy specimens from patients with ASA, patients with aspirin-tolerant asthma, and control subjects (n = 15 in each group). Concentrations of PGE(2) in bronchoalveolar lavage fluid were measured by using ELISA. The effects of PGE(2) and EP receptor agonists on CD3/CD28-stimulated cytokine production by PBMCs were measured by using ELISA. Airways responsiveness to LTD4 in vivo was measured in asthmatic patients by means of bronchial challenge.

Results: Compared with patients with aspirin-tolerant asthma, patients with ASA had increased bronchial mucosal neutrophil and eosinophil numbers but reduced percentages of T cells, macrophages, mast cells, and neutrophils expressing EP2. Both groups showed increased bronchial sensitivity to inhaled LTD4, but this did not correlate with mucosal expression of CysLT(1) or CysLT(2). Bronchoalveolar lavage fluid PGE(2) concentrations were comparable in all groups. In vitro PGE(2) inhibited cytokine production by PBMCs through EP2 but not other PGE(2) receptors.

Conclusion: Our data are consistent with the hypothesis that impaired inhibition of inflammatory leukocytes by PGE(2) acting through the EP2 receptor has a role in the pathogenesis of ASA. (J Allergy Clin Immunol 2012;129:1636-46.)