Background
Bronchoalveolar lavage (BAL) fluid prostaglandin D&sub2;(PGD&sub2;) levels are increased in patients with severe, poorly controlled asthma in association with epithelial mast cells (MCs). PGD&sub2;, which is generated by hematopoietic prostaglandin D synthase (HPGDS), acts on 3 G protein-coupled receptors, including chemoattractant receptor-homologous molecule expressed on TH2 lymphocytes (CRTH2) and PGD&sub2; receptor 1 (DP1). However, much remains to be understood regarding the presence and activation of these pathway elements in asthmatic patients.
Conclusion
The current study identifies coordinated upregulation of the PGD&sub2; pathway in patients with severe, poorly controlled, TH2-high asthma despite corticosteroid use.
Methods
Epithelial cells and BAL fluid were evaluated for HPGDS (quantitative real-time PCR/immunohistochemistry [IHC]) and PGD&sub2; (ELISA/liquid chromatography mass spectrometry) in relation to levels of MC proteases. Expression of the 2 inflammatory cell receptors DP1 and CRTH2 was evaluated on luminal cells. These PGD&sub2; pathway markers were then compared with asthma severity, level of control, and markers of TH2 inflammation (blood eosinophils and fraction of exhaled nitric oxide).
Objective
We sought to compare the expression and activation of PGD&sub2; pathway elements in bronchoscopically obtained samples from healthy control subjects and asthmatic patients across a range of disease severity and control, as well as in relation to TH2 pathway elements.
Results
Confirming previous results, BAL fluid PGD&sub2; levels were highest in patients with severe asthma (overall P = .0001). Epithelial cell compartment HPGDS mRNA and IHC values differed among groups (P = .008 and P < .0001, respectively) and correlated with MC protease mRNA. CRTH2 mRNA and IHC values were highest in patients with severe asthma (P = .001 and P = .0001, respectively). Asthma exacerbations, poor asthma control, and TH2 inflammatory markers were associated with higher PGD&sub2;, HPGDS, and CRTH2 levels.