Asthma and lower airway diseaseProstaglandin D2 pathway upregulation: Relation to asthma severity, control, and TH2 inflammation
Section snippets
Methods
Full experimental details are provided in the Methods section in this article’s Online Repository at www.jacionline.org.
Demographics
Bronchoscopic samples were obtained from 112 subjects, and groups did not differ by race or sex (Table I). SAs were older (overall P < .0001, all intergroup P < .0002) and had a higher body mass index compared with HCs (intergroup P < .0001). Less atopy and lower serum IgE levels and blood eosinophil numbers were found in HCs compared with asthmatic patients. SAs had the lowest FEV1 percent predicted values, which were lower than in all other groups (overall P < .0001, all intergroup P
Discussion
This study identified a coordinated upregulation of the PGD2 pathway, from enzyme to product to receptor, particularly in patients with severe, poorly controlled, TH2-associated asthma. Expanding on our previous study, BAL fluid PGD2 levels, measured by means of ELISA and confirmed by using the highly sensitive and specific LCMS, were highest in SAs.6 Levels of the likely enzymatic source of this PGD2, HPGDS, were also higher in the SA epithelium, correlated with its product (PGD2), and
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Supported by National Institute of Health/National Heart, Lung, and Blood Institute grants HL-69174, HL-109152-01, HL064937-10, NIH-F32 AI085633, and CTSI UL1 RR024153.
Disclosure of potential conflict of interest: M. L. Fajt has received grants from the National Institutes of Health (NIH). S. L. Gelhaus has received grants/has grants pending from the NIH. B. Freeman has received grants from the NIH; has received travel expenses from the NIH; has patents planned, pending, or issued by Complexa; has stock/stock options in Complexa and Nitromega. S. E. Wenzel has received consulting fees or honoraria from Actelion and Merck; has received payment for a Multicenter Study conducted for Array; has consultant arrangements with Amgen, Regeneron, and Novartis; and has grants/grants pending from Amgen, Genentech MedImmune, Sanofi Aventis, GlaxoSmithKline, and Merck. The rest of the authors declare that they have no relevant conflicts of interest.