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• W2059895067 abstract "BackgroundAirway remodeling in patients with severe steroid-refractory asthma might result from a reduced ability of steroid therapy to limit the transcription of remodeling factors by the bronchial epithelium.ObjectiveWe sought to compare the levels of transcripts encoding remodeling factors in bronchial epithelium of healthy volunteers and of asthmatic patients with either steroid-sensitive or steroid-refractory disease and to correlate these levels with hallmarks of airway remodeling.MethodsBy means of real-time quantitative PCR, we assessed the levels of 14 transcripts encoding remodeling factors, matrix metalolproteinases, and extracellular matrix proteins in laser-capture microdissected bronchial epithelium of healthy volunteers, patients with mild steroid-untreated asthma, and patients with steroid-sensitive and steroid-refractory asthma (n = 8-10 in each group). Histologic features of airway remodeling and endothelin-1 (EDN1) immunolocalization were determined by using frozen specimens.ResultsPatients with steroid-refractory asthma had greater levels of EDN1 transcripts (4.1-fold increase, P = .026) and protein (P = .0009) in their bronchial epithelium compared with patients with steroid-sensitive asthma. EDN1 mRNA levels and protein expression in asthmatic patients were negatively correlated with prebronchodilator and postbronchodilator FEV1 value (r2 ≥ 0.193, P ≤ .03), and they were positively related to airway smooth muscle areas (r2 = 0.253, P = .01 and r2 = 0.281, P = .005 for EDN1 mRNA and protein expression, respectively).ConclusionIncreased EDN1 synthesis by the bronchial epithelium characterizes severe refractory asthma and correlates with airway remodeling and airflow obstruction.Clinical implicationsTargeting EDN1 might represent a novel therapeutic strategy for severe steroid-refractory asthma. Airway remodeling in patients with severe steroid-refractory asthma might result from a reduced ability of steroid therapy to limit the transcription of remodeling factors by the bronchial epithelium. We sought to compare the levels of transcripts encoding remodeling factors in bronchial epithelium of healthy volunteers and of asthmatic patients with either steroid-sensitive or steroid-refractory disease and to correlate these levels with hallmarks of airway remodeling. By means of real-time quantitative PCR, we assessed the levels of 14 transcripts encoding remodeling factors, matrix metalolproteinases, and extracellular matrix proteins in laser-capture microdissected bronchial epithelium of healthy volunteers, patients with mild steroid-untreated asthma, and patients with steroid-sensitive and steroid-refractory asthma (n = 8-10 in each group). Histologic features of airway remodeling and endothelin-1 (EDN1) immunolocalization were determined by using frozen specimens. Patients with steroid-refractory asthma had greater levels of EDN1 transcripts (4.1-fold increase, P = .026) and protein (P = .0009) in their bronchial epithelium compared with patients with steroid-sensitive asthma. EDN1 mRNA levels and protein expression in asthmatic patients were negatively correlated with prebronchodilator and postbronchodilator FEV1 value (r2 ≥ 0.193, P ≤ .03), and they were positively related to airway smooth muscle areas (r2 = 0.253, P = .01 and r2 = 0.281, P = .005 for EDN1 mRNA and protein expression, respectively). Increased EDN1 synthesis by the bronchial epithelium characterizes severe refractory asthma and correlates with airway remodeling and airflow obstruction." @default.
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• W2059895067 date "2007-12-01" @default.
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• W2059895067 title "Augmented epithelial endothelin-1 expression in refractory asthma" @default.
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• W2059895067 doi "https://doi.org/10.1016/j.jaci.2007.09.023" @default.
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