Quantitative proteomics on bronchial biopsies from asthma and COPD: Effects of budesonide treatment

European Respiratory Journal(2011)

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摘要
The global proteome of individual bronchial biopsy material from asthma and COPD patients has not been fully ascertained. The aim was to determine if mechanisms of disease and responses to treatment can be detected in biopsies from patients with asthma and COPD, using a quantitative proteomics technology. Endobronchial biopsies, pre and post treatment, were taken from patients with asthma (n=12) and COPD (n=11), as well as non-smoking (n=3) and smoking (n=2) healthy controls. Patients were randomised to double blind treatment with either placebo or budesonide (800 μg daily for 3 months). Quantitative proteomics technology was used to identify and quantify biopsy proteins. Pathways analysis was conducted to identify global proteome differences. A total of 1937 proteins were identified from all subjects. Proteome differences in asthma and COPD and changes in response to treatment could be observed. Analysis of the global proteome of COPD revealed that the top protein network contained the function of connective tissue disorder and that metabolic pathways were most relevant. In comparison, the top network in asthma contained dermatological functions, with the pathways being more actin-based. Changes in the proteome could also be observed in response to treatment. The increased relevance of cellular biological processes and decrease of oxidative stress can be seen for both asthma and COPD. Of particular interest, hepatic fibrosis was more associated with the COPD proteome and is altered with budesonide treatment. These results show that proteome differences can be detected using quantitative proteomics technology on clinically relevant biopsies from individual patients.
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