Network analysis of quantitative proteomics on asthmatic bronchi: effects of inhaled glucocorticoid treatment

<p>Abstract</p> <p>Background</p> <p>Proteomic studies of respiratory disorders have the potential to identify protein biomarkers for diagnosis and disease monitoring. Utilisation of sensitive quantitative proteomic methods creates opportunities to determine individual patient proteomes. The aim of the current study was to determine if quantitative proteomics of bronchial biopsies from asthmatics can distinguish relevant biological functions and whether inhaled glucocorticoid treatment affects these functions.</p> <p>Methods</p> <p>Endobronchial biopsies were taken from untreated asthmatic patients (<it>n </it>= 12) and healthy controls (<it>n </it>= 3). Asthmatic patients were randomised to double blind treatment with either placebo or budesonide (800 μg daily for 3 months) and new biopsies were obtained. Proteins extracted from the biopsies were digested and analysed using isobaric tags for relative and absolute quantitation combined with a nanoLC-LTQ Orbitrap mass spectrometer. Spectra obtained were used to identify and quantify proteins. Pathways analysis was performed using Ingenuity Pathway Analysis to identify significant biological pathways in asthma and determine how the expression of these pathways was changed by treatment.</p> <p>Results</p> <p>More than 1800 proteins were identified and quantified in the bronchial biopsies of subjects. The pathway analysis revealed acute phase response signalling, cell-to-cell signalling and tissue development associations with proteins expressed in asthmatics compared to controls. The functions and pathways associated with placebo and budesonide treatment showed distinct differences, including the decreased association with acute phase proteins as a result of budesonide treatment compared to placebo.</p> <p>Conclusions</p> <p>Proteomic analysis of bronchial biopsy material can be used to identify and quantify proteins using highly sensitive technologies, without the need for pooling of samples from several patients. Distinct pathophysiological features of asthma can be identified using this approach and the expression of these features is changed by inhaled glucocorticoid treatment. Quantitative proteomics may be applied to identify mechanisms of disease that may assist in the accurate and timely diagnosis of asthma.</p> <p>Trial registration</p> <p>ClinicalTrials.gov registration <a href="http://www.clinicaltrials.gov/ct2/show/NCT01378039">NCT01378039</a></p

Patterns of airway inflammation and MMP-12 expression in smokers and ex-smokers with COPD

Abstract Background Smoking activates and recruits inflammatory cells and proteases to the airways. Matrix metalloproteinase (MMP)-12 may be a key mediator in smoke induced emphysema. However, the influence of smoking and its cessation on airway inflammation and MMP-12 expression during COPD is still unknown. We aimed to analyse airway inflammatory cell patterns in induced sputum (IS) and bronchoalveolar lavage (BAL) from COPD patients who are active smokers and who have ceased smoking >2 years ago. Methods 39 COPD outpatients – smokers (n = 22) and ex-smokers (n = 17) were studied. 8 'healthy' smokers and 11 healthy never-smokers were tested as the control groups. IS and BAL samples were obtained for differential and MMP-12+-macrophages count analysis. Results The number of IS neutrophils was higher in both COPD groups compared to both controls. The amount of BAL neutrophils was higher in COPD smokers compared to healthy never-smokers. The number of BAL MMP-12+-macrophages was higher in COPD smokers (1.6 ± 0.3 × 106/ml) compared to COPD ex-smokers, 'healthy' smokers and healthy never-smokers (0.9 ± 0.4, 0.4 ± 0.2, 0.2 ± 0.1 × 106/ml respectively, p Conclusion The lower amount of BAL neutrophils in COPD ex-smokers, compared to COPD smokers, suggests positive alterations in alveolar compartment after smoking cessation. Smoking and disease itself may stimulate MMP-12 expression in airway compartments (IS and BAL) from COPD patients.</p

Patterns of airway inflammation and MMP-12 expression in smokers and ex-smokers with COPD

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Patterns of airway inflammation and MMP-12 expression in smokers and ex-smokers with COPD-2

<p><b>Copyright information:</b></p><p>Taken from "Patterns of airway inflammation and MMP-12 expression in smokers and ex-smokers with COPD"</p><p>http://respiratory-research.com/content/8/1/81</p><p>Respiratory Research 2007;8(1):81-81.</p><p>Published online 14 Nov 2007</p><p>PMCID:PMC2200652.</p><p></p>OPD smokers, COPD ex-smokers and 'healthy' smokers

Patterns of airway inflammation and MMP-12 expression in smokers and ex-smokers with COPD-1

<p><b>Copyright information:</b></p><p>Taken from "Patterns of airway inflammation and MMP-12 expression in smokers and ex-smokers with COPD"</p><p>http://respiratory-research.com/content/8/1/81</p><p>Respiratory Research 2007;8(1):81-81.</p><p>Published online 14 Nov 2007</p><p>PMCID:PMC2200652.</p><p></p>-smokers, 'healthy' smokers and healthy never-smokers. Data are shown as mean ± SEM. *p < 0.05 compared to healthy never-smokers, #p < 0.05 compared to 'healthy' smokers

Patterns of airway inflammation and MMP-12 expression in smokers and ex-smokers with COPD-0

<p><b>Copyright information:</b></p><p>Taken from "Patterns of airway inflammation and MMP-12 expression in smokers and ex-smokers with COPD"</p><p>http://respiratory-research.com/content/8/1/81</p><p>Respiratory Research 2007;8(1):81-81.</p><p>Published online 14 Nov 2007</p><p>PMCID:PMC2200652.</p><p></p>ealthy' smokers and healthy never-smokers. Data are shown as mean ± SEM. *p < 0.05 compared to healthy never-smokers, #p < 0.05 compared to 'healthy' smokers