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Proteomic Analysis of Sputum from Adults and Children with Cystic Fibrosis and from Control Subjects
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Proteomic Analysis of Sputum from Adults and Children with Cystic Fibrosis and from Control Subjects
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Journal Article
Proteomic Analysis of Sputum from Adults and Children with Cystic Fibrosis and from Control Subjects
2005
Overview
Abstract
Rationale
Recurrent pulmonary exacerbations are associated with progressive lung disease in cystic fibrosis (CF). Current definitions of an exacerbation, although not precisely defined, include new/worsening symptoms, declining lung function, and/or changing radiologic appearance. Early diagnosis of exacerbations by rapid noninvasive means should expedite therapeutic intervention, thereby minimizing lung damage.
Objectives
To identify biomarkers of lung exacerbation for point-of-care monitoring of CF lung disease progression.
Methods
Saline-induced sputum was collected from adults with CF with an exacerbation and requiring hospitalization (FEV1 < 60%), a subset of these adults at hospital discharge, children with stable CF and preserved lung function (FEV1 > 70%), and control subjects (FEV1 > 80%). Sputum was arrayed by two-dimensional electrophoresis and differentially expressed proteins were identified by proteomic analysis.
Measurements and Main Results
Sputum profiles from adults with CF with an exacerbation were characterized by extensive proteolytic degradation and influx of inflammation-related proteins, with some adults with CF approaching a “healthy” protein profile after hospitalization. Two children with CF showed profiles and biomarker expression resembling those of adults with an exacerbation. Levels of differentially expressed myeloperoxidase, cleaved α1-antitrypsin, IgG degradation, interleukin-8, and total protein concentration, together with their correlation to FEV1, were statistically significant. Statistical correlation analyses indicated that changes in myeloperoxidase expression and IgG degradation were the strongest predictors of FEV1.
Conclusions
We identified extensive protein degradation and differentially expressed proteins as biomarkers of inflammation relating to pulmonary exacerbations. Prediction of exacerbation onset and more precise evaluation of the extent of resolution with treatment could be achieved by including biomarkers in standard assessment.
Publisher
Am Thoracic Soc,Oxford University Press,American Lung Association
Subject
/ Adult
/ alpha 1-Antitrypsin - metabolism
/ Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
/ Biological and medical sciences
/ Child
/ Cystic Fibrosis - enzymology
/ Cystic Fibrosis - physiopathology
/ Electrophoresis, Gel, Two-Dimensional
/ Enzyme-Linked Immunosorbent Assay
/ Female
/ Humans
/ Immunoglobulin G - metabolism
/ Male
/ Proteins
/ Psychology. Psychoanalysis. Psychiatry
/ Transfusions. Complications. Transfusion reactions. Cell and gene therapy
