Published ahead of print on September 15, 2005, doi:10.1164/rccm.200409-1215OC
© 2005 American Thoracic Society doi: 10.1164/rccm.200409-1215OC
Proteomic Analysis of Sputum from Adults and Children with Cystic Fibrosis and from Control SubjectsProteome Systems, Ltd; Department of Respiratory Medicine, Royal Prince Alfred Hospital, Sydney, Australia; and Department of Pediatrics, University of California, San Francisco, San Francisco, California Correspondence and requests for reprints should be addressed to Andrew Sloane, Ph.D., Proteome Systems Ltd, Unit 1, 35-41 Waterloo Road, North Ryde, Sydney, NSW 2113, Australia. E-mail: andrew.sloane{at}proteomesystems.com 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 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.
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1-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. 
