Proteomic analysis of sputum from adults and children with cystic fibrosis and from control subjects.
BACKGROUND
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.


OBJECTIVE
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 (FEV(1) < 60%), a subset of these adults at hospital discharge, children with stable CF and preserved lung function (FEV(1) > 70%), and control subjects (FEV(1) > 80%). Sputum was arrayed by two-dimensional electrophoresis and differentially expressed proteins were identified by proteomic analysis.


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 alpha(1)-antitrypsin, IgG degradation, interleukin-8, and total protein concentration, together with their correlation to FEV(1), were statistically significant. Statistical correlation analyses indicated that changes in myeloperoxidase expression and IgG degradation were the strongest predictors of FEV(1).


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.
Sloane
Andrew J
AJ
Proteome Systems Ltd, Unit 1, 35-41 Waterloo Road, North Ryde, Sydney, NSW 2113, Australia. andrew.sloane@proteomesystems.com
Lindner
Robyn A
RA
Prasad
Sindhu S
SS
Sebastian
Lucille T
LT
Pedersen
Susanne K
SK
Robinson
Michael
M
Bye
Peter T
PT
Nielson
Dennis W
DW
Harry
Jenny L
JL
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002648:Child; D003550:Cystic Fibrosis / Q000201:enzymology* / Q000503:physiopathology; D018450:Disease Progression; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D009195:Peroxidase / Q000378:metabolism*; D011379:Prognosis; D040901:Proteomics; D012720:Severity of Illness Index; D013183:Sputum / Q000737:chemistry*; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
D015415:Biomarkers; D007074:Immunoglobulin G; D016209:Interleukin-8; D000515:alpha 1-Antitrypsin; D009195:Peroxidase