Clinical Chemistry
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Clinical Chemistry 53: 636-644, 2007. First published February 15, 2007; 10.1373/clinchem.2006.076075
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Right arrow Proteomics and Protein Markers
(Clinical Chemistry. 2007;53:636-644.)
© 2007 American Association for Clinical Chemistry, Inc.

Proteomics and Protein Markers

Protein Expression Patterns Associated with Progression of Chronic Obstructive Pulmonary Disease in Bronchoalveolar Lavage of Smokers

Amelie Plymoth1,a, Claes-Göran Löfdahl1, Ann Ekberg-Jansson2, Magnus Dahlbäck3, Per Broberg4, Martyn Foster5, Thomas E. Fehniger4 and György Marko-Varga4

1 Department of Respiratory Medicine and Allergology, Lund University Hospital, Lund, Sweden.
2 Sahlgrenska University Hospital, Gothenburg, Sweden.
3 Department of Discovery Medicine and Epidemiology, AstraZeneca, Lund, Sweden.
4 Department of Biological Sciences, AstraZeneca R&D, Lund, Sweden.
5 Department of Safety Assessment, AstraZeneca R&D, Loughborrough, United Kingdom.

aAddress correspondence to this author at: Fax +46-46-146793; e-mail amelie.plymoth{at}med.lu.se.

Background: We modeled the expression of proteins in baseline bronchoalveolar lavage (BAL) samples from asymptomatic 60-year-old lifelong current smokers or healthy never-smokers, who were reevaluated after 6 to 7 years to record clinical outcome.

Methods: Applying a technology toolbox consisting of replicate 2-dimensional gel separations, image annotation, and mass spectrometry identification, we catalogued a global set of proteins that were differentially expressed in individuals by presence, absence, and intensity scores.

Results: By use of multivariate analysis, we selected a subset of proteins that accurately separated smokers from never-smokers based on composite scoring. Follow-up after 6 to 7 years identified a group of individuals who had progressed to chronic obstructive pulmonary disease (COPD), Global Initiative for Chronic Obstructive Lung Disease stage 2. The baseline BAL samples of these eventual COPD patients shared a distinct protein expression profile that could be identified using partial least-squares discriminant analysis. This pattern was not observed in BAL samples of asymptomatic smokers free of COPD at 6- to 7-year follow-up.

Conclusions: Our model suggests that certain patterns of protein expression occurring in the airways of long-term smokers may be detected in smokers susceptible to a progression of COPD disease, before disease is clinically evident.






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Copyright © 2007 by the American Association for Clinical Chemistry.