Received on July 7, 2006
Accepted on January 18, 2007

Proteomics and Protein Markers

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

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

^* To whom correspondence should be addressed. 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.