Molecular markers of early stage COPD in serum, sputum, and nasal epithelium from a case-control study

Authored by  N Chaudhary, A Elamin, E Guedj, J Hoeng, NV Ivanov, K Luettich, P Leroy, F Martin, M Peitsch, A Sewer, M Talikka, B Titz, G Vuillaume

Presented at SRNT 2015 21st Annual Meeting     


Philip Morris International is currently engaged in an effort to develop potentially reduced risk products (RRP) with the potential to reduce tobacco-related diseases compared with combustible cigarettes. COPD is a multicomponent disease of emphysema, chronic bronchitis, and small airway obstruction mainly caused by long-term exposure to tobacco smoking. COPD takes an average 20-25 years to develop, and it would be of interest to identify biomarkers of disease onset to predict the potential health impact of RRPs. One way to achieve this is to first identify molecular changes between COPD and asymptomatic smokers which would then need to be confirmed in a longitudinal study for their suitability as predictive biomarkers of COPD.

This work describes a molecular level (proteomics, transcriptomics, lipidomics) assessment conducted on samples, including induced sputum, nasal scrapes and serum, obtained from a case- control COPD study.  The aim was to identify a biomarker/panel of biomarkers for the differentiation of subjects with COPD, current smokers, former smokers and never-smokers.

Using microarray analysis, we have identified biological processes that were impacted in the nasal epithelium of COPD subjects compared with asymptomatic smokers. The down regulation of several pathways, including Jak/Stat, MAPK, and NFKB signaling were confirmed with two independent approaches, positioned in the context of basic cellular processes by a network- based approach. We further observed that early stage COPD status was reflected in the sputum proteome with 20 proteins showing differential abundance between COPD subjects and asymptomatic smokers. Finally, we have identified specific changes in serum lipid profiles in subjects with early stage COPD. Together, these molecular markers could be further examined with respect to their potential to indicate disease risk.