Discovery & Identification of biomarkers of Chronic Obstructive Pulmonary Disease Onset using a Case-control study design & Translational systems biology-Outline study plan

It is well known that the major cause of chronic obstructive pulmonary disease (COPD) is repeated long-term exposure to tobacco smoke. Philip Morris International is currently undergoing an effort to develop novel tobacco products with the potential to reduce tobacco related diseases. Since COPD takes on average 20-25 years to develop, in the absence of appropriate biomarkers, it would be necessary to conduct studies for at least this timeframe in order to assess the impact of novel products on COPD incidence. In an effort to significantly reduce this assessment timeframe for every novel product, it is necessary to identify biomarkers which change on exposure to tobacco smoke and precede clinical onset of COPD. Once identified, validated and qualified, these biomarkers may be used for assessing novel tobacco products through the comparison of these biomarkers in smokers of conventional tobacco product and novel, potentially reduced-risk tobacco products. There are many large academic-industry collaborations looking at the identification of COPD biomarkers, however, these studies focus on the identification of biomarkers of COPD progression and do not explore biomarkers of disease onset. For the purposes of investigating the impact of novel tobacco products on the onset of COPD, these biomarkers of progression represent disease already too advanced for our purposes. In order to identify these biomarkers, we are conducting an observational, non-interventional case-control study, in which we are recruiting 60 subjects that currently smoke and have COPD gold stage I or IIA. These subjects will be matched to 3 control groups, 60 never smokers, 60 healthy smokers and 60 healthy ex-smokers. In this study, we will collect induced sputum, whole blood, nasal fluid, nasal lavage and nasal scrapes for the discovery of biomarker signatures, using a combination of transcriptomics, proteomics and lipidomics to identify biomarker signatures which indicate the crucial link between cigarette smoke exposure and the onset of COPD. Using state-of-the-art computational platforms and using data generated from our pre-clinical experiments using models of COPD, as well as published data, we will be conducting high performance mass-spectrometric targeted analysis of the sputum, and looking for correlations in the blood and nasal samples. Once identified, the biomarkers will have to be analytically validated and clinically qualified. Although a consensus is emerging, there are no clear definitive guidelines on how this should be done, and it is a scientific discussion that we would very much like to be a part of and apply it to the outcomes of this study.