European Respiratory Review 2017 26: 160010; DOI: 10.1183/16000617.0010-2016
Dept of Pulmonary Medicine, Reunion Island University Hospital/South Reunion Island Hospital Group, Saint-Pierre, FranceINSERM, UMR 1188 Diabetes-Atherothrombosis Therapies Reunion Island Indian Ocean (DéTROI), Reunion Island Indian Ocean Cyclotron (CYROI) Platform, Sainte-Clotilde, FranceUniversity of Reunion Island, UMR 1188, Sainte-Clotilde, France
Comparison between the a) traditional and b) new holistic approach to biomedical research. The traditional approach starts with observation of symptoms. The symptoms are grouped into syndromes or diseases based on current knowledge of the pathophysiology of the disease. Phenotype B is detected through cluster analysis. Due to the limited number of variables used, phenotypes A and C are not detected. Pathophysiological knowledge leads to a focus on the most common, distinctive disease pattern. Cell and animal models are developed in order to identify targeted therapies for phenotype B. This process excludes rarer and less well understood phenotypes. The use of targeted therapy helps refine our understanding of the pathophysiology of phenotype B by identifying responders and nonresponders. Responder and nonresponder biomarkers may be discovered and screened for. In this traditional process, several phenotypes, such as A, C and nonresponders of B, will not benefit from innovative therapies. In summary, this reductionist process starts with symptoms and culminates in laboratory tests. In the holistic process, the subject may be symptomatic or healthy and the analysis of each individual takes into account conventional variables as well as a large body of data including, for instance, their microbiome, genetic data, sputum data, occupation, diet, etc. These data are fed into mathematical algorithms to model the outcome of each subject, generating “n” models, “n” predicted syndromes and “n” “diseases”. The pathophysiology will be studied in biological models and in silico models to identify therapies (or management) targeting defined groups (strata) of subjects and to propose preventive, predictive, personalised strategies. In the holistic process, the subject may be healthy, and the “syndrome” is based on biological data.