Pathogenesis of chronic obstructive pulmonary disease: understanding the contributions of gene-environment interactions across the lifespan

Abstract

The traditional view of chronic obstructive pulmonary disease (COPD) as a self-inflicted disease caused by tobacco</p><p>smoking in genetically susceptible individuals has been challenged by recent research findings. COPD can instead be</p><p>understood as the potential end result of the accumulation of gene–environment interactions encountered by an</p><p>individual over the lifetime. Integration of a time axis in pathogenic models of COPD is necessary because the</p><p>biological responses to and clinical consequences of different exposures might vary according to the age of an</p><p>individual at which a given gene–environment interaction occurs, as well as to the cumulative history of previous</p><p>gene–environment interactions. Future research should aim to understand the effects of dynamic interactions</p><p>between genes (G) and the environment (E) by integrating information from basic omics (eg, genomics, epigenomics,</p><p>proteomics) and clinical omics (eg, phenomics, physiomics, radiomics) with exposures (the exposome) over time</p><p>(T)—an approach that we refer to as GETomics. In the context of this approach, we argue that COPD should be</p><p>viewed not as a single disease, but as a clinical syndrome characterised by a recognisable pattern of chronic symptoms</p><p>and structural or functional impairments due to gene–environment interactions across the lifespan that influence</p><p>normal lung development and ageing.