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

smoking in genetically susceptible individuals has been challenged by recent research findings. COPD can instead be

understood as the potential end result of the accumulation of gene–environment interactions encountered by an

individual over the lifetime. Integration of a time axis in pathogenic models of COPD is necessary because the

biological responses to and clinical consequences of different exposures might vary according to the age of an

individual at which a given gene–environment interaction occurs, as well as to the cumulative history of previous

gene–environment interactions. Future research should aim to understand the effects of dynamic interactions

between genes (G) and the environment (E) by integrating information from basic omics (eg, genomics, epigenomics,

proteomics) and clinical omics (eg, phenomics, physiomics, radiomics) with exposures (the exposome) over time

(T)—an approach that we refer to as GETomics. In the context of this approach, we argue that COPD should be

viewed not as a single disease, but as a clinical syndrome characterised by a recognisable pattern of chronic symptoms

and structural or functional impairments due to gene–environment interactions across the lifespan that influence

normal lung development and ageing.