Early endotyping: A chance for intervention in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a syndrome that comprises several lung pathologies, but subphenotyping the various disease subtypes has been difficult. One reasonmay be that current efforts focused on studying COPD once it has occurred do not allow tracing back to the different origins of disease. This perspective proposes that emphysema originates when susceptible airway, endothelial, and/or hematopoietic cells are exposed to environmental toxins such as cigarette smoke, biomass fuel, or traffic emissions. These susceptible cell types may initiate distinct pathobiological mechanisms ("COPD endotypes") that ultimately manifest the emphysematous destruction of the lung. On the basis of evidence fromthe "airway" endotype, we suggest that grading these endotypes by severitymay allowbetter diagnosis of disease at early stages when intervention can be designed on the basis of the mechanisms involved. Therefore, genomic, proteomic, and metabolomic studies on at-risk patientswill be important in the identification of biomarkers that help designate each endotype. Together with understanding of the involved molecular pathways that lead to disease manifestation, these efforts may lead to development of intervention strategies.