Chronic obstructive pulmonary disease (COPD) is the 3rd leading cause of death in the US1, 2. Although COPD occurs predominantly in smokers, it is unknown why only a minority of smokers (~20-40%) develop chronic airflow limitation or destruction of distal airspaces (emphysema). Furthermore, most subjects will spend many years in a presymptomatic disease state (pre-COPD) before the onset of disease, even after smoking cessation. Identification of the at-risk presymptomatic current or former smoker is the crucial firt step needed to study early interventions that can prevent the development of COPD and emphysema. In pilot work we have identified multiple novel blood lipid (sphingomyelin and ceramide species) and protein biomarkers of COPD and emphysema. We hypothesize that some of these biomarkers will be stable molecular signature that can identify presymptomatic current and former smokers who are at risk for progression to symptomatic lung disease such as COPD and emphysema. Our proposal will measure candidate biomarkers in previously collected blood from three international longitudinal cohorts (COPDGene, SPIROMICS, and Big3) that contain large numbers of pre-symptomatic former or current smokers without COPD or emphysema, who have genome wide genotyping, and are followed 3-5 years with extensive clinical phenotyping including lung function and qHRCT.
The first aim will identify which biomarkers are association with progression of airflow limitation and emphysema in those who do not have COPD at baseline.
The second aim will investigate whether these signatures are stable over time and identify the genetic associations contributing to the biomarker signature.
Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death in the United States. The major risk factor is smoking; however, most smokers do not develop COPD and the factors that identify who goes from normal to abnormal lung function are unknown. This proposal will leverage multiple, large international cohorts which contain a large number of well characterized smokers with normal lung function and have been followed for at least 3-5 year. We will use stored biologic samples to identify which blood biomarker signatures are useful to predict which smokers are likely to progress from normal lung function or to emphysema. This knowledge may help develop novel diagnostic tests and therapies for early prevention and treatment of COPD before it starts. (End of Abstract)
| Bradford, Eric; Jacobson, Sean; Varasteh, Jason et al. (2017) The value of blood cytokines and chemokines in assessing COPD. Respir Res 18:180 |
