The respiratory community has traditionally defined respiratory health as the absence of lung disease. This definition results in early lung disease being defined as the first appearance of abnormal respiratory physiology, a paradigm that does not acknowledge that the transition from health to chronic lung disease develops over years, a period of time when lung disease interception strategies could be most efficacious. A public health strategy for chronic lung disease focused on disease interception mandates the detection of impaired respiratory health before chronic lung disease becomes clinically apparent. Our group has investigated the predictors and consequences of lung function decline in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a longitudinal cohort aged 18-30 at inception in 1985. We have identified features of impaired respiratory health that precede the development of chronic lung disease. These include: lower peak lung function in young adulthood, accelerated age-related decline in lung function, elevations in systemic inflammatory biomarkers, and the presence of respiratory symptoms. While we have documented the clinical relevance of impaired respiratory health, our work to-date does not provide a set of targets for the interception of chronic lung disease. We now propose to take advantage of CARDIA's unique platform to study the transition from impaired respiratory health to lung disease. In this renewal application to the CARDIA Lung study, we will build upon our work which has determined phenotypes of impaired lung health by collecting lung CT scans, pulmonary function, and nasal epithelial gene expression at the CARDIA year 35 examination. We will seek to validate phenotypes and identify endotypes of impaired respiratory health. We will test the hypothesis that imaging, blood, and nasal biomarkers serve as useful phenotypes and endotypes of impaired lung health and are associated with transitions to chronic lung disease through the following specific aims: (1) Determine multidimensional (integrating both longitudinal measures of lung function and CT lung injury) lifecourse trajectories associated with the future development of emphysema and interstitial change, (2) Using a proteomic discovery-platform, determine whether blood biomarkers predict divergent phenotypic manifestations of lung disease (emphysema vs. interstitial change) in the transition from impaired respiratory health to lung disease, (3) Determine whether CT lung injury, emphysema, and interstitial change are associated with altered gene expression in the nasal respiratory epithelium. This study will investigate factors associated with susceptibility versus resilience to lung disease and the pathobiologic changes associated with impaired lung health, and in doing so, will contribute to a foundation for the future interception of chronic lung disease.
Public health relevance: Through the identification of the earliest manifestations of impaired respiratory health we will contribute to knowledge that can be used to intercept the development of chronic lung disease. This new information can be used to develop strategies to reduce the overall burden of chronic lung diseases through primary prevention.
|Tedla, Yacob G; Yano, Yuichiro; Thyagarajan, Bharat et al. (2018) Peak lung function during young adulthood and future long-term blood pressure variability: The Coronary Artery Risk Development in Young Adults (CARDIA) study. Atherosclerosis 275:225-231|
|Reyfman, Paul A; Washko, George R; Dransfield, Mark T et al. (2018) Defining Impaired Respiratory Health. A Paradigm Shift for Pulmonary Medicine. Am J Respir Crit Care Med 198:440-446|
|Kalhan, Ravi; Dransfield, Mark T; Colangelo, Laura A et al. (2018) Respiratory Symptoms in Young Adults and Future Lung Disease. The CARDIA Lung Study. Am J Respir Crit Care Med 197:1616-1624|
|Mathew, Amanda R; Bhatt, Surya P; Colangelo, Laura A et al. (2018) Life-course Smoking Trajectories and Risk of Emphysema in Middle Age: The CARDIA Lung Study. Am J Respir Crit Care Med :|
|Kalhan, Ravi; Wilkins, John T; Hitsman, Brian L (2018) Tobacco Smoking Is a Medical Problem. We Ought to Treat It Like One. Am J Respir Crit Care Med 197:852-853|
|Cuttica, Michael J; Bhatt, Surya P; Rosenberg, Sharon R et al. (2017) Pulmonary artery to aorta ratio is associated with cardiac structure and functional changes in mild-to-moderate COPD. Int J Chron Obstruct Pulmon Dis 12:1439-1446|
|Moualla, Maan; Qualls, Clifford; Arynchyn, Alexander et al. (2017) Rapid decline in lung function is temporally associated with greater metabolically active adiposity in a longitudinal study of healthy adults. Thorax 72:1113-1120|
|Aaron, Carrie P; Hoffman, Eric A; Lima, Joao A C et al. (2017) Pulmonary vascular volume, impaired left ventricular filling and dyspnea: The MESA Lung Study. PLoS One 12:e0176180|
|Parikh, Megha A; Aaron, Carrie P; Hoffman, Eric A et al. (2017) Angiotensin-Converting Inhibitors and Angiotensin II Receptor Blockers and Longitudinal Change in Percent Emphysema on Computed Tomography. The Multi-Ethnic Study of Atherosclerosis Lung Study. Ann Am Thorac Soc 14:649-658|
|Bhatia, Sapna; Qualls, Clifford; Crowell, Thomas A et al. (2017) Rapid decline in lung function in healthy adults predicts incident excess urinary albumin excretion later in life. BMJ Open Respir Res 4:e000194|
Showing the most recent 10 out of 15 publications