Club cell secretory protein (CC16, also known as CC10, CCSP, and uteroglobin) is a homodimeric pneumoprotein encoded by the SCGB1A1 gene that is mainly produced by club cells and other airway epithelial cells but can be readily measured in circulation. A growing body of evidence indicates that this molecule plays a critical role in enhancing resilience to respiratory infections and reducing airway inflammation. In this context, our hypothesis is that low levels of circulating CC16 in childhood may serve as an early indicator of individuals who will develop airflow limitation, a precursor of early chronic obstructive pulmonary disease (COPD), in their young adult life. Because of the expected low prevalence of airflow limitation in young adult life, testing this hypothesis will require a large epidemiological consortium of birth cohorts that have serum/plasma samples available from childhood and have characterized the lung function of a large number of participants from birth into adult life.
Here we propose to measure CC16 levels in plasma samples collected at ages 7, 9, and 15 years from ALSPAC participants to determine whether deficits in circulating CC16 in childhood predict the development of airflow limitation and small airway disease, as precursors of early COPD, in young adult life. We will integrate multiple longitudinal measurements of CC16 in childhood and link them to lung function measurements (both spirometry and IOS) completed in adult life.