CC16 as a mediator of the effects of preterm birth on airflow limitation and asthma: a longitudinal study from birth to adult life

<bold>Background:</bold> Club cell secretory protein (CC16) is a pneumoprotein with anti-inflammatory and antimicrobial properties. <bold>Aims:</bold> Determine whether deficits in circulating CC16 mediate the effects of preterm birth (<37 weeks) on airflow limitation and asthma into adult life. <bold>Methods:</bold> Using the Swedish BAMSE birth cohort (N=2557, 9759 obs), we assessed plasma CC16 at ages 8 and 24, spirometry at 8, 16, 24, and asthma from 8-24. Longitudinal associations between preterm birth, CC16 levels, percent predicted FEV₁/FVC (ppFEV₁/FVC, GLI), and asthma were examined. CC16 was tested as a potential mediator for the relations of preterm birth to ppFEV₁/FVC and asthma. <bold>Results:</bold> Preterm birth was associated with reduced plasma CC16 (−1.15 ng/ml [95%CI -1.22, -1.08], p<0.0001), lower ppFEV₁/FVC (−2.1% [−3.2, -1.0], p=0.0003), and nearly doubled asthma risk (OR 1.89 [1.21, 2.96], p=0.005) from ages 8-24. CC16 deficits at ages 8 and 24 were related to concurrent decreased ppFEV₁/FVC (p=0.005) and increased asthma risk (p<0.0001). Mediation analyses indicated that CC16 mediated 17% and 24% of the effects of preterm birth on ppFEV₁/FVC and asthma at age 24, respectively. Results were similar (14% and 17%, respectively) after adjusting for confounders (Fig). <fig><object-id>erj;64/suppl_68/OA5576/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig> <bold>Conclusion:</bold> We reveal a novel role of CC16 as a mediator partly responsible for lung function deficits and asthma in young adults born prematurely.