The role of CC16 in the associations of preterm birth with lung function and asthma in adult life

Background: Club cell secretory protein (CC16) is a pneumoprotein that has anti-inflammatory and antimicrobial properties and whose levels are reduced in preterm infants. Objective: We sought to investigate the role of circulating CC16 in the association of preterm birth (<37 weeks) with lung function and asthma from childhood into young adult life in longitudinal and mediation analyses. Methods: Using the BAMSE (Swedish abbreviation for Barn/Children, Allergy, Milieu, Stockholm, Epidemiology) birth cohort (2,557 participants and 10,631 longitudinal observations), we assessed plasma CC16 (ages 8 and 24 years), spirometry (ages 8, 16, 24, and 26 years), and asthma (ages 8, 12, 16, 24, and 26 years). Longitudinal associations between preterm birth, CC16, percent predicted values of FEV₁/forced vital capacity (ppFEV₁/FVC), and asthma were examined in longitudinal multivariable mixed models. CC16 (ages 8-24 years) was tested as a mediator for the relationship of preterm birth to pre- and postbronchodilator ppFEV₁/FVC and asthma in adulthood (ages 24-26 years). Results: Preterm birth was associated with reduced plasma CC16 (−1.15 ng/mL; 95% CI, −1.22 to −1.08; P < .0001), lower ppFEV₁/FVC (−1.9%; 95% CI, −3.1 to −0.8; P = .001), and higher risk for asthma (1.83; 95% CI, 1.28 to 2.62; P = .001) across ages 8 to 26 years. CC16 deficits were related to decreased ppFEV₁/FVC (P < .0001) and increased risk for asthma (P = .007) in adulthood. Multivariable mediation analyses suggested that CC16 mediated 16% and 9% of the effects of preterm birth on ppFEV₁/FVC and asthma in adult life, respectively. Conclusions: Low CC16 is a potential mediator of the effects of prematurity on lung function deficits and asthma in young adulthood. Future studies should address whether CC16 can be used as a predictive biomarker and, possibly, a therapeutic target in individuals born preterm.