Research in Context
Evidence before this study
Low circulating concentrations of CC16 have been linked to subsequent accelerated decline in forced expiratory volume in 1 s (FEV1) in patients with chronic obstructive pulmonary disease (COPD). These observations are in line with experimental evidence that supports anti-inflammatory and antioxidative effects of this molecule in the lungs. However, whether low circulating CC16 concentrations predict decline in lung function and incidence of COPD in the general population remains unknown. Whether effects of CC16 on subsequent lung function are already present in childhood, before exposure to cigarette smoking, is also unknown. We completed several PubMed searches with the search terms “CC16”, “CC10”, “CCSP”, “uteroglobin”, “Clara cell”, “Club cell”, “COPD”, “emphysema”, “chronic bronchitis”, “asthma”, and “lung function”, without language restrictions. Several cross-sectional studies linking circulating CC16 to asthma, COPD, and lung function and two clinical studies linking circulating CC16 to subsequent decline in FEV1 among patients with COPD were identified. We did not, however, find any previous prospective studies that assessed baseline circulating CC16 concentrations in relation to lung function growth or decline, or in relation to subsequent incidence of COPD in the general population. The date of our last search was Nov 28, 2014.
Added value of this study
In six population-based cohorts, three of adults and three of children, we found consistent relations between low circulating baseline concentrations of CC16 and accelerated decline in lung function and incidence of COPD in adults and subsequent lung function growth deficits in children up to age 16 years. These results remained significant after adjustment for other known risk factors and they cannot be explained only by residual confounding by smoking. Our study provides novel evidence that implicates low CC16 concentrations as an independent risk factor for lung function deficits and COPD.
Implications of all the available evidence
Our results indicate the possible value of CC16 for risk stratification. Longitudinal studies designed to investigate determinants of circulating CC16 concentrations and to model serial CC16 measurements are warranted to establish conclusively the potential of this molecule in informing prevention or treatment of COPD.