Urine Club Cell 16-kDa Secretory Protein and Childhood Wheezing Illnesses After Lower Respiratory Tract Infections in Infancy

Abstract

Background: Infants with lower respiratory tract infections (LRTIs) are at an increased risk of developing childhood wheezing illnesses (including asthma), but it is not currently possible to predict those at risk for these long-term outcomes. The current objective was to examine whether urine levels of club cell 16-kDa secretory protein (CC16) at the time of an infant LRTI are associated with the development of childhood wheezing illnesses. Methods: Prospective study of 133 previously healthy infants enrolled during a healthcare visit for a LRTI and followed longitudinally for childhood wheezing illnesses. Urine levels of CC16 at the time of enrollment were measured after validating a commercially available enzyme-linked immunosorbent assay kit for serum. The outcome of interest was parental report of subsequent childhood wheeze (defined as ‡1 episode of wheezing following the initial LRTI) at the 1-year follow-up visit. Logistic regression was used for the main analysis. Results: The median (interquartile range) urine levels of CC16 (ng/mg of creatinine) at the time of an infant LRTI were 11.1 (7.7-20.1) for infants with subsequent childhood wheeze and 13.4 (8.3-61.1) for those without ( p = 0.11). In the main multivariate analysis using a logarithmic transformation of the urine levels of CC16, a twofold increase in urine levels of CC16 was associated with *30% decreased odds (OR = 0.74 [95% confidence interval (CI) 0.56-0.98], p = 0.04) of subsequent childhood wheeze after adjustment for potential confounders. Conclusions: An inverse association was found between urine levels of CC16 at the time of an infant LRTI and the odds of subsequent childhood wheeze. Urine CC16 may be a useful biomarker of the development of childhood wheezing illnesses after LRTIs in infancy.

Using urine metabolomics to understand the pathogenesis of infant respiratory syncytial virus (RSV) infection and its role in childhood wheezing

“…Recent developments in high-throughput molecular techniques provide an opportunity for understanding pathogenesis of RSV infection, but a biomarker that accurately and consistently predicts susceptibility to RSV infection, infection severity, and association with subsequent development of persistent wheezing and asthma has yet to be developed (Larkin and Hartert 2015; Openshaw 2013; Rosas-Salazar et al 2015). Metabolic pathways, as a mirror of the interactions between host cell and virus (Pearce and Pearce 2013; Peeples and Levine 1980), provide an opportunity to understand the mechanisms that underlie severe infections and pathways through which RSV ARI contributes to the development of asthma.…”

Urinary club cell protein 16 (CC16): Utility of its assay during acute bronchiolitis

“…The link between its levels and asthma has already been studied, but its relation to acute bronchiolitis has received less attention . We set out to determine whether CC16 could be a severity biomarker of epithelial damage during acute bronchiolitis and of recurrent wheezing in the sequelae.…”

Airway epithelial cell damage in asthma: mechanisms and biomarkers

“…Zhai and colleagues [66] using human data from a birth cohort, suggested that low circulating CCSP16 levels were not only a biomarker of airway pathology but may be implicated in the pathophysiology of the progressive airway damage that characterize obstructive lung diseases. Moreover, urinary CCSP16 may be a useful tool or biomarker for studying asthma and the integrity of the alveolar epithelium in children with lung injury [69].Emerging biomarkers:…”