title: 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.
authors.affiliation: Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University School of Medicine , Nashville, Tennessee. ; Vanderbilt Center for Asthma and Environmental Health Sciences Research, Vanderbilt University , Nashville, Tennessee.
authors.forename: Christian
authors.initials: C
authors.lastname: Rosas-Salazar
authors.affiliation: Department of Biostatistics, Vanderbilt University School of Medicine , Nashville, Tennessee. ; Vanderbilt Center for Asthma and Environmental Health Sciences Research, Vanderbilt University , Nashville, Tennessee.
authors.forename: Tebeb
authors.initials: T
authors.lastname: Gebretsadik
authors.affiliation: Division of General Pediatrics, Department of Pediatrics, Vanderbilt University School of Medicine , Nashville, Tennessee. ; Vanderbilt Center for Asthma and Environmental Health Sciences Research, Vanderbilt University , Nashville, Tennessee.
authors.forename: Kecia N
authors.initials: KN
authors.lastname: Carroll
authors.affiliation: Vanderbilt Center for Asthma and Environmental Health Sciences Research, Vanderbilt University , Nashville, Tennessee.
authors.forename: Sara
authors.initials: S
authors.lastname: Reiss
authors.affiliation: Vanderbilt Center for Asthma and Environmental Health Sciences Research, Vanderbilt University , Nashville, Tennessee.
authors.forename: Nancy
authors.initials: N
authors.lastname: Wickersham
authors.affiliation: Vanderbilt Center for Asthma and Environmental Health Sciences Research, Vanderbilt University , Nashville, Tennessee.
authors.forename: Emma K
authors.initials: EK
authors.lastname: Larkin
authors.affiliation: Vanderbilt Center for Asthma and Environmental Health Sciences Research, Vanderbilt University , Nashville, Tennessee.
authors.forename: Kristina M
authors.initials: KM
authors.lastname: James
authors.affiliation: Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University School of Medicine , Nashville, Tennessee.
authors.forename: E Kathryn
authors.initials: EK
authors.lastname: Miller
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta , Atlanta, Georgia .
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Anderson
authors.affiliation: Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine , Nashville, Tennessee. ; Vanderbilt Center for Asthma and Environmental Health Sciences Research, Vanderbilt University , Nashville, Tennessee.
authors.forename: Tina V
authors.initials: TV
authors.lastname: Hartert