Dataset Information

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.

SUBMITTER: Rosas-Salazar C

PROVIDER: S-EPMC4580139 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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

Rosas-Salazar Christian C Gebretsadik Tebeb T Carroll Kecia N KN Reiss Sara S Wickersham Nancy N Larkin Emma K EK James Kristina M KM Miller E Kathryn EK Anderson Larry J LJ Hartert Tina V TV

Pediatric allergy, immunology, and pulmonology 20150901 3

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 ...[more]

PMID: 26421213

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Project description:IMPORTANCE:Many preschool children develop recurrent, severe episodes of lower respiratory tract illness (LRTI). Although viral infections are often present, bacteria may also contribute to illness pathogenesis. Strategies that effectively attenuate such episodes are needed. OBJECTIVE:To evaluate if early administration of azithromycin, started prior to the onset of severe LRTI symptoms, in preschool children with recurrent severe LRTIs can prevent the progression of these episodes. DESIGN, SETTING, AND PARTICIPANTS:A randomized, double-blind, placebo-controlled, parallel-group trial conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute's AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by December 2014. Participants were 607 children aged 12 through 71 months with histories of recurrent, severe LRTIs and minimal day-to-day impairment. INTERVENTION:Participants were randomly assigned to receive azithromycin (12 mg/kg/d for 5 days; n?=?307) or matching placebo (n?=?300), started early during each predefined RTI (child's signs or symptoms prior to development of LRTI), based on individualized action plans, over a 12- through 18-month period. MAIN OUTCOMES AND MEASURES:The primary outcome measure was the number of RTIs not progressing to a severe LRTI, measured at the level of the RTI, that would in clinical practice trigger the prescription of oral corticosteroids. Presence of azithromycin-resistant organisms in oropharyngeal samples, along with adverse events, were among the secondary outcome measures. RESULTS:A total of 937 treated RTIs (azithromycin group, 473; placebo group, 464) were experienced by 443 children (azithromycin group, 223; placebo group, 220), including 92 severe LRTIs (azithromycin group, 35; placebo group, 57). Azithromycin significantly reduced the risk of progressing to severe LRTI relative to placebo (hazard ratio, 0.64 [95% CI, 0.41-0.98], P?=?.04; absolute risk for first RTI: 0.05 for azithromycin, 0.08 for placebo; risk difference, 0.03 [95% CI, 0.00-0.06]). Induction of azithromycin-resistant organisms and adverse events were infrequently observed. CONCLUSIONS AND RELEVANCE:Among young children with histories of recurrent severe LRTIs, the use of azithromycin early during an apparent RTI compared with placebo reduced the likelihood of severe LRTI. More information is needed on the development of antibiotic-resistant pathogens with this strategy. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT01272635.

Project description:BackgroundSeveral studies have reported that birth by caesarean section is associated with increased risk of lower respiratory tract infections in the child, but it is unclear whether this applies to any caesarean section or specifically to planned caesareans. Furthermore, although infections of the upper respiratory tract are very common during childhood, there is a scarcity of studies examining whether caesarean is also a risk factor for this site of infection.MethodsWe obtained data from two UK cohorts: the Millennium Cohort Study (MCS) and linked administrative datasets of the population of Wales through the Secure Anonymised Information Linkage (SAIL) databank. The study focused on term-born singleton infants and included 15,580 infants born 2000-2002 (MCS) and 392,145 infants born 2002-2016 (SAIL). We used information about mode of birth (vaginal delivery, assisted vaginal delivery, planned caesarean and emergency caesarean) from maternal report in the MCS and from hospital birth records in SAIL. Unplanned hospital admission for lower respiratory tract infection (LRTI) was ascertained from maternal report in the MCS and from hospital record ICD codes in SAIL. Information about admissions for upper respiratory tract infection (URTI) was available from SAIL only. Cox regression was used to estimate hazard ratios for each outcome and cohort separately while accounting for a wide range of confounders. Gestational age at birth was further examined as a potential added, indirect risk of planned caesarean birth due to the early delivery.FindingsThe rate of hospital admission for LRTI was 4.6 per 100 child years in the MCS and 5.9 per 100 child years in SAIL. Emergency caesarean was not associated with LRTI admission during infancy in either cohort. In the MCS, planned caesarean was associated with a hazard ratio of 1.39 (95% CI 1.03, 1.87) which further increased to 1.65 (95% CI 1.24, 2.19) when gestational age was not adjusted for. In SAIL, the adjusted hazard ratio was 1.10 (95% CI 1.05, 1.15), which increased to 1.17 (95% CI 1.12, 1.22) when gestational age was not adjusted for. The rate of hospital admission for URTI was 5.9 per 100 child years in SAIL. Following adjustments, emergency caesarean was found to have a hazard ratio of 1.09 (95% CI 1.05, 1.14) for hospital admission for URTI. Planned caesarean was associated with a hazard ratio of 1.11 (95% CI 1.06, 1.16) which increased to 1.17 (95% CI 1.12, 1.22) when gestational age was not adjusted for.ConclusionsThe risk of severe LRTIs during infancy is moderately elevated in infants born by planned caesarean compared to those born vaginally. Infants born by any type of caesarean may also be at a small increased risk of severe URTIs. The estimated effect sizes are stronger if including the indirect effect arising from planning the caesarean birth for an earlier gestation than would have occurred spontaneously. Further studies are needed to confirm these results.

Dataset Information

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

Publications

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

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