Dataset Information

Early Childhood Risk Factors for Decreased FEV1 at Age Six to Seven Years in Young Children with Cystic Fibrosis.

ABSTRACT: There are limited objective measures of the severity of lung disease before children are able to routinely perform spirometry, generally at age 6 years. Identifying risk factors for reduced lung function at age 6 provides opportunities to intervene and slow the progression of cystic fibrosis (CF) lung disease.To evaluate early childhood predictors of lung function at age 6-7 in a large U.S. CF cohort in the current era of widespread early eradication therapy for Pseudomonas aeruginosa (P. aeruginosa).Participants were children with CF enrolled before age 4 in the Early Pseudomonas Infection Control (EPIC) Observational Study, a multicenter, longitudinal study that enrolled P. aeruginosa-negative children not exceeding 12 years of age. Linear regression was used to estimate the association between potential early childhood risk factors and the best FEV1% predicted at age 6-7 years.Four hundred and eighty-four children (of 1,797 enrolled in the EPIC Observational Study) met the eligibility criteria for this analysis. Mean (SD) age at enrollment was 2.0 (1.3) years. In a multivariable model adjusted for age at enrollment, the following risk factors were significantly associated with lower mean (95% confidence interval) FEV1% predicted at age 6-7: weight percentile less than 10% during the year of enrollment (-5.3 [-9.1, -1.5]), P. aeruginosa positive during the year of enrollment (-2.8 [-5.7, 0.0]), crackles or wheeze during the year of enrollment (-5.7 [-9.4, -1.9]), mother's education of high school or less (-4.2 [-7.3, -1.2]), and mother smoked during pregnancy (-4.4 [-8.8, 0.1]).In this large U.S. cohort, we identified several early childhood risk factors for lower FEV1 at age 6-7 years, most of which are modifiable. Clinical trial registered with www.clinicaltrials.gov (NCT00097773).

SUBMITTER: Sanders DB

PROVIDER: S-EPMC4566413 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Publications

Early Childhood Risk Factors for Decreased FEV1 at Age Six to Seven Years in Young Children with Cystic Fibrosis.

Sanders Don B DB Emerson Julia J Ren Clement L CL Schechter Michael S MS Gibson Ronald L RL Morgan Wayne W Rosenfeld Margaret M

Annals of the American Thoracic Society 20150801 8

<h4>Rationale</h4>There are limited objective measures of the severity of lung disease before children are able to routinely perform spirometry, generally at age 6 years. Identifying risk factors for reduced lung function at age 6 provides opportunities to intervene and slow the progression of cystic fibrosis (CF) lung disease.<h4>Objectives</h4>To evaluate early childhood predictors of lung function at age 6-7 in a large U.S. CF cohort in the current era of widespread early eradication therapy ...[more]

PMID: 26288390

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Project description:Background:Culture-independent next generation sequencing has identified diverse microbial communities within the cystic fibrosis (CF) airway. The study objective was to test for differences in the upper airway microbiome of children with CF and healthy controls and age-related differences in children with CF. Methods:Oropharyngeal swabs and clinical data were obtained from 25 children with CF and 50 healthy controls aged ?6 years. Bacterial DNA was amplified and sequenced for the V4 region of 16S rRNA marker-gene. Alpha diversity was measured using operational taxonomic units (OTUs), Shannon diversity, and the inverse Simpson's index. Beta diversity was measured using Morisita-Horn and Bray-Curtis and Jaccard distances. General linear models were used for comparison of alpha diversity measures between groups to account for differences in demographics and exposures. Mixed effects general linear models were used for longitudinal comparisons 1) between children with CF of different ages and 2) between children with CF receiving CF transmembrane conductance regulator (CFTR) modulators, children with CF not receiving CFTR modulators, and healthy controls to adjust for repeated measures per subject. Results:Children with CF were more likely to have received antibiotics in the prior year than healthy controls (92% vs 24%, p < 0.001). Controlling age, race, ethnicity, length of breastfeeding, and having siblings, children with CF had a lower richness than healthy controls: OTUs 62.1 vs 83, p = 0.022; and trended toward lower diversity: Shannon 2.09 vs 2.35, p = 0.057; inverse Simpson 5.7 vs 6.92, p = 0.118. Staphylococcus, three Rothia OTUs, and two Streptococcus OTUs were more abundant in CF children versus healthy controls (all p < 0.05). Bray-Curtis and Jaccard distances, which reflect overall microbial community composition, were also significantly different (both p = 0.001). In longitudinally collected samples from children with CF, Morisita-Horn trended toward more similarity in those aged 0-2 years compared to those aged 3-6 years (p = 0.070). In children >2 years of age, there was a significant trend in increasing alpha diversity measures between children with CF not receiving CFTR modulators, children with CF receiving CFTR modulators, and healthy controls: OTUs 63.7 vs 74.7 vs 97.6, p < 0.001; Shannon 2.11 vs 2.34 vs 2.56, p < 0.001; inverse Simpson 5.78 vs 7.23 vs 7.96, p < 0.001. Conclusions:Children with CF have lower bacterial diversity and different composition of organisms compared with healthy controls. This appears to start in early childhood, is possibly related to the use of antibiotics, and may be partially corrected with the use of CFTR modulators.

Dataset Information

Early Childhood Risk Factors for Decreased FEV1 at Age Six to Seven Years in Young Children with Cystic Fibrosis.

Publications

Early Childhood Risk Factors for Decreased FEV1 at Age Six to Seven Years in Young Children with Cystic Fibrosis.

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