Dataset Information

TLR4 Polymorphism, Nasopharyngeal Bacterial Colonization, and the Development of Childhood Asthma: A Prospective Birth-Cohort Study in Finnish Children.

ABSTRACT: We aimed to explore the role of TLR4 (rs4986790) polymorphism in the nasopharyngeal (NP) bacterial colonization and its consequent impact on the development of childhood asthma. A semi-quantitative culture of NP swabs was performed on 473 children at 2 months of age and on 213 children at 13 months of age. TLR4 polymorphism was analyzed for 396 children. Children were followed from birth to the age of 7.5 years and the final outcome was physician-diagnosed asthma. The associations between TLR4 genotype, bacterial colonization, and asthma were analyzed. Children with TLR4 AG or GG genotype were more often colonized with Moraxella catarrhalis at 2 months of age (p = 0.009) and Haemophilus influenzae at 13 months of age (p = 0.018). Children who were colonized with H. influenzae at 13 months of age had a significantly higher risk of later development of asthma (p = 0.004). M. catarrhalis or H. Influenzae colonization at 2 months of age or TLR4 genotype Asp299Gly were not associated with the development of childhood asthma. TLR4 Asp299Gly polymorphism was associated with an increased risk of colonization of M. catarrhalis and H. influenzae in children. The colonization with H. influenzae at 13 months of age was associated with a higher risk of later development of childhood asthma.

SUBMITTER: Terasjarvi JT

PROVIDER: S-EPMC7397016 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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<i>TLR4</i> Polymorphism, Nasopharyngeal Bacterial Colonization, and the Development of Childhood Asthma: A Prospective Birth-Cohort Study in Finnish Children.

Teräsjärvi Johanna T JT Toivonen Laura L Vuononvirta Juho J Mertsola Jussi J Peltola Ville V He Qiushui Q

Genes 20200708 7

We aimed to explore the role of TLR4 (rs4986790) polymorphism in the nasopharyngeal (NP) bacterial colonization and its consequent impact on the development of childhood asthma. A semi-quantitative culture of NP swabs was performed on 473 children at 2 months of age and on 213 children at 13 months of age. <i>TLR4</i> polymorphism was analyzed for 396 children. Children were followed from birth to the age of 7.5 years and the final outcome was physician-diagnosed asthma. The associations between ...[more]

PMID: 32650475

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Project description:RationaleThe prevalence of childhood asthma has been increasing worldwide in parallel with childhood obesity.ObjectivesWe investigated whether there is a temporal relationship between early life weight gain (reflecting growth velocity) and early life body mass index (BMI) attained status (reflecting accumulative weight) with future risk of asthma in the Boston Birth Cohort.MethodsThis report includes 1,928 children from the Boston Birth Cohort with a mean age of 7.8 years (standard deviation, 3.3 yr), enrolled at birth and followed prospectively. Asthma was defined using physician diagnosis code (International Classification of Diseases, Ninth Revision, Clinical Modification code 493.xx) in children 2 years and older. We categorized the children by their weight gain trajectory on the basis of changes in z-scores: slow (less than -0.67), on track (-0.67 to 0.67), rapid (0.67-1.28), and extremely rapid (>1.28); and by their BMI attained status (underweight, normal weight, and overweight) during the first 4, 12, and 24 months. Poisson regression models with robust variance estimation were applied to examine the relationship between early life weight gain/attained BMI and asthma.ResultsDuring the first 4 months of life, 37% had on-track weight grain, 22% had slow weight gain, 15% had rapid weight gain, and 26% had extremely rapid weight gain. At 4 months, 61% were normal weight, 7% were underweight, and 32% were overweight. In adjusted analyses, extremely rapid early life weight gain during the first 4 and 24 months of life were each associated with increased risks of asthma (risk ratio, 1.34 for extremely rapid weight gain at 4 months; 95% confidence interval [CI], 1.06-1.70; risk ratio, 1.32 for extremely rapid weight gain at 24 months; 95% CI, 1.00-1.75) Similarly, overweight at 4, 12, and 24 months were each associated with an increased risk of asthma. Analyses that further adjusted for birthweight or preterm birth showed similar findings.ConclusionsIn this predominantly urban U.S. low-income minority birth cohort, excessive early life weight gain and overweight status were both associated with an increased risk of asthma in childhood.

Project description:BackgroundSevere bronchiolitis (ie, bronchiolitis requiring hospitalization) during infancy is a major risk factor for childhood asthma. However, the exact mechanism linking these common conditions remains unclear.ObjectivesThis study sought to examine the integrated role of airway microbiome (both taxonomy and function) and host response in asthma development in this high-risk population.MethodsThis multicenter prospective cohort study of 244 infants with severe bronchiolitis (median age, 3 months) examined the infants' nasopharyngeal metatranscriptomes (microbiomes) and transcriptomes (hosts), as well as metabolomes at hospitalization. The longitudinal relationships investigated include (1) major bacterial species (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis), (2) microbial function, and (3) host response with risks of developing asthma by age 6 years.ResultsFirst, the abundance of S pneumoniae was associated with greater risks of asthma (P = .01), particularly in infants with nonrhinovirus infection (Pinteraction = .04). Second, of 328 microbial functional pathways that are differentially enriched by asthma development, the top pathways (eg, fatty acid and glycolysis pathways; false discovery rate [FDR] < 1 × 10-12) were driven by these 3 major species (eg, positive association of S pneumoniae with glycolysis; FDR < 0.001). These microbial functional pathways were validated with the parallel metabolome data. Third, 104 transcriptome pathways were differentially enriched (FDR < .05)-for example, downregulated interferon-α and -γ and upregulated T-cell activation pathways. S pneumoniae was associated with most differentially expressed transcripts (eg, DAGLB; FDR < 0.05).ConclusionsBy applying metatranscriptomic, transcriptomic, and metabolomic approaches to a multicenter cohort of infants with bronchiolitis, this study found an interplay between major bacterial species, their function, and host response in the airway, and their longitudinal relationship with asthma development.

Dataset Information

TLR4 Polymorphism, Nasopharyngeal Bacterial Colonization, and the Development of Childhood Asthma: A Prospective Birth-Cohort Study in Finnish Children.

Publications

<i>TLR4</i> Polymorphism, Nasopharyngeal Bacterial Colonization, and the Development of Childhood Asthma: A Prospective Birth-Cohort Study in Finnish Children.

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