PurposeThe complex interplay between environmental and genetic factors plays an important role in the development of asthma. Several studies have yielded conflicting results regarding the 2 asthma-related risk factors: antibiotic usage during infancy and/or a history of bronchiolitis during early life and the development of asthma. In addition to these risk factors, we also explored the effects of Toll-like receptor 4 (TLR4) polymorphism on the development of childhood asthma.MethodsThis cross-sectional study involved 7,389 middle school students who were from 8 areas of Seoul, Korea, and completed the International Study of Asthma and Allergies in Childhood questionnaire. The TLR4 polymorphism rs1927911 was genotyped in 1,395 middle school students from two areas using the TaqMan assay.ResultsBronchiolitis in the first 2 years of life, antibiotic exposure during the first year of life, and parental history of asthma were independent risk factors for the development of asthma. When combined, antibiotic use and a history of bronchiolitis increased the risk of asthma (adjusted odds ratio [aOR]: 4.64, 95% confidence interval [CI]: 3.09-6.97, P value for interaction=0.02). In subjects with CC genotype of TLR4, antibiotic exposure and a history of bronchiolitis during infancy, the risk of asthma was increased, compared to subjects without these risk factors (aOR: 5.72, 95% CI: 1.74-18.87).ConclusionsEarly-life antibiotic exposures and a history of bronchiolitis are risk factors for asthma in young adolescents. Polymorphisms of TLR4 modified the influence of these environmental factors. Reducing antibiotic exposure and preventing bronchiolitis during infancy may prevent the development of asthma, especially in genetically susceptible subjects.

BackgroundAsthma is characterized by airway inflammation, and bronchial airways are particularly susceptible to oxidant-induced tissue damage.ObjectiveTo investigate the effect of dietary antioxidant intake and environmental tobacco smoke (ETS) on the risk of childhood asthma according to genotypes susceptible to airway diseases.MethodsThis cross-sectional study included 1124 elementary school children aged 7–12 years old. Asthma symptoms and smoking history were measured using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Intake of vitamin A (including retinol and β-carotene), C, and E was measured by a semi-quantitative food frequency questionnaire (FFQ). GSTP1 polymorphisms were genotyped from peripheral blood samples.ResultsETS was significantly associated with presence of asthma symptoms (adjusted odds ratio [aOR], 2.48; 95 % confidence interval [CI], 1.29–4.76) and diagnosis (aOR, 1.91; 95 % CI, 1.19–3.06). Dietary antioxidant intake was not associated with asthma symptoms, although ETS plus low vitamin A intake showed a significant positive association with asthma diagnosis (aOR, 2.23; 95 % CI, 1.10–4.54). Children with AA at nucleotide 1695 in GSTP1 who had been exposed to ETS and a low vitamin A intake have an increased risk of asthma diagnosis (aOR, 4.44; 95 % CI,1.58–12.52) compared with children who had not been exposed to the two risk factors. However, ETS exposure and low vitamin A intake did not significantly increase odds of asthma diagnosis in children with AG or GG genotypes.ConclusionLow vitamin A intake and ETS exposure may increase oxidative stress and thereby risk for childhood asthma. These relationships may be modified by gene susceptibility alleles of GSTP1.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-015-0093-0) contains supplementary material, which is available to authorized users.

Male infertility is a multifactorial condition. Unexplained male infertility is often caused by spermatogenesis dysfunction. Knockout of Pin1, an important regulator of cell proliferation and differentiation, produces male infertility phenotypes such as testicular immaturity and azoospermia with spermatogonia depletion and blood−testis barrier (BTB) dysfunction. Gene therapy has been clinically considered for the treatment of male infertility, but it is not preferred because of the risks of adverse effects in germ cells. Direct intracellular protein delivery using nanoparticles is considered an effective alternative to gene therapy; however, in vivo testicular protein delivery remains a pressing challenge. Here, we investigated the direct intracellular protein delivery strategy using a fibroin nanoparticle-encapsulated cationic lipid complex (Fibroplex) to restore intratesticular PIN1. Local intratesticular delivery of PIN1 via Fibroplex in Pin1 knockout testes produced fertile mice, achieving recovery from the infertile phenotypes. Mechanistically, PIN1-loaded Fibroplex was successfully delivered into testicular cells, including spermatogonial cells and Sertoli cells, and the sustained release of PIN1 restored the gene expression required for the proliferation of spermatogonial cells and BTB integrity in Pin1 knockout testes. Collectively, testicular PIN1 protein delivery using Fibroplex might be an effective strategy for treating male infertility.