Association Between Antibiotic Exposure, Bronchiolitis, and TLR4 (rs1927911) Polymorphisms in Childhood Asthma.
OBJECTIVE
The 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.


METHODS
This 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.


RESULTS
Bronchiolitis 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).


CONCLUSIONS
Early-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.
Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Korea. ; Childhood Asthma Atopy Center, Research Center for Standardization of Allergic Diseases, University of Ulsan College of Medicine, Seoul, Korea.
Eun
E
Lee
Department of Pediatrics, Seoul National University Bundang Hospital, Seungnam, Korea.
Ji-Won
JW
Kwon
Department of Pediatrics, Inje University Sanggye Paik Hospital, Seoul, Korea.
Hyo-Bin
HB
Kim
Asan Institute for Life Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Ho-Sung
HS
Yu
Asan Institute for Life Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Mi-Jin
MJ
Kang
Goucher College, Baltimore, USA.
Kyungmo
K
Hong
Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Korea. ; Childhood Asthma Atopy Center, Research Center for Standardization of Allergic Diseases, University of Ulsan College of Medicine, Seoul, Korea.
Song I
SI
Yang
Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Korea. ; Childhood Asthma Atopy Center, Research Center for Standardization of Allergic Diseases, University of Ulsan College of Medicine, Seoul, Korea.
Young Ho
YH
Jung
Asan Institute for Life Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Seung-Hwa
SH
Lee
Asan Institute for Life Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Kil Young
KY
Choi
Childhood Asthma Atopy Center, Research Center for Standardization of Allergic Diseases, University of Ulsan College of Medicine, Seoul, Korea.
Hye Lim
HL
Shin
DASEAN Institute for Health Development, Mahidol University, Salaya, Phutthamonthon, Nakhonpathom, Thailand.
Seo Ah
SA
Hong
Department of Pediatrics, Kosin University College of Medicine, Busan, Korea.
Hyung Young
HY
Kim
Department of Pediatrics, Korea. Cancer Center Hospital, Seoul, Korea.
Ju-Hee
JH
Seo
Department of Pediatrics, Inje University Haeundae Paik Hospital, Busan, Korea.
Byoung-Ju
BJ
Kim
Department of Pediatrics, Hallym University Sacred Heart Hospital, Anyang, Korea.
So Yeon
SY
Lee
Department of Pediatrics, Korea University Guro Hospital, Seoul, Korea.
Dae Jin
DJ
Song
Department of Pediatrics, Inje University Seoul Paik Hospital, Seoul, Korea.
Woo-Kyung
WK
Kim
Department of Pediatrics, National Health Insurance Corporation Ilsan Hospital, Ilsan, Korea.
Gwang Cheon
GC
Jang
Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Jung Yeon
JY
Shim
Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Korea. ; Childhood Asthma Atopy Center, Research Center for Standardization of Allergic Diseases, University of Ulsan College of Medicine, Seoul, Korea.
Soo-Jong
SJ
Hong
Asthma; Toll-like receptor 4; antibiotics; bronchiolitis; polymorphism