1. Early life prescription of antibiotics was associated with later development of wheezing, severe asthma exacerbations and a significantly lower induction of cytokines.
2. Antibiotic prescription did not have an effect on the development of atopy.
Evidence Rating Level: 2 (Good)
Study Rundown: The hygiene hypothesis states that lack of early exposure to infectious or symbiotic agents can consequently lead to later development of allergic conditions such as asthma. The current study examined how the use of antibiotics during early life factors into this hypothesis. This study longitudinally followed a group of children from birth until 11 years of age and examined the trends in antibiotic prescription and development of wheezing, asthma exacerbations, and/or hospitalizations. The study noted that early life prescription of antibiotics was associated with a higher risk of developing subsequent wheezing and severe asthma exacerbations. The authors also observed that children who receive early antibiotics had a lower cytokine production response to infectious agents such as RSV and rhinovirus 1B, when compared with children who did not receive antibiotics. Genomic analysis identified specific single nucleotide polymorphisms (SNPs) that were associated with the early prescription of antibiotics. This study’s strength lies in its large cohort design with the specific emphasis on determining a biologic basis for the association between early life antibiotics and later development of asthma. A key weakness of this study is its observational nature, which precluded drawing any causal relationship between antibiotics prescription and development of asthma. There is always the possibility that another hidden variable is modulating the link between the two.
The study was funded by Moulton Charitable Foundation and Medical Research Council.
In-Depth [prospective cohort]: This study followed 916 children from the Manchester Asthma and Allergy Study birth cohort. Children attended follow up visits at ages 1, 3, 5, 8, and 11 years at which point questionnaires and skin prick tests were administered.
Children who received antibiotics in the first year of life were more likely to wheeze than those who did not receive antibiotics (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.65-2.78; p<0.0001). Children who received antibiotics in the first year of life were also more likely to have severe asthma exacerbations (HR 2.11, 95% CI 1.26-3.50; p=0.004) and hospital admissions (HR 2.66, 95% CI 1.19-5.93; p=0.017).
At age 11, peripheral blood mononuclear cells were collected (n=231) to test against infectious agents such as rhinovirus 1B, RSV, and Haemophilus influenzae for stimulation testing. Children who received antibiotics had lower induction of IP10, IL-1β, and IFN-α when stimulated with RSV and rhinovirus 1B. Single nucleotide polymorphism (SNP) analysis showed that children carrying the G allele in ZPBP2 SNP rs11557467 and the C allele in ORMDL3 SNP rs4795405 were more likely to be prescribed antibiotics within the first year of life (HR 1.39, 95% CI 1.10-1.75; p=0.006 and HR 1.28, 95% CI 1.03-1.59; p=0.02 respectively).
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