“Hidden factors” behind antibiotics and asthma link

Analysis of a long-term study suggests that the association between antibiotic use in infancy and an increased risk of developing asthma — or exacerbating an existing condition — may not be a simple causal link.

Researchers on the Manchester Asthma and Allergy Study, published online on 15 May in The Lancet Respiratory Medicine, suggest that there are “hidden factors” behind the link and say their results offer new clues to the complex pathways between antibiotics and asthma. Their analysis found that an impaired viral immunity and genetic variants on chromosome 17 could contribute to the association.

Researchers analysed the cases of 800 children whose conditions were monitored from birth until the age of 11 years. Of those, 564 were prescribed an antibiotic before their first birthday and 409 had at least one episode of wheeze.

Among the cohorts antibiotic prescription before the age of one was associated with significantly increased risks of doctor-confirmed wheeze (hazard ratio [HR] 1.71, CI 1·32–2·23; P<0·0001) and severe wheeze or asthma exacerbation (HR 2.26, CI 1.03–4.94; P=0·041).

Also, among children with a history of wheezing, antibiotic prescription before the age of one was associated with significantly increased risks of severe wheeze or asthma exacerbation (HR 2.09, CI 1.51–2.90; P<0·0001) and hospital admission for asthma or wheeze (HR 2.64, CI 1.49–4.70; P=0·0009) in the two years after first antibiotic prescription.

There was also a link between prescription of antibiotics in infancy and children who were found to have significantly lower induction of cytokines at the age of 11. Cytokines are important in defence against respiratory and rhinoviruses and a deficiency of this protein indicates impaired immunity to viral infections, but had no impact on bacterial immunity in the cohorts.

Finally, the researchers found that variants at the chromosomal locus 17q21 — an established factor for asthma susceptibility — were associated with an increased likelihood of early-life antibiotic use.

The researchers say their observations suggest that the association between antibiotics and asthma might “arise as a consequence of bias, rather than causal relationship”.

They conclude: “Whether impaired antiviral immunity predated antibiotic use making antibiotic prescription more likely, or whether it is also a consequence of antibiotic use, will need further studies monitoring antiviral immunity throughout early and later childhood.”