Antibiotic use in infants with acute bronchiolitis predicts new-onset asthma

Naveed Saleh, MD, MS, for MDLinx | May 04, 2018

Early antibiotic use in children with acute bronchiolitis significantly predicts the development of new-onset asthma, according to researchers in a study published in Scientific Reports.

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Infants with acute bronchiolitis who use a penicillin, a cephalosporin, or a macrolide—especially azithromycin—have an increased risk for developing new-onset asthma during childhood.

“Although antibiotic use in early life increases the risk of asthma, the effect of antibiotic use by children for treatment of early-life bronchiolitis on the development of new-onset asthma is unknown,” wrote primary author, I-Lun Chen, MD, Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung City, Taiwan. “The aim of this study, which used the Taiwan National Health Insurance Research Database (NHIRD) 2010 database, was to assess the relationship of early-life antibiotic use for bronchiolitis with new-onset asthma in children.”

Asthma is mediated by environment and genetics. The “hygiene hypothesis” suggests that growing up in a hygienic environment (eg, reduced microbes) promotes T-helper type 2 (Th2) immunity.

“The association of early-life use of antibiotics with wheezing symptoms and allergic rhinoconjunctivitis in childhood, and the lack of adverse effects of antibiotics on atopic diseases in childhood among infants who live in rural environments, are consistent with this hypothesis,” according to the authors.

Researchers analyzed population-based data representing the effect of antibiotic use to treat early-life bronchiolitis on the development of new-onset asthma in Taiwanese children born between 2005 and 2010.

The authors classified patients who had experienced bronchiolitis as either developing later asthma or not developing the disease. In all, 2,082 children were assigned to the asthma and non-asthma groups.

The authors obtained data regarding antibiotic use from the outpatient prescription database, and calculated cumulative defined daily doses (DDD) to assess the effects of antibiotic dosage. They defined antibiotic usage as the prescription of at least one antibiotic—penicillins, cephalosporins, and macrolides—during the 5 years prior to the onset of asthma. Other antibiotics, including quinolones, sulphonamides, glycopeptides, and lincosamides, were evaluated separately.  

Researchers found that patients who first received an antibiotic by age 2 (aOR=1.67, 95% CI=1.27–2.19) or by age 3 (aOR=1.99, 95% CI=1.29–3.09) were significantly more likely to develop new-onset asthma.

On the basis of cumulative DDDs, the researchers divided patients who later developed asthma into three antibiotic-use groups: low dose, moderate dose, and high dose. They found that 11.2% of these children took low-dose, 26.8% took moderate-dose, and 33.8% took high-dose antibiotics, thus indicating a dose-dependent relationship.

After performing age-stratified analysis, the team found that the use of penicillins, cephalosporins, or macrolides predicted new-onset asthma. This effect was seen only in children younger than 5 years. Moreover, amoxicillin, erythromycin, and azithromycin also increased the risk for new-onset asthma.

Using conditional logistic regression analysis, they adjusted for covariates including age at asthma onset, sex, residential area, history of atopy and NSAID use, age at first use of antibiotics, and the specific antibiotic. However, they did not adjust their findings for socioeconomic status, exposure to second-hand smoke, and the presence of atopic diseases in parents and siblings, which is a limitation of the study.

“Our results provide evidence that infants with acute bronchiolitis who use a penicillin, a cephalosporin, or a macrolide—especially azithromycin—have an increased risk for developing new-onset asthma during childhood,” concluded the authors. “These results are consistent with the predictions of the hygiene hypothesis.”

To read more about this study, click here.

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