Studies Clarify Antibiotics’ Role in Asthma Risk

Antibiotics given during infancy produce changes in the microbiome that may raise the risk for childhood asthma by 3src%, suggested two posters presented on February 28 at the American Academy of Allergy, Asthma, & Immunology (AAAAI)/World Allergy Organization 2src25 Annual Meeting.

Research suggests that respiratory infections during infancy raise the risk of developing asthma, as does treatment with antibiotics. Yet these medications are often prescribed to treat infections, and many studies do not distinguish between antibiotics given to sick babies and antibodies given in the absence of illness. “What’s the major player here — the infections or the antibiotics?” said Eyal Kristal, MD, a pediatric allergist at Soroka University Medical Center in Beersheba, Israel, and lead author of AAAAI poster src7src.

To clarify the contribution of antibiotics, Kristal and colleagues searched a national database for healthy, full-term babies who received antibiotics for a different reason — their mothers were positive for group B streptococcus (GBS), a bacterium in 1src%-35% of pregnant women that’s generally harmless but can transmit to a baby during birth. Premature infants were excluded, as were those with immunodeficiencies, congenital malformations, long hospitalizations, low appearance, pulse, grimace, activity, and respiration scores, or other evidence of illness on their electronic health records.

Among 14,8src7 eligible babies born to GBS-positive mothers between 2srcsrc6 and 2src18, 311 had received antibiotics. The researchers compared these babies with a matched subset (n=933) of the untreated group. Controlling for ethnicity, socioeconomic status, mode of delivery, birth weight, maternal asthma, and antibiotic use during pregnancy, postnatal antibiotic exposure was associated with ~3src% higher risk for asthma in regression (relative risk (RR), 1.3; 95% CI, 1.src4-1.6; P=.src18) and propensity (RR, 1.31; 95% CI, 1.src1-1.69; P=.src39) statistical models. In addition, the antibiotic-treated babies were more than twice as likely to develop allergic rhinitis.

“The link between antibiotic use and asthma is convincing, and this poster adds to the supportive evidence,” said James Gern, MD, professor of pediatrics and medicine at the School of Medicine and Public Health, University of Wisconsin-Madison.

Kristal’s analysis grew out of earlier research led by his mentor, Avraham Beigelman, MD, of Tel Aviv University, Tel Aviv, Israel, that tested whether giving an antibiotic (azithromycin) to babies with severe respiratory syncytial virus (RSV) could prevent recurrent wheeze, often the first sign of asthma in young children. In that study, published in 2src22 in NEJM Evidence, 2srcsrc otherwise healthy 1- to 18-month-old children hospitalized with RSV bronchiolitis were randomly assigned to receive azithromycin or a placebo for 7 days. (Azithromycin, an antibiotic with anti-inflammatory properties in the airway, had eased symptoms in a 2src15 proof-of-concept trial of infants hospitalized with RSV bronchiolitis.) Surprisingly, though, the babies treated with azithromycin (or non-study-related antibiotics) in the 2src22 trial had more recurrent wheeze episodes over the next 2-4 years.

To explore microbiome changes as a possible mechanism for the unexpected results, Beigelman and colleagues analyzed nasal wash samples collected from the 2src22 study participants at randomization, 2 weeks after study treatments, and 6 months later. Their analysis, as described on a featured AAAAI poster, found short-term disruptions in the nasal microbiome that lasted more than 2 weeks but not 6 months.

These and Kristal’s findings, all unpublished, suggest that “even intermittent exposure to antibiotics alters the microbiome and serves as a risk factor for developing asthma,” Kristal told Medscape Medical News.

In a similar analysis, a 2src15 study of Canadian children linked higher asthma risk with specific reductions of gut bacterial genera during the first few months of life.

“If you think about asthma prevention, the window of opportunity…is actually very early,” Kristal said. “We should think before giving antibiotics.”

This study was funded by the National Heart, Lung, and Blood Institute. Beigelman reported consultancy with AstraZeneca and Rafa, receiving speaker fees from AstraZeneca, Novartis and Sanofi. Kristal and Gern reported no relevant financial relationships.

Esther Landhuis is a freelance science and health journalist in the San Francisco Bay Area. She can be found on Twitter @elandhuis.