Airway Microbiota Modifies Azithromycin’s Effect in Childhood Asthma Episodes

Asthma Inhaler Child
Asthma Inhaler Child
Airway microbiota may play a role in episode duration and may also modify the effect of azithromycin in asthma episodes in preschool children.

Azithromycin has been previously shown to reduce the duration and severity of asthma episodes in children, but the mechanisms behind these actions have remained largely undefined. Findings from a new study published in the American Journal of Respiratory and Critical Care Medicine suggest the airway microbiota may play a role in episode duration and may also modify the effect of azithromycin in asthma episodes in preschool children with recurrent asthma symptoms.

Researchers analyzed 139 airway samples obtained from 68 children (age range, 12-36 months) with recurrent asthma-like symptoms from the Copenhagen Studies on Asthma in Childhood 2010 (COPSAC2010) cohort. Children in this cohort study were previously randomly assigned to either azithromycin or placebo.

Overall, each child in this study had experienced a mean of 2 episodes. Samples demonstrated colonization with a range of bacteria during acute asthma episodes, but many of these episodes were dominated by airway pathogenic genera Haemophilus, Moraxella, Neisseria, and Streptococcus.

Duration of episodes following randomization was associated with microbiota richness, as identified by a 7.5% increased duration per 10 additional Operational Taxonomic Units (OTUs; 95% CI, 1%-14%; P =.025). Episode duration was also associated with 15 individual OTUs, including several Veillonella and Neisseria OTUs, as well as with microbial pneumotypes. The longest durations were observed in a Neisseria-dominated pneumotype.

Pretreatment microbiota richness increased azithromycin’s effect by 10% per 10 additional OTUs. There was a positive vs negative association between more OTUs and increased azithromycin effect (82 vs 58, respectively; P =.0032). Effect modification of azithromycin was also observed for 5 individual OTUs, including 3 that increased the effect and 2 decreased the effect (q<0.05).

Limitations of this study included the lack of posttreatment measurements for viruses or immune markers as well as the lack of collection of airway samples after treatment.

The researchers concluded that their “findings support the notion that the observed clinical effect of azithromycin treatment is in part mediated by azithromycin’s antibacterial effect.”


Thorsen J, Stokholm J, Rasmussen MA, et al. The airway microbiota modulates effect of azithromycin treatment for episodes of recurrent asthma-like symptoms in preschool children: a randomized clinical trial. Am J Respir Crit Care Med. Published online March 17, 2021. doi:10.1164/rccm.202008-3226OC