Investigators from the University of Copenhagen, Denmark, conducted a secondary analysis of data collected during a prospective study to evaluate the effects of airway microbiota on the duration of asthma-like symptoms in young children. Children who initially were enrolled in the Copenhagen Studies on Asthma in Children 2010 (COPSAC) were eligible for inclusion in the current analysis. For COPSAC, mother-child dyads were enrolled when the mother was in weeks 22-26 of pregnancy. After birth, parents recorded daily symptoms in their children on a longitudinal basis. Children were classified as having recurrent asthma-like symptoms if they had 5 episodes of ≥3 consecutive days of asthma-like symptoms in 6 months, ≥4 weeks of continuous symptoms, or an episode of symptoms leading to hospitalization or treatment with oral corticosteroids.
The current analysis included children 12-36 months old with recurrent asthma-like symptoms who were enrolled in a randomized controlled trial to assess the effect of azithromycin (10 mg/kg for 3 days) or placebo on duration of symptoms. At the initiation of treatment, a hypopharyngeal aspirate was obtained. PCR techniques were used to identify genera of bacteria and to group bacteria into operational taxonomic units (OTUs) based on sequence similarity. For the primary analysis, Poisson regression was used to assess the effect of number of OTUs on duration of symptoms. Subgroup analyses were done in participants randomized to azithromycin or placebo.
A total of 72 children with 158 episodes of recurrent asthma-like symptoms were enrolled in the azithromycin trial. Hypopharyngeal aspirates were obtained and analyzed on 139, and symptom diaries were completed on 129 of these episodes. The mean duration of symptoms during these episodes was 4 days and was significantly shorter in the 65 episodes occurring in children who received azithromycin compared to the 64 episodes in those randomized to placebo (P = 0.005). In the 139 hypopharyngeal aspirates, a total of 1,412 OTUs from 333 genera were identified; the median number of OTUs per aspirate was 45. The most common genera identified were Moraxella, Haemophilus, Streptococcus, and Neisseria. Overall duration of asthma-like episodes was significantly associated with number of OTUs (P = 0.025), with a 7.5% increase in duration per 10 OTUs increase. Specific patterns of OTUs (ie, composition of genera in the aspirate) also significantly were associated with episode duration. The number of OTUs significantly was associated with episode duration among children receiving placebo (12% increase in duration per 10 additional OTUs; P = 0.008), but not in those treated with azithromycin (P = 0.61).
The authors conclude that the airway microbiota is associated with the duration of asthma-like symptoms in pre-school children, and that this effect is modified...