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
; 204(2): 149-158, 2021 07 15.
Article
em En
| MEDLINE
| ID: mdl-33730519
ABSTRACT
Rationale Childhood asthma is often preceded by recurrent episodes of asthma-like symptoms, which can be triggered by both viral and bacterial agents. Recent randomized controlled trials have shown that azithromycin treatment reduces episode duration and severity through yet undefined mechanisms. Objectives:
To study the influence of the airway microbiota on the effect of azithromycin treatment during acute episodes of asthma-like symptoms.Methods:
Children from the COPSAC2010 (Copenhagen Prospective Studies on Asthma in Childhood 2010) cohort with recurrent asthma-like symptoms aged 12-36 months were randomized during acute episodes to azithromycin or placebo as previously reported. Before randomization, hypopharyngeal aspirates were collected and examined by 16S ribosomal RNA gene amplicon sequencing. Measurements and MainResults:
In 139 airway samples from 68 children, episode duration after randomization was associated with microbiota richness (7.5% increased duration per 10 additional operational taxonomic units [OTUs]; 95% confidence interval, 1-14%; P = 0.025), with 15 individual OTUs (including several Neisseria and Veillonella), and with microbial pneumotypes defined from weighted UniFrac distances (longest durations in a Neisseria-dominated pneumotype). Microbiota richness before treatment increased the effect of azithromycin by 10% per 10 additional OTUs, and more OTUs were positively versus negatively associated with an increased azithromycin effect (82 vs. 58; P = 0.0032). Furthermore, effect modification of azithromycin was found for five individual OTUs (three OTUs increased and two OTUs decreased the effect; q < 0.05).Conclusions:
The airway microbiota in acute episodes of asthma-like symptoms is associated with episode duration and modifies the effect of azithromycin treatment of the episodes in preschool children with recurrent asthma-like symptoms. Clinical trial registered with www.clinicaltrials.gov (NCT01233297).Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asma
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Azitromicina
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Microbiota
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Reinfecção
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Antibacterianos
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Etiology_studies
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Incidence_studies
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Observational_studies
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Risk_factors_studies
Limite:
Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Am J Respir Crit Care Med
Assunto da revista:
TERAPIA INTENSIVA
Ano de publicação:
2021
Tipo de documento:
Article