The Airway Microbiota Modulates Effect of Azithromycin Treatment for Episodes of Recurrent Asthma-like Symptoms in Preschool Children: A Randomized Clinical Trial

Research output: Contribution to journalJournal articlepeer-review

Standard

The Airway Microbiota Modulates Effect of Azithromycin Treatment for Episodes of Recurrent Asthma-like Symptoms in Preschool Children : A Randomized Clinical Trial. / Thorsen, Jonathan; Stokholm, Jakob; Rasmussen, Morten Arendt; Mortensen, Martin Steen; Brejnrod, Asker Daniel; Hjelmsø, Mathis; Shah, Shiraz; Chawes, Bo; Bønnelykke, Klaus; Sørensen, Søren Johannes; Bisgaard, Hans.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 204, No. 2, 2021, p. 149-158.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Thorsen, J, Stokholm, J, Rasmussen, MA, Mortensen, MS, Brejnrod, AD, Hjelmsø, M, Shah, S, Chawes, B, Bønnelykke, K, Sørensen, SJ & Bisgaard, H 2021, 'The Airway Microbiota Modulates Effect of Azithromycin Treatment for Episodes of Recurrent Asthma-like Symptoms in Preschool Children: A Randomized Clinical Trial', American Journal of Respiratory and Critical Care Medicine, vol. 204, no. 2, pp. 149-158. https://doi.org/10.1164/rccm.202008-3226OC

APA

Thorsen, J., Stokholm, J., Rasmussen, M. A., Mortensen, M. S., Brejnrod, A. D., Hjelmsø, M., Shah, S., Chawes, B., Bønnelykke, K., Sørensen, S. J., & Bisgaard, H. (2021). The Airway Microbiota Modulates Effect of Azithromycin Treatment for Episodes of Recurrent Asthma-like Symptoms in Preschool Children: A Randomized Clinical Trial. American Journal of Respiratory and Critical Care Medicine, 204(2), 149-158. https://doi.org/10.1164/rccm.202008-3226OC

Vancouver

Thorsen J, Stokholm J, Rasmussen MA, Mortensen MS, Brejnrod AD, Hjelmsø M et al. The Airway Microbiota Modulates Effect of Azithromycin Treatment for Episodes of Recurrent Asthma-like Symptoms in Preschool Children: A Randomized Clinical Trial. American Journal of Respiratory and Critical Care Medicine. 2021;204(2):149-158. https://doi.org/10.1164/rccm.202008-3226OC

Author

Thorsen, Jonathan ; Stokholm, Jakob ; Rasmussen, Morten Arendt ; Mortensen, Martin Steen ; Brejnrod, Asker Daniel ; Hjelmsø, Mathis ; Shah, Shiraz ; Chawes, Bo ; Bønnelykke, Klaus ; Sørensen, Søren Johannes ; Bisgaard, Hans. / The Airway Microbiota Modulates Effect of Azithromycin Treatment for Episodes of Recurrent Asthma-like Symptoms in Preschool Children : A Randomized Clinical Trial. In: American Journal of Respiratory and Critical Care Medicine. 2021 ; Vol. 204, No. 2. pp. 149-158.

Bibtex

@article{56d06d20f3c8496aa8a53ae6854a77c5,
title = "The Airway Microbiota Modulates Effect of Azithromycin Treatment for Episodes of Recurrent Asthma-like Symptoms in Preschool Children: A Randomized Clinical Trial",
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 Here, we studied the influence of the airway microbiota on the effect of azithromycin treatment during acute episodes of asthma-like symptoms. Methods Children from the Copenhagen Studies on Asthma in Childhood 2010 (COPSAC2010) cohort with recurrent asthma-like symptoms aged 12-36 months were randomized during acute episodes to azithromycin or placebo as previously reported. Prior to randomization, hypopharyngeal aspirates were collected and examined by 16S rRNA gene amplicon sequencing. Measurements and Main Results 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 vs. negatively associated with increased azithromycin effect (82 vs. 58, p=0.0032). Furthermore, effect modification of azithromycin was found for 5 individual OTUs (3 increased and 2 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 registration available at www.clinicaltrials.gov, ID: NCT01233297.",
author = "Jonathan Thorsen and Jakob Stokholm and Rasmussen, {Morten Arendt} and Mortensen, {Martin Steen} and Brejnrod, {Asker Daniel} and Mathis Hjelms{\o} and Shiraz Shah and Bo Chawes and Klaus B{\o}nnelykke and S{\o}rensen, {S{\o}ren Johannes} and Hans Bisgaard",
year = "2021",
doi = "10.1164/rccm.202008-3226OC",
language = "English",
volume = "204",
pages = "149--158",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "2",

}

RIS

TY - JOUR

T1 - The Airway Microbiota Modulates Effect of Azithromycin Treatment for Episodes of Recurrent Asthma-like Symptoms in Preschool Children

T2 - A Randomized Clinical Trial

AU - Thorsen, Jonathan

AU - Stokholm, Jakob

AU - Rasmussen, Morten Arendt

AU - Mortensen, Martin Steen

AU - Brejnrod, Asker Daniel

AU - Hjelmsø, Mathis

AU - Shah, Shiraz

AU - Chawes, Bo

AU - Bønnelykke, Klaus

AU - Sørensen, Søren Johannes

AU - Bisgaard, Hans

PY - 2021

Y1 - 2021

N2 - 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 Here, we studied the influence of the airway microbiota on the effect of azithromycin treatment during acute episodes of asthma-like symptoms. Methods Children from the Copenhagen Studies on Asthma in Childhood 2010 (COPSAC2010) cohort with recurrent asthma-like symptoms aged 12-36 months were randomized during acute episodes to azithromycin or placebo as previously reported. Prior to randomization, hypopharyngeal aspirates were collected and examined by 16S rRNA gene amplicon sequencing. Measurements and Main Results 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 vs. negatively associated with increased azithromycin effect (82 vs. 58, p=0.0032). Furthermore, effect modification of azithromycin was found for 5 individual OTUs (3 increased and 2 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 registration available at www.clinicaltrials.gov, ID: NCT01233297.

AB - 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 Here, we studied the influence of the airway microbiota on the effect of azithromycin treatment during acute episodes of asthma-like symptoms. Methods Children from the Copenhagen Studies on Asthma in Childhood 2010 (COPSAC2010) cohort with recurrent asthma-like symptoms aged 12-36 months were randomized during acute episodes to azithromycin or placebo as previously reported. Prior to randomization, hypopharyngeal aspirates were collected and examined by 16S rRNA gene amplicon sequencing. Measurements and Main Results 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 vs. negatively associated with increased azithromycin effect (82 vs. 58, p=0.0032). Furthermore, effect modification of azithromycin was found for 5 individual OTUs (3 increased and 2 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 registration available at www.clinicaltrials.gov, ID: NCT01233297.

U2 - 10.1164/rccm.202008-3226OC

DO - 10.1164/rccm.202008-3226OC

M3 - Journal article

C2 - 33730519

VL - 204

SP - 149

EP - 158

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 2

ER -

ID: 259829820