Efficacy of Macrolides on Acute Asthma or Wheezing Exacerbations in Children with Recurrent Wheezing: A Systematic Review and Meta-analysis

Overview

Journal Paediatr Drugs

Specialties Pediatrics
Pharmacology

Date 2020 Jan 16

PMID 31939108

Citations 4

Authors

Mauricio A Pincheira

Leonard B Bacharier

Jose A Castro-Rodriguez

Affiliations

Soon will be listed here.

Abstract

Introduction: The role of macrolides for treatment of children with acute asthma or wheezing exacerbations is unclear.

Objective: The aim of this systematic review was to evaluate the effectiveness of macrolides in children with recurrent wheezing presenting with acute asthma or wheezing exacerbation.

Methods: We conducted an electronic search in MEDLINE, EMBASE, CINAHL, LILACS, CENTRAL, and ClinicalTrials.gov.

Study Selection Criteria: Randomized controlled trials of macrolides (any macrolide) compared with placebo or standard treatment in children up to 18 years with recurrent wheezing/asthma presenting with an acute exacerbation.

Outcomes: Primary outcomes were need for hospitalization and/or time of acute asthma/wheezing symptoms resolution; secondary outcomes were duration of stay in the emergency department (ED)/clinic, severity of symptoms of the index episode, use of additional systemic corticosteroids or short active β-2 agonists, changes in lung function measures, ED visit/hospitalization during first week after index episode, time to next exacerbation, or adverse effects (AEs).

Results: Only three studies met the inclusion criteria (n = 334 children, 410 treated episodes); two studies included recurrent wheezers and the third included asthmatic children. There was no difference in hospitalization between groups, but children treated with macrolides had a significantly lower time to symptoms resolution than controls, although the magnitude of benefit remains to be quantified due to no normal distribution data presented. There was no difference in time to next episode of exacerbation (HR 0.96; 95% CI 0.71-1.28; I = 0%; p = 0.77). In one study, children receiving macrolides had a significant decrease in the severity of symptoms, decrease use of salbutamol, and another study showed improved lung function. No study evaluated antibiotic resistance development.

Conclusions: Limited evidence support that a macrolide trial could be considered in children with acute asthma or recurrent wheezing exacerbation.

Citing Articles

Differentially expressed serum proteins in children with or without asthma as determined using isobaric tags for relative and absolute quantitation proteomics.

Li M, Wu M, Qin Y, Liu H, Tu C, Shen B PeerJ. 2020; 8:e9971.

PMID: 33194371 PMC: 7646293. DOI: 10.7717/peerj.9971.

Interventions for escalation of therapy for acute exacerbations of asthma in children: an overview of Cochrane Reviews.

Craig S, Dalziel S, Powell C, Graudins A, Babl F, Lunny C Cochrane Database Syst Rev. 2020; 8:CD012977.

PMID: 32767571 PMC: 8078579. DOI: 10.1002/14651858.CD012977.pub2.

Role of long-term azithromycin therapy for severe bronchial asthma.

Al-Hajjaj M, Al Moamary M Ann Thorac Med. 2020; 15(2):47-48.

PMID: 32489436 PMC: 7259393. DOI: 10.4103/atm.ATM_38_20.

Childhood asthma heterogeneity at the era of precision medicine: Modulating the immune response or the microbiota for the management of asthma attack.

Lejeune S, Deschildre A, Le Rouzic O, Engelmann I, Dessein R, Pichavant M Biochem Pharmacol. 2020; 179:114046.

PMID: 32446884 PMC: 7242211. DOI: 10.1016/j.bcp.2020.114046.

References

Gielen V, Johnston S, Edwards M . Azithromycin induces anti-viral responses in bronchial epithelial cells. Eur Respir J. 2010; 36(3):646-54. DOI: 10.1183/09031936.00095809. View

Kaiser S, Huynh T, Bacharier L, Rosenthal J, Bakel L, Parkin P . Preventing Exacerbations in Preschoolers With Recurrent Wheeze: A Meta-analysis. Pediatrics. 2016; 137(6). DOI: 10.1542/peds.2015-4496. View

Koutsoubari I, Papaevangelou V, Konstantinou G, Makrinioti H, Xepapadaki P, Kafetzis D . Effect of clarithromycin on acute asthma exacerbations in children: an open randomized study. Pediatr Allergy Immunol. 2012; 23(4):385-90. DOI: 10.1111/j.1399-3038.2012.01280.x. View

Beigelman A, Isaacson-Schmid M, Sajol G, Baty J, Rodriguez O, Leege E . Randomized trial to evaluate azithromycin's effects on serum and upper airway IL-8 levels and recurrent wheezing in infants with respiratory syncytial virus bronchiolitis. J Allergy Clin Immunol. 2014; 135(5):1171-8.e1. PMC: 4426225. DOI: 10.1016/j.jaci.2014.10.001. View

Hansen M, Scott A, McCullough A, Thorning S, Aronson J, Beller E . Adverse events in people taking macrolide antibiotics versus placebo for any indication. Cochrane Database Syst Rev. 2019; 1:CD011825. PMC: 6353052. DOI: 10.1002/14651858.CD011825.pub2. View

Silva Filho L, Pinto L, Stein R . Use of macrolides in lung diseases: recent literature controversies. J Pediatr (Rio J). 2015; 91(6 Suppl 1):S52-60. DOI: 10.1016/j.jped.2015.08.002. View

Mandhane P, Paredes Zambrano de Silbernagel P, Aung Y, Williamson J, Lee B, Spier S . Treatment of preschool children presenting to the emergency department with wheeze with azithromycin: A placebo-controlled randomized trial. PLoS One. 2017; 12(8):e0182411. PMC: 5542589. DOI: 10.1371/journal.pone.0182411. View

Papi A, Brightling C, Pedersen S, Reddel H . Asthma. Lancet. 2017; 391(10122):783-800. DOI: 10.1016/S0140-6736(17)33311-1. View

Steel H, Theron A, Cockeran R, Anderson R, Feldman C . Pathogen- and host-directed anti-inflammatory activities of macrolide antibiotics. Mediators Inflamm. 2012; 2012:584262. PMC: 3388425. DOI: 10.1155/2012/584262. View

10.

Garner R, Kohen D . Changes in the prevalence of asthma among Canadian children. Health Rep. 2008; 19(2):45-50. View

11.

Lin C, Yeh T, Liu S, Lin H, Cheng Y, Hung H . Effects of Macrolide Treatment during the Hospitalization of Children with Childhood Wheezing Disease: A Systematic Review and Meta-Analysis. J Clin Med. 2018; 7(11). PMC: 6262331. DOI: 10.3390/jcm7110432. View

12.

Lougheed M, Garvey N, Chapman K, Cicutto L, Dales R, Day A . The Ontario Asthma Regional Variation Study: emergency department visit rates and the relation to hospitalization rates. Chest. 2006; 129(4):909-17. DOI: 10.1378/chest.129.4.909. View

13.

Rollins D, Beuther D, Martin R . Update on infection and antibiotics in asthma. Curr Allergy Asthma Rep. 2010; 10(1):67-73. DOI: 10.1007/s11882-009-0086-2. View

14.

Fleming-Dutra K, Friedman C, Hicks L . Early Azithromycin Treatment to Prevent Severe Lower Respiratory Tract Illnesses in Children. JAMA. 2016; 315(19):2121-2. PMC: 6457256. DOI: 10.1001/jama.2016.0918. View

15.

Nurmagambetov T, Kuwahara R, Garbe P . The Economic Burden of Asthma in the United States, 2008-2013. Ann Am Thorac Soc. 2018; 15(3):348-356. DOI: 10.1513/AnnalsATS.201703-259OC. View

16.

Volovitz B, Bilavsky E, Nussinovitch M . Effectiveness of high repeated doses of inhaled budesonide or fluticasone in controlling acute asthma exacerbations in young children. J Asthma. 2008; 45(7):561-7. DOI: 10.1080/02770900802005251. View

17.

Min J, Jang Y . Macrolide therapy in respiratory viral infections. Mediators Inflamm. 2012; 2012:649570. PMC: 3375106. DOI: 10.1155/2012/649570. View

18.

Stokholm J, Chawes B, Vissing N, Bjarnadottir E, Pedersen T, Vinding R . Azithromycin for episodes with asthma-like symptoms in young children aged 1-3 years: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2015; 4(1):19-26. PMC: 7164820. DOI: 10.1016/S2213-2600(15)00500-7. View

19.

Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M . Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015; 350:g7647. DOI: 10.1136/bmj.g7647. View

20.

Poole N, Shapiro D, Fleming-Dutra K, Hicks L, Hersh A, Kronman M . Antibiotic Prescribing for Children in United States Emergency Departments: 2009-2014. Pediatrics. 2019; 143(2). PMC: 6581044. DOI: 10.1542/peds.2018-1056. View