Effect of antibiotic use for acute bronchiolitis on new-onset asthma in children
Authors: Ting-Yi Wu
I-Lun Chen
Hsin-Chun Huang
Hsin-Yi Huang
Yu-Han Chang
Wei-Ju Yeh
Chih-Hsing Hung
Jau-Ling Suen
San-Nan Yang
Journal: Scientific Reports (2018)
Discipline: Multidisciplinary
Keywords: antibiotics; asthma; bronchiolitis; Taiwan; National Health Insurance Research Database
Affiliations: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung City, Taiwan., Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan., Teaching and Research Center of Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung City, Taiwan., Department of Pediatrics, E-DA Hospital and School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan. ., Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan. ., Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. ., Department of Pediatrics, Faculty of Pediatrics, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan. ., Department of Pediatrics, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung City, Taiwan. ., Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. .

Abstract:  Early-life use of antibiotics is associated with asthma. We examined the effect of antibiotic use for early-life bronchiolitis on the development of new-onset asthma in children from Taiwan between 2005 and 2010. Data were from the National Health Insurance Research Database 2010, and diseases were coded using the International Classification of Disease (ICD). We classified the patients, all of whom had bronchiolitis, as having asthma or not having asthma. Asthma was diagnosed using ICD criteria and by use of an inhaled bronchodilator and/or corticosteroid twice in one year. We identified age at asthma onset, sex, residential area, history of atopy and NSAID use, age at first use of antibiotics, and the specific antibiotic, and adjusted for these factors using conditional logistic regression analysis. Among all individuals, there was a relationship between risk of new-onset asthma with use of a high dose of an antibiotic (adjusted odds ratio [aOR] = 3.33, 95% confidence interval [CI] = 2.67-4.15). Among the different antibiotics, macrolides (aOR = 2.87, 95% CI = 1.99-4.16), and azithromycin specifically (aOR = 3.45, 95% CI = 1.62-7.36), had the greatest effect of development of asthma. 

Retracted: No

PubPeer comments:
 The authors of the article did not adequately describe the study population. The characteristics of the cohort, nor the frequency of the involved diseases in the population are discussed. No clear reference to descriptions from other literature are made for either. Data between 2001 and 2010 were used, but the manuscript claims to study asthma development between 2 and 18 years for children that develop bronchiolitis in these years between 0 and two years. Secondly, the definitions of cases and exposures are questionable. Only patients with acute bronchiolitis due to other infectious organisms (ICD9 466.19) are included, and not RSV bronchiolitis (466.11). The definition of antibiotic used was u201cprescription of at least one antibiotic in the five years before asthmau201d without linkage of the antibiotic use with bronchiolitis. Most antibiotic therapies were probably prescribed for other indications, which could have been before or after the bronchiolitis. Also, most of their u2018asthmau2019 cases are children under the age of five, which makes it very disputable that these children truly have asthma. Most studies do not include children under the age of 4 or 5 years because of that reason. Moreover, the challenges involved in asthma diagnosis for this age group increases the risk of reverse causation. The cumulative DDD is used to compare dosing, which works well for adult studies, but not for pediatrics as it does not account for the age or weight of the child. Thirdly, the design is not described. The article mentions propensity score matching in the results. The exact match is unclear, as is what factors go into the adjusted odds ratio. We do not learn whether all cases were used nor the justification for a 1:1 matching in this large database. Although the article discusses the influence of genetic and environmental factors in the development of asthma, the authors did not adjust the outcome for several vital factors. Mode of delivery, birth order, number of children in the household and gestational age are major risk factors for childhood asthma, which were not adjusted for in the study or mentioned in the study limitations. The aim of the study is not reached through the used design, and therefore no conclusions should be drawn from these data. This study only provides evidence that children who have non-RSV bronchiolitis and have u2018asthma-like symptomsu2019 (they are prescribed puffers twice in a year for something that could be asthma or get an asthma diagnosis mostly at an age that international standards are clear that they should not) use more antibiotics in the five years before that asthma diagnosis than children with non-RSV bronchiolitis without these asthma-like symptoms. ,