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Correspondence |

Antibiotic Use During the First Year of Life and Asthma FREE TO VIEW

Juan C. Celedón, MD, DrPH, FCCP
Author and Funding Information

Affiliations: Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA,  Centre for Disease Control, Vancouver, BC, Canada

Correspondence to: Juan C. Celedón, MD, DrPH, FCCP, Channing Laboratory, 181 Longwood Ave, Boston, MA 02115; e-mail: juan.celedon@channing.harvard.edu



Chest. 2006;130(5):1624-1625. doi:10.1378/chest.130.5.1624
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To the Editor:

In a recent issue of CHEST (March 2006),1Marra and colleagues reported the results of a metaanalysis of antibiotic use during the first year of life and asthma. On the basis of experimental findings and results of retrospective studies,2 it was postulated that antibiotic use leads to abnormalities in the intestinal flora of young children that could result in abnormal regulation of immune responses and, ultimately, in atopy. Because most children with asthma are sensitized to one or more allergens (atopic), a systematic review of antibiotic use and asthma should also assess the evidence for an association between antibiotic use and atopy.

Five epidemiologic studies23 found no significant association between postnatal antibiotic use and atopy defined objectively (eg, by allergy skin testing). Although one of those studies,3reported associations between antibiotic use and atopy in subgroup analysis, there was no adjustment for multiple statistical testing. More impressively, a nested case-control study of hay fever among 116,493 British children found no significant association between antibiotic use during the first year of life and hay fever, irrespective of class of antibacterial prescribed.4

The absence of an association between antibiotic use in infancy and atopy, and the nonsignificant association between antibiotic use in infancy and asthma in prospective studies5 that adjusted for confounders and/or examined the relation between antibiotic use and childhood asthma of late onset, strongly suggest “reverse causation” (ie, antibiotics are more often prescribed to young asthmatic children) as the most likely explanation for findings of retrospective studies. Because retrospective studies cannot exclude recall bias or assess reverse causation, combining the results of prospective and retrospective studies in a metaanalysis of antibiotic use and asthma is unsound. Although antibiotics should not be prescribed unnecessarily because of the potential for promotion of microbial resistance, postnatal antibiotic use is a very unlikely explanation for the increased prevalence of asthma in industrialized countries.

Dr. Celedón is supported by grants HL04370 and HL073373 from the National Institutes of Health.

Dr. Celedón declares that he has no conflicts of interest.

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Marra, F, Lynd, L, Coombes, M, et al (2006) Does antibiotic exposure during infancy lead to development of asthma? a systematic review and metaanalysis.Chest129,610-618. [CrossRef]
 
Celedón, JC, Weiss, ST Use of antibacterials in infancy: clinical implications for childhood asthma and allergies.Treat Respir Med2004;3,291-294. [CrossRef]
 
Johnson, CC, Ownby, DR, Alford, SH, et al Antibiotic exposure in early infancy and risk for childhood atopy.J Allergy Clin Immunol2005;115,1218-1224. [CrossRef]
 
Bremner, SA, Carey, IM, DeWilde, S, et al Early-life exposure to antibacterials and the subsequent development of hay fever in childhood in the UK: case-control studies using the General Practice Research Database and the Doctors’ Independent Network.Clin Exp Allergy2003;33,1518-1525. [CrossRef]
 
Celedón, JC, Fuhlbrigge, A, Rifas-Shiman, S, et al Antibiotic use in the first year of life and asthma in early childhood.Clin Exp Allergy2004;34,1011-1016. [CrossRef]
 
To the Editor:

We would like to thank Dr. Celedón1for his interest and viewpoint concerning our recently published review and meta-analysis.2 While Dr. Celedón brings up some salient points, it is important to clarify some of the issues.

We agree with Dr. Celedón that a systematic review of antibiotic use and atopy would make an interesting addition to the literature. We decided to focus on studies that investigated the association of antibiotic exposure and the development of asthma, as the definitions for this outcome were more homogeneous. Studies examining atopy and antibiotic exposure typically divide the outcomes into eczema, hay fever, and asthma and report odds ratios for these conditions separately. Thus, other atopic conditions, although related, are separate in scope of the topic of our metaanalysis.

We also agree with Dr. Celedón regarding the importance of differentiating prospective and retrospective studies. As such, in our article we fully investigated the impact that study design had on the association and reported separate odds ratios for each design type. We also provided in our discussion a detailed overview of the types of biases that could be influencing the results (especially in the retrospective studies). Of interest, in the main analysis, we could not include the largest prospective study3 (n = 29,238) that clearly showed an association between antibiotic exposure and asthma due to the way that the results were determined. Had it been possible to combine the results from this study3 with the other results, the summary measure of association for the prospective studies would have been noticeably influenced.

Therefore, while we do agree that it is unlikely that postnatal antibiotic use is the sole reason for the increased prevalence of asthma in industrialized countries, there remains potential that it is a contributing factor. In circumstances when there is an attempt being made to reduce exposure to antibiotics in all age groups, we feel that our data provide reason for added caution, especially concerning the unnecessary use of antibiotics in early childhood.

References
Celedón, J Antibiotic use during the first year of life and asthma [letter]. Chest. 2006;;130 ,.:1624
 
Marra, F, Lynd, L, Coombes, M, et al Does antibiotic exposure during infancy lead to development of asthma? A systematic review and meta-analysis.Chest2006;129,610-618. [CrossRef]
 
McKeever, TM, Lewis, SA, Smith, C, et al Early exposure to infections and antibiotics and the incidence of allergic disease: a birth cohort study with the West Midlands General Practice Research Database.J Allergy Clin Immunol2002;109,43-50. [CrossRef]
 

Figures

Tables

References

Marra, F, Lynd, L, Coombes, M, et al (2006) Does antibiotic exposure during infancy lead to development of asthma? a systematic review and metaanalysis.Chest129,610-618. [CrossRef]
 
Celedón, JC, Weiss, ST Use of antibacterials in infancy: clinical implications for childhood asthma and allergies.Treat Respir Med2004;3,291-294. [CrossRef]
 
Johnson, CC, Ownby, DR, Alford, SH, et al Antibiotic exposure in early infancy and risk for childhood atopy.J Allergy Clin Immunol2005;115,1218-1224. [CrossRef]
 
Bremner, SA, Carey, IM, DeWilde, S, et al Early-life exposure to antibacterials and the subsequent development of hay fever in childhood in the UK: case-control studies using the General Practice Research Database and the Doctors’ Independent Network.Clin Exp Allergy2003;33,1518-1525. [CrossRef]
 
Celedón, JC, Fuhlbrigge, A, Rifas-Shiman, S, et al Antibiotic use in the first year of life and asthma in early childhood.Clin Exp Allergy2004;34,1011-1016. [CrossRef]
 
Celedón, J Antibiotic use during the first year of life and asthma [letter]. Chest. 2006;;130 ,.:1624
 
Marra, F, Lynd, L, Coombes, M, et al Does antibiotic exposure during infancy lead to development of asthma? A systematic review and meta-analysis.Chest2006;129,610-618. [CrossRef]
 
McKeever, TM, Lewis, SA, Smith, C, et al Early exposure to infections and antibiotics and the incidence of allergic disease: a birth cohort study with the West Midlands General Practice Research Database.J Allergy Clin Immunol2002;109,43-50. [CrossRef]
 
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