Chest

Chest

Volume 157, Issue 2, February 2020, Pages 334-341
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Education and Clinical Practice: Original Research
Early-Life Exposure to Oral Antibiotics and Lung Function Into Early Adulthood

https://doi.org/10.1016/j.chest.2019.10.004Get rights and content

Background

Although there is ongoing debate regarding the impact of early postnatal exposure to antibiotics on the development of asthma, the possibility that antibiotic exposure may impair lung function has not previously been examined. Furthermore, it is unclear if specific types of antibiotics may have a greater effect, or if children with genetic mutations in the oxidative stress response glutathione S-transferase (GST) superfamily may be at greater risk.

Methods

Parent-reported data of childhood antibiotic use from birth to 2 years, including type and indication, were collected from a birth cohort of 620 infants with a family history of allergy. Spirometry was performed at age 12 and 18 years, and results are presented as z scores. Participants were genotyped for GST-P, GST-M, and GST-T polymorphisms. Linear regression models were used to investigate the associations while adjusting for confounding factors.

Results

Neither increasing days of exposure nor earlier exposure to antibiotics was associated with reduced FEV1 (at 18 years, per doubling of days of exposure = –0.03 z score units; 95% CI, –0.11 to 0.04) or FVC (< 0.01; 95% CI, –0.08 to 0.07). There was no evidence that GST-risk polymorphisms (M1, P1, and T1) increased susceptibility, and specific types of antibiotics also did not increase risk of lung function deficits.

Conclusions

Increasing exposure to oral antibiotics in early postnatal life was not associated with reduced lung function in children with a family history of allergic diseases. Although unwarranted use of antibiotics in children should be minimized, concerns regarding long-term lung health should not be a driving influence for this rationalization of use.

Section snippets

Study Design

The Melbourne Atopy Cohort Study (MACS) is a single-center study of children with a family history of allergic disease.15 A total of 620 full-term infants were recruited before birth, between 1990 and 1994, in Melbourne, Australia. Infants were eligible if one or more of their first-degree family members had asthma, allergic rhinitis, eczema, or severe food allergy. The study was originally a randomized trial of three infant formulas.16 Written informed consent was obtained from all mothers at

Study Population and Antibiotic Exposure

At baseline, approximately 60% of children had a parent with asthma (e-Table 2). A total of 575 (92.7%) participants were followed up to 2 years of age. Of these, 489 (78%) were followed up at either 6 or 7 years, 369 (58%) at 12 years, and 419 (68%) at 18 years of age (e-Fig 1). Only 11.3% of infants had not received any oral antibiotics by age 2 years (Table 1). The median cumulative exposure to antibiotics was 20 days, and the most commonly used class of antibiotic was penicillins (median,

Discussion

In this study of children with a family history of allergic disease, we found no evidence that either increasing days of antibiotic exposure or younger age at first exposure was associated with impaired lung function at age 12 and 18 years. There was also no evidence of a potential detrimental impact of antibiotic exposure in children with GST null genotypes or in those who had experienced early-life wheeze. Use of antibiotics for nonrespiratory indications, the least confounded form of

Conclusions

Increasing use of oral antibiotics in the first 2 years of life was not associated with reduced lung function among children with a parental history of allergic diseases.

Acknowledgments

Author contributions: A. J. L. takes responsibility for the content of the manuscript, including the data and analyses. S. C. D., M. J. A., A. J. L., C. J. L., C. M. B., and B. E. were all involved with acquiring funding and establishing study directions and protocols. S. C. D., C. J. L., and A. J. L. led the data acquisition at 18 years. J. H. led the genetic analyses within MACS. K. D. S. led the analysis and interpretation of the data with support from A. J. L. and B. E. The initial draft of

References (36)

  • H. Ma et al.

    Impact of childhood wheezing on lung function in adulthood: a meta-analysis

    PloS One

    (2018)
  • H. Fehrenbach et al.

    Airway remodeling in asthma: what really matters

    Cell Tissue Res

    (2017)
  • S. Kalghatgi et al.

    Bactericidal antibiotics induce mitochondrial dysfunction and oxidative damage in mammalian cells

    Sci Transl Med

    (2013)
  • M.A. Kohanski et al.

    Bactericidal antibiotics promote reactive oxygen species formation and inflammation in human sinonasal epithelial cells

    Int Forum Allergy Rhinol

    (2016)
  • J. Qu et al.

    Recent developments in the role of reactive oxygen species in allergic asthma

    J Thorac Dis

    (2017)
  • G. Bowatte et al.

    Traffic-related air pollution exposure over a 5-year period is associated with increased risk of asthma and poor lung function in middle age

    Eur Respir J

    (2017)
  • A.J. Lowe et al.

    Cohort profile: Melbourne Atopy Cohort Study (MACS)

    Int J Epidemiol

    (2017)
  • A.J. Lowe et al.

    Effect of a partially hydrolyzed whey infant formula at weaning on risk of allergic disease in high-risk children: a randomized controlled trial

    J Allergy Clin Immunol

    (2011)

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    FUNDING/SUPPORT: The first 6 years of the Melbourne Atopy Cohort Study (MACS) were funded (study formula and staff) by Nestec Ltd., a subsidiary of Nestlé Australia. The 12-year follow-up was funded by a project grant from the Asthma Foundation of Victoria. The National Health and Medical Research Council of Australia funded the 18-year follow-up [APP454856]. Support was also provided by CAPES [Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brazil, scholarship Karoliny dos Santos/Programa de Doutorado Sanduíche no Exterior/process number 88881.135266/2016-01].

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