Assessing the association of early life antibiotic prescription with asthma exacerbations, impaired antiviral immunity, and genetic variants in 17q21: A population-based birth cohort study
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BACKGROUND: The relationship between early-life antibiotic use and the development of wheeze and asthma has been reported in several studies but might arise as a consequence of bias rather than causal relationship. We investigated the association between antibiotic prescription and subsequent development of atopy, wheeze, and asthma exacerbations, and the relation of early life antibiotic prescription with anti-infective immunity and genetic variants on asthma susceptibility locus 17q21. METHODS: Children in a population-based birth cohort were followed from birth to age 11 years. Information on antibiotic prescription, wheeze, and asthma exacerbations was extracted from medical records, and the effect of antibiotic prescription assessed with longitudinal analyses. We assessed immune responses of peripheral blood mononuclear cells, taken at age 11 years, to viruses (rhinovirus and respiratory syncytial virus; RSV) and bacteria (Haemophilus influenzae and Streptococcus pneumoniae) in children who either received at least one or no antibiotic prescriptions in infancy. Finally, we assessed the association of 17q21 polymorphisms with antibiotic prescription. FINDINGS: Of 984 families who gave consent, we extracted data for 916 children. We noted significantly higher risk of physician-confirmed wheezing after antibiotic prescription (hazard ratio [HR] 1·71, 95% CI 1·32-2·23; p<0·0001) and severe wheeze or asthma exacerbation after antibiotic prescription (HR 2·26, 95% CI 1·03-4·94; p=0·041). In children who wheezed, the hazards of exacerbations (2·09, 1·51-2·90; p<0·0001) and admissions to hospital (2·64, 1·49-4·70; p=0·0009) were significantly increased in the 2 years after the first antibiotic prescription. Children who received antibiotics in infancy had significantly lower induction of cytokines, which are important in host defence against virus infections to both RSV and rhinovirus; there were no differences in antibacterial responses. Variants in 17q21 were associated with an increased risk of early life antibiotic prescription. INTERPRETATION: The association between antibiotics and asthma might arise through a complex confounding by indication. Hidden factors that may increase the likelihood of both early life antibiotic prescription and later asthma are an increased susceptibility to viral infections consequent upon impaired antiviral immunity and genetic variants on 17q21. FUNDING: Moulton Charitable Foundation and Medical Research Council.
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Early life antibiotic exposure in humans appears to impair antiviral immunity, but this relationship may not be causal and may be explained by genetic variants impacting antiviral immunity.
“Early life antibiotic exposure in humans also appears to impair antiviral immunity, however this relationship may not be causal but rather explained by genetic variants impacting antiviral immunity (Semic-Jusufagic et al., 2014).”
From Viral Infections, the Microbiome, and Probiotics (2021) · cites this paper as Semic-Jusufagic et al., 2014
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- Authors
- Semic-Jusufagic, A., Belgrave, D., Pickles, A., Telcian, A. G., Bakhsoliani, E., Sykes, A., Simpson, A., Johnston, S. L., & Custovic, A.
- Affiliations
- University of Manchester (GB)
- King's College London (GB)
- Asthma UK (GB)
- Venue
- The Lancet Respiratory Medicine
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 2
- Issue
- 8
- Pages
- 621-630
- ISSN
- 2213-2600 (ISSN-L)
- OpenAlex
- W1964394970
- Cited by
- 95
- References
- 30
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 10 · 2021: 6 · 2020: 3 · 2019: 16 · 2018: 10 · 2017: 11 · 2016: 13 · 2015: 4 · 2014: 9
- FWCI
- 8.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Lancet Respiratory Medicine (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- MRC (G0601361 and MR/K002449/1)
- JP Moulton Charitable Foundation (233015)
- MRC Centre (G1000758)
- Predicta FP7 Collaborative Project (260895)
- Topics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Antibiotic Use and Resistance
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Keywords
- childhood asthma, asthma exacerbations, wheezing, atopy, antiviral immunity, cytokine induction, respiratory syncytial virus, rhinovirus, Haemophilus influenzae, Streptococcus pneumoniae, confounding by indication, antibiotic overuse
- MeSH terms
- Age Factors, Anti-Bacterial Agents, Asthma, Cells, Cultured, Child, Child, Preschool, Chromosomes, Human, Pair 17, Egg Proteins, Follow-Up Studies, Genotype, Haemophilus influenzae, Humans, Infant, Infant, Newborn, Leukocytes, Mononuclear, Membrane Proteins, Drug Prescriptions, Prospective Studies, Surveys and Questionnaires, Respiratory Sounds, Rhinovirus, Risk Factors, Severity of Illness Index, Skin Tests, Streptococcus pneumoniae, Disease Progression, Polymorphism, Single Nucleotide
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