Early life antibiotics and asthma
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Cotswold Cottage, Oakridge, Stroud GL6 7NZ, UK; mikethomas@doctors.org.uk
Keywords: asthma; antibiotics
Cullinan et al1 present interesting data on the association between exposure to antibiotics in early life and the subsequent expression of atopy and asthma. In keeping with other studies, they report a positive association between antibiotic receipt over the first 5 years of life and asthma. The association was, however, largely accounted for by prescriptions issued for respiratory illnesses, and the authors conclude that reverse causation was the likely explanation for this association.
The inappropriate use of antibiotics for respiratory symptoms caused by unrecognised asthma is the main potential confounding factor in observational studies attempting to demonstrate a causal link between antibiotic receipt and atopic illnesses. It is certainly plausible that GPs may prescribe antibiotics in children with symptoms such as cough and wheeze in early life. Suggestions of a casual link are strengthened by demonstration of an association when antibiotics were used for symptoms not associated with asthma. The earlier study by Farooqui and Hopkins2 did, indeed, observe an association with non-respiratory use of antibiotics and asthma; in the study by Cullinan et al the association between non-respiratory indicated antibiotics and atopic asthma narrowly failed to reach statistical significance. The authors acknowledge that the study was only powered to show a doubling of the odds ratio for the association between early life antibiotic use and asthma, so an association remains possible in this cohort.
The most important limitation of the study, however, is the timing of the observed early life events in relation to secular changes in asthma prevalence and antibiotic prescribing, and hence the applicability of the results to modern day settings. This study observed events occurring 30 or more years ago in the parents of the Ashford birth cohort. As is well described, the prevalence of asthma has increased greatly over the last 30 years.3 There may also have been significant increases in antibiotic prescribing over this time. The subjects in this study received an average of 3.1 and a median of 3 antibiotic prescriptions over 5 years, while we found in a recent case-control study4 of 37 children with atopy and wheezing and 37 without either that the average and median number of antibiotic courses received during the first 5 years of life was 9.9 and 7 for wheezers and 6.3 and 5 for non-wheezers. There is also evidence of earlier prescribing of antibiotics in recent times; in our study group 89% of wheezers and 68% of non-wheezers received one or more courses of antibiotics in the first year, while in the Ashford study only 396 prescriptions were issued to 746 subjects in the first year, so a maximum of 53% children received any antibiotics.
It seems likely from the data presented that antibiotic exposure did not play a major causal role in promoting the asthma phenotype 30 years ago when both the prevalence of asthma and antibiotic prescribing to young children were significantly less than they are now, but the question of whether it may now be a significant and potentially modifiable factor remains unanswered.
References
Cullinan P, Harris J, Mills P, et al. Early prescription of antibiotics and the risk of allergic disease in adults: a cohort study. Thorax 2004;59:11–5.
Farooqui IS, Hopkin JM. Early childhood infection and atopic disorder. Thorax 1998;53:927–32.
Holgate ST. The epidemic of allergy and asthma. Nature 1999;402:B2–4.
Thomas M, Murray CS, Simpson B, et al. Early life antibiotic exposure and subsequent risk of asthma: a case control study. Thorax 2003;58:iii67.(M Thomas)
Keywords: asthma; antibiotics
Cullinan et al1 present interesting data on the association between exposure to antibiotics in early life and the subsequent expression of atopy and asthma. In keeping with other studies, they report a positive association between antibiotic receipt over the first 5 years of life and asthma. The association was, however, largely accounted for by prescriptions issued for respiratory illnesses, and the authors conclude that reverse causation was the likely explanation for this association.
The inappropriate use of antibiotics for respiratory symptoms caused by unrecognised asthma is the main potential confounding factor in observational studies attempting to demonstrate a causal link between antibiotic receipt and atopic illnesses. It is certainly plausible that GPs may prescribe antibiotics in children with symptoms such as cough and wheeze in early life. Suggestions of a casual link are strengthened by demonstration of an association when antibiotics were used for symptoms not associated with asthma. The earlier study by Farooqui and Hopkins2 did, indeed, observe an association with non-respiratory use of antibiotics and asthma; in the study by Cullinan et al the association between non-respiratory indicated antibiotics and atopic asthma narrowly failed to reach statistical significance. The authors acknowledge that the study was only powered to show a doubling of the odds ratio for the association between early life antibiotic use and asthma, so an association remains possible in this cohort.
The most important limitation of the study, however, is the timing of the observed early life events in relation to secular changes in asthma prevalence and antibiotic prescribing, and hence the applicability of the results to modern day settings. This study observed events occurring 30 or more years ago in the parents of the Ashford birth cohort. As is well described, the prevalence of asthma has increased greatly over the last 30 years.3 There may also have been significant increases in antibiotic prescribing over this time. The subjects in this study received an average of 3.1 and a median of 3 antibiotic prescriptions over 5 years, while we found in a recent case-control study4 of 37 children with atopy and wheezing and 37 without either that the average and median number of antibiotic courses received during the first 5 years of life was 9.9 and 7 for wheezers and 6.3 and 5 for non-wheezers. There is also evidence of earlier prescribing of antibiotics in recent times; in our study group 89% of wheezers and 68% of non-wheezers received one or more courses of antibiotics in the first year, while in the Ashford study only 396 prescriptions were issued to 746 subjects in the first year, so a maximum of 53% children received any antibiotics.
It seems likely from the data presented that antibiotic exposure did not play a major causal role in promoting the asthma phenotype 30 years ago when both the prevalence of asthma and antibiotic prescribing to young children were significantly less than they are now, but the question of whether it may now be a significant and potentially modifiable factor remains unanswered.
References
Cullinan P, Harris J, Mills P, et al. Early prescription of antibiotics and the risk of allergic disease in adults: a cohort study. Thorax 2004;59:11–5.
Farooqui IS, Hopkin JM. Early childhood infection and atopic disorder. Thorax 1998;53:927–32.
Holgate ST. The epidemic of allergy and asthma. Nature 1999;402:B2–4.
Thomas M, Murray CS, Simpson B, et al. Early life antibiotic exposure and subsequent risk of asthma: a case control study. Thorax 2003;58:iii67.(M Thomas)