Abstract
Our aim was to systematically review and meta-analyse longitudinal studies on antibiotic use and subsequent development of wheeze and/or asthma with regards to study quality, outcome measurement, reverse causation (RC; wheezing/asthma symptoms have caused prescription of antibiotics) and confounding by indication (CbI; respiratory tract infections leading to antibiotic use may be the underlying cause triggering asthma symptom development).
English-language papers and studies published before November 1, 2010 with longitudinal observational design were included. Study quality was assessed using the Newcastle–Ottawa scale.
We identified 21 longitudinal studies. The effect of antibiotic use on wheeze/asthma risk varied between studies. 18 studies were eligible for meta-analysis showing pooled OR 1.27 (95% CI 1.12–1.43) for wheeze/asthma. When we eliminated studies with possible RC and CbI, the pooled risk estimate in the nine remaining studies was attenuated to OR 1.12 (95% CI 0.98–1.26). Definition of wheeze/asthma and age at follow-up differed between studies. Three studies focused on wheeze/asthma beyond 5–6 yrs of age with the presence of active symptoms and/or medication (pooled OR 1.08, 95% CI 0.93–1.23; dominated by one study).
RC and CbI lead to overestimation of the association between antibiotic use and subsequent development of wheeze/asthma. Association was weak when fully adjusted for these types of bias. Heterogeneity of disease definition between studies could affect the results.
Footnotes
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Support Statement
J. Penders is supported by a grant from the Netherlands Asthma Foundation (3.2.07.022). I. Kummeling is supported by a grant from the Thrasher Research Fund.
Statement of Interest
None declared.
- Received July 6, 2010.
- Accepted January 2, 2011.
- ©ERS 2011
