Abstract
BackgroundPhase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) measured the global prevalence of symptoms of asthma in children. We undertook comprehensive analyses addressing risk factors for asthma symptoms in combination, at both the individual and the school level, to explore the potential role of reverse causation due to selective avoidance or confounding by indication.ObjectiveTo explore the role of reverse causation in risk factors of asthma symptoms.MethodsWe compared two sets of multilevel logistic regression analyses, using (a) individual level exposure data and (b) school level average exposure (ie prevalence), in two different age groups. In individual level analyses, reverse causation is a possible concern if individual level exposure statuses were changed as a result of asthma symptoms or diagnosis. School level analyses may suffer from ecologic confounding, but reverse causation is less of a concern because individual changes in exposure status as a result of asthma symptoms would only have a small effect on overall school exposure levels.ResultsThere were 131 924 children aged 6‐7 years (2428 schools, 25 countries) with complete exposure, outcome and confounder data. The strongest associations in individual level analyses (fully adjusted) were for current paracetamol use (odds ratio = 2.06; 95% confidence interval 1.97‐2.16), early life antibiotic use (1.65; 1.58‐1.73) and open fire cooking (1.44; 1.26‐1.65). In school level analyses, these risk factors again showed increased risks.There were 238 586 adolescents aged 13‐14 years (2072 schools, 42 countries) with complete exposure, outcome and confounder data. The strongest associations in individual level analyses (fully adjusted) were for current paracetamol use (1.80; 1.75‐1.86), cooking on an open fire (1.32; 1.22‐1.43) and maternal tobacco use (1.23; 1.18‐1.27). In school level analyses, these risk factors again showed increased risks.Conclusions & clinical relevanceThese analyses strengthen the potentially causal interpretation of previously reported individual level findings, by providing evidence against reverse causation.
Highlights
Asthma is becoming increasingly important as a childhood disease on a global basis.[1]
The International Study of Asthma and Allergies in Childhood (ISAAC), using a simple and inexpensive standardized methodology,[3,4,5] has documented a wide variation of asthma prevalence in different parts of the world,[6,7] and a number of papers have been published addressing the findings for individual risk factors, with several associations observed.[8,9,10,11,12,13,14,15,16,17,18,19,20]
For some risk factors the cross‐sectional nature of the study means that such analyses may be subject to “reverse causation” if individual level exposure statuses were changed as a result of asthma symptoms or diagnosis
Summary
Asthma is becoming increasingly important as a childhood disease on a global basis.[1]. For some risk factors the cross‐sectional nature of the study means that such analyses may be subject to “reverse causation” if individual level exposure statuses were changed as a result of asthma symptoms or diagnosis. This may occur due to selective avoidance (eg if the child's mother stops smoking because the child has developed asthma) or “confounding by indication” (eg if exposures such as paracetamol or antibiotics are taken in response to symptoms which are related to the subsequent development of asthma). We conducted analyses stratified by country‐level affluence to examine the extent to which associations and biases differed
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