Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
Department of Paediatrics: Child and Youth Health, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Clin Exp Allergy. 2019 Apr;49(4):430-441. doi: 10.1111/cea.13325. Epub 2019 Jan 23.
Phase 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.
To explore the role of reverse causation in risk factors of asthma symptoms.
We 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.
There 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 RELEVANCE: These analyses strengthen the potentially causal interpretation of previously reported individual level findings, by providing evidence against reverse causation.
三期国际儿童哮喘和过敏研究（ISAAC）测量了儿童哮喘症状的全球流行率。我们进行了综合分析，以个体和学校两个层面探讨了哮喘症状的危险因素，以探索由于选择性回避或指示性混淆而导致的反向因果关系的潜在作用。
探讨反向因果关系在哮喘症状危险因素中的作用。
我们比较了两种多层次逻辑回归分析，一种使用个体层面的暴露数据，另一种使用学校层面的平均暴露（即患病率），分别在两个不同的年龄组中进行。在个体层面分析中，如果个体层面的暴露状况因哮喘症状或诊断而发生变化，则可能存在反向因果关系的问题。学校层面分析可能受到生态混杂的影响，但反向因果关系的问题较小，因为哮喘症状导致的个体暴露状况变化只会对整体学校暴露水平产生微小影响。
共有 131924 名 6-7 岁儿童（2428 所学校，25 个国家）具有完整的暴露、结局和混杂因素数据。个体层面分析中（完全调整后）最强的关联是当前使用对乙酰氨基酚（比值比=2.06；95%置信区间 1.97-2.16）、生命早期使用抗生素（1.65；1.58-1.73）和明火烹饪（1.44；1.26-1.65）。在学校层面分析中，这些危险因素再次显示出增加的风险。共有 131924 名 13-14 岁青少年（2072 所学校，42 个国家）具有完整的暴露、结局和混杂因素数据。个体层面分析中（完全调整后）最强的关联是当前使用对乙酰氨基酚（1.80；1.75-1.86）、明火烹饪（1.32；1.22-1.43）和母亲吸烟（1.23；1.18-1.27）。在学校层面分析中，这些危险因素再次显示出增加的风险。
这些分析通过提供反对反向因果关系的证据，加强了先前报告的个体层面发现的潜在因果关系解释。
