Are environmental risk factors for current wheeze in the International Study of Asthma and Allergies in Childhood (ISAAC) phase three due to reverse causation?
Journal
Clin Exp Allergy
Date Issued
2019
Author(s)
Richard J. Silverwood
Charlotte E. Rutter
Edwin A. Mitchell
M. Innes Asher
Luis Garcia‐Marcos
David P. Strachan
Neil Pearce
the ISAAC Phase Three Study Group (A Brêborowicz, G Lis, R Câmara, ML Chiera, JM Lopes dos Santos, C Nunes, J Rosado Pinto, E Vlaski, P Fuimaono V Pisi, G Wong, DY Goh, HJ Zar, HB Lee, RM Busquets, I Carvajal‐Urueña, G García‐Hernández, L García‐Marcos, C González Díaz, A López‐Silvarrey Varela, M Morales‐ Suárez‐Varela, EG Pérez‐Yarza, OA Musa)
DOI
10.1111/cea.13325
Abstract
Background: 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.
Objective: To explore the role of reverse causation in risk factors of asthma
symptoms.
Methods: 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.
Results: 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.
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.
Objective: To explore the role of reverse causation in risk factors of asthma
symptoms.
Methods: 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.
Results: 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.
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