Early Life Exposure to Farm Animals and Symptoms of Asthma, Rhinoconjunctivitis and Eczema

An ISAAC Phase Three Study

Bert Brunekreef; Erika Von Mutius; Gary K Wong; Joseph A Odhiambo; Tadd O Clayton


Int J Epidemiol. 2012;41(3):753-761. 

In This Article


ISAAC Phase Three is a repetition and expansion of the first phase of ISAAC, which documented large differences in the prevalence of childhood symptoms of asthma and allergy across the world.[3,4]

As in ISAAC Phase One, parents of the 6- to 7-year olds completed the written questionnaire at home. Schools were randomly selected from within a defined geographical area. Centres obtained ethical approval from their local ethics committee, or, for the minority of centres that did not have an ethics committee, some other approving body such as The Ministry of Health. The method of consent was determined by the local ethics committee and informed consent was obtained from parents of all participating children. Centres obtained their own funding. Adherence to the ISAAC Protocol was assessed and centres with serious discrepancies were excluded. Minor deviations from the protocol were identified with footnotes to the results tables in the publications presenting the Phase Three results.[5,6] In this article, we focus on 'current wheeze' ('Has your child had wheezing or whistling in the chest in the past 12 months?'), 'asthma ever' ('Has your child ever had asthma?'), symptoms of 'rhinoconjunctivitis' ('In the past 12 months, has your child had a problem with sneezing, or a runny, or blocked nose when you (he/she) did not have a cold or the flu?' and 'In the past 12 months, has this nose problem been accompanied by itchy-watery eyes?') and symptoms of 'eczema' ('Has your child had this itchy rash at any time in the past 12 months?' and 'Has this itchy rash at any time affected any of the following places: the folds of the elbows, behind the knees, in front of the ankles, under the buttocks, or around the neck, ears or eyes?'). The eczema questions were preceded by the question 'Has your child ever had an itchy rash coming and going for at least 6 months?' We have also analysed 'symptoms of severe asthma', defined as participants who, according to the written questionnaire, in the past 12 months, have had four or more attacks of wheeze, or >1 night per week sleep disturbance from wheeze, or wheeze affecting speech. This definition is based on previous ISAAC analyses that showed a combination of these features of more severe wheezing episodes correlated significantly more closely with asthma mortality and hospital admissions than current wheeze alone.[7] In ISAAC Phase Three, an optional environmental questionnaire (EQ) was administered in addition to the core symptom questionnaire to test a number of specific aetiological hypotheses.[3] The environmental questionnaire included questions on diet, heating and cooking fuels, exercise, exposure to farm animals and pets, family size, birth order, socio-economic status, use of antibiotics and anti-pyretics, breastfeeding, birth weight, immigrant status, environmental tobacco smoke and frequency of truck traffic in street of residence. The complete questionnaire can be found on the ISAAC website (www.isaac.auckland.ac.nz). The questions that this article relates to are:

  1. In your child's first year of life did he/she have regular (at least once a week) contact with farm animals (e.g. cattle, pigs, goats, sheep or poultry) (Y/N)?

  2. Has this child's mother had regular (at least once a week) contact with farm animals (e.g. cattle, pigs, goats, sheep or poultry) while being pregnant with this child (Y/N)?

These questions were only included in the questionnaires for the 6- to 7-year olds, so our analysis was restricted to this age category and could not be extended to the 13- to 14-year olds.

ORs have been calculated using generalized linear-mixed models (GLMMs) for a binomial distribution and logit link and with the centres being modelled as a random effect. The analyses on all study participants were adjusted for gender, region of the world, language and gross national income (GNI). Regions of the world were: Africa, Asia-Pacific, Eastern Mediterranean, Latin America, North America, Northern and Eastern Europe, Oceania, Indian Subcontinent and Western Europe. The written questionnaire was translated from English into 53 languages, according to the ISAAC Phase Three protocol[3] that required back translation to English and comparison with the original.[8] For the analysis, languages were categorized as Arabic, Chinese, English, Hindi, Indonesian, Portuguese, Spanish and 'other' (comprising many different languages). In addition to the combined analyses, further analyses were conducted after stratification for gender and GNI. For GNI, countries were classified as 'affluent' or 'non-affluent' using a 2001 GNI value of US$ 9205 per capita as cut-off, which separates high-income countries from the low- (≤US$ 745), lower middle- (746–2975 US$) and upper middle- (2976–9205 US$) income countries.[9] Finally, multivariate analyses (GLMM) were conducted to check whether associations between symptoms and farm animal exposure were confounded by certain other variables in the environmental questionnaire such as maternal education, cooking fuel, maternal and paternal smoking, television watching, exercise, siblings (older and younger), fast food, truck traffic exposure and paracetamol use. In a sensitivity analysis, the effect of additional adjustment for cat and dog exposure in the first year of life was investigated. Centres were treated as simple random effects but region was included in the model as a fixed effect to account for the differences in level between regions.

The final worldwide data set comprised 144 centres from 61 countries with 388 811 6- to 7-year-old children. Centres that had not undertaken the EQ were then excluded from the data set leaving a final EQ data set of 75 centres from 32 countries with 220 408 children. For inclusion in this analysis, centres were required to have ≥70% of participants with data on reported animal exposure. Six centres were accordingly excluded leaving 69 centres in 28 countries with 194 794 children with data on farm animal exposure. In the fully adjusted analyses, we excluded centres with <70% response rates. Missing values on covariables led to further reductions in the number of children included in the analyses and we documented to what extent results were influenced by these selections and adjustments.


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