This study found a positive global relationship between childhood symptoms of current asthma, rhinoconjunctivitis and eczema and farm animal exposure in the first year of life as well as farm animal exposure of the child's mother during pregnancy. The associations were driven by the non-affluent countries (especially upper and lower middle income) as there was little relationship between farm animal exposure and symptoms in the affluent countries that were studied. There was no evidence for protective effects of farm animal exposure in affluent countries.
The strengths of the ISAAC study are worldwide coverage, the use of standardized and validated methods of symptom reporting, and an extremely large population size. Limitations include the reliance on parent-completed questionnaires and absence of objective measurements of exposure and allergy status.
Could these results have been produced by bias? It seems unlikely that parents of children with allergic symptoms over-report exposure to farm animals in pregnancy or the first year of life, as this exposure is not widely discussed in the media or by physicians treating their children. There was also little evidence of selection bias when children who had insufficient data on potential confounding variables were excluded from the analyses. If anything, the crude analyses for the complete populations produced higher ORs than the crude analyses that were restricted to children with full confounder data (comparing column 1 with column 2 in Table 2 and Table 3). There was little evidence of confounding by the individual or community-level confounders that were assessed in these analyses (comparing column 2 with column 3 in Table 2 and Table 3). We cannot exclude the possibility of residual confounding by unmeasured or inadequately measured risk factors but the pattern just described is also compatible with some underestimation of the ORs related to non-random missing values.
Growing up on a farm has been associated with protection against allergic sensitization and disease in several studies (for instance).[10,11] Exposure to farm animals during pregnancy and during the first years of life has been suggested as one of the possible factors to explain this association. A European study conducted in five different countries found protective associations between pig exposure on farms and asthma, but a positive association with sheep on the farm. The same study found protective associations with living on a farm for wheeze and rhinitis but not eczema, and a protective association with farm milk consumption for symptoms of rhinoconjunctivitis but not wheeze and eczema. A recent study found that a higher diversity of microbial exposure on farms was associated with less asthma and atopy. Very few studies from non-affluent countries have been reported on this subject. A study from China has analysed exposure to farm animals and found a strongly positive association with childhood wheezing, asthma, cough and phlegm but not with rhinitis. One explanation given to explain not finding a protective effect was that the Chinese children in this study were still growing up in less hygienic circumstances with ubiquitous exposure to microbial agents. A small study among urban and rural children living in Nepal found a protective effect on asthma of cattle being indoors at night but not from cattle kept outdoors. Interestingly, keeping poultry indoors (which was more frequently reported than keeping cattle indoors at night) was associated with increased asthma prevalence in this study. A large study from Belarus found protective associations between exposure to farm animals and symptoms of wheeze, rhinoconjunctivitis and eczema in 6-year-old children as established with the ISAAC questionnaire. The population was described as mixed urban–rural, and a high percentage of parents (61.2%) reported contact with farm animals. It was suggested that the level of hygiene in Belarus was already very high at the time of this study, reducing exposure to microbial agents in general in this population. A population study from Russia and Finland found a positive association between allergic asthma and exposure to farm animals in pregnancy and early in life in both the countries. The explanation offered was that the children and their mothers, not living on farms themselves, had had occasional rather than frequent or continuous exposure to farm animals, limiting exposure to agents that may confer protection at higher exposures. In the ISAAC study, most children were studied in urban or semi-urban areas rather than in farming communities. In fact, almost half of the study centres were located in cities with more than one million inhabitants. Exposure to farm animals in pregnancy and the first year of life may have been occasional rather than frequent or continuous in most of these populations as well. This is supported by our finding that equally large proportions of subjects were exposed in pregnancy only, or during the first year only, compared with subjects being exposed in both periods as indicated in Table 5. Urban livestock farming is widespread in many cities in developing countries and exposure to farm animals may exhibit different patterns in such countries compared with the developed world.
How could a positive relationship between early farm animal exposure and childhood allergic symptoms be explained? Some farm animals, such as horses, produce allergens to which children may become sensitized. However, asthma and rhinitis are predominantly non-allergic in non-affluent compared with in affluent countries[22,23] and it seems unlikely that early life exposure to farm animals would noticeably increase Immunoglobulin-E (IgE)-mediated allergic symptoms at age 6–7 years. High exposure to endotoxin in the farming environment has been associated with increased non-atopic airway symptoms and bronchial hyper-responsiveness in farmers. Endotoxin was also associated with increased non-atopic wheeze in farm children studied in Germany, Switzerland and Austria and early-life exposure to endotoxin was associated with increased wheeze at ages 1–7 years in an urban birth cohort followed in Boston, USA. This suggests that increased endotoxin exposure associated with early life contact with farm animals in mostly urban children could possibly be responsible for the associations seen in our study. It is also possible that contact to farm animals increases exposure to certain helminths which may produce respiratory symptoms later in childhood.[26–29] Farm cats and dogs have been found with high prevalence of Toxocara and Toxoplasma[30,31] in some studies, and toxocara infections have been associated not only with wheezing symptoms but also with but also with allergic rhinitis and with skin manifestations. A study from China documented high rates of helminth infections in dogs posing a threat to public health. We adjusted our analyses for early life cat and dog exposure and found that the associations between farm animal exposure and symptoms were independent of early cat and dog exposure. Small-scale livestock farming is common in many cities in non-affluent countries in the world, and may produce a different type of exposure to farm animal products than is encountered on traditional farms located in affluent countries.
Whether such observations help to explain the associations we show in this article remains speculative, however. More detailed studies on farm animal exposure and childhood symptoms of wheeze, rhinoconjunctivitis and eczema among children living in non-affluent countries are needed.
We conclude that exposure to farm animals during pregnancy and in the first year of life is associated with increased symptoms of asthma, rhinoconjunctivitis and eczema in 6- to 7-year-old children living in non-affluent countries.
Supplementary Data are available at IJE online.
The main source of funding for the work done in this article by the ISAAC International Data Centre (IIDC) are the BUPA Foundation and the Auckland Medical Research Foundation. Many New Zealand funding bodies have contributed support for the IIDC (the Health Research Council of New Zealand, the Asthma and Respiratory Foundation of New Zealand, the Child Health Research Foundation, the Hawke's Bay Medical Research Foundation, the Waikato Medical Research Foundation, Glaxo Wellcome New Zealand, the NZ Lottery Board and Astra Zeneca New Zealand). Glaxo Wellcome International Medical Affairs supported the Regional Coordination and the ISAAC International Data Centre.
We are grateful to the children and parents who willingly cooperated and participated in ISAAC Phase Three and the coordination and assistance by the school staff is sincerely appreciated. The authors also acknowledge and thank the many funding bodies throughout the world that supported the individual ISAAC centres and collaborators and their meetings. The funders of the study had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.
Int J Epidemiol. 2012;41(3):753-761. © 2012 Oxford University Press
Copyright 2007 International Epidemiological Association. Published by Oxford University Press. All rights reserved.