Commentary: Geographical heterogeneity of asthma

Guy B Marks

Institute of Respiratory Medicine, University of Sydney, Australia. E-mail: g.marks{at}unsw.edu.au

The marked regional variation in the prevalence of asthma and other atopic diseases,1,2 together with increases in the prevalence of asthma over time (e.g.3), strongly imply that environmental factors are important in the aetiology of allergic disease.

In this issue of the International Journal of Epidemiology Stewart et al.4 have investigated the observed geographical heterogeneity to gain insights into the aetiology of these diseases. They used data on the prevalence of reported wheeze, symptoms of rhinoconjunctivitis and symptoms of eczema among school-age children in 155 centres in 56 countries. Their most consistent finding was that the prevalence of each of these symptoms was lower in the countries in the lowest quartile of the distribution of per capita gross national product (GNP) than in the remaining countries.

The strengths of this investigation include the use of data collected from five continents spanning a wide range of environmental and socioeconomic conditions. Although many local investigators were involved, the steering committee went to great lengths to standardize the study methods, including the use of a videotaped depiction of wheezing in an attempt to overcome cultural and linguistic variation in the description of this symptom. The use of ecological analysis may reveal associations which are not apparent in studies of relatively homogeneous populations of individuals in single communities.5 However, there are limitations to the interpretation of these data. The information on the exposure of interest, per capita GNP, is only available at a national level, whereas the prevalence data are based on the study of one or more communities within each of the 56 countries. These communities may not be representative of the country as a whole. This is particularly the case in countries in economic transition where urban-rural and other regional differences may be extreme.

High per capita income cannot directly cause atopic disease. The findings of this analysis, which are broadly consistent with other, more limited comparisons of atopic disease prevalence between economically disparate, but geographically and ethnically close, communities (e.g.6,7), should lead to the exposition of hypotheses about the origins of this variation. What is it about living in poorer countries that protects against the expression of atopic disease? Or conversely, what are people who live in countries with higher per capita GNP exposed to which causes atopic disease? Expressing the problem in this way highlights the difficulty in solving it. There are so many differences between these countries. However, some factors have biological plausibility and/or are supported by cross-sectional and cohort studies conducted in individuals. These include diet and obesity, allergen exposures in the home environment, and infections in early childhood.

Some features of nutrition and diet have been linked to asthma and atopic disorders. Reduced in utero nutrition, manifest as a lower birthweight or lower ponderal index (birthweight in proportion to birth length), has been shown to be protective against asthma and eczema.8,9 The biological mechanism underlying this association remains unknown. While this hypothesis would be consistent with the observed reduced risk of atopic disease in low GNP countries, other proposed dietary risk factors such as lack of fish intake10 are not consistent with the observed ecological association.

The extent of early life exposure to inhalant allergens influences the subsequent acquisition of sensitization to those allergens.11 However, it remains unclear to what extent the presence of any atopy, as opposed to specific sensitization, is explained by the level of allergen exposure. Furthermore, it is unlikely that there is any strong relation between national wealth and the level of domestic allergen exposure.

The relation between childhood infections and subsequent atopy and asthma is complex. Parents of schoolchildren with asthma recall that their children had respiratory infections in infancy more commonly than other parents. However, this is likely to represent recall and unmasking bias12 rather than an aetiological association. Indeed, there is evidence to suggest that respiratory and non-respiratory viral infections and other systemic infections in early life may actually protect against the development of atopy.1316 The observation that children who are born into large sibships17 or who attend child care centres from an early age18 are relatively protected against the development of atopy is consistent with this hypothesis. It may also be consistent with the finding that children who live on farms with livestock in early life are less likely to develop atopy.19 The proposed mechanism for this protective effect of early life infections is immune deviation: infectious agents induce the establishment of clones of antigen-specific memory T lymphocytes which secrete anti-allergic cytokines.20 It is at least plausible that children living in countries with low per capita GNP are exposed to more of these atopy-protecting infections than children in wealthier countries.

Stewart et al.'s observations pose a challenge. No-one would wish to solve the problem of allergic disease by reducing national wealth. The challenge is to identify what consequence of increased national wealth increases the risk of expression of allergic disease and to establish whether this can be modified while retaining the other economic, social and health benefits of national development.

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