The relationship of per capita gross national product to the prevalence of symptoms of asthma and other atopic diseases in children (ISAAC)

Alistair W Stewarta, Ed A Mitchellb, Neil Pearcec, David P Strachand and Stephan K Weilande on behalf of the ISAAC Steering Committee

a Department of Community Health, University of Auckland, Auckland, New Zealand.
bDepartment of Paediatrics, University of Auckland, Auckland, New Zealand.
cDepartment of Medicine, Wellington Clinical School, University of Otago, Wellington, New Zealand.
dDepartment of Public Health Sciences, St Georges Hospital Medical School, London, UK.
eInstitut Für Epidemiologie un Sozialmedizin, Westfälische Wilhelms Universität, Münster, Germany.

Reprint requests to: Alistair W Stewart, Department of Community Health, Faculty of Medicine and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand. E-mail: aw.stewart{at}auckland.ac.nz

Abstract

Background Increasing prevalence and worldwide variation in asthma and other atopic diseases suggest the influence of environmental factors, at least one possibly related to socioeconomic wellbeing. This paper examines the relationship of symptoms of asthma, rhinitis and eczema with gross national product per capita (GNP per capita).

Methods The prevalences of atopic symptoms in 6–7- and 13–14-year-old children were assessed in 91 centres (from 38 countries) and 155 centres (from 56 countries), respectively, in the International Study of Asthma and Allergy in Childhood (ISAAC). These symptoms were related to 1993 GNP per capita for each country as reported by the World Bank. The relationships between symptoms of atopic diseases and infant mortality, the human development index and 1982 GNP per capita were also considered.

Results The countries in the lowest quartile of GNP per capita have the lowest median positive responses to all the questions on symptoms of asthma, rhinitis and eczema. There was a statistically significant positive association between wheeze in the last 12 months and GNP per capita in the 13–14-year age group, but not in the 6–7-year age group. There was also a positive association between GNP per capita and eczema in both age groups.

Conclusions The positive associations between GNP per capita and atopic symptoms being of only moderate strength suggests that the environmental factors are not just related to the wealth of the country.

Keywords Allergies, asthma, children, ecological, eczema, GNP per capita, rhinitis, wheeze, ISAAC

Accepted 1 March 2000

The International Study of Asthma and Allergy in Childhood (ISAAC) found marked worldwide variation in prevalence of symptoms of asthma, eczema and allergic rhinoconjunctivitis.14 In general the prevalence of asthma in developing countries is lower than that in developed countries. Strachan proposed that ‘... social and demographic variations in allergy prevalence argue strongly for environmental influences on allergic sensitisation ...'.5 Furthermore, the prevalence of asthma is increasing.6 Although genetic factors are important, they cannot explain the increase in prevalence or worldwide variation. This has led to the suggestion that there must be some environmental factors producing these changes. Increasing pollution,7,8 decreasing infection9 and changes in diet have all been suggested.1012 Any environmental factor must be changing and must vary between countries. At least one environmental factor would appear to be associated with socioeconomic wellbeing, but this has only been examined at the individual level.1316

This ecological study examines the association of the prevalence of symptoms of asthma and other atopic diseases with gross national product per capita (GNP per capita) at a centre and country level where GNP per capita is being used as a surrogate for socioeconomic status of the country.

Methods

Prevalence data for the symptoms of asthma and allergy variables were obtained from the ISAAC study. The selection of centres and children have been described in detail elsewhere.14 In brief, for children 13 and 14 years of age in 155 centres from 56 countries, either all schools or a random selection of schools in a defined area were chosen. All children in classes of the appropriate age completed a short written questionnaire and in 99 of these centres the children also watched a video depicting various wheezing situations and then responded to questions. For children, aged 6 or 7 years in 91 centres in 38 countries from either all schools or a random selection of schools, a parent completed the same written questionnaire but the video option was omitted.

The questions considered here asked about the presence of symptoms of asthma and allergies. The asthma-related question asked children whether they had wheezing or whistling in the chest in the last 12 months. The question on rhinoconjunctivitis asked whether they had a problem with sneezing or a runny or blocked nose without signs of a cold in the last 12 months and whether this was accompanied by itchy-watery eyes. The eczema questions asked children if they had an itchy relapsing rash in the last 12 months that had affected the skin creases at some time. Also, the older children were asked whether they had breathed, in the last 12 months, like the wheezing young person on the video. Responses to all questions were yes or no, missing data being treated as a negative response.

To assess the severity of wheezing a question about the frequency of sleep disturbance was asked. Those responding that this occurred one or more nights a week having responded positively to the wheezing question were considered to have severe wheezing. A similar question was asked to get a measure of severity of the itchy rash. A severe itchy relapsing skin rash was one which kept the respondent awake one or more nights per week on average in the last year.

As an assessment of the socioeconomic status of a country we have used the gross national product per capita (GNP per capita) as reported by the World Bank.17 Purchasing power parity adjusted GNP per capita would be the preferred measure but was not available for eight countries. The GNP per capita measures the total domestic and foreign value added income claimed by residents. We used the 1993 GNP per capita (in US dollars) and also the 1982 GNP per capita18 as this was the approximate year of birth of the older children. As the calculation of GNP per capita can vary slightly, only the one source has been used and no estimate for Iran was available. Infant mortality and the human development index (HDI) have been suggested as measures of socioeconomic development of a country and we also considered these variables.17,19,20 The HDI is a composite of three basic components of human development: longevity (life expectancy), knowledge (combination of adult literacy and mean years of schooling) and standard of living (gross domestic product per capita adjusted for purchasing power parity).

The GNP per capita and the other factors are reported for a country whereas the ISAAC study allows the estimation of the atopic condition at a centre level. In Figure 1Go this results in countries being shown in vertical columns, each point representing a centre within that country.



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Figure 1 The association between prevalence of wheeze in the last 12 months (from the written questionnaire) among 13–14-year olds measured in centres and GNP per capita ($US) for each country

 
To simply display changes in the level of atopic symptoms with increasing GNP per capita, GNP per capita for each country in the age group has been divided into quartiles. Within these quartiles the centre with the median proportion of children responding positively is located and its value reported along with the values from the centres at the 10th and 90th percentiles. The numbers of centres in each quartile differ because of the varying number of centres per country. This procedure has also been used for infant mortality and HDI.

Assuming a linear relationship between the proportion of children who responded positively to the question on atopic symptoms and the GNP per capita of the country in which they went to school, the data were modelled using a generalized linear mixed model.21 This model was used to allow each centre to be considered as if randomly selected from within its country and so account for the clustering effect. The model used a binomial error but assumed the identity link so that there was a simple linear association between the outcome measure and GNP per capita. The calculations were done using the SAS macro GLIMMIX.22

Results

There was a very wide range of GNP per capita values from the countries participating in the ISAAC study (Table 1Go). The African countries of Ethiopia, Kenya and Nigeria along with India had GNP per capita values <=$US300 whilst Sweden and the US had GNP per capita values >$24 000 and Japan had highest GNP per capita of $31 490. The median GNP per capita for the 55 countries for which we had values was $US3610. The GNP per capita information for Iran was not available and so two centres were excluded, leaving 153 and 89 centres for 13–14- and 6–7-year-old children, respectively.


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Table 1 The prevalence of atopic symptoms during the last 12 months in children from two age groups in 55 countries ordered by gross national product (GNP) per capita
 
For the children aged 13–14 years, the proportion responding positively to the wheezing variable ranged from 1.6% up to a centre with 36.7%, for rhinoconjunctivitis the range was 1.4% to 39.8%, for itchy relapsing skin rash the range was 0.3% to 20.5% and for the video question the responses ranged from 0.6% to 19.5% (Table 1Go). For children aged 6–7 years the proportion responding positively to the wheezing variable ranged from 0.8% up to 32.1%, for rhinoconjunctivitis the range was 0.8% to 16.7% and for itchy relapsing skin rash the range was 0.0% to 18.4%. The centre proportions of severe wheezing varied from 0.1% to 6.3% in the older children and from 0.3% to 10.0% in the younger children.

Table 2Go shows that as GNP per capita increased there was a general increase in the median proportion of children responding positively. In particular, the lowest quartile has, for all variables at both ages, the smallest median prevalence. For 13–14-year-old children there was no clear trend in the other three quartiles but the 6–7-year-old children show, for all the questions, the largest quartile decreased compared with the second to largest GNP per capita quartile.


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Table 2 The median prevalence (with 10th and 90th percentiles) of atopic symptoms during the last 12 months in children from two age groups by centre grouped into four approximately equally sized groups based on the country gross national product (GNP) per capita
 
Assuming a linear relationship between GNP per capita and the atopic disease symptom measures, the changes in the percentage responding positively for each change of US$1000 of GNP per capita, as given by the generalized linear mixed model, are shown in Table 3Go. The percentage changes and the associated 95% CI are given. For children aged 13–14 years the proportion in a centre wheezing had an estimated increase of 0.31% with a US$1000 increase in GNP per capita (Figure 1Go). Increases of 0.16%, 0.12% and 0.14% were estimated for rhinoconjunctivitis, itchy relapsing skin rash and wheezing as measured by the video, respectively, while for the younger children an increase of 0.16% with a US$1000 increase in GNP per capita was estimated for itchy relapsing skin rash. The use of purchasing power parity adjusted GNP per capita in the subset of countries in which data were available showed similar results with most of the relationships being slightly stronger.


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Table 3 The relationship between gross national product (GNP) per capita and symptoms of atopic disease by age group
 
As GNP per capita may measure different characteristics of countries when viewed across the large range of countries involved in ISAAC, we have performed the same analyses using the much more homogeneous European countries only. In these 12 countries, all members of the European Union, there was no indication of a significant (5% level) association and the parameter estimates are, in some cases, of the opposite sign to those from the analysis based on all centres (Table 4Go).


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Table 4 The relationship between gross national product (GNP) per capita and symptoms of atopic disease by age group in countries of the European Union onlya
 
Alternative measures of socioeconomic status are infant mortality and HDI. In the 44 countries for which we had infant mortality data, it showed no relationship with the wheezing and other questions. For example, for each of the quartiles of infant mortality, in increasing order, the median centre had 10.4%, 8.3%, 10.2% and 16.1% of its 13–14-year-old children wheezing in the last 12 months. The HDI generally showed a stronger association with symptoms than did infant mortality. However, in the 13–14-year age group little relationship with HDI was seen with the exception being wheeze in the last 12 months where there was a positive relationship (P = 0.007). The median centre percentage of 13–14-year-old children wheezing in the last 12 months were 6.4%, 9.7%, 9.9% and 26.7% for the quartiles of HDI. In the 6–7-year age group, where there was no information from the African countries in particular, there was a positive relationship for wheeze, rhinoconjunctivitis and itchy relapsing skin rash. Both infant mortality and HDI range widely for countries with GNP per capita less than US$6000 but very little for countries above this level. Rank correlations between GNP per capita, HDI and infant mortality were all over 0.85 as was the rank correlation between HDI and infant mortality in countries with GNP per capita under US$6000. Despite the high correlations these variables showed different associations with the atopic symptom variables.

The GNP per capita at the time of birth of the older children, taken as 1982, was available in 45 of the ISAAC countries as the constituent republics of the Soviet Union were not listed separately at that time. This variable showed a greater effect size for wheezing in the last 12 months than the 1993 GNP per capita and, when modelled together, the 1982 GNP per capita measure showed some tendency to contribute to the explanation of current wheeze over the effect of the 1993 GNP per capita (P = 0.075). For the rhinoconjunctivitis and itchy rash conditions, the 1982 GNP per capita did not show any better relationship than the 1993 GNP per capita.

Discussion

This ecological study examined the relationship of GNP per capita to asthma and other atopic diseases in children of two age groups. This is in contrast to many epidemiological study designs where information is available at the individual level. It is emphasized that a correlation between variables based on group (ecological) characteristics may not necessarily be reproduced between variables based on individual characteristics. This may result in inappropriate inferences from ecological data, referred to as the ‘ecological fallacy’.23 However, ‘if the environment is important, then appropriate analysis should be at the environmental level’.19 The increasing prevalence and worldwide variation of asthma and other atopic diseases are most likely to be caused by environmental factors and hence ‘ecological analyses ... are the most useful way to examine the effect of social environment on health’.19

Gross national product comprises gross domestic product (GDP) plus the income residents receive from abroad less similar payments made to non-residents who contributed to the domestic economy. The GDP measures the total output of goods and services for final use produced by residents and non-residents and includes an allowance for non-money income (e.g. people who grow their own fruit and vegetables). The figures for GNP per capita are GNP in US dollar values converted from domestic currencies using single-year official exchange rates divided by the population of the country in that year. The GNP/GDP statistics suffer from known defects such as the quality and quantity of the raw data and the exclusion of some activities like the black market and domestic work the extent of which also varies between countries. The importance of the correction for purchasing power parity may also vary from country to country. Nevertheless, we believe there is no evidence that these statistics are so biased as to distort their use as an index of the relative underlying socioeconomic state of the countries. We have used just one source for our statistics, the World Development Report, produced by the World Bank, to reduce some of the potential error. Previous studies have shown that GNP per capita correlates with mortality.24,25

We found a statistically significant positive association between wheeze in the last 12 months and GNP per capita in the 13–14-year age group, but not in the 6–7-year age group. We also found a significant association between GNP per capita and eczema that was consistent in both age groups. There was no association between GNP per capita and rhinoconjunctivitis in either age group. However, these linear regression models may not be representing the relationship correctly given that the simple tabulations show a positive association at the lower GNP per capita levels but not at the higher levels.

The EU countries give a different picture when compared with the results from all centres. It could be that there is too little data to give a clear picture. It may be that the production giving rise to the GNP per capita represents a different ratio of characteristics (e.g. health, manufacturing, etc.) in the EU countries compared with the other countries under study. A third option is that the relationship between GNP per capita and symptoms of atopic disease is not linear and the positive associations shown in Table 3Go arise from an association in underdeveloped countries only.

As the socioeconomic influence may have occurred at the time the child was born we also considered the GNP per capita at that time. For the 13- and 14-year-old children there was some indication that, for the wheezing questions only, the relationship with the GNP per capita at the time of their birth may have been stronger than for the recent GNP per capita. However, this was not reflected in the consideration of rhinoconjunctivitis or the eczema measure. The relationship between the year in which GNP per capita was recorded and the year of birth of the child could reflect different aspects of the society. The GNP per capita could be a surrogate for the current health situation but it could also be a reflection of the health infrastructure in which case the GNP per capita in the past or even better a GNP per capita history may be more relevant.

An alternative measure of the social status of a country, HDI, is an attractive variable, in that it includes three measures of wellbeing of the community. We found, however, that developed countries tended to cluster at the top of the scale with little heterogeneity, which limited its usefulness. Infant mortality could also reflect the socioeconomic status of a country but, like HDI, it does not have a desirable distribution and we could not show a relationship with the wheezing and other allergic variables.

The option that the relationship is not linear fits with Table 2Go which shows the countries in the lowest GNP per capita quartile consistently having the lowest median while the order of the medians in the other quartiles are less consistent. This could occur if there was a threshold effect. As GNP per capita increases towards a certain level there are changes in society which are common to most countries and result in increasing symptoms of atopic diseases. Countries with GNP per capita above the threshold however, may differ in the type of goods and services produced as the GNP per capita increases such that symptoms may or may not be affected. For example, the proportion of GNP per capita used on health care expenditure has little association in a group of countries with GNP per capita over $US 12 000.25 Unfortunately neither HDI nor infant mortality discriminate between these wealthier countries and so do not shed further light on associations between symptoms of atopic disease and the socioeconomic status of the countries.

We considered GNP per capita as a measure of socioeconomic status of a country similarly to considering income as a measure of socioeconomic status at the individual level. The relatively weak association between socioeconomic wellbeing and atopic diseases is important, as it indicates that any environmental factor is not just related to the wealth of the country. However, as we have demonstrated an association, we recommend that GNP per capita should be included as a potential confounder for many of the subsequent ecological analyses on the ISAAC Phase One data.

Acknowledgments

The authors are indebted to the collaborators in the participating centres and all parents, children, teachers, and other school staff who participated in the surveys. We also thank Prof. Conrad Blyth, Professor of Economics at the University of Auckland, for his helpful advice on the interpretation of gross national product. The ISAAC prevalence data were collated by the ISAAC International Data Centre, Auckland, New Zealand, with financial support from HRCNZ, ARFNZ, NCHRF, HBMRF, WMRF, GWNZ and Astra NZ. Glaxo-Wellcome IMA contributed funding for regional co-ordination in ISAAC. Weiland and Strachan are members of the ISAAC Europe collaboration, supported in part by the European Union Biomed 2 programme (BMH4 CT98 3670).

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