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Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. ISAAC
  5. Materials and methods
  6. Results
  7. Discussion
  8. Conclusion
  9. ISAAC Steering Committee
  10. Acknowledgements
  11. References

Despite considerable research, the aetiology of asthma and allergic disease remains poorly understood. The International Study of Asthma and Allergies In Childhood (ISAAC), was founded to maximize the value of epidemiological research into asthma and allergic disease by establishing a standardized methodology and facilitating international collaboration. It has achieved its specific aims which are to describe the prevalence and severity of asthma, rhinitis and eczema in children living in different centres and to make comparisons within and between countries; to obtain baseline measures for assessment of future trends in the prevalence and severity of these diseases; and to provide a framework for further aetiological research into genetic, lifestyle, environmental and medical care factors affecting these diseases.

 The ISAAC design comprises three phases. Phase One used simple core written questionnaires for two age groups, and was completed in 156 collaborating centres in 56 countries and a total of 721 601 children participated. In the 13–14 years age group 155 centres from 56 countries participated, of which 99 centres completed a video questionnaire. For the 6–7 years age group there were 91 collaborating centres in 38 countries. ISAAC Phase One has demonstrated a large variation in the prevalence of asthma symptoms in children throughout the world including hitherto unstudied populations. It is likely that environmental factors were responsible for major differences between countries. The results provide a framework for studies between populations in contrasting environ-ments which are likely to yield new clues about the aetiology of asthma. ISAAC Phase Two will investigate possible aetiological factors, particularly those suggested by the findings of Phase One. ISAAC Phase Three will be a repetition of Phase One in the year 2000 to assess trends in prevalence.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. ISAAC
  5. Materials and methods
  6. Results
  7. Discussion
  8. Conclusion
  9. ISAAC Steering Committee
  10. Acknowledgements
  11. References

There is considerable concern that the prevalence of asthma and allergic diseases is increasing in western and developing countries. However, the aetiology of these conditions remains poorly understood despite a large volume of clinical and epidemiological research within populations which has been directed at explaining why some individuals and not others develop asthma and allergies. Investigation of the reasons for variations in prevalence between populations may be a more fertile source of new aetiological clues, but little is known about worldwide variations in the prevalence of asthma and allergic diseases.

 Asthma is one of the most important diseases of childhood, causing substantial morbidity [1]. Increases in the rates of hospital admission and primary care contacts for asthma in childhood have led to concern that the prevalence or severity of wheezing illness may be increasing in children worldwide.

 A number of surveys first conducted in the 1960s and 1970s have been repeated in recent years using similar methodology. These surveys consistently show an increase in the prevalence of wheezing illness (irrespective of diagnosis) in the UK, Australasia, Scandinavia, Israel and Taiwan, although the magnitude of the increase varies considerably between studies [2[3][4][5][6][7][8][9][10]–11]. Two of these studies have included an objective assessment of bronchial reactivity in the same location at two points in time [4, 11].

 Geographical variations in the prevalence of wheezing illness in children have been found in surveys comparing up to four countries, in South-east Asia [12], Poland and Sweden [13], and other groups of countries [14, 15], but little difference was found in Australasia [16]. A major study in adults, the European Community Respiratory Health Survey (ECHRS) [17, 18], studied men and women aged 20–44 years, mainly from European centres, and found variation between countries. None of these surveys has included developing countries. Differences within countries have been found in Papua New Guinea [19] and southern Africa [20, 21] with urban areas having higher prevalence than rural areas. While genetic factors predispose to asthma, studies of children whose parents have migrated from developing to developed countries suggest that there is an increased risk of asthma associated with the environment or lifestyle of an industrialized society [22].

 Much research has been conducted into the reasons why some individuals rather than others develop asthma and other atopic diseases such as rhinitis and eczema. A major risk factor is a family history of atopic disease but a range of environmental factors are also considered im-portant in the expression of disease. Such studies within populations have shed little light on the reasons why the occurrence of atopic disease varies from population to population. Factors affecting the prevalence of disease at a population level may be different to those that deter-mine which individuals within a population are at great-est risk [23]. In addition, the relationship of the three atopic conditions may be different between populations. Ecological analyses between populations may reveal further important risk factors. One obstacle to the in-vestigation of population differences (and of trends) has been the lack of a suitable and generally accepted method of measuring the prevalence and severity of asthma and other atopic diseases in children. Another obstacle has been the absence of a coordinated research programme to obtain and analyse comparative data. The International Study of Asthma and Allergies in Childhood (ISAAC) has been developed to address these issues.

ISAAC

  1. Top of page
  2. Abstract
  3. Introduction
  4. ISAAC
  5. Materials and methods
  6. Results
  7. Discussion
  8. Conclusion
  9. ISAAC Steering Committee
  10. Acknowledgements
  11. References

ISAAC developed from a merging of two multinational collaborative projects each investigating variations in childhood asthma at the population level. These were an initiative from Auckland, New Zealand to conduct an international comparative study of asthma severity, and an initiative from Bochum, Germany for an international study to monitor time trends and determinants of the prevalence of asthma and allergies in children.

 ISAAC is a unique project that has attracted worldwide interest and unprecedented large-scale participation. ISAAC Phase One uses simple methods for measuring the prevalence of childhood asthma, allergic rhinitis and atopic eczema for international comparisons, suitable for different geographical locations and languages [24, 25].

 The aims of ISAAC Phase One were to describe the prevalence and severity of asthma, rhinitis and eczema in children living in different centres and to make comparisons within and between countries; to obtain baseline measures for assessment of future trends in the prevalence and severity of these diseases; and to provide a framework for further aetiological research into lifestyle, environmental, genetic and medical care factors affecting these diseases. By September 1997 these aims had been achieved, marked by an ISAAC symposium at the 1997 annual congress of the European Respiratory Society in Berlin.

Materials and methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. ISAAC
  5. Materials and methods
  6. Results
  7. Discussion
  8. Conclusion
  9. ISAAC Steering Committee
  10. Acknowledgements
  11. References

ISAAC Phase One used core questionnaires designed to assess the prevalence and severity of asthma and allergic disease in defined populations. The methods are described in the ISAAC Phase One manual and a previous paper concerning rationale and methods [25]. Phase One data collection was completed in 1995, and the worldwide variations in the prevalence of asthma symptoms [26], rhinoconjunctivitis [27], and an overview of these symptoms have been published [28]. ISAAC Phase Two will involve studies in informative centres of aetiological factors particularly those suggested by Phase One. ISAAC Phase Three will be a repetition of Phase One after at least five years. ISAAC is organized by the ISAAC Steering Committee including Regional Coordinators, supported by National Coordinators, and contributed to by collaborating centres.

Collaborating centres and registration

Centres were recruited from around the world through scientific networks, focusing on locations of particular interest. Each collaborating centre was responsible for completing a registration document and obtaining its own funding. The first centre began its survey in 1991, but most centres undertook the data collection in 1994 and 1995.

Subjects and sampling frame

The older age group, 13–14 years, was chosen to reflect the period when mortality from asthma is more common and to enable the use of both a self-completed question-naire and a video questionnaire. The younger age group, 6–7 years, was chosen to give a reflection of the early childhood years, and is the youngest age when children are usually at school.

 The sampling frame was school children of two age groups (13–14 years and 6–7 years) within a specified geographical area (ISAAC Centre), for which a detailed map was provided. The ISAAC centre was most commonly an urban area, and a minority of ISAAC centres were regions within a country, or a whole country. The sampling frame was representative of the geographical area, without selection by urban or rural residence or variations in socioeconomic status, and included either all schools with children within the age group or a random sample of such schools.

 The recommended sample size was 3000, to ensure good prevalence estimates for severe asthma. For a sample size of 3000 the 95% confidence interval around an estimate of 1% is 0.64–1.33 and around an estimate of 30% is 28.4–31.6. Centres with limited resources or small populations were included in the prevalence comparisons, providing that the sample size was at least 1000 per age group. A high response rate of children within schools was sought and the majority of centres achieved more than 80%.

Phase One core questionnaire modules

Three one page questionnaires were developed by the original collaborators. These were agreed for use in the International Study of Asthma and Allergies in Childhood at a workshop in Bochum, Germany, 8–10 December 1991. The written questionnaires on wheezing, allergic rhinitis and atopic eczema for the 13–14 years age group were a requirement for participation in ISAAC Phase One. Written questionnaires to parents for the 6–7 years age group were strongly recommended, and used in nearly two-thirds of centres. The aim of compiling a standardized ‘core’ questionnaire was to ensure that comparable information on the basic epidemiology of atopic illnesses and their diagnosis is obtained from as many surveys as possible. The exact wording of questions followed, as far as possible, questions which have been used in published questionnaires and which have found differences between populations, and where validity has been assessed. The asthma symptoms questionnaires are found in Tables 1 and 2. Most of the questions used for asthma symptoms include both sensitive and specific indicators of asthma [29]. Questions about the date of completion of the questionnaire, child’s date of birth, age and sex were also included. The severity of asthma symptoms was assessed by three questions that asked about the following symptoms in the last 12 months: number of attacks of wheezing; sleep disturbed due to wheezing; wheezing severe enough to limit speech to only one or two words at a time between breaths.

Table 1.  . Core questionnaire wheezing module for 13–14 years olds Thumbnail image of
Table 2.  . Core questionnaire wheezing module for 6–7 years olds Thumbnail image of

Translation. In 81% of centres the written questionnaire was translated from English into one or more local languages, with some centres using English and local language versions. The method of translation was standardized, according to guidelines developed in Germany [30] and adapted for ISAAC (ISAAC Document 41). These guidelines included the use of translators familiar with asthma terminology, consultation with the local community, and back translation to English by an independent translator. The written questionnaires were used in 41 different languages. English was used most commonly, followed by Spanish, Italian, Hindi, Chinese, Portuguese, Malay and Marathi, and other languages made up the remainder.

Video questionnaire. A video using the audio-visual presentation of young people with clinical symptoms and signs of asthma was completed, where possible, by the 13–14 years age group [31, 32]. The children themselves were shown the video and answered the questionnaire at the time. The video elicited information without using written language terms to describe asthma symptoms. Although not compulsory, the video was strongly recommended and was used in 99 centres with the original ‘European’ English language version in 32 centres and the revised ‘International’ version in 67 centres. Both versions show five sequences of young persons with different manifestations of asthma. Two scenes were the same in both versions: the first scene with a young person wheezing while at rest, and the fourth scene of a young person waking at night with coughing. The European version showed only European children, and the questions were written in English, with local verbal translation of instructions where appropriate. The International version had scenes with children of different ethnic groups, there was no written language and the questions were verbally asked in the local language. This version has been validated in children in a Hong Kong population [33].

Data management and analysis

Information on the questionnaires was entered, by each collaborating centre or a national centre, on to the computer exactly as recorded by the child or parent. The entry of data was checked and data were transferred to the ISAAC International Data Centre (Auckland) using the protocol described in the ISAAC Coding and Data Transfer Manual.

 The 13–14 years and 6–7 years age groups were analysed separately. Symptom prevalences in each centre were calculated by dividing the number of positive responses to each question by the number of completed questionnaires for the written and video questionnaires separately. Thus apparent inconsistencies between responses to the stem and branch questions were accepted and not recoded. Basic descriptive summaries of the data were compiled by centre and country, in both age groups, along with correlations between variables. The within and between country variances were estimated using a generalized linear mixed model.

Quality control measures

The Steering Committee required documentation of the procedures for the study from each centre as a prerequisite for inclusion in publications of ISAAC world wide results. Centres completed a Registration Document before starting the study and followed the protocol described in the published ISAAC Manual and ISAAC Coding and Data Transfer Manual. All data submitted to the ISAAC International Data Centre were checked. Coding errors, omissions and inconsistencies in the demographic information were corrected with the assistance of the collaborator. A final report on all aspects of methodology actually used was completed for each centre and agreed between the ISAAC International Data Centre and the collaborators. This report included information about the sampling frame, sampling methods, participation rate of schools and of children within schools, the data entry method, and details of translation.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. ISAAC
  5. Materials and methods
  6. Results
  7. Discussion
  8. Conclusion
  9. ISAAC Steering Committee
  10. Acknowledgements
  11. References

One hundred and fifty-six collaborating centres in 56 countries met the requirements for this analysis, with a total of 721 601 participating children. The national coordinators and principal investigators of the ISAAC collaborating centres are listed in the Appendix. Response rates of children within participating schools in the older age group averaged 92% and in the younger age group averaged 89%. Detailed results of the asthma symptoms are summarized here, and published elsewhere [26].

13–14 years age group

In the 13–14 years age group 155 centres from 56 countries participated, with a total of 463 801 participating children. Thirty countries were represented by more than one centre. The geographical distribution of centres is illustrated on a world map ( Fig. 1).

image

Figure 1. 4 years age group; each point represents one centre.

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 For the question ‘Have you had wheezing or whistling in the chest in the last 12 months?’ there was a very wide range of prevalences, up to 15-fold differences, between countries, ranging from 2.1% to 32.2%. Countries that had a prevalence of 12-month wheeze under 10% were found mainly in Asia, Northern Africa, Eastern Europe and the Eastern Mediterranean regions, and those over 20% were found mainly in the UK, Australasia, North America and Latin America. The between-country variation was greater than the within-country variation.

 The prevalences for the three questions on severity of asthma symptoms showed a similar pattern to 12-month wheezing. Using appropriate correlations we found that the proportion of wheezers with severe symptoms changes little with increasing prevalence of wheeze.

 Every country had some children who reported having ‘asthma’ at some time in their lives, but the range in prevalence was very large, ranging from 1.6% to 28.2.%. The reporting of 12-month wheeze was generally higher than the reporting of ‘asthma ever’, in some countries much higher.

 Exercise wheeze in the last 12 months was reported more frequently than wheeze in the last 12 months in most countries The proportion of children reporting wheezing with exercise in the last 12 months ranged from 2.3% to 43.4%.

 Dry night cough in the last 12 months was reported more frequently than 12-month wheeze in most countries. The proportion of children reporting dry night cough in the last 12 months ranged from 4.0% to 42.3%.

 The video questionnaire was completed in 99 collaborating centres in 42 countries, with a total of 304 796 children. The geographical distribution of centres completing the video questionnaire is illustrated, by centre on a world map ( Fig. 2). There was a wide range of prevalence rates between countries, showing more than 15-fold differences.

image

Figure 2. . World map for 13–14 years age group video questionnaire; each point represents one centre.

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 The overall pattern of international differences shown by the 13–14-year-olds who took part in both the video and written questionnaires was similar. Video prevalence estimates were generally lower than written estimates for comparable questions in centres in the majority of countries.

6–7 years age group

For the 6–7 years age group there were 91 collaborating centres in 38 countries, with a total of 257 800 partici-pating children. Seventeen countries were represented by more than one centre. The geographical distribution of centres is illustrated on a world map ( Fig. 3).

image

Figure 3. . World map for collaborating centres, 6–7 years age group; each point represents one centre.

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 For positive answers to the question ‘Has your child had wheezing or whistling in the chest in the last 12 months?’ there was more than a 5-fold difference in prevalence between countries (4.1–32.1%). Some centres in countries with extreme values in the older age group did not provide data for the younger age group. The between-country variation was greater than the within-country variation for all questions.

 Both age groups were studied in 90 centres, and the correlations between the two age groups for the different symptoms were high. For the question about wheezing in the last 12 months, 57 centres had a lower prevalence in the younger age group, and 33 centres had a higher prevalence in the younger age group. The 6–7 years age group also had lower prevalences than the 13–14 years age group for all the other symptoms except any sleep disturbance due to wheezing.

 The proportion of wheezy children with severe asthma symptoms changed little with increasing prevalence of wheeze.

 Some parents from all countries reported ‘asthma ever’ in their children, but the range in prevalence was very large, ranging from 1.4% to 27.2%. In some countries the reporting of 12-month wheeze was much higher than the reporting of ‘asthma ever’, whereas in other countries there was more ‘asthma’ than ‘wheeze’.

 Exercise wheeze in the last 12 months was reported less frequently than 12-month wheeze in all countries. The proportion of reported wheezing with exercise in the last 12 months ranged from 1.6% to 16.5%. In contrast to the lower rates of exercise wheeze in this age group, dry night cough in the last 12 months was reported more frequently than 12-month wheeze in most countries. The proportion of parents of children reporting dry night cough in the last 12 months ranged from 5.9% to 39.5%.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. ISAAC
  5. Materials and methods
  6. Results
  7. Discussion
  8. Conclusion
  9. ISAAC Steering Committee
  10. Acknowledgements
  11. References

ISAAC Phase One has demonstrated, by means of simple standardized questionnaires, that there are large variations in the prevalence of asthma symptoms throughout the world. The self-reported 12-month prevalence of wheezing among 13–14 years age group between countries ranged from 2.1% to 32.2%. Parent-reported 12-month prevalence of wheezing in 6–7 years age group ranged from 4.1% to 32.1%. The highest values for 12-month prevalence of wheeze were found in developed English-speaking countries, and some Latin American non-English-speaking countries. There were considerable variations within regions; for example, within Europe, the 12-month prevalence in the 13–14 years age group varied from under 5% in centres in some countries to over 30% in others, and in Latin America from under 10% in one country, to over 25% in another. Our analysis shows that there is consistently more variation between countries than within countries.

 Previous international comparisons have drawn attention to variations in the prevalence of childhood asthma, but ISAAC Phase One comprises by far the most extensive international survey of asthma symptoms ever performed. Adherence to the protocol ensured that, within centres, there was standardization of the questionnaires and methods of administration and that schools were selected without bias from the defined geographical area. These centres, however, may not represent the prevalence of asthma symptoms throughout the whole country, and we have been unable to compare rural with urban areas. Moreover, there may have been important variation within some centres, for example between affluent and poor areas, which the ISAAC Phase One study did not examine. Targets for the sample size ensured there was sufficient precision in the prevalence estimates obtained. By recommending that at least half of the survey be done before the main pollen season it was hoped that variation due to seasonal factors would be reduced; in the event, studies in New Zealand [34], the UK and Germany have found that the 12-month period prevalence of the various wheezing symptoms is not significantly affected by the season of the survey.

 There were 13 centres in 10 countries reported in both the ECHRS and ISAAC studies. The rankings of prevalence of wheeze in the last 12 months were similar with the English-speaking countries (Australia, New Zealand, Republic of Ireland, UK) having the highest and Italy and Greece the lowest rates.

 While there is no accepted definition of asthma and the identification of asthma by questionnaire remains a contentious issue. The ISAAC collaboration agreed that the cardinal symptom of asthma would be that which reflects variable narrowing of the airways and that this is best described (in English) as ‘wheezing or whistling in the chest’. The questionnaire incorporated questions taken from pre-existing questionnaires with sensitive questions for asthma and more specific questions which related to the severity of asthma. In recent years a number of studies have compared responses to the ISAAC core wheezing questions with other indicators of asthma including physician diagnosis [35], other questionnaires [36] and physiological measures [11, 36, 37]. These indicate a level of sensitivity and specificity which is acceptable for the purposes of multicentre international comparisons.

 Although the significance of very mild wheezing may be questioned, the occurrence of frequent, sleep disturbing or speech-limiting attacks are accepted widely as clinically important. We also observed large international variations in the prevalence of these three more specific symptoms, and broadly, the worldwide pattern of prevalence of more severe symptoms followed that of any 12-month wheezing. However, we found that the order of countries ranking highest for the prevalence of ‘sleep disturbance due to wheezing one or more nights per week in the last 12 months’ and ‘wheeze severe enough to limit speech to only one or two words at a time between breaths’ were different from 12-month wheeze, while 4 or more attacks in the last 12 months was similar to 12-month wheeze. The explanations for the variation between prevalence and severity would be of particular interest, and may include differences in the management of asthma between countries. However, ISAAC Phase One did not collect information on asthma management but this will be recommended for ISAAC Phase Two.

 The proportion of wheezy children with severe asthma symptoms varied little with increasing prevalence of wheezy children in the population. This means the high prevalences found in some centres are not explained by excessive inclusion of children with mild wheeze. These findings suggest that factors affecting the prevalence of asthma also affect the severity of asthma, and the factors which especially affect the prevalence of severe asthma should be studied.

 The questionnaire was used across cultures and languages and therefore, its validity may have varied. Some languages do not have an equivalent of ‘wheezing’ as understood by English speakers. The high prevalence in English-speaking countries, especially in those most accustomed to using ‘wheezing’ as a term in surveys, suggests there may be some language bias associated with the written questionnaire, as suggested by the findings of the ECHRS [22], or that the population has a higher awareness of asthma. However, we also observed high prevalences in Spanish- and Portuguese-speaking countries in South America suggesting that other factors too are likely to be important in determining asthma symptom prevalence. There were also large variations within Spanish, Portuguese and Chinese languages. The overall pattern of international differences observed with the written questionnaire was maintained among those centres that employed the video questionnaire. The majority of centres showed a greater response to the written compared with the video questions, but large variation was observed with individual questions. There needs to be further exploration of responses to questions across languages and cultures.

 Considerable variation was observed in the prevalence of a positive response to the question concerning whether the child had ever had ‘asthma’. This question probably indicates the level of perceived or diagnosed asthma in the various centres but is a less reliable measure for epidemiological purposes [38]. Even in those centres with the lowest prevalences, 1.4%, asthma is clearly an important medical diagnosis. Up to one-third of children reported ‘asthma’ in the countries of highest prevalence.

 A conspicuous feature of these data is the high rates of asthma symptoms in countries whose predominant lang-uage is English and further study of possible aetiological factors common to these countries is a high priority. In contrast, while high rates of asthma symptoms were also found in some non-English-speaking countries, rates were not uniformly high between countries sharing the same language. The variations are unlikely to be explained entirely by interpretation of language, given the similar trends found between written and video questionnaires, and provide important opportunities for further study.

 ISAAC Phase One which examined the prevalence of reported asthma symptoms in children, has set the framework from which to study a variety of factors contributing to asthma, and provides a baseline from which to measure future trends. The most important outcome of ISAAC will be to advance our understanding of the causes of asthma, by studying factors acting at a population level. Although genetic factors are important risk factors for individuals within populations, migrant studies indicate they are unlikely to be responsible for the large variations in asthma which exist between populations and cannot be responsible for the recent upward trends within populations [25]. Environmental factors are likely to be more important and offer the greatest opportunities for prevention. An attractive current theory, supported by experimental evidence, is that increased hygiene and health care in western countries has altered the pattern of exposure to infection in early life in such a way as to predispose the immune system towards the atopic response [39, 40]. There are also a number of theories concerning the provocation of asthma by various agents including aeroallergens, diet, indoor and outdoor pollution. The ISAAC group is now using the prevalence data reported here to conduct ecological analyses between populations to test these and other hypotheses, about the aeitology of asthma.

Plans for ISAAC Phase Two

The ISAAC Steering Committee is proposing a coordinated international study to follow Phase One. This next study, known as ‘ISAAC Phase Two – International’, will investigate variations in prevalence which emerge from Phase One. Comparisons between populations (centres) will be undertaken using objective measures of disease, and assessment of environment, lifestyle, and clinical management. Populations which are potentially informative will be chosen, such as those with contrasting prevalence of disease, environmental exposures, management or genetic factors. Measurements on representative samples of these populations will be undertaken using standardized ISAAC instruments. The sample sizes may be smaller than those recommended for Phase One and the age groups will be appropriate for the procedures to be undertaken.

 In addition, local ‘ISAAC Phase Two’ studies are now planned or underway in a number of countries and regions with smaller groups of centres in regional or national groups, encouraged by regional or national coordinators.

 The ISAAC Steering Committee has developed additional standardized questions about cough, and the medical care of asthma, rhinitis and eczema. Standardized protocols have also been developed for child contact instruments including physical examination of the skin for flexural dermatitis, airway responsiveness testing using hypertonic saline challenge, skin prick tests for atopy, measurements of total and specific serum IgE, and storage of blood samples for potential future genetic analyses. Measures of bronchial hyperresponsiveness are being used to see whether these support the questionnaire results. Measures of atopy (using allergen skin tests and IgE measurements) are being used to see to what extent variations in wheezing illness are reflected in variations in atopy. The ISAAC Phase Two modules have been compiled [41] and the feasibility and validity of the methodology has been shown in Germany [42]. Phase Two studies will also systematically obtain environmental data such as indoor exposure to allergens and pollutants to contribute to the ecological analyses.

Plans for ISAAC Phase Three

Divergent time trends are of particular interest in exploring the role of environmental factors. Centres that participated in ISAAC Phase One will be invited to participate in ISAAC Phase Three. The field work will be carried out in the year 2000, allowing a minimum 5-year interval after Phase One. The design of Phase Three will be as similar as possible to the corresponding Phase One study. The same sampling frame, method of selecting schools and method of selecting children within schools will be used. Centres that did not include the 6–7 years age group or the video questionnaire will be encouraged to do these for Phase Three to provide new information.

Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. ISAAC
  5. Materials and methods
  6. Results
  7. Discussion
  8. Conclusion
  9. ISAAC Steering Committee
  10. Acknowledgements
  11. References

ISAAC Phase One, a worldwide study of asthma symptoms is a major step forward in using population differences in prevalence to gain new insights into the causes of asthma. The simplicity of the questionnaire method enabled a wide range of countries in most regions of the world to participate but was necessarily accompanied by some uncertainty as to international comparability. However, the large variations found are most unlikely to be explained by methodological factors alone. The existence of such wide variation between populations provides an epidemiological opportunity for new investigations into the causes of asthma.

ISAAC Steering Committee

  1. Top of page
  2. Abstract
  3. Introduction
  4. ISAAC
  5. Materials and methods
  6. Results
  7. Discussion
  8. Conclusion
  9. ISAAC Steering Committee
  10. Acknowledgements
  11. References

N Aït-Khaled (IUATLD, Paris, France)1

G Anabwani (Princess Marina Hospital, Gaborone, Botswana)1

HR Anderson (St George’s Hospital Medical School, London, UK)

MI Asher (University of Auckland, Auckland, New Zealand)1,2,3

R Beasley (Wellington School of Medicine, Wellington, New Zealand)3,4

B Björkstén (University Hospital, Linköping, Sweden)1,3

ML Burr (University of Wales, College of Medicine, Cardiff, United Kingdom)

J Crane (Wellington School of Medicine, Wellington, New Zealand)

U Keil (Universität Münster, Münster, Germany) 1

CKW Lai (The Chinese University of Hong Kong, Hong Kong)1

J Mallol (University of Santiago, Santiago, Chile)1

FD Martinez (University of Arizona, Tucson, USA)1

EA Mitchell (University of Auckland, Auckland, New Zealand)

S Montefort (University of Malta Medical School, Malta)1

N Pearce (Wellington School of Medicine, Wellington, New Zealand)

CF Robertson (Royal Children’s Hospital, Parkville, Australia)

JR Shah (Jaslok Hospital and Research Centre, Bombay, India)1

B Sibbald (University of Manchester, Manchester, UK)

AW Stewart (University of Auckland, Auckland, New Zealand)

DP Strachan (St George’s Hospital Medical School, London, UK)3

E von Mutius (Kinderklinik der Universität, München, Germany)

SK Weiland (Universität Münster, Münster, Germany)1,3,5

HC Williams (University Hospital, Nottingham, UK)

1Regional Coordinators;

2Chairperson of the ISAAC Steering Committee;

3ISAAC Executive;

4Coordinator, Phase One;

5Coordinator, Phase Two;

ISAAC International Data Centre: MI Asher (director), TO Clayton, PE Ellwood, EA Mitchell, AW Stewart.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. ISAAC
  5. Materials and methods
  6. Results
  7. Discussion
  8. Conclusion
  9. ISAAC Steering Committee
  10. Acknowledgements
  11. References

We are indebted to the collaborators in the participating centres and all parents, children, teachers and other school staff who participated in the surveys. There are many field workers and funding agencies who supported data collection, and national, regional and international meetings, including the meetings of the ISAAC Steering Committee. Unfortunately these are too numerous to mention (they will be acknowledged elsewhere) but we particularly wish to thank the funders who supported the ISAAC International Data Centre including the Health Research Council of New Zealand, the Asthma and Respiratory Foundation of New Zealand, the National Child Health Research Foundation, the Hawke’s Bay Medical Research Foundation, the Waikato Medical Research Foundation, Glaxo Wellcome New Zealand, and Astra New Zealand. We also wish to thank Glaxo Wellcome International Medical Affairs for funding the regional coordinating centres.

Appendix: Centres and Principal Investigators

Albania

Tiranë A Priftanji; Allergy Clinic, University Hospital

Algeria

Algiers A Bezzaoucha; Chu Bab el Oued, Service d’Epidemiologie

Argentina

Buenos Aires; Rosario N Salmun*; Fundación para el Estudio del Asma y otras Enfermedades Alérgicas

Australia

Adelaide D Kennedy; Respiratory Medicine, Adelaide Children’s Hospital

Melbourne C Robertson*; Department of Thoracic Medicine, Royal Children’s Hospital

Perth L Landau; Faculty of Medicine and Dentistry, The University of Western Australia

Sydney (6–7 years) J Peat; Department of Medicine, University of Sydney

Sydney (13–14 years) A Bauman; School of Community Medicine, The University of New South Wales

Austria

Salzburg J Riedler*; Kinderspital

Urfahr-Umgebung G Haidinger; Department of Epidemiology, Institute of Tumorbiology/Cancer Research, University of Vienna

Belgium

Antwerp PA Vermeire; Department of Respiratory Medicine, University of Antwerp

Brazil

Curitiba NA Rosário; Department of Pediatrics, Federal University of Parana

Porto Alegre R Stein; Respiratory Sciences Center, College of Medicine

Recife PGdM Bezerra; Instituto Materno Infantil de Pernambuco

Salvador LSdF Souza; Faculty of Medicine, Federal University of Bahia

São Paulo D Solé*; Division of Allergy, Universidade Federal de São Paulo

Canada

Hamilton M Sears*; Firestone Regional Chest & Allergy Unit, St. Joseph’s Hospital–McMaster University

Saskatoon B Taylor; IWK–Grace Emergency

Chile

Central Santiago I Sanchez; Departamento de Pediatria, Universidad Catolica de Chile

Punta Arenas L Amarales; Children’s Respiratory Service, Regional Hospital ‘Lautaro Navarro’

South Santiago E Cortez; Department of Paediatric Respiratory Medicine, Hospital El Pino, University of Santiago de Chile

Valdivia M Calvo-Gil; Instituto de Pediatria, Facultad de Medicina, Universidad Austral de Chile

China

Beijing Y Chen*; Capital Institute of Pediatrics

Chongqing K-H Chen; Children’s Hospital

Guangzhou N-S Zhong; Director, Guangzhou Institute of Respiratory Disease

Shanghai M Bao-Shan; The Central Hospital of Zhabei District of Shanghai

Wulumuqi M-L Xiao; Department of Paediatrics, The First Affiliated Hospital, Xinjiang Medical College

Costa Rica

San José ME Soto-Quirós; Unidad de Enseñanza, Hospital Nacional de Niños, San José

Estonia

Narva; Tallinn M-A Riikjärv*; Tallinn Children’s Hospital

Ethiopia

Addis Ababa K Melaku*; Department of Internal Medicine, Addis Ababa University

Jima B Seyoum; Department of Internal Medicine, Addis Ababa University

Finland

Helsinki M Kajosaari; Helsinki University Central Hospital

Kuopio County J Pekkanen*; Department of Environmental Epidemiology, National Public Health Institute

Lappland Area L Soininen; Provincial Administrative Board of Lappland

Turku and Pori CountyTA Koivikko; Turku University Central Hospital

France

Marseille D Charpin*; Service de Pneumologie-Allergologie, Hôpital Nord

Montpellier P Godard; Clinic des Maladies Respiratoires, Hôpital Arnaud de Villeneuve

Pessac A Taytard; Centre Hospitalier Universitaire de Bordeaux, Service des Maladies Respiratoires

Strasbourg E Quoix; Service de Pneumologie, Hôpital Civil

West MarneI Annesi; INSERM, U.169: Recherches en Epidémiologie, Villejuif Cedex

Georgia

Kutaisi N Khetsuriani; USA Center for Disease Control and Prevention Project in Georgia

Tbilisi A Gamkrelidze*; Department of Allergology, Tbilisi Medical University

Germany

Greifswald A Kramer; Institut für Hygiene und Umweltmedizin

Münster U Keil*; Institut für Epidemiologie und Sozialmedizin, Westfälische Wilhelms Universität

Greece

Athens C Gratziou; Pulmonary and Critical Care Department, Evgenidio Hospital

Hong Kong

Hong Kong (6–7 years) YL Lau; Department of Paediatrics, University of Hong Kong

Hong Kong (13–14 years) C Lai*; Department of Medicine, The Chinese University of Hong Kong

India

Akola R Maheshwari; Bhartia Municipal Hospital

Bombay (16)MK Joshi; K.B. Bhabha Hospital

Bombay (17)UA Pai; Pediatrician

Bombay (18)K Raghaven; L.T.M. Medical College

Borivali VA Khatav; Dr Khatav’s Mother & Child Hospital

Chandigarh L Kumar; Postgraduate Institute of Medical Education and Research

Jodhpur KC Jain; Pioneer Medical Centre

Kottayam TU Sukumaran; Institute of Child Health Medical College

Madras (2)S Rajajee; The Childs Trust Hospital

Madras (3)N Somu; Institute of Child Health

New Delhi (7)K. Chopra; GR Sethi; Maulana Azad Medical College

Neyveli G Jayaraj; Occupational Health, Neyveli Lignite Corporation Hospital

Orissa PK Kar; Ispat Hospital

Pune NM Hanumante; Consulting Pediatrician, ‘Happy Clinic’

Indonesia

BandungB Karnen*; Department of Medicine, Medical Faculty, University of Indonesia

Iran

Rasht; Tehran M-R Masjedi*; National Research Institute of Tuberculosis & Lung Disease, Shaheed Beheshti University of Medical Sciences and Health Services

Italy

Ascoli Piceno S Bonini; Consultorio Familiare USL 24

Cosenza E Bonci; Università degli Studi di Roma ‘La Sapienza’, Istituto di Clinica Pediatrica

Cremona F Rusconi; Isituto di Clinica di Perfezionamento, Azienda Ospedaliera, Clinica Pediatrica ‘G. e D. De Marchi’

Emilia-Romagna M Biocca; CDS Aziende USL, Città di Bologna e Ravenna

Empoli L Chetoni; Centro Studi Prevenzione Oncologica (CSPO), U.O. Epidemiologia USL 10/E

Firenze E Chellini; Centro Studi Prevenzione Oncologica (CSPO) U.O. Epidemiologia USL 10/E

Frosinone R Ronchetti; Università degli Studi di Roma ‘La Sapienza’, Istituto di Clinica Pediatrica, Policlinico Umberto I°

Milano L Bisanti; Regione Lombardia Servizio di Epidemiologia

Roma F Forastiere*; Osservatorio Epidemiologico

Siena E Renzoni; Istituto Malattie Respiratorie, Università di Siena, Ospedale Le Scotte

Torino G Ciccone; Servizio Universitario, Epidemiologia dei Tumori, Azienda Ospedaliera S.G. Battista

Trento S Piffer; Azienda Provinciale Sanitaria, Osservatorio Epidemiologico

Verona A Boner; Clinica Pediatrica, Università di Verona

Viterbo G Corbo; Servizio di Fisiopatologia Respiratoria, Università Cattolica del Sacro Cuore

Japan

Fukuoka S Nishima; The National Minami Fukuoka Chest Hospital

Kenya

Eldoret FO Esamai; Department of Child Health and Paediatrics, Moi University

Nairobi JA Odhiambo*; Respiratory Diseases Research Unit, Kenya Medical Research Institute

Kuwait

Kuwait JA Al-Momen; Al-Amiri Hospital

Latvia

Riga; Rural LatviaM Leja*; Latvia Medical Academy, Human Ecology Institute

Lebanon

Beirut FM Ramadan; Department of Medicine, American University of Beirut

Malaysia

Alor Setar KH Teh; Department of Paediatrics, Hospital Alor Setar

Ipoh WY Lim; Department of Paediatrics, Ipoh Hospital

Klang Valley J de Bruyne*; Department of Paediatrics, University Hospital

Kota Bharu BS Quah; School of Medical Sciences, University Sains Malaysia

Muar KW Chum; Johor Child Specialist Clinic, Hospital Muar

Malta

Malta S Montefort; Department of Medicine, University of Malta Medical School

Mexico

CuernavacaI Romieu; Centro Panamericano de Ecologia Humana y Salud

Morocco

Casablanca; Marrakech Z Bouayad*; Service de Pneumologie, Centre Hospitalier Ibnou Rochd

Rabat A Bennis; Résidence du Minaret

New Zealand

Auckland I Asher*; Department of Paediatrics, University of Auckland

Bay of Plenty C Moyes; Department of Child Health, Whakatane Hospital

Christchurch P Pattemore; Department of Paediatrics, Christchurch School of Medicine

Hawke’s Bay D Barry; Department of Paediatrics, Memorial Hospital

Nelson R Mackay; Department of Paediatrics, Nelson Hospital

Wellington J Crane; Department of Medicine, Wellington School of Medicine

Nigeria

Ibadan BO Onadeko; Department of Medicine, University College Hospital

Oman

Al-Khod BMS Al Riyami; Department of Medicine, Sultan Qaboos University

Pakistan

Karachi ZA Bhutta; Faculty of Health Sciences, The Aga Khan University

Panama

David-Panamá G Cukier; Neumologo-Pediatria

Paraguay

Asunción JA Guggiari-Chase; Sociedad Paraguaya de Alergia e Immunología

Peru

Lima P Chiarella; Departamento de Pediatria, Universidad Peruana Cayetano Heredia

Philippines

Metro Manilla F Cua-Lim; St Lukes Medical Center

Poland

Krakow G Lis*; 1st Department of Pediatrics, Polish-American Children’s Hospital

Poznan A Breborowizc; Department of Pediatric Pulmonology, University of Medical Sciences

Portugal

Funchal FD Borges; Serviço de Medicina, Centro Hospitalar do Funchal

Lisbon J Rosado Pinto*; Serviço de Immunoalergologia, Hospital de Dona Estefânia

Portimão C Nunes; Administração Regional de Saúde do Algarve (ARS)

Porto JL dos Santos; Serviço de Pediatria, Hospital de Matosinhos

Rep. of Ireland

Rep. of IrelandL Clancy; Respiratory Research Centre, St James’s Hospital

Romania

Cluj D Dumitrascu; Allergy Department, University Medicine and Pharmacology

Russia

Moscow R Khaitov; Institute of Immunology, National Research Center

Singapore

Singapore B-W Lee; Children’s Medical Center, National University Hospital

South Africa

Cape Town H Nelson; Department of Community Health Medical School, Observatory 7925

South Korea

Provincial Korea; Seoul S-I Lee*; Samsung Medical Center, Department of Pediatrics

Spain

Barcelona RM Busquets; Servicio de Pediatría, Hospital del Mar, Universidad Autónoma de Barcelona

Bilbao AD Rubio; Department of Pediatrics, Basque Country University

Cádiz AR Asensio; Sevicio Andaluz de Salud, Districto Bahia-Vejer

Cartagena L García-Marcos*; Universidad de Murcia, Dirección de Salud Area II

Castellón A Arnedo-Pena; Sección de Epidemiologia, Dirección Territorial Sanidad

Pamplona F Guillén Grima; Universidad Pública de Navarra, Departamento de Ciencias de la Salud

Valencia MMM Suárez-Varela; Department of de Medicina Preventiva i Salut Pública, Bromatologia, Toxicologia i Medicina Legal

Valladolid A Blanco Quirós; Dpto Pediatria, Facultad de Medicina

Sweden

Linköping N-I Kjellman; Department of Pediatrics, University Hospital

Stockholm/Uppsala T Foucard; Department of Paediatrics, Uppsala University Children’s Hospital

Taiwan

Taipei K-H Hsieh*; Director, Chang Gung Children’s Hospital

Thailand

Bangkok P Vichyanond*; Department of Pediatrics, Faculty of Medicine, Mahidol University

Chiang Mai M Trakultivakorn; Department of Pediatrics, Chiang Mai University Hospital

United Kingdom

Anglia and Oxford; North-east and Yorkshire; North Thames; North-west; South and West; South Thames; Scotland; Trent; Wales; West Midlands

HR Anderson*; Department of Public Health Sciences, St Georges Hospital Medical School

Guernsey D Jeff; Director of Public Health, Guernsey

Isle of Man PV Powell; Acting Director of Public Health, DHSS

Jersey CR Grainger; Medical Officer of Health, Public Health Services

Sunderland MH Shamssain; School of Health Sciences, University of Sunderland

Surrey/Sussex D Strachan; Department of Public Health Sciences, St Georges Hospital Medical School

Uruguay

Montivideo D Holgado de Cuesta; Pulmonology–Allergology, Hospital Pereira Rossell

USA

Chicago V Persky; Epidemiology & Biostatistics, School of Public Health, The University of Chicago at Illinois

Seattle G Redding; Division of Pediatric Pulmonary Medicine, Children’s Hospital & Medical Center

Uzbekistan

Samarkand, Tashkent T Aripova*; Institute of Immunology, Uzbek Ministry of Public Health

* National Co-ordinator

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. ISAAC
  5. Materials and methods
  6. Results
  7. Discussion
  8. Conclusion
  9. ISAAC Steering Committee
  10. Acknowledgements
  11. References
  • 1
    Anderson HR, Bland JM, Patel S, Peckham C. The natural history of asthma in childhood. J Epidemiol Community Health 1986; 40:121 9.
  • 2
    Hsieh KH & Shen JJ. Prevalence of childhood asthma in Taipei, Taiwan and other Asian Pacific countries. J Asthma 1988; 25:73 82.
  • 3
    Aberg N. Asthma and allergic rhinitis in Swedish conscripts. Clin Exp Allergy 1989; 19:59 63.
  • 4
    Burr ML, Butland BK, King S, Vaughan-Williams E. Changes in asthma prevalence: two surveys 15 years apart. Arch Dis Child 1989; 64:1118 25.
  • 5
    Shaw RA, Crane J, O’donnell TV, Porteous LE, Coleman ED. Increasing asthma prevalence in a rural New Zealand adolescent population. 1975–89 Arch Dis Child 1990; 65:1319 23.
  • 6
    Burney PG, Chinn S, Rona RJ. Has the prevalence of asthma increased in children? Evidence from the national study of health and growth. Br Med J 1990; 300:1306 10.
  • 7
    Haahtela T, Lindholm H, Bjorkstein F, Koskenvuo K, Laitenen LA. Prevalence of asthma in Finnish young men. Br Med J 1990; 301:266 8.
  • 8
    Robertson CF, Heycock E, Bishop J, Nolan T, Olinsky A, Phelan PD. Prevalence of asthma in Melbourne school children: changes over 26 years. Br Med J 1991; 302:1116 8.
  • 9
    Laor A, Cohen L, Danon YL. Effects of time, sex, ethnic origin and area of residence on prevalence of asthma in Israeli adolescents. Br Med J 1993; 307:841 4.
  • 10
    Whincup PH, Cook DG, Strachan DP, Papacosta O. Time trends in respiratory symptoms in childhood over a 24 year period. Arch Dis Child 1993; 68:729 34.
  • 11
    Peat JK, Van Den Berg RH, Green WF, Mellis CM, Leeder SR, Woolcock AJ. Changing prevalence of asthma in Australian children 1982–92. Br Med J 1994; 308:1591 6.
  • 12
    Leung R & Ho P. Asthma, allergy, and atopy in three south-east Asian populations. Thorax 1994; 49:1205 10.
  • 13
    Bråbäck L, Breborowicz A, Dreborg S, Knutsoson A, Pieklik H, Björkstén B. Atopic sensitisation and respiratory symptoms among Polish and Swedish school children. Clin Exp Allergy 1994; 24:826 35.
  • 14
    Burr ML, Limb ES, Andrae S, Barry DM, Nagel F. Childhood asthma in four countries. A comparative survey. Int J Epidemiol 1994; 23:341 7.
  • 15
    Robertson CF, Bishop J, Sennhauser FH, Mallol J. International comparison of asthma prevalence in children. Australia, Switzerland, Chile. Pediatr Pulmonol 1993; 16:219 26.
  • 16
    Asher MI, Pattemore PK, Harrison AC, Mitchell EA, Rea HH, Stewart AW, Woolcock AJ. International comparison of the prevalence of asthma symptoms and bronchial hyperresponsiveness. Am Rev Resp Dis 1988; 138:524 9.
  • 17
    Burney PGJ, Luczynska C, Chinn S, Jarvis D. The European Community Respiratory Health Survey. Eur Respir J 1994; 7:954 60.
  • 18
    European Community Respiratory Health Survey (ECRHS). Variations in the prevalence of respiratory symptoms, self-reported asthma attacks, and use of asthma medication in the European Community Respiratory Health Survey (ECRHS). Eur Respir J 1996; 9:687 95.
  • 19
    Turner KJ, Dowse GK, Stewart GA, Alpers MP. Studies on bronchial hyperreactivity, allergic responsiveness and asthma in rural and urban children of the highlands of Papua New Guinea. J Allergy Clin Immunol 1986; 77:558 66.
  • 20
    Van Niekerk CH, Weinberg EG, Shore SC, Heese HV, Van Schalkwyk DJ. Prevalence of asthma: a comparative study of urban and rural Xhosa children. Clin Allergy 1979; 9:319 24.
  • 21
    Keeley DJ, Neill P, Gallivan S. Comparison of the prevalence of reversible airways obstruction in rural and urban Zimbabwean children. Thorax 1991; 46:549 53.
  • 22
    Waite DA, Eyles EF, Tonkin SL, O’donnell TV. Asthma prevalence in Tokelauan children in two environments. Clin Allergy 1980; 10:71 5.
  • 23 The strategy of preventive medicine. Rose G (ed.). Oxford University Press
    1993.
  • 24
    Pearce N, Weiland SK, Keil U, Langridge P, Anderson HR, Strachan D, Bauman A, Young L, Gluyas P, Ruffin D, Crane J, Beasley R. Self-reported prevalence of asthma symptoms in children in Australia, England, Germany and New Zealand: an international comparison using the ISAAC protocol. Eur Resp J 1993; 6:1455 61.
  • 25
    Asher MI, Keil U, Anderson HR, Beasley R, Crane J, Martinez F, Mitchell EA, Pearce N, Sibbald B, Stewart AW, Strachan D, Weiland SK, Williams HC. International study of asthma and allergies in childhood (ISAAC): rationale and methods. Eur Respir J 1995; 8:483 91.
  • 26
    The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Worldwide variations in the prevalence of asthma symptoms: the International Study of Asthma and Allergies in Childhood (ISAAAC). Eur Resp J 1998; 12:315 35.
  • 27
    Strachan D, Sibbald B, Weiland SK et al. Worldwide variations in prevalence of symptoms of allergic rhino-conjunctivitis in children: the International Study of Asthma and Allergies in Childhood (ISAAC). Paediatr Allergy Immunol 1997; 8:161 76.
  • 28
    The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis and atopic eczema: ISAAC. Lancet 1988; 351:1225 32.
  • 29
    Burney PGJ, Laitinen LA, Perdrizet S, Huckauf H, Tattersfield AE, Chinn S, Poisson N, Heeren A, Britton JR, Jones T. Validity and repeatability of the IUATLD (1984) Bronchial Symptoms Questionnaire: an international comparison. Eur Respir J 1989; 2:940 5.
  • 30
    Weiland SK, Kugler J, Von Mutius E, Schmitz N, Fritzch Ch, Wahn U, Keil U. The language of pediatric asthma patients: verbal descriptors of symptoms in Germany. Monatsschr Kinderheilkd 1993; 141:878 882 (in German).
  • 31
    Shaw RA, Woodman K, Ayson M, Dibdin S, Winkleman R, Crane J, Beasley R, Pearce N. Measuring the prevalence of bronchial hyperresponsiveness in children. Int J Epidemiol 1995; 24:597 602.
  • 32
    Shaw RA, Crane J, Pearce N, Burgess CD, Bremner P, Woodman K, Beasley R. Comparison of a video questionnaire with the IUATLD written questionnaire for measuring asthma prevalence. Clin Exper Allergy 1992; 22:561 8.
  • 33
    Lai CKW, Chan JKW, Wong G, Ho A, Choy D, Lau J, Leung R. Comparison of the ISAAC video questionnaire (AVQ3.0) with the ISAAC written questionnaire for estimating asthma associated with bronchial hyperreactivity. Clin Exp Allergy 1997; 27:540 5.
  • 34
    Stewart AW, Asher MI, Clayton TO, Crane J, D’souza W, Ellwood PE, Ford RPK, Mitchell EA, Pattemore PK, Pearce N. The effect of season-of-response to ISAAC questions about asthma, rhinitis and eczema in children. Int J Epdemiol 1997; 26:126 36.
  • 35
    Jenkins MA, Clarke JR, Carlin JB, Robertson CF, Hopper JL, Dalton MF, Holst DP, Choi K, Giles GG. Validation of questionnaire and bronchial hyperresponsiveness against respiratory physician assessment in the diagnosis of asthma. Int J Epidemiol 1996; 25:609 16.
  • 36
    Ehrlich RI, Toit DD, Jordaan E, Volmink JA, Weinberg EG, Zwarenstein M. Prevalence and reliability of asthma symptoms in primary school children in Cape Town. Int J Epidemiol 1995; 24:1138 46.
  • 37
    Reidler J, Reade T, Dalton M, Holst D, Robertson C. Hyper-tonic saline challenge in an epidemiological survey of asthma in children. Am Rev Resp Crit Care Med 1994; 150:1632 9.
  • 38
    Strachan DP. Epidemiology. In Childhood asthma and other wheezing disorders. Silverman M (ed.). Chapman Hall, London 1995.
  • 39
    Martinez F. Role of viral infections in the inception of asthma and allergies during childhood: could they be protective? Thorax 1994; 49:1189 91.
  • 40
    Holt PG. Environmental factors and primary T-cell sensitisation to inhalant allergens in infancy: reappraisal of the role of infections and air pollution. Pediatr Allergy Immunol 1995; 6:1 10.
  • 41
    ISAAC Steering Committee. Phase II Modules of the International Study of Asthma and Allergies in Childhood (ISAAC). Münster, 1998.
  • 42
    Weiland SK, Von Mutius E, Leupold W, Stender M, Werner B, Mrach M, Hirsch Th, Menken G, Duhme H, Keil U. Bronchial responsiveness to hypertonic saline in relation to asthma and atopy in 8–11 year old children. Eur Resp J 1997; 10 (Suppl. 25):304s (abstract).