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ISAAC Phase Two

Background

The ISAAC Steering Committee developed a more intensive protocol known as "ISAAC Phase Two - International". This study investigated variations in prevalence which emerged from Phase One using child contact modules involving 10-12 year old children. Comparisons between populations (centres) have been undertaken using objective measures of disease, and assessment of environment, lifestyle, and clinical management. Populations which were potentially informative were involved, such as those with contrasting prevalence of disease, environmental exposures, management or genetic factors. The 10-12 year age group was chosen as they were more likely to understand the procedures than 6-7 year old children and to be more compliant that 13-14 year old adolescents. ISAAC Phase Two began in 1998 and was coordinated by Professor Stephan Weiland in Munster and subsequently in Ulm, Germany which is the Phase Two Data Centre.

Aims

The aims of Phase Two were:

To describe the prevalence of 'objective' markers of asthma and allergies in children living in different centres, and to make comparisons within and between centres.
To assess the relation between the prevalence of 'objective' markers of asthma and allergies and the prevalence of symptoms of these conditions in children living in different centres.
To estimate to what extent the variation in the prevalence and severity of asthma and allergies in children between centres can be explained by differences in known or suspected risk factors or by differences in disease management.
To explore new aetiologic hypotheses regarding the development of asthma and allergies in children.

Methods

Measurements on representative samples of these populations were undertaken using standardised ISAAC instruments. The sample sizes were smaller than those recommended for Phase One to reflect the more intensive sampling procedures. A sample size of 1000 children per centre was recommended.

ISAAC Phase Two measured features of asthma, rhinoconjunctivitis and eczema which were not measured in Phase One. Additional standardised questions about cough, and the medical care of asthma, rhinitis and eczema were also developed. In addition there was a management and a "risk factor" questionnaire. Standardised protocols were also developed for child contact instruments including physical examination of the skin for flexural dermatitis and airway responsiveness testing using hypertonic saline aerosol challenge, skin prick tests for atopy, total and specific serum IgE, and storage of blood samples for genetic analyses and gene-environment interactions and endotoxin and house dust mite antigen measurement in the homes. The bronchial hyperresponsiveness measurement test was used to see whether it supported the questionnaire results. Measures of atopy (using allergen skin tests and IgE measurements) were used to see to what extent variations in wheezing illness are reflected in variations in atopy. A compilation of all the ISAAC instruments has been published¹, and the methodology has been validated in Germany². Phase Two studies also systematically obtained environmental data such as indoor exposure to allergens and pollutants to contribute to the ecological analyses.

ISAAC Phase Two International was undertaken in 30 centres in 22 countries. Nineteen of these centres from 13 countries are from the European Union: Albania, Estonia, France, Germany (2 centres), Greece (2 centres), Iceland, Italy, Latvia, Netherlands, Norway, Spain (4 centres), Sweden (2 centres) and the United Kingdom. The 11 centres outside Europe are in 9 countries: Brazil, China (3 centres), Ecuador, Georgia, Ghana, India, New Zealand, Turkey and Palestine.

Findings

ISAAC Phase Two has enabled the description of variation in disease prevalence beyond the level measured in Phase One by core questionnaires. Markers of disease have been related to individual exposure to environmental factors and genetic markers. ISAAC Phase Two has shown little evidence of genetic factors³ in asthma and that most asthma, rhinoconjunctivitis and eczema has a non-allergic basis, especially in developing countries^{4,5,6,7,8,9,10,11,12,}.

Funding

The coordination and central laboratory analyses of the European centres were funded by the Fifth Framework Programme of European Commission (QLK4-CT-1999-01288).
The following bodies funded the local studies. Spain: Fondo de Investigacion Sanitaria (grant code 00/1092E; Almeria); Fondo de Investigacion Sanitaria (grant code 00/1092E ; Cartagena); Fondo de Investigacion Sanitaria (grant code 00/1092E; Madrid); Fondo de Investigacion Sanitaria (grant code 00/1092E; Valencia). Turkey: Scientific and Technical Research Council of Turkey (grant code SPAG-2237), Treatment and Research Foundation of Turkey for Allergy, Asthma and Immunology and the Research foundation of Hacettepe University, Faculty of Medicine (Ankara). Greece: The Thorax Foundation Research Center (Athens); The Thorax Foundation Research Center (Thessaloniki). France: French Institute of Health and Medical Research (Institut National de la Santé et de la Recherche Médicale (INSERM), grant code IDS 337/4D001D and 737/69480), Ministère de l'Emploi et de la Solidarité (grant code 227/7HL02D), Mutuelle Générale de l'Education Nationale (grant code 257/8PL01F) and Agence de l’Environnement et de la Maitrise de l’Energie ADEME/PRIMEQUAL 96 (grant code FJ012B; Créteil). Germany: German Ministry of Education and Research (grant code 01 EE 9411-3; Dresden); German Ministry of Education and Research (grant code 01 EE 9411-3; Munich); Rudolf and Clothilde Eberhardt-Foundation (Ulm). Italy: Lazio Regional Health Authority (Rome). New Zealand: Health Research Council of New Zealand, Asthma and Respiratory Foundation of New Zealand and Hawkes Bay Medical Research Foundation (Hastings). Sweden: The Swedish Foundation for Health Care Sciences and Allergy Research (Linköping and Östersund). India: Jaslok Hospital & Research Centre (Mumbai). West Bank: Al-Quds University, Directorate General for International Cooperation and Belgian Technical Cooperation (Ramallah). The Netherlands: Dutch Ministries of the Environment, of Health and of Transport (Utrecht). UK: South Thames National Health Service Regional and Development project SPGS (West Sussex). The centres in Mumbai, Ankara, Kintampo (Ghana), Riga (Latvia), Tallinn (Estonia), Tblisi (Georgia) and Tirana (Albania) were supported, at least in part, by European members of the ISAAC Steering Committee.