articles worldwide time trends in the prevalence of...

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www.thelancet.com Vol 368 August 26, 2006 733

Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveysM Innes Asher, Stephen Montefort, Bengt Björkstén, Christopher K W Lai, David P Strachan, Stephan K Weiland, Hywel Williams, and the ISAAC Phase Three Study Group*

SummaryBackground Data for trends in prevalence of asthma, allergic rhinoconjunctivitis, and eczema over time are scarce. We repeated the International Study of Asthma and Allergies in Childhood (ISAAC) at least 5 years after Phase One, to examine changes in the prevalence of symptoms of these disorders.

Methods For the ISAAC Phase Three study, between 2002 and 2003, we did a cross-sectional questionnaire survey of 193 404 children aged 6–7 years from 66 centres in 37 countries, and 304 679 children aged 13–14 years from 106 centres in 56 countries, chosen from a random sample of schools in a defined geographical area.

Findings Phase Three was completed a mean of 7 years after Phase One. Most centres showed a change in prevalence of 1 or more SE for at least one disorder, with increases being twice as common as decreases, and increases being more common in the 6–7 year age-group than in the 13–14 year age-group, and at most levels of mean prevalence. An exception was asthma symptoms in the older age-group, in which decreases were more common at high prevalence. For both age-groups, more centres showed increases in all three disorders more often than showing decreases, but most centres had mixed changes.

Interpretation The rise in prevalence of symptoms in many centres is concerning, but the absence of increases in prevalence of asthma symptoms for centres with existing high prevalence in the older age-group is reassuring. The divergent trends in prevalence of symptoms of allergic diseases form the basis for further research into the causes of such disorders.

IntroductionThe International Study of Asthma and Allergies in Childhood (ISAAC) epidemiological research programme was established in 1991 because of concern that asthma and allergies were increasing in prevalence and severity, but little was known about the scale of the problem worldwide or the factors affecting prevalence.1 Until the 1990s, most studies of the prevalence of asthma and allergies had been undertaken in the UK, Australia, and New Zealand. The ISAAC investigators believed that new information would be contributed by the participation of other countries, including developing countries, with comparisons between, rather than within populations, helped by standardised methods.

The enormous participation in ISAAC Phase One, in which 700 000 children from 156 centres in 56 countries were included, demonstrated the worldwide concern about asthma and allergies. The participatory ISAAC approach with simple questionnaires enabled the collection of comparable data from children throughout the world.2 The large variations in the worldwide prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema that were recorded, even in genetically similar groups,3–6 suggested that environmental factors underlie the variations. Many aspects of environments have been examined in ecological analyses of data from ISAAC Phase

One,7–14 and have provided some support for hypotheses that economic development,15 dietary factors,7,8 climate,9 infections,10 and pollens,11 might influence some of this variation.

In ISAAC Phase Two, causes are studied in more detail in 30 study centres in 22 countries, with detailed questionnaires and objective measurements of physiological variables and indoor exposure.16 From the outset, ISAAC Phase Three was planned to assess time trends in the prevalence of symptoms by repeating the original cross-sectional study after at least 5 years. Our aim was to examine the hypothesis that the prevalence of asthma, allergic rhinoconjunctivitis, and eczema is increasing in some, but not all, regions of the world. The findings might give further clues about the causes of these conditions by revealing information about geographical variation in the rate of change in symptom prevalence for the three disorders.

MethodsISAAC Phase Three is a repetition of a multicountry cross-sectional survey of two age-groups of school children—6–7 years and 13–14 years—undertaken at least 5 years after the baseline survey, ISAAC Phase One. Phase One study participants were identified through random samples of schools in defined geographical areas, or by

Lancet 2006; 368: 733–43

*Members listed at end of report

Department of Paediatrics, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1010, New Zealand (M I Asher MBChB); Department of Medicine, University of Malta, Malta (S Montefort MD); Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (B Björkstén MD); Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, SAR China (C K W Lai DM); Division of Community Health Sciences, St Georges, University of London, UK (D P Strachan MD); Department of Epidemiology, University of Ulm, Ulm, Germany (S K Weiland MD); and Centre for Evidence Based Dermatology, Queen’s Medical Centre University Hospital, Nottingham, UK (H Williams PhD)

Correspondence to: Prof Innes Asher [email protected]

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including all schools where the area had less than 3000 children of the age-group. In ISAAC Phase Three, the study centres chose the children either by new random samples of schools in that area or by going back to the same schools chosen at random in Phase One. All centres aimed to complete the study for the older age-group. Inclusion of the younger age-group was optional, since it was more resource intensive because of the greater involvement of parents, and thus was not completed in every centre. The study instruments are straightforward standardised questionnaires with questions about symptoms of asthma, allergic rhinoconjunctivitis, and eczema. Each centre did Phase Three in the same way as Phase One to ensure the data obtained were comparable. Details of the study design and methods are described elsewhere.17 Centres were expected to obtain ethics approval and parental consent according to the requirements of the country, and to fund their own study. This study reports data for centres that completed both ISAAC Phase One and Phase Three, and achieved ISAAC quality-control standards for both phases.17 More detailed information regarding the trends for each disease, including the asthma video questionnaire used with the 13–14 year age-group, will be presented in separate reports. Answers to written questions were reported by parents for children and were self-reported for adolescents. In this study, we estimated asthma symptoms on the basis of positive answers to the written question: “Have you (has your child) had wheezing or whistling in the chest in the past 12 months?” Current allergic rhinoconjunctivitis symptoms were estimated on the basis of positive answers to both these questions: “In the past 12 months, have you (has your child) had a problem with sneezing or a runny or blocked nose when you (he/she) did not have a cold or the flu?” and if yes, “In the past 12 months, has this nose problem been accompanied by itchy watery eyes?” Current eczema symptoms were estimated on the basis of positive answers to two questions: “Have you (has your child) had this itchy rash at any time in the past 12 months?” and, “Has this itchy rash at any time affected any of the following places: the folds of the elbows; behind the knees; in front of the ankles; under the buttocks; or around the neck, ears, or eyes.” These questions were preceded by the question “Have you (has your child) ever had a skin rash which was coming and going for at least 6 months?” In Phase One, eczema defined in this way was called atopic eczema, but is now referred to as eczema, as recommended by the World Allergy Organisation.18

The written questionnaire was translated from English according to ISAAC guidelines,4 into one local language in 72% centres, and into more than one in 7% centres. In Phase Three, the written questionnaires were used in 39 languages. English was the most common language (31% of centres), followed by Spanish (16%), Italian and Portuguese (8%), Arabic and Chinese (6%), Malay (4%), German, Hindi, and Russian (3%), and 29 other languages made up the remainder.

We assessed centres for adherence to the protocol, and similarity between methods in Phases One and Three. Centres that had deficiencies in their methods or differences between the phases that could potentially seriously affect comparability of the estimates (such as low response rates) were excluded. Others with less serious deviations from the protocol were included, but their deviations were noted.

We derived an estimate of the absolute yearly rate of change in symptoms of asthma, allergic rhinoconjunctivitis, and eczema for each centre and an SE adjusted for the effect of cluster sampling.19 Increases or decreases of more than 1 SE could then be derived from these estimates. The level of 1 SE rather than 2 SE was chosen to show broad patterns of change rather than statistical significance. We used Bland-Altman plots to illustrate the yearly change versus mean prevalence of Phases One and Three for each centre. This mode of presentation was chosen to remove the influence of sampling error (regression to the mean)20 when comparing the trends in higher or lower prevalence areas. We assessed heterogeneity of the centre-specific estimates of change in prevalence for the three disorders.

Role of the funding sourceThe funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

ResultsThe ISAAC Phase Three studies were completed to the ISAAC standards in 172 data sets: 66 centres in 37 countries in the 6–7 year age-group (summarised in table 1 with full information in webtable 1) and in 106 centres from 56 countries in the 13–14 year age-group (summarised in table 1 with full information in webtable 2). Altogether, 190 data sets were received for both age-groups and 12 were excluded because of low response rates, four because of different sampling frames, and two because there were fewer than 1000 participants. 193 404 children participated from the younger age-group, and 304 679 from the 13–14 year age-group with mean response rates of 85% and 91% respectively. Both age-groups were studied in most centres, but in 44 centres in 28 countries, data were available for 13–14 year age-group only (these centres were most of the centres in English-speaking Africa, all those in French-speaking Africa and China, and some centres in Latin America, northern and eastern Europe, eastern Mediterranean, and western Europe). One centre provided data for 6–7 year age-group only. Of centres that provided data for both age-groups, data from two centres were excluded for the 13–14 year age-group because of low response rates and one because of a change of sampling frame (footnoted in webtable 2). The seven centres that did not have an ethics committee available to review the study design and the

See Online for webtables 1 and 2

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four centres that did not seek ethical approval are also shown in the footnote for webtables 1 and 2.

We recorded data within a year for each centre for Phases One and Three. The Phase One study took place between 1992 and 1998 (mostly 1994–95) and the Phase Three study between 1999 and 2004 (mostly 2002–03) (webtables 1 and 2). The time between Phases One and Three averaged 7 years (range 5–10 years, SD 1·2 years).

Although the mean prevalence for centres increased slightly for each of the three disorders in both age-groups,

there was wide variation between centres that could not be explained by random sampling variation (test for heterogeneity p<0·0001, figure 1). Webtables 1 and 2 show the details of the time trends (summary data in table 1) and their pattern is shown in figures 2–4. For both age-groups, whereas most centres showed divergent changes of more than 1 SE in prevalence of the three disorders, more than a quarter of centres showed changes in the same direction (table 2). For the younger age-group, the centres that showed increases in all three disorders more frequently

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6–7 year age-groupAfrica (English-speaking)

Nigeria 7·0 2396 86·2 4·8 5·6 0·10 0·19 3·7 3·6 −0·01 0·17 4·5 5·0 0·07 0·13Asia-Pacific

Hong Kong 6·0 4448 96·0 9·1 9·4 0·03 0·16 13·7 17·7 0·67 0·23 3·9 4·6 0·12 0·09Indonesia 6·0 2503 88·1 4·2 2·8 −0·22 0·11 3·9 3·6 −0·04 0·12 ·· ·· ·· ··Japan 8·0 2958 90·7 17·4 18·2 0·10 0·12 7·8 10·6 0·35 0·11 ·· ·· ·· ··Malaysia (3) 6·3 9940 84·1 6·5 5·8 −0·12 0·07 4·1 4·8 0·11 0·06 9·5 12·6 0·49 0·10Singapore 7·0 5389 92·0 15·7 10·2 −0·80 0·24 8·5 8·7 0·02 0·15 2·8 8·9 0·87 0·18South Korea (2) 5·0 6018 94·7 13·3 5·8 −1·45 0·28 9·8 8·7 −0·18 0·12 8·8 11·3 0·52 0·13Taiwan 7·0 4832 96·8 9·6 9·8 0·04 0·13 14·6 24·2 1·37 0·17 3·5 6·7 0·46 0·08Thailand (2) 6·0 7315 77·2 8·2 11·9 0·47 0·23 7·3 10·4 0·30 0·25 11·9 16·7 0·79 0·13

Eastern MediterraneanIran (2) 6·0 6065 88·4 5·4 12·0 1·14 0·11 1·5 2·2 0·12 0·05 1·1 2·0 0·13 0·05Malta 7·0 3795 79·7 8·8 14·9 0·86 0·16 7·2 8·9 0·24 0·11 4·2 4·0 −0·03 0·07Sultanate of Oman 6·0 4130 97·5 7·1 8·4 0·21 0·12 6·2 7·0 0·13 0·10 4·2 4·2 0·00 0·08

Indian subcontinentIndia (6) 7·5 18 877 89·4 6·2 6·8 0·06 0·17 3·2 3·9 0·05 0·08 3·0 2·4 0·00 0·07

Latin AmericaBrazil 7·0 3047 68·2 21·3 24·4 0·44 0·20 12·5 12·0 −0·07 0·14 6·8 6·8 0·00 0·12Chile (3) 7·0 9310 88·9 18·2 17·9 −0·06 0·12 8·2 12·3 0·56 0·08 10·9 12·9 0·26 0·08Costa Rica 8·0 3234 80·9 32·1 37·6 0·69 0·20 11·6 15·9 0·54 0·14 8·7 8·9 0·02 0·09Mexico 8·0 2579 84·3 8·6 8·4 −0·03 0·11 8·6 7·2 −0·17 0·10 4·9 4·0 −0·11 0·08Panama 6·0 2942 92·5 23·5 22·7 −0·13 0·20 7·1 11·7 0·77 0·18 7·9 14·4 1·09 0·17

North AmericaBarbados 6·0 2759 85·9 18·9 19·5 0·11 0·18 5·5 6·4 0·15 0·10 6·7 9·2 0·42 0·12Canada 9·0 1255 63·3 14·1 18·2 0·47 0·15 8·2 10·8 0·29 0·12 8·7 12·0 0·36 0·12

Northern and eastern EuropeAlbania 5·0 2896 87·6 7·6 5·0 −0·53 0·15 4·1 3·9 −0·03 0·13 2·5 3·7 0·24 0·10Estonia 7·0 2385 85·6 9·3 9·6 0·05 0·11 3·5 4·2 0·11 0·08 9·8 11·5 0·24 0·12Georgia 7·0 2666 92·9 9·3 6·9 −0·34 0·14 3·9 2·8 −0·16 0·11 5·1 2·4 −0·39 0·16Lithuania 7·0 2772 92·0 4·6 6·6 0·28 0·10 3·2 3·8 0·08 0·08 2·3 3·0 0·09 0·08Poland (2) 7·0 4496 81·9 10·9 13·6 0·38 0·13 7·2 13·0 0·78 0·11 6·3 11·5 0·77 0·08Russia 6·0 2730 95·2 11·1 11·4 0·05 0·17 5·6 4·7 −0·16 0·09 9·4 6·6 −0·46 0·12Sweden 8·0 2089 63·8 10·3 10·2 −0·01 0·13 8·0 6·9 −0·14 0·12 19·5 22·3 0·35 0·18Ukraine 4·0 1950 99·1 12·2 12·5 0·07 0·36 9·7 7·7 −0·51 0·28 6·2 5·3 −0·21 0·17

OceaniaAustralia 9·0 2968 81·9 27·2 20·0 −0·80 0·16 9·8 12·9 0·34 0·11 11·1 17·1 0·67 0·11New Zealand (4) 9·5 10 873 85·2 23·6 22·2 −0·11 0·07 9·5 11·4 0·19 0·05 14·3 15·0 0·08 0·06

Western EuropeAustria (2) 7·0 6876 87·8 7·8 7·4 −0·05 0·07 5·1 6·1 0·15 0·06 5·7 6·1 0·05 0·06Belgium 7·0 5645 77·8 7·3 7·5 0·02 0·08 4·9 5·8 0·13 0·06 7·7 11·6 0·56 0·09Germany 5·0 3830 82·4 9·6 12·8 0·65 0·17 5·4 6·9 0·30 0·12 6·7 7·9 0·23 0·12Italy (6) 8·0 11 287 92·5 7·5 7·9 0·07 0·05 5·4 6·5 0·15 0·04 5·8 10·1 0·53 0·04Portugal (3) 7·0 5365 65·1 13·2 12·9 −0·07 0·10 8·7 9·3 0·16 0·10 9·6 9·7 0·09 0·12Spain (6) 7·3 18 941 77·2 6·2 9·5 0·44 0·05 5·4 7·9 0·33 0·04 3·4 5·9 0·31 0·03UK 5·0 1843 91·9 18·4 20·9 0·50 0·30 9·8 10·1 0·05 0·24 13·0 16·0 0·60 0·28

13–14 year age-groupAfrica (English-speaking)

Ethiopia 8·0 3195 96·8 10·7 9·1 −0·20 0·19 10·6 9·9 −0·09 0·15 19·9 19·0 −0·12 0·18Kenya (2) 6·0 6312 99·8 13·9 15·8 0·35 0·23 14·2 21·2 0·94 0·25 10·4 15·2 0·83 0·21Nigeria 6·0 3142 99·7 10·7 13·0 0·38 0·33 39·7 16·4 −3·88 0·69 17·7 7·7 −1·66 0·49South Africa 7·0 5037 83·4 16·1 20·3 0·60 0·30 15·1 20·7 0·80 0·23 8·3 13·3 0·71 0·18

Africa (French-speaking)Algeria 6·0 4203 89·6 5·9 8·7 0·48 0·20 9·9 20·7 1·80 0·40 3·2 6·5 0·56 0·13Morocco (2) 6·5 3466 100·0 7·8 10·4 0·00 0·31 13·1 21·6 1·12 0·41 10·7 21·8 1·72 0·26Tunisia 5·0 3042 99·9 8·5 11·9 0·67 1·62 35·8 23·2 −2·52 0·83 8·0 9·4 0·28 0·42

Asia-PacificChina (2) 7·0 7044 96·7 4·3 6·0 0·24 0·10 8·1 10·4 0·33 0·10 1·2 1·4 0·05 0·03Hong Kong 7·0 3321 99·5 12·4 8·6 −0·55 0·11 24·0 22·6 −0·21 0·32 2·7 3·3 0·08 0·07Indonesia 6·0 2826 99·6 2·1 5·2 0·52 0·19 5·3 4·8 −0·08 0·17 1·2 2·2 0·16 0·08

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than centres with decreases in all three disorders were Asia-Pacific, Indian subcontinent (India), North America, eastern Mediterranean, and western Europe, whereas in

the older age-group they were Africa, Asia-Pacific, India, Latin America, and northern and eastern Europe. For both age-groups, most centres reported a change of 1 SE or

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Japan 8·0 2520 94·6 13·4 13·0 −0·05 0·21 14·9 17·6 0·34 0·16 ·· ·· ·· ··Malaysia (3) 6·3 8955 91·5 10·1 8·9 −0·13 0·15 13·9 16·2 0·53 0·20 8·9 9·9 0·19 0·17Philippines 7·0 3658 77·5 12·3 8·4 −0·55 0·24 15·3 11·0 −0·61 0·33 5·2 7·8 0·37 0·13Singapore 7·0 4217 93·9 9·8 11·4 0·24 0·21 15·1 16·5 0·20 0·22 7·4 9·2 0·25 0·09South Korea (2) 5·0 10 263 96·4 7·7 8·7 0·20 0·11 10·2 11·6 0·28 0·12 3·8 5·7 0·39 0·08Taiwan 6·0 6378 95·9 5·4 7·0 0·26 0·07 11·7 17·8 1·02 0·19 1·4 4·1 0·45 0·05Thailand (2) 6·0 8207 94·6 13·1 11·6 −0·21 0·22 15·5 21·0 0·84 0·37 8·2 9·6 0·39 0·17

Eastern MediterraneanIran (2) 6·5 6123 99·8 10·9 13·2 0·17 0·21 7·5 9·8 0·31 0·16 2·6 4·4 0·30 0·09Kuwait 6·0 2882 91·6 17·1 7·6 −1·59 0·47 12·6 10·7 −0·32 0·31 8·4 6·1 −0·38 0·26Malta 7·0 4136 90·0 16·0 14·6 −0·20 0·18 29·0 20·9 −1·15 0·39 7·7 5·4 −0·33 0·14Pakistan 6·0 2999 96·0 8·5 11·7 0·53 0·49 18·1 16·8 −0·22 0·51 9·6 13·2 0·61 0·37Sultanate of Oman 6·0 3747 97·2 8·9 8·4 −0·08 0·21 11·4 15·2 0·63 0·23 4·7 7·1 0·39 0·14

Indian subcontinentIndia (8) 7·1 20 767 90·6 6·7 6·4 0·02 0·14 6·3 10·0 0·43 0·14 4·3 3·7 −0·03 0·12

Latin AmericaArgentina 5·0 3445 99·4 11·2 13·6 0·48 0·24 17·4 16·9 −0·09 0·36 7·4 6·3 −0·23 0·22Brazil (5) 7·4 15 681 91·5 22·7 19·9 −0·42 0·17 16·2 15·8 −0·05 0·19 5·3 4·2 −0·08 0·05Chile (3) 6·7 9175 89·3 10·2 15·5 0·84 0·13 10·7 22·2 1·12 0·19 9·6 16·1 0·86 0·16Costa Rica 8·0 2436 69·6 23·7 27·3 0·46 0·24 14·3 17·7 0·43 0·16 7·2 6·3 −0·11 0·11Mexico 8·0 1431 85·9 6·6 11·6 0·63 0·13 9·4 7·1 −0·28 0·13 4·4 2·8 −0·20 0·09Panama 6·0 3183 92·9 17·6 22·9 0·88 0·19 9·4 11·7 0·40 0·18 7·8 14·5 1·11 0·17Paraguay 5·0 3000 99·3 19·4 20·9 0·31 0·32 34·5 45·1 2·12 0·62 10·8 17·7 1·38 0·35Peru 6·0 3022 99·2 26·0 19·6 −1·06 0·57 19·4 18·7 −0·12 0·34 8·2 10·5 0·38 0·21Uruguay 8·0 3177 90·8 19·0 17·9 −0·13 0·20 16·0 10·6 −0·67 0·18 7·2 5·2 −0·25 0·14

North AmericaBarbados 5·0 2498 70·6 17·7 20·8 0·62 0·44 11·0 11·8 0·16 0·25 5·0 7·0 0·40 0·19USA 8·0 2422 86·6 22·9 22·3 −0·07 0·27 13·4 19·1 0·71 0·28 8·5 8·3 −0·03 0·11

Northern and eastern EuropeAlbania 6·0 2983 86·6 2·6 3·4 0·12 0·09 4·0 5·5 0·24 0·15 0·8 2·0 0·19 0·06Estonia 7·0 3603 93·3 8·6 9·3 0·09 0·13 4·7 6·3 0·22 0·09 6·6 8·7 0·29 0·13Finland 7·0 3051 98·8 13·1 19·0 0·84 0·19 15·3 15·5 0·04 0·17 13·2 15·6 0·34 0·17Georgia 7·0 2650 88·9 3·6 5·1 0·21 0·13 4·5 4·5 −0·01 0·11 2·8 1·8 −0·14 0·08Latvia 10·0 1283 94·8 8·3 10·5 0·22 0·14 5·3 4·5 −0·08 0·07 5·2 3·4 −0·19 0·09Lithuania 6·0 2723 90·5 8·2 6·7 −0·24 0·22 5·6 4·6 −0·17 0·15 1·7 1·8 0·02 0·07Poland (2) 7·5 4420 90·4 7·8 10·2 0·35 0·11 8·8 18·9 1·35 0·12 5·0 8·5 0·44 0·08Romania 7·0 3019 92·8 3·0 22·7 2·81 0·23 5·2 14·3 1·29 0·17 6·3 5·4 −0·13 0·17Russia 6·0 3769 97·2 9·9 11·2 0·22 0·21 7·8 11·7 0·65 0·15 4·9 3·8 -0·18 0·12Sweden 8·0 2679 81·2 12·6 9·7 −0·36 0·13 11·1 10·4 −0·09 0·15 15·8 12·9 −0·37 0·13Ukraine 4·0 2428 98·9 12·9 20·9 2·01 0·55 11·2 11·2 −0·01 0·53 5·3 5·7 0·11 0·23

OceaniaNew Zealand (5) 9·0 13 317 89·2 29·7 26·7 −0·39 0·13 19·1 18·0 −0·13 0·10 12·9 8·8 −0·44 0·08

Western EuropeAustria 8·0 1439 86·0 11·8 15·1 0·41 0·20 9·2 9·7 0·06 0·17 5·3 7·5 0·28 0·13Belgium 7·0 3250 96·6 12·0 8·3 −0·52 0·17 14·5 16·9 0·34 0·18 6·7 7·2 0·07 0·11Channel Islands (2) 5·5 2021 85·1 35·1 26·5 −1·62 0·44 17·3 15·0 −0·45 0·21 17·0 11·0 −1·04 0·23Germany 5·0 4132 93·9 14·2 17·5 0·68 0·21 14·4 15·0 0·12 0·17 7·1 7·7 0·12 0·12Isle of Man 6·0 1716 88·7 33·4 31·2 −0·36 0·30 20·1 20·2 0·02 0·28 15·6 11·1 −0·76 0·23Italy (9) 7·9 11 192 92·3 9·4 8·4 −0·22 0·07 14·3 15·5 0·07 0·10 6·2 7·7 0·16 0·05Portugal (4) 7·8 10 630 80·3 9·5 12·0 0·32 0·09 7·0 9·5 0·40 0·08 4·4 5·1 0·16 0·05Republic of Ireland 8·0 3089 90·9 29·1 26·7 −0·30 0·19 19·3 15·5 −0·48 0·19 13·6 8·6 −0·62 0·11Spain (8) 7·6 26 149 86·1 9·3 9·6 0·04 0·05 13·9 15·0 0·10 0·07 4·1 4·0 −0·01 0·03UK (6) 7·3 19 226 88·4 31·0 24·7 −0·71 0·14 18·9 15·3 −0·57 0·09 14·7 10·6 −0·39 0·08

Numbers of centres is one for each country, unless otherwise indicated in brackets next to country name.

Table 1: Country totals for numbers of centres and children, response rate, 12-month prevalence of asthma, allergic rhinoconjunctivitis, and eczema symptoms in both phases, average change per year, and SE of the change by age-group (full information in webtables 1 and 2)

more in prevalence of at least one disorder. For the 6–7 year age-group, two of the 64 centres recorded reductions in all three disorders, 16 recorded increases, and 45 mixed changes (one centre reported no changes). For the 13–14 year age-group, 11 of 105 centres noted decreases in all three disorders, 20 showed increases, and 74 showed mixed changes.

In the 6–7 year age-group, the prevalence of asthma symptoms changed by 1 SE or more in most centres (59%). Of the 39 centres with changes, prevalence increased in 25

and decreased in 14 (table 2), and increases occurred more often than decreases for all levels of mean prevalence. In the 13–14 year age-group, the prevalence of asthma symptoms changed by 1 SE or more in most centres (77%). Of the 82 centres with changes, about equal numbers showed an increase (42) and a decrease (40) in prevalence (table 2). For lower mean prevalence values, more centres showed increases in prevalence of 1 SE or more, but for centres with higher mean prevalence, decreases in prevalence of 1 SE or more were more common (figure 1).

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In the 6–7 year age-group, the prevalence of symptoms of allergic rhinoconjunctivitis changed by 1 SE or more in most centres (80%). Of the 53 centres with changes, 44 showed an increase and nine a decrease in prevalence (table 2). Prevalence increased more often than it decreased for all levels of mean prevalence. In the 13–14 year age-

group, the prevalence of allergic rhinoconjunctivitis changed by 1 SE or more in most centres (70%). Of the 74 centres with changes, 48 reported an increase and 26 a decrease in prevalence (table 2), and prevalence increased more often than it decreased for all levels of mean prevalence.

Prevalence reduced by ≥1 SE per yearLittle change (<1 SE)Prevalence increased by ≥1 SE per year

6–7 year age-group


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Figure 2: World map showing direction of change in prevalence of asthma symptoms for 6–7 year age-group and 13–14 year age-groupEach symbol represents a centre. Blue triangle=prevalence reduced by ≥1 SE per year. Green square=little change (<1 SE). Red triangle=prevalence increased by ≥1 SE per year.

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The prevalence of eczema symptoms in the 6–7 year age-group changed by 1 SE or more in most centres (81%). Of the 52 centres with changes, 44 recorded an increase and eight a decrease in prevalence (table 2), and prevalence increased more often than it decreased for all levels of mean prevalence. In the 13–14 year

age-group, prevalence of eczema symptoms changed by 1 SE or more in most centres (75%). Of the 79 centres with changes, 47 noted an increase and 32 a decrease in prevalence (table 2). For lower mean prevalence values, more centres showed increases in prevalence of 1 SE or more than showed decreases, but for centres with

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Figure 3: World map showing direction of change in prevalence of allergic rhinoconjunctivitis symptoms for 6–7 year age-group and 13–14 year age-groupEach symbol represents a centre. Blue triangle=prevalence reduced by ≥1 SE per year. Green square=little change (<1 SE). Red triangle=prevalence increased by ≥1 SE per year.

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higher mean prevalence, there was no clear pattern (figure 1).

For all centres combined, the proportion of children with symptoms of more than one disorder rose slightly from Phase One to Phase Three. For those with all three disorders the proportion rose from 0·8 to 1·0% in the 6–7 year age-group and from 1·1 to 1·2% in the 13–14 year age-group; for

those with both asthma and allergic rhinoconjunctivitis, the proportion rose from 1·9 to 2·2% in the 6–7 year age-group and from 3·2 to 3·5% in the 13–14 year age-group; for those with both allergic rhinoconjunctivitis and eczema, the proportion rose from 0·7 to 1·1% in the 6–7 year age-group and from 1·3 to 1·5% in the 13–14 year age-group. For those with both asthma and eczema, the proportion Ref number

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Figure 4: World map showing direction of change in prevalence of eczema symptoms for 6–7 year age-group and 13–14 year age-groupEach symbol represents a centre. Blue triangle=prevalence reduced by ≥1 SE per year. Green square=little change (<1 SE). Red triangle=prevalence increased by ≥1 SE per year.

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increased from 1·1 to 1·2% in the 6–7 year age-group, but did not change in the 13–14 year age-group (1·1%).

DiscussionWe have obtained worldwide comparable population estimates of direction and size of change in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema, using identical instruments. For almost all centres, time trend data had not been previously recorded. This study included a large number of centres from around the world, and a large proportion of the centres participated in both Phase One and Phase Three, with about two-thirds of the original centres replicating the protocol and achieving high response rates. The simplicity of the study tools, design, and communication enhanced acceptability and participation.2

Clear patterns for the change in prevalence were noted. Most centres showed a change in prevalence of 1 SE or more for at least one disorder, with increases being more common than decreases, and occurring more commonly in the younger age-group than the older age-group. The changes were greatest for eczema in the younger age-group, and for allergic rhinoconjunctivitis in both age-groups. The only regions where increases in prevalence of all three disorders occurred more often in both age-groups than decreases were Asia Pacific and India. A pattern of more increases than decreases was noted for all levels of mean

prevalence, apart from in the older age-group at high prevalences, for which asthma symptoms more commonly decreased, and eczema symptoms, which showed no clear pattern.

These patterns might be a due to a greater effect of environmental change in younger people for allergic rhinoconjunctivitis and eczema, but not asthma, or a cohort effect, where an environmental change took place at a later date that affected the prevalence in the younger age-group, but not the older age-group. For example, in northern and eastern Europe, rapid environmental change took place in the 1990s (after the collapse of the communist systems) and is thus more likely to have affected the 6–7 year age-group in Phase Three than the 13–14 year age-group who were born before these changes occurred. In developing countries, wheezing seems to be less related to atopy than does allergic rhinoconjunctivitis and eczema.21

The variations in symptom prevalence in most regions suggests that the factors that affect these conditions vary in different locations. For example, in Latin America, several centres had high prevalence rates, similar to those in centres in some developed countries, despite large differences between socioeconomic status and living conditions in these countries,22 and showed little change over 7 years. Factors that affect asthma and allergies might act in different ways in developed countries than in developing countries, or their interaction with socio-

Region Asthma symptoms Allergic rhinoconjunctivitis symptoms

Eczema symptoms* All disorders

Increase Decrease Little change Increase Decrease Little change Increase Decrease Little change Increase Decrease Mixed or little change


English-speaking Africa 0 0 1 0 0 1 0 0 1 0 0 1

Asia-Pacific 2 5 5 7 2 3 10 0 0 2 0 8

Eastern Mediterranean 4 0 0 3 0 1 1 0 3 1 0 3

Indian sub continent 2 2 2 2 1 3 3 2 1 1 0 5

Latin America 2 1 4 5 1 1 3 2 2 0 0 7

North America 1 0 1 2 0 0 2 0 0 1 0 1

Northern and eastern Europe 2 2 5 3 4 2 6 3 0 1 1 7

Oceania 1 2 2 5 0 0 2 0 3 0 0 5

Western Europe 11 2 7 17 1 2 17 1 2 10 1 9

Total 25 14 27 44 9 13 44 8 12 16 2 46


Africa† 5 2 2 6 2 1 6 1 2 4 0 5

Asia-Pacific 6 4 5 9 1 5 10 1 3 3 0 11

Eastern Mediterranean 2 2 2 3 2 1 4 2 0 1 2 3

Indian Sub-Continent 2 4 2 5 1 2 1 3 4 1 0 7

Latin America 7 3 5 8 3 4 6 6 3 4 1 10

North America 1 0 1 1 0 1 1 0 1 0 0 2

Northern & Eastern Europe 9 2 1 6 2 4 5 4 3 3 0 9

Oceania 0 3 2 1 2 2 0 4 1 0 1 4

Western Europe 10 20 4 9 13 12 14 11 9 4 7 23

Total 42 40 24 48 26 32 47 32 26 20 11 74

Data are number. *Two centres for the 6–7 year age-group and one centre for the 13–14 year age-group were unable to provide valid eczema symptom data. †Includes English-speaking and French-speaking Africa.

Table 2: Number of centres with changes (increase ≥1SE, decrease ≥1SE and little change <1SE) by region, disorder, and age-group

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economic status might be important. If a single factor accounts for the changes in prevalence, it would need to have a strong effect and be prevalent worldwide,23 but to date, such a factor has not been identified. The factors that cause variation in prevalence might differ from one location to another and from one age-group to another, and could be related to aspects of lifestyle, dietary habits, microbial exposure,24 economic status, indoor or outdoor environment, climatic variation, awareness of disease, or management of symptoms. There is likely to be a constellation of environmental factors associated with the development process that relate to the worldwide changes, including loss of protective factors and addition of risk factors, and these might be different for each of the three disorders. These will be explored in the environmental analyses of ISAAC Phase Three.17

The strengths of this study include the large number of centres that participated worldwide, the use of standardised methods that were duplicated in repeat surveys and achieved high response rates, the use of disease symptoms rather than disease labels, and the completion of rigorous central methods and data checks. The time interval (mean 7 years) was probably adequate to detect changes in centres in which environmental changes might be occurring rapidly, such as in China, and to detect changes which might be occurring more slowly. We avoided the possibility of regression to the mean by using the mean prevalence when assessing the change between Phase One and Phase Three, rather than a simple plot of the difference between Phase Three and Phase One relative to the Phase One prevalence, which would give rise to correlations, even when there is no relation between the prevalences recorded in Phase One and Phase Three prevalences.20 The pattern of changes in prevalence is more varied than expected on the basis of chance alone, and the heterogeneity indicates that there are many factors that influence change in disease prevalence. Apart from questionnaire responses, no objective measures of allergic diseases were obtained, but these will be examined in ISAAC Phase Two. Prevalence has been examined at two time points only, so calculation of mean yearly change cannot be interpreted with confidence as a consistent linear change during the study. The self-selection of centres, which were mainly urban, means that the centres included might not be representative of its country or region, especially for the younger age-group, for which fewer centres participated. Self-reporting of symptoms by the older children could have led to higher estimates in this group than for the younger children, whose parents’ responses were recorded.

In addition to the ISAAC studies, we are aware of five other studies of trends in population prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in children and adolescents that have used similar methods. In the counties of Troms and Finnmark in Norway, divergent trends in symptom prevalence were recorded.25 In centres in eastern and southwest Germany, investigators reported no change in prevalence of asthma,

hayfever, or IgE;21,26 whereas in another study in east Germany, prevalence of hayfever symptoms increased, but not asthma or eczema symptoms.27 In Aberdeen, UK, the prevalence of asthma symptoms plateaued while the prevalence of eczema and hayfever symptoms increased.28 In Ankara, Turkey, a significant fall in the cumulative prevalence of allergic rhinitis was noted, with a slight insignificant rise in asthma and eczema.29 Tallinn in Estonia is the only centre included in the present study for which trends for asthma, allergic rhinoconjunctivitis, and eczema had been studied previously.30 Little change was reported in prevalence of wheezing, rhinitis, and itching rash between cross-sectional studies completed in 1992–93 and 1996–97.

We have provided estimates of trends for symptoms of asthma, allergic rhinoconjunctivitis, and eczema. The data have direct relevance for health-service delivery in the countries included in the study as well as providing a basis for understanding these disorders. In almost all centres, there was a change in prevalence of one or more of the disorders over time. Although changes in mean annual prevalence to the order of 0·5% might sound small, such changes could have substantial public-health implications, especially since the increases took place most commonly in heavily populated countries. Urban centres in developing countries might have few resources to implement management programmes for these diseases in the face of overwhelming infectious diseases. However, interest from centres in developing countries in collaborating in this study shows that they are concerned that asthma and allergies in children are emerging as important public-health problems.ISAAC Phase Three Study GroupISAAC Steering Committee—N Aït-Khaled* (Union Internationale Contre la Tuberculose et les Maladies Respiratoires, Paris, France), H R Anderson (Division of Community Health Sciences, St Georges, University of London, London, UK), M I Asher (Department of Paediatrics, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand), R Beasley*, (Medical Research Institute of New Zealand, Wellington, New Zealand), B Björkstén* (Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden), B Brunekreef (Institute of Risk Assessment Science, Universiteit Utrecht, Netherlands), W Cookson (Asthma Genetics Group, Wellcome Trust Centre for Human Genetics, University of Oxford, UK), J Crane (Wellington Asthma Research Group, Wellington School of Medicine, New Zealand), P Ellwood (Department of Paediatrics, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand), S Foliaki* (Centre for Public Health Research, Massey University, Wellington, New Zealand), U Keil* (Institut für Epidemiologie und Sozialmedizin, der Universität Münster, Germany), C K W Lai* (Department of Medicine and Therapeutics, The Chinese University of Hong Kong, SAR China), J Mallol* (Department of Respiratory Medicine, Hospital CRS El Pino, University of Santiago de Chile, Chile), C Robertson (Department of Respiratory Medicine, Royal Children’s Hospital, Parkville, Australia), E A Mitchell (Department of Paediatrics, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand), S Montefort* (Department of Medicine, University of Malta, Malta), J Odhiambo* (Centre Respiratory Diseases Research Unit, Kenya Medical Research Institute, Nairobi, Kenya), N Pearce (Centre for Public Health Research, Massey University, Wellington, New Zealand), J Shah* (Jaslok Hospital & Research Centre, Mumbai, India), A W Stewart (School of Population Health, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand), D P Strachan (Division of Community Health Sciences, St Georges,

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University of London, London, UK), E von Mutius (Dr von Haunerschen Kinderklinik de Universität München, Germany), S K Weiland (Department of Epidemiology, University of Ulm, Germany), H Williams (Centre for Evidence Based Dermatology, Queen’s Medical Centre, University Hospital, Nottingham, UK). *Regional Coordinators.ISAAC International Data Centre—M I Asher, T O Clayton, P Ellwood, T Milne, E A Mitchell, Department of Paediatrics, and A W Stewart, School of Population Health, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand.ISAAC Phase Three principal investigators—Listed in Webtables 1 and 2.ISAAC Phase Three national coordinators—Listed in Webtables 1 and 2 marked || and †.Additional national coordinators—V Aguirre (Chile), C Lai (SAR China), J Shah (India), K Baratawidjaja (Indonesia), S Nishima (Japan), M Baeza-Bacab (Mexico), P Manning (Republic of Ireland), B Lee (Singapore), L Nilsson (Sweden).

ContributorsAll authors participated in the development, design, analysis, and interpretation of this work and in the writing of this paper.

Conflict of interest statementThe named authors declare that they have no conflict of interest.

AcknowledgmentsWe thank the children and parents who participated in ISAAC Phases One and Three; the school staff for their assistance and help with coordination; the Phase One principal investigators1 and the Phase Three principal investigators and their colleagues; the many funding bodies throughout the world that supported the individual ISAAC centres and collaborators and their meetings. The ISAAC International Data Centre was supported by 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 New Zealand Lottery Board, and Astra Zeneca New Zealand. Glaxo Wellcome International Medical Affairs supported the regional coordination and the ISAAC International Data Centre.

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and Allergies in Childhood (ISAAC): rationale and methods. Eur Respir J 1995; 8: 483–91.

2 Enarson DA. Fostering a spirit of critical thinking: the ISAAC story. Int J Tuberc Lung Dis 2005; 9: 1.

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4 ISAAC Steering Committee. Worldwide variations in the prevalence of asthma symptoms: the International Study of Asthma and Allergies in Childhood (ISAAC). Eur Respir J 1998; 12: 315–35.

5 Strachan D, Sibbald B, Weiland S, et al. Worldwide variations in prevalence of symptoms of allergic rhinoconjunctivitis in children: the International Study of Asthma and Allergies in Childhood (ISAAC). Pediatr Allergy Immunol 1997; 8: 161–76.

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8 Ellwood P, Asher MI, Björkstén B, et al. Diet and asthma, allergic rhinoconjunctivitis and atopic eczema symptom prevalence: an ecological analysis of the International Study of Asthma and Allergies in Childhood (ISAAC) data. Eur Respir J 2001; 17: 436–43.

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10 von Mutius E, Pearce N, Beasley R, et al. International patterns of tuberculosis and the prevalence of symptoms of asthma, rhinitis and eczema. Thorax 2000; 55: 449–53.

11 Burr M, Emberlin J, Treu R, Cheng S, Pearce N, and the ISAAC Phase One Study Group. Pollen counts in relation to the prevalence of allergic rhinoconjunctivitis, asthma and atopic eczema in the International Study of Asthma and Allergies in Childhood (ISAAC). Clin Exp Allergy 2003; 33: 1675–80.

12 Mitchell EA, Stewart AW, on behalf of the ISAAC Phase One Study Group. The ecological relationship of tobacco smoking to the prevalence of symptoms of asthma and other atopic diseases in children: the International Study of Asthma and Allergies in Childhood (ISAAC). Eur J Epidemiol 2001; 17: 667–73.

13 Foliaki S, Nielsen SK, Björkstén B, et al. Antibiotic sales and the prevalence of symptoms of asthma, rhinitis, and eczema: The International Study of Asthma and Allergies in Childhood (ISAAC). Int J Epidemiol 2004; 33: 558–63.

14 Anderson HR, Poloniecki JD, Strachan DP, et al. Immunization and symptoms of atopic disease in children: results from the International Study of Asthma and Allergies in Childhood. Am J Public Health 2001; 91: 1126–29.

15 Stewart AW, Mitchell EA, Pearce N, Strachan DP, Weiland SK, on behalf of the ISAAC Steering Committee. The relationship of per capita gross national product to the prevalence of symptoms of asthma and other atopic diseases in children (ISAAC).Int J Epidemiol 2001; 30: 173–79.

16 Weiland SK, Björkstén B, Brunekreef B, et al. Phase II of the International Study of Asthma and Allergies in Childhood (ISAAC II): rationale and methods. Eur Respir J 2004; 24: 406–12.

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18 Johansson SG, Bieber T, Dahl R, et al. Revised nomenclature for allergy for global use: report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol 2004; 113: 832–36.

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20 Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; 1: 307–10.

21 Zollner IK, Weiland SK, Piechotowski I, et al. No increase in the prevalence of asthma, allergies, and atopic sensitisation among children in Germany: 1992–2001. Thorax 2005; 60: 545–48.

22 Mallol J, Solé D, Asher I, Clayton T, Stein R, Soto-Quiroz M. Prevalence of asthma symptoms in Latin America: the International Study of Asthma and Allergies in Childhood (ISAAC). Pediatr Pulmonol 2000; 30: 439–44.

23 Strachan DP. Family size, infection and atopy: the first decade of the “hygiene hypothesis”. Thorax 2000; 55 (suppl 1): S2–10.

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29 Kalyoncu AF, Selcuk ZT, Enunlu T, et al. Prevalence of asthma and allergic diseases in primary school children in Ankara, Turkey: two cross-sectional studies, five years apart. Pediatr Allergy Immunol 1999; 10: 261–65.

30 Riikjärv MA, Annus T, Bråbäck L, Rahu K, Björkstén B. Similar prevalence of respiratory symptoms and atopy in Estonian schoolchildren with changing lifestyle over 4 yrs. Eur Respir J 2000; 16: 86–90.

Webtable 1: Participating centres, principal investigators, numbers of children, response rate, 12-month prevalence of asthma, allergic rhinoconjunctivitis, and eczema symptoms for each centre, by region, in both phases, average change per year and SE of the change, 6–7 year age group

Principal Investigator

Years between phases

Phase Three Asthma symptoms Allergic rhinoconjunctivitis symptoms Eczema symptoms

Number of children

Response rate (%)

Phase One

Phase Three

Change per year SE Phase

One Phase Three


One Phase Three

Change per year SE

Africa (English-speaking) Nige ria Ibadan* BO Onadeko 7.0 2396 86.2 4.8 5.6 0.10 0.19 3.7 3.6 -0.01 0.17 4.5 5.0 0.07 0.13 Region Total 7.0 2396 86.2 4.8 5.6 0.10 0.19 3.7 3.6 -0.01 0.17 4.5 5.0 0.07 0.13 Asia-Pacific Hong Kong Hong Kong YL Lau 6.0 4448 96.0 9.1 9.4 0.03 0.16 13.7 17.7 0.67 0.23 3.9 4.6 0.12 0.09 Indonesia Bandung† CB Kartasasmita 6.0 2503 88.1 4.2 2.8 -0.22 0.11 3.9 3.6 -0.04 0.12 Japan Fukuoka‡,§ H Odajima 8.0 2958 90.7 17.4 18.2 0.10 0.12 7.8 10.6 0.35 0.11 Malaysia Alor Setar¶ KH Teh 7.0 3786 84.1 6.2 5.7 -0.07 0.10 3.6 4.2 0.09 0.09 9.6 12.7 0.45 0.21 Klang Valley J de Bruyne|| 6.0 3044 78.0 7.8 7.4 -0.07 0.16 5.0 6.2 0.21 0.10 8.7 12.0 0.55 0.15 Kota Bharu BS Quah 6.0 3110 91.0 5.6 4.3 -0.21 0.11 3.8 4.2 0.06 0.08 10.2 12.9 0.46 0.16 Country Total 6.3 9940 84.1 6.5 5.8 -0.12 0.07 4.1 4.8 0.11 0.06 9.5 12.6 0.49 0.10 Singapore Singapore** DYT Goh 7.0 5389 92.0 15.7 10.2 -0.80 0.24 8.5 8.7 0.02 0.15 2.8 8.9 0.87 0.18 South Korea Provincial Korea H-B Lee|| 5.0 4258 93.8 12.4 5.6 -1.38 0.31 9.3 8.6 -0.14 0.12 8.0 10.9 0.60 0.13 Seoul H-B Lee|| 5.0 1760 97.0 15.1 6.5 -1.71 0.56 10.9 9.0 -0.38 0.28 10.7 12.0 0.28 0.24 Country Total 5.0 6018 94.7 13.3 5.8 -1.45 0.28 9.8 8.7 -0.18 0.12 8.8 11.3 0.52 0.13 Taiwan Taipei J-L Huang|| 7.0 4832 96.8 9.6 9.8 0.04 0.13 14.6 24.2 1.37 0.17 3.5 6.7 0.46 0.08 Thailand Bangkok P Vichyanond|| 6.0 4209 72.8 11.0 15.0 0.68 0.21 10.0 13.4 0.58 0.29 12.5 16.9 0.73 0.20 Chiang Mai M Trakultivakorn 6.0 3106 83.9 5.5 7.8 0.38 0.14 4.8 6.2 0.24 0.14 11.4 16.3 0.82 0.15 Country Total 6.0 7315 77.2 8.2 11.9 0.47 0.23 7.3 10.4 0.30 0.25 11.9 16.7 0.79 0.13 Region Total 6.3 43403 88.2 10.0 8.9 -0.06 0.09 8.5 10.6 0.18 0.10 8.1 11.0 0.47 0.09 Eastern Mediterranean I ran Rasht M-R Masjedi|| 6.0 3057 97.4 5.3 15.3 1.67 0.13 1.2 2.4 0.21 0.06 1.3 3.0 0.29 0.06 Tehran M-R Masjedi|| 6.0 3008 80.9 5.5 8.6 0.51 0.14 1.9 1.9 0.00 0.07 0.8 1.1 0.04 0.05 Country Total

alta 6.0 6065 88.4 5.4 12.0 1.14 0.11 1.5 2.2 0.12 0.05 1.1 2.0 0.13 0.05

M Malta†† S Montefort|| 7.0 3795 79.7 8.8 14.9 0.86 0.16 7.2 8.9 0.24 0.11 4.2 4.0 -0.03 0.07 Sultanate of Oman (Oman) Al-Khod O Al-Rawas|| 6.0 4130 97.5 7.1 8.4 0.21 0.12 6.2 7.0 0.13 0.10 4.2 4.2 0.00 0.08 Region Total 6.3 13990 88.2 6.8 11.7 0.79 0.08 4.5 5.4 0.14 0.08 2.9 3.2 0.08 0.04 Indian Sub-Continent (South-east Asia) India Jodhpur†† KC Jain 9.0 2114 70.5 3.5 2.4 -0.12 0.08 2.4 2.9 0.05 0.07 1.9 0.9 -0.11 0.05 Kottayam TU Sukumaran 7.0 2619 96.4 24.6 23.0 -0.23 0.29 9.6 8.6 -0.13 0.40 11.5 2.3 -1.32 0.16 Mumbai (16)‡‡,§§ MK Joshi 8.0 2865 95.5 3.8 2.5 -0.15 0.12 2.6 2.1 -0.07 0.05 1.9 1.8 -0.01 0.06




Number of children

Response rate (%)

Phase One

Phase Three


One Phase Three


One Phase Three

Change per year SE

Mumbai (18) AV Pherwani 8.0 4862 99.2 1.8 4.7 0.36 0.11 1.5 3.5 0.25 0.08 0.9 2.4 0.19 0.07 New Delhi (7) SK Sharma 7.0 3706 82.4 6.9 6.0 -0.12 0.24 3.4 4.5 0.15 0.08 2.8 4.2 0.21 0.08 Pune NM Hanumante 6.0 2711 90.4 2.3 4.0 0.28 0.10 1.6 1.8 0.04 0.07 1.5 2.0 0.08 0.07 Region Total 7.5 18877 89.4 6.2 6.8 0.06 0.17 3.2 3.9 0.05 0.08 3.0 2.4 0.00 0.07 Latin America Br azil São Paulo¶¶

hileD Solé|| 7.0 3047 68.2 21.3 24.4 0.44 0.20 12.5 12.0 -0.07 0.14 6.8 6.8 0.00 0.12

C Punta Arenas¶ L Amarales 7.0 3052 87.1 17.1 17.5 0.06 0.20 8.8 11.2 0.35 0.12 9.5 12.1 0.37 0.13 South Santiago P Aguilar 7.0 3075 90.4 16.9 14.7 -0.31 0.18 7.7 13.7 0.87 0.14 10.5 14.8 0.61 0.14 Valdivia|| || MA Calvo 7.0 3183 89.2 20.5 21.4 0.12 0.20 8.0 11.9 0.56 0.16 12.6 11.7 -0.13 0.13 Country Total

ica 7.0 9310 88.9 18.2 17.9 -0.06 0.12 8.2 12.3 0.56 0.08 10.9 12.9 0.26 0.08

Costa R Costa Rica**

icoME Soto-Quirós|| 8.0 3234 80.9 32.1 37.6 0.69 0.20 11.6 15.9 0.54 0.14 8.7 8.9 0.02 0.09

Mex Cuernavaca**

maI Romieu 8.0 2579 84.3 8.6 8.4 -0.03 0.11 8.6 7.2 -0.17 0.10 4.9 4.0 -0.11 0.08

Pana David-Panamá G Cukier 6.0 2942 92.5 23.5 22.7 -0.13 0.20 7.1 11.7 0.77 0.18 7.9 14.4 1.09 0.17 Region Total 7.1 21112 83.8 19.9 21.4 0.07 0.12 9.1 12.1 0.32 0.06 8.7 10.5 0.13 0.06 North America Barbados Barbados*,*** ME Howitt|| 6.0 2759 85.9 18.9 19.5 0.11 0.18 5.5 6.4 0.15 0.10 6.7 9.2 0.42 0.12 Canada Saskatoon‡‡,¶¶,** D Rennie 9.0 1255 63.3 14.1 18.2 0.47 0.15 8.2 10.8 0.29 0.12 8.7 12.0 0.36 0.12 Region Total 7.5 4014 77.3 16.8 19.1 0.32 0.12 6.6 7.8 0.21 0.07 7.6 10.1 0.39 0.08 Northern & Eastern Europe Alba nia Tiranë A Priftanji|| 5.0 2896 87.6 7.6 5.0 -0.53 0.15 4.1 3.9 -0.03 0.13 2.5 3.7 0.24 0.10 Esto nia

nd

Tallinn M-A Riikjärv|| 7.0 2385 85.6 9.3 9.6 0.05 0.11 3.5 4.2 0.11 0.08 9.8 11.5 0.24 0.12 Georgia Kutaisi M Gotua|| 7.0 2666 92.9 9.3 6.9 -0.34 0.14 3.9 2.8 -0.16 0.11 5.1 2.4 -0.39 0.16 Lithuania Kaunas*

aJ Kudzyte|| 7.0 2772 92.0 4.6 6.6 0.28 0.10 3.2 3.8 0.08 0.08 2.3 3.0 0.09 0.08

Pol Kraków G Lis|| 6.0 2497 81.3 14.3 14.5 0.02 0.20 10.2 14.5 0.72 0.17 7.3 10.4 0.51 0.14 Poznan A Brêborowicz 8.0 1999 82.8 8.1 12.5 0.54 0.13 4.6 11.1 0.81 0.10 5.4 12.9 0.94 0.11 Country Total 7.0 4496 81.9 10.9 13.6 0.38 0.13 7.2 13.0 0.78 0.11 6.3 11.5 0.77 0.08 Russia Novosibirsk*

denEG Kondiourina 6.0 2730 95.2 11.1 11.4 0.05 0.17 5.6 4.7 -0.16 0.09 9.4 6.6 -0.46 0.12

Swe Linköping*,¶¶

ineH Vogt 8.0 2089 63.8 10.3 10.2 -0.01 0.13 8.0 6.9 -0.14 0.12 19.5 22.3 0.35 0.18

Ukra Kharkiv*,††† V Ognev|| 4.0 1950 99.1 12.2 12.5 0.07 0.36 9.7 7.7 -0.51 0.28 6.2 5.3 -0.21 0.17 Region Total 6.4 21984 86.0 9.7 9.6 0.05 0.06 5.7 6.4 0.10 0.06 7.0 8.2 0.18 0.08




Number of children

Response rate (%)

Phase One

Phase Three


One Phase Three


One Phase Three

Change per year SE

Oceania Australia Melbourne‡‡,**,‡‡‡,§§§ C Robertson|| 9.0 2968 81.9 27.2 20.0 -0.80 0.16 9.8 12.9 0.34 0.11 11.1 17.1 0.67 0.11 New Zealand Auckland MI Asher|| 9.0 3541 84.6 22.5 22.4 -0.02 0.12 9.8 11.0 0.14 0.09 14.4 14.3 0.00 0.12 Bay of Plenty C Moyes 9.0 2150 79.9 24.0 23.7 -0.04 0.15 8.7 11.3 0.30 0.10 13.8 13.8 0.01 0.12 Christchurch P Pattemore 10.0 3315 86.0 27.2 22.3 -0.49 0.13 11.2 12.9 0.17 0.09 15.8 18.5 0.27 0.10 Nelson R Mackay 10.0 1867 92.0 18.7 20.2 0.15 0.13 7.5 9.3 0.18 0.11 12.0 11.6 -0.05 0.12 Country Total 9.5 10873 85.2 23.6 22.2 -0.11 0.07 9.5 11.4 0.19 0.05 14.3 15.0 0.08 0.06 Region Total 9.4 13841 84.5 24.3 21.8 -0.21 0.06 9.6 11.7 0.21 0.05 13.6 15.5 0.21 0.05 Western Europe Aus tria Kärnten*,‡,‡‡,¶¶¶ G Haidinger|| 7.0 4847 86.0 7.8 7.5 -0.05 0.08 4.7 5.7 0.14 0.07 5.1 5.8 0.10 0.07 Urfahr-Umgebung‡,***,¶¶¶ G Haidinger|| 7.0 2029 92.6 7.7 7.3 -0.05 0.14 6.0 7.1 0.17 0.12 7.3 6.6 -0.11 0.12 Country Total

um 7.0 6876 87.8 7.8 7.4 -0.05 0.07 5.1 6.1 0.15 0.06 5.7 6.1 0.05 0.06

Belgi Antwerp¶¶¶,|| || ||

yJ Weyler 7.0 5645 77.8 7.3 7.5 0.02 0.08 4.9 5.8 0.13 0.06 7.7 11.6 0.56 0.09

Germa n Münster taly

U Keil|| 5.0 3830 82.4 9.6 12.8 0.65 0.17 5.4 6.9 0.30 0.12 6.7 7.9 0.23 0.12 I Emilia-Romagna C Galassi 8.0 2265 97.0 7.4 8.9 0.19 0.10 5.4 6.4 0.13 0.08 5.4 10.3 0.61 0.10 Empoli MG Petronio 8.0 1152 91.4 8.7 9.7 0.13 0.15 4.4 6.6 0.28 0.12 5.3 8.6 0.41 0.13 Firenze E Chellini 8.0 1036 83.9 9.9 8.6 -0.17 0.19 6.3 6.4 0.01 0.13 5.5 10.0 0.56 0.15 Milano** L Bisanti 8.0 2249 96.6 7.0 7.6 0.08 0.11 5.8 7.1 0.16 0.10 6.8 10.0 0.39 0.10 Roma** F Forastiere|| 8.0 2224 86.2 7.2 8.4 0.16 0.09 5.1 6.4 0.16 0.08 5.5 10.2 0.58 0.10 Torino G Ciccone 8.0 2361 95.9 6.4 5.4 -0.13 0.10 5.1 6.2 0.13 0.10 5.5 10.6 0.64 0.12 Country Total

gal 8.0 11287 92.5 7.5 7.9 0.07 0.05 5.4 6.5 0.15 0.04 5.8 10.1 0.53 0.04

Portu Funchal¶¶ (Madeira Island) R Câmara 7.0 1819 63.5 14.7 11.0 -0.54 0.18 11.2 9.2 -0.29 0.19 12.4 10.0 -0.34 0.18 Lisbon**,¶¶ JE Rosado Pinto|| 7.0 2477 60.4 13.1 14.2 0.15 0.16 8.6 10.0 0.19 0.13 11.1 10.2 -0.12 0.16 Portimao** C Nunes 7.0 1069 83.6 11.0 13.2 0.31 0.27 5.0 7.9 0.41 0.16 2.6 8.0 0.78 0.18 Country Total

ain 7.0 5365 65.1 13.2 12.9 -0.07 0.10 8.7 9.3 0.16 0.10 9.6 9.7 0.09 0.12

Sp Bilbao** C González Díaz 7.0 3157 77.3 8.0 12.4 0.61 0.13 6.5 8.9 0.34 0.10 4.4 6.8 0.33 0.08 Cartagena** L García-Marcos|| 9.0 2948 72.3 8.4 11.1 0.30 0.09 6.7 8.1 0.15 0.08 2.7 4.5 0.21 0.05 Castellón¶ A Arnedo-Pena 8.0 3915 88.1 4.7 8.3 0.45 0.08 3.8 6.3 0.31 0.07 3.1 5.3 0.28 0.06 Madrid*,*** G Garcia Hernández 5.0 2347 89.0 6.6 9.4 0.55 0.19 8.6 11.1 0.51 0.24 4.1 6.0 0.38 0.13 Pamplona F Guillén-Grima 7.0 3176 78.7 3.5 7.1 0.51 0.08 3.6 6.6 0.43 0.08 3.2 7.0 0.54 0.08 Valencia**,¶¶ MMM Suárez-Varela 8.0 3398 64.5 6.2 9.3 0.39 0.09 4.4 7.5 0.39 0.07 3.2 5.9 0.33 0.06 Country Total UK

7.3 18941 77.2 6.2 9.5 0.44 0.05 5.4 7.9 0.33 0.04 3.4 5.9 0.31 0.03

Sunderland MH Shamssain 5.0 1843 91.9 18.4 20.9 0.50 0.30 9.8 10.1 0.05 0.24 13.0 16.0 0.60 0.28 Region Total 7.2 53787 80.6 8.1 9.7 0.20 0.03 5.7 7.3 0.22 0.02 5.8 8.3 0.33 0.03 Global Total 7.1 193404 84.8 11.1 11.6 0.13 0.04 6.6 8.3 0.17 0.03 6.9 8.6 0.21 0.03

*Phase One data not published in Phase One papers. †Eczema symptoms data not available for Phase One. ‡Ethics approval not sought. §Eczema data excluded due to incorrect translation. ¶No ethics committee available to review study design. ||ISAAC National Coordinator. **Sampling at different times of the year in Phase One and Phase Three. ††Questionnaire components not administered in prescribed order. ‡‡13-14 year age group data not

available or excluded. §§<10 schools if ≥10 schools in sampling frame for Phase Three. ¶¶6–7 year age group Phase Three response rate <70%. || ||Sampling frame modified between Phase One and Phase Three. ***Data recoded to eliminate inconsistent responses. †††<5 years between Phase One and Phase Three. ‡‡‡Additional questions administered before or within ISAAC questionnaire. §§§Single data entry with no checks for Phase Three. ¶¶¶Single data entry with no checks. || || ||Different translations used for Phase One and Phase Three. Numbers in parentheses after centre names indicate ISAAC registration number for that centre as assigned by the national coordinator. Additional names in parentheses after region, country, or centre names indicate previous name as used in ISAAC Phase One publications.

Webtable 2: Participating centres, principal investigators, numbers of children, response rate, 12-month prevalence of asthma, allergic rhinoconjunctivitis, and eczema symptoms for each centre, by region, in both phases, average change per year and SE of the change, 13–14 year age group Principal

Investigator



Number of children

Response rate (%)

Phase One

Phase Three


One Phase Three


One Phase Three

Change per year SE

Africa (English-speaking) Ethiopia Addis Ababa K Melaku 8.0 3195 96.8 10.7 9.1 -0.20 0.19 10.6 9.9 -0.09 0.15 19.9 19.0 -0.12 0.18 Kenya Eldoret FO Esamai 6.0 3289 100.0 10.4 13.8 0.58 0.29 12.1 22.4 1.72 0.41 11.4 15.5 0.67 0.35 Nairobi* L Ng’ang’a† 6.0 3023 99.7 17.2 18.0 0.12 0.28 16.2 19.8 0.62 0.27 9.5 14.9 0.90 0.24 Country Total 6.0 6312 99.8 13.9 15.8 0.35 0.23 14.2 21.2 0.94 0.25 10.4 15.2 0.83 0.21 Nigeria Ibadan BO Onadeko 6.0 3142 99.7 10.7 13.0 0.38 0.33 39.7 16.4 -3.88 0.69 17.7 7.7 -1.66 0.49 South Africa Cape Town HJ Zar† 7.0 5037 83.4 16.1 20.3 0.60 0.30 15.1 20.7 0.80 0.23 8.3 13.3 0.71 0.18 Region Total 6.6 17686 94.0 13.5 15.4 0.18 0.15 18.3 18.2 0.25 0.23 12.7 14.0 0.36 0.15 Africa (French-speaking) Algeria Wilaya of Algiers‡ (West Algiers) B Benhabylès 6.0 4203 89.6 5.9 8.7 0.48 0.20 9.9 20.7 1.80 0.40 3.2 6.5 0.56 0.13 Morocco§ Casablanca|| Z Bouayad† 6.0 1777 100.0 9.9 16.0 1.03 0.36 15.5 28.1 2.11 0.47 12.0 23.0 1.83 0.36 Marrakech||,** Z Bouayad† 7.0 1689 99.9 5.6 4.4 -0.16 0.14 10.4 14.7 0.62 0.33 9.2 20.5 1.61 0.35 Country Total 6.5 3466 100.0 7.8 10.4 0.00 0.31 13.1 21.6 1.12 0.41 10.7 21.8 1.72 0.26 Tunisia Sousse‡ M Jerray 5.0 3042 99.9 8.5 11.9 0.67 1.62 35.8 23.2 -2.52 0.83 8.0 9.4 0.28 0.42 Region Total 6.0 10711 95.6 7.7 10.2 0.15 0.40 18.7 21.7 1.07 0.35 8.6 12.3 0.78 0.23 Asia-Pacific China Beijing Y-Z Chen† 7.0 3530 97.8 5.1 7.2 0.30 0.13 7.9 10.2 0.33 0.15 1.6 1.2 -0.06 0.05 Guangzhou N-S Zhong 7.0 3514 95.7 3.4 4.8 0.20 0.11 8.4 10.7 0.33 0.13 0.8 1.6 0.12 0.04 Country Total 7.0 7044 96.7 4.3 6.0 0.24 0.10 8.1 10.4 0.33 0.10 1.2 1.4 0.05 0.03 Hong Kong Hong Kong G Wong 7.0 3321 99.5 12.4 8.6 -0.55 0.11 24.0 22.6 -0.21 0.32 2.7 3.3 0.08 0.07 Indonesia Bandung CB Kartasasmita 6.0 2826 99.6 2.1 5.2 0.52 0.19 5.3 4.8 -0.08 0.17 1.2 2.2 0.16 0.08 Japan Fukuoka††,‡‡ H Odajima 8.0 2520 94.6 13.4 13.0 -0.05 0.21 14.9 17.6 0.34 0.16 Malaysia Alor Setar|| KH Teh 7.0 2941 91.3 8.9 9.3 0.05 0.25 16.7 16.3 -0.06 0.38 9.7 12.2 0.36 0.27 Klang Valley** J de Bruyne† 6.0 3025 91.0 12.3 11.6 -0.11 0.24 14.6 19.8 0.87 0.27 9.3 9.2 -0.02 0.28 Kota Bharu BS Quah 6.0 2989 92.4 6.9 5.8 -0.20 0.15 9.7 12.5 0.46 0.31 7.2 8.5 0.22 0.35 Country Total 6.3 8955 91.5 10.1 8.9 -0.13 0.15 13.9 16.2 0.53 0.20 8.9 9.9 0.19 0.17 Philippines Metro Manila††,§§,¶¶ F Cua-Lim† 7.0 3658 77.5 12.3 8.4 -0.55 0.24 15.3 11.0 -0.61 0.33 5.2 7.8 0.37 0.13 Singapore Singapore DYT Goh 7.0 4217 93.9 9.8 11.4 0.24 0.21 15.1 16.5 0.20 0.22 7.4 9.2 0.25 0.09 South Korea Provincial Korea H-B Lee† 5.0 7375 96.3 7.5 8.5 0.21 0.13 10.0 11.5 0.30 0.15 3.5 5.7 0.46 0.09




Number of children

Response rate (%)

Phase One

Phase Three


One Phase Three


One Phase Three

Change per year SE

Seoul H-B Lee† 5.0 2888 96.7 8.3 9.1 0.16 0.23 10.7 11.9 0.24 0.23 4.6 5.7 0.23 0.15 Country Total 5.0 10263 96.4 7.7 8.7 0.20 0.11 10.2 11.6 0.28 0.12 3.8 5.7 0.39 0.08 Taiwan Taipei J-L Huang† 6.0 6378 95.9 5.4 7.0 0.26 0.07 11.7 17.8 1.02 0.19 1.4 4.1 0.45 0.05 Thailand Bangkok P Vichyanond† 6.0 4669 93.8 13.5 13.9 0.06 0.25 15.4 23.9 1.41 0.50 6.8 10.4 0.60 0.18 Chiang Mai M Trakultivakorn 6.0 3538 95.7 12.6 8.7 -0.65 0.32 15.6 17.2 0.26 0.51 9.6 8.6 -0.16 0.30 Country Total 6.0 8207 94.6 13.1 11.6 -0.21 0.22 15.5 21.0 0.84 0.37 8.2 9.6 0.39 0.17 Region Total 6.4 57389 93.9 8.7 8.8 0.07 0.07 13.1 15.1 0.32 0.11 4.7 6.3 0.17 0.07 Eastern Mediterranean Iran Rasht|| || M-R Masjedi† 7.0 3004 99.8 9.7 15.6 0.85 0.33 5.9 7.2 0.18 0.18 3.1 4.5 0.21 0.13 Tehran M-R Masjedi† 6.0 3119 99.8 12.4 10.9 -0.24 0.25 9.3 12.3 0.50 0.21 2.1 4.3 0.36 0.11 Country Total 6.5 6123 99.8 10.9 13.2 0.17 0.21 7.5 9.8 0.31 0.16 2.6 4.4 0.30 0.09 Kuwait Kuwait||,|| ||,*** JA al-Momen 6.0 2882 91.6 17.1 7.6 -1.59 0.47 12.6 10.7 -0.32 0.31 8.4 6.1 -0.38 0.26 Malta Malta††† S Montefort† 7.0 4136 90.0 16.0 14.6 -0.20 0.18 29.0 20.9 -1.15 0.39 7.7 5.4 -0.33 0.14 Pakistan Karachi N Mahmood† 6.0 2999 96.0 8.5 11.7 0.53 0.49 18.1 16.8 -0.22 0.51 9.6 13.2 0.61 0.37 Sultanate of Oman (Oman) Al-Khod O Al-Rawas† 6.0 3747 97.2 8.9 8.4 -0.08 0.21 11.4 15.2 0.63 0.23 4.7 7.1 0.39 0.14 Region Total 6.3 19887 95.4 12.0 11.6 -0.10 0.13 15.4 14.3 0.18 0.25 5.5 6.7 0.17 0.10 Indian Sub-Continent (South-east Asia) India Borivali** VA Khatav 8.0 1004 99.9 3.4 1.5 -0.24 0.17 3.2 3.9 0.09 0.21 1.7 0.9 -0.09 0.11 Chandigarh L Kumar 6.0 3122 99.4 4.2 5.5 0.23 0.13 5.4 13.6 1.37 0.26 3.5 3.6 0.02 0.17 Chennai (3)** (Madras (3)) G Setty 7.0 2181 94.8 6.0 3.5 -0.37 0.18 3.2 5.6 0.34 0.20 1.6 1.2 -0.05 0.07 Jodhpur¶ KC Jain 9.0 2341 79.6 10.8 5.3 -0.62 0.38 9.2 13.0 0.43 0.27 6.2 2.7 -0.39 0.35 Kottayam TU Sukumaran 7.0 3685 98.5 17.8 15.4 -0.35 0.52 21.4 13.2 -1.16 0.34 20.5 9.3 -1.61 0.35 Mumbai (18) AV Pherwani 7.0 2982 99.4 3.6 4.6 0.13 0.19 3.4 6.3 0.41 0.28 1.8 1.4 -0.06 0.20 New Delhi (7) SK Sharma 6.0 3469 86.7 13.0 5.3 -1.28 0.33 10.4 11.6 0.20 0.34 5.5 3.5 -0.33 0.14 Pune§§,|| || NM Hanumante 7.0 1983 70.8 1.8 2.8 0.14 0.08 1.6 5.1 0.51 0.08 0.6 2.1 0.22 0.08 Region Total 7.1 20767 90.6 6.7 6.4 0.02 0.14 6.3 10.0 0.43 0.14 4.3 3.7 -0.03 0.12 Latin America Argentina Córdoba‡ CE Baena-Cagnani† 5.0 3445 99.4 11.2 13.6 0.48 0.24 17.4 16.9 -0.09 0.36 7.4 6.3 -0.23 0.22 Brazil Curitiba N Rosário 6.0 3628 90.5 18.4 18.9 0.09 0.25 14.1 17.0 0.47 0.25 3.9 3.7 -0.04 0.10 Porto Alegre|| || GB Fischer 9.0 3007 97.0 24.7 18.2 -0.72 0.17 17.6 14.2 -0.38 0.12 4.8 4.1 -0.08 0.07 Recife‡‡‡ M de Britto 8.0 2865 95.5 19.7 19.1 -0.07 0.23 11.3 14.2 0.36 0.15 4.6 4.8 0.03 0.09 Salvador|| || L de Freitas Souza 7.0 3020 80.5 27.0 24.6 -0.33 0.58 25.0 21.1 -0.56 0.59 9.2 5.1 -0.58 0.13 São Paulo¶¶,|| || D Solé† 7.0 3161 96.5 23.3 18.7 -0.65 0.22 12.6 12.1 -0.07 0.18 3.7 3.5 -0.02 0.09 Country Total 7.4 15681 91.5 22.7 19.9 -0.42 0.17 16.2 15.8 -0.05 0.19 5.3 4.2 -0.08 0.05 Chile Punta Arenas|| L Amarales 7.0 3044 89.6 7.8 13.6 0.83 0.16 9.6 14.1 0.64 0.14 6.4 13.2 0.97 0.17 South Santiago P Aguilar 6.0 3026 84.8 11.1 17.0 0.98 0.20 12.7 26.3 2.27 0.31 10.9 22.0 1.86 0.31




Number of children

Response rate (%)

Phase One

Phase Three


One Phase Three


One Phase Three

Change per year SE

Valdivia§§§ MA Calvo 7.0 3105 94.1 11.5 16.0 0.63 0.24 9.8 26.3 2.35 0.30 11.4 13.1 0.25 0.21 Country Total 6.7 9175 89.3 10.2 15.5 0.84 0.13 10.7 22.2 1.12 0.19 9.6 16.1 0.86 0.16 Costa Rica Costa Rica§§,|| || ME Soto-Quirós† 8.0 2436 69.6 23.7 27.3 0.46 0.24 14.3 17.7 0.43 0.16 7.2 6.3 -0.11 0.11 Mexico Cuernavaca|| || I Romieu 8.0 1431 85.9 6.6 11.6 0.63 0.13 9.4 7.1 -0.28 0.13 4.4 2.8 -0.20 0.09 Panama David-Panamá G Cukier 6.0 3183 92.9 17.6 22.9 0.88 0.19 9.4 11.7 0.40 0.18 7.8 14.5 1.11 0.17 Paraguay Asunción|| JA Guggiari-Chase 5.0 3000 99.3 19.4 20.9 0.31 0.32 34.5 45.1 2.12 0.62 10.8 17.7 1.38 0.35 Peru Lima P Chiarella† 6.0 3022 99.2 26.0 19.6 -1.06 0.57 19.4 18.7 -0.12 0.34 8.2 10.5 0.38 0.21 Uruguay Montevideo D Holgado† 8.0 3177 90.8 19.0 17.9 -0.13 0.20 16.0 10.6 -0.67 0.18 7.2 5.2 -0.25 0.14 Region Total 6.9 44550 90.9 17.8 18.8 0.32 0.10 15.5 18.5 0.17 0.13 7.2 9.0 0.01 0.07 North America Barbados Barbados‡,§§,|| || || ME Howitt† 5.0 2498 70.6 17.7 20.8 0.62 0.44 11.0 11.8 0.16 0.25 5.0 7.0 0.40 0.19 USA Seattle|| || GJ Redding 8.0 2422 86.6 22.9 22.3 -0.07 0.27 13.4 19.1 0.71 0.28 8.5 8.3 -0.03 0.11 Region Total 6.5 4920 77.6 19.7 21.5 0.12 0.24 11.9 15.4 0.41 0.22 6.4 7.6 0.08 0.10 Northern & Eastern Europe Albania Tiranë A Priftanji† 6.0 2983 86.6 2.6 3.4 0.12 0.09 4.0 5.5 0.24 0.15 0.8 2.0 0.19 0.06 Estonia Tallinn M-A Riikjärv† 7.0 3603 93.3 8.6 9.3 0.09 0.13 4.7 6.3 0.22 0.09 6.6 8.7 0.29 0.13 Finland Kuopio County J Pekkanen† 7.0 3051 98.8 13.1 19.0 0.84 0.19 15.3 15.5 0.04 0.17 13.2 15.6 0.34 0.17 Georgia Kutaisi M Gotua† 7.0 2650 88.9 3.6 5.1 0.21 0.13 4.5 4.5 -0.01 0.11 2.8 1.8 -0.14 0.08 Latvia Riga V Svabe 10.0 1283 94.8 8.3 10.5 0.22 0.14 5.3 4.5 -0.08 0.07 5.2 3.4 -0.19 0.09 Lithuania Kaunas‡ J Kudzyte† 6.0 2723 90.5 8.2 6.7 -0.24 0.22 5.6 4.6 -0.17 0.15 1.7 1.8 0.02 0.07 Poland Kraków G Lis† 7.0 2545 95.4 7.5 9.4 0.27 0.17 11.8 19.3 1.07 0.19 4.6 8.9 0.61 0.13 Poznan A Brêborowicz 8.0 1875 84.5 7.9 11.2 0.41 0.14 6.5 18.4 1.49 0.13 5.3 8.1 0.34 0.10 Country Total 7.5 4420 90.4 7.8 10.2 0.35 0.11 8.8 18.9 1.35 0.12 5.0 8.5 0.44 0.08 Romania Cluj D Dumitrascu 7.0 3019 92.8 3.0 22.7 2.81 0.23 5.2 14.3 1.29 0.17 6.3 5.4 -0.13 0.17 Russia Novosibirsk‡ EG Kondiourina 6.0 3769 97.2 9.9 11.2 0.22 0.21 7.8 11.7 0.65 0.15 4.9 3.8 -0.18 0.12 Sweden Linköping††† H Vogt 8.0 2679 81.2 12.6 9.7 -0.36 0.13 11.1 10.4 -0.09 0.15 15.8 12.9 -0.37 0.13 Ukraine Kharkiv‡,¶¶¶ V Ognev† 4.0 2428 98.9 12.9 20.9 2.01 0.55 11.2 11.2 -0.01 0.53 5.3 5.7 0.11 0.23 Region Total 6.9 32608 91.8 8.1 11.6 0.26 0.09 7.7 10.5 0.28 0.08 6.0 6.6 0.06 0.07




Number of children

Response rate (%)

Phase One

Phase Three


One Phase Three


One Phase Three

Change per year SE

Oceania New Zealand Auckland MI Asher† 8.0 2870 92.3 26.5 22.5 -0.51 0.34 18.9 18.8 -0.01 0.24 12.4 8.9 -0.43 0.21 Bay of Plenty**,§§ C Moyes 9.0 1976 76.2 29.5 20.6 -0.98 0.21 18.7 15.3 -0.38 0.15 13.8 8.1 -0.62 0.20 Christchurch P Pattemore 10.0 3116 88.2 29.6 27.9 -0.17 0.23 19.4 15.9 -0.36 0.18 12.3 7.0 -0.52 0.11 Nelson R Mackay 10.0 2305 90.5 31.0 28.0 -0.29 0.19 17.4 15.3 -0.21 0.29 12.8 7.5 -0.53 0.15 Wellington N Pearce 8.0 3050 96.9 31.7 32.6 0.11 0.25 19.8 23.2 0.43 0.18 13.2 12.1 -0.13 0.14 Region Total 9.0 13317 89.2 29.7 26.7 -0.39 0.13 19.1 18.0 -0.13 0.10 12.9 8.8 -0.44 0.08 Western Europe Austria Urfahr-Umgebung|| || ||,**** G Haidinger† 8.0 1439 86.0 11.8 15.1 0.41 0.20 9.2 9.7 0.06 0.17 5.3 7.5 0.28 0.13 Belgium Antwerp¶¶,|| ||,†††† J Weyler 7.0 3250 96.6 12.0 8.3 -0.52 0.17 14.5 16.9 0.34 0.18 6.7 7.2 0.07 0.11 Channel Islands Guernsey P Standring 5.0 1248 90.2 35.0 26.5 -1.70 0.52 17.7 16.3 -0.29 0.31 15.1 11.2 -0.78 0.29 Jersey§§,‡‡‡‡ R Goulding 6.0 773 78.1 35.2 26.5 -1.44 0.77 16.9 12.9 -0.66 0.34 18.9 10.7 -1.37 0.33 Country Total 5.5 2021 85.1 35.1 26.5 -1.62 0.44 17.3 15.0 -0.45 0.21 17.0 11.0 -1.04 0.23 Germany Münster U Keil† 5.0 4132 93.9 14.2 17.5 0.68 0.21 14.4 15.0 0.12 0.17 7.1 7.7 0.12 0.12 Isle of Man Isle of Man A Steriu 6.0 1716 88.7 33.4 31.2 -0.36 0.30 20.1 20.2 0.02 0.28 15.6 11.1 -0.76 0.23 Italy Cosenza|| ||,‡‡‡‡ E Bonci 8.0 925 88.1 7.1 4.1 -0.38 0.23 12.7 9.3 -0.43 0.35 4.4 3.6 -0.10 0.11 Emilia-Romagna C Galassi 8.0 1347 94.9 10.4 8.1 -0.29 0.14 15.7 13.5 -0.27 0.16 6.9 8.8 0.23 0.13 Empoli MG Petronio 8.0 1229 91.7 13.5 7.6 -0.73 0.21 15.8 12.2 -0.45 0.32 4.9 5.2 0.04 0.15 Firenze E Chellini 8.0 1383 88.4 10.5 8.7 -0.22 0.18 18.4 15.7 -0.34 0.28 5.9 8.0 0.27 0.18 Milano|| || L Bisanti 8.0 1410 96.6 10.6 8.9 -0.21 0.17 16.4 18.5 0.27 0.33 7.0 8.4 0.18 0.11 Roma|| || F Forastiere† 8.0 1325 93.3 9.8 11.4 0.20 0.18 14.7 22.2 0.93 0.22 4.9 7.8 0.37 0.11 Siena P Sestini 8.0 1082 91.6 13.0 10.5 -0.30 0.26 17.6 20.0 0.29 0.27 7.4 10.0 0.33 0.27 Torino G Ciccone 8.0 1180 98.5 8.6 10.9 0.29 0.22 15.1 17.5 0.30 0.27 9.4 10.3 0.10 0.23 Trento S Piffer 7.0 1311 87.5 5.9 4.1 -0.26 0.11 9.0 9.8 0.11 0.16 5.6 6.7 0.16 0.12 Country Total 7.9 11192 92.3 9.4 8.4 -0.22 0.07 14.3 15.5 0.07 0.10 6.2 7.7 0.16 0.05 Portugal Funchal§§ (Madeira Island) R Câmara 7.0 3161 73.2 10.6 9.0 -0.23 0.16 7.7 8.7 0.15 0.18 5.4 4.5 -0.13 0.13 Lisbon§§ JE Rosado Pinto† 9.0 3024 77.5 11.1 14.6 0.40 0.12 6.5 10.5 0.44 0.09 4.0 5.6 0.17 0.07 Portimao|| || C Nunes 8.0 1109 85.6 8.1 9.7 0.20 0.21 8.8 7.1 -0.21 0.30 1.8 4.9 0.38 0.12 Porto JM Lopes dos Santos 7.0 3336 89.7 7.4 13.1 0.82 0.16 6.2 10.3 0.57 0.13 4.4 5.3 0.13 0.08 Country Total 7.8 10630 80.3 9.5 12.0 0.32 0.09 7.0 9.5 0.40 0.08 4.4 5.1 0.16 0.05 Republic of Ireland Republic of Ireland§§§§ L Clancy 8.0 3089 90.9 29.1 26.7 -0.30 0.19 19.3 15.5 -0.48 0.19 13.6 8.6 -0.62 0.11 Spain Barcelona RM Busquets 9.0 3066 87.6 14.3 9.0 -0.59 0.13 11.7 10.5 -0.14 0.13 3.9 2.6 -0.14 0.06 Bilbao|| || C González Díaz 7.0 3401 89.4 11.9 13.7 0.26 0.17 17.2 14.5 -0.38 0.21 4.5 4.0 -0.07 0.08 Cartagena|| || L García-Marcos† 9.0 3998 79.6 10.5 10.7 0.01 0.12 16.8 15.6 -0.14 0.16 5.8 4.0 -0.20 0.08 Castellón|| A Arnedo-Pena 8.0 4024 91.2 7.1 7.1 0.00 0.10 13.4 15.9 0.31 0.20 2.9 4.1 0.15 0.07 Madrid‡,|| || || G Garcia Hernández 5.0 2652 93.2 7.6 10.1 0.49 0.25 13.1 18.7 1.11 0.44 3.8 5.2 0.30 0.13 Pamplona F Guillén-Grima 7.0 2932 82.6 5.5 8.0 0.36 0.13 14.6 15.8 0.16 0.22 4.2 4.0 -0.02 0.08




Number of children

Response rate (%)

Phase One

Phase Three


One Phase Three


One Phase Three

Change per year SE

Valencia§§ MM Suárez-Varela 8.0 3132 78.3 11.0 10.3 -0.09 0.14 12.0 12.6 0.08 0.14 3.3 4.1 0.10 0.06 Valladolid A Blanco Quirós 8.0 2944 91.0 6.1 8.2 0.25 0.11 12.7 17.1 0.55 0.13 4.6 4.5 -0.01 0.07 Country Total 7.6 26149 86.1 9.3 9.6 0.04 0.05 13.9 15.0 0.10 0.07 4.1 4.0 -0.01 0.03 UK North Thames§§§§,** HR Anderson† 7.0 2356 87.7 30.5 26.6 -0.55 0.30 15.9 15.0 -0.14 0.24 16.0 11.2 -0.69 0.30 Scotland§§§§ JB Austin 7.0 4662 88.9 36.7 27.8 -1.28 0.23 20.3 15.1 -0.75 0.18 16.7 11.8 -0.71 0.16 South Thames§§§§,** HR Anderson† 7.0 2432 84.5 31.3 26.2 -0.74 0.48 16.6 14.5 -0.30 0.20 16.6 10.4 -0.88 0.20 Sunderland MH Shamssain 6.0 2193 91.0 19.9 16.1 -0.65 0.26 18.5 14.3 -0.69 0.29 10.9 10.3 -0.09 0.22 Surrey/Sussex D Strachan 10.0 5082 90.8 26.8 22.7 -0.41 0.17 22.5 17.6 -0.49 0.14 10.5 9.5 -0.10 0.10 Wales M Burr 7.0 2501 85.2 33.6 27.5 -0.87 0.28 18.5 12.7 -0.83 0.15 15.3 10.6 -0.67 0.19 Country Total 7.3 19226 88.4 31.0 24.7 -0.71 0.14 18.9 15.3 -0.57 0.09 14.7 10.6 -0.39 0.08 Region Total 7.4 82844 87.5 15.4 15.2 -0.07 0.10 14.4 14.5 0.02 0.05 7.7 7.1 0.00 0.04 Global Total 7.0 304679 90.9 13.2 13.7 0.06 0.05 13.6 15.1 0.18 0.04 7.0 7.6 0.06 0.03 *Data recoded to eliminate inconsistent responses for Phase Three. †ISAAC National Coordinator. ‡Phase One data not published in Phase One papers. §Country grouped in a different region in Phase One. ¶Questionnaire components not administered in prescribed order. ||No ethics committee available to review study design. **<10 schools if ≥10 schools in sampling frame for Phase Three e. ††Ethics approval not sought. ‡‡Eczema data excluded due to incorrect translation. §§13–14 year age group Phase Three response rate <80%. ¶¶Single data entry with no checks for Phase Three. || ||Sampling at different times of the year in Phase One and Phase Three. ***No date of interview or age on questionnaire. †††Additional questions administered before or within ISAAC questionnaire. ‡‡‡No date of birth on questionnaire. §§§Sampling frame modified between Phase One and Phase Three. ¶¶¶<5 years between Phase One and Phase Three. || || ||Data recoded to eliminate inconsistent responses. ****Single data entry with no checks. ††††Different translations of questionnaire used for Phase One and Phase Three. ‡‡‡‡Sample included fewer than 1000 participants for Phase Three. §§§§Additional questions administered before or within ISAAC questionnaire for Phase Three

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