INTERNATIONAL

STUDYOF

ASTHMAAND Manual

ALLERGIESIN

CHILDHOOD
2

Auckland(NZ) /Mnster(FRG)

December1993(2nd edition)
 1

INDEX Page

1.0 WhatisISAAC? 3
1.1 Purpose 3
1.2 Overviewofstudydesign 3
1.3 Requirementsforparticipants 4
2.0 Developmentandadministrationoftheproject 5
2.1 History 5
2.2 Organisationalstructure 6
2.3 Funding 9
3.0 Scientificbackground 10
3.1 Asthma 10
3.2 Rhinitis 11
3.3 Eczema 11
3.4 Significanceoftheproposedstudy 12
4.0 AimsandObjectives 12
5.0 Methods 13
5.1 Overview 13
5.2 Collaboratingcentres 13
5.2.1 Countries 13
5.2.2 Researchcentres 13
5.2.3 Investigators 13
5.3 Subjects 14
5.3.1 Selection 14
5.3.2 Ethnicgroupandgender 14
5.3.3 Samplesize 15
5.4 Studydesign 16
5.4.1 DetailsofPhaseOnecoremodules 16
5.4.2 PlansforPhaseTwoSupplementaryModules 18
5.4.3 Seasonofdatacollection 18
5.5 Nonparticipation 19
5.6 Qualitycontrol 19
6.0 Datahandlingandanalysis 19
6.1 Dataqualityandhandling 20
6.2 Analyses 21
6.3 Ownershipofdata 21
2

Page

7.0 Studyinstruments 22
7.1 Instructionsforcompletingquestionnaireanddemographicquestions
22
7.2 Module1.1Corequestionnaireforwheezingandasthma 24
7.2.1 Development,validation 26
7.3 Module1.2:Corequestionnaireforrhinitis 28
7.3.1 Questionnaires 28
7.3.2 Development,validation 30
7.4 Module1.3:Corequestionnaireforeczema 31
7.4.1 Questionnaires 31
7.4.2 Development,validation 33
7.5 Module1.4:Videoquestionnaire 35
7.5.1 Questionnaire 35
7.5.2 Development,validation 36
7.6 Furthercommentsonvalidationofinstruments 37
7.7 Presentationandtranslation 38
8.0 Ethicsandconduct 39
8.1 Ethicalcommitteeapproval 39
8.2 Modelforapproachingschools 39
8.2.1 Sampleinformationletterfor1314yearolds 39
8.2.2 Sampleinformationletterfor67yearolds 41
8.3 Modelforapproachingparents 42
8.3.1 Sample information sheet for parents/guardians of 1314 year
olds 42
8.3.2 Sampleinformationsheetforparents/guardiansof67yearolds
43
8.4 Guidelinesforfieldworkers 44
9.0 DataTransfer 46
10.0 Contactaddresses 47
11.0 Bibliography 51

1.0 WhatisISAAC?
1.1 Purpose

The aetiology of asthma and allergic disease remains poorly understood

despite considerable research. Epidemiology has the potential to add
greatlytoourunderstandingbyelucidatingtheriskfactorsforasthmaand
allergic disease and thereby suggesting productive avenues for research
intocausation.Epidemiologicalstudieshavesofarfailedtoreachtheirfull
potential because of lack of standardisation in casedefinition and
methodologywhichlimitsthevalueofspatialandtemporalcomparisons.
ISAAC,theInternationalStudyofAsthmaandAllergiesinChildhood,was
founded to maximise the value of epidemiological research into asthma
and allergic disease by establishing a standardised methodology and
facilitatinginternationalcollaboration.Itsspecificaimsareto:
1. Describe theprevalenceandseverityofasthma,rhinitisandeczema
in children living in different centres and to make comparisons
withinandbetweencountries.
2. Obtain baseline measures for assessment of future trends in the
prevalenceandseverityofthesediseases.
3. Provide a framework for further aetiological research into genetic,
lifestyle, environmental and medical care factors affecting these
diseases.

1.2 Overviewofstudydesign

TheISAACstudydesigncomprisesthreephases.PhaseIisacompulsory
core study designed to assess the prevalence and severity of asthma and
allergic disease in defined populations. Phase II, which has yet to be
developed, will investigate possible aetiological factors, particularly those
suggestedbythefindingsofPhaseI.PhaseIIIwillbearepetitionofPhaseI
afteraperiodofthreeyears.

This document is primarily concerned with Phase I. In this Phase each

researchcentreshouldrecruitarandomsampleof3000childrenaged1314
years.Childrenwillbeascertainedthroughschoolclassregistersandasked
tocompletetheISAACcorequestionnairesonasthma,rhinitisandeczema.
Casedefinitions and severity are established by asking about cardinal
4

symptoms,notbyreferencetolabelsordiagnoses(althoughthesewillbe
recorded). It is strongly recommended, but not compulsory, that the
children also complete a video questionnaire on asthma. The video
questionnaire was developed in response to translation problems with
written questionnaires and obviated the need to describe symptoms
verbally.Thevalidityoftheresearchinstrumentshasbeeninvestigated.

It is strongly recommended, but not compulsory, that each centre also

recruitanadditionalsampleof3000childrenaged67years.Childrenwill
be identified through school class registers and their parents asked to
complete the core questionnaires on asthma, rhinitis, and eczema. The
videoquestionnairewillnotbeadministeredtothisagegroup.

It is envisaged that certain research centres may wish to incorporate the

ISAACcoreprotocolintoalargerormorefocusedinvestigationofasthma
and allergy. The ISAAC core protocol has therefore been designed to
accommodate additional questionnaire material and supplementary
investigations.

A detailed description of the scientific background, protocol, and

developmentofinstrumentsisprovidedbelow.

1.3 Requirementsforparticipants
1. Prospective research centres must produce a detailed research
protocol showing how the ISAAC Phase I protocol will be
implementedlocally.Keyissuestobeaddressedinclude:themethod
for sampling schools; the geographical definition of the centre; the
approach to ethnic group comparisons if these are being made; the
seasonofdatacollection;ifappropriate,methodoftranslatingISAAC
core questionnaire into other language(s); evidence that ethical and
othernecessarypermissionshavebeengranted.
2. Eachresearchcentreisresponsibleforobtainingitsownfunding.
3. Each centre is responsible for coding and entering its own data. A
copy of the data required for international and interregional
comparisons must be made available in suitable electronic form to
theISAACexecutiveforanalysisatthedesignateddatacentre.
4. Each centre may publish its own data without the approval of
ISAAC. All publications and communications arising from
 5

comparisons of more than five international centres require the

approval of ISAAC and will be authored by ISAAC whose
participantswillbeidentified.

We invite the widest possible participation in ISAAC, and welcome

interested investigators to participate in the development of further
studies. Investigators with research experience in the epidemiology of
asthmaand/orallergicdiseasesareparticularlyencouragedtojoinISAAC.
Research centres able to access distinctive populations (by virtue of their
geography,raceand/orethniccharacteristics)aresimilarlywelcome.

2.0 Developmentandadministrationoftheproject
2.1 History

ISAAC emerged from preexisting multinational collaborations regarding

childhoodasthmaepidemiologyincluding:
October 1989 Development of standardised questionnaire for
measuring asthma prevalence in the UK (London), New Zealand
(Auckland),andAustralia(Melbourne).
May 1990 Investigators in Auckland, New Zealand, approached
experiencedinvestigatorsinfivecountriestoestablishacollaborative
group interested in conducting international comparative studies of
asthmaseverityinchildren.
December 1990 An international workshop on monitoring trends
anddeterminantsofasthmaandallergieswasconvenedinBochum,
Germany.InterestedresearchersfromGermany,UK(London),New
Zealand(Wellington),andtheUSAestablishedacollaborativegroup
todevelopastandardisedprotocol.
March1991MergingoftheAucklandandBochuminitiatives.
June1991Formationofasteeringcommitteefortheorganisationof
internationalcollaborativestudiesofchildhoodasthmaandallergies.
The countries represented included New Zealand (Auckland,
Wellington),UK(London),andGermany(Bochum).
December 1991 Second international workshop on monitoring
trends and determinants of asthma and allergies was convened in
6

Bochum, Germany, to finalise a standard protocol for research.

Presentation of the pilot study involving Wellington, Bochum,
London,SydneyandAdelaide.SteeringCommitteewasextendedto
includeUSA(Tucson).
December 1992 Third International Workshop on International
StudyofAsthmaandAllergiesinChildhoodinLondon.

2.2 Organisationalstructure

Generalapproach

TheorganisationofISAACconsistsoffourlevels:
theSteeringCommittee(includingtheExecutive)
regionalcoordinators
nationalcoordinators
collaboratingcentres

Thegeneralapproachisthat,inaparticularregion,aregionalcoordinator
is appointed by the steering committee, who then recruits national
coordinators. A regional meeting of national coordinators is held to
organise the implementation of Phase I in the region. The national
coordinatorsthencompletetherecruitmentofcollaboratingcentresintheir
own countries and a national meeting is held prior to the start of data
collection.Thisgeneralapproachisflexible.Forexample,manyEuropean
centreshavealreadystarteddatacollection,orareabouttostart,andsome
instancesanationalmeetinghasalreadybeenheld.

Collaboratingcentres

Theresponsibilitiesofthecollaboratingcentresareto:
completetheregistrationform
liaisewiththenationalcoordinator
carryoutPhaseIaccordingtotheprotocolinthemanual
forwardacleandatasettothenationalcoordinator
 7

Nationalcoordinators

The national coordinators are generally responsible for a single country.

However, in some instances they may be responsible for several small
neighbouring countries, particularly if these only have one collaborating
centreand/orifnosuitablenationalcoordinatorsareavailable.

Theresponsibilitiesofthenationalcoordinatorsareto:
recruitandregistercollaboratingcentres
organise translation and production of the Phase I manual and
questionnaires
organise a national meeting of collaborating centres to organise the
implementationofPhaseI
liaise with the collaborating centres and provide assistance when
required,includingcleaningofthedata
liaisewiththeregionalcoordinators
check and forward the clean national data sets to the regional
coordinators
organiseafurthernationalmeetingofcollaboratingcentrestodiscuss
theresultsofPhaseI

Regionalcoordinators

Theregionalcoordinatorsareresponsibleforabroadregionoftheworld.
TheregionswillgenerallybebasedonthesixWHOregionsoftheworld,
since these are widely used and logically organised. However, in some
instances a WHO region may be split into subregions, if the number of
collaboratingcentresorcountriesislarge.
8

TheISAACregionsarecurrentlyasfollows:
WHOregion ISAACregion

Europe WesternEurope
EasternEurope/Baltics
Americas NorthAmerica
LatinAmerica
Africa Africa
SouthEastAsia SouthEastAsia
WesternPacific AsiaPacific
Oceania
EasternMediterranean EasternMediterranean

Theresponsibilitiesoftheregionalcoordinatorsareto:
recruitnationalcoordinators
help national coordinators with translation and production of the
PhaseImanualandquestionnaires,andapprovalofthefinalversion
beforeuse
organise a meeting of national coordinators to organise the
implementation of Phase I (prior to the national meetings specified
above)
assistwithnationalmeetings
liaise with national coordinators and provide assistance when
required, including official feedback from the Steering Committee,
andcheckingofnationaldatasets
liaisewiththeSteeringCommittee,andparticipateinmeetingsofthe
ExtendedSteeringCommittee
organise a further meeting of national coordinators to discuss the
resultsofPhaseIandtoplanPhaseII

TheSteeringCommittee

TheSteeringCommitteehasrecentlybeenexpandedandnowincludesthe
Regional Coordinators, and the Module Leaders (of the various Phase II
 9

modulesthatareunderdevelopment),inadditiontotheoriginalmembers
oftheSteeringCommittee.

TheresponsibilitiesoftheSteeringCommitteeare:
recruitregionalcoordinators
assistwiththeregionalmeetings
liaise with regional coordinators and provide assistance when
required
coordinatetheimplementationandconductofPhaseI
organisethefurtherdevelopmentofmodulesandmethodsforPhase
II
coordinatetheanalysesandpublicationsofdata
organisefutureinternationalISAACmeetings

ThefullSteeringCommitteewillmeetannually.

TheExecutive

TheISAACstudyiscoordinatedonadaytodaybasisbyathreemember
executive.Thecurrentexecutiveconsistsof:
Dr.InnesAsher(DataCoordination)
Prof.RichardBeasley(ImplementationofPhaseI)
Dr.DavidStrachan(MethodsDevelopment)

TheExecutiveischairedbyDr.Asher.

2.3 Funding

Each research centre is responsible for obtaining its own funding. At the
time of writing, funding has been successfully obtained from the Health
ResearchCouncilofNewZealandforthreeNewZealandcentres,fromthe
LocallyOrganisedResearchFundoftheDepartmentofHealthinEngland
foroneEnglishcentre,andfromtheMinistryforWork,HealthandSocial
Affairs of the German State of North RhineWestphalia for one German
centre.InFrancethreecentresobtainedcompleteandanotherthreecentres
obtained partial funding. In Italy two centres are funded and in Spain
10

fundinghasbeenobtainedforfourcentres.Fundingsupportisexpectedto
beobtainedinthenearfutureforanumberofothercentres.

3.0 Scientificbackground
There is considerable concern regarding a possible increase in the
prevalenceandincidenceofasthmaandallergiesinWesterncountries.

3.1 Asthma

Asthma is one of the most important diseases of childhood in developed

countries.Estimatesofthe12monthperiodprevalenceofparentreported
wheezingillnessvarygreatlybutrangefrom1015%intheUKto30%in
Australasiaandamongstthese,theproportionwithadiagnosisofasthma
ranges from 3070%. About one third of those affected by asthma
experiencerestrictionofactivitiesandlossofschool.Antiasthmaticdrugs
are the most frequently used prescribed therapy in childhood. There is
evidencethattheprevalenceandseverityofasthmaisincreasing.Hospital
admissionshaveincreasedtoagreaterdegreeinmanycountriesandthis
has been attributed both to changes in medical practice and changes in
prevalence. A number of countries experienced epidemics of mortality in
the1960sandsubsequentlyafurtherepidemicoccurredinNewZealand.

Atnationalandtoalesserextentsubnationalleveltherearegeographical
variations in prevalence, mortality and hospital admissions. The cause of
these regional variations is unknown. It is known that genetic factors
predispose to asthma and other atopic disorders but migrant studies
indicate that the reasons for regional variations are environmental rather
than genetic. An environmental factor might act either by inducing the
asthmatictendencyinageneticallysusceptibleindividualorbyinciting
attacks in individuals who have become asthmatic. Little is known about
inducing factors and while something is known about inciting factors
(infection, allergens, inhaled irritants, emotion, exercise), their role in
explaining regional differences is obscure. There is general concern that
factorsassociatedwithmodernlifestyleandenvironment(e.g.airpollution
ordiet)mayberesponsiblebutevidenceismeagre.Afurthercomplication
is the possibility that some forms of treatment might themselves be
increasingmortalityandmorbidity.
 11

3.2 Rhinitis

There are no widely agreed criteria for the diagnosis or classification of

noninfectious rhinitis. The principle symptoms of noninfectious rhinitis
aresneezing,runningnose(rhinorrhea),and/ornasalblockage.Patientsare
generallyclassifiedaccordingtothesuspectedaetiologyoftheircondition
into allergic and nonallergic types. Rhinitis is labelled allergic when a
causativeallergencanbeidentified.Otherwiseitislabellednonallergic.
Thisapproachtoclassificationisproblematicinthatitisimpossibletobe
certain that a nonallergic subject would not prove reactive to some
allergenyettobeexamined.

Surprisinglylittleisknownabouttheprevalenceordistributionofrhinitis.
Veryfewstudieshaveusedstandardisedcasedefinitionsandthemajority
havefocusedonhayfever(seasonalallergicrhinitis)leavingotherformsof
the condition unstudied. The estimated prevalence of hay fever among
schoolchildrenindifferentcountrieshasbeenreportedtovarybetween0.5
and 28%. There is also evidence the prevalence of hay fever may vary
between different geographical regions within countries. Britain, Sweden
and the United States have reported increases in the prevalence of
diagnosed hay fever in recent decades. Possible explanations for
differencesinprevalenceovertimeandbetweenplaces,includedifferences
in the diagnostic criteria of doctors, differences in patients consulting
behaviour, and differences in putative environmental provoking factors
(e.g.aeroallergenburden,airpollution).

3.3 Eczema

Little is known about the epidemiology of eczema or atopic dermatitis.

However, geographical variations in prevalence have been described in
Britain and these closely match regional variations in hayfever. This
suggests withincountry variation in the underlying atopic tendency.
Comparisons over time in Britain and Denmark have suggested that
eczema (as reported by parents) is more common among more recent
generationsofchildren.

Intheory,eczemaismorereadilyconfirmedbyobjectiveteststhaneither
asthma or rhinitis. However, there are currently no internationally
accepted criteria for definition of atopic dermatitis. A list of major and
12

minor criteria proposed by Hanifin and Rajka in the 1970s have been
furtherevaluatedandwidelyappliedinclinicalstudiesbuthavenotbeen
definedandstandardisedinamannersuitableforepidemiologicalstudies.
A team of British dermatologists are currently developing and validating
definitions of atopic dermatitis based on questionnaire data with or
without clinical signs. The former, which correspond closely to the major
criteria proposed by Hanifin and Rajka, have been incorporated into the
initialphaseofthepresentstudy.

3.4 Significanceoftheproposedstudy

Muchresearchhasbeenconductedintothereasonswhysomeindividuals
rather than others develop asthma and other atopic diseases such as
rhinitis and eczema. The main finding has been that a family history of
atopic disease is a major risk factor. Environmental factors nevertheless
remainimportantintheexpressionofdiseasebutstudiesatanindividual
level have had rather limited value in identifying what those factors are.
Another approach is to investigate why the level of disease varies from
population to population. Factors affecting the prevalence of disease at a
populationlevelmaybedifferent.Indeedtherearesomefactorswhichcan
only be studied in this way because whole populations may be fairly
evenlyexposedtothefactor,thusprecludingepidemiologicalstudywithin
the population. There is little firm evidence concerning the reasons for
trends in atopic disease (and of atopic status per se) within populations.
Oneobstacletotheinvestigationofpopulationdifferences(andoftrends)
hasbeenthelackofasuitableandgenerallyacceptedmethodofmeasuring
the prevalence and severity of asthma and other atopic diseases in
children.Theotherobstaclehasbeentheabsenceofacoordinatedresearch
programmetoobtainandanalysecomparativedata.TheISAACstudyhas
beendevelopedtoaddressthesequestions.

4.0 AimsandObjectives
1. To describe the prevalence and severity of asthma, rhinitis and
eczema in children living in different centres and to make
comparisonswithinandbetweencountries.
2. To obtain baseline measures for assessment of future trends in the
prevalenceandseverityofthesediseases.
 13

3. To provide a framework for further aetiological research into

lifestyle, environmental, genetic and medical care factors affecting
thesediseases.

5.0 Methods
5.1 Overview

Thecollaborativestudieswillbeconductedinthreephases.PhaseIisthe
corestudydescribedindetailhere.PhaseIIinvolvesmoredetailedstudies
of aetiological factors and clinical examination of subgroups of children.
PhaseIIIwillbearepetitionofPhaseIafterthreeyears.

5.2 Collaboratingcentres

5.2.1 Countries

Thiswillbeamulticentrestudy,involvingasmanycentresandcountries
as wish to collaborate who can meet the requirements of the study
protocol. It is hoped that many countries will have at least two centres
participating to enable a within country comparison as well as between
countrycomparisons.

5.2.2 Researchcentres

An ISAAC research centre is a distinctive population in terms of its

geography, race and/or ethnic characteristics, where one or more named
investigatorshaveagreedtofollowtheISAACstudyprotocoldescribedin
thismanual.Whereexistingdatasuggestregionaldifferencesinasthmaor
allergic diseases, participation of these centres will be of particular value.
The sample of children taking part in ISAAC should not previously have
been recruited systematically for research into asthma or allergies
(although individual children may have been so involved). However,
investigators may wish to use ISAAC as the first stage in new local
researchabouttheseconditions.

5.2.3 Investigators

Investigators who have experience with asthma or its epidemiology,

especiallyinchildren,areparticularlyencouragedtojoinISAAC.
14

5.3 Subjects

5.3.1 Selection

The population of interest is school children within a given geographical

area.Arandomsampleoftwoagegroupsofchildrenwillbestudied:1314
yearoldsand67yearolds.Thesamplingunitwillbeaschoolforeachage
group. Each school in the centre which would contain the age group of
interestwillbeallocatedanumber,andtheschoolswillbeselectedusinga
table of random numbers. Sampling of each age group will be separate.
Once a school has been chosen, two school years will be chosen which
includethosewiththegreatestproportionof13yearoldsand14yearolds;
those with the greatest proportion of 6 year olds, and 7 year olds. It is
recognisedthattherewillbesomechildrenoutsidethespecifiedageranges
ineachclasschosen.Thesechildrenmaybeincludedinthedatacollection,
butwillbeexcludedfromanalysisfortheinternationalcomparison.

The younger age group has been chosen to give a reflection of the early
childhood years, when asthma is common, and admission rates are
particularly high. However some centres may not have the resources to
proceedwiththeyoungeragegroup.Theolderagegrouphasbeenchosen
toreflecttheperiodwhenmortalityfromasthmaismorecommon.School
childrenarethemostaccessiblepeopleofanyagegroup.

A minimum of 10 schools (or all the schools) per centre are needed to
obtain a representative sample. If a selected school refuses participation,
thentheschoolwillbereplacedbyanotherchosenatrandom.Noeligible
childrenwillbeexcludedfromthesample.

If a school for disabled children (e.g. blind, intellectually handicapped) is

chosen, they will be studied. However it is acknowledged that there may
beadisproportionatenumberofchildrenofthe1314yearagegroupwho
are unable to participate in such a school. This would be one reason for
nonparticipation.

5.3.2 Ethnicgroupandgender

Where comparisons between ethnic groups are planned, the question on

ethnicity should preferably follow that used in the most recent Census of
 15

Populations in the individual centre. There will be a question to identify

thegenderofthechild.

5.3.3 Samplesize

The aim is to detect differences, if they exist, which are meaningful

clinically,epidemiologically,economicallyandforhealthservicedelivery.
The sample size required to detect differences in severity of asthma is
higher than that required to detect the same magnitude in differences in
prevalence of asthma because severe asthma is less common. The sample
size estimates are stringent because of the number of hypotheses being
tested and the need to be certain of the results in such a major study. A
samplesizeof3000hasbeenchosen,whichgivesthefollowingpower:
1. Prevalenceofwheezing
Ifthetrueoneyearprevalenceofwheezingis30%inonecentreand25%in
another centre, with a sample size of 3000, the study power to detect this
differencewillbe99%atthe1%levelofsignificance.
2. Severityofwheezing
Ifthetrueoneyearprevalenceofsevereasthmais5%inonecentreand3%
inanothercentrewithasamplesizeof3000thestudypowertodetectthis
differencewillbe90%atthe1%levelofsignificance.

It is recognised that some centres may have limited resources or

populationsbutitisneverthelessdesirableforthemtobeincludedinthe
prevalence comparisons. Centres with sample sizes in the range of 1000
2999 will only be included in the prevalence comparisons but not the
severity comparisons. This summary table of sample size and power
considerations shows the effect of changing sample size on the power of
detectingdifferencesintheprevalenceofasthma:
16

Samplesizeandpowerconsiderations
Table1a
Prevalenceoftroublesomeasthma
POWER(%) Differencebeingtested
(significancelevel1%)
Samplesize 5%v3% 5.5%v3% 6%v3% 6%v4%
3000 90 98 99 82
2500 83 95 99 72
2000 71 89 97 60
1500 55 70 90 44
1000 34 53 71 26

Table1b
Severityofsleepdisturbanceduetowheezing
Samplesize Differencebeingtested
(significancelevel1%) (%populationwhoareinadifferentresponse
category,e.g.neverwokenwithwheeze,woken
lessthanonenightperweek)
Power(%) 20% 25% 30%
90 3000 2100 1500
80 2500 1700 1200
70 2150 1400 1000
60 1800 1200 900

5.4 Studydesign

5.4.1 DetailsofPhaseOnecoremodules

Three one page questionnaires have been developed by the current

collaborators. These were agreed for use at the International Study of
AsthmaandAllergiesinChildhoodataworkshopinBochum,Germany,8
10 December 1991. The aim of compiling a core questionnaire is to
ensure that comparable information on the basic epidemiology of
wheezing illness and its diagnosis is obtained from as many surveys as
possible. The exact wording of questions follows, as far as possible,
 17

questions which have been used on published questionnaires and which

havefounddifferencesbetweenpopulations.

Itisanticipatedthatindividualinvestigatorsmaywishtosupplementthem
with questions of their own, but they should endeavour to retain the
general form of the questionnaire, including the flow and stemming, as
indicated.Anyadditionalquestionsshouldcomeattheendofthefourcore
modules. Consideration must be given to the effect this may have on
participation.

In Section 7, the core questionnaires are presented, along with a

commentaryabouttheirdevelopmentandvalidation.The1314yearolds
willbepresentedwiththewrittenquestionnairesonwheezing,rhinitisand
eczema, and if feasible, the video questionnaire. Investigators are also
encouraged to recruit the sample of 67 year olds, whose parents will be
asked to complete the appropriate written questionnaires on wheezing,
rhinitisandeczema.Thefollowingoutlinesummarisesthisdesign:

PhaseIModules 1314years 67years

1.1Corequest.onwheezing compulsory stronglyrecommended

1.2Corequest.onrhinitis compulsory stronglyrecommended

1.3Corequest.oneczema compulsory stronglyrecommended

1.4Videoquest.onwheezing stronglyrecommended notused

18

5.4.2 PlansforPhaseTwoSupplementaryModules

The December 1992 London meeting established working groups with a

coordinator to develop the instruments for Phase II. This manual covers
only Phase I, but collaborators are invited to contribute to the design of
PhaseIIinstruments.Itisenvisagedthattherewillbeatleastthefollowing
modules:

Module2.1: Management medications

healthservicedelivery

Module2.2: Indoorenvironmentalriskfactors
physicalconditions
chemicalirritants
allergens

Module2.3: Otherrespiratorysymptoms

Module2.4: Bronchialresponsivenesstesting

Module2.5: Skintestsforatopy

Module2.6: SerumIgE

Module2.7: Physicalexamination

Developmentofthesemoduleswillincludepilotstudiesinsomecentres.

It is anticipated that there will be future phases of the study, probably

including the following: repeat prevalence and severity studies; cohort
followupstudies;casecontrolstudies.

5.4.3 Seasonofdatacollection

It is recognised that the season of the year may influence the reported
prevalence of symptoms of rhinitis or eczema. However there is little
evidence that the reported one year prevalence of symptoms of asthma
varies over seasons from studies which have included Autumn, Winter,
and Spring. Analysis of data inadults (Wellington, New Zealand), young
adults (London, United Kingdom) and in children (Munich, Federal
 19

Republic of Germany) shows no significant monthly variation in the

reported one year prevalence. The date of data collection must be
documented and at least half of the study population should be
investigatedbeforethemainpollenseasonofthestudyarea.

5.5 Nonparticipation

A participation rate of at least 90% will be sought. It is a concern that

absent children may be away from school because of asthma or allergies.
Thereforestrenuouseffortsneedtobemadetocontactthesechildrenand
offer the opportunity of participation in the study. In the case of children
whereconsenthasbeenrefused,demographicdata(age,sex,ethnicgroup)
fromtheschoolwillbesought.

In the case of the younger age group, if the initial questionnaire is not
returnedwithinoneweek,theinformationletterandquestionnairewillbe
sentagain.

5.6 Qualitycontrol

Thereisparticularimportanceattachedtothequalityofthedatacollection
and procedures in ISAAC, so that there will be confidence in the results.
Prospective research centres must produce a detailed research protocol
showinghowtheISAACPhaseIprotocolwillbeimplementedlocally.Key
issues to be addressed include: the method for sampling schools; the
geographical definition of the centre; the approach to ethnic group
comparisons if these are being made; the season of data collection; if
appropriate, method of translating ISAAC core questionnaire into other
language(s); evidence that ethical and other necessary permissions have
been granted. In addition, a statement should be included indicating the
intenttoachieveahighparticipationrateandnomorethan5%ofthedata
missingfromthecompletedquestionnaireforms.

6.0 Datahandlingandanalysis
Eachgroupofsubjectswillbetreatedseparately:67yearolds,1314year
olds,andsubjectsofeachethnicgroupwhereamajorcomparisonisbeing
made (sample size 3000 for each ethnic group). Each parameter of
20

prevalence and severity will be compared between locations. The cluster

effectisnotexpectedtobegreat,butwillbeadjustedforintheanalysis.

6.1 Dataqualityandhandling

The completed questionnaire must not be changed under any

circumstances.Datashouldbeenteredonthecomputerexactlyasrecorded
on the completed questionnaire. Any changes to data entered should be
done so for an explicit reason and documented. Those changes should be
madetoacopyoftheoriginalcomputerdatafile.

Ifquestions1and2arenotcompletedinthewheezingquestionnaire,that
questionnairewillbeexcludedfromanalysis,butallavailabledatashould
stillbeenteredonthecomputer.Acodingmanualisnecessarysothatthe
corequestionswillbecodedinastandardmanner(seeSection9).

A scheme to handle blank or inconsistent stem and branch questions will

bedevelopedsothatasingledenominatorforprevalencecanbeused.This
willassumethatparentsofsymptomaticchildrenwillbeunlikelytoleave
questionsblankandthatthecategoryinthelast12monthsinabranch
questionoverridesanegativeorblankstem.Arangecheckwillbeusedto
identifyanyotherinconsistency.

Each centre will be responsible for coding its own data and data entry,
althoughinsomeregions/countriesonecentremaytakeresponsibilityfor
this. One Data Centre will be chosen for the international comparison of
the core data set. Data will be sent to the Data Centre as ASCII files in
standard format, detailed in the coding manual; data on disks will be
returned to each centre for their own use. A copy of data required for
international comparisons will be retained in the DataCentre for analysis
alongwithdatareceivedfromtheothercentres.Datawillbeenteredona
PCwiththerequisitecapacityandmemory,interfacingwithamainframe
for more complex analyses. The results of data analyses will be
communicated to the other centres as information is produced, and input
on the data analyses will be sought from the other collaborators.
Collaborators are encouraged to visit the Data Centre and work with its
staffoncollaborativeanalyses.
 21

6.2 Analyses

The objective of the study is to describe the prevalence and severity of

asthma, rhinitis and eczema in children living in different centres and to
makecomparisonswithinandbetweencountries(Seesection4,Part1).

Basicdescriptivesummariesofthedatawillbecompiledandpresentedin
an ISAAC Data Book. This Data Book will be the basic reference for the
whole study and will describe prevalence and severity of asthma, rhinitis
and eczema in both age groups for males and females in each of the
countriesparticipating.

Comparisonsbetweendifferentcentresontheratesofeventswillbemade
using methods appropriate to the situation. Crude rates can be compared
by using contingency tables or logistic regression. Comparison of
standardized rates or data that needs controlling for confounding will
require analysis by suitable multivariate methods (most probably logistic
regression).

The ancillary questions will be treated in the same manner as the major
questions on prevalence and severity. Summaries for each centre will be
recordedintheDataBookandcomparisonsmadeappropriately.

Datawillbeanalysedwithineachcountry(andcentreiflargeenough)as
wellastheinternationalcomparisons.Thiswillallowfortheintroduction
ofadditionalvariablesthatthecountrymayhaveincorporated.

Seasonality, methods of survey sampling, age standardisation and any

otherissueswillbeconsideredintheanalysisoftheISAACdata.

6.3 Ownershipofdata

Each centre owns their own data. However, the collaborating centres will
be recognised by the group title International Study of Asthma and
Allergies in Childhood (ISAAC). All publications and communications
involvinginternationalcomparisonswillbeauthoredbytheISAACStudy
Groupwhosecollaboratorswillbeidentified.
22

7.0 Studyinstruments
Thecontentofthequestionnaireswhichappearbelowisfixed.Seesection
7.1forfurthercomments.

7.1 Instructions for completing questionnaire and demographic

questions

Examples of instructions for completing questionnaires and demographic

questionsaregivenbelow.

13and14yearolds

On this sheet are questions about your name, school, and birth dates.
Pleasewriteyouranswerstothesequestionsinthespaceprovided.
Allotherquestionsrequireyoutotickyouranswerinabox.Ifyoumakea
mistake put a cross in the box and tick the correct answer. Tick only one
optionunlessotherwiseinstructed.
Examples of how to mark questionnaires: Age 13
years
YES NO


SCHOOL:

TODAY'S DATE:
Day Month Year

YOUR NAME:

YOUR AGE:
years

YOUR DATE OF BIRTH:

Day Month Year

(Tick all your answers for the rest of the questionnaire)

Are you: MALE FEMALE

Optional questions on ethnicity here

 23

6and7yearolds

On this sheet are questions about your childs name, school, and birth
dates.Pleasewriteyouranswerstothesequestionsinthespaceprovided.

Allotherquestionsrequireyoutotickyouranswerinabox.Ifyoumakea
mistake put a cross in the box and tick the correct answer. Tick only one
optionunlessotherwiseinstructed.
Examples of how to mark questionnaires: Age 6
years

YES NO


SCHOOL:

TODAY'S DATE:
Day Month Year

CHILDS NAME:

CHILDS AGE:
years

CHILDS
DATE OF BIRTH:
Day Month Year

(Tick all your answers for the rest of the questionnaire)

Is your child a: BOY GIRL

Optional questions on ethnicity here

24

7.2 Module1.1 Corequestionnaireforwheezingandasthma

Questionnairefor13and14yearolds

1 Haveyoueverhadwheezing Yes
orwhistlinginthechest
atanytimeinthepast? No

IFYOUHAVEANSWEREDNOPLEASESKIPTOQUESTION6

2 Haveyouhadwheezingor Yes
whistlinginthechest
inthelast12months? No

IFYOUHAVEANSWEREDNOPLEASESKIPTOQUESTION6

3 Howmanyattacksofwheezing None
haveyouhad 1to3
inthelast12months? 4to12
Morethan12

4 Inthelast12months,howoften,onaverage,has
yoursleepbeendisturbedduetowheezing?

Neverwokenwithwheezing
Lessthanonenightperweek
Oneormorenightsperweek

5 Inthelast12months,haswheezing Yes
everbeensevereenoughtolimityour
speechtoonlyoneortwo No
wordsatatimebetweenbreaths?

6 Haveyoueverhadasthma? Yes
No

7 Inthelast12months,hasyour Yes
chestsoundedwheezy
duringorafterexercise? No

8 Inthelast12months,haveyou Yes
hadadrycoughatnight,
apartfromacoughassociatedwith No
acoldorchestinfection?
 25

Questionnairefor6and7yearolds

1 Hasyourchildeverhadwheezing Yes
orwhistlinginthechest
atanytimeinthepast? No

IFYOUHAVEANSWEREDNOPLEASESKIPTOQUESTION6

2 Hasyourchildhadwheezingor Yes
whistlinginthechest
inthelast12months? No

IFYOUHAVEANSWEREDNOPLEASESKIPTOQUESTION6

3 Howmanyattacksofwheezing None
hasyourchildhad 1to3
inthelast12months? 4to12
Morethan12

4 Inthelast12months,howoften,onaverage,has
yourchildssleepbeendisturbedduetowheezing?

Neverwokenwithwheezing
Lessthanonenightperweek
Oneormorenightsperweek

5 Inthelast12months,haswheezing Yes
everbeensevereenoughtolimityour
childsspeechtoonlyoneortwo No
wordsatatimebetweenbreaths?

6 Hasyourchildeverhadasthma? Yes
No

7 Inthelast12months,hasyour Yes
childschestsoundedwheezy
duringorafterexercise? No

8 Inthelast12months,hasyour Yes
childhadadrycoughatnight,
apartfromacoughassociatedwith No
acoldorchestinfection?

26

7.2.1 Development,validation

These questions are designed as a minimum set for inclusion in self

completed or interviewadministered questionnaires used in population
surveys of respiratory disease in children. Note that enquiry about
symptoms proceeds from the relatively mild to the relatively severe, and
precedesenquiryaboutdiagnosis.

These questions (selfcomplete version) were included in a pilot study

conductedamong8,0001314yearoldsinfourcentresduring1991.

Thejustificationfortheindividualquestionsisasfollows:

Qu.1. ThisisbasedontheIUATLDquestionnaire.Itdoesnotmention
attacks of wheezing, in order to identify children with
persistent symptoms which are not obviously characterised as
episodesorattacks.Thisisseenasaverysensitivequestion.

Qu.2. Limitationtoa12monthperiodreduceserrorsofrecalland(at
leastintheory)shouldbeindependentofmonthofcompletion.
Thisisconsideredtobethemostusefulquestionforassessing
theprevalenceofwheezingillness.

Qus.3,4. These questions offer two alternative quantitative measures of

the frequency of wheezing. Problems with the concept of
attacks (see above) and difficulty in quantifying the frequency
of recurrent asthma lead to the inclusion of question 4 to
identifyandquantifypersistentwheeze.

Qu.5. There is a dearth of epidemiological information relating to

acute severe asthma, which is of direct relevance for
internationalcomparisonsofhospitaladmissionsandmortality
statistics.Thisquestionaimstofillthisgap.

Qu.6. All respondents are asked about diagnosed asthma, as

occasionally asthma may be diagnosed in the absence of
wheeze(onthebasisofrecurrentnocturnalcoughetc.).

Qu.7. Although logically this question belongs as a stem question

under number 2 (where it was used in the pilot study), it has
been found in certain Australasian surveys to identify some
 27

children who deny (or whose parents deny) wheezing or

whistlingatquestion1or2.

Qu.8. Nocturnal cough is widely accepted as an alternative

presentationofasthma,andthisquestionhasbeenincludedto
increasetheoverallsensitivityofthequestionnaire,althoughits
specificityinpopulationsurveysremainsunclear.
28

7.3 Module1.2: Corequestionnaireforrhinitis

7.3.1 Questionnaires

Questionnairefor13and14yearolds

All questions are about problems which occur when you DO NOT have a cold or the
flu.

1 Haveyoueverhadaproblemwithsneezing, Yes
orarunny,orblockednosewhenyou
DIDNOThaveacoldortheflu? No

IFYOUHAVEANSWEREDNOPLEASESKIPTOQUESTION6

2 Inthepast12months,haveyouhadaproblem Yes
withsneezing,orarunny,orblockednose
whenyouDIDNOThaveacoldortheflu? No

IFYOUHAVEANSWEREDNOPLEASESKIPTOQUESTION6

3 Inthepast12months,hasthisnoseproblem Yes
beenaccompaniedbyitchywateryeyes? No

4 Inwhichofthepast12monthsdidthis
noseproblemoccur?(Pleasetickanywhichapply)

January May September

February June October
March July November
April August December

5 Inthepast12months,howmuchdidthisnose
probleminterferewithyourdailyactivities?:

Notatall
Alittle
Amoderateamount
Alot

6 Haveyoueverhadhayfever? Yes
No

 29

Questionnairefor6and7yearolds

1 Haveyourchildeverhadaproblemwithsneezing, Yes
orarunny,orblockednosewhenhe/she
DIDNOThaveacoldortheflu? No

IFYOUHAVEANSWEREDNOPLEASESKIPTOQUESTION6

2 Inthepast12months,hasyourchildhadaproblem Yes
withsneezing,orarunny,orblockednose
whenhe/sheDIDNOThaveacoldortheflu? No

IFYOUHAVEANSWEREDNOPLEASESKIPTOQUESTION6

3 Inthepast12months,hasthisnoseproblem Yes
beenaccompaniedbyitchywateryeyes? No

4 Inwhichofthepast12monthsdidthis
noseproblemoccur?(Pleasetickanywhichapply)

January May September

February June October
March July November
April August December

5 Inthepast12months,howmuchdidthisnoseproblem
interferewithyourchildsdailyactivities?:

Notatall
Alittle
Amoderateamount
Alot

6 Hasyourchildeverhadhayfever? Yes
No

30

7.3.2 Development,validation

Theprincipalaimsareto:(1)distinguishbetweenrhiniticandnonrhinitic
individuals in the general population; (2) predict which subjects with
rhinitisarelikelytobeatopic;and(3)givesomeindicationoftheseverity
ofrhinitisamongaffectedindividuals.

Thejustificationforindividualquestionsisasfollows:

Qu.1. Thisquestionwasfoundtohaveapositivepredictivevalueof
80%indetectingrhinitisinacommunitysampleofadults(aged
1665years)insouthwestLondon.

Qu.2. Asfor1above.

Qu.3. This symptom had the highest positive predictive value (78%)
indetectingatopyamongsubjectswithrhinitis.

Qu.4. Thisquestionpermitssubjectswithrhinitistobeseparatedinto
thosewithseasonalsymptomsaloneandthosewithaperennial
problem. The method maximises precision in classification, is
devoidofsubjectivedefinitionsofseason,andcouldbeused
byanycountryregardlessofclimate.Thenumberofmonthsa
subject is affected could be used as a quantitative indicator of
severity. Seasonal exacerbations had a positive predictive
valueof71%indetectingatopyamongsubjectswithrhinitis.

Qu.5. While this is a crude qualitative measure of severity, it

correlated well with other indicators of morbidity including
reportedsymptomseverity,interferencewithspecificactivities
ofdailylivingandmedicalserviceuse.

Qu.6. Thisquestionpermitsinvestigationofthelabellingofrhinitisin
relation to the prevalence of rhinitic symptoms. The label
hayfeverhadapositivepredictivevalueof71%indetecting
atopyamongsubjectswithrhinitis.
 31

7.4 Module1.3: Corequestionnaireforeczema

7.4.1 Questionnaires

Questionnairefor13and14yearolds

1 Haveyoueverhad Yes
anitchyrashwhichwascomingand
goingforatleastsixmonths? No

IFYOUHAVEANSWEREDNOPLEASESKIPTOQUESTION6

2 Haveyouhadthisitchy Yes
rashatanytimeinthelast12months? No

IFYOUHAVEANSWEREDNOPLEASESKIPTOQUESTION6

3 Hasthisitchyrashatanytimeaffected Yes
anyofthefollowingplaces: No

thefoldsoftheelbows,behindtheknees,
infrontoftheankles,underthebuttocks,
oraroundtheneck,earsoreyes?

4 Hasthisrashclearedcompletelyatanytime Yes
duringthelast12months? No

5 Inthelast12months,howoften,onaverage,haveyou
beenkeptawakeatnightbythisitchyrash?

Neverinthelast12months
Lessthanonenightperweek
Oneormorenightsperweek

6 Haveyoueverhadeczema? Yes
No

32

Questionnairefor6and7yearolds

1 Hasyourchildeverhad Yes
anitchyrashwhichwascomingand
goingforatleastsixmonths? No

IFYOUHAVEANSWEREDNOPLEASESKIPTOQUESTION6

2 Hasyourchildhadthisitchy Yes
rashatanytimeinthelast12months? No

IFYOUHAVEANSWEREDNOPLEASESKIPTOQUESTION6

3 Hasthisitchyrashatanytimeaffected Yes
anyofthefollowingplaces: No

thefoldsoftheelbows,behindtheknees,
infrontoftheankles,underthebuttocks,
oraroundtheneck,earsoreyes?

4 Atwhatagedidthis Under2years
itchyrashfirstoccur? Age24years
Age5ormore

5 Hasthisrashclearedcompletelyatanytime Yes
duringthelast12months? No

6 Inthelast12months,howoften,onaverage,has
yourchildbeenkeptawakeatnightbythisitchyrash?

Neverinthelast12months
Lessthanonenightperweek
Oneormorenightsperweek

7 Hasyourchildeverhadeczema? Yes
No

 33

7.4.2 Development,validation

These questions are designed as a minimum set for inclusion in self

completed or interviewadministered questionnaires used in population
surveysofallergicorskindiseaseinchildren.

Itisanticipatedthatindividualinvestigatorsmaywishtosupplementthem
with questions of their own, but they should endeavour to retain the
general form of the questionnaire, including the flow and stemming, as
indicated.Notethatenquiryaboutsymptomsproceedsfromtherelatively
mildtotherelativelysevere,andprecedesenquiryaboutdiagnosis.

Thejustificationfortheindividualquestionsisasfollows:

The numbering refers to the version for completion by parents. The

questiononageatonsethasbeenexcludedfromtheselfreportedversion
becauserecallofrashesininfancybychildrenintheirteensislikelytobe
incomplete.

Qu.1. This screening question was evaluated in a UK pilot study of

factors which discriminated typical mildmoderate atopic
dermatitis from nonatopic eczema and other inflammatory
dermatoses presenting for the first time in British hospital
outpatient clinics. A positive response to this question was
obtainedforall36casesofatopicdermatitispresentingatages
519 years, and 91% of 120 cases of all ages. Taken alone,
however,ithadspecificityofonly44%atages519and48%at
allages.

Qu.2. Followingtheformofthecorequestionnairesforwheezingand
rhinitis, further enquiry focuses only on those children with
recentrashes,tominimiseproblemsofincompleteandselective
recall.

Qus.3,4. IntheUKstudy,thespecificity(i.e.thepowertoexcludenon
atopic forms of eczema and other inflammatory dermatoses)
was improved substantially by considering flexural
involvementandageatonset.Inthe519agegroup(basedon
36 cases of atopic dermatitis and 27 control subjects) the
sensitivitywas94%andspecificity81%ifflexuralinvolvement
34

alonewereincluded,andsensitivity92%withspecificity96%if
casedefinition was based on both flexural involvement and
onsetbefore5yearsofage.

Qus.5,6. These two questions have been included as measures of the

severity of the dermatitis, one assessing chronicity, the other
morbidity. A question on the extent of skin involvement was
considered and rejected as infeasible for questionnairebased
studies.

Qu.7. This question may need to be modified slightly in countries

where a number of diagnostic labels are in common use (e.g.
Has your child ever had any of the following: ...?). A
supplementary stem question (If yes, was this diagnosed by a
doctor?)wasconsideredoptional.

 35

7.5 Module1.4: Videoquestionnaire

7.5.1 Questionnaire

1. Hasyourbreathingeverbeenlikethis?:
atanytimeinyourlife? YES NO
ifYES,:inthelastyear? YES NO
ifYES,:oneormoretimesamonth? YES NO

2. Hasyourbreathingbeenlikethegirlsinthevideofollowingexercise?
atanytimeinyourlife? YES NO
ifYES,:inthelastyear? YES NO
ifYES,:oneormoretimesamonth? YES NO

3. Haveyoubeenwokenlikethisatnight?:
atanytimeinyourlife? YES NO
ifYES,:inthelastyear? YES NO
ifYES,:oneormoretimesamonth? YES NO

4. Haveyoubeenwokenlikethisatnight?:
atanytimeinyourlife? YES NO
ifYES,:inthelastyear? YES NO
ifYES,:oneormoretimesamonth? YES NO

5. Hasyourbreathingbeenlikethis?:
atanytimeinyourlife? YES NO
ifYES,:inthelastyear? YES NO
ifYES,:oneormoretimesamonth? YES NO

36

7.5.2 Development,validation

In response to translation problems with written questionnaires a video

questionnaire has been developed and validated in Wellington, New
Zealand. This attempts to minimise difficulties of comparability of
informationinlargesurveysamongdiversepopulations.Inparticularthe
video questionnaire was developed to avoid problems of translation and
comprehension of terms such as wheeze or whistling from the chest
andtheiruseinculturallyheterogeneouspopulations.

The video involves sequences of asthma symptoms in young persons

(generallylateteens);threesequencesinvolvevariousscenesofwheezing
whereasthefinaltwosequencesinvolveotherasthmasymptoms.Thefive
sequencesare:

1. Ayoungpersonwheezing(whileatrest)
2. Wheezingafterexercise
3. Wakingatnightwithwheezing
4. Wakingatnightwithcoughing
5. Asevereattackofasthma,involvingdifficultybreathingatrest.

After each sequence, students are asked to write down there answers to
questionspresentedonthevideo.ThesearepresentedinModule1.4.They
areaskedtospecifywhethertheirbreathinghaseverbeenlikethatofthe
person in the video; if so they are asked whether this has occurred in the
last year; if so they are asked whether this occurs more often than once a
week.Thevideotakeslessthan10minutestoplay.

Centres are strongly encouraged to present the video questionnaire.

However it is acknowledged that in some centres, logistic or technical
factors may make this impossible. The video has the advantage of
obtainingdatafromalargenumberofchildrenquicklyandefficiently.
 37

7.6 Furthercommentsonvalidationofinstruments

We have set out to use questionnaires with both sensitive and specific
questions. The validity of questionnaire measurements of asthma or
wheezetobeusedinthecorestudyhavebeenconsideredasfollows:

1. Repeatability

Severalstudiesindicatethatquestionnairesofthistypeaboutasthma,have
a good level of repeatability even when translated into languages other
than English (Salome et al 1987, Burney et al 1989, Clifford et al 1989).
Earlierversionsofthewrittenandvideoquestionnairesonwheezingand
asthmahavebeenshowntoberepeatable(Shawetal).

2. Contentvalidity

Thequestionshavefacevalidity;forsomequestionsonseverityitisvery
difficulttoobtaindatatovalidatethequestions(e.g.forquestionsonnight
waking a true validation would require prospective home data collection
for one year; for questions about the worst attack it would require
prospectiveobservationsonallasthmaattacks).

3. Constructvalidity

There has already been a major pilot study of written and video
questionnaires on wheezing and asthma, which are very similar to the
PhaseIcorequestionnaires(Pearceetal).Itwasthefirstoccasioninwhich
thevideoquestionnairehadbeenusedinaninternationalcomparison.The
similarities and differences found between countries were generally
consistent with previously published work, and the video and written
questionnairesshowedasimilarpatternofresults.

Thequestionnairesweregenerallyansweredinaconsistentfashion.

4. Concurrentvalidity

In the pilot study the reported prevalences of wheezing were relatively

high in this selfreporting sample of 1215 year olds compared with
estimates in previous surveys involving parental completion of
questionnaires. Therefore further investigation of this observation will be
made in at least two centres: parentcompleted and selfcompleted
38

questionnaires will be simultaneously compared in this age group.

Andersonetalwillbestudyingthevalidityofthethreecorequestionnaires
among13yearoldsusingadetailedinterview.

The pilot study has demonstrated that presentation of the written

questionnaire before the video does not affect responses to the video;
howeverpresentationofthevideofirstdoesaffectresponsestothewritten
questionnaire.

5. Predictivevalidity

Frequent and persistent wheezing episodes are associated with chest

deformity, residual airways obstruction, radiological evidence of
hyperinflation,andpresenceofrhonchiintheintervalphase(Gillametel
1970,McNicoletal1970).Wheezingatage7yearspredictslaterwheezing
andthisisincreasedifoneusesfrequencyofepisodesatage7(Anderson
etal1986).

Although bronchial hyperresponsiveness (BHR) has in the past been

equatedwithasthma,populationstudieshaveshownthatitsrelationship
toasthmasymptomsandasthmadiagnosisisnotclose(Josephs,Pattemore
et al). This is probably because it is only one of several mechanisms
underling clinical asthma. BHR cannot be regarded as the gold standard
(theoneobjectiveindicatorofasthma).Nevertheless,BHRisanimportant
factorinasthma,anditsrelationshiptothetoolsbeingusedisofparticular
interest. The prevalence of wheeze found by questionnaire relates to the
response to an exercise provocation test (Barry & Burr 1991) and other
measures of BHR (Burney et al 1989). Previous work with the video
questionnairehasshownittohavereasonablesensitivityandspecificityfor
BHRinanEnglishspeakingpopulation(Shawetal).

7.7 Presentationandtranslation

Itisimportantthatthequestionnairesarepreparedinaconsistentmanner.
Theorderofyes/noresponseshasbeendefined.Thelayoutandprintingof
the questionnaires will be standard with each module being printed on a
singlepage.The4questionnairesfor1314yearoldsareusuallypresented
on one piece of folded paper with the video questionnaire to be showing
on the back when folded. Alternatively they may be presented separately
withadequateidentificationoneachpage.
 39

Translation of questionnaires from English to other languages will be

standardised.TheEnglishversionwillbetranslated,andthenthatversion
translated back to English. These procedures will involve several
translators, in an attempt to define the best nonEnglish version for each
region.Insomecountries(e.g.NewZealand)theinformationsheetmaybe
translatedintothemainnonEnglishlanguages,butnotthequestionnaires,
providingthevastmajorityofthepopulationareconversantwithwritten
English.

8.0 Ethicsandconduct
8.1 Ethicalcommitteeapproval

Each centre will need to obtain the necessary Ethics Committee approval
priortothestartofthestudy.Sampleinformationsheetsappearbelow.

8.2 Modelforapproachingschools

What follows is one example of the approach to schools. Centres must

proceed according to their local rules. A final goal should be a high
participationrate.

Once Ethics Committee approval has been obtained, the school principal
will be approached for his/her cooperation with the study. Then the data
collection will be able to commence with the cooperation of the class
teachers.Itisveryimportantthattheasthma,allergies,rhinitisandeczema
are not explicitly mentioned to school staff pupils and parents in
relationshiptothestudy.

8.2.1 Sampleinformationletterfor1314yearolds

DearChairmanofBoardofTrustees/Principal/Teachers

re: New Zealand Survey of Breathing, Nose and Skin Problems in

Children

Weareinvitingsomechildrenatyourschooltotakepartinanimportant
studyaboutchildhealthwiththeapprovaloftheirparents.Manyschools
in Auckland are taking part in the study, and by random sampling
40

techniques,yourschoolhasbeenselected.Wewishtostudychildrenaged
13and14years.

ThissurveyisbeingcarriedoutinrandomlyselectedschoolsinAuckland,
Wellington, Christchurch, Nelson and Hawkes Bay, and also in many
overseas countries including Australia, Canada, USA, Britain and
Germany.TheAucklandsurveyisfundedbytheHealthResearchCouncil
ofNewZealand.Thepurposeofthestudyistounderstandmoreaboutthe
increasingproblemofrespiratorysymptomsinchildrenofthisagegroup.

Foryourschool,itwouldmean:

1. Identifying classes in which 1314 year olds are found and making
availableacopyoftheclasslistswithdateofbirthifpossible.

2. During this term one of our research team would bring information
sheets for parents (copy enclosed) to the school, to be distributed to
alltheselectedchildrenoneweekbeforethestudyteamcometoyour
school.

3. We would return the next week to ask these children to complete

written questionnaires (copy enclosed) and to watch a video about
exercise and breathing which lasts about ten minutes. We would
requireabout40minutesintotal.

4. Wewouldcomebackaboutaweeklater,withthequestionnairesand
showthevideotoanychildrenwhowereabsentonthefirstoccasion
anaskthemtocompletethesurvey.

One of our research team will be in contact with you soon to discuss this
survey further. In the meantime if there is any further information you
requireaboutthesurvey,pleasedonothesitatetocontactoneofus.Ifyou
are unable to reach us directly by telephone, please leave a message with
oursecretaryMrsChrisThomas.

This survey has the approval of the University of Auckland Human

Subjects Ethics Committee, whose Chairman you may contact directly
aboutethicalmatters(careoftheSecretary,UniversityofAucklandHuman
Subjects Ethics Committee, University of Auckland, Private Bag 92019,
Auckland;phone3737599,ext6204).
 41

Yourssincerely

...............

8.2.2 Sampleinformationletterfor67yearolds

DearChairmanofBoardofTrustees/Principal/Teachers

re: New Zealand Survey of Breathing, Nose and Skin Problems in

Children

Weareinvitingsomechildrenatyourschooltotakepartinanimportant
studyaboutchildhealthwiththeapprovaloftheirparents.Manyschools
in Auckland are taking part in the study, and by random sampling
techniques,yourschoolhasbeenselected.Wewishtostudychildrenaged
67years.

ThissurveyisbeingcarriedoutinrandomlyselectedschoolsinAuckland,
Wellington, Christchurch, Nelson and Hawkes Bay, and also in many
overseas countries including Australia, Canada, USA, Britain and
Germany.TheAucklandsurveyisfundedbytheHealthResearchCouncil
ofNewZealand.Thepurposeofthestudyistounderstandmoreaboutthe
increasingproblemofrespiratorysymptomsinchildrenofthisagegroup.

Foryourschool,itwouldmean:

1. Identifyingclassesinwhich67yearoldsarefoundandhavingready
acopyoftheclasslistsfortheresearcher.

2. Oneofourresearchteamwillthencomeandnameeachsurveyform
anddistributethembyclasstobetakenhome.

3. We will send information sheets, and questionnaires (copies

enclosed) to the parents of the children who will be asked to
complete the questionnaire and return it to your school, to be
collectedbytheresearcher.

4. Wewouldfollowupanynonreturnedforms.

5. We would wish to have information on the date of birth and sex of

anypotentiallyeligiblechildrenwhodonotparticipateinthesurvey.
42

One of our research team will be in contact with you soon to discuss this
survey further. In the meantime if there is any further information you
requireaboutthesurvey,pleasedonothesitatetocontactoneofus.Ifyou
are unable to reach us directly by telephone, please leave a message with
oursecretaryMrsChrisThomas.

This survey has the approval of the University of Auckland Human

Subjects Ethics Committee, whose Chairman you may contact directly
aboutethicalmatters(careoftheSecretary,UniversityofAucklandHuman
Subjects Ethics Committee, University of Auckland, Private Bag 92019,
Auckland;phone3737599,ext6204).

Yourssincerely

...............

8.3 Modelforapproachingparents

An information sheet will be sent home with each participating child,

givingdetailsaboutthestudy.Theinformationsheetwillbetranslatedup
tofourofthemostcommonlanguagesusedbyfamiliesofeligiblechildren.

1314yearolds: The information sheet has an additional paragraph

giving the parent the right to refuse their childs
participationinthestudy.

67yearolds: Parentscompletionofthequestionnaireimpliesconsent.

8.3.1 Sampleinformationsheetforparents/guardiansof1314yearolds

DearParent/Guardian

Weareinvitingyourchildtotakepartinanimportantsurveyaboutchild
health with the approval of your school. Many schools in Auckland are
takingpartinthestudyandallclassmatesofyourchildarebeingaskedto
take part. First, your child will be asked to complete three brief
questionnaires. Then a 10 minute video about exercise and breathing will
be shown to your child in his/her class and your child will be asked to
complete a further brief questionnaire. This will take up to 40 minutes of
classtime.
 43

ThissurveyisbeingcarriedoutinrandomlyselectedschoolsinAuckland,
Wellington,Christchurch,Nelson,HawkesBayandalsoinmanyoverseas
countries including Australia, Canada, USA, Britain and Germany. The
AucklandsurveyispartlyfundedbytheHealthResearchCouncilofNew
Zealand.

We ask you to consider this information sheet, and if you agree to your
childtakingpartinthesurvey,thenyouneedtotakenoaction.Ifyoudo
not wish your child to answer the questionnaire, please telephone the
number listed at the bottom of this page tomorrow. Your childs
questionnaire will be treated confidentially; only a code number will be
enteredinthecomputer.

This survey has the approval of your childs schools Board of Trustees,
Principal and teachers. It also has the approval of the University of
AucklandHumanSubjectsEthicsCommittee.

If there is any further information you require about the study, please
contactoneofus.

Yourssincerely

..............

8.3.2 Sampleinformationsheetforparents/guardiansof67yearolds

DearParent/Guardian

Weareinvitingyourchildtotakepartinanimportantsurveyaboutchild
health with the approval of your school. Many schools in Auckland are
takingpartinthestudyandallclassmatesofyourchildarebeingaskedto
take part. For each child, a parent/guardian is being asked to complete a
questionnaire.

ThissurveyisbeingcarriedoutinrandomlyselectedschoolsinAuckland,
Wellington,Christchurch,Nelson,HawkesBayandalsoinmanyoverseas
countries including Australia, Canada, USA, Britain and Germany. The
AucklandsurveyispartlyfundedbytheHealthResearchCouncilofNew
Zealand.
44

We ask you to consider this information sheet, and if you agree to your
child taking part in the survey, then we would like you to complete the
attached questionnaire. Your childs questionnaire will be treated
confidentially;onlyacodenumberwillbeenteredinthecomputer.

This survey has the approval of your childs schools Board of Trustees,
Principal and teachers. It also has the approval of the University of
AucklandHumanSubjectsEthicsCommittee.

If there is any further information you require about the study, please
contactoneofus.

Yourssincerely

..............

8.4 Guidelinesforfieldworkers

ISAACresearchstaffandfieldworkersshouldnotusethetermsasthma,
allergy,rhinitisoreczemawhen

(i) advertisingthestudy

(ii) presentingwrittenmaterialaboutthestudy

(iii) speakingaboutthestudytoschoolstaff,parents,children

(iv) speakingto1314yearoldchildrenintheclassroom.

The phrases breathing survey or a survey about breathing problems

areacceptabletermstouse.

Thetitleofthequestionnairesmustnotincludethewordsasthma,allergy,
rhinitis, eczema or ISAAC. An alternative title could be A survey of
Breathing, Nose and Skin Problems. Coding should not appear on the
questionnairesdeliveredtothechildrenortheirparents.Improvedlayout
of the questionnaires is being developed and tested by the New Zealand
steeringcommitteemembers,andwillberecommendedforuseinthefield.
PleasecontactInnesAsherforcopiesofthesequestionnaires.
 45

67yearolds
Once eligible children are identified, ISAAC staff will send the
questionnairetotheparent/guardianeitherthroughtheschoolorbypost.
The parent/guardian will be asked to return the questionnaire by a
mechanismwhichincursnofinancialcosttothem.

1314yearolds
Thequestionnaireswillbeadministeredtoagroupofchildreninaschool
inonesessionatatime.Eachsessionwillcompriseverbalinstructionson
thethreesectionsbeforehandingthequestionnairesoutandinstructionsto
leave the video questions until the video is shown. Alternatively, the
questionnaires may be presented on separate sheets of paper.
Administrationwilltheninclude:

(i) handing out and completion of the written questionnaire on

wheezing

(ii) handingoutandcompletionofthewrittenquestionnaireonrhinitis

(iii) Handingoutandcompletionofthewrittenquestionnaireoneczema

Theorderofpresentationofthecorequestionnairesisofimportance:they
shouldalwaysbepresentedwheezingrhinitiseczema.

(iv) Handing out the written questions for the video questionnaire
followedimmediatelybytheshowingofthevideoquestionnaire;the
writtenquestionsarecompletedwhilethisisbeingshown.Thevideo
questionnairemustalwaysbeshownafterthewrittenquestionnaires

In presenting the video, there must be adequate technical adequacy and

visualandaudioqualitytoensuresubjectsseeitwellandhearitcorrectly.

If questionnaires have clearly not been completed in a comprehensible

fashion, then they could be represented to the person who originally
completed them for one further attempt. The research worker should not
give advice about the responses that might be given. Once the
questionnaire is completed, it must not be changed by research workers
underanycircumstances.
46

9.0 DataTransfer
The coding manual is available upon request from the regional
coordinators.

 47

10.0 Contactaddresses

ISAACExecutive:

InnesAsher(Chairperson)
DepartmentofPaediatrics
SchoolofMedicine
UniversityofAuckland
PrivateBag
Auckland
NewZealand
Ph: *64(9)3737999
Fax: *64(9)3737486

RichardBeasley
DepartmentofMedicine
WellingtonSchoolofMedicine
P.O.Box7343
WellingtonSouth
Wellington
NewZealand
Ph *64(4)3855999
Fax *64(4)3895725

DavidStrachan
DepartmentofPublicHealthSciences
StGeorgesHospitalMedicalSchool
CranmerTerrace
Tooting
LondonSW170RE
UnitedKingdom
Ph: *44(81)7255429
Fax: *44(81)7253584

48

RegionalcoordinatorsforISAAC

EUROPE

WesternEurope

UlrichKeil,StephanWeiland
InstitutfrEpidemiologieundSozialmedizin
WestflischeWilhelmsUniversitt
VonEsmarchStrae56
D48129Mnster
Germany
Ph: *49(251)835396
Fax: *49(251)835300

EasternEurope/Baltics

BengtBjrkstn
DepartmentofPaediatrics
UniversityHospital
S58185Linkping
Sweden
Ph: *46(13)221331
Fax: *46(13)148265

AMERICA

NorthAmerica

FernandoMartinez
RespiratorySciencesCenter
UniversityofArizona
HealthSciencesCenter
Tucson,AZ85724
USA
Ph: *1(602)6267780
Fax: *1(602)6266970
 49

LatinAmerica

JavierMallol
Clasificador14A
LaSerena
Chile
Ph: *56(51)
Fax: *56(51)215678

AFRICA

GabrielAnabwani
DepartmentofPaediatrics
FacultyofHealthSciences
P.O.Box4606
Eldoret
Kenya
Ph:
Fax: *254(321)33041

WESTERNPACIFIC

AsiaPacific

ChrisLai
DepartmentofMedicine
TheChineseUniversityofHongKong
PrinceofWalesHospital
Shatin
NewTerritories
HongKong
Ph: *8526363127
Fax: *8526375396
50

Oceania

InnesAsher
DepartmentofPaediatrics
SchoolofMedicine
UniversityofAuckland
PrivateBag
Auckland
NewZealand
Ph: *64(9)3737999
Fax: *64(9)3737486

SOUTHEASTASIA

J.R.Shah
JaslokHospitalandResearchCentre
15,DrGDeshmukhMarg
Bombay400026
India
Ph: *91(22)4933333

 51

11.0 Bibliography
Aberg N. Asthma and allergic rhinitis in Swedish conscripts. Clin Exp
Allergy1989;19:5963.

Anderson HR, Bailey PA, Cooper JS, Palmer JC, West S. Medical care of
asthmaandwheezingillnessinchildren:acommunitysurvey.JEpidemiol
CommHealth1983;37:1806.

Anderson HR, Bailey PA, Cooper JS, Palmer JC, West S. Morbidity and
school absence caused by asthma and wheezing illness. Arch Dis Child
1983;58:777784.

AndersonHR,BlandJM,PatelS,PeckhamC.Thenaturalhistoryofasthma
inchildhood.JEpidemiolCommHealth1986;40:121129.

AsherMI,PattemorePK,HarrisonAC,MitchellEA,ReaHH,StewartAW,
Woolcock AJ. International comparison of the prevalence of asthma
symptomsandbronchialhyperresponsiveness.AmRevRespDis1988;138:
524529.

Australian Bureau of Statistics. 198990 National Health Survey. Asthma

and other respiratory conditions, Australia. Catalogue No. 4373.0
Canberra:CommonwealthofAustralia,1991.

Barry DMJ, Burr ML, Limb ES. Prevalence of asthma among 12 year old
childreninNewZealandandSouthWales:acomparativesurvey.Thorax
1991:46:405409.

Britton WJ, Woolcock AJ, Peat JK, Sedgwick CJ, Lloyd DM, Leeder SR.
Prevalence of bronchial hyperresponsiveness in children: the relationship
betweenasthmaandskinreactivitytoallergensintwocommunities.IntJ
Epidemiol1986;15:202209.

BurneyPGJ,LaitinenLA,PerdrizetS,HuckaufH,TattersfieldAE,ChinnS,
PoissonN,HeerenA,BrittonJR,JonesT.Validityandrepeatabilityofthe
IUATLD (1984) Bronchial Symptoms Questionnaire: an international
comparison.EurRespirJ1989;2:9405.
52

CliffordRD,RadfordM,HowellJB,HolgateST.Prevalenceofrespiratory
symptomsamong7and11yearoldchildrenandassociationwithasthma.
ArchDisChild1989;64:11181125.

Cockcroft DW, Hargreave FE. Airway hyperresponsiveness. Relevance of

randompopulationdatatoclinicalusefulness.AmRevRespDis1990:142:
497500.

DiepgenTL,FartaschM,HornsteinOP.Evaluationandrelevanceofatopic
basic and minor features in patients with atopic dermatitis and in the
generalpopulation.ActaDermVenereol[Stockholm]1989;Suppl144:50
54.

FlemingDM,CrombieDL.PrevalenceofasthmaandhayfeverinEngland
andWales.BrMedJ1987;294:279283.

Gillam GL, McNicol KN, Williams HE. Chest deformity, residual airways
obstructionandhyperinflation,andgrowthinchildrenwithasthma.Arch
DisChild1970;45,789799.

Golding J, Peters T. Eczema and hayfever. In Butler NR, Golding J (eds).

From birth to five. A study of the health and behaviour of Britains five
yearolds.Oxford:Pergamon,1986;171186.

Hagy GW, Settipane GA. Bronchial asthma, allergic rhinitis and allergy
skintestsamongcollegestudents.JAllergy1969;44:323332.

Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm

Venereol[stockholm]1980;92:4447.

Josephs LK, Gregg I, Mullee MA, Holgate ST. Nonspecific bronchial

reactivity and its relationship to the clinical expression of asthma: a
longitudinalstudy.AmRevRespDis1989:140:350357.

Josephs LK, Gregg I, Holgate ST. Does nonspecific bronchial

responsiveness indicate the severity of asthma? Eur Respir J 1990; 3: 220
227.

McNicol KN, Williams HE, Allan J, McAndrew I. Spectrum of asthma in

childrenIII,psychologicalandsocialcomponents.BrMedJ1973;4:1620.
 53

MontgomerySmithJ.Epidemiologyandnaturalhistoryofasthma,allergic
rhinitisandatopicdermatitis(eczema).In:MiddletonE,ReedCE,EllisEF,
Adkinson NF, Yunginger JW, eds. Allergy: principles and practice. St
Louis:CVMosby,1983:771803.

Mutius E von, Fritzsch C, Weiland SK, Rll G, Magnussen H. The

prevalence of asthma and atopic disorders among children in the united
Germany:adescriptivecomparison.BMJ1993;305:13959.

PattemorePK,AsherMI,HarrisonAC,MitchellEA,ReaHH,StewartAW.
Theinterrelationshipamongbronchialhyperresponsiveness,thediagnosis
ofasthma,andasthmasymptoms.AmRevRespDis1990;142:54954.

Pearce N, Weiland S, Keil U, Langridge P, Anderson R, Strachan D,

BaumannA,YoungL,CraneJ,BeasleyR.Prevalenceofasthmasymptoms
inchildreninAustralia,England,GermanyandNewZealand.EurRespJ
1993;inPress.

Robertson CF, Heycock E, Bishop J, Nolan T, Olinsky A, Phelan PD.

PrevalenceofasthmainMelbourneschoolchildren:changesover26years.
BrMedJ1991;302:11168.

Salome CM, Peat JK, Britton WJ, Woolcock AJ. Bronchial

hyperresponsiveness in two populations of Australian school children. I.
Relation to respiratory symptoms and diagnosed asthma. Clin Allergy
1987;17:27181.

SchulzLarsen F, Holm NV, Henningsen K. Atopic dermatitis. A genetic

epidemiological study in a populationbased twin sample. J Am Acad
Dermatol1986;15:487494.

Shaw RA, Crane J, ODonnell TV, Porteous LE, Coleman ED. Increasing
asthma prevalence in a rural New Zealand adolescent population: 1975
1989.ArchDisChid1990;65:131923.

ShawRA,CraneJ,PearceN,BurgessCD,BremnerP,WoodmanK,Beasley
R. Comparison of a video questionnaire with the IUATLD written
questionnaire for measuring asthma prevalence. Clin Exper Allergy 1992;
22:561568.
54

Shaw RA, Crane J, ODonnell TV et al. The use of a videotaped

questionnaireforstudyingasthmaprevalence:apilotstudyamongstNew
Zealandadolescents.MedJAust1992;157:3114.

SibbaldB,RinkE.Epidemiologyofseasonalandperennialrhinitis:clinical
presentationandmedicalhistory.Thorax1991;46:895901.

Speight ANP, Lee DA, Hey EN. Underdiagnosis and undertreatment of

asthmainchildhood.BrMedJ1983:286:12531256.

Strachan DP, Golding J, Anderson HR. Regional variations in wheezing

illness in British children: effect of migration during early childhood. J
EpidemiolCommunityHealth1990;44:231236.

Taylor B, Wadsworth M, Wadsworth J, Peckham C. Changes in the

reported prevalence of childhood eczema since the 193945 war. Lancet
1984;ii:125557.