Phase One Manual

8/13/2019 Phase One Manual

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Manual

CHILDHOOD

ALLERGIESIN

ASTHMAAND

STUDYOF

INTERNATIONAL


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Auckland(NZ) /Mnster(FRG)

December1993(2nd edition)


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INDEX Page

1.0 WhatisISAAC? 31.1 Purpose 31.2 Overviewofstudydesign 31.3 Requirementsforparticipants 42.0 Developmentandadministrationoftheproject 52.1 History 52.2 Organisationalstructure 62.3 Funding 93.0 Scientificbackground 103.1 Asthma 103.2 Rhinitis 113.3 Eczema 113.4 Significanceoftheproposedstudy 124.0 AimsandObjectives 125.0 Methods 135.1 Overview 135.2 Collaboratingcentres 13

5.2.1 Countries 135.2.2 Researchcentres 135.2.3 Investigators 13

5.3 Subjects 145.3.1 Selection 145.3.2 Ethnicgroupandgender 145.3.3 Samplesize 15

5.4 Studydesign 165.4.1 DetailsofPhaseOnecoremodules 165.4.2 PlansforPhaseTwoSupplementaryModules 185.4.3 Seasonofdatacollection 18

5.5 Nonparticipation 195.6 Qualitycontrol 196.0 Datahandlingandanalysis 196.1 Dataqualityandhandling 206.2 Analyses 216.3

Ownershipofdata 21


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Page

7.0 Studyinstruments 227.1 Instructionsforcompletingquestionnaireanddemographicquestions 227.2 Module1.1Corequestionnaireforwheezingandasthma 24

7.2.1 Development,validation 267.3 Module1.2:Corequestionnaireforrhinitis 28

7.3.1 Questionnaires 287.3.2 Development,validation 30

7.4 Module1.3:Corequestionnaireforeczema 317.4.1 Questionnaires 317.4.2 Development,validation 33

7.5 Module1.4:Videoquestionnaire 357.5.1 Questionnaire 357.5.2 Development,validation 36

7.6 Furthercommentsonvalidationofinstruments 377.7 Presentationandtranslation 388.0 Ethicsandconduct 398.1 Ethicalcommitteeapproval 398.2 Modelforapproachingschools 39

8.2.1 Sampleinformationletterfor1314yearolds 398.2.2 Sampleinformationletterfor67yearolds 41

8.3 Modelforapproachingparents 428.3.1 Sample information sheet for parents/guardians of 1314 yearolds 428.3.2 Sampleinformationsheetforparents/guardiansof67yearolds 43

8.4 Guidelinesforfieldworkers 449.0 DataTransfer 4610.0 Contactaddresses 4711.0 Bibliography 51


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1.0 WhatisISAAC?1.1 PurposeThe aetiology of asthma and allergic disease remains poorly understooddespite 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 asthmaand allergic disease by establishing a standardised methodology and

facilitatinginternationalcollaboration.Itsspecificaimsareto:

1. Describe theprevalenceandseverityofasthma,rhinitisandeczemain children living in different centres and to make comparisons

withinandbetweencountries.

2. Obtain baseline measures for assessment of future trends in theprevalenceandseverityofthesediseases.

3. Provide a framework for further aetiological research into genetic,lifestyle, environmental and medical care factors affecting these

diseases.

1.2 OverviewofstudydesignTheISAACstudydesigncomprisesthreephases.PhaseI isacompulsory

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 investigatepossibleaetiological 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


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symptoms,notbyreference to labelsordiagnoses(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 Requirementsforparticipants1. 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 arebeing made; the

seasonofdatacollection;ifappropriate,methodoftranslatingISAACcore 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 mustbe made available in suitable electronic form to

theISAACexecutiveforanalysisatthedesignateddatacentre.

4. Each centre may publish its own data without the approval ofISAAC. All publications and communications arising from


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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 welcomeinterested 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.

2.0Development

and

administration

of

the

project

2.1 HistoryISAAC emerged from preexisting multinational collaborations regarding

childhoodasthmaepidemiologyincluding:

October 1989 Development of standardised questionnaire formeasuring asthma prevalence in the UK (London), New Zealand

(Auckland),andAustralia(Melbourne).

May 1990 Investigators in Auckland, New Zealand, approachedexperiencedinvestigatorsinfivecountriestoestablishacollaborative

group interested in conducting internationalcomparativestudiesof

asthmaseverityinchildren.

December 1990 An international workshop on monitoring trendsanddeterminantsofasthmaandallergieswasconvenedinBochum,

Germany.InterestedresearchersfromGermany,UK(London),New

Zealand(Wellington),andtheUSAestablishedacollaborativegrouptodevelopastandardisedprotocol.

March1991MergingoftheAucklandandBochuminitiatives. June1991Formationofasteeringcommitteefortheorganisationof

internationalcollaborativestudiesofchildhoodasthmaandallergies.

The countries represented included New Zealand (Auckland,

Wellington),UK(London),andGermany(Bochum).

December 1991 Second international workshop on monitoringtrends and determinants of asthma and allergies was convened in


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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 InternationalStudyofAsthmaandAllergiesinChildhoodinLondon.

2.2 OrganisationalstructureGeneralapproach

TheorganisationofISAACconsistsoffourlevels:

theSteeringCommittee(includingtheExecutive) regionalcoordinators nationalcoordinators collaboratingcentresThegeneralapproachisthat,inaparticularregion,aregionalcoordinator

is appointed by the steering committee, who then recruits national

coordinators. A regional meeting of national coordinators is held toorganise 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


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Nationalcoordinators

The national coordinators are generally responsible for a single country.

However, in some instances they maybe responsible for several small

neighbouring countries, particularly if these only have one collaboratingcentreand/orifnosuitablenationalcoordinatorsareavailable.

Theresponsibilitiesofthenationalcoordinatorsareto:

recruitandregistercollaboratingcentres organise translation and production of the Phase I manual and

questionnaires

organise a national meeting of collaborating centres to organise theimplementationofPhaseI liaise with the collaborating centres and provide assistance when

required,includingcleaningofthedata

liaisewiththeregionalcoordinators check and forward the clean national data sets to the regional

coordinators

organiseafurthernationalmeetingofcollaboratingcentrestodiscusstheresultsofPhaseI

Regionalcoordinators

Theregionalcoordinatorsareresponsibleforabroadregionoftheworld.

TheregionswillgenerallybebasedonthesixWHOregionsoftheworld,

since these are widely used and logically organised. However, in some

instances a WHO region maybe split into subregions, if the number ofcollaboratingcentresorcountriesislarge.


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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 theimplementation 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,andparticipateinmeetingsoftheExtendedSteeringCommittee

organise a further meeting of national coordinators to discuss theresultsofPhaseIandtoplanPhaseII

TheSteeringCommittee

TheSteeringCommitteehasrecentlybeenexpandedandnowincludesthe

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


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modulesthatareunderdevelopment),inadditiontotheoriginalmembers

oftheSteeringCommittee.

TheresponsibilitiesoftheSteeringCommitteeare:

recruitregionalcoordinators assistwiththeregionalmeetings liaise with regional coordinators and provide assistance when

required

coordinatetheimplementationandconductofPhaseI organisethefurtherdevelopmentofmodulesandmethodsforPhase

II coordinatetheanalysesandpublicationsofdata organisefutureinternationalISAACmeetingsThefullSteeringCommitteewillmeetannually.

TheExecutive

TheISAACstudyiscoordinatedonadaytodaybasisbyathreemember

executive.Thecurrentexecutiveconsistsof:

Dr.InnesAsher(DataCoordination) Prof.RichardBeasley(ImplementationofPhaseI) Dr.DavidStrachan(MethodsDevelopment)TheExecutiveischairedbyDr.Asher.

2.3 FundingEach research centre is responsible for obtaining its own funding. At the

time of writing, funding hasbeen successfully obtained from the Health

ResearchCouncilofNewZealandforthreeNewZealandcentres,fromthe

LocallyOrganisedResearchFundoftheDepartmentofHealthinEngland

foroneEnglishcentre,andfromtheMinistryforWork,HealthandSocial

Affairs of the German State of North RhineWestphalia for one German

centre.InFrancethreecentresobtainedcompleteandanotherthreecentresobtained partial funding. In Italy two centres are funded and in Spain


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fundinghasbeenobtainedforfourcentres.Fundingsupportisexpectedto

beobtainedinthenearfutureforanumberofothercentres.

3.0 ScientificbackgroundThere is considerable concern regarding a possible increase in the

prevalenceandincidenceofasthmaandallergiesinWesterncountries.

3.1 AsthmaAsthma isoneof themost importantdiseasesofchildhood indeveloped

countries.Estimatesofthe12monthperiodprevalenceofparentreported

wheezing illnessvarygreatlybutrangefrom1015% in theUK to30% inAustralasiaandamongstthese,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

admissionshave increasedtoagreaterdegree inmanycountriesand this

hasbeen attributedboth to changes in medical practice and changes in

prevalence.Anumberofcountriesexperiencedepidemicsofmortality inthe1960sandsubsequentlyafurtherepidemicoccurredinNewZealand.

Atnationalandtoalesserextentsubnationalleveltherearegeographical

variations in prevalence, mortality and hospitaladmissions. 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

thangenetic.Anenvironmental factormightacteitherbyinducing theasthmatictendencyinageneticallysusceptibleindividualorbyinciting

attacks in individualswhohavebecomeasthmatic.Little isknownabout

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 beincreasingmortalityandmorbidity.


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3.2 RhinitisThere are no widely agreed criteria for the diagnosis or classification of

noninfectious rhinitis. The principle symptoms of noninfectious rhinitis

aresneezing,runningnose(rhinorrhea),and/ornasalblockage.Patientsaregenerallyclassifiedaccordingtothesuspectedaetiologyoftheircondition

into allergic and nonallergic types. Rhinitis is labelled allergic when a

causativeallergencanbeidentified.Otherwiseitislabellednonallergic.

Thisapproachtoclassification isproblematic inthat it is impossible tobe

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 fordifferencesinprevalenceovertimeandbetweenplaces,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 EczemaLittle is known about the epidemiology of eczema or atopic dermatitis.

However, geographical variations in prevalence havebeen 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.

In theory,eczema ismorereadilyconfirmedbyobjective tests thaneither

asthma or rhinitis. However, there are currently no internationallyaccepted criteria for definition of atopic dermatitis. A list of major and


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minor criteria proposed by Hanifin and Rajka in the 1970s have been

furtherevaluatedandwidelyappliedinclinicalstudiesbuthavenotbeen

definedandstandardisedinamannersuitableforepidemiologicalstudies.

A teamofBritishdermatologistsarecurrentlydevelopingandvalidating

definitions of atopic dermatitis based on questionnaire data with or

withoutclinicalsigns.The former,whichcorrespondclosely to themajor

criteria proposedby Hanifin and Rajka, havebeen incorporated into the

initialphaseofthepresentstudy.

3.4 SignificanceoftheproposedstudyMuchresearchhasbeenconductedintothereasonswhysomeindividuals

rather than others develop asthma and other atopic diseases such asrhinitis and eczema. The main finding hasbeen 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 ata

populationlevelmaybedifferent.Indeedtherearesomefactorswhichcan

only be studied in this way because whole populations may be fairlyevenlyexposedtothefactor,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.TheISAACstudyhasbeendevelopedtoaddressthesequestions.

4.0 AimsandObjectives1. To describe the prevalence and severity of asthma, rhinitis and

eczema in children living in different centres and to make

comparisonswithinandbetweencountries.

2. To obtainbaseline measures for assessment of future trends in theprevalenceandseverityofthesediseases.


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3. To provide a framework for further aetiological research intolifestyle, environmental, genetic and medical care factors affecting

thesediseases.

5.0 Methods5.1 OverviewThecollaborativestudieswillbeconducted inthreephases.PhaseI isthe

corestudydescribedindetailhere.PhaseIIinvolvesmoredetailedstudies

of aetiological factors and clinical examination of subgroups of children.

PhaseIIIwillbearepetitionofPhaseIafterthreeyears.

5.2 Collaboratingcentres5.2.1 CountriesThiswillbeamulticentrestudy, 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 asbetween

countrycomparisons.

5.2.2 ResearchcentresAn 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

allergicdiseases,participationof thesecentreswillbeofparticularvalue.Thesampleofchildren takingpart in ISAACshouldnotpreviouslyhave

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 InvestigatorsInvestigators who have experience with asthma or its epidemiology,especiallyinchildren,areparticularlyencouragedtojoinISAAC.


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5.3 Subjects5.3.1 SelectionThepopulationof interest is school childrenwithina given geographicalarea.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 willbe separate.

Once a school hasbeen chosen, two school years willbe chosen which

includethosewiththegreatestproportionof13yearoldsand14yearolds;

those with the greatest proportion of 6 year olds, and 7 year olds. It isrecognisedthattherewillbesomechildrenoutsidethespecifiedageranges

ineachclasschosen.Thesechildrenmaybeincludedinthedatacollection,

butwillbeexcludedfromanalysisfortheinternationalcomparison.

The younger age group hasbeen 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.Theolderagegrouphasbeenchosentoreflecttheperiodwhenmortalityfromasthmaismorecommon.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.

Ifaschool fordisabledchildren (e.g.blind, intellectuallyhandicapped) ischosen, theywillbestudied.However it isacknowledged that theremay

beadisproportionatenumberofchildrenofthe1314yearagegroupwho

are unable to participate in such a school. This wouldbe one reason for

nonparticipation.

5.3.2 EthnicgroupandgenderWhere comparisonsbetween ethnic groups are planned, the question on

ethnicityshouldpreferably follow thatused in themostrecentCensusof


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Populations in the individual centre. There willbe a question to identify

thegenderofthechild.

5.3.3 SamplesizeThe 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

prevalenceofasthmabecausesevereasthma is lesscommon.Thesample

size estimates are stringentbecause of the number of hypothesesbeing

tested and the need tobe certain of the results in such a major study. A

samplesizeof3000hasbeenchosen,whichgivesthefollowingpower:1. PrevalenceofwheezingIfthetrueoneyearprevalenceofwheezingis30%inonecentreand25%in

anothercentre,withasamplesizeof3000, thestudypower todetect this

differencewillbe99%atthe1%levelofsignificance.

2. SeverityofwheezingIfthetrueoneyearprevalenceofsevereasthmais5%inonecentreand3%

inanothercentrewithasamplesizeof3000thestudypowertodetectthisdifferencewillbe90%atthe1%levelofsignificance.

It is recognised that some centres may have limited resources or

populationsbut it isneverthelessdesirablefor themtobe included in the

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:


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Samplesizeandpowerconsiderations

Table1a

PrevalenceoftroublesomeasthmaPOWER(%)

(significancelevel1%)

Differencebeingtested

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

(significancelevel1%)

Differencebeingtested

(%populationwhoareinadifferentresponse

category,e.g.neverwokenwithwheeze,wokenlessthanonenightperweek)

Power(%) 20% 25% 30%

90 3000 2100 1500

80 2500 1700 1200

70 2150 1400 1000

60 1800 1200 900

5.4 Studydesign5.4.1 DetailsofPhaseOnecoremodulesThree 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 ofwheezing illness and its diagnosis is obtained from as many surveys as

possible. The exact wording of questions follows, as far as possible,


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questions which havebeen used on published questionnaires and which

havefounddifferencesbetweenpopulations.

Itisanticipatedthatindividualinvestigatorsmaywishtosupplementthem

with questions of their own, but they should endeavour to retain thegeneral 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

commentaryabout theirdevelopmentandvalidation.The1314yearolds

willbepresentedwiththewrittenquestionnairesonwheezing,rhinitisandeczema, and if feasible, the video questionnaire. Investigators are also

encouraged to recruit the sample of 67 year olds, whose parents willbe

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


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5.4.2 PlansforPhaseTwoSupplementaryModulesThe 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 ofPhaseIIinstruments.Itisenvisagedthattherewillbeatleastthefollowing

modules:

Module2.1: Management medications

healthservicedelivery

Module2.2: Indoorenvironmentalriskfactors

physicalconditionschemicalirritants

allergens

Module2.3: Otherrespiratorysymptoms

Module2.4: Bronchialresponsivenesstesting

Module2.5: Skintestsforatopy

Module2.6: SerumIgE

Module2.7: Physicalexamination

Developmentofthesemoduleswillincludepilotstudiesinsomecentres.

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

including the following: repeat prevalence and severity studies; cohort

followupstudies;casecontrolstudies.

5.4.3 SeasonofdatacollectionIt 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,andSpring.Analysisofdata inadults(Wellington,NewZealand),young

adults (London, United Kingdom) and in children (Munich, Federal


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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 NonparticipationA participation rate of at least 90% willbe sought. It is a concern that

absentchildrenmaybeaway fromschoolbecauseofasthmaorallergies.

Thereforestrenuouseffortsneedtobemadetocontactthesechildrenand

offer theopportunityofparticipation in thestudy. In thecaseofchildren

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 QualitycontrolThereisparticularimportanceattachedtothequalityofthedatacollection

andprocedures in ISAAC,so that therewillbeconfidence 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 shouldbe included indicating theintenttoachieveahighparticipationrateandnomorethan5%ofthedata

missingfromthecompletedquestionnaireforms.

6.0 DatahandlingandanalysisEachgroupofsubjectswillbetreatedseparately:67yearolds,1314year

olds,andsubjectsofeachethnicgroupwhereamajorcomparisonisbeing

made (sample size 3000 for each ethnic group). Each parameter of


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prevalence and severity willbe comparedbetween locations. The cluster

effectisnotexpectedtobegreat,butwillbeadjustedforintheanalysis.

6.1 DataqualityandhandlingThe completed questionnaire must not be changed under any

circumstances.Datashouldbeenteredonthecomputerexactlyasrecorded

on the completed questionnaire. Any changes to data entered shouldbe

doneso foranexplicitreasonanddocumented.Thosechangesshouldbe

madetoacopyoftheoriginalcomputerdatafile.

Ifquestions1and2arenotcompletedinthewheezingquestionnaire,that

questionnairewillbeexcludedfromanalysis,butallavailabledatashould

stillbeenteredonthecomputer.Acodingmanualisnecessarysothatthe

corequestionswillbecodedinastandardmanner(seeSection9).

Ascheme tohandleblankor inconsistentstemandbranchquestionswill

bedevelopedsothatasingledenominatorforprevalencecanbeused.This

willassumethatparentsofsymptomaticchildrenwillbeunlikelytoleave

questionsblankand that thecategoryin the last12months inabranch

questionoverridesanegativeorblankstem.Arangecheckwillbeusedto

identifyanyotherinconsistency.

Each centre willbe responsible for coding its own data and data entry,

although insomeregions/countriesonecentremaytakeresponsibilityfor

this. One Data Centre willbe chosen for the international comparison of

the core data set. Data willbe 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

internationalcomparisonswillberetained in theDataCentreforanalysisalongwithdatareceivedfromtheothercentres.Datawillbeenteredona

PCwiththerequisitecapacityandmemory,interfacingwithamainframe

for more complex analyses. The results of data analyses will be

communicated to theothercentresas information isproduced,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.


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6.2 AnalysesThe 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 willbe thebasic reference for the

wholestudyandwilldescribeprevalenceandseverityofasthma,rhinitis

and eczema in both age groups for males and females in each of the

countriesparticipating.

Comparisonsbetweendifferentcentresontheratesofeventswillbemade

usingmethodsappropriate to thesituation.Cruderatescanbecompared

by using contingency tables or logistic regression. Comparison of

standardized rates or data that needs controlling for confounding will

require analysisby suitable multivariate methods (most probably logistic

regression).

The ancillary questions willbe treated in the same manner as the major

questions on prevalence and severity. Summaries for each centre willbe

recordedintheDataBookandcomparisonsmadeappropriately.

Datawillbeanalysedwithineachcountry(andcentre if largeenough)as

wellasthe internationalcomparisons.Thiswillallowfortheintroduction

ofadditionalvariablesthatthecountrymayhaveincorporated.

Seasonality, methods of survey sampling, age standardisation and any

otherissueswillbeconsideredintheanalysisoftheISAACdata.

6.3 OwnershipofdataEachcentreowns theirowndata.However, thecollaboratingcentreswill

be recognised by the group title International Study of Asthma and

Allergies in Childhood (ISAAC). All publications and communications

involvinginternationalcomparisonswillbeauthoredbytheISAACStudy

Groupwhosecollaboratorswillbeidentified.


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7.0 StudyinstrumentsThecontentofthequestionnaireswhichappearbelowisfixed.Seesection

7.1forfurthercomments.

7.1 Instructions for completing questionnaire and demographicquestions

Examplesof instructions for completingquestionnairesanddemographic

questionsaregivenbelow.

13and14yearolds

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

Allotherquestionsrequireyoutotickyouranswerinabox.Ifyoumakea

mistakeputacross in theboxand tick thecorrectanswer.Tickonlyone

optionunlessotherwiseinstructed.

Exampl es of how t o mark quest i onnai r es: Age

years

13

YES NO

SCHOOL:

TODAY' S DATE:

Day Mont h Year

YOUR NAME:

YOUR AGE:

years

YOUR DATE OF BI RTH:

Day Mont h Year

( Ti ck al l your answer s f or t he r est of t he quest i onnai r e)

Ar e you: MALE FEMALE

Opt i onal quest i ons on et hni ci t y her e


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6and7yearolds

On this sheet are questions about your childs name, school, andbirth

dates.Pleasewriteyouranswerstothesequestionsinthespaceprovided.

Allotherquestionsrequireyoutotickyouranswerinabox.Ifyoumakea

mistakeputacross in theboxand tick thecorrectanswer.Tickonlyone

optionunlessotherwiseinstructed.

Exampl es of how t o mark quest i onnai r es: Age

years

6

YES NO

SCHOOL:

TODAY' S DATE:

Day Mont h Year

CHI LD S NAME:

CHI LD S AGE:

years

CHI LD SDATE OF BI RTH:

Day Mont h Year

( Ti ck al l your answer s f or t he r est of t he quest i onnai r e)

I s your chi l d a: BOY GI RL

Opt i onal quest i ons on et hni ci t y her e


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7.2 Module1.1 CorequestionnaireforwheezingandasthmaQuestionnairefor13and14yearolds

1

Haveyou

ever

had

wheezing

Yes

orwhistlinginthechest

atanytimeinthepast? No

IFYOUHAVEANSWEREDNOPLEASESKIPTOQUESTION6

2 Haveyouhadwheezingor Yes

whistlinginthechest

inthelast12months? No


3 Howmanyattacksofwheezing None

haveyouhad 1to3

inthelast12months? 4to12

Morethan12

4 Inthelast12months,howoften,onaverage,has

yoursleepbeendisturbedduetowheezing?

NeverwokenwithwheezingLessthanonenightperweek

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?


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Questionnairefor6and7yearolds

1 Hasyourchildeverhadwheezing Yes

orwhistlinginthechest

atanytimeinthepast? No


2 Hasyourchildhadwheezingor Yes

whistlinginthechest

inthelast12months? No


3 Howmanyattacksofwheezing None

hasyourchildhad 1to3

inthelast12months? 4to12

Morethan12


yourchildssleepbeendisturbedduetowheezing?

Neverwokenwithwheezing

Lessthanonenightperweek


5 Inthelast12months,haswheezing Yes

everbeensevereenoughtolimityour

childsspeechtoonlyoneortwo No

wordsatatimebetweenbreaths?

6 Hasyourchildeverhadasthma? Yes

No

7 Inthelast12months,hasyour Yeschildschestsoundedwheezy

duringorafterexercise? No

8 Inthelast12months,hasyour Yes

childhadadrycoughatnight,

apartfromacoughassociatedwith No

acoldorchestinfection?


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7.2.1 Development,validationThese 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 aboutsymptomsproceeds 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.Itdoesnotmentionattacks of wheezing, in order to identify children with

persistentsymptomswhicharenotobviouslycharacterisedas

episodesorattacks.Thisisseenasaverysensitivequestion.

Qu.2. Limitationtoa12monthperiodreduceserrorsofrecalland(at

leastintheory)shouldbeindependentofmonthofcompletion.

This isconsidered tobe themostusefulquestionforassessing

theprevalenceofwheezingillness.

Qus.3,4. Thesequestionsoffer twoalternativequantitativemeasuresof

the frequency of wheezing. Problems with the concept of

attacks (seeabove)anddifficulty inquantifying 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 questionundernumber2 (where it wasused in thepilotstudy), ithas

been found in certain Australasian surveys to identify some


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27

children who deny (or whose parents deny) wheezing or

whistlingatquestion1or2.

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

presentationofasthma,andthisquestionhasbeenincludedtoincreasetheoverallsensitivityofthequestionnaire,althoughits

specificityinpopulationsurveysremainsunclear.


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7.3 Module1.2: Corequestionnaireforrhinitis7.3.1 QuestionnairesQuestionnairefor13and14yearoldsAllquestionsareaboutproblemswhichoccurwhenyouDONOThaveacoldor the

flu.

1 Haveyoueverhadaproblemwithsneezing, Yes

orarunny,orblockednosewhenyou

DIDNOThaveacoldortheflu? No


2 Inthepast12months,haveyouhadaproblem Yes

withsneezing,orarunny,orblockednose

whenyouDIDNOThaveacoldortheflu? No


3 Inthepast12months,hasthisnoseproblem Yes

beenaccompaniedbyitchywateryeyes? No

4

Inwhich

of

the

past

12

months

did

this

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


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1 Haveyourchildeverhadaproblemwithsneezing, Yes

orarunny,orblockednosewhenhe/she

DIDNOThaveacoldortheflu? No


2 Inthepast12months,hasyourchildhadaproblem Yes

withsneezing,orarunny,orblockednose

whenhe/sheDIDNOThaveacoldortheflu? No


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


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7.3.2 Development,validationTheprincipalaimsareto:(1)distinguishbetweenrhiniticandnonrhinitic

individuals in the general population; (2) predict which subjects with

rhinitisarelikelytobeatopic;and(3)givesomeindicationoftheseverityofrhinitisamongaffectedindividuals.

Thejustificationforindividualquestionsisasfollows:

Qu.1. Thisquestionwasfoundtohaveapositivepredictivevalueof

80%indetectingrhinitisinacommunitysampleofadults(aged

1665years)insouthwestLondon.

Qu.2. Asfor1above.

Qu.3. Thissymptomhad thehighestpositivepredictivevalue (78%)

indetectingatopyamongsubjectswithrhinitis.

Qu.4. Thisquestionpermitssubjectswithrhinitistobeseparatedinto

thosewithseasonalsymptomsaloneandthosewithaperennial

problem. The method maximises precision in classification, is

devoidofsubjectivedefinitionsofseason,andcouldbeused

byanycountryregardlessofclimate.Thenumberofmonthsa

subject isaffectedcouldbeusedasaquantitative indicatorof

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.


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7.4 Module1.3: Corequestionnaireforeczema7.4.1 QuestionnairesQuestionnairefor13and14yearolds1 Haveyoueverhad Yes

anitchyrashwhichwascomingand

goingforatleastsixmonths? No


2 Haveyouhadthisitchy Yes

rashatanytimeinthelast12months? No


3 Hasthisitchyrashatanytimeaffected Yes

anyofthefollowingplaces: No

thefoldsoftheelbows,behindtheknees,

infrontoftheankles,underthebuttocks,

oraroundtheneck,earsoreyes?

4

Hasthis

rash

cleared

completely

at

any

time

Yes

duringthelast12months? No

5 Inthelast12months,howoften,onaverage,haveyou

beenkeptawakeatnightbythisitchyrash?

Neverinthelast12months



6 Haveyoueverhadeczema? YesNo


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1 Hasyourchildeverhad Yes

anitchyrashwhichwascomingand

goingforatleastsixmonths? No


2 Hasyourchildhadthisitchy Yes

rashatanytimeinthelast12months? No


3 Hasthisitchyrashatanytimeaffected Yes

anyofthefollowingplaces: No

thefoldsoftheelbows,behindtheknees,

infrontoftheankles,underthebuttocks,

oraroundtheneck,earsoreyes?

4 Atwhatagedidthis Under2years

itchyrashfirstoccur? Age24years

Age5ormore

5 Hasthisrashclearedcompletelyatanytime Yes

duringthelast12months? No


yourchildbeenkeptawakeatnightbythisitchyrash?

Neverinthelast12months



7 Hasyourchildeverhadeczema? Yes

No


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7.4.2 Development,validationThese 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 inflammatorydermatoses 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. Followingtheformofthecorequestionnairesforwheezingandrhinitis, 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


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34

alonewereincluded,andsensitivity92%withspecificity96%if

casedefinition was based on both flexural involvement and

onsetbefore5yearsofage.

Qus.5,6. These two questions havebeen included as measures of theseverity 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 tobe 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: ...?). Asupplementarystemquestion (Ifyes,was thisdiagnosedbya

doctor?)wasconsideredoptional.


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7.5 Module1.4: Videoquestionnaire7.5.1 Questionnaire1.

Has

your

breathing

ever

been

like

this?:

atanytimeinyourlife? YES NO

ifYES,:inthelastyear? YES NO

ifYES,:oneormoretimesamonth? YES NO

2. Hasyourbreathingbeenlikethegirlsinthevideofollowingexercise?




3. Haveyoubeenwokenlikethisatnight?:atanytimeinyourlife? YES NO



4. Haveyoubeenwokenlikethisatnight?:




5. Hasyourbreathingbeenlikethis?:atanytimeinyourlife? YES NO




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38

questionnaires will be simultaneously compared in this age group.

Andersonetalwillbestudyingthevalidityofthethreecorequestionnaires

among13yearoldsusingadetailedinterview.

The pilot study has demonstrated that presentation of the writtenquestionnaire before the video does not affect responses to the video;

howeverpresentationofthevideofirstdoesaffectresponsestothewritten

questionnaire.

5. PredictivevalidityFrequent and persistent wheezing episodes are associated with chest

deformity, residual airways obstruction, radiological evidence of

hyperinflation,andpresenceofrhonchi inthe intervalphase(Gillametel

1970,McNicoletal1970).Wheezingatage7yearspredictslaterwheezing

andthisisincreasedifoneusesfrequencyofepisodesatage7(Anderson

etal1986).

Although bronchial hyperresponsiveness (BHR) has in the past been

equatedwithasthma,populationstudieshaveshown that itsrelationship

toasthmasymptomsandasthmadiagnosisisnotclose(Josephs,Pattemore

et al). This is probably because it is only one of several mechanisms

underling clinical asthma. BHR cannotbe regarded as the gold standard

(theoneobjectiveindicatorofasthma).Nevertheless,BHRisanimportant

factorinasthma,anditsrelationshiptothetoolsbeingusedisofparticular

interest. The prevalence of wheeze foundby 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 PresentationandtranslationItisimportantthatthequestionnairesarepreparedinaconsistentmanner.

Theorderofyes/noresponseshasbeendefined.Thelayoutandprintingof

thequestionnaireswillbestandardwitheachmodulebeingprintedona

singlepage.The4questionnairesfor1314yearoldsareusuallypresented

ononepieceof foldedpaperwith thevideoquestionnaire tobeshowingon thebackwhen folded.Alternatively theymaybepresentedseparately

withadequateidentificationoneachpage.


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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 thebest nonEnglish version for each

region.Insomecountries(e.g.NewZealand)theinformationsheetmaybe

translatedintothemainnonEnglishlanguages,butnotthequestionnaires,

providingthevastmajorityofthepopulationareconversantwithwritten

English.

8.0 Ethicsandconduct8.1

Ethical

committee

approval

Eachcentrewillneed toobtain thenecessaryEthicsCommitteeapproval

priortothestartofthestudy.Sampleinformationsheetsappearbelow.

8.2 ModelforapproachingschoolsWhat 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 hasbeen obtained, the school principal

willbeapproached forhis/hercooperationwith thestudy.Then thedata

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 Sampleinformationletterfor1314yearoldsDearChairmanofBoardofTrustees/Principal/Teachers

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

Children

Weare invitingsomechildrenatyourschooltotakepart inan important

studyaboutchildhealthwiththeapprovaloftheirparents.Manyschools

in Auckland are taking part in the study, and by random sampling


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40

techniques,yourschoolhasbeenselected.Wewishtostudychildrenaged

13and14years.

ThissurveyisbeingcarriedoutinrandomlyselectedschoolsinAuckland,

Wellington, Christchurch, Nelson and Hawkes Bay, and also in manyoverseas 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 makingavailableacopyoftheclasslistswithdateofbirthifpossible.

2. During this termoneofourresearch teamwouldbring informationsheets forparents(copyenclosed) to theschool, tobedistributed to

alltheselectedchildrenoneweekbeforethestudyteamcometoyour

school.

3. We would return the next week to ask these children to completewritten questionnaires (copy enclosed) and to watch a video aboutexercise andbreathing which lasts about ten minutes. We would

requireabout40minutesintotal.

4. Wewouldcomebackaboutaweeklater,withthequestionnairesandshowthevideotoanychildrenwhowereabsentonthefirstoccasion

anaskthemtocompletethesurvey.

Oneofourresearch teamwillbe incontactwithyousoon todiscuss this

survey further. In the meantime if there is any further information you

requireaboutthesurvey,pleasedonothesitatetocontactoneofus.Ifyou

areunable toreachusdirectlyby telephone,please leaveamessagewith

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).


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Yourssincerely

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

8.2.2Sample

information

letter

for

6

7

year

olds

DearChairmanofBoardofTrustees/Principal/Teachers

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

Children

Weare invitingsomechildrenatyourschooltotakepart inan important

studyaboutchildhealthwiththeapprovaloftheirparents.Manyschools

in Auckland are taking part in the study, and by random samplingtechniques,yourschoolhasbeenselected.Wewishtostudychildrenaged

67years.


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. Identifyingclassesinwhich67yearoldsarefoundandhavingreadyacopyoftheclasslistsfortheresearcher.

2. Oneofourresearchteamwillthencomeandnameeachsurveyformanddistributethembyclasstobetakenhome.

3. We will send information sheets, and questionnaires (copiesenclosed) 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.

Wewouldwish tohave informationon thedateofbirthandsexofanypotentiallyeligiblechildrenwhodonotparticipateinthesurvey.


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Oneofourresearch teamwillbe incontactwithyousoon todiscuss this

survey further. In the meantime if there is any further information you

requireaboutthesurvey,pleasedonothesitatetocontactoneofus.Ifyou

areunable toreachusdirectlyby telephone,please leaveamessagewith

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 ModelforapproachingparentsAn 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/guardiansof1314yearoldsDearParent/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.Thena10minutevideoaboutexerciseandbreathingwill

be shown to your child in his/her class and your child willbe asked to

completea furtherbriefquestionnaire.Thiswill takeup to40minutesof

classtime.


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43


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 willbe treated confidentially; only a code number willbe

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/guardiansof67yearoldsDearParent/Guardian

Weareinvitingyourchildtotakepartinanimportantsurveyaboutchild

health with the approval of your school. Many schools in Auckland are

takingpartinthestudyandallclassmatesofyourchildarebeingaskedtotakepart.Foreachchild,a parent/guardian isbeing asked to complete a

questionnaire.


Wellington,Christchurch,Nelson,HawkesBayandalsoinmanyoverseas

countries including Australia, Canada, USA, Britain and Germany. The

AucklandsurveyispartlyfundedbytheHealthResearchCouncilofNew

Zealand.


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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 GuidelinesforfieldworkersISAACresearchstaffandfieldworkersshouldnotusethetermsasthma,

allergy,rhinitisoreczemawhen

(i) advertisingthestudy(ii) presentingwrittenmaterialaboutthestudy(iii) speakingaboutthestudytoschoolstaff,parents,children(iv) speakingto1314yearoldchildrenintheclassroom.The phrases breathing survey or a survey aboutbreathing 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 thequestionnaires isbeing developedand testedby theNewZealand

steeringcommitteemembers,andwillberecommendedforuseinthefield.

PleasecontactInnesAsherforcopiesofthesequestionnaires.


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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 onwheezing

(ii) handingoutandcompletionofthewrittenquestionnaireonrhinitis(iii) HandingoutandcompletionofthewrittenquestionnaireoneczemaTheorderofpresentationofthecorequestionnairesisofimportance:theyshouldalwaysbepresentedwheezingrhinitiseczema.

(iv) Handing out the written questions for the video questionnairefollowedimmediatelybytheshowingofthevideoquestionnaire;the

writtenquestionsarecompletedwhilethisisbeingshown.Thevideo

questionnairemustalwaysbeshownafterthewrittenquestionnaires

In presenting the video, there mustbe adequate technical adequacy and

visualandaudioqualitytoensuresubjectsseeitwellandhearitcorrectly.

If questionnaires have clearly notbeen completed in a comprehensible

fashion, then they could be represented to the person who originally

completed them forone furtherattempt.Theresearchworkershouldnot

give advice about the responses that might be given. Once the

questionnaire is completed, it must notbe changedby research workers

underanycircumstances.


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9.0 DataTransferThe coding manual is available upon request from the regional

coordinators.


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10.0ContactaddressesISAACExecutive:

InnesAsher(Chairperson)

DepartmentofPaediatrics

SchoolofMedicine

UniversityofAuckland

PrivateBag

Auckland

NewZealand

Ph: *64(9)3737999Fax: *64(9)3737486

RichardBeasley

DepartmentofMedicine

WellingtonSchoolofMedicine

P.O.Box7343

WellingtonSouth

Wellington

NewZealand

Ph *64(4)3855999

Fax *64(4)3895725

DavidStrachan

DepartmentofPublicHealthSciences

StGeorgesHospitalMedicalSchool

CranmerTerrace

TootingLondonSW170RE

UnitedKingdom

Ph: *44(81)7255429

Fax: *44(81)7253584


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RegionalcoordinatorsforISAAC

EUROPE

WesternEurope

UlrichKeil,StephanWeiland

InstitutfrEpidemiologieundSozialmedizin

WestflischeWilhelmsUniversitt

VonEsmarchStrae56

D48129Mnster

Germany

Ph: *49(251)835396Fax: *49(251)835300

EasternEurope/Baltics

BengtBjrkstn


UniversityHospital

S58185Linkping

Sweden

Ph: *46(13)221331

Fax: *46(13)148265

AMERICA

NorthAmerica

FernandoMartinezRespiratorySciencesCenter

UniversityofArizona

HealthSciencesCenter

Tucson,AZ85724

USA

Ph: *1(602)6267780

Fax: *1(602)6266970


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LatinAmerica

JavierMallol

Clasificador14A

LaSerenaChile

Ph: *56(51)

Fax: *56(51)215678

AFRICA

GabrielAnabwani

DepartmentofPaediatricsFacultyofHealthSciences

P.O.Box4606

Eldoret

Kenya

Ph:

Fax: *254(321)33041

WESTERNPACIFIC

AsiaPacific

ChrisLai

DepartmentofMedicine

TheChineseUniversityofHongKong

PrinceofWalesHospital

ShatinNewTerritories

HongKong

Ph: *8526363127

Fax: *8526375396


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Oceania

InnesAsher


SchoolofMedicineUniversityofAuckland

PrivateBag

Auckland

NewZealand

Ph: *64(9)3737999

Fax: *64(9)3737486

SOUTHEASTASIA

J.R.Shah

JaslokHospitalandResearchCentre

15,DrGDeshmukhMarg

Bombay 400026

India

Ph: *91(22)4933333


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school absence causedby asthma and wheezing illness. Arch Dis Child

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AndersonHR,BlandJM,PatelS,PeckhamC.Thenaturalhistoryofasthma

inchildhood.JEpidemiolCommHealth1986;40:121129.

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Woolcock AJ. International comparison of the prevalence of asthma

symptomsandbronchialhyperresponsiveness.AmRevRespDis1988;138:

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Barry DMJ, Burr ML, Limb ES. Prevalence of asthma among 12 year old

children inNewZealandandSouthWales:acomparativesurvey.Thorax

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Prevalence ofbronchial hyperresponsiveness in children: the relationshipbetweenasthmaandskinreactivitytoallergens intwocommunities.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.


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CliffordRD,RadfordM,HowellJB,HolgateST.Prevalenceofrespiratory

symptomsamong7and11yearoldchildrenandassociationwithasthma.

ArchDisChild1989;64:11181125.

Cockcroft DW, HargreaveFE. Airway hyperresponsiveness.Relevance ofrandompopulationdatatoclinicalusefulness.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.

GillamGL,McNicolKN,WilliamsHE.Chestdeformity,residualairways

obstructionandhyperinflation,andgrowthinchildrenwithasthma.Arch

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GoldingJ, PetersT.Eczemaandhayfever. InButler NR, GoldingJ (eds).

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skintestsamongcollegestudents.JAllergy1969;44:323332.

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Venereol[stockholm]1980;92:4447.

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longitudinalstudy.AmRevRespDis1989:140:350357.

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

responsiveness indicate theseverityofasthma?EurRespirJ1990;3:220

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

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MontgomerySmithJ.Epidemiologyandnaturalhistoryofasthma,allergic

rhinitisandatopicdermatitis(eczema).In:MiddletonE,ReedCE,EllisEF,

Adkinson NF, Yunginger JW, eds. Allergy: principles and practice. St

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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.

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hyperresponsiveness in two populations of Australian school children. I.

Relation to respiratory symptoms and diagnosed asthma. Clin Allergy

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

epidemiological study in a populationbased twin sample. J Am Acad

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

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SibbaldB,RinkE.Epidemiologyofseasonalandperennialrhinitis:clinicalpresentationandmedicalhistory.Thorax1991;46:895901.

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asthmainchildhood.BrMedJ1983:286:12531256.

Strachan DP, GoldingJ, Anderson HR. Regional variations in wheezing

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Documents

Phase One Manual