asthma and allergies: where in the world are we now?

Innes AsherDepartment of Paediatrics: Child and Youth Health

The University of Auckland

Chair of the International Study of Asthma and Allergies in Childhood (ISAAC)

http://isaac.auckland.ac.nz

© ISAAC 2011

Asthma and allergies:Where in the world are we now?

Ehara tāku toa i te toa takitahi ēngari he toa takimano e

My strength is not mine alone, but that of many

In This Lecture

1. ISAAC: The International Study of Asthma and Allergies in Childhood

2. Some commonly held beliefs – have they been changed by ISAAC?

3. What is happening in New Zealand?

Asthma EczemaRhinitis

© ISAAC 2011

International Study of Asthma and Allergies in Childhood ISAAC studies three conditions

ISAAC – how did it start?

© ISAAC 2011

ISAAC Formed in 1991 From Two Initiatives

1. Does New Zealand have more severe asthma than other English speaking countries?(NZ asthma deaths and admissions were high)

2. Monitoring trends and underlying causes of asthma and allergies in childhood – following the fall of the Berlin wall.(genetically similar populations, different environments)

© ISAAC 2011

Rationale of ISAAC

● Increasing concern about asthma and allergies.

● A fresh look was needed with a world population view –between populations rather than within populations.

● Most of world not yet studied – may add something.

● A standardised and coordinated approach was needed to obtain comparable worldwide data.

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Few Centres With Information on Prevalence* of Asthma Symptoms in Children up to 1991

* Prevalence = how common it is

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© ISAAC 2011

ISAAC: 306 research centres in 105 countries

Local collaborating centres

National coordinators

Regional coordinators

Organisation of ISAAC

Steering Committee(IA Chair)

International Data Centre (Auckland)

© ISAAC 2011

● The Auckland Medical Research Foundation● The Health Research Council of NZ● The Asthma and Respiratory Foundation of NZ● The National Child Health Research Foundation● The Hawke's Bay Medical Research Foundation● The Waikato Medical Research Foundation● Glaxo Wellcome NZ, and International Medical Affairs● Astra NZ● Maurice & Phyllis Paykel Trust● BUPA Foundation● NZ Lotteries Commission● The University of Auckland

Funders of The ISAAC Programme inNew Zealand

© ISAAC 2011

Asthma, rhinitis and eczemaCommonly held beliefs in 1991

o Diseases of only affluent western countrieso More severe in affluent than non-affluent countrieso On the increase in western countrieso Strongly associated with allergy

© ISAAC 2011


o More allergen exposure is causing the high rates of asthma and rhinitis

o Air pollution is a key reason for high rates of asthmao Genetics will explain differences in asthma rates

© ISAAC 2011

ISAAC – what did we do?

© ISAAC 2011

ISAAC Phase One 1991 – 1998● Worldwide prevalence (questionnaires)● ISAAC Phase One ecological analyses

ISAAC Phase Two 2000 – 2004● Questionnaires & additional markers

ISAAC Phase Three 2001 – 2005● Repetition of Phase One● Addition of more centres● Environmental questionnaire

The ISAAC Programme

© ISAAC 2011

● Multicentre cross-sectional studies of children in randomly sampled schools.

● 13-14 year olds and optional 6-7 year olds.

● 3000 per age group per centre.

● Standardised validated simple written questionnaires (optional video asthma questionnaire in 13-14 year olds).

ISAAC Methods: Phases One & Three

Asher MI et al. Eur Respir J 1995; 8: 483-91.Ellwood P et al. Int J Tub Lung Dis 2005; 9: 10-16. © ISAAC 2011

Similar, but these differences:

● Smaller number of children, centres and countries.

● 9-11 year old children.

● Addition of child contact modules including allergy skin prick tests and IgE.

ISAAC Methods: Phase Two

Weiland SK et al. Eur Respir J 2004; 24: 406-12. © ISAAC 2011

How many took part? ISAAC Phase Three

Countries Centres Participants Response Rate (%)

13-14 year

6-7 year

97

61 233

144

798,685

388,811

88

85

© ISAAC 2011

The Prevalence of Asthma Symptoms Between Populations

Current wheeze definition

Yes to:

“Have you (Has your child) had wheezing or whistling in the chest in the past 12 months?”

© ISAAC 2011

Current wheeze and at least one of:●≥4 attacks of wheeze●≥1 night per week sleep disturbance from wheeze●wheeze limiting speech

Definition of Symptoms of Severe Asthma

© ISAAC 2011Lai CKW et al. Thorax 2009; 64: 476-83.

ISAAC – what did we find?

© ISAAC 2011

Asthma, rhinitis and eczema: diseases of ONLY affluent western countries?

© ISAAC 2011

Lai CKW et al. Thorax 2009; 64: 476-83. © ISAAC 2011

Asthma, rhinitis and eczema: diseases of ONLY affluent western countries?

NOT TRUE

© ISAAC 2011

Asthma, rhinitis and eczema: more severe in affluent than non-affluent countries?

© ISAAC 2011

Asthma, rhinitis and eczema: more severe in affluent than non-affluent countries?

NOT TRUE

© ISAAC 2011

Asthma, rhinitis and eczema: on the increase in western countries?

© ISAAC 2011

Increase in Current Wheeze in School Children, 1973 - 1995

Year

Current Wheeze

(%)

1970 1975 1980 1985 1990 1995 20000

5

10

15

20

25

30New Zealand

New Zealand

Australia

Wales

England

England

Scotland & England

Scotland

Magnus P, Jaakkola JJ. BMJ 1997; 14: 1795-9. © ISAAC 2011

Asthma, rhinitis and eczema: on the increase in western countries?

PARTLY TRUE

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Is air pollution a key reason for high rates of asthma?

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No relationship between air pollution and symptoms of asthma

Asher MI et al. Resp Research 2010; 11: 8.

Exposure Direction of Association

Air pollution -

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What about trucks?

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Brunekreef B, et al. Environ Health Perspect 2009; 117: 1791-8.

Current wheeze & truck traffic in street of residence “almost the whole day” vs “never” (13-14 yr olds)

© ISAAC 2011

Odds Ratio1.35 (1.22-1.48)

Is air pollution a key reason for high rates of asthma?

NOT TRUEbut truck traffic causes more asthma

symptoms in some childrenMore study needed!

© ISAAC 2011

Which other environmental factors

may influence how common asthma, rhinitis

and eczema symptoms are in populations?

© ISAAC 2011

Current Wheeze and Gross National Income (GNI), 13-14 Year Age Group

GNI Per Capita (US$)0 10000 20000 30000 40000

CurrentWheeze

(%)

0

10

20

30

40

Lai CKW et al. Thorax 2009; 64: 476-83.World Bank. Data for 2001; http://go.worldbank.org/U9BK7IA1J0 (accessed 8 October 2007). © ISAAC 2011

Current wheeze and tobacco consumption



Tobacco (females)

© ISAAC 2011

Exposures in the child first year of life and symptoms (individual questionnaires)

Antibiotic use in the 1st year of life

Paracetamol use in the 1st

year of life

Fully adjustedOdds Ratio (95%CI)

1.70 (1.60-1.80)

1.46 (1.36-1.56)

Foliaki S et al. J Allergy Clin Immunol 2009; 124: 982-9.Beasley R et al. Lancet 2008; 372: 1039-48.

© ISAAC 2011

Which dietary factors are important?

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Current Wheeze and Diet

Nagel G et al. Thorax 2010; 65: 516-522


Burger consumption

Trans fatty acids

Plant based foodsFresh fruitFresh vegetablesFishMediterranean diet

© ISAAC 2011

Protective Effect of Breastfeeding

Nagel G, et al. Eur Respir J 2009; 33: 993-1002. © ISAAC 2011

CountriesNon-allergic Allergic

High income countries

protective no effect

Current wheezers

no effect

Low and middle income countries

no effect

Is more allergen exposure causing the high rates of asthma and rhinitis?

© ISAAC 2011

Lower rates of rhinitis with high pollen in centres



Pollens

© ISAAC 2011

Is more allergen exposure causing the high rates of asthma and rhinitis?

NOT TRUE

© ISAAC 2011

Asthma, rhinitis and eczema: strongly associated with allergy ?

© ISAAC 2011

Association of Current Wheeze & Skin Prick Test Reactivity

Weinmayr G et al. Am J Respir Crit Care Med 2007; 176: 565-74. © ISAAC 2011

Allergen exposure

Allergic tendency

AsthmaRhinitisEczema

Source: N Pearce 2011© ISAAC 2011

Models of asthma causation (Neil Pearce)

Allergen exposure

Allergic tendencyAsthma

Rhinitis

Eczema



Allergen exposure

Allergic tendencyAsthma

Rhinitis

EczemaOtherexposures



Asthma and eczemagenetics

o Massive developments in genetics over 20 yearso Have completed genome-wide association and

interactions studies (GWAS & GWIS)o In largest study ever - 15 billion genotypes - very few

associations found, none newo None useful predictors of disease in individual peopleo Findings explain only a fraction of the familial

aggregation

o EXCEPTION is the fillaggrin gene mutations & eczema© ISAAC 2011

Asthma

Childhood onset

© ISAAC 2011Moffatt MF et al for the GABRIEL Consortium. A large-scale, consortium-based genomewide association study of asthma N Engl J Med 2010; 363(13): 1211-21

Loci associated with IgE were not associated with asthma


o Diseases of only affluent western countries – NOT TRUEo More severe in affluent than non-affluent countries –

NOT TRUEo On the increase in western countries – PARTLY TRUEo Strongly associated with allergy – NOT STRONGLY

© ISAAC 2011


o More allergen exposure is causing the high rates of asthma and rhinitis – NOT TRUE

o Air pollution is a key reason for high rates of asthma –NOT TRUE but watch out for trucks......

o Genetics will explain differences in asthma rates – NOT YET

© ISAAC 2011

Further directions

● Asthma rhinitis and eczema symptoms are a big global problem, and the global burden is increasing – more research needed.

● Environmental factors are key, and we need to find out which matter most, especially in low and middle income countries.

● Understand the mechanisms of and influences on non-allergic asthma.

● Deliver good asthma, rhinitis and eczema management to all children with asthma in the world.

© ISAAC 2011

Asthma symptoms in NZ among the highest in the world13-14 Year Age Group

Country (prevalence %)

Albania (3.4)China (3.5)

Georgia (5.1)Indonesia (5.1)

Syrian Arab Republic (5.2)India (5.4)

Cameroon (5.7)Samoa (5.8)Taiwan (5.9)

Hungary (6.1)Egypt (7.0)

Lithuania (7.5)Republique Democratique du Congo (7.5)

Kuwait (7.6)Kyrgyzstan (7.6)

Italy (8.1)Bulgaria (8.2)

Nouvelle Caledonie (8.2)Belgium (8.3)Croatia (8.4)

Sultanate of Oman (8.4)Philippines (8.4)Hong Kong (8.6)

Palestine (8.7)Morocco (8.7)

Algeria (8.7)South Korea (8.8)

Former Yugoslav Republic of Macedonia (FYROM) (8.8)Mexico (8.9)

Malaysia (8.9)Ethiopia (9.1)Estonia (9.3)

Serbia and Montenegro (9.7)Sweden (9.7)Gabon (10.2)Poland (10.3)

Fiji (10.4)Latvia (10.5)

Thailand (10.5)Cook Islands (10.6)

Iran (10.7)Japan (10.7)Spain (10.8)

Pakistan (10.9)Russia (11.2)

Polynesie Francais (11.3)Singapore (11.4)

Portugal (11.4)Colombia (12.0)

Netherlands (12.2)Jordan (12.3)

Argentina (12.4)Sudan (12.5)

Niue (12.7)Nigeria (13.0)

Trinidad and Tobago (13.3)Bolivia (13.5)

Tunisia (13.7)Canada (13.7)

Nicaragua (13.8)Malta (14.6)Chile (14.9)

Austria (15.1)Venezuela (15.4)

Ukraine (15.8)Uruguay (15.8)

Kenya (15.9)Kingdom of Tonga (16.2)

Ecuador (16.7)Togo (16.8)

Germany (17.5)Cuba (17.8)

République de Guinée (18.6)Finland (19.0)

Brazil (19.0)South Africa (19.2)Cote d'Ivoire (19.3)

Peru (19.6)Tokelau (19.7)

Congo (19.9)Barbados (20.8)Paraguay (20.9)

USA (21.0)Reunion Island (21.5)

Honduras (22.0)Romania (22.7)Panama (22.9)

Sri Lanka (23.0)United Kingdom (24.5)

New Zealand (26.3)Channel Islands (26.5)

Republic of Ireland (26.7)Costa Rica (27.3)

Vietnam (29.5)Australia (30.6)

El Salvador (30.8)Isle of Man (31.2)

Prevalence (%)0 5 10 15 20 25 30 35 40

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© ISAAC 2011

6-7 Yrs 13-14 Yrs 20–44 yrs

Wheeze in the past year

22.2% 26.7% 25.9%

Asher MI, et al. N Z Med J 2008; 121: 52-63.ECRHS. Eur Respir J 1996; 9, 687-95.Lai CKW, et al. Thorax 2009; 64: 476-83.

How common are symptoms of asthma in New Zealand?

© ISAAC 2011

6-7 Yrs 13-14 Yrs


22.2% 26.7%

Asher MI, et al. N Z Med J 2008; 121: 52-63.ECRHS. Eur Respir J 1996; 9, 687-95.Lai CKW, et al. Thorax 2009; 64: 476-83.

Symptoms of asthma are reducing

© ISAAC 2011

Maori Pacific European


28.5% 25.2% 20.7%

Ellison-Loschmann L, et al. Int J Tuberc Lung Dis 2009; 13: 775-82.

Symptoms are higher and going up in Māori children and lower and going down in European.

– the gap is widening

© ISAAC 2011

Maori Pacific EuropeanWheeze in the past year

28.5% 25.2% 20.7%

≥4 wheezing attacks in the past year

9.3% 7.1% 6.8%

≥1 night waking from wheeze in the past year

17.1% 16.4% 12.1%

≥ 1 wheeze affecting speech in the past year

6.2% 5.1% 2.9%

Asthma ever 38.8% 26.4% 29.0%

Ellison-Loschmann L, et al. Int J Tuberc Lung Dis 2009; 13: 775-82.

More severe asthma symptoms are more common Māori children

© ISAAC 2011

Addressing the Inequalities in NZ

What have we done to try to make some improvements?

●Paediatric asthma guideline discussed some issues.

●More Maori and Pacific health providers.

●Pharmac/BPAC working to lower reliever:preventer prescriptions in Maori and Pacific (‘Space to breathe’).

© ISAAC 2011

Addressing the Inequalities in NZ

What needs to be done?

●Address the root disparities in the underlying influences on health through government policy. – see www.cpag.org.nz

●Address all the recommendations of He Mate Huangō 1991 including

• Reduce cost of doctors visits and prescriptions

• Improve housing

© ISAAC 2011

http://www.cpag.org.nz/�

http://isaac.auckland.ac.nz

Thanks to children, parents, school staff, ISAAC staff and collaborators, funders

© ISAAC 2011

asthma and allergies: where in the world are we now?

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