Global Asthma Report 2014

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Global

Asthma

Network

The Global

Asthma Report2014


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Copyright 2014 The Global Asthma Network

All rights reserved. No part of this publication may be reproduced without the permissionof the authors and publisher.

ISBN: 9780473291259 PRINT | 9780473291266 ELECTRONICThe mention or photographs of specific companies or of certain manufacturers productsdoes not imply that they are endorsed or recommended by the Global Asthma Networkin preference to others of a similar nature that are not mentioned. The Global AsthmaNetwork does not warrant that the information contained in this publication is completeand correct and shall not be liable for any damages incurred as a result of its use.

Suggested citation: The Global Asthma Report 2014. Auckland, New Zealand: GlobalAsthma Network, 2014.

Global

AsthmaNetwork

www.globalasthmanetwork.org

Asthma may affectas many as334 million people.*

*For explanation see Chapter 2 How many people have asthma?


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11

GLOBAL ASTHMA REPORT 2014

Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2

Executive Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

R e c o m m e n d a t i o n s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

THE GLOBAL ASTHMA NETWORK . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

1. Global Asthma Network. . . . . . . . . . . . . . . . . . . . . . . . . . . . 10Innes Asher, Nils Billo, Karen Bissell, Chiang Chen-Yuan,Philippa Ellwood, Asma El Sony, Luis Garca-Marcos, JavierMallol, Guy Marks, Neil Pearce, David Strachan

PART ONE: THE BURDEN OF ASTHMA . . . . . . . . . . . . . . . . . . . . . . .14 2. Global Burden of Disease due to Asthma. . . . . . . 16 Guy Marks, Neil Pearce, David Strachan, Innes Asher

3. Hospital Admissions for Asthma. . . . . . . . . . . . . . . . . . 22 David Strachan, Ramyani Gupta, Luis Garca-Marcos

4. Asthma Mortality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 David Strachan, Elizabeth Limb, Neil Pearce, Guy Marks

5. Wheezing in Infants. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 Javier Mallol, Luis Garca-Marcos, Paul Brand

6. The Economic Burden of Asthma. . . . . . . . . . . . . . . . . 36 Mohsen Sadatsafavi, J Mark FitzGerald

7. Factors Affecting Asthma . . . . . . . . . . . . . . . . . . . . . . . . . .39 Neil Pearce, David Strachan

PART TWO: MANAGEMENT OF ASTHMA ANDCAPACITY BUILDING . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .42

8. National Asthma Strategies. . . . . . . . . . . . . . . . . . . . . . . . 44 Tari Haahtela, Olof Selroos, Philippa Ellwood,

Nadia At-Khaled 9. Asthma Management Guidelines . . . . . . . . . . . . . . . . 48 Philippa Ellwood, Innes Asher, Karen Bissell, Guy Marks,

Asma El Sony, Eamon Ellwood

10. Access to Quality-Assured, Affordable AsthmaMedicines. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52

Karen Bissell, Christophe Perrin

11. Quality of Inhalers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 Christophe Perrin, Luis Garca-Marcos, Javier Mallol,

Karen Bissell

12. Asthma Management in Low-Income

Countries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .61 Karen Bissell, Chiang Chen-Yuan, Nadia At-Khaled,

Christophe Perrin

13. Short Courses Relevant to Asthma Research andPolicy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65

Neil Pearce, Nils Billo, Karen Bissell

PART THREE: ASTHMA - A GLOBAL PRIORITY. . . . . . . . . . . . . . . . . 66 14. Asthma as a Lung Health Priority in Low- and

Middle-Income Countries. . . . . . . . . . . . . . . . . . . . . . . . . . 68 Asma El Sony, Nadia At-Khaled, Javier Mallol

15. Asthma as an NCD Priority. . . . . . . . . . . . . . . . . . . . . . . . . 72 Neil Pearce, Javier Mallol

Appendices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .76

Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78

Appendices A-D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .801


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The Global Asthma Report 2014 has been prepared by the Global Asthma Network (GAN) Steering Group and invitedauthors with additional expertise. It provides substantial up-to-date information about asthma: each chapter is a state-of-the-art summary of what is known and where the gaps lie, and each makes recommendations to authorities onrequired actions. Included are findings from new GAN surveys on asthma guidelines, national asthma strategies andaccess to quality-assured, affordable asthma medicines.

Designed for government ministers, policy-makers, health authorities, health professionals, patient supportorganisations and people living with asthma, this report gives an update of what is known about the global burden ofasthma, management of asthma and capacity building, and ways of making asthma a global priority.

It is encouraging to see that recognition of asthma as a global problem has increased since the first Global AsthmaReport 2011 was published by the International Union Against Tuberculosis and Lung Disease (The Union) andInternational Study of Asthma and Allergies in Childhood (ISAAC).

GAN was established in 2012, building on the work pioneered and achieved by the ISAAC programme over the preceding20 years and the asthma management work of The Union in low- and middle-income countries. The people involved infounding GAN, from each organisation, were largely those involved in publishing the Global Asthma Report 2011.

GAN is a worldwide collaboration, involving more than half the worlds countries. It will undertake global surveys ofasthma in children and adults to measure and monitor asthma and its burden, providing the essential data called forby the World Health Organization. No one else is currently doing this work. GAN aims to reduce asthma suffering byimproving asthma care globally, with a focus on low-and middle-income countries, achieving this through research,capacity building, and access to effective asthma management and care including qualityassured essential asthma

medicines.

Elsewhere, there have been other developments increasing the visibility of asthma. On 19 September 2011, the GeneralAssembly of the United Nations (UN) made a political declaration on the prevention and control of non-communicablediseases (NCDs), focussing world attention on the increasing threat of asthma and other NCDs to global health, socialwelfare and economic development, especially in low- and middle-income countries. This was followed in 2013 by tworeports from the World Health Organization (WHO) on NCDs: A Global Action Plan 2013-2020 and Global MonitoringFramework. In July 2014 the UN held a review meeting. In his opening address the UN Secretary General, Ban Ki-moon,said

The global epidemic of NCDs is a major and growing challenge to development. Each year, in developing countriesalone, strokes, heart attacks, cancer, diabetes or asthma kill more than 12 million people between the ages of 30 and70.

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While estimating the number of people in the world with asthmaremains difficult due to the many gaps in the data, the GlobalBurden of Diseases Study (GBD) published in 2012 gave us thelatest estimate of asthma prevalence, indicating that as many as334 million people in the world have asthma, and that the relatedburden is high.

Since 2012, WHO has published guidelines for the prevention andcontrol of asthma in primary health care in low-resource settings.Guidelines on asthma from other organisations, including the GlobalInitiative on Asthma (GINA), have been updated. The EuropeanAcademy of Allergy and Clinical Immunology (EAACI) has publisheda Global Atlas of Asthma. The Forum of International RespiratorySocieties (FIRS) has published its report Respiratory diseases inthe world. Realities of today opportunities for tomorrow, whichhighlights asthma as one of the top 5 respiratory diseases in the

world.

All these activities, concerns, developments and knowledgeinform contents of the Global Asthma Report 2014 and itsrecommendations. We hope you will find it useful. We will continueto work together to increase the worldwide understanding of thisdisease, and to reduce the burden and suffering from asthma, overthe next few years.

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Innes Asher

ChairThe Global Asthma Network


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With good long-term management, the burden of asthma can be reduced.

In the Global Asthma Report 2014, the Global Asthma Network (GAN) has brought together an up-to-date overview ofthe key issues regarding asthma globally.

When examining the burden of asthma today, there is much to be concerned about.

Asthma is a common chronic non-communicable disease that affects as many as 334 million people of all ages in allparts of the world. It is a cause of substantial burden to people, often causing a reduced quality of life, not only due toits physical effects, but also its psychological and social effects. The various estimates of its economic burden, mostlydue to productivity loss, are all significant. Further, avoidable asthma deaths are still occurring due to inappropriatemanagement of asthma, including over-reliance on reliever medication rather than preventer medication. Asthma is aparticularly serious burden in low- and middle-income countries least able to afford the costs.

While our knowledge has increased, the remaining gaps in the data are significant.

While hospital admissions save lives during acute asthma attacks, there are many places where the number of hospital

admissions is too high, and the reasons for this need more research. The factors affecting asthma also require furtherresearch. New surveys are needed to update asthma trends, assess the burden of asthma and access to effectivemanagement. Meanwhile, GAN is working towards closing the data gaps.

But much of this burden of disease and lack of information is avoidable.

Asthma which is well controlled imposes far less of an economic and personal burden than non-controlled asthma.Strategies towards improving access and adherence to evidence-based therapies can therefore be effective in reducingthe personal and economic burden of asthma in all countries. Implementation of relatively simple measures within asystematic national or local strategy can improve early detection of asthma and provide effective preventive treatment.Asthma management guidelines are an essential part of successfully managing asthma and promoting the delivery ofquality asthma care; these are widely available.

Political commitment and action are required to make the burden of asthma a thing of thepast.

The Global Asthma Report 2014 makes many recommendations to the World Health Organization (WHO), governments,health authorities and health professionals, which, if followed, will transform asthma globally from a burden to aninconvenience.

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As part of their asthma strategy, every country needs:

An up-to-date approach to the diagnosis and managementof wheezing in young children. This is an evolving field. Thisreport includes a review of recurrent wheezing in infants includinginformation from a recent international study. If an infant presentswith frequent and/or severe episodes of recurrent wheezing theyshould be diagnosed and managed as asthma, unless there isevidence to the contrary.

Guaranteed access to quality-assured essential asthmamedicines. This is vital to improving asthma outcomes. Essential

asthma medicines need to be on all national lists of essentialmedicines and reimbursed medicines; this is not yet the case.Essential asthma medicines are inhalers which are complex devices,requiring accurate manufacturing to produce a reliable dosewith particles of an inhalable size. Many devices on the marketare substandard or unaffordable. WHO has a key role in settingstandards for these medicines, and all parties must working to makethem affordable.

Effective policy action on known, remediable causes of asthma

such as parental smoking (for children) and occupational exposures(for adults).

Capacity building of trained health professionals.This is vitaland can be enabled by participation in research. Short coursesin research generally, or asthma research in particular, provideopportunities for upskilling in research for those with limited timeand resources.

In low- and middle-income countries, efforts should be accelerated to

make asthma a lung health priority. Asthma management and controlis feasible even in low-income countries, and it should be on everyonesagenda. In 2012 WHO published guidelines for asthma management inlow-income settings.

GAN will work with others to achieve better asthma outcomes throughundertaking global surveys of asthma in children and adults, research,capacity building, improving access to effective asthma managementand care, including quality-assured essential medicines, and throughadvocacy activities.

Together, we can ensure that asthma is managed so that its associateddisability, death, and economic drain is massively reduced even ifprevalence rises.

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The World Health Organization (WHO) should add essential asthma medicines to their Prequalification

Programme, promote the standardisation of the dosagesof active ingredients in combined inhalers and theharmonisation of quality requirements for inhalersacross international reference documents such as the

pharmacopoeias.

Governments should

commit to research, intervention, and monitoringto reduce the burden of asthma in the world. Globalsurveillance of asthma requires standardised measuresof asthma implemented in large scale surveys of bothchildren and adults in diverse settings worldwide;

include asthma in all their actions arising from the WHOGlobal Action Plan for the Prevention and Control ofNon-communicable Diseases (NCDs) 2013-2020, and theWHO NCD Global Monitoring Framework;

ensure that they have a list of essential medicines forasthma which includes both inhaled corticosteroids andbronchodilator in dosages recommended by WHO, andthat these are available, quality-assured, and affordablefor everyone in their countries;

ensure all asthma inhalers procured, distributed and soldin their countries meet international quality standards;

particularly in low-income countries, makecommitments to ensure that the supply of quality-assured, affordable essential asthma medicines isuninterrupted, health professionals are appropriatelytrained, and health services are organised to manageasthma;

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particularly in low- and middle-income countries make asthma ahealth priority, in order to more quickly invest in asthma research

relevant to their populations, integrate care at community andprimary health care levels with appropriate referral procedures,and develop capacity in standard case management of asthma;

strengthen policies to reduce tobacco consumption, encouragehealthy eating and reduce exposure to potentially harmfulchemicals, smoke and dust. Funders need to support furtherresearch to identify causes of asthma;

measure and monitor the economic costs of asthma in theircountries, including health care costs and productivity losses.

Health authorities in all countries should

develop national strategies and action plans to improve asthmamanagement and reduce costs;

ensure the availability of nationally approriate asthmamanagement guidelines and provide access for everyone to thequality-assured, affordable essential asthma medicines thoseguidelines recommend;

encourage their health professionals to attend short coursesrelevant to asthma research and policy;

collect counts of hospital admissions in children and adults, fromdefined catchment populations, to monitor trends in asthma overtime;

report rates of asthma deaths in children and adults to monitorprogress in asthma care and as an early warning of epidemics of

fatal asthma.

Health professionals in all countries should

regard frequent or severe recurrent wheezing in infancy as part ofthe spectrum of asthma;

ensure that their country is represented in the Global AsthmaNetwork (GAN).

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A world where no-onesuffers from asthma8


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THE GLOBALASTHMA

NETWORK

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Global AsthmaNetwork

The Global Asthma Network

(GAN) has grown out of theInternational Study of Asthmaand Allergies in Childhood(ISAAC) and the InternationalUnion Against Tuberculosis andLung Disease (The Union). It aimsto reduce asthma suffering byimproving asthma care globally

with a focus on low- and middle-income countries. GAN willachieve this through undertakingglobal surveys of asthma inchildren and adults, research,capacity building, improvingaccess to effective asthmamanagement and care, includingquality-assured essential

medicines, and through regularadvocacy activities.

GAN plays a crucial role in collectingasthma data on adults and children globally;this data is not being obtained by any othergroup. In 2012 the leader of the World HealthOrganization (WHO), Dr Margaret Chan, said

Accurate assessment of the global,

regional and country health situation and

trends is critical for evidence-based decisionmaking in public health. The real need is

to close the data gaps, especially in low-and

middle-income countries.

For asthma this is exactly what GAN isdoing closing the data gaps.

GAN was established in 2012 toimprove asthma care globally (www.globalasthmanetwork.org). GAN is a newcollaboration between individuals from

ISAAC - isaac.auckland.ac.nz/ (now woundup) and The Union - www.theunion.org.

GAN is building on the work achievedby the ISAAC programme (1991-2012),which has an impressive track record ofundertaking surveys which have contributedextensive data on asthma and allergies inchildren, monitoring these diseases overtime, and researching possible causes. GANis operating on the same principles usedin ISAAC of collaborative and systematicapplication of standardised methodologiesable to be used in all settings in the world.In addition to asthma in children, GAN willstudy asthma in adults. Surveys will beconducted and repeated as resources allow.

GAN is led by an 11-member internationalSteering Group responsible for developingand overseeing its work programme. Long-term targets have been developed (Figure 1).

The GAN Data Centre is located in Auckland,New Zealand. The Data Centre leads thesurveys, communicates methodologies,

1. Innes Asher, Nils Billo, Karen Bissell, Chiang Chen-Yuan, Philippa Ellwood, Asma ElSony, Luis Garca-Marcos, Javier Mallol, Guy Marks, Neil Pearce, David Strachan

Closing the world datagaps for asthma inchildren and adults willbe a key activity of theGlobal Asthma Network.

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analyses data, oversees publications, anddevelops and maintains the GAN website.

Methods

GAN welcomes participation from centresin all countries in the world. In August 2014there were 276 centres in 119 countries thathad expressed an interest in participating inGAN (Figure 2).

Principal Investigators in each centrecomplete surveys about asthma in theircentre and country. Surveys are of two types:

on-line surveys of GAN Principal Investigatorsabout specific topics, and questionnairesurveys undertaken through schools. Highparticipation rates are sought in all surveys.In 2013/14, GAN surveys of the first type werecompleted, on national asthma strategies,asthma management guidelines and access toquality-assured, affordable asthma medicines;the findings are summarised in Chapters 8, 9and 10.

Surveys of the second type are planned to

start in 2015. Each centre will be invited toundertake a survey using the GAN protocoland questionnaires. Two age groups ofchildren will be involved (13-14 year olds and6-7 year olds), as well as parents/caregivers ofeach child. The adolescents and the parentsof the children will be asked to completequestionnaires based on ISAAC, includingadditional questions on asthma managementand the environment; for the adults, questionswill be based on the European Community

Respiratory Health Survey.Participants will be selected from

randomly sampled schools within a specifiedgeographical area (or all schools) around eachstudy centre. Within each country at least oneurban and one rural centre will be soughtso that the different influences of theseenvironments on asthma can be explored.A sample size of 3000 per age group percentre will be used to give sufficient power todetect differences in the severity of asthma.

For smaller populations, such as a smallisland nation, all pupils (and their parents/caregivers) of the age group will be selected.

Tools to enable centres to follow and use themethodology will be available on the GANwebsite.

Impact

GAN is currently the only global study ofasthma in populations (following on from theISAAC programme) and will contribute newinformation on adult as well as childhood asthma.GAN connects with others who strive for a worldwhere no-one suffers from asthma and hasestablished communication with worldwideorganisations concerned with respiratory

health and non-communicable diseases (NCDs),especially in low-and middle-income countries.

ISAAC demonstrated that asthma and

allergies are global health problems and thatenvironmental factors are key. GAN is continuingthis work. The value of GAN is attested to by thelarge number of centres that have expressed aninterest in participating, and the fact that majorinternational respiratory and NCD advocacyorganisations involved in monitoring andpreventing chronic respiratory disease haveexpressed their support for GAN.

GAN has set ambitious targets to decreasesevere asthma by 50% by 2025 and to increase

the access to quality-assured essential asthmamedicines (Figure 1). If these targets are achieved,then the burden of, and suffering from, asthma in

proportion of symptomatic people with asthma

not on inhaled corticosteroids

time off work/school because of asthma

unplanned visits for asthma

hospital admissions for asthma severity of asthma

mortality from asthma

Decrease severe asthma by 50% by 2025

Increase the access to quality-assured

essential asthma medic ines by 2018:

On the WHO prequalifi cation list - 2014

On National Essential Medicines Lists - 2015 Available in all coun tries - 2018

Affo rdable in all coun tries - 2018

Figure 1:

Targets of the Global Asthma Network

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Strive for a world where no-onesuffers from asthma.

Be the asthma surveillance hubfor the world.

Raise the profile of asthma as anon-communicable disease.

Stimulate and encouragecapacity building in low- andmiddle-income countries.

Promote access to appropriatemanagement of asthma.

Research ways of reducing theburden of asthma.

ASPIRATIONS OF THEGLOBAL ASTHMA NETWORK

Empowerment

Solidarity

Independence

Quality

Accountability

VALUES OF THE GLOBALASTHMA NETWORK

Mission of the GlobalAsthma Network:

To prevent asthma andimprove asthma careglobally with a focus onlow- and middle-incomecountries.

The network will achievethis through enhancedsurveillance, research,capacity building, andaccess to effectiveasthma care, includingquality-assured essentialmedicines.

Vision of the Global

Asthma Network:A world where no-onesuffers from asthma.

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1313

the world will be markedly reduced.

Conclusion

GAN seeks to build on the work of ISAAC andThe Union to lessen the suffering from asthma inthe world through surveillance of asthma, research,capacity building, improving access to effectiveasthma management and care, including quality-

assured essential medicines, and to advocate forasthma to be high on the public health agenda.

Health professionals in allcountries should ensure thattheir country is represented inthe Global Asthma Network.

Key Recommendation

Figure 2:

Global Asthma Network participating centres, August 2014

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1414

Asthma does not haveto be a burden or

cause suffering.


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PART ONE:

THE BURDEN OFASTHMA

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Gl b l B d f


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Figure 1:Prevalence of asthma symptoms among 13-14 year olds (ISAAC).

The showsthe centresreportingthe highest

prevalence

Source: Lai CKW, et al. Thorax 2009

20%

10 to


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Figure 2:Prevalence of severe asthma among 13-14 year olds(ISAAC).

7.5%

5 to


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analyses from 2000-2002. These numbers arenot precise, rather they are estimated from the

best data available. However, as the followingparagraphs illustrate, there are many gaps inasthma statistics. There is no evidence that thenumber of people with asthma in the worldhas increased from 235 to 334 million betweenour 2011 and 2014 reports; rather this situationillustrates the need for high quality data onasthma to be collected in an ongoing way.

Much of the information on which the laterestimate is based is already out of date, as the lastglobal surveys of the proportion of the populationwho have asthma (that is, prevalence) werecarried out about 10 years ago. Unfortunately

the World Health Organization (WHO) is notundertaking any future global asthma monitoring

work; however the Global Asthma Network (GAN)plans to continue this work with worldwidestudies to find out how the pattern of asthma ischanging in children and adults (See Chapter 1).

To make comparisons of the prevalence ofasthma between different parts of the world,and changes over a period of time, standardisedmeasurements are needed (that is, measurementsdone in the same way at different places andtimes). The most common way of doing this isby questionnaire, which is feasible for large scalesurveys. Using this approach The InternationalStudy of Asthma and Allergies in Childhood

(ISAAC) undertook its latest survey between 2000and 2003.

ISAAC found that about 14% of the worldschildren were likely to have had asthmaticsymptoms in the last year and, crucially, theprevalence of childhood asthma varies widelybetween countries, and between centres withincountries studied (Figure 1). These conclusionsresulted from ISAACs ground-breaking surveyof a representative sample of 798,685 childrenaged 13-14 years in 233 centres in 97 countries.(A younger age group of children (6-7 years)was also studied by ISAAC and the findingswere generally similar to the older children).These adolescents were asked whether they

Figure 3: Prevalence of symptoms of asthma in the past 12 months among persons aged 18 to 45years in 70 countries, World Health Survey 2002-2003. Source: To T, et al. BMC Public Health 2012.

0 - 10%

> 10% - 15%

> 15% - 20%

> 20% - 25%

> 25%

No standardised data

available

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0 200 400 600 800 1000

1 - 4 yrs

5 - 9 yrs

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55 - 59 yrs

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65 - 69 yrs

70 - 74 yrs

75 - 79 yrs

80+ yrs

DALYs (per 100,000)

females

males

Source: Institute for Health Metrics and Evaluation(IHME).

Figure 4:Burden of disease,measured by disabilityadjusted life years(DALYs see explanation p20)per 100,000 populationattributed to asthmaby age group and sex.Global population, 2010.

had experienced wheeze in the preceding 12months. Prevalence of recent wheeze varied

widely (Figure 1). The highest prevalence (>20%)was generally observed in Latin America and inEnglish-speaking countries of Australasia, Europeand North America as well as South Africa.The lowest prevalence (


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or more times per week, and/or any episodesof wheeze severe enough to limit the ability tospeak, also varied substantially, but was > 7.5% inmany centres (Figure 2).

The prevalence of asthma in younger adults

varies widely as it does in children. Overall, 4.3%of respondents to WHOs World Health Surveyaged 18-45 in 2002-2003 reported a doctor sdiagnosis of asthma, 4.5% had reported eithera doctors diagnosis or that they were takingtreatment for asthma, and 8.6% reported thatthey had experienced attacks of wheezing orwhistling breath (symptoms of asthma) in thepreceding 12 months (Figure 3). The highestprevalence was observed in Australia, Northernand Western Europe and Brazil. The World HealthSurvey, which was conducted about the same

time as ISAAC, used a different survey methodwhich may contribute to some of the differencesin the findings within a region. The prevalenceof asthma was measured by questionnaireadministered to 177,496 persons aged 18 to 45years living in 70 countries.

Much less is known about the prevalence ofasthma in middle-aged and older adults. Thisreflects both a paucity of survey data and thegreater difficulty of distinguishing asthma fromother respiratory conditions, such as chronicobstructive pulmonary disease (COPD) inolder age groups. There are no internationallystandardised comparisons of asthma prevalencein the elderly.

Is asthma becoming more orless common?

Asthma symptoms became more commonin children from 1993 to 2003 in many low- and

middle-income countries which previously hadlow levels, according to ISAAC. However, in mosthigh-prevalence countries, the prevalence ofasthma changed little and even declined in afew countries. Factors responsible for increasingasthma rates are not fully understood, butenvironmental and lifestyle changes play the keyroles (see Chapter 7). What has happened to theprevalence and severity of asthma since 2003? Wedo not know because there have been no sur veys.

What is the impact ofasthma on rates of disabilityand premature death?

The burden of asthma, measured by disability

and premature death, is greatest in childrenapproaching adolescence (ages 10-14) andthe elderly (ages 75-79) (Figure 4). The lowestimpact is borne by those aged 30-34. Theburden is similar in males and females at agesbelow 30-34 years but at older ages the burdenis higher in males. This sex difference increaseswith increasing age. Figure 4 shows the GBDsmeasure of health loss attributable to specificdiseases, for asthma. The GBD used mortalitystatistics and health survey data, where available,

to estimate, for many countries of the world, twocomponents of disease burden: years of life lostdue to premature death, and years of life livedwith disability. The latter quantifies both theextent of disability and its duration. The years oflife prematurely lost, and the years of life livedwith disability are added together and expressedas disability adjusted life years (DALYs), which isthe measure of burden of disease.

Among people aged less than 45 years,most of the burden of disease is disability. The

GBD estimated that asthma was the 14th mostimportant disorder in terms of global years livedwith disability. However, for people in olderage groups, premature death due to asthmacontributes more to the burden of disease (Figure5).

Asthma has a global distribution with arelatively higher burden of disease in Australiaand New Zealand, some countries in Africa, theMiddle East and South America, and North-Western Europe (Figure 6).

Conclusion

The global burden of disease due to asthmahas become better understood throughstandardised measurement of the proportion ofthe population who have asthma, severe asthma,disability due to asthma and/or who have diedfrom asthma. Little is known about asthma in themany countries where it has not been studied,and little information is available about asthma inadults over the age of 45.

Governments should committo research, intervention, andmonitoring to reduce the burdenof asthma in the world. Globalsurveillance of asthma requiresstandardised measures ofasthma implemented in largescale surveys of both childrenand adults in diverse settings

worldwide.

Key Recommendation

334 million people have asthma. 14% of the worlds children

experience asthma symptoms.

8.6% of young adults (aged 18-45)experience asthma symptoms.

4.5% of young adults have beendiagnosed with asthma and/orare taking treatment for asthma.

The burden of asthma is greatestfor children aged 10-14 and theelderly aged 75-79.

Asthma is the 14th mostimportant disorder in the world interms of the extent and durationof disability.

THE GLOBAL BURDEN OF

ASTHMA: CURRENT ESTIMATES

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80+y

rs

DALYs(per100,0

00

)

YLL

YLD

Figure 5:

Components of disabilityadjusted life years(DALYs): years lived with

disability (YLD) andyears of life lost (YLL)per 100,000 populationattributed to asthmaby age group. Globalpopulation, 2010. (see DALYexplanation on p20)

Figure 6: Disability adjusted life years (DALYs) per 100,000 population attributed to asthma bycountry, both sexes, 2010.

Source: Institute for Health Metrics and Evaluation(IHME).

Source: Institute for Health Metrics and Evaluation (IHME).

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Hospital Admissionsfor Asthma

Hospital admissions for asthma have

been proposed as a target indicatorof improvements in asthma care, butthe factors underlying variations inhospital admission rates are poorlyunderstood. Admission to hospitalduring an asthma attack may indicatethe first episode in the diseaseor a failure of preventive care forestablished asthma. Hospital caremay be important to prevent a fataloutcome in severe or troublesomeasthma. Historically, the relationshipbetween asthma prevalence, severity,admissions, and mortality rates inhigh-income countries has beencomplex. Changes in the admissionrate over time correlate (albeit

imperfectly) with changes in theprevalence and severity of childhoodasthma. However, the relative rankingof national admission rates for asthmais not consistent between children andadults.

David Strachan, Ramyani Gupta, Luis Garca-Marcos3.

Hospital admissions for asthma

may be used as an indirectindicator of the burden ofmore severe asthma and theefficacy of care. However thefactors underlying variationsin hospital admission rates are

poorly understood and need

more research.

International Comparisons

Many attacks of asthma are mild and self-limiting and never present for hospital treatment.The proportion of acute episodes which resultin hospital admission varies greatly betweencountries, depending upon the accessibility andaffordability of the health care system, the localthresholds for referral from community to hospital,and from outpatient or emergency visits toinpatient care.

National hospital admission statistics aremainly limited to high-income countries in Europe,North America and Australasia. Data are lackingfor most low- and middle-income countries. InEuropean countries, among all age groups, asthma

contributes 0.6% of hospital admissions and 0.4%of all inpatient bed-days. Figure 1 shows an almosttenfold variation in age-standardised admission

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0 50 100 150 200 250 300 350

Italy

Portugal

Cyprus

Iceland

Luxembourg

Spain

Switzerland

Netherlands

Austria

Croatia

*Malta

Germany

Finland

Czech Republic

Israel

Slovenia

Ireland

France

Norway

Poland

United Kingdom

Denmark

Hungary

Belgium

Slovakia

Latvia

Lithuania

Romania

Earliest (2000-2004)

Latest (2008-2012)

Figure 1:

Age-standardised

admission rates forasthma for earliest andlatest available year inEuropean countriesordered by latestadmission rate.

Note: earlier data correspondsapproximately to the InternationalStudy of Asthma and Allergies inChildhood (ISAAC) Phase Three studyperiod.

* No data available for earliest timeperiod.

No data available for latest timeperiod.

Source: WHO Hospital Morbidity Database,accessed November 2013, plus Eurostat (for someearlier data).

Age-standardised discharge rate per 100,000

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rates for asthma between European countries inrecent years.

These all-ages rates conceal considerablevariation in hospital admission rates betweenchildren (where rates are generally higher)

and adults. Caution should be exercised wheninterpreting geographical differences and trendsover time in asthma admission rates for pre-school children (where diagnostic overlap withacute bronchitis and bronchiolitis may occur)and for older adults (where chronic obstructivepulmonary disease may be confused withasthma).

Among 23 European countries, in recentyears, there were close correlations between thenational admission rates for younger and older

children, and between younger and older adults(see Appendices Figures 1-3), but the correlationsbetween rates for adults and children are lessimpressive (Figure 2).

Trends over time

In most, but not all, European countries, age-standardised asthma admission rates declinedthrough the last decade (Figure 1). In somecountries, the reduction was two-fold or greater, alarger change than has been proposed as a targetindicator of improvements in asthma care, for

example by the Global Initiative for Asthma (GINA)and the Global Asthma Network. This recentdecline is largely due to a reduction in admissionrates among children, which is part of a longer-term rise and fall, peaking in the early 1990s.This is shown schematically in Figure 3 (based ondata from several European countries, the UnitedStates of America, Canada, Australia, New Zealand,Hong Kong and Singapore).

Taking a 50-year perspective, the epidemicof asthma admissions bears no temporal

relationship to two epidemics of asthma mortality(in the 1960s and the 1980s, related to the useof older asthma relievers with potentially toxicside effects), nor to time trends for self-reportedasthma prevalence (Figure 3). However, data from

the United Kingdom show a peak of primary carecontacts for acute asthma, particularly amongchildren, in the early 1990s, similar to that ofasthma hospital admissions. This suggests arise and fall in the incidence of asthma attacksin the community, rather than simply a change

in patterns of referral to secondary care, or areduction in the severity threshold for admissionto the hospital ward.

An international comparison of time trends inasthma admissions and asthma drug sales in 11countries during the 1990s found that increasedsales of inhaled corticosteroids (preventermedication) were associated with a decline inrates of hospital admissions for asthma. However,inhaled corticosteroids became more widelyused for asthma during the 1980s, a period

of increasing hospital admission rates amongchildren. Thus, it is not possible to draw firmconclusions about the extent to which uptakeof effective preventer medication has reducedhospital admission rates for asthma in high-income countries.

0

1

2

3

4

5

6

7

8

9

0 10 20 30 40 50 60 70

Rank correlaton:

r = 0.33, p=0.12

Source: WHO Hospital Morbidity

Database, accessed November 2013.

Admissions per 100,000 per year, age 5-14

Admissionsp

er100,0

00peryear,age20-44

Figure 2:Asthma admission rates for European countries, age 5-14 v20-44 years. Relationship of hospital

admissions to other

measures of the burden ofasthma

When national asthma admission ratesfor children were compared with the asthmasymptoms prevalence and severity data forcentres (but not whole countries) participating inthe International Study of Asthma and Allergiesin Childhood (ISAAC) Phase One study around1995, a highly significant positive correlation wasfound between national admission rates and the

prevalence of more severe asthma symptoms in13-14 year olds (14 countries), but not in 6-7 yearolds (11 countries). However, a similar analysis(prepared for this chapter) of ISAAC Phase Threedata (collected around 2002) for 15 Europeancountries with data in the older age-group, and11 European countries in the younger age-group,found no statistically significant correlationsbetween how the countries ranked against eachother for national admission rates in childrenand how they ranked for any measure of wheezeor asthma prevalence, including more severesymptoms.

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0

1

2

3

4

5

6

7

8

9

10

1955

1995

1990

1985

1980

1975

1970

1965

1960

2010

2005

2000

1955

1995

1990

1985

1980

1975

1970

1965

1960

2010

2005

2000

0

1

2

3

4

5

6

7

8

9

10

0

5

10

15

20

195

5

199

5

199

0

198

5

198

0

197

5

197

0

196

5

196

0

201

0

200

5

200

0

Self-reported asthmaper 100 children

Asthma admissionsper 1,000 children

Asthma mortalityper 1,000,000 children

Figure 3:

Long-term time trendsin self-reported asthmaprevalence, hospital

admission ratesand mortality ratesfor asthma amongchildren in high-incomecountries.

Source: Chawla J, et al. Pediatric Pulmonology2012.

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Such comparisons need to be interpreted withcaution, because ISAAC centres are self-selected andare not necessarily representative of the countries inwhich they are located. Additionally, between-countrycomparisons at a single point in time are potentiallybiased in many ways. However, some of these biases

become less relevant if within-country changes areexamined over time.

For countries with ISAAC study centres participatingin both Phase One and Phase Three, Figure 4 plots theannual change in childhood hospital admission rates(~1995-2002) against the change in the prevalenceof wheeze causing 13-14 year old children to wake atnight at least once a week. Over this period, admissionrates declined in all these countries except Hong Kongand Poland. There was a significant positive correlationbetween the decline in prevalence of severe asthma

symptoms between Phase One and Phase Three andthe decline in the corresponding national admissionrates for childhood asthma over a similar period.

-2.5

-2

-1.5

-1

-0.5

0

0.5

1

-0.15 -0.1 -0.05 0 0.05 0.1 0.15

Rank correlaton:

r = 0.63, p= 0.03

Figure 4:

Annual change inhospital admission

rates for childhoodasthma (ages 5-14) bychange in prevalenceof nocturnal wheezingamong 13-14-year-oldsin countries with oneor more ISAAC centresproviding prevalencedata for both ISAACPhase One (around 1995)and ISAAC Phase Three(around 2002).

Sources: National admissions data from AndersonHR et al. IJE 2008; (updated by WHO HospitalMorbidity Database). Prevalence data fom PearceNE et al. Thorax 2007.

Average annual change in nocturnal wheeze prevalence (per 100,000 children)Averageannualchangein

asthmaadmissionrateaged5-14(per10,0

00)

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Conclusion

Asthma admission rates have been proposed asa target indicator for monitoring progress towardsimproved asthma care. Large reductions in admissionshave occurred already over the last decade in several

countries.

However, currently routinely collected informationis almost entirely restricted to high-income countries,limiting the value of admission rates for surveillanceof the global burden of asthma. Large unexplainedchanges in admission rates have occurred over thepast 25 years, particularly for childhood asthma, butinternational correlations of within-country change inprevalence versus within-country change in admissionrates provide some support for the concept thatchanges in hospital admission rates can be used as an

indirect indicator of the burden of more severe asthmain the community.

In countries which routinely collect admissionsdata, changes in hospital admissions over time maybe used as an indirect indicator of the burden of moresevere asthma. Before admission rates can be used asan indirect indicator of the global burden of severeasthma, more countries need to collect admissionsdata.

Health authorities in allcountries should collect countsof hospital admissions inchildren and adults from defined

catchment populations, tomonitor trends in asthma overtime.

Key Recommendation

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Deaths due to asthma are

uncommon but are of seriousconcern because many of them arepreventable. Most deaths certifiedas caused by asthma occur in olderadults, although comparisons ofmortality rates have tended to focusupon children and younger adults.Over the past 50 years, mortalityrates in these younger age groups

have fluctuated markedly in severalhigh-income countries, attributed tochanges in medical care for asthma,especially the introduction of newasthma medications.

David Strachan, Elizabeth Limb, Neil Pearce, Guy Marks4.

International comparisons

Asthma is a rare cause of mortality,contributing to less than 1% of all deaths in mostcountries worldwide. Rates of death from asthmarise almost exponentially from mid-childhood to

old age, so the majority of asthma deaths occurafter middle age. However, there is considerablepotential for diagnostic confusion with otherforms of chronic respiratory disease in the olderage groups, so comparisons of mortality rateshave tended to focus on children and youngeradults.

International mortality statistics for asthmaare limited to those countries reporting a fullset of causes of death. Figure 1 compares the

mortality rates (age-standardised) for asthma

among countries reporting asthma separatelyin recent years (around 2010). For some of theless populous countries with few asthma deaths,there is a substantial range of uncertainty aroundthe published rate. However, among the morepopulous countries there is a 100-fold variation

in age-adjusted rates, for instance between theNetherlands (low) and South Africa (high).

When the comparisons are limited to 5-34year olds (Figure 2), numbers of deaths are fewerand margins of error are larger, but the disparitiespersist.

Trends over time

The Global Burden of Disease (GBD) Study

estimates that age-standardised death rates from

Asthma Mortality

Avoidable asthmadeaths are stilloccurring due toinappropriatemanagement ofasthma, includingover-reliance onreliever medicationrather than preventermedication.

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0 50 100 150 200 250 300

South AfricaRodriguesMauritus

FijiPhilippines

EgyptUzbekistan

MaldivesKyrgyzstan

Serbia and Montenegro, Former

ThailandAzerbaijan

SerbiaTFYR Macedonia

Republic of MoldovaJordan

GeorgiaRomaniaHungaryBulgaria

QatarRepublic of Korea

KuwaitCyprusEstoniaBahrain

LatviaLuxembourg

NorwayIsrael

PolandNew Zealand

AustraliaDenmark

United KingdomGermany

MaltaCroataAustria

LithuaniaUnited States of America

JapanFrance

SpainHong Kong SAR

IrelandBelgiumSlovakiaFinland

SloveniaSweden

Czech RepublicIcelandCanada

PortugalItaly

Netherlands

High-income countries

Low- and middle-

income countries

Figure 1:

Age-standardised

asthma mortality ratesfor all ages 2001-2010from countries whereasthma is separatelycoded as a cause ofdeath, ordered bymortality rate and

country income group.*Source: WHO Detailed Mortality Database,February 2014 update.

*Data standardised to the World StandardPopulation. Calculated from the average numberof deaths and average population for each 5-yearage-group over the period 2001-2010, using allavailable data for each country (the number ofavailable years over this period ranged from 1to 10).

Age-standardised deaths per million population

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0 5 10 15 20 25 30 35

South AfricaPhilippines

FijiMauritusThailandMaldives

UzbekistanJordan

GeorgiaKyrgyzstan

Serbia and Montenegro, FormerSerbia

HungaryAzerbaijan

EgyptBulgaria

Republic of MoldovaRomania

RodriguesTFYR Macedonia

New ZealandUnited States of America

United KingdomAustralia

KuwaitMalta

BahrainIreland

Hong Kong SARQatarJapan

CanadaLatvia

FranceGermany

SpainBelgiumNorway

Denmark

Czech RepublicRepublic of Korea

NetherlandsIsrael

AustriaPoland

SlovakiaLithuania

FinlandPortugalSwedenCroata

LuxembourgEstonia

Italy

SloveniaCyprusIceland

High-income countries

Low- and middle-

income countries

Figure 2:

Age-standardisedasthma mortality ratesfor ages 5-34 years

only, 2001-2010 fromcountries where asthmais separately coded as acause of death, orderedby mortality rate andcountry income group.*

Source: WHO Detailed Mortality Database,

February 2014 update.

*Data standardised to the World StandardPopulation. Calculated from the average numberof deaths and average population for each 5-yearage-group over the period 2001-2010, using allavailable data for each country (the number ofavailable years over this period ranged from 1to 10).

Age-standardised deaths per million population

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asthma fell by about one-third between 1990and 2010: from 250 per million to 170 per millionamong males, and from 130 per million to 90 permillion among females. These worldwide figuresinclude all ages.

More detailed comparisons have beenmade over a longer time period in high-incomecountries, focussing on younger age groups.Over the past half-century, there have been twodistinct peaks in asthma mortality in a number ofhigh-income countries (Chapter 3, Figure 3).

The first, during the mid-to-late 1960s,represented an approximately 50% increase inasthma death rates among 5-34 year olds. It isgenerally attributed to the introduction of high-dose isoprenaline inhalers as an asthma reliever

medication, which can have toxic effects on theheart during acute asthma attacks. When thesemedications were withdrawn, the 1960s epidemicof asthma deaths subsided.

The second epidemic, during the mid-1980s,represented an increase of approximately 38%

in asthma death rates among 5-34 year olds. Inat least some of the affected countries, it wasprobably due to the widespread use of fenoterol,another inhaled asthma medication withpotential cardiac toxicity. However, this secondepidemic was also observed in some countries,

such as the United States of America, wherefenoterol was never approved or widely used.

Relationship of mortalityto other measures of theburden of asthma

Taking a 50-year perspective, the epidemicsof asthma mortality (related to the use of olderasthma relievers with potentially toxic sideeffects) understandably bear little relationship

to the time trends for asthma prevalence orhospital admission rates for asthma. In severalhigh-income countries, asthma admission ratesamong children rose to a peak in the 1990s,after the 1980s peak in asthma mortality.However, both hospital admission rates and

asthma mortality rates among children havebeen declining since 2000 in countries wherethey have been measured, whereas asthmaprevalence has been stable or rising in manycountries (Chapter 3, Figure 3).

When national asthma mortality rates forchildren were compared with the asthmasymptoms prevalence and severity data for theInternational Study of Asthma and Allergiesin Childhood (ISAAC) Phase One centres inthe same countries, a significantly positivecorrelation was found between childhoodasthma mortality and the prevalence of moresevere asthma symptoms in both 6-7 yearolds (29 countries) and 13-14 year olds (38countries).

Such comparisons need to be interpretedwith caution, because ISAAC centres are notnecessarily representative of the countriesin which they are located. However, whencomparing mortality and hospital admissionrates, national data can be used in bothinstances. Figure 3 shows this comparison for

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0.0

2.0

4.0

6.0

8.0

10.0

12.0

14.0

16.0

0 50 100 150 200 250

Rank correlaton:

r = 0.44, p= 0.03

24 European countries which have reportedrecent data for both outcomes. There is asignificantly positive correlation between

mortality and admission rates for asthma at allages.

Avoidable factors in asthmadeaths

Although asthma mortality rates havedeclined in many high-income countries,confidential enquiries in the United Kingdomhave suggested that avoidable factors still playa part in the majority of asthma deaths.

The most recent comprehensive review,of 195 asthma deaths in the United Kingdomduring 2012-2013, found that nearly half diedwithout seeking medical assistance or beforeemergency medical care could be provided, andthe majority were not under specialist medicalsupervision during the year prior to death.Only one-quarter had been provided with apersonal asthma action plan, acknowledged toimprove asthma care, and there was evidence

of excessive prescribing of short-acting relievermedication, under-prescribing of preventermedication, and inappropriate prescribing

of long-acting beta-agonist bronchodilatorinhalers as the sole form of treatment.

These observations, from a high-incomecountry with a tradition of evidence-basedmedicine and a national health service which isfree at the point of use, suggest that improvedaccess to appropriate asthma medicationis a key goal in reducing asthma mortalityworldwide.

ConclusionAsthma deaths represent the tip of the

iceberg with respect to the global burden ofasthma. Although the risk of any individualasthmatic patient dying of their disease isthankfully very low, continued surveillance ofasthma mortality rates is essential to monitorprogress in asthma care, and as an earlywarning of epidemics of fatal asthma, as haveoccurred in the past half-century.

Figure 3:

Age-standardisedasthma mortality ratesand age-standardisedhospital admission ratesfor asthma, in European

countries providingrecent data for both(2001-2010).

Sources: WHO Detailed Mortality Database,February 2014 update, WHO Hospital MorbidityDatabase, accessed November 2013.

Age-standardised asthma admission rate per 100,000

Age-standardisedasthmamortalityratepermillion

Health authorities in allcountries should report ratesof asthma deaths in childrenand adults to monitor progressin asthma care and as an earlywarning of epidemics of fatal

asthma.

Key Recommendation

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Javier Mallol, Luis Garca-Marcos, Paul Brand5.

International Study onWheezing in Infants

The largest multi-centre study of wheezingin the first year of life, the International Study onWheezing in Infants (Estudio Internacional deSibilancias en Lactantes, EISL), has contributednew information about therapeutic approachesto recurrent wheezing (RW). Data from this cross-

sectional study including 30,093 children in 17centres: 25,030 in 12 centres in Latin America and5,063 from 5 centres in Europe were publishedin 2010 (Figure 1). RW in the first year of life,defined as having three or more episodes ofwheezing during that time, is common (20%), witha high proportion of these infants suffering fromfrequent and severe episodes. EISL found that32.2% of infants with RW have 7 or more episodes(32.3% in Latin America and 31.8% in Europe);71% reported visits to the Emergency Department

(ED) due to wheezing (74% in Latin America and55% in Europe); and 26.8% reported admissionfor wheezing during the first year of life (28.4%

in Latin America and 14.2% in Europe) (Figure2). Overall, these figures imply a high burden ofhealth costs for countries and parents in terms ofuse of health facilities and medications.

The Common Cold

EISL found a strong association betweenRW during the first year of life (both in affluent

and non-affluent countries) and: common viralrespiratory illnesses (the symptoms of suchillnesses are that of a cold) during the first 3months of life; attending day-care; wheezing inthe first three months of life; male gender; themother smoking during pregnancy; and familyhistory of asthma or rhinitis. Breast feeding for>3 months and high maternal education showeda protective effect. Thus, avoiding smokingduring pregnancy, delaying day-care attendance,breastfeeding babies for at least 3 months, andimproving maternal education could be effectivestrategies for decreasing the prevalence of RW.

Wheezing in Infants

Recurrent wheezing in infants is the

most common clinical expressionof asthma at that age. It shouldno longer be considered a benigncondition that disappears later inchildhood, particularly becausemany of these infants developfrequent and severe episodes.Early diagnosis and effectivemanagement of troublesome

recurrent wheezing may decreasethe high proportion of infants withrecurrent wheezing who havesevere episodes as well as visits tothe Emergency Department andadmissions for wheezing during thefirst year of life.

Recurrent wheezing ininfants, particularly ifthey are presenting withfrequent and/or severeepisodes, should bediagnosed and managedas asthma, unlessthere is evidence to thecontrary.

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There is increasing evidence that having acold in the first year of life plays an importantrole in the commencement and/or maintenanceof wheezing and asthma in early life. Wheezingillnesses in infants, caused by human rhinovirusand respiratory syncytial virus (RSV) among

other things, are robust predictors of subsequentdevelopment of asthma, decreased lung function,and increased bronchial responsiveness in schoolage children. Common cold viruses are by far themost frequent cause of asthma exacerbations atany age.

While there is no consensus on theeffectiveness of medical interventions for RW inthe first year of life, these infants - particularlyif episodes are frequent and/or severe - arefrequently treated with asthma medicines, both in

hospitals and in primary care. Ninety-one percentof infants with RW used inhaled bronchodilators

and 46% used inhaled corticosteroids (ICS) withdifferences between regions (Figure 2). Evidence-based guidelines also suggest using clinicalseverity signs (higher frequency and severity ofwheezing episodes) as key indicators for startingtherapy with ICS in preschool wheeze, with the

aim of decreasing the number and severity ofwheezing exacerbations. The ways that wheezingis classified in preschool children in clinical andepidemiological studies do not reliably predictthe outcome of wheeze over time or the responseto ICS treatment. In addition, these classificationsof wheezing are difficult to identify in clinicalpractice and can even change within the first yearof life. Thus these classifications of wheeze arenot helpful for clinicians when they are decidingtreatment for infants with RW.

Management

The effectiveness of ICS in treating childrenwith more severe or persistent symptoms ofpreschool wheeze in children over 12 months ofage is well established. In EISL the high proportionof infants with severe symptoms of RW leading toED visits, hospital admissions, sleep disturbance,

and impaired quality of life, may be partlyexplained by poor recognition and managementof infants with troublesome recurrent asthmasymptoms. Contributing factors may includea reluctance to diagnose asthma in youngchildren, a delay in starting proper treatment,prescription of medicines with doubtful efficacy(antileukotrienes) or proven absence of efficacy(antibiotics, cough syrups, antihistamines, amongothers), or poor education of parents about how touse inhalers and spacers. We suggest outcomes forinfants with RW would be improved if the use of

ICS could be improved, i.e. a sufficient dose takenover a sufficient time with good adherence.

Figure 1: Prevalence of recurrent wheezing during the first year of life in European and LatinAmerican centres.

0 5 10 15 20 25 30 35 40

Bilbao

Cartagena

La Corua

Valencia

Zwolle

Europe

Latin America

Barranquilla

Belem

Belo Horizonte

Caracas

Curitiba

Fortaleza

Merida

Porto Alegre

Recife

Santiago de Chile

Sao Paulo

Valdivia

Recurrent wheezing prevalence (%)

Source: Mallol J, et al. Thorax. 2010.

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0 10 20 30 40 50 60 70 80 90 100

Inhaled bronchodilator

Inhaled corticosteroids

Leukotrien-receptor antagonist

Upper Respiratory Tract

Infection in first 3 months of life

Frequent sleep disturbance

Severe episodes

Visits to emergency room

Admissions to hospital

Europe

Latin America

Figure 2:

Reported severity, medications and other variables in infants with recurrent wheezing during thefirst year of life. Source: Mallol J, et al. Thorax. 2010.

Response (%)

Health professionals in allcountries should regard frequentor severe recurrent wheezing ininfancy as part of the spectrumof asthma.

Key Recommendation

Conclusion

The EISL data strongly supports the needfor efficient, realistic, and easy-to-implement

strategies for the education and managementof infants with recurrent asthma symptoms,directed at both parents and health careworkers, especially in developing countries. Earlyidentification and proper management of infantswith recurrent troublesome asthma symptomsis likely to decrease the prevalence of severeepisodes, ED visits and hospital admissions,use of inappropriate medications, and othercomplications. This requires a paradigm shift:health care workers and authorities should no

longer consider RW in infancy, especially whenfrequent and/or severe episodes are present, as abenign condition.

35

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Burden of Asthma

It is difficult to quantify the global

economic burden of asthma, butestimates for separate countriesand regions are tremendouslyhigh. The indirect costs ofasthma, especially its negativeimpact on productivity, is atleast as large as its direct costs.Attempts to reduce the economicburden of asthma should move

towards better managementof asthma. Improving accessto care and adherence toevidence-based treatment canreduce the economic burdenof asthma, even in locationswhere prevalence is rising.

Challenges in estimating theglobal economic burden ofasthma

Diseases can cause economic loss in a numberof ways. They can impose direct costs throughconsumption of resources (e.g., hospitalisations,physician visits, and medications), as well asindirect costs through loss of productivity.Globally, as a major non-communicable disease,asthma creates a tremendous economic burden,although the exact quantification of this burdenis challenging. What is clear is that the economicburden of asthma is high, adding to the need for itto be recognised as a public health priority.

Attaching numbers to the economic burdenof asthma is fraught with several challenges.One challenge is how to attribute resources toasthma. For example, it is difficult to tease out

the contribution of asthma to depression in apatient with both conditions, or to attribute how

many days of sick leave are due to asthma. Evenestimating the prevalence of asthma, a key factorin estimating the burden at the regional andnational level, is difficult, as seen in Chapter 2,given the inconsistencies in definition, as well asunder-diagnosis and over-diagnosis of asthma indifferent subgroups of individuals.

What we know about the

global burden of asthmaMost studies on the burden of asthma are

from developed countries, where national surveysof diseases and large, administrative databases,can be interrogated to provide a broad pictureof the burden. The one systematic review (2009)illustrates the variation within countries and therelative lack of information from low-and middle-income countries. A recent study in the UnitedStates of America estimated that the total cost

of asthma to society was $56 billion in 2007, or$3,259 per person per year (in 2009 US dollars).

6. Mohsen Sadatsafavi, J Mark FitzGerald

Controlled asthmaimposes far less ofan economic burdenthan non-controlledasthma. Strategiestowards improving

access and adherenceto evidence-basedtherapies can thereforebe effective in reducingthe economic burdenof asthma in bothdeveloped anddeveloping countries.

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A further European study in 2011 has estimatedthe total cost of asthma in that year to be 19.3billion among Europeans aged from 15 to 64

years (in 2011 Euros). In a separate study in theAsia-Pacific region, the sum of direct and indirectcosts of asthma per person per year ranged from$184 in Vietnam to $1,189 in Hong Kong (in 2000US dollars). Furthermore, there is a significantvariation in cost estimates even among thestudies from the same country. For example,US-based estimates of the cost of asthmaper person vary up to five-fold. Despite theheterogeneous settings and different numbers,many studies have pointed towards the fact thatthe indirect cost of asthma is at least as large as

its direct costs. This is not a surprising finding:disability from asthma affects individuals whoare often at the most productive phase of theirworking lives, and parents of dependent childrenwith asthma are also often in the workforce.Research also suggests that the contribution ofpresenteeism (individual loss of function whenat work) is larger than absenteeism (inability tocome to work) in patients with asthma. A recentCanadian study has shown that, compared withcontrolled asthma, uncontrolled asthma results

in a $184 (in 2012 Canadian dollars) loss ofproductivity during a week for such a person, 90%of which is attributable to presenteeism.

The preventable burden ofasthma: the importance ofclinical control

Currently, asthma cannot be cured, andthere are limited evidence-based options toprevent its development. The emphasis ofasthma management is therefore focused onachieving clinical control with an added priorityof preventing the future risk of exacerbations.Strategies which result in well-controlled asthmaare associated with a significant reduction ineconomic burden compared to uncontrolleddisease, as shown by programmes implementedin Salvador (Brazil) and Finland (for moreexamples see Chapter 8). Despite the wideavailability of effective medications for severaldecades, asthma remains uncontrolled in a

substantial proportion of the population. Thus,the incremental economic burden of uncontrolled

asthma is of particular relevance to decisionmakers as it represents the aspect of the burdenthat is preventable.

Low adherence as a majorcause of preventable burden

Research in diverse jurisdictions, including

both developed and developing countries, hasconsistently shown that adherence to controllermedications is poor. The evidence linkingadherence to controller medications with betterasthma outcomes is strong, making adherencea modifiable factor and a potential target forreducing the economic burden of asthma.

Improving access to careand adherence to evidence-based medication

Given the proven benefit of existing essentialasthma medicines for most asthma patients,improving access and adherence to suchtreatments should be a major global priority (see

chapter 12). In developing countries, additionalbarriers to delivering effective managementmay include poverty, poor education, andpoor infrastructure, indicating that a morecomprehensive approach is required, includingpolitical commitment to better asthma care(see Chapter 12). In both developing anddeveloped countries, improving adherence tocontroller treatment requires education of bothcare providers and patients about its long-termbenefits. Developing interventions such as sharedcare models for asthma management, or theuse of communication technologies to facilitateinteraction between patients and care providers,

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Governments should measureand monitor the economic costsof asthma in their countries,including health care costs and

productivity losses.

Key Recommendation

can be beneficial. The role of health literacy andthe socio-cultural context in which the patientsfind themselves are also important.

A small fraction (less than 10%) of patientswith asthma which is difficult to control(refractory asthma) do not respond toconventional controller therapies and dependon treatments that are currently very expensiveand only accessible in certain parts of theworld. Reducing the cost of these treatmentsand making them accessible across the worldwill help reduce the burden due to refractoryasthma. This requires the coordinated effortsof industry, government, non-governmental

organisations (NGOs), and international

organisations such as the World HealthOrganization (WHO).

ConclusionMost countries have not yet estimated the

costs of asthma. Where it has been estimated,the economic burden of asthma is great becauseof direct healthcare costs, and indirect costs, as aresult of loss of productivity due to people beingabsent from work, or working less effectivelywhile at work. The impact of these indirect costswould be diminished by improving asthmacontrol, through improving access to goodmanagement including medicines.

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7Factors Affecting


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Neil Pearce, David Strachan7.

Genetics:One part of the picture

Asthma often runs in families, and identical twins are more likely to both be asthmaticthan are non-identical twins. Nevertheless, only about half of the identical twins with anasthmatic co-twin are themselves asthmatic, indicating a contribution from both geneticand non-genetic factors.

Large studies of asthma in the general population have recently identified a small

number of genetic variants that influence asthma risk, mainly in children. These variantsare frequently found in populations of European origin, but their association with asthmais too weak to predict reliably which individuals will develop the disease.

The role of allergy?Asthma used to be thought of as an allergic disease, where allergen exposure causes

sensitisation to allergens and continued exposure leads to the processes in the airwaywhich lead to asthma symptoms. While allergy is a potential underlying factor for upto half of the people with asthma, the remainder have no allergic features. In low- andmiddle-income countries the proportion of people with non-allergic asthma is greaterthan in high-income countries. Furthermore, some occupational causes of asthma donot appear to involve allergy. These non-allergic mechanisms are currently not wellunderstood.

Parental smoking(for children) andoccupational exposures

(for adults) are theclearest examples ofremediable causes ofasthma.

Asthma

A wide variety of factors areknown to affect asthma, butno one specific cause, eitherbiological or environmental, hasbeen identified. Studies indicatethe contribution of both geneticand non-genetic factors. Whenconsidering non-genetic factorsaffecting asthma, it is important todistinguish between the triggers of

asthma attacks (which are widelyrecognised) and the causes of theunderlying asthmatic process ortrait (about which much less isknown). Both groups of factorsmay contribute to the severity andpersistence of asthma.

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consistent evidence that pets are either a risk


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Common triggers: Thecommon cold and exercise

Asthma attacks are commonly triggered byupper respiratory tract infections, including

common colds, and by exercise. Less frequently,they are related to tobacco smoke exposure, acuteemotional stress, or to the consumption of certainfoods, beverages, or medicines.

Environmental factors that may provokeasthma attacks include inhaled allergens(commonly dust mites and animal fur; lesscommonly pollens, moulds, and allergensencountered in the workplace); and inhaledirritants (cigarette smoke, fumes from cooking,heating or vehicle exhausts, cosmetics, and

aerosol sprays), and medicines (including aspirin).

Causes of the underlyingasthma trait - environmentalfactors: Facts and theories

Environmental factors are much more likelythan genetic factors to have caused the largeincrease in the numbers of people in the worldwith asthma, but we still do not k now all thefactors which may be important and how theyinteract with each other.

Secondhand smoke is a confirmed riskSecondhand tobacco smoke has been

confirmed as a risk for asthma both in childhoodand adulthood (see references at the end ofthe report). Pre-natal exposure may also be

important. This is considered to be a causalassociation, implying that the prevalence (andseverity) of asthma would be reduced if exposureto secondhand smoke could be reduced. The roleof other indoor air pollutants, such as cooking onan indoor open fire, as causes of the asthmatictendency is less clear and less consistent than fortobacco smoke.

Link to mould and damp is uncertainDampness and mould growth are more

common in the homes of asthmatic children andadults. However, the causal nature of this linkremains uncertain, inviting further research. Fewpeople with asthma are demonstrably allergic tofungal moulds. Dampness in homes is associatedwith both allergic and non-allergic forms ofasthma.

Animals in the home and on the farmExposure to furry pets is often less common

among asthmatic children and adults, due to

avoidance or removal of pets by allergic families.When this is taken into account, there is no

factor or a protective factor.

In contrast, several large studies, mainlyin temperate countries, have shown a lowerprevalence of asthma among children living onfarms. These children also have fewer allergies,

but this does not totally explain the apparentprotection against asthma. No specific cause hasbeen identified for this protective effect of farmupbringing, but diversity of microbial exposuremay be an underlying factor.

Antibiotics and paracetamol:cause or effect?

Asthma symptoms are more common amongchildren who were treated with antibiotics in earlychildhood. However, the direction of cause and

effect here is uncertain. Symptoms of wheezingcommonly develop for the first time in infancyand may be treated with antibiotics before theyare recognised as the early manifestations ofasthma.

Similar considerations of reverse causality apply to the possible link between paracetamol(acetaminophen) exposure in infancy and asthmaat school age paracetamol may have been givenfor early symptoms of asthma, or for infectionsthat may themselves increase the risk of asthma.

Recent paracetamol use by adolescents andadults is also more common among those withasthma symptoms, but this may also be reversecausality; people with asthma symptoms mayavoid using aspirin, since it is a known triggerof wheezing attacks in a small proportion ofasthmatics, who use paracetamol instead.

Occupational exposuresOccupational asthma may develop in persons

with no previous history of chest disease and can

sometimes persist after exposure to the causalagent is removed. High-risk occupations includebaking, woodworking, farming, exposure tolaboratory animals, and use of certain chemicals,notably paints containing isocyanates. Perhapsthe most widespread occupational exposure is tochemical cleaning agents, both in workplace anddomestic settings.

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Preventive and remedial Dont smoke or go near second hand


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measures

Eat a balanced dietProlonged exclusive breastfeeding was once

thought to protect against allergic diseases,including asthma, but extensive research hasshown that this is not the case. Many componentsof diet during later childhood and adult life havebeen studied in relation to asthma. The balanceof evidence suggests that diets that are widelyrecommended to prevent cardiovascular diseasesand cancer may slightly reduce the risk of asthma.A link has been established between obesity andasthma, although the mechanisms are not clear.

Avoid exposure to causal agentsOccupational exposures provide some of

the clearest examples of remediable causesof asthma. Special care is required in high-riskoccupations (baking, woodworking, farming,exposure to laboratory animals, and use ofcertain chemicals, notably paints containingisocyanates) to minimise inhalation of potentiallyharmful substances, and care to reduce exposureto chemical cleaning agents in the home is alsoneeded.

smokeSmokefree environments are important for

people of all ages. Little is known about thefactors affecting asthma after middle age, whenthere is substantial overlap between the reversible

airflow obstruction, which is typical of asthma,and the irreversible airflow obstruction of chronicobstructive pulmonary disease (COPD). Activesmoking is a major and remediable cause ofCOPD, and probably contributes to some casesof adult-onset asthma. Smoking should thereforebe discouraged among both asthmatics and non-asthmatics alike.

Conclusion

Environmental factors are much more likelythan genetic factors to have caused the largeincrease in the numbers of people in the worldwith asthma. Tobacco smoking and secondhandtobacco smoke are avoidable by the individual.Occupational exposure is a risk diminishableby both workplace practices and governmentpolicies. These and other factors require furtherresearch.

Governments should strengthenpolicies to reduce tobaccoconsumption, encourage healthyeating, and reduce exposure to

potentially harmful chemicals,smoke, and dust. Funders needto support further research toidentify causes of asthma.

Key Recommendation

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Quality-assuredh d


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asthma medicines

need to reacheveryone withasthma.


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43

PART TWO:

MANAGEMENTOF ASTHMA

AND CAPACITYBUILDING

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National AsthmaStrategies8 T i H ht l Ol f S l Phili Ell d N di At Kh l d


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Successfully managedasthma

When asthma is successfully managed, theperson with asthma will have no symptomsor only very mild symptoms, no attacks, noemergency department visits, no limitationof exercise or activities, no loss of sleep dueto asthma, minimal use of an asthma relievermedicine(


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Several other encouraging examples nowexist, e.g. in Poland, Portugal, Brazil, and recentlyin Costa Rica. As not all such programmes arereported, we encourage publication of strategiesand outcomes. The problems to be addressedare different in high-income compared to low-and middle-income countries, and the solutionsneed to be tailored according to local needs andresources. There is, however, no question that theburden of asthma can be markedly reduced usingstrategies that have been adapted to the localsocietal, economic and health care environments.

Patients from a low resource setting in Salvador,Brazil, received free medication for asthmaand rhinitis in accordance with international

guidelines. The outcome was impressive. Thecosts for asthma care were reduced on averageby US$ 733 per patient per year for the familiesand by US$ 387 per patient per year for the publichealth system. In the entire Salvador populationa 74% reduction in asthma hospitalisationrates occurred after the implementation of theprogramme. The educational effort targeting bothpatients and professionals was paid back in a fewyears. In Benin, in 2008 a pilot study of asthmamanagement was conducted. The cohort analysisafter one year of standardised management (seeChapter 12) demonstrated a dramatic decrease inasthma severity, the number of exacerbations and

hospitalisations (see Chapter 14).

Asthma burden canbe rapidly reduced by

the implementation ofrelatively simple measureswithin a systematicstrategy to improveearly detection and

provide effective anti-inflammatory treatment.

Generic Asthma Plan - to be adjusted for local and national needsReduce burden, promote health, support people with asthma!

4-Step Action PlanBackground

NEW BODY OF

KNOWLEDGE

EPIDEMIOLOGY

ECONOMY

EVIDENCE

CONCLUSIONS STRATEGIC CHOICES GOALS,

MEASURES

ACTIVITIES

Disability caused by

asthma can be

prevented

Morbidity

Prevalence

Costs

.

. Implementation ofbest practice is

highly cost-effective

both on the patient

and societal levels

Public health

problem

Need for broadconsensus

Need for action

Identification ofkey stakeholders

Focus on patients

Focus on severeasthma to stopexacerb/attacks

Focus on effectiveuse of availableresources andregisters

Practical action plan, not aconsensus report

Strategies for: 1)thosediseased, 2)generalpopulation

Quantitative and qualitativegoals

Focus on primary healthcare and outpatientsservices

Promotion of asthma health

Asthma Control Tools forguided self-managementtostop exacerb/attacks

Search for critical mass forchange through educationand counselling

1-3 keymessages forthe public

3-5 numericalgoals forHealth Care toreduce theburden

Tools to beused locally

Measures tofollowoutcomes

Time lines

Leadership, steeringgroup (local, national)

Capacity building,funding

New internet-basednetworking withspecialists, GPs, nurses,pharmacists

In diagnostic work,improving earlydetection

In treatment, improvingeffective use of ICS

Education and publicity(with NGOs)

Legislation (essentialmedication, anti-smoking)

Feedback, follow-upProcess evaluation

Outcome evaluation

.

.

.

Figure 2:

Strategic flowfor an asthma

plan.

Source: Haahtela T, et al.

Allergy 2008.

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Figure 3:National asthma strategies for children and adults in countries responding to the GlobalA th N t k 2013


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Inhaled corticosteroids areessential to success

Asthma projects and programmes inArgentina, Australia, Brazil, China, Japan, Mexico,the Philippines, Russia, South Africa, and Turkey

were discussed in 2009 in Berlin by a group ofexperts in asthma care, the Advancing AsthmaCare Network. Their report Asthma programmesin diverse regions of the world: challenges,successes and lessons learnt concluded thatthe major barriers for all programmes are: 1) lowrates of dissemination and implementation oftreatment guidelines, 2) low levels of continuingmedical education and training of primaryhealth care professionals, and 3) poor accessto and distribution of inhaled corticosteroids.

Additionally, under-diagnosis and inadequate

treatment further limit the success of lessdeveloped programmes.

All successful asthma programmes seem tohave the following characteristics: 1) improvingearly diagnosis and the introduction of first-linetreatment with anti-inflammatory medication(mainly inhaled corticosteroids), 2) improvinglong-term disease control, 3) introducingsimple means for guided self-management toproactively prevent exacerbations/attacks, and4) effective education and networking withgeneral practitioners, nurses and pharmacists. Asystematic approach is required and must aimto motivate and organise. Improvements can beachieved with relatively simple means. All themain stakeholders should be represented whenmultidisciplinary actions are being planned.

Especially important is the involvement ofthe non-governmental patient organisations,which are aware of the grass-root problems. Anyprogrammes should set 3-5 goals, preferablyaccompanying each with at least one quantifiableindicator and target. For example, one goal couldbe to reduce asthma exacerbations, measured bythe number of emergency visits, with the targetof reducing emergency visits by 50% over thenext 3-5 years. For each goal, more specific targets(what to do?), tools (how to do it?) and outcomes(what to follow and measure?) should be defined(Figure 1). The strategic flow for a programme isindicated in Figure 2.

Regardless of the health care system andits coverage, experience gained from nationaland local interventions sho

Global Asthma Report 2014

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