GINA2009

Pg 31, left column, end of paragraph 2, insert: See Appendix B, GINA Pocket Guide updated 2009 for information on Asthma Combination Medications For Adults and Children 5 Years and Older.

Pg 31: right column, insert reference 215.			Cates CJ,		Asthma Management and Prevention in Children 5 Years
Cates MJ. Regular treatment with salmeterol for chronicand Younger. Available at www.ginasthma.org
asthma: serious adverse eventsCochrane. Database of
Systematic Reviews2008, Issue 3. Art. No.: CD006363					Pg 61, right column, second paragraph: Change Evidence
Pg 70, right column, second paragraph, insert reference					A to Evidence B.
369. Tata LJ, Lewis SA, McKeever TM, Smith CJ, Doyle					Pg 70, right column, second paragraph, first phrase delete
P, Smeeth L, Gibson JE, Hubbard RB. Effect of maternal					and replace with: Although there is a general concern
asthma, exacerbations and asthma medication use on					about the use of any medication in pregnancy,….
congenital malformations in offspring: a UK population-
based studyThorax.	. 2008 Nov;63(11):981-7. Epub 2008				D. Committee recommended changes:
Aug 4.					1. Asthma Control: Based on a number of recent
Pg 70, right column, second paragraph, replace reference					publications, the Committee recommended significan
268. Bakhireva LN, Schatz M, Jones KL, Chambers CD;					changes to the section on Classification of Asthma, pa
Organization of Teratology Information Specialists					22 – 23. Figure 2-4 has been deleted. Former Figure 2-5
Collaborative Research Group. Asthma control during					(now appears as Figure 2-4), has been modified. This
								REPRODUCE!
pregnancy and the risk of preterm delivery or impairedmodified Figure also appears on page 58 (as Figure 4.3-
fetal growthAnn Allergy.		Asthma Immunol.	2008		1).		OR
Aug;101(2):137-43
					2. Grading Evidence: The GINA Science Committee is
Pg 71, left column, third paragraph, replace reference 279.					developing a system to identify recommendations whe
Shaaban R, Zureik M, Soussan D, Neukirch C, Heinrich J,					there maybe controversy or debate between efficacy and
Sunyer J, et al. Rhinitis and onset of asthma: a					cost. In addition there are some recommendations that
longitudinal population-basedLancetstudy.2008. Sep					have a less robust evidence base. In this context we
20;372(9643):1049-57.						ALTER
					possible role for the GRADE methodology providing a
					framework collate the evidence and create evidence
Pg 78, delete reference 150.					tables. To assess the feasibility of this approach tw
					questions were reviewed in 2009 to begin the work:
C. Changes or modifications to the text.				NOT
Pg xiv – xvii:Delete section Executive Summary:DO					a. In adults with asthma, does monoclonal anti-IgE,
					omalizumab, compared to placebo improve patient out-
			-		comes?
Managing Asthma in Children 5 Years and Younger. This
has been replaced with new repGlobalrt Strategy for
Asthma Management and Prevention in Children 5 Years					b. In adults with acute exacerbations of asthma, does
and Younger.					intravenous magnesium sulphate compared to placebo
Pg 28, left column line 10, delete: and other systemic					improve patient important outcomes?
steroid-sparing therapies.					Evidence tables were produced and are being evaluated
Pg 29, Figure 3-1: Change FluticasoneMATERIALto Fluticasone					and the results from this work are being prepared for
					publication. Further information will be provided in
propionate.					2010 update.
COPYRIGHTED

Pg 31, left column, beginning of paragraph 3, insert:

…when used as a combination medication with inhaled glucocorticosteroids…

Pg 37, Figure 3-4: Change Fluticasone to Fluticasone propionate.

Pg 59, Figure 4.3-2: Modifications to clarify wording on

Figure; modify lower segment to read Global Strategy for

ix

INTRODUCTION

Asthma is a serious public health problem throughoutaimtheto enhance communication with asthma specialist world, affecting people of all ages. When uncontrolled,primary-care health professionals, other health care asthma can place severe limits on daily life, and isworkers, and patient support organizations. The Execut

sometimes fatal.		Committee continues to examine barriers to implementa
				REPRODUCE!
		of the asthma management recommendations, especially
In 1993, the Global Initiative for Asthma (GINA) was		the challenges that arise in primary-care settings an
formed. Its goals and objectives were described in adeveloping1995			countries.
NHLBI/WHO Workshop Report,	Global Strategy for
Asthma Management and Prevention.	This Report	While early diagnosis of asthma and implementation of
(revised in 2002), and its companion documents, have		appropriate therapy significantly reduce the socioeco
been widely distributed and translated into many		burdens of asthma and enhance patientsi quality of li

languages. A network of individuals and organizationsmedications continue to be the major component of the interested in asthma care has been created and severalcost of asthma treatment. For this reason, the pricing country-specific asthma management programs have asthma medications continues to be a topic for urgent been initiated. Yet much work is still required tonereduceand a growing area of research interest, as this ha

morbidity and mortality from this chronic disease.important implications for the overall costs of asthm
		ALTER	OR
In January 2004, the GINA Executive Committee		management.
recommended that theGlobal Strategy for Asthma		Moreover, a large segment of the worldis population lives
Management and Prevention	be revised to emphasize	in areas with inadequate medical facilities and meage

asthma management based on clinical control, rather thanfinancial resources. The GINA Executive Committee classification of the patient by severity. This imprecognizesrtant that “fixed” international guidelines an paradigm shift for asthma care reflects the progressscienthatific protocols will not work in many locations. has been made in pharmacologic care of patients. Many the recommendations found in this Report must be

asthma patients are receiving, or have received, someadapted to fit local practices and the availability of h
asthma medications. The role of the health care	NOT
	care resources.
professional is to establish each patientis current level of
DO
treatment and control, then adjust treatment- to gainAsandthe GINA Committees expand their work, every effort

maintain control. This means that asthma patients shouwilldbe made to interact with patient and physician g
FUTURE CHALLENGES	MATERIAL	(GARD). Through the work of the GINA Committees, and

experience no or minimal symptoms (including at night),atnational, district, and local levels, and in multiple have no limitations on their activities (includingcarephysicalsettings, to continuously examine new and innov exercise), have no (or minimal) requirement for rescueapproaches that will ensure the delivery of the best a

	medications, have near normal lung function, and	care possible. GINA is a partner organization in a program
	experience only very infrequent exacerbations.	launched in March 2006 by the World Health Organization,
	COPYRIGHTED	the Global Alliance Against Chronic Respiratory Diseases
		in cooperation with GARD initiatives, progress toward

In spite of laudable efforts to improve asthma care overbetterthecare for all patients with asthma should be past decade, a majority of patients have not benefitedsubstantialfrom in the next decade.

advances in asthma treatment and many lack even the rudiments of care. A challenge for the next severalMETHODOLOGYyears is to work with primary health care providers and public

health officials in various countries to design, implA. Preparationment, of yearly updates:Immediately

and evaluate asthma care programs to meet local needs. following the release of an updated GINA Report in 2002, The GINA Executive Committee recognizes that this isthea Executive Committee appointed a GINA Science difficult task and, to aid in this work, has formedCommittee,several charged with keeping the Report up-to-date groups of global experts, including: a DisseminationbyTaskreviewing published research on asthma managemen Group; the GINA Assembly, a network of individuals whoand prevention, evaluating the impact of this researc care for asthma patients in many different health thcare management and prevention recommendations in the settings; and regional programs (the first two beingGINAGINAdocuments, and posting yearly updates of these Mesoamerica and GINA Mediterranean). These efforts documents on the GINA website. The first update was

x

posted in October 2003, based on publications from	as possible, while at the same time recognizing that o
January 2000 through December 2002. A second update	the values of the GINA Report has been to provide
appeared in October 2004, and a third in October 2005,	background information about asthma management and

each including the impact of publications from Januarythescientific information on which management through December of the previous year. recommendations are based.

The process of producing the yearly updates began withInJanuary 2006, the Committee met again for a two-day

Pub Med search using search fields established bysessionthe during which another in-depth evaluation of

Committee: 1)asthma, All Fields, All ages, only items with	chapter was conducted. At this meeting, members
abstracts, Clinical Trial, Human, sorted by Authors;and	reviewed the literature that appeared in 2005—using the
2) asthma AND systematic, All fields, ALL ages, only items	same criteria developed for the update process. The lis
with abstracts, Human, sorted by Author. In addition,	of 285 publications from 2005 that were considered is

peer-reviewed publications not captured by Pub Med couldposted on the GINA website. At the January meeting, it be submitted to individual members of the Committeewas clear that work remaining would permit the report t providing an abstract and the full paper were submittedbefinished during the summer of 2006 and, accordingly

(or translated into) English.	the Committee requested that as publications appeared
		REPRODUCE!
	throughout early 2006, they be reviewed carefully for th
	OR

All members of the Committee received a summary of impact on the recommendations. At the Committeeis next

citations and all abstracts. Each abstract was assignedmeetoing in May, 2006 publications meeting the search two Committee members, and an opportunity to provide ancriteria were considered and incorporated into the curr opinion on any single abstract was offered to all membersdrafts. of the chapters, where appropriate. A final meet

specifically identify modifications that shouldrepresentativesbemade. from the GINA Science Committee have

Members evaluated the abstract or, up to her/his	of the Committee was held in September 2006, at which
judgment, the full publication, by answering specificpublicationswrttenthat appear prior to July 31, 2006 were
questions from a short questionnaire, indicating consideredwheth for their impact on the document.
		ALTER
the scientific data presented affected recommendations in
the GINA Report. If so, the member was asked to	Periodically throughout the preparation of this report,
	NOT

The entire GINA Science Committee met on a regular	met with members of the GINA Assembly (May and
basis to discuss each individual publication thatSeptember,was 2005 and May 2006) to discuss the overall
-	theme of asthma control and issues specific to each o
judged by at least one member to have an impactDOon
MATERIAL	chapters. The GINA Assembly includes representative
asthma management and prevention recommendations,

and to reach a consensus on the changes in the Report. from over 50 countries and many participated in these

Disagreements were decided by vote.	interim discussions. In addition, members of the A
	were invited to submit comments on a DRAFT document

The publications that met the search criteria for eachduring the summer of 2006. Their comments, along with

yearly update (between 250 and 300 articles per year)	comments received from several individuals who were
mainly affected the chapters related to clinical	invited to serve as reviewers, were considered by the
management. Lists of the publications considered byCommitteethe in September, 2006.
COPYRIGHTED
Science Committee each year, along with the yearly
updated reports, are posted on the GINA website,	Summary of Major Changes
www.ginasthma.org.
	The major goal of the revision was to present informat
B. Preparation of new 2006 report:In January 2005,	about asthma management in as comprehensive manner

the GINA Science Committee initiated its work on thisaspossiblenew but not in the detail that would normally b report. During a two-day meeting, the Committee found in a textbook. Every effort has been made to sele established that the main theme of the new report shouldkeyreferences, although in many cases, several other be the control of asthma. A table of contents was publications could be cited. The document is intende developed, themes for each chapter identified, and writingbearesource; other summary reports will be prepared, teams formed. The Committee met in May and Septemberincluding a Pocket Guide specifically for the care of 2005 to evaluate progress and to reach consensus on and young children with asthma.

messages to be provided in each chapter. Throughout its work, the Committee made a commitment to develop a document that would: reach a global audience, be based

on the most current scientific literature, and be as concise

xi

	Some of the major changes that have been made in this		• No (twice or less/week) need for reliever treatment
	report include:		• Normal or near-normal lung function results
	1. Every effort has been made to produce a more		• No exacerbations
	streamlined document that will be of greater use to busy
		9. Emphasis is given to the concept that increased use
	clinicians, particularly primary care professionals. The
		especially daily use, of reliever medication is a warn
	document is referenced with the up-to-date sources so that				REPRODUCE!
		deterioration of asthma control and indicates the need
	interested readers may find further details on various
	topics that are summarized in the report.	reassess treatment.
		10. The roles in therapy of several medications have
	2. The whole of the document now emphasizes asthma evolved since previous versions of the report:
	control. There is now good evidence that the clinical		• Recent data indicating a possible increased risk of
	manifestations of asthma—symptoms, sleep disturbances,
			asthma-related death associated with the use of lon
	limitations of daily activity, impairment of lung function, and
	use of rescue medications—can be controlled with		acting2	-agonists in a small group of individuals
			resulted in increased emphasis on the message th
	appropriate treatment.
			long-acting-agonists should not be used as
				2
	3. Updated epidemiological data, particularly drawn from		monotherapy in asthma, and must only be used in
			combination with an appropriate dose of inhaled
	the reportGlobal Burden of Asthma, are summarized.		glucocorticosteroid.OR
	Although from the perspective of both the patient and• Leukotriene modifiers now have a more prominent
	society the cost to control asthma seems high, the cost of
	not treating asthma correctly is even higher.		role as controller treatment in asthma, particularly
			adults. Long-acting oral-agonists alone are no
					2
			longer presented as an option for add-on treatment at
	4. The concept of difficult-to-treat asthma is introduced and
			anyALTERstep of therapy, unless accompanied by inhaled
	developed at various points throughout the report. Patients
			glucocorticosteroids.
	with difficult-to-treat asthma are often relatively insensitive
			• Monotherapy with cromones is no longer given as an
	to the effects of glucocorticosteroid medications, and may
			alternative to monotherapy with a low dose of inhale
	sometimes be unable to achieve the same level of controlNOT
	as other asthma patients.	DO	glucocorticosteroids in adults.
			• Some changes have been made to the tables of
			equipotent daily doses of inhaled glucocorticoste
	5. Lung function testing by spirometry or-peak expiratory
	MATERIAL		for both children and adults.
	flow (PEF) continues to be recommended as an aid to

diagnosis and monitoring. Measuringvariabilitythe of

11. The six-part asthma management program detailed in airflow limitation is given increased prominence, as it is key to

previous versions of the report has been changed. The both asthma diagnosis and the assessment of asthma control.

current program includes the following five compone 6. The previous classification of asthma by severity intoComponent 1. Develop Patient/Doctor Partnership Intermittent, Mild Persistent, Moderate Persistent, and ComponSeverent 2. Identify and Reduce Exposure to Risk

COPYRIGHTED	professionals discuss and agree on the goals of treatm
Persistent is now recommended only for research purposes.		Factors
	Component 3.	Assess, Treat, and Monitor Asthma
7. Instead, the document now recommends a classificationComponent 4.		Manage Asthma Exacerbations
of asthma by level of control: Controlled, Partly Controlled,Component 5.		Special Considerations
or Uncontrolled. This reflects an understanding that asthma

severity involves not only the severity of the underly12. The ingclusion of Component 1 reflects the fact that disease but also its responsiveness to treatment,effectiveand that management of asthma requires the develop severity is not an unvarying feature of an individualofpartnership between the person with asthma and hi patientis asthma but may change over months or years. or her health care professional(s) (and parents/caregiver

8. Throughout the report, emphasis is placed on the	in the case of children with asthma). The partnership
	formed and strengthened as patients and their health
concept that the goal of asthma treatment is to achieve
and maintain clinical control. Asthma control is defined as:
	develop a personalized, written self-management action
• No (twice or less/week) daytime symptoms	plan including self-monitoring, and periodically rev
	patientis treatment and level of asthma control. Educat

• No limitations of daily activities, including exercise

remains a key element of all doctor-patient interaction

• No nocturnal symptoms or awakening because of asthma

xii

13. Component 3 presents an overall concept for asthma evidence levels2 and plans to review and consider the management oriented around the new focus on asthma possible introduction of this approach in future rep

control. Treatment is initiated and adjusted in a continuousextending it to evaluative and diagnostic aspects of
cycle (assessing asthma control, treating to achieve
control, and monitoring to maintain control) driven by the
patientis level of asthma control.		Table A. Description of Levels of Evidence
		Evidence				Sources of			Definition
14. Treatment options are organized into five “Steps”		Category				Evidence
			A		Randomized controlled trials				Evidence is from endpoints		of
reflecting increasing intensity of treatment
		(dosages		and/or					well designed CTs that
number of medications) required to achieve control.		At all			(RCTs). Rich body of data.
									provide a consistent pattern of
Steps, a reliever medication should be provided for as-									findings in the population for
									which the recommendation
needed use. AtSteps 2 through5 , a variety of controller
									is made. Category A requires
medications are available.									substantial numbers of studies
									involving substantial numbers
									of participants.
15. If asthma is not controlled on the current treatment					Randomized controlled trials				Evidence is from endpoints of
regimen, treatment should be stepped up until controlBis
					(RCTs). Limited body of data.				intervention studies that
achieved. When control is maintained, treatment can be							OR		REPRODUCE!include only a limited number
									of patients, posthoc or
stepped down in order to find the lowest step and dose of
									subgroup analysis of RCTs, or
treatment that maintains control.				ALTER					meta-analysis of RCTs. In
									general, Category B pertains
									when few randomized trials
16. Although each component contains management									exist, they are small in size,
advice for all age categories where these are considered									they were undertaken in a
									population that differs from the
relevant, special challenges must be taken into account in									target population of the recom-
making recommendations for managing asthma in children									mendation, or the results are
									somewhat inconsistent.
in the first 5 years of life. Accordingly, an Executive					Nonrandomized trials.				Evidence is from outcomes of
Summary has been prepared—and appears at the end of			C
					Observational studies.				uncontrolled or nonrandomized
this introduction—that extracts sections on diagnosis and									trials or from observational
management for this very young age group.	NOT								studies.
17. It has been demonstrated in a variety of settingsDO			D		Panel consensus judgment.				This category is used only in
			that						cases where the provision of
-									some guidance was deemed
patient care consistent with evidence-based asthma guide-
lines leads to improved outcomes. However, in order to									valuable but the clinical
									literature addressing the
effect changes in medical practice and consequent									subject was insufficient to
improvements in patient outcomes, evidence-based									justify placement in one of the
									other categories. The Panel
guidelines must be implemented and disseminated at									Consensus is based on
national and local levels. Thus, a chapter has been									clinical experience or
									knowledge that does not meet
added on implementation of asthma guidelines in health									the above-listed criteria.
systems that details the process and economics of
MATERIAL		REFERENCES
guideline implementation.
		1. Jadad AR, Moher M, Browman GP, Booker L, Sigouis C,
LEVELS OF EVIDENCE		Fuentes M,et al.Systematic reviews and meta-analyses
		on treatment of asthma: critical evaluationBMJ								.
In this document, levels of evidence are assigned 2000;320:537to-40.
management recommendations where appropriate in		2. Guyatt G, Vist G, Falck-Ytter Y, Kunz R, Magrini N,
Chapter 4, the Five Components of Asthma Management.		Schunemann H. An emerging consensus on grading
Evidence levels are indicated in boldface type enclosedrecommendations?in Available from URL:
parentheses after the relevant statementEvidence—.g.A, ().		http://www.evidence-basedmedicine.com.
The methodological issues concerning the use of evidence

fromCOPYRIGHTEDmeta-analyses were carefully considered1 .

This evidence level schemeTabl A( ) has been used in previous GINA reports, and was in use throughout the preparation of this document. The GINA Science Committee was recently introduced to a new approach to

xiii

				OR	REPRODUCE!
			ALTER
		NOT
	DO
	-
COPYRIGHTED	MATERIAL

	DO	NOT
	-
COPYRIGHTED	MATERIAL

		REPRODUCE!
CHAPTER
	OR	1
ALTER

DEFINITION

AND

OVERVIEW

	KEY POINTS:	Wheezing appreciated on auscultation of the chest is
		most common physical finding.

•Asthma is a chronic inflammatory disorder of the

airways in which many cells and cellular elementsThe main physiological feature of asthma is episodic a play a role. The chronic inflammation is associatedobstruction characterized by expiratory airflow limit

with airway hyperresponsiveness that leads toThe dominant pathological feature is airway inflammat recurrent episodes of wheezing, breathlessness,ometimes associated withREPRODUCE!airway structural changes chest tightness, and coughing, particularly at night

or in the early morning. These episodes are usuallyAsthma has significant genetic and environmental associated with widespread, but variable, airflowcomponents, but since its pathogenesis is not clear, obstruction within the lung that is often reversibleof its definition is descriptive. Based on the fun

flare-ups and severe exacerbations should be rare. The chronic inflammation is associated with airway

	hyperresponsiveness that leads to recurrent episodes of
• Asthma is a problem worldwide, with an estimated	wheezing, breathlessness, chest tightness, and coughing,
		OR
300 million affected individuals.	particularly at night or in the early morning. These
	episodes are usually associated with widespread, but
cost of not treating asthma correctly is even higher.ALTER

• Although from the perspective of both the patientvariable,and airflow obstruction within the lung that is often society the cost to control asthma seems high, thereversible either spontaneously or with treatment.

NOTBecause there is no clear definition of the asthma

•A number of factors that influence a personis riskphenotype,of researchers studying the development of t developing asthma have been identified. Thesecomplexcan disease turn to characteristics that can be be divided into host factors (primarily genetic)meandsured objectively, such as atopy (manifested as th

environmental factors.		DO	presence of positive skin-prick tests or the clinic
			response to common environmental allergens), airway
		-
	MATERIAL		hyperresponsiveness (the tendency of airways to narr
• The clinical spectrum of asthma is highly variable,
			excessively in response to triggers that have littl
and different cellular patterns have been observed,
			effect in normal individuals), and other measures of
but the presence of airway inflammation remains a
consistent feature.			allergic sensitization. Although the association bet
			asthma and atopy is well established, the precise lin
			between these two conditions have not been clearly and
COPYRIGHTED			comprehensively defined.
This chapter covers several topics related to asthma,

including definition, burden of disease, factors tThatereinfluenceis now good evidence that the clinical manifest the risk of developing asthma, and mechanisms. It isof asnothma—symptoms, sleep disturbances, limitation intended to be a comprehensive treatment of these topdailycs,activity, impairment of lung function, and us but rather a brief overview of the background that informsrescuemedications—can be controlled with appropriate the approach to diagnosis and management detailed in treatment. When asthma is controlled, there should be subsequent chapters. Further details are found in morthe than occasional recurrence of symptoms and severe reviews and other references cited at the end of theexacerbationschapter. should be1 rare.

DEFINITI N

Asthma is a disorder defined by its clinical, physiological, and pathological characteristics. The predominant feature of the clinical history is episodic shortness of breath, particularly at night, often accompanied by cough.

2 DEFINITION AND OVERVIEW

*(http://www.ginasthma.org/ReportItem.asp?l1=2&l2=2&intId=94).

DEFINITION AND OVERVIEW

Detailed reference information about the burden of as can be found in the repGlobalrt Burden of Asthma * .

Further studies of the social and economic burden of asthma and the cost effectiveness of treatment are n in both developed and developing countries.

Prevalence, Morbidity, and Mortality

THE BURDEN OF ASTHMA

Social and Economic Burden

Social and economic factors are integral to understandi asthma and its care, whether viewed from the perspect Asthma is a problem worldwide, with an estimated 300 of the individual sufferer, the health care profess

2,3
million affected individuals. Despite hundreds of reportsentities that pay for health care. Absence from school
on the prevalence of asthma in widely differing					days lost from work are reported as substantial social a
					economic consequences of asthma in studies from the
populations, the lack of a precise and universally accepted
					Asia-Pacific region, India, Latin America, the United
definition of asthma makes reliable comparison of reported								9-12
					Kingdom, and the United States.
prevalence from different parts of the world problematic.
Nonetheless, based on the application of standardized
methods to measure the prevalence of asthma and					The monetary costs of asthma, as estimated in a variety
3		4			of health care systems including those of the Unite
wheezing illness in childrenandadults, it appears that
					13-15			16
the global prevalence of asthma ranges from 1% to 18% of States						and the United Kingdomare substantial.
		2,3			In analyses of economic burden of asthma, attention
the population in differentFigurecountries1-1 ) . (There
					needs to be paid to both direct medical costs (hospital
is good evidence that international differences in asthma								REPRODUCE!
					admissions and cost of medications) and indirect, non
symptom prevalence have been reduced, particularly in										17
					medical costs (time lost from work, premature. death)
the 13-14 year age group, with decreases in prevalence in
North America and Western Europe and increases in					For example, asthma is a major cause of absence from
							OR
							4-6,121
					work in many countries, including Australia, Sweden,
prevalence in regions where prevalence was previously									16,18-20
low. Although there was little change in the overall the United Kingdom, and the United States.
					Comparisons of the cost of asthma in different regio
prevalence of current wheeze, the percentage of children
					lead to a clear set of conclusions:
reported to have had asthma increased significantly, possi-
bly reflecting greater awareness of this condition and/orALTER
					• The costs of asthma depend on the individual patient
changes in diagnostic practice. The increases in asthma
					level of control and the extent to which exacerbation
symptom prevalence in Africa, Latin America and parts of
Asia indicate that the global burden of asthma is					are avoided.
					NOT
continuing to rise, but the global prevalence differences
					• Emergency treatment is more expensive than planned
126					treatment.
are lessening. The World Health Organization has
estimated that 15 million disability-adjustedDOlife years
		-			• Non-medical economic costs of asthma are substantial.
(DALYs) are lost annually due to asthma, representing 1%
		2			• Guideline-determined asthma care can be cost effect
of the total global disease burden. Annual worldwide
deaths from asthma have been estimated at 250,000 and					• Families can suffer from the financial burden of
mortality does not appear to correlate well with prevalence
					asthma.
(Figure 1-1 )2,3 . There are insufficient data to determine the
likely causes of the described variations in prevalence
within and between populations.					Although from the perspective of both the patient and
					society the cost to control asthma seems high, the cos
									122
		MATERIAL
					not treating asthma correctly is even. Properhigher
		2, 3
	Figure 1-1. Asthma Prevalence and Mortality				treatment of the disease poses a challenge for indivi
	COPYRIGHTED				health care professionals, health care organizations, an
					governments. There is every reason to believe that th
					substantial global burden of asthma can be dramatically
					reduced through efforts by individuals, their healt
					providers, health care organizations, and local and
					national governments to improve asthma control.

Permission for use of this figure obtained from J. Bousquet.

3

FACTORS INFLUENCING THE DEVELOPMENT AND EXPRESSION OF ASTHMA

asthma in developed than in developing nations, in poor compared to affluent populations in developed nations, and in affluent compared to poor populations in developi nations—likely reflect lifestyle differences su exposure to allergens, access to health care, etc.

factors to determine asthma susceptibility. In addition,

airway hyperresponsiveness,REPRODUCE!atopy, and allergic

Much of what is known about asthma risk factors comes Factors that influence the risk of asthma can be divided

into those that cause the development of asthma and from studies of young children. Risk factors for th

	those that trigger asthma symptoms; some do both.							development of asthma in adults, particularlyde novo in
								adults who did not have asthma in childhood, are less
	The former include host factors (which are primarily
								well defined.
	genetic) and the latter are usually environmental factors
	(Figure 1-2 )21 . However, the mechanisms whereby they
								The lack of a clear definition for asthma presents a
	influence the development and expression of asthma are
	complex and interactive. For example, genes likely							significant problem in studying the role of diffe
								factors in the development of this complex disease,
	interact both with other genes and with environmental
				22,23				because the characteristics that define asthma (e.g.,
	developmental aspects—such as the maturation of the
								sensitization) are themselves products of complex
	immune response and the timing of infectious exposures
								gene-environment interactions and are therefore both
	during the first years of life—are emerging as important										OR
								features of asthma and risk factors for the developme
	factors modifying the risk of asthma in the genetically
	susceptible person.							of the disease.
								Host Factors
									ALTER
			Figure 1-2. Factors Influencing the Development
			and Expression of Asthma
								Genetic. Asthma has a heritable component, but it is not
								simple. Current data show that multiple genes may be
		HOST FACTORS
											24,25
								involved in the pathogenesis of asthma,anddifferent
			Genetic, e.g.,					NOT
								genes may be involved in different ethnic groups. T
			• Genes pre-disposing to atopy					search for genes linked to the development of asthma h
			• Genes pre-disposing to airway hyperresponsiveness
					DO			focused on four major areas: production of allergen-
			Obesity		-			specific IgE antibodies (atopy); expression of airway
			Sex					hyperresponsiveness; generation of inflammatory
		ENVIRONMENTAL FACTORS						mediators, such as cytokines, chemokines, and growth
								factors; and determination of the ratio between Th1 and
			Allergens					Th2 immune responses (as relevant to the hygiene
			• Indoor: Domestic mites, furred animals (dogs, cats,								26
			mice), cockroach allergen, fungi, molds, yeasts					hypothesis of asthma).
			• Outdoor: Pollens, fungi, molds, yeasts					Family studies and case-control association analyses h
				MATERIAL				identified a number of chromosomal regions associated
			Infections (predominantly viral)
			Occupational sensitizers					with asthma susceptibility. For example, a tendency
			Tobacco smoke					produce an elevated level of total serum IgE is co-inher
			• Passive smoking					with airway hyperresponsiveness, and a gene (or genes)
			• Active smoking					governing airway hyperresponsiveness is located near
			Outdoor/Indoor Air Pollution					major locus that regulates serum IgE levels on
			Diet					chromosome 5q 27 . However, the search for a specific
								gene (or genes) involved in susceptibility to atopy or
								asthma continues, as results to date have been
	Additionally, some characteristics have been linked to an									24,25
								inconsistent.

increasedCOPYRIGHTEDrisk for asthma, but are not themselves true causal factors. The apparent racial and ethnic differences

In addition to genes that predispose to asthma there ar in the prevalence of asthma reflect underlying genetic

genes that are associated with the response to asthma variances with a significant overlay of socioeconomic and

treatments. For example, variations in the gene encodi environmental factors. In turn, the links between asthma

the beta-adrenoreceptor have been linked to difference and socioeconomic status—with a higher prevalence of

4 DEFINITION AND OVERVIEW