GINA2009

a patientis exposure to some of these categories of riskFurred animals. Complete avoidance of pet allergens is factors (e.g., smoking cessation, reducing exposureimpossible,to as the allergens are ubiquitous and can be

secondhand smoke, reducing or eliminating exposurefoundto		in many environments outside the,includinghome
occupational agents known to cause symptoms, and			64
	schools, public transportation, and cat-free buildings.
		65	66

avoiding foods/additives/drugs known to cause symptoms)Although removal of such animals from the home is improves the control of asthma and reduces medicationencouraged, even after permanent removal of the animal

exacerbations than those whose asthma is not well-

REPRODUCE!

needs. In the case of other factors (e.g., allergens, viralcanbe many months before allergen levels decrease67 and infections and pollutants), measures where possiblethe clinical effectiveness of this and other inter

should be taken to avoid these. Because many asthma

remains unprovenFigure(

4.2-1 ).

patients react to multiple factors that are ubiquitous in

the environment, avoiding these factors completely

Fisgure 4.2-1: Effectiveness of Avoidance Measures

for Some Indoor Allergens*

usually impractical and very limiting to the patient. Thus,

medications to maintain asthma control have an important

Measure

Evidence

Evidence

role because patients are often less sensitive to these risk

of effect

of clinical

factors when their asthma is under good control. Patients

on allergen

benefit

levels

with well-controlled asthma are less likely to experience

House dust mites

364

Encase bedding in impermeable covers Some

None

controlled.

OR

(adults)

Indoor Allergens

Some

(children)

o

Some

None

Among the wide variety of allergen sources in human Wash bedding in the hot cycle (55C)-60

dwellings are domestic mites, furred animals,

Replace carpets with hard flooring

Some

None

cockroaches, and fungi. However, there is conflictingAcaricides and/or tannic acid

Weak

None

Minimize objects that accumulate dust

None

evidence about whether measures to create a low-allergen

ALTER

None

environment in patientsi homes and reduce exposure

toVacuum cleaners with integral HEPA filterWeak

None

indoor allergens are effective at reducing asthma

and double-thickness bags

54,55

Remove, hot wash, or freeze soft toysNone

None

symptoms

. The majority of single interventions have

NOT

failed to achieve a sufficient reduction in allergen load to

55-57

Pets

lead to clinical improvement. It is likely that no single

intervention will achieve sufficient benefitsDO

Removeto becat/dogcostfrom the home

Weak

None

-

None

effective. However, among inner-city children withKeepatopicpet from main living areas/bedroomsWeak

asthma, an individualized, home-based, comprehensive

HEPA-filter air cleaners

Some

None

environmental intervention decreased exposure to

indoor

Weak

None

allergens and resulted in reduced asthma-associated

Wash pet

None

None

58

Replace carpets with hard flooring

morbidity. More properly powered and well-designed

Vacuum cleaners with integral HEPA filtNoner

None

studies of combined allergen-reduction strategies in large

groups of patients are needed.

and double-thickness bags

MATERIAL

*Adapted from Custovic A, Wijk RG. The effectiveness of measures to change the

indoor environment in the treatment of allergic rhinitis and asthma: ARIA update

Domestic mites. Domestic mite allergy is a universal(in collaboration with GA(2)LEN). Allergy 2005;60(9):1112-1115.

59

health problem. Since mites live and thrive in many sites

throughout the house, they are difficult to reduceCockroachesand

. Avoidance measures for cockroaches

impossible to eradicateFigure( 4.2-1 ). No single measure

include eliminating suitable environments (restri

COPYRIGHTED

is likely to reduce exposure to mite allergens, and singlehavensby caulking and sealing cracks in the plasterw chemical and physical methods aimed at reducing miteand flooring, controlling dampness, and reducing the allergens are not effective in reducing asthma symptomsavailability of food), restricting access (sealing ent

in adults (Evidence A ). One study showed some	such as around paperwork and doors), chemical control,
55,60-62

efficacy of mattress encasing at reducing airway and traps. However, these measures are only partially

hyperresponsiveness in chil(Evidenceren B ). An	effective in removing residual(EvidallergncensC ).
63	68

integrated approach including barrier methods, dust removal,

and reduction of microhabitats favorable to mites hasFungibeen. Fungal exposure has been associated with suggested, although its efficacy at reducing symptomsexacerbations from asthma and the number of fungal

has only been confirmed in deprived populations withsporesa		can best be reduced by removing or cleaning mold
specific environmental exposure(Evidence B ) and a	laden objects. In tropical and subtropical climates, fu
58		69

recommendation for its widespread use cannot be mademay. grow on the walls of the house due to water seepage

ASTHMA MANAGEMENT AND PREVENTION

55

Outdoor Allergens

and humidity. To avoid this, the walls could be tiledexacerbationsor by a variety of mechanisms, including cleaned as necessary. Air conditioners and dehumidifiersandpollution, increases in respirable allergens, and may be used to reduce humidity to levels less thanchanges50% in temperature/humidity.

and to filter large fungal spores. However, air conditioning

Avoidance of unfavorable environmental conditions is and sealing of windows have also been associated with

usually unnecessary for patients whose asthma is increases in fungal and house dust mite70 . allergens

controlled. For patients with asthma that is diffic control, practical steps to take during unfavorable environmental conditions include avoiding strenuou

Indoor Air Pollutants	identification of occupationalREPRODUCE!sensitizers and the
	of sensitized patients from any further exposure a
	important aspects of the management of occupational
		OR
The most important measure in controlling indoor airasthma (Evidence B ). Once a patient has become
pollutants is to avoid passive and active smoking.	sensitized to an occupational allergen, the level of exp
	ALTER

physical activity in cold weather, low humidity, or hi Outdoor allergens such as pollens and molds are impossible

pollution; avoiding smoking and smoke-filled rooms; an to avoid completely. Exposure may be reduced by closing

windows and doors, remaining indoors when pollen and staying indoors in a climate-controlled environment.

mold counts are highest, and using air conditioning if

Occupational Exposures possible. Some countries use radio, television, and the

Internet to provide information on outdoor allergen levelsOccupational. exposures account for a substantial The impact of these measures is difficult to assessproportion. of adult asthma incidence357 . The early

Secondhand smoke increases the frequency and severitynecessary to induce symptoms may be extremely low, an of symptoms in children with asthma. Parents/caregiversresulting exacerbations become increasingly severe. of children with asthma should be advised not to smokeAttempts to reduce occupational exposure have been

and not to allow smoking in rooms their children usesuccessful.In especially in industrial settings, an addition to increasing asthma symptoms and causingselonsitizers,g- such as soy castor bean, have been replaced term impairments in lung function, active cigarettelessmokingallergenic substances80 (Evidence B ). Prevention of

DO
reduces the efficacy of inhaled and systemic glucocorticoslatexNOT sensitization-	has been made possible by the produ

teroids (Evidence B ), and smoking cessation needs to beof hypoallergenic gloves, which are powder free and have
71,72
vigorously encouraged for all patients with asthma whoasmokelower.allergen content(Evidence C ). Although more
Other major indoor air pollutants include nitric-	81,82
	oxide,expensive than untreated gloves, they are cost effec
MATERIAL
nitrogen oxides, carbon monoxide, carbon dioxide, sulfur
73	Food and Food Additives
dioxide, formaldehyde, and biologicals (endotoxin).
Installation of non-polluting, more effective heating (heat
	Food allergy as an exacerbating factor for asthma is

	pump, wood pellet burner, flued gas) in the homes of uncommon and occurs primarily in young children. Food
	children with asthma does not significantly improve lung
			avoidance should not be recommended until an allergy has
	function but does significantly reduce symptoms of			83
			been clearly demonstrated (usually by oral challenges).
	asthma, days off school, healthcare utilization, and visits to
	365		When food allergy is demonstrated, food allergen avoidanc
	COPYRIGHTED		confirmation of their relevance requires double-blin
	a pharmacist.		84	).
			can reduce asthma exacerbations(Evidence D
	Outdoor Air Pollutants		Sulfites (common food and drug preservatives found i
			such foods as processed potatoes, shrimp, dried fruit
			beer, and wine) have often been implicated in causing
	Several studies have suggested that outdoor pollutants
			severe asthma exacerbations but the likelihood of a
	aggravate asthma symptoms , possibly having an addi-reaction is dependent on the nature of the food, the le
	74, 356
	tive effect with allergen. exposureOutbreaks of asthma
		75	of residual sulfite, the sensitivity of the patie
	exacerbations have been shown to occur in relationship to
			residual sulfite and the mechanism of the sulfit
	increased levels of air pollution, and this may be related to85
			reaction. The role of other dietary substances—includ
	a general increase in pollutant levels or to an increase in
			the yellow dye tartrazine, benzoate, and monosodium
	specific allergens to which individuals are. sensitized
		76-78	glutamate—in exacerbating asthma is probably minimal
	Most epidemiological studies show a significant
	association between air pollutants–such as ozone,		challenge before making specific dietary restricti
	nitrogen oxides, acidic aerosols, and particulate
	matter–and symptoms or exacerbations of asthma. On		Drugs
	occasion, certain weather and atmospheric conditions,
	e.g., thunderstormsfavor the development of asthma		Some medications can exacerbate asthma. Aspirin and
	79

56 ASTHMA MANAGEMENT AND PREVENTION

other nonsteroidal anti-inflammatory drugs can causeexacerbations have been documented. Similarly, asthma
	102
severe exacerbations and should be avoided in patientsmay improve, worsen, or remain unchanged during pregnancy.
with a history of reacting to these. Betaagents-blocker	103
	A randomized clinical trial of a self-regulation, telephone
86

drugs administered orally or intraocularly may exacerbatecounseling intervention emphasizing sex and gender role bronchospasm Evidence( A ) and close medical supervisionin the management of asthma indicated that a program with a

87
is essential when these are used by patients. withfocusasthmaon asthma management problems particular to women
			358	patients
Beta blockers have a proven benefit in the managementcanofsignificantly assist female asthma.
patients with acute coronary syndromes and for secondary
prevention of coronary events. Data suggest that patients
	COMPONENT 3: ASSESS, TREAT,
with asthma who receive newer more cardio-selective beta
blockers within 24 hours of hospital admission for anANDacuteMONITOR ASTHMA
366, 367
coronary event have lower in-hospital mortality. rates
Influenza Vaccination
	KEY POINTS:
Patients with moderate to severe asthma should be advised
88		• The goal of asthma treatment, to achieve and
to receive an influenza vaccination everyor atyleastar
when vaccination of the general population is advised.		maintain clinical control, can be reached in a
However, routine influenza vaccination89 ofandchildren			REPRODUCE!
		majority of patients with a pharmacologic
90		intervention strategy developed in partnership
adultswith asthma does not appear to protect them from
asthma exacerbations or improve asthma control. Inactivated between theORpatient/family and the doctor.
influenza vaccines are associated with few side effects
		ALTER

and are safe to administer to asthmatic adults and children•Treatment should be adjusted in a continuous cyc over the age of 3 years, including those with difficultdriven-to-treatby the patientsi asthma control status. I

asthma . There are data to suggest that intranasal		asthma is not controlled on the current treatment
91
vaccination in children under age 3 may be associated		regimen, treatment should be stepped up until
with an increased incidence of asthma exacerbations.		control is achieved. When control is maintained fo
92
		least three months, treatment can be stepped down.
Obesity	NOT• In treatment-naïve patients with persistent as

the severity of asthma99 . However, sinusitis and asthmaadjusted in a continuous cycle driven by changes in

	Increases in body mass index (BMI) have been associated with treatment should be startedStep 2 at,or, if very sympto-
	increased prevalence of asthma, although the mechanisms behind
	93				matic (uncontrolled),Stepat3 . For Steps 2 through5 ,
	this association are uncl. Weightar reduction inDOobese				a variety of controller medications are available.
			-
	patients with asthma has been demonstrated to improve lung
		94
	function, symptoms, morbidity, and health(EvidencestatusB ).				• At each treatment step, reliever medication shoul
	Emotional Stress				be provided for quick relief of symptoms as need
					• Ongoing monitoring is essential to maintain cont
	Emotional stress may lead to asthma exacerbations, primarily
					and to establish the lowest step and dose of
	because extreme emotional expressions (laughing, crying,
	anger, or fear) can lead to hyperventilation and hypocapnia,				treatment to minimize cost and maximize safety
		95,96
	which can cause airway narrowingMATERIAL. Panic attacks, which
	are rare but not exceptional in some patients with asthma,
	97,98			INTRODUCTION
	have a similar effect. However, it is important to note that
	asthma is not primarily a psychosomatic disorder.
				The goal of asthma treatment, to achieve and maintain
	Other Factors That May Exacerbate Asthma				104,344
				clinical control, can be reached in a majority of patient
				with a pharmacologic intervention strategy developed i
	Rhinitis, sinusitis, and polyposis are frequently associated
				partnership between the patient/family and the doctor
	with asthma and need to be treated. In children, antibiotic
				Each patient is assigned to one of five “treatment st
	treatment of bacterial sinusitis has been shown to reduce
	COPYRIGHTED			depending on their current level of control and treatm

may simply coexist. Apart from sinusitis, there is little
asthma control status. This cycle involves:
evidence that bacterial infections exacerbate asthma.	• Assessing Asthma Control
Gastroesophageal reflux can exacerbate asthma, especially
in children, and asthma sometimes improves when the reflux•Treating to Achieve Control
is corrected . Many women complain that their asthma	• Monitoring to Maintain Control
100,101

is worse at the time of menstruation, and premenstrualIn this Component, this cycle is described for long-t

ASTHMA MANAGEMENT AND PREVENTION

57

treatment of asthma. Treatment for exacerbations isMaintain Control below). If asthma is partly controlled, an

detailed in Component 4.			increase in treatment should be considered, subject
			whether more effective options are available (e.g.,
ASSESSING ASTHMA CONTROL			increased dose or an additional treatment), safety and c
			of possible treatment options, and the patientis sati
			with the level of control achieved. The scheme presen
Each patient should be assessed to establish his or her
			inFigure 4.3-2 is based upon these principles, but the
current treatment regimen, adherence to the current
regimen, and level of asthma control. A simplified			range and sequence of medications used in each clini
			setting will vary depending on local availability (for
scheme for recognizing controlled, partly controlled, and
uncontrolled asthma in a given week is provided in			other reasons), acceptability, and preference.
Figure 4.3-1 . This is a working scheme based on current
opinion and has not been validated. Several composite			Treatment Steps for Achieving Control
	105		Most of the medications available for asthma patients,
control measures (e.g., Asthma Control Test,Asthma
106-108			when compared with medications used for other chronic
Control Questionnaire, Asthma Therapy Assessment
109	110		diseases, have extremely favorable therapeutic ratios
Questionnaire, Asthma Control Scoring System)
have been developed and are being validated for various
			Each step represents treatment options that, although
				REPRODUCE!
applications, including use by health care providersoftoidentical efficacy, are alternatives for controlli

assess the state of control of their patientsi asthmaStepsand1 to5 provideORoptions of increasing efficacy, ex by patients for self-assessments as part of a writtenforStep 5 where issues of availability and safety in

personal asthma action plan. Uncontrolled asthma may the selection of treatmentStep 2 is. the initial treatment progress to the point of an exacerbation, and immediatemost treatment-naïve patients with persistent asth

steps, described in Component 4, should be taken to		symptoms. If symptoms at the initial consultation
regain control.		that asthma is severely uncontrolledFigure 4.3(-1 ),
		treatmentALTERshould be commencedStepat3 .
TREATING TO ACHIEVE CONTROL		At each treatment step, a reliever medicatrapidon-onset(
		bronchodilator, either short-acting or long-acting) shou
The patientis current level of asthma control and currentNOT
DO		be provided for quick relief of symptoms. However,

treatment determine the selection of pharmacologicregular use of reliever medication is one of the elem

treatment. For example, if asthma is not controlled on the
			defining uncontrolled asthma, and indicates that con
current treatment regimen, treatment should- be stepped
			treatment should be increased. Thus, reducing or elimi
up until control is achieved. If control has been maintained
			the need for reliever treatment is both an important g
for at least three months, treatment can be stepped down
			and measure of success of treatmentSteps. For2
with the aim of establishing the lowest step and dose of
treatment that maintains controlMonitoring(seeto			through5 , a variety of controller medications are availabl
	Figure 4.3-1. Levels of Asthma Control
Characteristic		Controlled		Partly Controlled	Uncontrolled
		MATERIAL		(Any measure present in any week)
		(All of the following)
Daytime symptoms		Twice or less/week		More than twice/week	Three or more features
					of partly controlled
Limitations of activities		None		Any
					asthma present in
Nocturnal symptoms/awakening		None		Any	any week* †
Need for reliever/		Twice or less/week		More than twice/week
rescue treatment
Lung function (PEF or FEV 1 )‡		Normal		< 80% predicted or personal best
	COPYRIGHTED			(if known)

B. Assesment of Future Risk(risk of exacerbations, instability, rapid decline in lung function, side-effect)

Features that are associated with increased risk of adverse events in the future include: FEV 1* exposure to cigarette smoke, high dose medications

* Any exacerbation should prompt review of maintenance treatment to ensure that it is adequate.

† By definition, an exacerbation in any week makes that an uncontrolled week.

‡ Lung function is not a reliable test for children 5 years and younger.

58 ASTHMA MANAGEMENT AND PREVENTION

Figure 4.3-2.

Management Approach Based On Control

For Children Older Than 5eY ra ,slodA cse stne and tludA s

evelL of Control

Reduce

aerT

tment

cA

tion

REPRODUCE!

Controlled

Maintain and find lowest controlling step

Partly controlled

Consider stepping up to gain control

Uncontrolled

Increase

Step up until controlled

Exacerbation

Treat

a sxe

ca re bat noi

OR

Step 1

Step 2

Step 3

Step 5

ALTERStep 4

Reduce

rT ae emt tnspetS

Increase

NOT

Asthma education

Environmental control

As needed rapid-

DO

acting β2-agonist

As needed rapid-acting β2-agonist

-

MATERIAL

Select one

oT

Step

t3

reat

em

tn ,

TotS pe 4 treatm tne ,

Select one

select

eno

mro ore

add ie ther

Low-dose inhaled

Low-dose ICS plus

Medium-or high-dose

Oral glucocorticosteroid

ICS plus long-acting

ICS*

long-acting β2-agonist

(lowest dose)

β2-agonist

Controller

Leukotriene

Medium-or

options***

Leukotriene

Anti-IgE

modifier*

high-dose ICS

modifier

treatment

COPYRIGHTED

Low-dose ICS plus

Sustained release

leukotriene modifier

theophylline

Low-dose ICS plus

sustained release

theophylline

* ICS = inhaled glucocorticosteroids

**= Receptor antagonist or synthesis inhibitors

*** = referred controller options are shown in shaded boxes

Alternative reliever treatments include inhaled anticholinergics, short-acting oral 2 -agonists, some long-acting 2 -agonists, and short-acting theophylline. Regular dosing with short and long-acting 2 -agonist is not advised unless accompanied by regular use of an inhaled glucocorticosteroid.

Figure 4.3-2: Management Approach Based on Control For Children 5 Years and Younger

Global Strategy for Asthma Management and Prevention in Children 5 Years and Younger. Availablewww.ginasthmaat .org .

ASTHMA MANAGEMENT AND PREVENTION

59

Step 1: As-needed reliever medication. Step 1 patients who are unable or unwilling to use inhaled treatment with an as-needed reliever medication isglucocorticosteroids, or who experience intolerable si reserved for untreated patients with occasional daytimeeffects such as persistent hoarseness from inhale symptoms (cough, wheeze, dyspnea occurring twice orglucocorticosteroid treatment and those with concomit less per week, or less frequently if nocturnal) ofallergicshort rhinitis124,125 (Evidence C ).

duration (lasting only a few hours) comparable with

controlled asthmaFigure(	4.3-1 ). Between episodes, the							REPRODUCE!
						Other options are available but not recommended for
patient is asymptomatic with normal lung function and									in
						routine use as initial or first-lineSt pcontrollers2 .
there is no nocturnal awakening. When symptoms are Sustained-release theophyllinehas only weak anti-
more frequent, and/or worsen periodically, patients require								126-130
regular controller treatmentStep(see2 or higher) in						inflammatory and controller efficacy(Evidence B ) and
						is commonly associated with side effects that range
addition to as-needed reliever medication(Evidence B ).						trivial to intolerable. Cromones (nedocromil sodium
			111-113				131,132
For the majority of patientsStep 1 in,a rapid-acting inhaled						and sodium cromoglycate)have comparatively low
						efficacy, though a favorable safety (profileEvidence A ).
2 -agonistis the recommended reliever treatment								133-136
			114
(Evidence A ). An inhaled anticholinergic, short-acting oral
						Step 3: Reliever medication plus one or two
-agonist, or short-acting theophylline may be considered
2						controllers. At Step 3 , the recommended option for
as alternatives, although they have a slower onset ofadolescents and adults is to combinelow-dosea of
action and higher risk of sideEvidenceeffectsA ). (						inhaled glucocorticosteroid with an inhaled long-acti
						monthsALTERwith this regEvidencemen ( A ). The long-acting
Exercise-induced bronchoconstriction						2 -agonist,eitherORin a combination inhaler device or as
		. Physical activity is					137-144	(Evidence A ). Because of
						separate components
an important cause of asthma symptoms for most asthma
						the additive effect of this combination, the low-dos
patients, and for some it is the only cause. However,
						glucocorticosteroid is usually sufficient, and nee
exercise-induced bronchoconstriction often indicates that
						be increased if control is not achieved within 3 or 4
						NOT
the patient's asthma is not well controlled, and stepping
up controller therapy generally results in the reduction of
						2 -agonist formoterol, which has a rapid onset of action
exercise-related symptoms. For those patients who still							145-148
						whether given alone or in combination inhaler with
experience exercise-induced bronchoconstriction despite							149,150
						budesonide , has been shown to be as effective as
otherwise well-controlled asthma, and for those in whom
						short-acting-agonist in acute asthma exacerbation.
exercise-induced bronchoconstriction is the only mani-							2
				-		However its use as monotherapy as a reliever medicatio
festation of asthma, a rapid-acting inhaled-agonist					DO	is strongly discouraged since it must always be use
			2
European Respiratory Society,MATERIALthe European Academy of								152,153
(shortor long-acting), taken prior to exercise or to relieve
					115	association with an inhaled glucocorticosteroid.
symptoms that develop after exercise, is recommended.
A leukotriene modifieror cromone		117	are alternatives
116,345						For all children but particularly those 5 years and youn

	(Evidence A ). Training and sufficient warm-up also combination therapy has been less well studied and th
	reduce the incidence and severity of exercise-induced
		118,119		addition of a long-acting- onist may not be as
					2
	bronchoconstriction(Evidence B ). Information on			effective as increasing the dose of inhaled glucocor
	treatment of exercise-induced asthma in athletes can be				151-153
	found in a Joint Task Force Report prepared by the			steroids in reducing exacerbations. However, the
				interpretation of some studies is problematic as not
			359	children received concurrent inhaled glucocorticostero.
	Allergy and Clinical Immunology, and GA(2)LENand the
	World Anti-Doping Agency website (www.wada-ama.org).			If a combination inhaler containing formoterol and
	Step 2: Reliever medication plus a single controller.			budesonide is selected, it may be used for both rescu
				and maintenance. This approach has been shown to
	TreatmentSteps 2 through5 , combine an as-needed
				result in reductions in exacerbations and improvemen
	reliever treatment with regular controller treatment. At
	Step 2 , a low-dose inhaled glucocorticosteroidis			asthma control in adults and adolescents at relatively
					154-157
				doses of treatment(Evidence A ). Whether this
	recommended as the initial controller treatment for asthma
		111,120		approach can be employed with other combinations of
	patients of all ages(Evidence A ). Equivalent doses of controller and reliever requires further study.
	inhaled glucocorticosteroids, some of which may be given
	as aCOPYRIGHTEDsingle daily dose, are providedFigurein 3-1 for			Another option for both adults and children, but the one
	adults and Figurein		3-4 for children older than 5 years..
					158
				recommended for children, is to increase mediumto a -
					104,159-161
	Alternative controller medicationsleukotrieneinclude			dose of inhaled glucocorticosteroids(Evidence A ).
				For patients of all ages on mediumor high-dose of
	121-123	(Evidence A ), appropriate particularly for
	modifiers			inhaled glucocorticosteroid delivered by a pressurize

60 ASTHMA MANAGEMENT AND PREVENTION

	metered-dose inhaler, use of a spacer device is					Step 5: Reliever medication plus additional controller
	recommended to improve delivery to the airways, reduceoptions. Addition oralf glucocorticosteroidsto other
	oropharyngeal side effects, and reduce systemic							179
						controller medications may be effective(Evidence D )
	162-164	(Evidence A ).						180
	absorption					but is associated with severe side(EvidenceeffectsA )
	Another option atStep 3 is to combine a low-dose inhaled					and should only be considered if the patientis asthma
						remains severely uncontrolledStep 4onmedications with
			165-173			daily limitation of activities and frequent exacerb
	glucocorticosteroid with leukotriene modifiers
	(Evidence A	). Alternatively, the use of sustained-release
			129			Patients should be counseled about potential side eff
						and all other alternative treatments must be consider
	theophylline given at low-dose may be considered
	(Evidence B ). These options have not been fully studied
	in children 5 years and younger.					Addition ofanti-IgE treatmentto other controller medications
	Step 4: Reliever medication plus two or more					has been shown to improve control of allergic asthma
						when control has not been achieved on combinations of
	controllers. The selection of treatmentStep 4atdepends					other controllers including high-doses of inhaled or o
	on prior selectionsStepsat 2 and 3 . However, the order in						181-186
						glucocorticosteroids(Evidence B ).
	which additional medications should be added is based, as
	far as possible, upon evidence of their relative efficacy in							REPRODUCE!
						MONITORING TO MAINTAIN CONTROL
	clinical trials. Where possible, patients who are not
	controlled onStep 3 treatments shouldeferredbe			to a		When asthma controlORhas been achieved, ongoing
	health professional with expertise in the management
						monitoring is essential to maintain control and to es
	of asthmafor investigation of alternative diagnoses and/or
	causes of difficult-to-treat asthma.					the lowest step and dose of treatment necessary, whic
						minimizes the cost and maximizes the safety of tre
	The preferred treatmentStepat4 is to combine a					On the other hand, asthma is a variable disease, and treat
	mediumor high-dose of inhaled glucocorticosteroid ment hasALTERto be adjusted periodically in response to los
	with a long-acting inhaled-agonist.However, in					control as indicated by worsening symptoms or the
			2			development of an exacerbation.
	most patients, the increase from a mediumto a high-dose
	of inhaled glucocorticosteroid provides relativelyNOTlittle
		104,159-161,174				Asthma control should be monitored by the health care
	additional benefit (Evidence A ), and the high-					professional and preferably also by the patient at regu
	dose is recommended only on a trial basis for 3 to 6
						intervals, using either a simplified scheme as pre
				DO
	months when control cannot be achieved with-medium-
						Figure 4.3-1 or a validated composite measure of control.
	dose inhaled glucocorticosteroid combined with a long-
						The frequency of health care visits and assessment
	acting -agonist and/or a third controller (e.g. leukotriene
	2		130,175,346			depends upon the patientis initial clinical severity
	modifiers or sustained-release theophylline )					patientis training and confidence in playing a role in
	(Evidence B	). Prolonged use of high-dose inhaled				going control of his or her asthma. Typically, patients
	glucocorticosteroids is also associated with increased
						seen one to three months after the initial visit, and
	potential for adverse effects. At mediumand high-doses,
						three months thereafter. After an exacerbation, follow
	twice-daily dosing is necessary for most but not all inhaled
						should be offered within two weeks to one month
		176				(Evidence D ).
	glucocorticosteroids(Evidence ). With budesonide,
			MATERIAL
	efficacy may be improved with more frequent dosing (four
	177					Duration and Adjustments to Treatment
	times daily)(Evidence B ). (Refer toFigure 3-1 for
	(EvidenceCOPYRIGHTEDA ). The addition of a low-dosesustainedof				-	some of the consequences of long-term inflammation o

adults andFigure 3-4 for children older than 5 years for

recommendations on dosing and frequency for differentFor most classes of controller medications, improveme

inhaled glucocorticosteroids.)	begins within days of initiating treatment, but th
	may only be evident after 3 or 4 months. In severe and
Leukotriene modifiersa add-on treatment to medium-to	187, 360
	chronically undertreated disease, this can take even. lon
	188
high-dose inhaled glucocorticosteroids have been shown
	The reduced need for medication once control is achieve
to provide benefitEvidence( A ), but usually less than that
165-168,175,178	is not fully understood, but may reflect the reversa
achieved with the addition of a long--actingagonist
2
130	the airways. Higher doses of anti-inflammatory medi
release theophyllineto mediumor high-dose inhaled	may be required to achieve this benefit than to maint
glucocorticosteroid and long-acting-agonist may also
2	Alternatively, the reduced need for medication might
provide benefitEvidence( B )129 .
	simply represent spontaneous improvement as part of

cyclical natural history of asthma. Rarely, asthma may go

ASTHMA MANAGEMENT AND PREVENTION

61

into remission particularly in children aged 5 years and•When asthma is controlled inhaledwith gluco-

younger and during puberty. Whatever the explanation, corticosteroids in combination with controllers

in all patients the minimum controlling dose of treatmentother than long-acting-agonists, the dose of

2

must be sought through a process of regular follow-up andinhaled glucocorticosteroid should be reduced by 50%

staged dose reductions.	until a low-dose of inhaled glucocorticosteroid is
	reached, then the combination treatment stopped as
At other times treatment may need to be increased either		REPRODUCE!
	described aboveEvidence(		).

in response to loss of control or threat of loss of control

(return of symptoms) or an acute exacerbation, which is• Controller treatment may be stoppedif the patientis defined as a more acute and severe loss of control that asthma remains controlled on the lowest dose of requires urgent treatment. (An approach to exacerbationscontroller and no recurrence of symptoms occurs for

is provided in Component 4.4.)	one year (Evidence D ).
Stepping Down Treatment When Asthma Is Controlled	Stepping Up Treatment In Response To Loss Of Control

There is little experimental data on the optimal timing,Treatment has to be adjusted periodically in response

	sequence, and magnitude of treatment reductions inworsening control, which may be recognized by the mino
	asthma, and the approach will differ from patient to recurrencepatient or worsening of symptoms. Treatment
							195
	depending on the combination of medications and theoptions are as follows:
	doses that were needed to achieve control. These				ALTER	OR
	changes should ideally be made by agreement between				• Rapid-onset, short-acting or long-acting-
					agonist bronchodilatorsRepeated.			2
								dosing with
	patient and health care professional, with full discussion of
	potential consequences including reappearance of				bronchodilators in this class provides temporary re
					until the cause of the worsening symptoms passe
	symptoms and increased risk of exacerbations.
					The need for repeated doses over more than one or
	Although further research on stepping down asthma				two days signals the need for review and possible
					increase of controller therapy.
	treatment is needed, some recommendations can be
				NOT• Inhaled glucocorticosteroidsTemporarily.
	made based on the current evidence:								doubling
	• When inhaled glucocorticosteroidsinalonem dium-				the dose of inhaled glucocorticosteroids has not be
					demonstrated to be effective, and is no longer
	to high-doses are being used, a 50% reduction in dose
	189-191		-DO		recommended194,196 (Evidence A ). A four-fold or
	2 -agonist, the preferredMATERIALapproach to is to begin by				rapid and long-acting-agonist bronchodilator
	should be attempted at 3 month intervals(Evidence B ).				greater increase has been demonstrated to be
	• Where control is achieved at a low-dose of inhaled				equivalent to a short course of oral glucocorticostero
								195
					in adult patients with an acute deterioration
	glucocorticosteroids alone, in most patients treatment
	192,193				(Evidence A ). The higher dose should be maintained
	may be switched to once-daily dosing( vidence A ).				for seven to fourteen days but more research is nee
	• When asthma is controlled withcombination of				in both adults and children to standardize the approac
	inhaled glucocorticosteroid and long-acting				• Combination of inhaled glucocorticosteroids and
	COPYRIGHTEDinhaled glucocorticosteroid monotherapy at the same
					consequence of early intervention at a very early s
	reducing the dose of inhaled glucocorticosteroid by						2
	approximately 50% while continuing the long-acting				(e.g. formoterol) for combined relief and control.
	150				The use of the combination of a rapid and long-acting
	2 -agonist (Evidence B ). If control is maintained,				-agonist (formoterol) and an inhaled glucocortico-
	further reductions in the glucocorticosteroid should2 be
	attempted until a low-dose is reached, when the long-steroid (budesonide) in a single inhaler both as a
	acting2 -agonist may be stoppedEvidence(		D ). An		controller and reliever is effective in maintain
					level of asthma control and reduces exacerbations
	alternative is to switch the combination treatment to
	194				requiring systemic glucocorticosteroids and
	once-daily dosing. A second alternative is to				111,156,157,197		(Evidence A ). The benefit
	discontinue the long-actiagonist-	at an earlier			hospitalization
	2				in preventing exacerbations appears to be the
	stage and substitute the combination treatment with

dose contained in the combination inhaler. However, of a threatened exacerbation since studies involv

	137, 368
this is more likely to lead to loss of asthma controldoubling or quadrupling doses of combination
(Evidence B ).	treatment once deterioration is established (for 2 o
	more days) show some benefit but results are

inconsistent195 . Because there are no studies using

62 ASTHMA MANAGEMENT AND PREVENTION

this approach with other combinations of controller	complete cessation. A history of past tobacco smokin
and relievers, other than budesonide/formoterol, the	is associated with a reduced likelihood of complete

alternative approaches described in this section shouldasthmabe control, and this is only partly attributable used for patients on other controller therapies. the presence of fixed airflow obstruction. In add Combination therapy with budesonide and formoterol usedcurrent smoking reduces the effectiveness of

	both as maintenance and rescue has been shown to reduce				199
			and oral glucocorticosteroids. Counseling and smok-
	asthma exacerbations in children ages 4 years and older		ing cessation programs should be offered to all ast
	347		patients who smoke.
	with moderate to severe asthma.
	• The usual treatment for an acute exacerbation is a • Investigate the presencecomorbiditiesof that may
	high-dose of-agonist and a burst of systemic		aggravate asthma. Chronic sinusitis, gastroesophage
	2
	glucocorticosteroids administered orally or		reflux, and obesity/obstructive sleep apnea have be
	intravenously. (Refer to Component 4 for more
			reported in higher percentages in patients with d
	information.)
			to-treat asthma. Psychological and psychiatric
	Following treatment for an exacerbation of asthma,		disorders should also be considered. If found, the
			comorbidities should be addressed and treated as
	maintenance treatment can generally be resumed at		appropriate, although REPRODUCE!the ability to improve asthma
	previous levels unless the exacerbation was associated				200,348
	with a gradual loss of control suggesting chronic		control by doing so remains unconfirmed.
				OR
	undertreatment. In this case, provided inhaler technique
	has been checked, a step-wise increase in treatmentWhen these reasons for lack of treatment response have
		been considered and addressed, a compromise level of
	(either in dose or number of controllers) is indicated.
		control may need to be accepted and discussed with the
	Difficult-to-Treat Asthma	patient to avoid futile over-treatment (with its atte
		cost and potential for adverse effects). The objectiv
			ALTER
		then to minimize exacerbations and need for emergenc
	Although the majority of asthma patients can obtain the

targeted level of controlFigure( 4.3-1 ), some patients will medical interventions while achieving as high a leve

		104		clinical control with as little disruption of activi
	not do so even with the best therapy. Patients who do			NOTfew daily symptoms as possible. For these difficul
			DO
	not reach an acceptable level of controlStepat4 (reliever			patients, frequent use of rescue medication is acce
	medication plus two or more controllers ) can be		-	is a degree of chronic lung function impairment.
		198
	considered to have difficult-to-treat. Theseasthma			cautiously and slowly at intervals not more frequent
		MATERIAL
	patients may have an element of poor glucocorticosteroid
				Although lower levels of control are generally associate
	responsiveness, and require higher doses of inhaled
				with an increased risk of exacerbations, not all patien
	glucocorticosteroids than are routinely used in patients
	whose asthma is easy to control. However, there is			with chronically impaired lung function, reduced act
				levels, and daily symptoms have frequent exacerbation
	currently no evidence to support continuing these high-
				In such patients, the lowest level of treatment that
	doses of inhaled glucocorticosteroids beyond 6 months in
	the hope of achieving better control. Instead, dose			the benefits achieved at the higher doses of treatme
				should be employed. Reductions should be made
	optimization should be pursued by stepping down to a
	COPYRIGHTED			172
	dose that maintains the maximal level of control achieved
	on the higher dose.			to 6 months, as carryover of the effects of the higher
				may last for several months and make it difficult to
				the impact of the dose reductionEvide ce( D ). Referral to
	Because very few patients are completely resistant to
				physician with an interest in and/or special focus o
	glucocorticosteroids, these medications remain a mainstay
				asthma may be helpful and patients may benefit from
	of therapy for difficult-to-treat asthma, while additional
				phenotyping into categories such as allergic, aspirin
	diagnostic and generalized therapeutic options can and
	should also be considered:			sensitive, and/or eosinophilic.asPathmaients
				201
	• onfirm thediagnosisof asthma. In particular, the			categorized as allergic might benefit from anti-IgE
				therapy , and leukotriene modifiers can be helpful fo
				183
	presence of COPD must be excluded. Vocal cord			patients determined to be aspirin sensitive (who are
				eosinophilic as well).
	dysfunction must be considered.

•Investigate and confirmcompliancewith treatment. Incorrect or inadequate use of medications remains the most common reason for failure to achieve control.

•Considersmoking, current or past,and encourage

ASTHMA MANAGEMENT AND PREVENTION

63

COMPONENT 4: MANAGE ASTHMA EXACERBATIONS

KEY POINTS:

patients with a history of near-fatal asthma and also appe to be more likely in males. A clinically useful tool to the likelihood of asthma-related hospitalizations or emergency department visits in adults with severe difficult to treat asthma has been349 .described

• Exacerbations of asthma (asthma attacks or acute Strategies for treating exacerbations, though general asthma) are episodes of progressive increase inare best adapted and implemented at a local 204,205level. shortness of breath, cough, wheezing, or chest Severe exacerbations are potentially life threatening

tightness, or some combination of these symptoms.

their treatment requires close supervision. Patient

severe exacerbations should be encouraged to see their

• Exacerbations are characterized by decreases in physician promptly or, depending on the organization of

expiratory airflow that can be quantified and monitored
by measurement of lung function (PEF1 ).or FEV					local health services, to proceed to the nearest clinic
					hospital that provides emergency access for patients
					acute asthma. Close objective monitoring (PEF) of the
• The primary therapies for exacerbations include the
					response to therapy is essential.
repetitive administration of rapid-acting inhaled									REPRODUCE!
bronchodilators, the early introduction of systemic
					The primary therapies for exacerbations include—in th
glucocorticosteroids, and oxygen supplementation.
					order in which they are introduced, depending on sever
								OR
• The aims of treatment are to relieve airflow					repetitive administration of rapid-acting inhaled bronch
					early introduction of systemic glucocorticosteroids
obstruction and hypoxemia as quickly as possible,								202
and to plan the prevention of future relapses.					oxygen supplementation. The aims of treatment are to
					relieve airflow obstruction and hypoxemia as quickly
• Severe exacerbations are potentially life					possible, and to plan the prevention of future relapse
							ALTER
threatening, and their treatment requires close
					Patients at high risk of asthma-related death require
supervision. Most patients with severe asthma
exacerbations should be treated in an acute care attention and should be encouraged to seek urgent care
					early in the course of their exacerbations. These pati
facility. Patients at high risk of asthma-relatedNOT
death also require closer attention.		DO			include those:
						• With a history of near-fatal asthma requiring intu
• Milder exacerbations, defined by a reduction-				in					206
peak flow of less than 20%, nocturnal awakening,						and mechanical ventilation
						• Who have had a hospitalization or emergency care
and increased use of short acting-agonists can
	2					visit for asthma in the past year
usually be treated in a community setting.
						• Who are currently using or have recently stopped
						using oral glucocorticosteroids
INTRODUCTION
						• Who are not currently using inhaled
								207
						glucocorticosteroids
Exacerbations of asthma (asthma attacks or acute asthma)						• Who are overdependent on rapid-acting inhaled
	MATERIAL
are episodes of progressive increase in shortness of breath,-agonists, especially those who use more than one
COPYRIGHTED
cough, wheezing, or chest tightness, or some combinationcanister of salbutamol (or equivalent) monthly
of these symptoms. Exacerbations usually have a						2				208
						• With a history of psychiatric disease or psychosoc
										350
progressive onset but a subset of patients (mostly adults)problems, including the use of sedatives
									209

361
present more acutely. Respiratory distress is common. • With a history of noncompliance with an asthma
Exacerbations are characterized by decreases in expiratorymedication plan.
airflow that can be quantified by measurement of lung
function (PEF or FEV1 )202 . These measurements are more Response to treatment may take time and patients shoul
reliable indicators of the severity of airflow limitationbe closelythanmonitoredis	using clinical as well as object

the degree of symptoms. The degree of symptoms may,measurements. The increased treatment should conti however, be a more sensitive measure of the onset ofuantil measurements of lung function1 ) (PEFreturnor FEV exacerbation because the increase in symptoms usuallyto their previous best (ideally) or plateau, at which ti

precedes the deterioration in peak flow. Still,rate a	decision to admit or discharge can be made based upon
203

minority of patients perceive symptoms poorly, and maythese values. Patients who can be safely discharged w have a significant decline in lung function withouthave significantresponded within the first two hours, at which change in symptoms. This situation especially affectsdecisions regarding patient disposition can be made.

64 ASTHMA MANAGEMENT AND PREVENTION