G lobal

INitiative for
A sthma
 GINA Workshop Report

Evidence Category Sources of Evidence

A Randomized clinical trials
Rich body of data
B Randomized clinical trials
Limited body of data
C Non-randomized trials
Observational studies
D Panel judgment consensus
 Definition of Asthma

 A chronic inflammatory disorder of the airways

 Many cells and cellular elements play a role
 Chronic inflammation leads to an increase in
airway hyperresponsiveness with recurrent
episodes of wheezing, coughing, and
shortness of breath
 Widespread, variable, and often reversible
airflow limitation
 Mechanisms Underlying the
Definition of Asthma

Risk Factors
(for development of asthma)

INFLAMMATION
INFLAMMATION

Airway
Hyperresponsiveness Airflow Obstruction

Risk Factors Symptoms

(for exacerbations)
 Burden of Asthma

 Asthma
Asthma is
is one
one of
of the
the most
most common
common chronic
chronic
diseases
diseases worldwide
worldwide
 Prevalence
Prevalence increasing
increasing in
in many
many countries,
countries,
especially
especially in
in children
children
 A
A major
major cause
cause of
of school/work
school/work absence
absence
 An
An overall
overall increase
increase in
in severity
severity of
of asthma
asthma
increases
increases the
the pool
pool of
of patients
patients at
at risk
risk for
for
death
death
Worldwide
Variation in
Prevalence of
Asthma
Symptoms

International Study of
Asthma and Allergies in
Children (ISAAC)

Lancet 1998;351:1225
 Increasing Prevalence of Asthma in
Children/Adolescents

Finland
{1966
1989
(Haahtela et al)
al)
Sweden
{1979
1991
(Aberg et al)
al)

Japan
{1982
1992
(Nakagomi et al)
al)
Scotland
{1982
(Rona et al)
al)1992
UK
{1994
1989
(Omran et al)
al)
USA
(NHIS) {1982
1992

{1989
New Zealand 1975
(Shaw et al)
al)

Australia
{1982
(Peat et al)
al)1992

0 5 10 15 20 25 30 35
Prevalence (%)
 Trends in Prevalence of Asthma
By Age, U.S., 1985-1996
80 Rate/1,000 Persons
Age (years)
70
<18

60 18-44
45-64
50 65+
Total (All Ages)
40

30

20
85 86 87 88 89 90 91 92 93 94 95 96
Year
 Hospitalization Rates for Asthma
by Age, U.S., 1974 - 1997

Rate/100,000 Persons
40
35 <15
30 15-44
45-64
25
65+
20
15
10
5
0
74 76 78 80 82 84 86 88 90 92 94 96

Year
 Death Rates for Asthma
By Race, Sex, U.S., 1980-1998

Rate/100,000 Persons
5
Black Female

4
Black Male

3
White Female

White Male
1

0
1980 1985 1990 1995 2000
Year
 Factors that Exacerbate Asthma

 Allergens
 Air Pollutants
 Respiratory infections
 Exercise and hyperventilation
 Weather changes
 Sulfur dioxide
 Food, additives, drugs
 Risk Factors that Lead to
Asthma Development

Host Factors Environmental Factors

 Genetic predisposition  Indoor allergens
 Outdoor allergens
 Atopy
 Occupational sensitizers
 Airway hyper-
 Tobacco smoke
responsiveness
 Air Pollution
 Gender  Respiratory Infections
 Race/Ethnicity  Parasitic infections
 Socioeconomic factors
 Family size
 Diet and drugs
 Obesity
 Is it Asthma?

 Recurrent episodes of wheezing

 Troublesome cough at night
 Cough or wheeze after exercise
 Cough, wheeze or chest tightness after
exposure to airborne allergens or pollutants
 Colds “go to the chest” or take more than
10 days to clear
 Asthma Diagnosis

 History and patterns of symptoms

 Physical examination
 Measurements of lung function
 Measurements of allergic status to
identify risk factors
 Classification of Severity

CLASSIFY SEVERITY
Clinical Features Before Treatment
Nocturnal
Symptoms Symptoms FEV1 or PEF

STEP 4 Continuous  60% predicted

Limited physical Frequent
Severe Variability > 30%
Persistent activity

STEP 3 Daily 60 - 80% predicted

> 1 time week Variability > 30%
Moderate Attacks affect activity
Persistent
STEP 2 > 2 times a month  80% predicted
> 1 time a week
Mild but < 1 time a day Variability 20 - 30%
Persistent
< 1 time a week
STEP 1  22 times  80% predicted
Asymptomatic times aa month
month
Intermittent and normal PEF Variability < 20%
between attacks
The presence of one feature of severity is sufficient to place patient in that category.
 Six-part Asthma Management Program

Control of Asthma

 Minimal (ideally no) chronic symptoms

 Minimal (infrequent) exacerbations
 No emergency visits
 Minimal (ideally no) need for “as needed” use of
β2-agonist
 No limitations on activities, including exercise
 PEF circadian variation of less than 20 percent
 (Near) normal PEF
 Minimal (or no) adverse effects from medicine
 Six-Part Asthma Management
Program
.
 The most effective management is to
prevent airway inflammation by
eliminating the causal factors
 Asthma can be effectively controlled in
most patients, although it can not be
cured
 The major factors contributing to asthma
morbidity and mortality are under-
diagnosis and inappropriate treatment
 Six-Part Asthma Management
Program

 Any asthma more severe than

intermittent asthma is more effectively
controlled by treatment to suppress and
reverse airway inflammation than by
treatment only of acute
bronchoconstriction and symptoms
 Six-part Asthma Management Program
Part 2: Assess and Monitor Asthma Severity
with Symptom Reports and Measures of Lung
Function

 Symptom reports
 Use of reliever medication
 Nighttime symptoms
 Activity limitations
 Spirometry for initial assessment. Peak Expiratory Flow for
follow-up:
 Assess severity
 Assess response to therapy
 PEF monitoring at home
 Important for those with poor perception of symptoms
 Daily measurement recorded in a diary
 Assesses the severity and predicts worsening
 Guides the use of a zone system for asthma self-management
 Arterial blood gas for severe exacerbations
 Typical Spirometric (FEV11)
Tracings
Volume

FEV1

Normal Subject

Asthmatic (After Bronchodilator)

Asthmatic (Before Bronchodilator)

1 2 3 4 5
Time (sec)

Note: Each FEV1 curve represents the highest of three repeat measurements
A Simple Index of PEF Variation

800 Highest PEF (670)

700
PEF (L/min)

600

500

Lowest morning PEF (570) Morning PEF

400 Evening PEF

300
0 7 14
Days

Minimum morning PEF ( % recent best): 570/670 = 85%

(From Reddel, H.K. et al. 1995)
 Six-part Asthma Management Program
Part 4: Establish Medication Plans for
Long-Term Asthma Management in
Infants and Children

 At present, inhaled glucocorticosteroids

are the most effective controller
medications and are recommended for
persistent asthma at any step of severity

 Long-term treatment with inhaled

glucocorticosteroids markedly reduces the
frequency and severity of exacerbations
 Six-part Asthma Management Program
Part 3: Avoid Exposure to Risk
Factors

 Reduce
Reduce exposure
exposure to
to indoor
indoor allergens
allergens
 Avoid
Avoid tobacco
tobacco smoke
smoke
 Avoid
Avoid vehicle
vehicle emission
emission
 Identify
Identify irritants
irritants in
in the
the workplace
workplace
 Explore
Explore role
role of
of infections
infections on
on asthma
asthma
development,
development, especially
especially in
in children
children and
and
young
young infants
infants
 Part 4: Long-term Asthma Management
Stepwise Approach to Asthma Therapy

The choice of treatment should be guided by:

 Severity of the patient’s asthma
 Patient’s current treatment
 Pharmacological properties and availability of
the various forms of asthma treatment
 Economic considerations
Cultural preferences and differing health care
systems need to be considered.
 Part 4: Long-term Asthma Management

Pharmacologic Therapy

Controller Medications:
 Inhaled glucocorticosteroids
 Systemic glucocorticosteroids

 Cromones

 Methylxanthines

 Long-acting inhaled β -agonists

2

 Long-acting oral β2-agonists

 Leukotriene modifiers
 Part 4: Long-term Asthma Management

Pharmacologic Therapy

Reliever Medications:
 Rapid-acting inhaled β2-agonists
 Systemic glucocorticosteroids
 Anticholinergics
 Methylxanthines
 Short-acting oral β2-agonists
 Part 4: Long-term Asthma Management
Stepwise Approach to Asthma
Therapy - Adults
Outcome: Best
Outcome: Asthma Control Possible Results

Controller:
 Daily inhaled
corticosteroid
Controller:  Daily long –  When
acting inhaled asthma is
Controller:  Daily inhaled β2-agonist controlled,
Controller: Daily inhaled corticosteroid reduce
None  Daily long-
 plus (if needed) therapy
corticosteroid -Theophylline-SR
acting inhaled
β2-agonist -Leukotriene
-Long-acting inhaled
 Monitor
β2- agonist
-Oral corticosteroid

Reliever: Rapid-acting inhaled β2-agonist prn

STEP 1: STEP 2: STEP
STEP 3:
3: STEP 4: STEP
Moderate Severe STEP Down
Down
Intermittent Mild Persistent Moderate
Persistent
Persistent Persistent
Alternative controller and reliever medications may be considered (see text).
 Recommended Asthma Medications
Step 1: Adults

Severity Daily Controller Other Options (in order

Medications of cost)
Step 1: • None • None
Intermittent

Reliever Medication: Rapid-acting inhaled β2- agonist prn, not more

than 3-4 times a day. Once control is achieved and maintained for at
least 3 months, gradual reduction of therapy should be tried.
 Recommended Asthma Medications
Step 2: Adults

Severity Daily Controller Other Options (in order

Medications of cost)
Step 2: • Inhaled • Sustained-release
Mild glucocorticosteroid theophylline, or
Persistent (< 500 μg BDP or • Cromone, or
equivalent) • Leukotriene modifier

Reliever Medication: Rapid-acting inhaled β2- agonist prn, not more

than 3-4 times a day. Once control is achieved and maintained for at
least 3 months, gradual reduction of therapy should be tried.
 Recommended Asthma Medications
Step 3: Adults
Severity Daily Controller Other Options (in order of cost)
Medications
Step 3: • Inhaled • Inhaled glucocorticosteroid (500 – 1000
Moderate glucocorticosteroid μg BDP or equivalent) plus sustained-
persistent (200 – 1000 μg BDP or release theophylline, or
equivalent) • Inhaled glucocorticosteroid (500 – 1000
plus long-acting inhaled μg BDP or equivalent) plus long-acting
β2- agonist inhaled β2- agonist, or
• Inhaled glucocorticosteroid at higher
doses (> 1000 μg BDP or equivalent), or
• Inhaled glucocorticosteroid (500 –
1000 μg BDP or equivalent) plus
leukotriene modifier

Reliever Medication: Rapid-acting inhaled β2- agonist prn, not more

than 3-4 times a day. Once control is achieved and maintained for at
least 3 months, gradual reduction of therapy should be tried.
 Recommended Asthma Medications
Step 4: Adults
Severity Daily Controller Medications Other Options
Step 4 • Inhaled glucocorticosteroid
Severe ( > 1000 μg BDP or equivalent) plus
persistent long-acting inhaled β2- agonist
• plus one or more of the following,
if needed:
- Sustained-release theophylline
- Leukotriene modifier
- Long-acting inhaled β2- agonist
- Oral glucocorticosteroid

Reliever Medication: Rapid-acting inhaled β2- agonist prn, not more

than 3-4 times a day. Once control is achieved and maintained for at
least 3 months, gradual reduction of therapy should be tried.
 Part 4: Long-term Asthma Management

Allergen-specific Immunotherapy

 Greatest benefit of specific immunotherapy using

allergen extracts has been obtained in the treatment of
allergic rhinitis
 A number of questions must be addressed regarding
the role of specific immunotherapy in asthma therapy
 Specific immunotherapy should be considered only after
strict environmental avoidance and pharmacologic
intervention, including inhaled glucocorticosteroids, have
failed to control asthma
 Perform only by trained physician
 Six-part Asthma Management Program
Part 5: Establish Plans for
Managing Exacerbations

Treatment of exacerbations depends on:

 The patient
 Experience of the health care professional
 Therapies that are the most effective for
the particular patient
 Availability of medications
 Emergency facilities
 Six-part Asthma Management Program
Part 5: Establish Plans for
Managing Exacerbations

Primary therapies for exacerbations:

• Repetitive administration of rapid-acting
inhaled β22-agonist
• Early introduction of systemic
glucocorticosteroids
• Oxygen supplementation
Closely monitor response to treatment
with serial measures of lung function
 Six-part Asthma Management Program
Part 5: Managing Severe Asthma
Exacerbations

 Severe exacerbations are life-

threatening medical emergencies

 Care must be expeditious and treatment

is often most safely undertaken in a
hospital or hospital-based emergency
department
 Emergency Department Management

Acute Asthma
Initial Assessment
History, Physical Examination, PEF or FEV1

Initial Therapy
Bronchodilators; O2 if needed
Good Response
Incomplete/Poor Response Respiratory Failure

Observe for at Add Systemic Glucocorticosteroids

least 1 hour
Good Response Poor Response
If Stable,
Discharge to Discharge Admit to Hospital Admit to ICU
Home
 Six-part Asthma Management Program

Part 6: Provide Regular

Follow-up Care

Continual monitoring is essential to assure that

therapeutic goals are met. Frequent follow-up visits
are necessary to review:
 Home PEF and symptom records
 Techniques in use of medications
 Risk factors and their control
Once asthma control is established, follow-up
visits should be scheduled (at 1 to 6 month intervals
as appropriate)
 Six-part Asthma Management Program

Special Considerations

Special considerations are required to

manage asthma in relation to:
 Pregnancy
 Surgery
 Physical activity
 Rhinitis, sinusitis, and nasal polyps
 Occupational asthma
 Respiratory infections
 Gastroesophageal reflux
 Aspirin-induced asthma
 Six-part Asthma Management
Program: Summary

 Asthma
Asthma can
can be
be effectively
effectively controlled,
controlled, although
although itit
cannot
cannot be
be cured
cured

 Effective
Effective asthma
asthma management
management programs
programs include
include
education,
education, objective
objective measures
measures ofof lung
lung function,
function,
environmental
environmental control,
control, and
and pharmacologic
pharmacologic therapy
therapy

 A
A stepwise
stepwise approach
approach toto pharmacologic
pharmacologic therapy
therapy is
is
recommended.
recommended. The The aim
aim is
is to
to accomplish
accomplish the
the
goals
goals of
of therapy
therapy with
with the
the least
least possible
possible medication
medication
 Six-part Asthma Management
Program: Summary (continued)


 Anything
Anything more
more than
than mild,
mild, occasional
occasional asthma
asthma is
is
more
more effectively
effectively controlled
controlled by
by suppressing
suppressing
inflammation
inflammation than
than by
by only
only treating
treating acute
acute
bronchospasm
bronchospasm

 The
The availability
availability of
of varying
varying forms
forms ofof treatment,
treatment,
cultural
cultural preferences,
preferences, and
and differing
differing health
health care
care
systems
systems need
need toto be
be considered
considered
http://www.ginasthma.com
 Part 4: Long-term Asthma Management
Stepwise Approach to Asthma
Therapy - Adults
Outcome: Best
Outcome: Asthma Control Possible Results

Controller:
 Daily inhaled
corticosteroid
Controller:  Daily long –  When
acting inhaled asthma is
Controller:  Daily inhaled β2-agonist controlled,
Controller: Daily inhaled corticosteroid reduce
None  Daily long-
 plus(if needed) therapy
corticosteroid -Theophylline-SR
acting inhaled
β2-agonist -Leukotriene
-Long-acting inhaled
 Monitor
β2- agonist
-Oral corticosteroid

Reliever: Rapid-acting inhaled β2-agonist prn

STEP 1: STEP 2: STEP
STEP 3:
3: STEP 4: STEP
Moderate Severe STEP Down
Down
Intermittent Mild Persistent Moderate
Persistent
Persistent Persistent
Alternative controller and reliever medications may be considered (see
text).
 Stepwise Approach to Asthma Therapy: Adults
Step 1: Intermittent Asthma

Daily Controller Reliever

Medications Medications

None required Rapid-acting inhaled  2-agonist

for symptoms (but < once a week)

Rapid-acting inhaled  2-agonist,

cromone, or leukotriene modifier
before exercise or exposure to
allergen

 Continuously review medication technique, compliance and environmental control

 Review treatment every three months.
 Step up if control is not achieved; step down if control is sustained for at least 3 months
 Preferred treatments are in bold print
 Stepwise Approach to Asthma Therapy: Adults
Step 2: Mild Persistent Asthma

Daily Controller Reliever

Medications Medications
Inhaled glucocorticosteroid Rapid-acting inhaled  2-agonist
(< 500 μg BDP or equivalent) for symptoms (but < 3-4 times/day)

Other options (order by cost): Other options:

 sustained-release theophylline, or  inhaled anticholinergic, or
 Cromone, or  short-acting oral 2-agonist, or
 leukotriene modifier  short-acting theophylline

 Continuously review medication technique, compliance and environmental control.

 Review treatment every three months
 Step up if control is not achieved; Step down if control is sustained for at least 3 months
 Preferred treatments are in bold print
 Stepwise Approach to Asthma Therapy: Adults
Step 3: Moderate Persistent Asthma

Daily Controller Reliever

Medications Medications
Inhaled glucocorticosteroid, (200 – 1000 μg BDP Rapid-acting inhaled
or equivalent) plus long-acting inhaled  2-agonist for symptoms
β2agonist (but < 3 - 4 times/day)
Other options (order by cost):
 Inhaled glucocorticosteroid (500 – 1000 μg BDP Other options:
equivalent) plus sustained-release theophylline, or  inhaled anticholinergic or
 Inhaled glucocorticosteroid (500 – 1000 μg BDP  short-acting oral
equivalent) plus long-acting inhaled β2- agonist, or 2-agonist or
 inhaled glucocorticosteroid at higher doses  short-acting theophylline
(> 1000 μg BDP equivalent), or
 Inhaled glucocorticosteroid (500 – 1000 μg BDP
equivalent) plus leukotriene modifier
 Continuously review medication technique, compliance and environmental control.
 Review treatment every three months.
 Step up if control is not achieved; Step down if control is sustained for at least 3 months.
 Preferred treatments are in bold print.
 Stepwise Approach to Asthma Therapy: Adults
Step 4: Severe Persistent Asthma

Daily Controller Reliever

Medications Medications
Inhaled glucocorticosteroid, (> 1000 μg Rapid-acting inhaled
BDP or equivalent) plus long-acting  2-agonist for symptoms
inhaled β2agonist (but < 3-4 times/day)

plus one or more of the following, if Other options:

needed (order by cost):  inhaled anticholinergic or
 sustained-release theophylline, or  short-acting oral
 leukotriene modifier or 2-agonist or
 oral glucocorticosteroid  short-acting theophylline

 Continuously review medication technique, compliance and environmental control.

 Review treatment every three months.
 Step up if control is not achieved; Step down if control is sustained for at least 3 months.
 Preferred treatments are in bold print.
 Nebulized Isotonic Magnesium
• Lancet 2003;361:9375:2114-7
• Isotonic Mg & Albuterol vs. Saline &
Albuterol
• 52 pts.-Fev1<50%
• Nebulizer at ½, 1, 1 ½ hrs.
• Mean Fev1-1.95 liters vs. 1.55 liters
• P=.0003 Magnesium=250mmol(289
mosml)