STEPPING DOWN APPROACH

OF ASTHMA BRONCHIALE
(GINA 2011)
C. Martin Rumende

Divisi Pulmonologi Departemen Ilmu
Penyakit Dalam FKUI/RSCM
G
IN
A
lobal
itiative for
sthma
Definition of Asthma
A chronic inflammatory disorder of the airways
Many cells and cellular elements play a role
Chronic inflammation is associated with airway
hyperresponsiveness that leads to recurrent
episodes of wheezing, breathlessness, chest
tightness, and coughing
Widespread, variable, and often reversible
airflow limitation
GINA Program Objectives
Increase appreciation of asthma as a global public
health problem
Present key recommendations for diagnosis and
management of asthma
Provide strategies to adapt recommendations to
varying health needs, services, and resources
Identify areas for future investigation of particular
significance to the global community

Levels of Asthma Control
(Preferably over 4 weeks)

Characteristic
Controlled
(All of the following)
Partly controlled
(Any present in any week)
Uncontrolled
Daytime symptoms
None (2 or less /
week)
More than
twice / week
3 or more
features of
partly
controlled
asthma
present in
any week

Limitations of
activities
None Any
Nocturnal
symptoms /
awakening
None Any
Need for rescue /
reliever
treatment
None (2 or less /
week)
More than
twice / week
Lung function
(PEF or FEV
1
)
Normal
< 80% predicted or
personal best (if
known) on any day
Exacerbation None One or more / year 1 in any week
1. Develop Patient/Doctor
Partnership
2. Identify and Reduce Exposure
to Risk Factors
3. Assess, Treat and Monitor
Asthma
4. Manage Asthma Exacerbations
Asthma Management and Prevention
Program: Five Components
Revised 2011
Asthma Management and Prevention Program
Component 3: Assess, Treat
and Monitor Asthma
The goal of asthma treatment, to
achieve and maintain clinical
control, can be achieved in a
majority of patients with a
pharmacologic intervention strategy
developed in partnership between
the patient/family and the health
care professional
Asthma Management and Prevention Program
Component 3: Assess, Treat
and Monitor Asthma
Depending on level of asthma control,
the patient is assigned to one of five
treatment steps
Treatment is adjusted in a continuous
cycle driven by changes in asthma
control status. The cycle involves:
- Assessing Asthma Control
- Treating to Achieve Control
- Monitoring to Maintain Control
A stepwise approach to pharmacological
therapy is recommended
The aim is to accomplish the goals of
therapy with the least possible medication
Although in many countries traditional
methods of healing are used, their efficacy
has not yet been established and their use
can therefore not be recommended
Asthma Management and Prevention Program
Component 3: Assess, Treat
and Monitor Asthma
The choice of treatment should be guided by:
Level of asthma control
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

Asthma Management and Prevention Program
Component 3: Assess, Treat
and Monitor Asthma
Component 4: Asthma Management and Prevention Program
Controller Medications
Inhaled glucocorticosteroids
Leukotriene modifiers
Long-acting inhaled
2
-agonists
Systemic glucocorticosteroids
Theophylline
Cromones
Long-acting oral
2
-agonists
Anti-IgE
Systemic glucocorticosteroids
Estimate Comparative Daily Dosages of Inhaled
Glucocorticosteroids for Adults and Children > 5 years
Drug

Low Daily Dose (g) Medium Daily Dose (g) High Daily Dose (g)

Beclomethasone 200-500 >500-1000

>1000
Budesonide

200-400

400-800 800 - 1600
Budesonide-Neb
Inhalation Suspension
250-500 >500-1000 >1000
Ciclesonide 80 160 >160-320 >320-1280
Flunisolide 500-1000 >1000-2000 >2000
Fluticasone 100-250 >250-500 >500
Mometasone furoate 200-400 > 400-800 >800-1200
Triamcinolone acetonide 400-1000 >1000-2000 >2000
Component 4: Asthma Management and Prevention Program
Reliever Medications
Rapid-acting inhaled
2
-agonists
Anticholinergics
Theophylline
Short-acting oral
2
-agonists

Global Strategy for Asthma
Management and Prevention
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

controlled
partly controlled
uncontrolled
exacerbation
LEVEL OF CONTROL
maintain and find lowest
controlling step
consider stepping up to
gain control
step up until controlled
treat as exacerbation
TREATMENT OF ACTION
TREATMENT STEPS
REDUCE INCREASE
STEP
1
STEP
2
STEP
3
STEP
4
STEP
5
R
E
D
U
C
E

I
N
C
R
E
A
S
E

Step 1 As-needed reliever medication
Patients with occasional daytime symptoms of
short duration
A rapid-acting inhaled
2
-agonist is the
recommended reliever treatment (Evidence A)
When symptoms are more frequent, and/or
worsen periodically, patients require regular
controller treatment (step 2 or higher)
Treating to Achieve Asthma Control
Step 2 Reliever medication plus a single
controller
A low-dose inhaled glucocorticosteroid is
recommended as the initial controller
treatment for patients of all ages (Evidence A)
Alternative controller medications include
leukotriene modifiers (Evidence A)
appropriate for patients unable/unwilling to
use inhaled glucocorticosteroids
Treating to Achieve Asthma Control
Step 3 Reliever medication plus one or two
controllers
For adults and adolescents, combine a low-dose
inhaled glucocorticosteroid with an inhaled long-
acting
2
-agonist either in a combination inhaler
device or as separate components (Evidence A)
Inhaled long-acting
2
-agonist must not be used
as monotherapy
For children, increase to a medium-dose inhaled
glucocorticosteroid (Evidence A)
Treating to Achieve Asthma Control
Additional Step 3 Options for Adolescents and Adults
Increase to medium-dose inhaled
glucocorticosteroid (Evidence A)
Low-dose inhaled glucocorticosteroid
combined with leukotriene modifiers
(Evidence A)
Low-dose sustained-release theophylline
(Evidence B)
Treating to Achieve Asthma Control
Step 4 Reliever medication plus two or more
controllers
Selection of treatment at Step 4 depends
on prior selections at Steps 2 and 3
Where possible, patients not controlled on
Step 3 treatments should be referred to a
health professional with expertise in the
management of asthma
Treating to Achieve Asthma Control
Step 4 Reliever medication plus two or more controllers
Medium- or high-dose inhaled glucocorticosteroid
combined with a long-acting inhaled
2
-agonist
(Evidence A)
Medium- or high-dose inhaled glucocorticosteroid
combined with leukotriene modifiers (Evidence A)
Low-dose sustained-release theophylline added
to medium- or high-dose inhaled
glucocorticosteroid combined with a long-acting
inhaled
2
-agonist (Evidence B)
Treating to Achieve Asthma Control
Treating to Achieve Asthma Control
Step 5 Reliever medication plus additional controller options
Addition of oral glucocorticosteroids to other
controller medications may be effective
(Evidence D) but is associated with severe
side effects (Evidence A)
Addition of anti-IgE treatment to other
controller medications improves control of
allergic asthma when control has not been
achieved on other medications (Evidence A)
Treating to Maintain Asthma Control
When control as been achieved,
ongoing monitoring is essential to:
- maintain control
- establish lowest step/dose treatment
Asthma control should be monitored
by the health care professional and
by the patient
Treating to Maintain Asthma Control
Stepping down treatment when asthma is controlled
When controlled on medium- to high-dose
inhaled glucocorticosteroids: 50% dose
reduction at 3 month intervals (Evidence
B)
When controlled on low-dose inhaled
glucocorticosteroids: switch to once-daily
dosing (Evidence A)
Treating to Maintain Asthma Control
Stepping down treatment when asthma is controlled
When controlled on combination inhaled
glucocorticosteroids and long-acting
inhaled
2
-agonist, reduce dose of inhaled
glucocorticosteroid by 50% while
continuing the long-acting
2
-agonist
(Evidence B)
If control is maintained, reduce to low-
dose inhaled glucocorticosteroids and
stop long-acting
2
-agonist (Evidence D)
Treating to Maintain Asthma Control
Stepping up treatment in response to loss of control
Rapid-onset, short-acting or long-
acting inhaled 2-agonist
bronchodilators provide temporary
relief.
Need for repeated dosing over more
than one/two days signals need for
possible increase in controller therapy
Treating to Maintain Asthma Control
Stepping up treatment in response to loss of control
Use of a combination rapid and long-acting
inhaled
2
-agonist (e.g., formoterol) and an
inhaled glucocorticosteroid (e.g., budesonide)
in a single inhaler both as a controller and
reliever is effecting in maintaining a high level
of asthma control and reduces exacerbations
(Evidence A)
Doubling the dose of inhaled glucocortico-
steroids is not effective, and is not
recommended (Evidence A)
Asthma management - a continuous process
is needed to ensure that control is maintained
Adapted from GINA 2011 (www.ginasthma.org)
RESCUE USE
> 2 /WEEK
Party
Controlled
Uncontrolled
NO
Consider
Step-up
maintenance
treatment
Initiate
treatment
GINA 2009
When should you step down?

When control is maintained for at least 3
months, treatment can be stepped down
with the aim of establishing the lowest step
and dose of treatment that maintains
control

ss
ICS/LABA 50/250g bd
n=660
ICS/LABA 50/100g bd
n=208
ICS 250g bd
n=188
12 16 20 24
Screening
End of
treatment
SABA
only
2 0 4 8
Run-in period

Double-blind treatment period
Weeks
Stepping-down Bateman study
Randomisation
Primary endpoint: mean morning PEF

Secondary endpoints: Asthma control, symptoms, and rescue albuterol usage
Bateman et al. J Allergy Clin Immunol 2006
ICS/LABA 50/250 bid

(two lines show groups that were
randomised during blinded phase)
Maintenance of asthma control
during step down
0
20
40
60
80
100
2 4 6 8 10 12
%

o
f

w
e
l
l
-
c
o
n
t
r
o
l
l
e
d

s
u
b
j
e
c
t
s

Weeks
Open-label period
Run-in
Well controlled in 68% over 4 weeks
68%
4-wk control
assessment
Bateman et al. J Allergy Clin Immunol 2006
Maintenance of asthma control
during step down
14 16 18 20 22 24
ICS 250 bid
0
20
40
60
80
100
2 4 6 8 10 12
%

o
f

w
e
l
l
-
c
o
n
t
r
o
l
l
e
d

s
u
b
j
e
c
t
s

Weeks
Open-label period
ICS/LABA 50/250
Run-in
Double-blind period
4 wks
Well
controlled
ICS/LABA 50/250 bid

(two lines show groups that were
randomised during blinded phase)
ICS/LABA 50/100 bid
Bateman et al. J Allergy Clin Immunol 2006
Conclusion: Stepping down to a lower dose of
ICS/LABA is more effective than switching to an ICS
alone
THANK YOU