12. Asthma: an evolving concept
1995- 2002 Guidelines for the clinical
management of asthma base specific treatment
recommendations on the assessment of
disease severity
Medication regimens depend on the severity of
disease with a step-wise treatment approach.
13. Asthma: an evolving concept
1995- 2002 Guidelines for the clinical
management of asthma base specific
treatment recommendations on the
Treatment based on severity
assessment of disease severity
21. GINA Guidelines 2002
Focus on ICS and ß2-agonists
Severe
persistent
Moderate
persistent
Mild
Intermittent persistent
Short-acting ß2 prn
ICS
LABA
Preferred
22. Treatment in GINA 2002
Intermittent
Mild
persistent
Moderate
persistent
Severe
Persistent
ßß22 pprrnn
IICCSS
LABA
• Severity classification
• Stepwise treatment according
to severity
23. Stepwise Approach to Therapy
for Adults and Children >5 Years
Step 1
Mild Intermittent
No Daily
Medication
Step 2
Mild Persistent
Preferred:
Low-dose ICS
Step 3
Moderate Persistent
Step 4
Severe Persistent
High-dose ICS +
LABA
(+ systemic
corticosteroids
if needed)
Preferred:
Low- to Med-dose
ICS + LABA
( to med-dose
ICS+ LABA if
needed)
NIH/NHLBI Guideline Update. June 2002. NIH Publication No. 02-5075.
25. Worldwide epidemiological evaluation of asthma
control level
AIRLA
Asthma Insights and Reality
AIRLA
Asthma Insights and Reality
in Latin America
in Latin America
1. Rabe et al. Eur Respir J 2000; 16: 802-807
2. www.asthmainamerica.com
3. Lai et al. Eur Respir J 2003; 111: 263-268
7 European countries
2803 patients with asthma1
2509 patients with asthma2
8 Asian-Pacific countries
3206 patients with asthma3
11 Latin American countries
2184 patients with asthma
26. AIR Studies:
AAsthma IInside and RReality
AIRCEE
AIRA
AIRNZ
Face to face or phone call questionnaires conducted in 30 countries in
11339 patients
27. (AIR Studies)
Over estimate asthma control
Patient perception of asthma control level
Total Control
Rabe et al. Eur Respir J 2000;
www.asthmainamerica.com;
Lai et al. JACI 2003;
Adachi et al. Arerugi 2002;
Patient %
USA W. Europe Asia-Pacific Japan
Rabe et al. J Allergy Clin Immunol 2004
60
50
40
30
20
10
0
Patients with severe symptoms
Well control
Middle/East
Europe
28.
29. Use of Inhaled Corticosteroids
Mild
Moderate
Severe
Asia Pacific Japan W Europe
C&E Europe USA
ICS are underused
0 5 10 15 20 25 30 35
Percentage of respondents
Rabe et al. Eur Respir J 2000;
www.asthmainamerica.com;
Lai et al. J Allergy Clin Immunol 2003;
Data on file
11
13
30
16
12
11
17
26
18
9
9
18
26
20
16
30. High Symptoms Frequency
51
61
56
51
Asia Pacific
C&E Europe
59
Japan
41 36 41
44
100
80
60
40
20
0
Rabe et al. Eur Respir J 2000;
www.asthmainamerica.com;
Lai et al. JACI 2003;
Adachi et al. Arerugi 2002;
Rabe et al. J Allergy Clin Immunol 2004
Sekerel et al. Respir Med 2006
74
W Europe
USA
Turkey
92
62
Day time symptoms Nocturnal symptoms
Last 4 weeks
% of patients
31. High frequency of hospital and
emergency room visits
Asia Pacific
C&E Europe
0 10 20 30 40 50
Rabe et al. Eur Respir J 2000;
www.asthmainamerica.com;
Lai et al. J Allergy Clin Immunol 2003;
Adachi et al. Arerugi 2002;
Rabe et al. J Allergy Clin Immunol 2004
Sekerel et al. Respir Med 2006
10
7
9
15
13
10
23
19
48
25
19
21
Japan
W Europe
USA
Turkey
Hospitalised
in past year
Hospital
emergency
room visits in
past year
% of patients
35. GOAL: Study design
8- week control assessment
4- week control assessment
Phase I
Phase II
SFC 50/100
or FP 100
SFC 50/250
or FP 250
SFC 50/500
or FP 500
Step 1
Step 2
Step 3
Visit 1 2 3 4 5 6 7 8 9
Week –4 0 4 12 24 36 48 52 56
GOAL Study, SFC = Salmeterol/fluticasone propionate Bateman E, et al. ARJCCM
36. GGOOAALL RReessuullttss
Gaining Optimal Asthma Control (GOAL)
study, one of the largest studies utilizing both
combination and separate therapies, explored
the potential of achieving total control of
asthma symptoms.
In this study, treatment was optimized in
those with uncontrolled asthma symptoms,
by increasing combination therapy at three
monthly reviews until all asthma-related
symptoms were abolished
37. GOAL: Gaining Optimal Asthma controL
Target TOTAL CONTROL
Current level
of control
WELL CONTROLLED
Dose titration
Start with low doses
Increase dose until ‘Total Control’
or maximum dose is reached
Bateman ED et al. Am J Respir Crit Care Med 2004; 170: 836-44
38. GOAL : Change of the control
TToottaall ccoonnttrrooll WWeellll--ccoonnttrrooll
IInnaaddeeqquuaattee ccoonnttrrooll EExxaacceerrbbaattiioonn
Bateman et al. ERS 2006, Allergy 2008 in press
39. GINA: goals of treatment 2006
"The aim of asthma management
should be control of the disease"
40.
41.
42. Aim of Asthma Therapy
CONTROL
Daytime symptoms None
( 0-2 / week)
/ awakening None
Limitations of
activities None
Nocturnal symptoms
Need for rescue /
“reliever” treatment None
( 0-2 / week)
FEV1 or PEF Normal
Exacerbation None
43.
44. LLEEVVEELL OOFF CCOONNTTRROOLL
controlled
partly controlled
uncontrolled
exacerbation
TTRREEAATTMMEENNTT OOFF AACCTTIIOONN
maintain and find lowest
controlling step
consider stepping up to
gain control
step up until controlled
treat as exacerbation
REDUCE INCREASE
TREATMENT STEPS
STEP
1
STEP
2
STEP
3
STEP
4
STEP
5
INCREASE REDUCE
45. REDUCE TREATMENT STEPS INCREASE
Step 1 Step 2 Step 3 Step 4 Step 5
Asthma Education
Enviromental Control
As needed
rapid acting b2
agonists
As needed rapid acting b2 agonists
Controller
options
Select one Select one Add one or
more
Add one or
both
Low-dose ICS Low-dose ICS +
LABA
Medium or high
dose ICS+
LABA
Oral steroid
LTRA Medium or high
dose ICS
LTRA Anti-IgE
Low-dose ICS
+ LTRA
Theophylline
Low-dose ICS
+ Theophylline
GINA 2006
As needed rapid acting B2-agonist
46.
47. •Day symptoms
•Night symptoms
•Reliever
•PEFR
•Exacerbation
•Limitation of activity
•Controlled
•Partly controlled
•Uncontrolled
47
GGIINNAA 22000066
Assessing asthma control
Treating to achieve asthma control
Monitoring to maintain control
2006
1. B2-agonist prn
2. ICS (low dose) or LTM
3. ICS (low dose) + LABA
4. ICS (Med-high dose) + LABA,LTM,theophylline
5. ICS (high dose) + LABA + prednisolone
In treatment-naïve patients started at Step 2.
In very symptomatic (uncontrolled) started at Step 3.
52. The Traditional Approach
Stepwise Incremental Management
IInn the traditional ‘step-wise’ asthma guideline
model, therapy classes are added and doses
increased when control is not achieved.
Most patients use regular ICS ‘preventer’
treatment and an additional SABA inhaler used
on an ‘as-needed’ basis
53. The Traditional Approach
When patients remain uncontrolled on ICS, LABA
treatment is added, increasingly in the form of a
fixed-dose ICS/LABA combination inhaler.
The traditional approach has been to prescribe an
ICS/LABA combination inhaler providing sufficient
doses of ICS and LABA to achieve control, and to
provide additional SABA for ‘rescue’ use – so most
patients will use at least two different inhalers
54. Asthma symptoms are variable over
Barnes PJ
Acute inflammation
Chronic inflammation
Structural changes
Steroid
response
Time
time and in severity
55. Poor
asthma
control
Optimal
asthma
control
Combination Strategy:
Traditional approach
SABA
Time
(months, weeks, days)
ICS
+
LABA
57. Two major different approaches have been put
forward to asthma management.
The first approach (Gaining Optimal Asthma
Control) is promoted by the producers of
fluticasone/salmeterol and recommends to step
up ICS to the dose needed to achieve optimal
asthma control in order to keep the patient
symptom free and to prevent exacerbations
58. The Traditional Approach
In The Traditional approach , fixed dosing
(fixed-dose ICS/LABA combination inhaler)
aimed to achieve “well controlled asthma”
or “total asthma control” according to the
GOAL study.
With this approach, there may be a risk for
over treatment, since the majority of patients
ended the study on the highest treatment dose.
60. Therapeutic Ratio of Inhaled Steroids
500 μg/day
(BDP equivalent)
Anti-inflammatory
Effects
Systemic
Side
Effects
Response
Dose
Lipworth BJ, et al. Drug Safety 2000;23:11.
61. Risks of Overtreatment
Dose-response curve means benefits of
increased ICS dose may be minimal
Side-effects – dysphonia, candida
Purpura, skin thinning – dose response
≥400mcg/day
Adrenal suppression – occurs ≥800mcg/day
Osteoporosis occurs ≥800mcg/day – every
500mcg increase – 9% increase in fractures
Loke. Thorax 2011;66:699-708
62. INSPIRE: INternational aSthma Patients Inside REsearch
Physicians recruited asthma patients
(n:2406)
On ICS or ICS+LABA
With phone calls
Asthma control parameters; asthma
variability; patients perception
Partridge M. BMC Pulmonary Medicine 2006; 6:13
63. Despite ICS or ICS/LABA maintenance,
74% of patients used rescue therapy
each day
SABA Use (puffs/day in last week)
0 10 20 30 40 50
None
1-2
3-4
5-8
9+
Number of inhalations
% of patients
Base: all patients (n=2,406)
Partridge MR at al, BMC Pulmonary Medicine 2006; 6:13
64. INSPIRE: Despite ICS or ICS/LABA therapy, only
30% of patients were well-controlled
according to the ACQ
50 % Uncontrolled (poor)
ACQ-6 Summary Score
Well-controlled: 0.0 to 0.74
Not well controlled: 0.75 to 1.5
Uncontrolled: 1.5+
30 % Well-controlled
20 % Not well-controlled
65. Braido et al. Allergy 2009; 64: 937-943
Achieving control in asthmatic
patients: still a critical issue?
122 patients
51.3% LABA + ICS
16 PTZ high-dose L + I
122 patients
51.3% LABA + ICS
16 PTZ high-dose L + I
Total control Well controlled Uncontrolled
18.75
56.25 25.00
44.30
8.20
patients treated with the total sample
high-dose ICS + LABA
Levels of asthma control in the total sample (right),
47.50
and in the subgroup of patients treated with high-dose ICS + LABA (left)
66. Single Maintenance And Reliever Therapy
(SMART)
using the budesonide-formoterol
combination inhaler
SymbicortTM
67.
68. Single maintenance and reliever
therapy (SMART)
The most important difference with fixed dosing
is that patients use a single inhaler with
SMART (instead of one inhaler with
budesonide/formoterol and a separate inhaler
containing reliever medication).
69. Single maintenance and reliever
therapy (SMART)
The second approach (SMART) is promoted by the
producers of budesonide/formoterol and recommends
a low maintenance dose which can be adjusted up or
down according to the clinical control of asthma.
IInn In the SMART model, the patient is only provided
with an ICS/LABA single inhaler, used both for
maintenance treatment and for additional rescue use
in place of SABA.
70. Symbicort SMART
Symbicort Maintenance And Reliever Therapy
P.
It provides rapid symptom
relief and improved control
Inflammation and
Bronchoconstriction
Patients do not require a
separate SABA
71. Single maintenance and reliever
therapy (SMART)
With the SMART approach, patients use a
maintenance dose of budesonide/formoterol
160/4.5 mg b.i.d. or 320/9 mg b.i.d. in a single
inhaler.
In addition, they are allowed to use budesonide/
formoterol 160/4.5 mg as needed with a maximum
of extra 10 as-needed inhalations per day.
72. Traditional standard treatment manages the two
components of asthma separately*
Maintenance Inhaler
Daily use
Prevention
BronchoconstrictioIInnffllaammmmaattiioonn Bronchoconstrictionn
Rescue Inhaler
Rapid symptom relief
Does not address
underlying
inflammation
* Canadian Asthma Consensus Report., CMAJ; 1999
73. Symbicort SMART
Syymmbbiiccoorrtt Maintenance And Reliever Therapy
Formoterol
(greitas simptomų
slopinimas ir ilgai
trunkantis bronchus
plečiantis poveikis)
Budesonide
(priešuždegiminis
vaistas, pradeda
veikti per keletą
valandų*)
SABA
papildomo
inhaliatoriaus
simptomams
slopinti
77. SMART approach
Use of Formoterol / Budesonide for both rescue
and maintenance
– Maintenance dose single inhaler (1–2 puff
160/4.5 BID) plus extra puffs from the same
inhaler up to a total of 12 puffs per day.
– Those patients who require such high dose
should seek medical advice to step up therapy
that may include use of short course of oral
prednisone.
78. TRADITIONAL APPROACH AND SYMBICORT
MAINTENANCE AND RELIEVER THERAPY
(SMART)
As needed
β2
As needed
Symbicort
Daily medication use
(maintenance and relief)
Traditional Approach
Fixed Symbicort
+ prn SABA
Days with symptoms
Maintenance
Maintenance
Symbicort
SMART
Most days patients
use no reliever
Time
iilllluussttrraattiivvee
79. SMART approach
Although short-acting bronchodilators provide
rapid relief of symptoms they fail to address the
accompanying eosinophilic inflammation known
to precede exacerbations in asthma.
One potential advantage of the SMART strategy is
that patients will simultaneously receive additional
doses of inhaled corticosteroids alongside a
bronchodilator when they use their combined
inhaler for symptom relief.
80. The concept behind Symbicort Turbuhaler SMART™ is
to treat the inflammation with every inhalation, whether
used for maintenance or relief
81. SMART Approach
IInn In the SMART model, the patient is only
provided with an ICS/LABA inhaler, used both for
maintenance treatment and for additional rescue use
in place of SABA.
This results in a variable ICS dose which is higher
when the patient is more symptomatic.
The rationale is that the higher ICS use at the time
of increased symptoms improves outcomes by
reducing exacerbation risk,and in fact allows lower
total ICS exposure without compromising outcomes.
82. SMART
Van der Molen T, Partridge MR, Myrseth SE and Busse W. ERS , 2005
83. Single maintenance and reliever
therapy (SMART)
SMART is currently only possible in inhalers
containing the LABA formoterol, as its rapid onset
of action (comparable to that of SABA
preparations) allows its use as a rapid-onset rescue
medication , with a maximum dose of 72 mcg/day.
SymbicortTM formulations contain 6 or 12 mcg per
actuation with SMART generally using 6mcg
formulations, and total daily use should not usually
exceed 12 puffs/day.
84. SMART strategy is unique to Symbicort®
Budesonide
• Anti-inflammatory agent
• Demonstrated dose
response
• Greater efficacy in
combination with
formoterol vs. higher doses
of budesonide alone
+ Formoterol
• Long-acting bronchodilator
• Onset as rapid as salbutamol
(1-3 minutes)
• Demonstrated dose
response 6 μg to 48 μg/day
Only Symbicort® can be
prescribed in this manner
85. Onset And Duration - LIPOPHILICITY
Salbutamol
Hydrophilic
Short duration
Fast onset
Formoterol
Intermediate
Long duration
Fast onset
Salmeterol
Lipophilic
Long duration
Slow onset
86. Classes of b2-agonists
fast onset, short duration fast onset, long duration
inhaled terbutaline
inhaled salbutamol
inhaled formoterol
slow onset, short duration slow onset, long duration
oral terbutaline
oral salbutamol inhaled salmeterol
oral bambuterol
MAINTENANCE
AS NEEDED
Duration
short long of action
Speed
of action
Fast
Slow
87. Pharmacology of LABAs: Differences
Between Formoterol and Salmeterol
Both salmeterol and formoterol are more lipophilic
than SABA’s and this property accounts for their
longer duration of action.
After inhalation, both formoterol and salmeterol
will first contact the epithelium. Since both drugs are
lipophilic, a proportion will diffuse through the
epithelial cell membrane with a subsequent release
of small amounts that can activate B2-receptors.
88. Pharmacology of LABAs: Differences
Between Formoterol and Salmeterol
Formoterol is less lipophilic than salmeterol and
therefore a larger proportion will rapidly diffuse
through the airway wall to exert a relaxation effect on
airway smooth muscle cells.
This property of formoterol accounts for its more
rapid onset of action which is similar to that of
salbutamol
89. Pharmacology of LABAs: Differences
Between Formoterol and Salmeterol
Currently two different LABAs are available, ie
formoterol and salmeterol. The most important
difference between both LABAs is a more rapid
onset of action of formoterol (2–5 minutes) when
compared to salmeterol (15–30 minutes).
Formoterol has a more rapid onset of action which
facilitates its use as a reliever therapy.
90. Pharmacology of LABAs: Differences
Between Formoterol and Salmeterol
In addition, the effects of formoterol were dose
dependent i.e.there is better bronchodilatation on
increasing the dose of formoterol in contrast to
salmeterol that appears to have no dose response
relationship, did not show a clear additional effect
at doses higher than 50 mg
91. Pharmacology of LABAs: Differences
Between Formoterol and Salmeterol
The above mentioned properties, make formoterol
more suitable for use as both maintenance and
reliever medication than salmeterol.
Formoterol is a more dynamic drug compared to
salmeterol and hence the SMART finds a mention in
the Gina guidelines
92. Total daily medication use
(maintenance and relief)
Fixed Symbicort
+ prn SABA
Fixed Symbicort
+ prn Symbicort
(Symbicort SMART)
If a combination inhaler containing formoterol and
budesonide is selected, it may be used for both rescue and
maintenance. This approach has been shown to result in
reductions in exacerbations and improvements in asthma
control in adults and adolescents at relatively low doses of
treatment (Evidence A) … page60 GINA 2007
94. Adherence to treatment
is a weak point
in asthma management
Cutler and Everett. NEJM 2010; 362: 1553-1555
95. Evolution in Asthma Management
Use
Medication Maintenance
+ prn SABA
Therapy used over time One inhaler:
Maintenance &
relief
Rapid adjustments in
controller replacing
SABA
Maintenance
+ prn Symbicort
No adjustment in
controller
96. Evolution in Asthma Management
Use
Medication Maintenance
+ prn SABA
Therapy used over time One inhaler:
Maintenance &
relief
Rapid adjustments in
controller replacing
SABA
Maintenance
+ prn Symbicort
No adjustment in
controller
SSMMAARRTT ==
SSiinnggllee iinnhhaalleerr MMaaiinntteennaannccee
AAnndd RReelliieevveerr TThheerraappyy
GOAL
97. One or many?
or
WWhhiicchh ttrreeaattmmeenntt wwoouulldd yyoouu cchhoooossee??
98. SMART Studies
(Symbicort Maintenance And Reliever Therapy )
Late action
Early Action
Instant Action
Time Symptom
Exacerbation
Asthma Control
Symptom
102. AHEAD: Study Design
Six-month, double-blind, double-dummy
Run-in
2 inh. budesonide/formoterol 160/4.5 μg b.i.d. plus as-needed
(n=1154)
1 inh. fluticasone/salmeterol 50/500 μg b.i.d. plus terbutaline
0.4 mg as-needed (n=1155)
Regular ICS
≥500 μg plus
LABA*
R
Enrolled: 3346
Randomized: 2309
Visit: 1 2 3 4 5
Week: –2 0 4 13 26
Randomization
*Only if taken as maintenance treatment before study entry
Bousquet et al. AHEAD trial. Respir Med 2008; accepted.
103. Symbicort SMART reduces asthma
exacerbation rates more effectively
than fixed combination
Exacerbations (events/100 patients/year)
* Extrapolated to one year from six month
result
-39%
23
32
38
40
30
20
10
0
Seretide 50/250
μg bid + SABA
Symbicort 320/9
μg bid + SABA
Symbicort SMART 160/4.5
μg bid + as needed
COMPASS: Kuna P et al, Int J Clin Prac. 2007; 61: 725-736
* **
* P<0.001 vs. Seretide
+ SABA
** P<0.01 vs. 2x
Symbicort + SABA
• A six month double-blind study including 3,335 patients
104. Symbicort SMART reduces numbers of
hospitalizations and ER treatments
Hospitalizations/ER treatment (events/100
patients/year)
* Extrapolated to one year from six month
result
16
10 10
20
10
0
Seretide 50/250
μg bid + SABA
Symbicort 320/9
μg bid + SABA
Symbicort SMART 160/4.5
μg bid + as needed
COMPASS: Kuna P et al, Int J Clin Prac. 2007; 61: 725-736
-39%
*
* P<0.01 vs. Seretide
+ SABA
• A six month double-blind study including 3,335 patients
105. Symbicort SMART reduces drug load of
oral corticosteroids
days with use of oral streoids
619
1044
1132
1200
800
400
0
Seretide 50/250
μg bid + SABA
Symbicort 320/9
μg bid + SABA
Symbicort SMART 160/4.5
μg bid + as needed
• A six month double-blind study including 3,335 patients
COMPASS: Kuna P et al, Int J Clin Prac. 2007; 61: 725-736
-45%
106. Symbicort SMART reduces the use of
daily reliever
Inhalations use/patient/24 hours
0.93
0.58
1
0.5
0
Seretide + SABA Symbicort SMART
COSMOS: Vogelmeier C et al, Eur Respir J. 2005; 26: 819-828
-38%
*
* P<0.001
• Maintenance dose of Seretide titrated on clinicians’ judgment to be either 2x50/100 μg; 2x50/250 μg or 2x50/500 μg
• Maintenance dose of Symbicort 160/4.5 μg; 1 or 2 puffs bid based on clinicians’ judgment
• One year randomized real life study including 2,143 patients
107. Symbicort SMART reduces the use of
daily reliever
Inhalations use/patient/24 hours
0.93
0.58
1
0.5
0
Seretide + SABA Symbicort SMART
COSMOS: Vogelmeier C et al, Eur Respir J. 2005; 26: 819-828
-38%
*
* P<0.001
• Maintenance dose of Seretide titrated on clinicians’ judgment to be either 2x50/100 μg; 2x50/250 μg or 2x50/500 μg
• Maintenance dose of Symbicort 160/4.5 μg; 1 or 2 puffs bid based on clinicians’ judgment
• One year randomized real life study including 2,143 patients
108.
109.
110. Summary
• Symbicort SMART, compared to higher
doses of fixed Bud/Form or Sal/Flu:
– Prolonged the time to a first severe
exacerbation
– Reduced the rate of severe exacerbations
– Reduced overall steroid load (inhaled and
oral corticosteroids)
111.
112. Symbicort Turbuhaler SMART™ was incorporated
in the 2008 Global Initiative for Asthma (GINA)
guidelines .
Currently, Symbicort® is the only ICS/LABA
approved so far for maintenance and reliever
therapy in the adult population.
113. GINA guidelines 2008
The use of the combination of a rapid and long-acting
β2-agonist (formoterol) and an inhaled
costeroid (budesonide) in a single inhaler both as
a controller and reliever is effective in maintaining
a high level of asthma control and reduces
exacerbations requiring systemic corticosteroids
and hospitalizations (Evidence A).
114. GINA guidelines 2008
Combination therapy with budesonide and
formoterol used both as maintenance and rescue
has been shown to reduce asthma exacerbations in
moderate to severe asthma patients.
The benefit in preventing exacerbations appears
to be the consequence of early intervention at a
very early stage of a threatened exacerbation.
117. Asthma is a variable disease
Increased
Use of reliever
medication or
symptoms
Asthma control
Decreased
Time
Allergens &
viral infection
Cold weather
& exercise
Exacerbation Exacerbation
118. What are we trying to achieve asthma
control?
TTiimmee ((mmoonntthhss))
Achieve and maintain
Variable control,
symptom-based
Uncontrolled
Level of control
122. Step 1 – as-needed inhaled short-acting
beta2-agonist (SABA)
122
*For children 6-11 years, theophylline is not recommended, and preferred Step 3 is medium dose
ICS
**For patients prescribed BDP/formoterol or BUD/formoterol maintenance and reliever therapy
123. Step 1 – as-needed reliever inhaler
Preferred option: as-needed inhaled short-acting
beta2-agonist (SABA)
SABAs are highly effective for quick relief
of asthma symptoms (3-5 min)
Not recommended for regularly scheduled
GINA 2014
124. Step 1
Other options
– Consider adding regular low dose ICS , in
addition to as-needed SABA, for patients
at risk of exacerbations (Evidence B).
– For more frequent symptoms, or the presence
of any exacerbation risk factors such as FEV1
< 80% personal best or predicted or
an exacerbation in the previous 12
months, indicate that regular controller
treatment is needed ( Evidence B).
125. Other options not recommended for routine
use
In adults, inhaled anticholinergic agents like
ipratropium, oral SABA or short-acting
theophylline are potential alternatives to SABA
for relief of asthma symptoms
However, these agents have a slower onset of
action than inhaled SABA ( Evidence A ), and oral
SABA and theophylline have a higher risk of side-effects.
126. The rapid-onset LABA, formoterol is as effective
as SABA as a reliever medication in adults
and children, but use of regular or frequent
LABA without ICS is strongly discouraged
because of the risk of exacerbations
( Evidence A ) .
127.
128. No controller
1. Asthma Sx or need for SABA < twice a month
2. No waking due to asthma in last month
3. No risk factors for exacerbations
4. No exacerbations in the last year
5. Normal lung function
129. Step 2 – low-dose controller + as-needed
inhaled SABA
129
*For children 6-11 years, theophylline is not recommended, and preferred Step 3 is medium dose
ICS
**For patients prescribed BDP/formoterol or BUD/formoterol maintenance and reliever therapy
130. Step 2 : Low dose controller medication
plus as-needed reliever medicatoin
Preferred option: regular low dose ICS plus as-needed
inhaled SABA
Low dose ICS reduces symptoms and reduces
risk of exacerbations and asthma-related
hospitalization and death ( Evidence A ) .
131.
132. Step 2 – Low dose controller + as-needed
Other options
– Leukotriene receptor antagonists (LTRA) with
as-needed SABA
– Less effective than low dose ICS
– May be used for some patients
with both asthma and allergic
rhinitis, or
– In patients who are unable or
unwilling to use ICS , or
– For patients who experience
intolerable side-effects from ICS
SABA
GINA 2014
133. Step 2 – Low dose controller + as-needed
Other options
– Combination low dose ICS/long-acting beta2-
agonist (LABA) as the initial maintenance
controller treatment with as-needed SABA
– Reduces symptoms and
increases lung function
compared with ICS alone.
– More expensive, and does not
further reduce exacerbations
GINA 2014
SABA
134. Step 2 – Low dose controller + as-needed
Other options
– Intermittent ICS with as-needed SABA for
purely seasonal allergic asthma with no
interval symptoms
– Start ICS immediately symptoms
commence, cease 4 weeks after
end of exposure
SABA
GINA 2014
135. Step 2 – Low dose controller + as-needed
Other options
– Options not recommended for routine use
sustained-release theophylline has only weak
efficacy in asthma ( Evidence B) and side
effects are common, and may be life-threatening
at higher doses
SABA
GINA 2014
136. Step 3 – one or two controllers + as-needed
inhaled reliever
*For children 6-11 years, theophylline is not recommended, and preferred Step 3 is medium dose ICS
**For patients prescribed BDP/formoterol or BUD/formoterol maintenance and reliever therapy
137. Step 3 – one or two controllers + as-needed
inhaled reliever
Before considering step-up
Check inhaler technique and adherence,
confirm diagnosis
Adults/adolescents: preferred options are either
combination low dose ICS/LABA as maintenance
treatment plus as-needed SABA as reliever, OR
Combination low dose ICS/formoterol as both
maintenance and reliever treatment regimen
GINA 2014
138. In at-risk patients, the low dose ICS/formoterol
maintenance and reliever regimen * significantly
reduces exacerbations and provides similar levels
of asthma control at relatively low doses of ICS,
compared with a fixed dose of ICS/LABA as
maintenance treatment or a higher dose of ICS,
both with as-needed SABA ( Evidence A ).
*Approved only for low dose budesonide/formoterol
and low dose beclometasone/formoterol
140. For adult and adolescent patients with >= 1
exacerbation in the last 12 month , low dose
ICS/formoterol maintenance and reliever regimen*
, is more effective than the same fixed dose
combination of ICS/LABA as maintenance
treatment with as-needed SABA ( Evidence A ).
*Approved only for low dose budesonide/formoterol
and low dose beclometasone/formoterol
141. Step 3 – one or two controllers + as-needed
inhaled reliever
Children 6-11 years: preferred option is medium dose
ICS with as-needed SABA
Other options
– Adults/adolescents: Increase ICS dose to medium
dose or add LTRA or low dose sustained release
theophylline to low dose ICS (less effective than
low dose ICS/LABA)
– Children 6-11 years – add LABA , low dose
ICS/LABA (similar effect as increasing ICS)
GINA 2014
142. Step 4 – two or more controllers + as-needed
inhaled reliever
*For children 6-11 years, theophylline is not recommended, and preferred Step 3 is medium dose ICS
**For patients prescribed BDP/formoterol or BUD/formoterol maintenance and reliever therapy
143. Step 4 – two or more controllers +
as-needed inhaled reliever
Before considering step-up
– Check inhaler technique and adherence , confirm
diagnosis
Adults or adolescents: preferred option is
combination low dose ICS/formoterol as maintenance
and reliever regimen, OR
Combination medium dose ICS/LABA with as-needed
SABA
GINA 2014
144. The selection of Step 4 treatment depends on the
prior selection at step 3
For adult and adolescent patients with >= 1
exacerbations in the previous year, combination low
dose ICS/formoterol as maintenance and reliever
treatment is more effective in reducing exacerbations
than the same dose of maintenance ICS/LABA or
higher doses of ICS ( Evidence A ).
This regimen can be prescribed with low dose
ICS/formoterol as in step 3 , the maintenance dose
may be increased if necessary.
GINA 2014
145. The selection of Step 4 treatment depends on
the prior selection at step 3
For patients taking low dose maintenance
ICS/LABA with as-needed SABA, whose asthma
is not adequately controlled, treatment may be
increased to medium dose ICS/LABA
( Evidence B )
146. Step 4 – two or more controllers + as-needed
inhaled reliever
Other options (adults or adolescents)
– Trial of high dose combination ICS/LABA, but
little extra benefit and increased risk of side-effects
– Increase dosing frequency (for budesonide-containing
inhalers)
– Add-on LTRA or low dose theophylline
GINA 2014
147. Other options (adults or adolescents)
Combination high-dose ICS/LABA may be
considered in adults and adolescents, but the
increase in ICS dose generally provides little
additional benefit. ( Evidence A ) , and there is
an increased risk of side-effects .
A high dose is recommended only on a trial
basis for 3-6 months when good asthma control
cannot be achieved with medium dose ICS plus
LABA and/or a third controller ( e.g. LTRA or
sustained-release theophylline , Evidence B )
148. Other options for adults or adolescents that can
be added to a medium – or high-dose ICS
including LTRA , or low dose sustained-release
theophylline are less efficacious than adding
LABA
Theophylline should not be used in children.
For children 6-11 years, if asthma is not well
controlled on moderate dose ICS, then is to refer
the child for expert assessment and advice
Other options
149. Step 5 – higher level care and/or
add-on treatment
*For children 6-11 years, theophylline is not recommended, and preferred Step 3 is medium dose ICS
**For patients prescribed BDP/formoterol or BUD/formoterol maintenance and reliever therapy
150. Step 5 – higher level care and/or
add-on treatment
Preferred option is referral for specialist
investigation and consideration of add-on
treatment
– If symptoms uncontrolled or exacerbations
persist despite Step 4 treatment, check inhaler
technique and adherence before referring
– Add-on omalizumab (anti-IgE) is suggested
for patients with moderate or severe allergic
asthma that is uncontrolled on Step 4
treatment ( Evidence A ).
151. Step 5 – higher level care and/or add-on
treatment
Other add-on treatment options at Step 5 include:
– Add-on low dose oral corticosteroids
(≤7.5mg/day prednisone equivalent): this may
benefit some adult patients with severe
asthma ( Evidence D ), but has significant
systemic side-effects.
– Patients should be assessed and monitored
for risk of corticosteroid-induced osteoprosis
– Bronchial thermoplasty for selected patients
152. SStteepp 11 Step 2 Step 3 Step 4 Step 5
As needed rapid-acting b2-agonist
Select one Select one Add one or
more
Add one or
more
Low-dose
ICS
Low-dose
ICS/LABA
Med-high
ICS/LABA Oral steroids
Leukotriene
modifier
Med-high
dose ICS
Leukotriene
modifier Anti-IgE
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IICCSS++LLTTMM TThheeoopphhyylllliinnee
LLooww
IICCSS++TThheeoo
GINA 2013
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155. REMEMBER TO….
Step up if … uncontrolled Sx, exacerbations
or risks, but check Dx, inhaler technique and
adherence first
Step down if … Sx controlled for 3 months +
low risk for exacerbations
“ Ceasing ICS is not advised”
Past 4 wk – Sx 3x/day in the daytime; most nights/every nights
Past yr – 21x/wk during a typical wk
We can just use data on the severe persistent asthmatics to illustrate the underusage of ICS
Note to Chris:
I think we should include all grades for now. It’s quite interesting that the ICS use is so similar between symptom severity grades, particularly persistent severity grades. We can always delete any groups later if you wish to simplify the slide.
More then 90% of our patients were experiencing daytime symptoms during the last 4 weeks and two thirds of them were having night awakenings.
When emergency visits due to asthma were considered, almost half of them required an urgent/emergency visit. And one quarter of them were hospitalised in past year.
Slide 7
•The most up-to-date definition of asthma, taken from the GINA guidelines, emphasises
the persistent underlying inflammation of the airways, present in all severities of asthma
•Specific types of inflammatory cells are involved
•The characteristic symptoms are variable over time and in severity
Just over half of the sample are uncontrolled as measured by the ACQ6.
Asthma Control Questionnaire (ACQ) was developed by E.F. Juniper et al1. Using the 6-item Asthma Control Questionnaire (ACQ-6; FEV1 item omitted; scale 0-6), patients were defined as well controlled (WC; ACQ-6 mean score 0-0.74), not well controlled (NWC; score 0.75-1.5) and uncontrolled (UC; score &gt; 1.5). Patients recall their experience during the previous 7 days and respond to each question using a 6-point scale.
On average, during the past week, how often were you woken by your asthma during the night?
On average, during the past week, how bad were your asthma symptoms when you woke up in the morning?
In general, during the past week, how limited were you in your activities because of your asthma?
In general, during the past week, how much shortness of breath did you experience because of your asthma?
In general, during the past week, how much of the time did you wheeze?
On average, during the past week, how many puffs of short-acting bronchodilator have you used each day?
1 Juniper EF, O&apos;Byrne PM, Guyatt GH, Ferrie PJ, King DR. Development and validation of a questionnaire to measure asthma control. European Respiratory Journal 1999;14(4):902-7.
The point being made by this slide is that Symbicort single inhaler therapy (SSIT) or Symbicort maintenance and reliever therapy (SMART) is different from any other adjustable approach such as SAMD, GOAL or the Sont and Green studies which were all dependent on a complex algorithm to adjust maintenance treatment.
With SMART adjustment becomes automatic based on the need for reliever
The point being made by this slide is that Symbicort single inhaler therapy (SSIT) or Symbicort maintenance and reliever therapy (SMART) is different from any other adjustable approach such as SAMD, GOAL or the Sont and Green studies which were all dependent on a complex algorithm to adjust maintenance treatment.
With SMART adjustment becomes automatic based on the need for reliever
Important to note that all patients used fixed dose BUD/FOR during run-in.
Many of the factors that contribute to the development and persistence of asthma also lead to variability. This variability is often beyond the control of either the patient or physician.
The variable nature of asthma means that most patients experience periods of good asthma control and periods of worsening asthma symptoms.
Asthma exacerbations can be triggered by various stimuli including allergens, infections, environmental factors and exercise. This slide presents a ‘hypothetical representation’ of this process.
During exacerbations, patients tend to use their reliever medication to control their symptoms without also increasing their anti-inflammatory medication as they should. Changes to the controller medication dose are usually only made if asthma worsening persists long enough for the patient to make a visit to the physician.
