5. Q1. Mild asthma is estimated to accounts for ….. of the
asthma population.
a) 25-50%
b) 10-30%
c) 70-90%
d) < 10%
e) 50-75%
6. Q2. Which of the following statement is true concerning mild
asthma?
a) Mild asthma can be controlled by Step 1 or 2 treatment.
b) Symptoms of mild asthma could disappear as patients grow up.
c) Inhaled Corticosteroid is not necessary for treating mild asthma.
d) Both (a) and (c)
e) Both (b) and (c)
7. Q3. What is the preferred choice of controller for Step 1
treatment according to the latest GINA guideline?
a) Daily low-dose ICS-formoterol
b) As-needed low-dose ICS-formoterol
c) Low-dose ICS+LABA
d) As-needed medium-dose ICS
e) As-needed SABA
8. Although evidence based treatments are available in most countries,
asthma control remains suboptimal, and asthma-related deaths
continue to be an ongoing concern.
21. FOR INTERNAL USE ONLY. STRICTLY CONFIDENTIAL.
DO NOT COPY, DETAIL OR DISTRIBUTE EXTERNALLY.
2
1
Why are there concerns about SABA-only
treatment?
22. The risks of SABA were the focus of extensive research in the 1980s and
1990s following two international epidemics of asthma deaths , with case
control studies showing that over-use of SABA was associated with
increased risk of asthma-related death.
Randomised controlled trials found no advantage in regular versus as-
needed SABA and, by the late 1990s, most guidelines recommended as-
needed rather than regular SABA.
23. Although SABA provides a quick relief of symptoms, SABA only
is associated with increased risk of exacerbations and lower lung
function, its Regular use increases allergic responses and airway
inflammation.
Higher use of SABA is associated with adverse clinical outcomes :
Dispensing of ≥3 canisters per year (average 1.7 puffs/day) is associated with
higher risk of emergency department presentations (Stanford, AAAI 2012)
Dispensing of ≥12 canisters per year is associated with higher risk of death
24. Patients and many doctors are shocked to hear that one salbutamol (short-
acting beta agonist, SABA) canister contains 200 puffs of the drug and that
this, should last patients at least a year with well-controlled asthma, in
which they use it less than twice per week.
There has been some concern about overuse of SABA inhalers for some
time, in that whilst they do give immediate bronchodilator relief, they fail to
address the underlying pathophysiology, which is an inflammatory process.
25.
26.
27. Patients develop an over reliance on a SABA and are willing to use
them as the primary treatment regardless of asthma severity. ...
Even in patients with mild persistent asthma, the number was quite
similar, with 75% patients using SABA and only 30% using ICS.
28. FOR INTERNAL USE ONLY. STRICTLY CONFIDENTIAL.
DO NOT COPY, DETAIL OR DISTRIBUTE EXTERNALLY.
Why are there concerns about mild
asthma?
29. Mild asthma, often termed mild intermittent or mild persistent asthma,
is defined by the Global Initiative in Asthma (GINA) management
strategy as patients who meet the criteria for step 1 and step 2
treatment strategies.
Although these patients have fewer symptoms, they are the main and
largest subgroup of asthma patients.
Epidemiological data shows that mild asthma accounts for 50 -75% of
the total population of asthma patients.
30.
31. “There is a perception that infrequent symptoms mean low-risk, but
the evidence is that patients with mild asthma still have severe
attacks”
Patients with apparently mild asthma are at risk of serious adverse
events
30–37% of adults with acute asthma
16% of patients with near-fatal asthma
15–20% of adults dying of asthma
32. Mild persistent asthmatic patients constitute a significant proportion of
patients ,Generally, it is believed that between 50 to 75% of patients with
asthma can be considered as having mild asthma.
These patients might be considered the “silent majority” of asthmatics.
This is because they rarely visit their primary care physician with
symptoms of asthma.
33. Although the symptoms may not be very troublesome or frequent,
airway inflammation is usually present in those with mild asthma &
patients may be at risk of acute asthma exacerbations and death.
Until recently, very little attention has been paid to the morbidity
associated with mild persistent asthma and very few studies have been
evaluated the responses of this patient population to treatment.
34. Historically, there has been a perception that patients with intermittent
symptoms are not at risk of asthma attacks.
Evidence from adult studies showed that airways inflammation occurs at
a very early stage of the disease even in patients with intermittent
asthma,
Early introduction of daily inhaled corticosteroid (ICS) in adults & children
> 5years with mild asthma symptoms reduced the risk of severe asthma
exacerbation by almost half, with better asthma control although it did
35. Many guidelines over the past 50 years have recommended SABA
as the first line to treat asthma and to move on to ICS when that
proved to be unsuccessful in controlling symptoms.
36.
37. Previous versions of Global Initiative for Asthma (GINA) suggested
that mild asthma (GINA 1/2 ) in adults can be well managed with
Reliever medications, for example, short-acting beta2 agonists
(SABA) alone or with
Additional use of controllers such as regular low-dose inhaled
corticosteroids (ICS).
38. We now know that asthma, is principally a disease of inflammation, even
in those with infrequent or intermittent symptoms.
Widely used international guidelines update their recommendation for the
consideration of ICS use as Step 1 treatment in all adults, adolescents &
children over 6 years with mild asthma, even in those with infrequent
symptoms, to reduce the risk of severe, potentially life-threatening
exacerbations .
39.
40. Step 1 treatment is for
patients with symptoms
<twice/month and no risk
factors for exacerbations
Previously, no controller
was recommended for
Step 1, i.e. SABA-only
treatment was
‘preferred’
GINA 2018 – main treatment figure
41.
42. Preferred option: as-needed inhaled short-acting beta2-agonist (SABA)
SABAs are highly effective for relief of asthma symptoms
However …. there is insufficient evidence about the safety of treating asthma
SABA alone
This option should be reserved for patients with infrequent symptoms (less than
twice a month) of short duration, and with no risk factors for exacerbations
Other options
Consider adding regular low dose inhaled corticosteroid (ICS) for patients at risk
exacerbations
Step 1 – as-needed reliever inhaler 2018
GINA 2017
43.
44. Daily Low dose ICS has been suggested by GINA since 2014 in step1
to reduce the risk of severe exacerbations
However, patients with symptoms less than twice a month are unlikely
to take ICS regularly, leaving them exposed to the risks of SABA-only
treatment
46. Preferred option: regular low dose ICS with as-needed inhaled SABA
Low dose ICS reduces symptoms and reduces risk of exacerbations and asthma-
related hospitalization and death
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 if patient will not
use ICS
Combination low dose ICS/long-acting beta2-agonist (LABA)
with as-needed SABA
Reduces symptoms and increases lung function compared with ICS
More expensive, and does not further reduce exacerbations
Intermittent ICS with as-needed SABA for purely seasonal allergic asthma with no
interval symptoms
Start ICS immediately symptoms commence, and continue for 4 weeks after pollen season
ends
Step 2 – Low dose controller + as-needed SABA 2018
GINA 2017
49. Given the low frequency or non-bothersome nature of symptoms in
mild asthma, patients’ adherence towards their controller
medications, especially to ICS is usually not satisfactory.
Such patients often rely on SABAs alone to relieve symptoms, which
may contribute to SABA overuse
This may particularly occur if SABAs are available in pharmacies as
non-prescription medicines as is the case, for example, in egypt
50.
51. In people with mild asthma, the perception of quick-relief evident
when SABAs are used may also contribute to over-reliance on SABAs
and other similar relievers, compared to controllers where the
actions of the medications are not immediately perceivable.
Overuse of relievers such as SABAs has been associated with poor
asthma outcomes, such as exacerbations and even deaths.
52. Patient satisfaction with, and reliance on, SABA treatment is reinforced by its
rapid relief of symptoms, its prominence in ED and hospital management of
exacerbations, and low cost .
Patients commonly believe that “My reliever gives me control over my
asthma”, so they often don’t see the need for additional treatment .
56. Although GINA is evidence-based and is updated on an annual basis, there
are some contradictions in the management of patients with mild asthma.
Firstly, for patients of mild intermittent asthma (GINA step 1), the guideline
suggests as-needed use of SABA, which neglects the underlying inflammatory
nature of asthma and puts patients at risk of acute exacerbations as is shown
in placebo controlled trials where patients receive a SABA compared to ICS.
57.
58. `
For patients with mild persistent asthma (GINA step 2) who have already
accepted the idea of as-needed treatment on step 1, it may confuse them
when the severity of the disease progresses to step 2 where we switch the
emphasis to using a SABA as the primary treatment to regular ICS and
SABA on an as needed basis.
They have to change and accept the long-term anti-inflammatory treatment
strategy, which means fixed-dose regular maintenance and preventive
therapy
59. Secondly, beta-2 agonists relieve symptoms rapidly and effectively, giving
asthma patients significant improvements, leading to a sense that a
SABA is more effective than ICS.
Thus patients develop an over reliance on a SABA and are willing to use
them as the primary treatment regardless of asthma severity.
60.
61.
62. When the reliever is SABA, poor adherence with maintenance controller
exposes the patient to risks of SABA-only treatment
Evidence suggests that the adverse associations of SABAs are not
necessarily a result of the direct actions of the drugs, but because they may
be used preferentially by patients instead of regular ICS or ICS combinations
with long-acting β2 agonists and may mask worsening asthma symptoms .
65. The recommended treatment of mild asthma is regular maintenance ICS with SABA
as a separate inhaler used when needed for symptom relief, however the benefits of
regular ICS use in actual clinical practice are limited by poor adherence and low
prescription rates.
An alternative strategy would be the symptom driven (as-required or prn) use of a
combination ICS/SABA or ICS/LABA inhaler as a reliever rather than regular
maintenance therapy
The rationale for this approach is to titrate both ICS and B-agonist dose according to
need and enhance ICS use in otherwise poorly adherent patients who overrely on
their reliever B-agonist inhaler
66. This strategy will only work if the B-agonist component has a rapid onset of action for
symptom relief.
There is evidence to suggest that this regimen has advantages over ICS therapy and
might represent an effective ,safe and novel therapy for the treatment of intermittent
and mild asthma
67. fast onset, short duration fast onset, long duration
slow onset, short duration slow onset, long duration
inhaled terbutaline
inhaled salbutamol
inhaled formoterol
oral terbutaline
oral salbutamol inhaled salmeterol
oral bambuterol
M
A
I
N
T
E
N
A
N
C
E
AS NEEDED
Duration
of actionlongShort
Classes of b2-agonists
Speed
of action
Fast
Slow
81. The year of 2018 is potentially a unique time for changing the treatment
strategy for mild asthma.
Both SYGMA1 and SYGMA2 studies showed that in mild asthma patients,
budesonide-formoterol as needed treatment was better than terbutaline as
needed treatment in control asthma symptom and in reducing exacerbations.
As needed use of budesonide-formoterol was non-inferior to the budesonide
maintenance treatment in terms of reducing exacerbations with no need to
routinely use a twice daily medication and greatly reduced the exposure to ICS.
82. The SYGMA studies provide a new treatment strategy in mild asthma but will
require regulatory approval and then acceptance by patients, clinicians and
payers.
This strategy is one that a patient will likely be more adherent to and should
be even more effective in a real world setting.
These data clearly show that SABA PRN should not be considered as the
primary treatment for mild asthma.
90. The SYGMA 1 and 2 trials compared as-needed versus maintenance
regimens for the budesonide-formoterol combination, however,
there are other ICS-formoterol combination/s (beclometasone-
formoterol) available on the market which may potentially be used
in a similar fashion.
91. Combination inhalers of salmeterol with an ICS, such as Seretide, are not
suitable.
Salmeterol should not be used for the relief of acute asthma symptoms
because it has a significantly slower onset of action than either
formoterol, salbutamol or terbutaline.
91
92.
93. The evidence for another regimen (using an ICS inhaler whenever an
as-needed SABA is used) is again indirect and extrapolated from
trials which recruited patients deemed to be requiring treatment in
Step 2 such as :
1. BEST (Beclomethasone plus Salbutamol Treatment)
2. TREXA (Treating Children to Prevent Exacerbations of Asthma)
3. BASALT (Best Adjustment Strategy for Asthma in the Long Term)
94.
95.
96.
97. Rescue use of beclomethasone and albuterol in a single inhaler for mild
asthma (N Engl J Med. 2007 May)
CONCLUSIONS:
In patients with mild asthma, the symptom-driven use of inhaled beclomethasone
(250 microg) and albuterol (100 microg) in a single inhaler is as effective as
regular use of inhaled beclomethasone (250 microg twice daily) and is associated
with a lower 6-month cumulative dose of the inhaled corticosteroid.
98.
99. Use of beclomethasone dipropionate as rescue treatment for children
with mild persistent asthma (TREXA): a randomised, double-blind,
placebo-controlled trial (Lancet. 2011 Feb)
INTERPRETATION:
Children with mild persistent asthma should not be treated with rescue
albuterol alone and the most effective treatment to prevent exacerbations is
daily inhaled corticosteroids.
Inhaled corticosteroids as rescue medication with albuterol might be an
effective step-down strategy for children with well controlled mild asthma
it is more effective at reducing exacerbations than is use of rescue albuterol
107. The new GINA 2019 asthma treatment recommendations represent
significant shifts in asthma management at Steps 1 and 2 of the 5
treatment steps.
The report acknowledges an emerging body of evidence suggesting the
non safety of SABAs overuse in the absence of concomitant controller
medications.
108. Adherence to regular ICS is considered an issue in patients with very mild
asthma requiring only Step 1 treatment. Non-adherent patients may thus
be exposed to SABAs alone if they are prescribed regular ICSs.
Further, the use of as-needed ICS-formoterol also has the advantage of lower
exposure to ICSs
109. As-Needed Symbicort Beats Rescue Albuterol for Mild Asthma
For safety reasons, GINA no longer recommends treatment with
SABA reliever alone in Step 1.
’ As-needed low dose ICS-formoterol now the preferred reliever at all
Steps (1-5), displacing as needed SABA to ‘other reliever.
110. The new GINA 2019 does not support SABA-only therapy in mild
asthma and has included new off-label recommendations such as :
Symptom-driven (as-needed) low dose ICS-formoterol or
“Low dose ICS taken whenever SABA is taken”.
These recommendations represent a clear deviation from decades of
clinical practice mandating the use of symptom-driven SABA treatment
alone in those with mild asthma.
114. Step 1 is for patients with symptoms less than twice a month, and with
no exacerbation risk factors
As-needed low dose ICS-formoterol (off-label)
Evidence
Indirect evidence from SYGMA 1 of large reduction in severe exacerbations
SABA-only treatment in patients eligible for Step 2 therapy (O’Byrne, NEJMed
Step 1 – ‘preferred’ controller option
115. Low dose ICS taken whenever SABA is taken (off-label)
As Separate or Combination ICS and SABA inhalers
Evidence
Indirect evidence from studies in patients eligible for Step 2 treatment
(BEST, TREXA, BASALT)
Daily ICS is no longer listed as a Step 1 option
This was included in GINA 2014-18, but with high probability of poor
adherence
Now replaced by more feasible as-needed controller options for Step 1
Step 1 - other controller option
116.
117. Step 2 – there are two ‘preferred’ controller options
1- Regular low dose ICS with as-needed SABA
For patients requiring Step 2 treatment, GINA 2019 has retained the
previous recommendation for preferred controller treatment as daily low
dose ICS with as needed SABA .
This is based on cumulative evidence demonstrating that regular low dose
use substantially reduces asthma symptoms, increases lung function,
improves QoL and reduces risks of severe exacerbations, hospitalizations
or death.
118. Step 2 – there are two ‘preferred’ controller options
1- Regular low dose ICS with as-needed SABA
For patients requiring Step 2 treatment, GINA 2019 has retained the
previous recommendation for preferred controller treatment as daily low
dose ICS with as needed SABA .
This is based on cumulative evidence demonstrating that regular low dose
use substantially reduces asthma symptoms, increases lung function,
improves QoL and reduces risks of severe exacerbations, hospitalizations
death.
Poor adherence with ICS is common in mild asthma , and that this would
expose patients to the risks of SABA-only treatment .
119. Step 2 – there are two ‘preferred’ controller options
2- As-needed low dose ICS-formoterol (off-label; all evidence with budesonide-
formoterol)
Another preferred controller option in Step 2 in the 2019 GINA
recommendations is the newly included, as-needed low dose ICS-formoterol
label) combination which reflects the clinical concern of non-adherence to
low dose ICSs in people with milder forms of asthma (needing Step 1 and Step
treatment) and resultant exposure to SABA monotherapy with such non-
adherence,
120. Step 2 – other controller options
1- Low dose ICS taken whenever SABA taken (off-label, separate or combination
inhalers)
2-Another option: leukotriene receptor antagonist (less effective for
exacerbations)
130. The new GINA 2019 report highlights significant updates in mild asthma
management and these recommendations represent a clear deviation
from decades of clinical practice mandating the use of symptom-driven
SABA treatment alone in those with mild asthma.
Budesonide/formoterol (ICS/LABA; Symbicort) is being recommended
as the new rescue inhaler for Step 1 therapy in asthma (i.e. Mild
asthma). Traditionally albuterol (SABA) has always been the rescue
inhaler.
131. We have learned that the pathophysiology of asthma involves
inflammatory pathways, not just bronchoconstriction, so using an
ICS/LABA combo mechanistically makes more sense.
The Sygma & Novel Start trials both have shown budesonide/formoterol
PRN to be more effective in reducing asthma exacerbations than SABA's,
which is why GINA has made this big change in recommendations.
132. As-needed low dose ICS-formoterol now the preferred reliever at all
Steps (1-5), displacing as needed SABA to ‘other reliever’ according to
the latest GINA guideline.
The new inclusions of strategies such as symptom-driven (as-needed)
ICS-formoterol and “ICS taken whenever SABA is taken” are based on
several key trials.
It is important to note though that this is still an off-label use at this
point, but the evidence is there.
