6. 6
• a chronic inflammatory disorder of the airways …… in
susceptible individuals, inflammatory symptoms are
usually associated with widespread but variable airflow
obstruction and an increase in airway response to a
variety of stimuli.
• Obstruction is often reversible, either spontaneously
or with treatment.
Asthma definition
7. 7
• Diagnosis of asthma is a clinical one….there is no
standardised definition of the type, severity or frequency
of symptoms, nor of the findings on investigation.
• Presence of symptoms…wheeze, cough, breathlessness,
chest tightness… airway hyperresponsiveness…airway
inflammation…
13. 13
• Inflammation in asthma patients can be present
during symptom-free periods:
– Symptoms resolve quickly. Inflammation, however, as
measured by airway hyperresponsiveness, takes far longer
• As chronic inflammation causes an increase in airway
hyperresponsiveness, if the inflammation is not
controlled, symptoms are likely to reoccur.
20. 20
In patients with a high probability of asthma:
Record the patient as likely to have asthma and commence
a carefully monitored initiation of treatment (typically 6-
weeks of inhaled steroids)
Assess status with a validated symptom questionnaire
and/or lung function (FEV1 at clinic visits or by domiciliary
serial peak flows)
In those with a good objective response to treatment,
confirm the diagnosis of asthma
If response is poor, check adherence and inhaler technique,
arrange further tests & consider alternative diagnoses.
30. 30
Aim of management
Aim of asthma management is to control the disease
Complete Control is defined as
1. No daytime symptoms
2. No night-time awakening due to asthma
3. No need for rescue medication
4. No asthma attacks
5. No limitations on activity including exercise
6. Normal lung function (in practical terms FEV1 and/or
PEF>80% predicted or best)
7. Minimal side effects from medication.
31. 31
Underlying principles of management
•Before initiating drug
treatment check
– Compliance with
existing treatment
– Inhaler technique
– Eliminate trigger factors
34. How do we apply the
stepwise approach?
• Start treatment at the step most
appropriate to initial severity
• Achieve early control
Maintain control
by stepping up
treatment as
necessary.
35. Stepping down
Ensure regular review of
patients as treatment is
stepped down
Decide which drug to step
down first and at what rate
When control is
good,
step down
39. 39
• For those with mild-intermittent asthma or
exercise-induced asthma, occasional use of
reliever therapy may be the only treatment
required.
40. 40
• The following medicines act as short-acting
bronchodilators:
Inhaled short-acting β 2 agonists
Inhaled ipratropium bromide
β 2 agonist tablets or syrup
Theophyllines.
• Inhaled SABA works more quickly and/or with
fewer side effects than the alternatives
41. 41
• Prescribe an inhaled short-acting β2 agonist as
short term reliever therapy for all patients
with symptomatic asthma.
43. 43
Salbutamol is the commonly used inhaled bronchodilator
therapy .
It is a short- acting ß-2 agonist, has a rapid onset of action
(within five minutes) and usually provides 4–6 hours of
bronchodilation.
It should be used as a reliever therapy and is in the first
step of all guidelines on asthma management.
44. 44
The use of albuterol syrup has fallen out of favor over
the past decade with the advent of better modalities of
targeted, inhaled delivery systems (e.g., MDI with
spacer/holding chamber, nebulizer solution).
• AAAAI Guidelines (2004, p88) prefer inhaled beta2-
agonists to oral because higher concentrations are
delivered more effectively to the airways, the onset of
action is substantially shorter, and systemic side effects
can be avoided or minimized.
• Authors concluded lack of updated information was a possible reason that community-
based PCPs continued to prescribe syrup.
Special Consideration – Albuterol Syrup
45. 45
It is important that while reviewing a patient with asthma,
the practitioner establishes how often the patient needs the
reliever therapy.
Need for frequent bronchodilator therapy, especially for
interval symptoms such as exercise intolerance or night
coughs, may indicate escalation of therapy – i.e. initiation
of step 2 of asthma management.
46. 46
Increasing use of SABA treatment or the use of SABA >
2 days a week for symptom relief (not prevention of EIB)
generally indicates inadequate asthma control and the
need for initiating or intensifying anti-inflammatory
therapy.
Regularly scheduled, daily, chronic use of SABA is not
recommended.
47. 47
The use of short-acting inhaled beta2-agonists
on a daily basis, or increasing use, indicates
the need for additional long term control
therapy.
48. 48
Good asthma control is associated with little or no need for
short-acting β2 agonist.
Anyone prescribed more than one short acting bronchodilator
inhaler device a month should be identified and have their
asthma assessed urgently and measures taken to improve
asthma control if this is poor.
51. 51
• Inhaled corticosteroids are the recommended
& most effective preventer drug for adults and
children with asthma , for achieving overall
treatment goals.
52. 52
• There is an increasing body of evidence demonstrating
that, at recommended doses, ICS are also safe and
effective in children under five with asthma.
53. 53
o ICS Should be considered for adults, children aged
5–12 &children under the age of five with any of
the following features :
– Using inhaled SABA three times a week or more
– Symptomatic three times a week or more
– Waking one night a week
In addition, ICS should be considered in adults & children
aged 5–12 who have had an asthma attack requiring oral
corticosteroids in the last two years
54. 54
In mild to moderate asthma, starting at very high doses
of ICS and stepping down confers no benefit.
Start patients at a dose of inhaled corticosteroids
appropriate to the severity of disease.
A reasonable starting dose of inhaled corticosteroids will
usually be low dose for adults and very low does for
children .
Starting dose of inhaled steroid
55. 55
The doses of ICS are expressed as very low (generally
paediatric doses), low (generally starting dose for
adults), medium and high .
Adjustments to doses will have to be made for other
inhaler devices and other corticosteroid molecules
60. 60
• In adults, a reasonable starting dose of inhaled
corticosteroids will usually be 400 micrograms BDP
per day and in children 200 micrograms BDP per day.
• Titrate the dose of inhaled corticosteroid to the
lowest dose at which effective control of asthma is
maintained
61. 61
Is important that while considering a change of the type of
steroids or inhaler device used (e.g.Turbohaler), equivalent
doses of inhaled steroids relative to beclometasone are
given before the change is initiated to avoid any inadvertent
risk of overdosing with steroids.
62. 62
BDP and budesonide are approximately equivalent in clinical
practice, although there may be variations with different delivery
devices.
At present a 1:1 ratio should be assumed when changing between
BDP and budesonide.
Fluticasone provides equal clinical activity to BDP& budesonide
at half the dosage
Mometasone appears to provide equal clinical activity to BDP
and budesonide at half the dosage.
COMPARISON OF INHALED CORTICOSTEROIDS
63. 63
Most current ICS are slightly more effective when taken
twice rather than once daily, but may be used once daily
in some patients with milder disease and good or
complete control of their asthma.
There is little evidence of benefit for dosage frequency
more than twice daily.
Give inhaled corticosteroids initially twice daily (except
ciclesonide which is given once daily).
Frequency of dosing of inhaled corticosteroids
64. 64
ICS usage as a preventer therapy should be
explained to the patients in simple, plain terms.
66. 66
The safety of ICS is of crucial importance and a balance
between benefits and risks for each individual needs to
be assessed.
Account should be taken of other topical steroid therapy
when assessing systemic risk
In adults there is little evidence that low doses cause any
short term detrimental effects apart from the local side
effects of dysphonia and oral candidiasis. However, the
possibility of long term effects on bone has been raised.
67. 67
While the use of ICS may be associated with adverse
effects (including the potential to reduced bone mineral
density) with careful ICS dose adjustment this risk is
likely to be outweighed by their ability to reduce the
need for multiple bursts of oral corticosteroids.
Titrate the dose of inhaled corticosteroid to the lowest
dose at which effective control of asthma is maintained.
68. 68
1. Oropharyngeal candidiasis
2. Hoarseness
3. Coughing
To reduce the potential for adverse affects:
Use the lowest dose necessary to maintain control.
Administer with spacers/holding chambers.
Advise patients to (Rinse with water , gargle and
spit out) after inhalation.
Local side effects
73. Children’s Healthcare of Atlanta
Dose, drug, &
route dependent
ICS for Asthma: Benefits and Risks
Reduces
inflammation
Most effective
long-term control
medication for
asthma*
Decreases
morbidity / mortality
Generally known
and can be
monitored
Benefits
Risks
74. 74
• Current and previous smoking reduces the effect of ICS,
which may be overcome with increased doses.
• Patients should be advised that smoking reduces the
effectiveness of therapy.
• Clinicians should be aware that higher doses of inhaled
corticosteroids may be needed in patients who are
smokers or ex-smokers
Smoking & Inhaled corticosteroids
75. 75
Stepping down therapy once asthma is controlled is
recommended , but often not implemented leaving some
patients overtreated.
Patients should be maintained at the lowest possible dose
of inhaled corticosteroid.
Reduction in inhaled corticosteroid dose should be slow
as patients deteriorate at different rates.
76. 76
Stepping down therapy
Reductions should be considered every three months,
decreasing the dose by approximately 25–50% each time.
Regular review of patients as treatment is stepped down
is important .
77. 77
• Inhaled steroids are the first choice
– Alternative initial preventer therapies are available
but are less effective than ICS
• LTRA
• Theophyllines
• Antihistamines and ketotifen are ineffective
79. Treatment Options for adult Patients
Not Controlled on Inhaled Steroids
Patients not controlled on inhaled steroids
Increase the
dose of inhaled
steroid
Add leukotriene
receptor
antagonists
Add long-acting
beta2-agonists
Add
theophylline
82. 82
A proportion of patients with asthma may not be
adequately controlled at step 2 (with low-dose ICS
alone).
Before initiating a new drug therapy practitioners
should recheck adherence , inhaler technique and
eliminate trigger factors.
Initial add on therapy
83. 83
Fate of inhaled drugs – Good Technique
Swallowed
GI tract
Deposited in lung
Lungs
Metabolism or absorption
from the lung
Liver
Oral
bioavailability
Absorption
from gut
First-pass
metabolism
Systemic
Circulation
Mouth
pharynx
mucociliary
clearance
80%
20%
Schematic representation of potential dose distribution
A Guide to Aerosol Delivery Devices for Respiratory Therapists. American Association for
Respiratory Care. 1st Edition. Page 1.
Webpage: http://www.aarc.org/education/aerosol_devices/
Adapted from Barnes et al. AJRCCM 1998;157:S1-S53
84. 84
Fate of inhaled drugs – Good Technique
Swallowed
GI tract
Deposited in lung
Lungs
Metabolism or absorption
from the lung
Liver
Oral
bioavailability
Absorption
from gut
First-pass
metabolism
Systemic
Circulation
Mouth
pharynx
mucociliary
clearance
80%
20%
Schematic representation of potential dose distribution
A Guide to Aerosol Delivery Devices for Respiratory Therapists. American Association for
Respiratory Care. 1st Edition. Page 1.
Webpage: http://www.aarc.org/education/aerosol_devices/
Adapted from Barnes et al. AJRCCM 1998;157:S1-S53
Swallowed
GI tract
Deposited in lung
Lungs
Metabolism or absorption
from the lung
Liver
Oral
bioavailability
Absorption
from gut
First-pass
metabolism
Systemic
Circulation
Mouth
pharynx
mucociliary
clearance
95%
5%
Schematic representation of potential dose distributionAdapted from Barnes et al. AJRCCM 1998;157:S1-S53
A Guide to Aerosol Delivery Devices for Respiratory Therapists. American Association for
Respiratory Care. 1st Edition. Page 1.
Webpage: http://www.aarc.org/education/aerosol_devices/
Fate of inhaled drugs – Poor Technique
85. 85
No exact dose of ICS can be deemed the correct dose
at which to add another therapy.
The addition of other treatment options to ICS has
been investigated at doses from 200–1,000 micrograms
BDP in adults and up to 400 micrograms BDP in
children
86. 86
Many patients will benefit more from add-on therapy
than from increasing ICS above doses as low as 200
micrograms BDP/day.
At doses of ICS above 800 micrograms BDP/day side
effects become more frequent.An absolute threshold
for introduction of add-on therapy in all patients
cannot be defined.
88. 88
In children over five,, options for initial add-on
therapy are limited to LABA and LTRA, with evidence
to support both individually, but insufficient evidence to
support use of one over the other
LABA are not licensed for use in children under
5 years of age
90. Children’s Healthcare of Atlanta
• Recent data indicating a possible increased risk of asthma
Related death associated with use of LABA in a small
group of individuals has resulted in increased emphasis
on the message that:
• LABA should not be used as monotherapy in asthma &
must only be used in combination with an appropriate
dose of ICS.
91. 91
Long-acting inhaled β2 agonists should only be started in
patients who are already on inhaled corticosteroids, and
the inhaled corticosteroid should be continued.
The benefits of these medicines used in conjunction with
ICS in the control of asthma symptoms outweigh any
apparent risks.
SAFETY OF LONG-ACTING Β2 AGONISTS
92. 92
In efficacy studies, where there is generally good adherence,
there is no difference in efficacy in giving ICS and a LABA
in combination or in separate inhalers.
In clinical practice, however, it is generally considered that
combination inhalers aid adherence and also have the
advantage of guaranteeing that the LABA is not taken
without the ICS
102. 10
2
In selected adult patients who are poorly controlled
with ICS and LABA or in selected adult patients on
medium dose ICS alone:
You can use of budesonide/formoterol in a single
inhaler as rescue medication instead of a short-acting
β2 agonist, in addition to its regular use as controller
therapy has been shown to be an effective treatment
regimen
103. 10
3
Single inhaler therapy (combining maintenance and reliever
therapy) in patients already on ICS/LABA combinations
reduces the number of asthma attacks requiring oral
steroids or hospitalisation but may increase the number
of adverse events.
Patients taking rescue budesonide/formoterol once a day or
more on a regular basis should have their treatment
reviewed.
Combination inhalers used as maintenance and reliever
therapy are not licensed for children under the age of 18.
106. 10
6
If control remains poor on a low dose ICS
plus a LABA:
1) Re-check the diagnosis
2) Assess adherence to existing medication
3) Check inhaler technique before stepping up therapy.
107. 10
7
If there is no improvement when a LABA is
added to a low dose ICS, Stop the LABA and
try:
An increased dose of ICS (from low dose to medium
dose in adults)
Add LTRA
Add long acting muscarinic antagonist (LAMA)
113. 11
3
If there is an improvement when a LABA is
added to a low dose ICS, but control remains
inadequate: :
Continue LABA and increase the dose of ICS (from
low dose to medium dose in adults)
Continue LABA and ICS and add LTRA or LAMA
or a theophylline
114. 11
4
There is insufficient evidence to suggest that addition
of LAMA to ICS in patients inadequately controlled
on ICS alone has any benefit over addition of LABA
to ICS.The addition of LABA to ICS remains the first
choice for add-on treatment in adults.
In adults with asthma who do not respond to ICS
plus LABA, the addition of LAMA to ICS is a possible
alternative .
115. 11
5
Theophyllines may improve lung function & symptoms,
but side effects occur more commonly .
Slow-release β 2 agonist tablets may also improve lung
function and symptoms, but side effects occur more
commonly.
Addition of short-acting anticholinergics is generally of
no value.
118. 11
8
If control remains inadequate on medium dose of
ICS plus LABA, the following interventions can
be considered:
1. Increase the ICS to high dose (adults) or
2. Add a leukotriene receptor antagonist or
3. Add a SR theophylline or
4. Add slow release β2 agonist tablets, although caution
needs to be used in patients already on long-acting β2
agonists or
5. Add a long acting muscarinic antagonists(LAMA).
119. 11
9
There are no controlled trials indicating which of these
is the best option, although the potential for side
effects is greater with theophyllines and β2 agonist
tablets.
If a trial of an add-on treatment is ineffective, stop the
drug (or in the case of increased dose of inhaled
corticosteroid, reduce to the original dose).
122. 12
2
Some patients with very severe asthma not controlled at
step 5 with high-dose ICS, and who have also been tried
on or are still taking long-acting β-agonists, leukotriene
antagonists or theophyllines, require regular long-term
steroid tablets.
Steroid tablets in the lowest dose providing adequate
control.
Prednisolone is the most widely used steroid for
maintenance therapy in patients with chronic asthma..
123. 12
3
ANTI-IgE MONOCLONAL ANTIBODY
Omalizumab is a humanised monoclonal antibody which
binds to circulating IgE, reducing levels of free serum IgE.
In adults and children over 6 years of age, it is licensed in
the UK with the following indication: patients on high-
dose ICS and long-acting β2 agonists who have impaired
lung function, are symptomatic with frequent asthma
attacks, and have allergy as an important cause of their
asthma.
124. 12
4
Omalizumab is given as a subcutaneous injection every
two or four weeks depending on IgE level and weight.
The total IgE must be <1,300 international units
(IU)/ml for children over 6 years of age.
In adults and children >12 years, the licensed indication
is a IgE up to 1,500 IU/ml but there is no published
data to support its efficacy and safety above 700 IU/ml.
125. 12
5
Local skin reactions may occur ,Anaphylaxis, presenting
as bronchospasm, hypotension, syncope, urticaria, and/or
angioedema of the throat or tongue has been reported
to occur after administration of omalizumab.Anaphylaxis
has occurred as early as the first dose, but has also
occurred after one year.
Due to risk of anaphylaxis, omalizumab should only be
administered to patients in a healthcare setting under
direct medical supervision.
126. 12
6
Omalizumab given by subcutaneous injection may be
considered in patients with a high steroid burden to
reduce the steroid burden for the patient.
Omalizumab treatment should only be initiated in
specialist centres with experience of evaluation and
management of patients with severe and difficult
asthma.
127. 12
7
Stepping down therapy once asthma is controlled is
recommended, but often not implemented leaving
some patients overtreated..
Regular review of patients as treatment is stepped
down is important.
