Pediatric Asthma

4
Pharmacological
Management
of Asthma in Children 5 Years and
Younger Based on Different Global
Guidelines

5
Asthma is the most common chronic disease of
childhood & the leading cause of childhood morbidity
from chronic disease as measured by school
absences, emergency department visits and
hospitalizations.
Asthma Typically begins in early childhood, with
earlier onset in males than females .
Burden of Asthma in Children

6
Atopy is present in the majority of children with asthma
who are over 3 years old, and allergen-specific
sensitization is one of the most important risk factors
for the development of asthma.
However, no intervention has yet been shown to
prevent the development of asthma, or modify its long-
term natural course.

7
Asthma is a heterogeneous disease, usually
characterized by chronic airway inflammation.
It is defined by the history of respiratory symptoms
such as wheeze, shortness of breath, chest tightness
and cough that vary over time and in intensity,
together with variable expiratory airflow limitation.
NEW!

Children’s Healthcare of Atlanta
Pathology of Asthma
Inflammation
Airway Hyper-responsiveness Airway Obstruction
Symptoms of Asthma

9
Unfortunately…asthma is a major cause of
chronic morbidity and mortality throughout the
world and there is evidence that its prevalence
has increased considerably over the past 20
years, especially in children.
Fortunately…asthma can be effectively
treated and most patients can achieve good
control of their disease.
Global Initiative for Asthma (2012)

10
• Asthma is a common heterogeneous disorder in
children, the prevalence of asthma in Western
countries is around 10%.
• Many young children, approximately 30% of all
children, have airway symptoms like cough and
wheeze. However, only 1/3 of these children with
symptoms will develop asthma later in life.

11
• Asthma diagnosis in this age group is difficult
• Respiratory symptoms (wheezing and cough) also
common in children without asthma
• Not possible to routinely assess airflow limitation
(spirometry)
Diagnosis of Asthma in Children 5 Years
and Younger

12
Wheezing—Asthma?
Wheezing with upper respiratory infections is very
common in small children, but:
Many of these children will not develop asthma.
Asthma medications may benefit patients who
wheeze whether or not they have asthma.
All that wheezes is not
asthma.

• Parents often use wheezing as a non-specific label
to describe any abnormal respiratory noise.
• It is important to distinguish wheezing – a
continuous, high-pitched musical sound coming from
the chest – from other respiratory noises, such as
stridor .

14
• Wheezing is one of the most problems for which
preschool children are seen in the pediatrician's
office.
• Further, children who wheeze once are likely to
wheeze again, making recurrent wheeze a frequent
problem.
• Many parents who report “wheezing” or “noisy
breathing” in their child expect a diagnosis of
asthma. However, not all wheezing is asthma

16
• Often the first question asked, either by the
parent or by the pediatrician, is “Does this
wheezing episode represent an asthma
diagnosis?” - The main issue still is the difficulty
in coming to a correct diagnosis.

17
• The parent, on the other hand, really wants to
know if their child will need medication and
treatment beyond the preschool years and is
obviously reluctant to subject their child to
medication when they appear well most of the
time

18
• Wheezing in preschool children is a heterogeneous
condition with multiple phenotypes.
Wheezy phenotypes:
Epidemiological patterns of wheezing
(Time trend-based classification)
 Temporal patterns of wheezing
(Symptom-based classification)

19
• Time trend-based classification: this system was
based on analysis of data from a cohort study,It
included :
1)Transient wheeze (symptoms began and ended
before the age of 3 years)
2)Persistent wheeze (symptoms began before the
age of 3 years and continued beyond the age of
6 years)
3)Late-onset wheeze (symptoms began after the
age of 3 years).

Natural History of Childhood Wheeze
Age (Years)
WheezingPrevalence
Non-atopic
wheezers
Transient early
wheezers
IgE-associated
wheeze/asthma
0 3 6
11
Martinez. J Allergy Clin Immunol 1999;104:S169-S174.

22
Epidemiological patterns of wheezing
Transient early wheezing
• Describes the pattern of respiratory symptoms
starting in the first year of life. Generally, transient
wheezing in infants is not associated with a family
history of asthma or allergic sensitization.
• The primary risk factor for this phenotype seems
to be reduced pulmonary function in infancy,
which remains low up to the age of 16.

23
• Other risk factors for transient wheezing include:
prematurity, male gender, prenatal maternal
smoking, as well as postnatal exposure to tobacco
smoke.
• Transient early wheeze characteristically resolves
around the age of 3.

24
• Passive prenatal smoking is associated with lower
lung function, probably due to underdevelopment
of the bronchial tree, and is the most important
and preventable risk factor for early transient
wheeze.

25
• Passive postnatal smoking has a negative effect
on all types of respiratory symptoms in infants and
preschool children and constitutes a significant
risk factor for upper airways infections,
bronchiolitis, worsening of asthma symptoms, and
decreased lung function.

28
Nonatopic wheezing
• attacks are principally due to recurrent
viral infections.
• Nonatopic wheezers have normal lung function in
early life but intermittent airways obstruction
secondary to viral infections.
• The origin of wheezing in these children is not
clear.

29
Persistent 'atopic' wheezing
• Develop asthma in later childhood, more often
have their first episode of wheeze after the first
year of life, discrete attacks with symptom-free
intervals, symptoms that worsen at night,
frequent symptoms, a family history of asthma,
elevated serum IgE and peripheral blood
eosinophilia.
• They have normal lung function in infancy but
develop airways obstruction in the first years of
life.

31
• In the large majority of wheezing infants,
wheezing is transient and benign. These
children neither need nor respond to asthma
medication and a wait-and-see policy before
trying medication is justified.
• The majority of wheezy infants will end up being
free of symptoms at the age of 6, and have no
indication for maintenance anti-inflammatory
drugs

32
• Eighty percent of the children who wheeze
during the first year of life do not wheeze after
the age of 3.
• Sixty percent of the children that wheeze in the
second year of life and 30-40% of those who
wheeze in the third year have stopped wheezing
when they are older than 3 years of age .

33
• The medical literature commonly cites
epidemiologic criteria such as wheezing in the
first 3 years of life, transient versus persistent
wheeze, or atopic versus nonatopic, but these
categories can be determined only
retrospectively and give no guide to treatment,
so are not useful for the clinician .

34
• Prospective allocation of individual children to
these phenotypes has been unreliable in ‘real-
life’ clinical situations, and the clinical
usefulness of these systems remains a subject
of active investigation.
• Defining wheezing via temporal patterns may be
more useful for the busy clinician.

35
• The European Respiratory Society Task Force
recommends differentiating wheezing phenotypes
that provide the pediatrician with some evidence
that can assist with treatment into:
1)Episodic viral wheezing
2)Multiple-trigger wheezing.

37
Episodic viral wheeze (EVW):
• The child wheezes only with usually clinically
diagnosed viral upper respiratory infections and is
otherwise totally symptom free (without
symptoms between these episodes).
• Recurrent wheezing occurs in a large proportion
of children aged 5 years or younger.

38
Viral-induced wheezing
• Many young children may wheeze with viral
infections wheezing in this age group is a highly
heterogeneous condition, and not all wheezing in
this age group indicates asthma.
• Therefore, deciding when wheezing with a
respiratory infection is truly an initial or recurrent
clinical presentation of childhood asthma is
difficult .

39
• Wheezing episodes are generally associated with
a clinical diagnosis of viral upper respiratory tract
infection (URTI). Rhinovirus, respiratory syncytial
virus (RSV), coronavirus, parainfluenza virus, and
adenovirus are commonly cited in research
studies
• Possible underlying factors include preexisting
impaired lung function, tobacco smoke exposure,
prematurity, and atopy

40
The commonest clinical pattern, especially in pre-
school children and infants, is episodes of
wheezing, cough and difficulty breathing
associated with viral upper respiratory infections
(colds), with no persisting symptoms.
Most of these children will stop having recurrent
chest symptoms by school age.

41
Repeated episodes commonly occur seasonally,
and some children experience severe symptoms
from these wheezing episodes..
In most children episodic viral wheezing declines
over time, but it can persist into school age or
become multiple-trigger wheezing.

42
It does not appear that children with episodic viral
wheezing have an increased risk of atopy or
respiratory symptoms after age 14 years.
Additionally, there is no evidence that treatment
with any particular drug in a preventive manner will
prevent future airway remodeling, airflow
obstruction, or prevent asthma

43
A minority of those who wheeze with viral
infections in early life will go on to develop
wheezing with other triggers so that they develop
symptoms between acute episodes (interval
symptoms) similar to older children with classical
atopic asthma
Children who have persisting or interval
symptoms are most likely to benefit from
therapeutic interventions.

44
Multiple trigger wheeze (MTW):
 Viral illness is not the only trigger for wheezing
episodes, which can also include other triggers such
as exercise , smoke and allergen exposure.
 Patients in this category demonstrate symptoms
between episodes.

45
 Multiple trigger wheeze is associated with more
airflow obstruction than episodic viral wheeze,
and the airway pathology (eosinophilic
inflammation and remodelling) is similar to
childhood and adult asthma.
 By contrast, episodic viral wheeze is not
associated with evidence of eosinophilic
inflammation, so the use of inhaled
corticosteroids in this group is questionable.

48
What are the broad treatment strategies for
children with preschool wheeze?
Before any drugs are prescribed for either episodic
viral wheeze or multiple trigger wheeze, it is essential
to ensure that the home environment is optimal,
particularly that the child is not exposed to tobacco
smoke; parental smoking “not in front of the children”
does not protect them from harm
A birth cohort study found that air pollution can
increase vulnerability to preschool wheeze

50
Treating episodic viral wheeze
• Intermittent symptoms should be treated with
intermittent therapy (and in practice this is likely to
be what parents do anyway).
• Intermittent symptoms are best treated with
intermittent therapy, with short-acting
bronchodilators usually being first-line therapy.
• If additional therapy is required, ICSs, leukotriene
modifiers, or combination therapy are options.

51
• If treatment needs to be escalated beyond
intermittent β2 agonist or anticholinergic because
of failure to control symptoms, the next options are
intermittent leucotriene receptor antagonist
(montelukast), intermittent inhaled corticosteroids,
or both.
• Treatment was initiated at the onset of symptoms
of a respiratory tract infection and continued for a
minimum of a week or until symptoms had
disappeared for 48 hours.

52
• Studies suggest that a trial of montelukast in
preschool children with troublesome viral induced
wheeze is worth attempting.
• Intermittent ICS for the treatment of episodic viral
wheezing is partially effective as a strategy for the
treatment of mild episodic viral wheeze of
childhood.

53
• No current evidence favors maintenance low-
dose ICS in the prevention and management of
episodic mild viral-induced wheeze
• There is no evidence to support the use of
regular inhaled corticosteroids in preschool
children who do not wheeze between viral colds.

54
• In those children with really severe episodic
wheeze who require repeated admission to
hospital or have prolonged disruptive symptoms
managed at home, however, a trial of
prophylactic inhaled corticosteroids can be
given.
• Trials should be short, however, with close
monitoring of symptoms and rapid stopping if
there is no improvement or decreasing doses as
tolerated .

55
• Treatment should be reviewed and discontinued
if there is no benefit.
• There is no evidence to suggest the optimal
duration of the therapeutic trial, but six to eight
weeks would seem a reasonable time period.
• If the viral wheezing improves on treatment,
regular attempts should still be made to reduce
the dose.

56
• Whatever the context of therapeutic trials in
preschool children, they should be for a fixed time
period (such as six to eight weeks) and
discontinued at the end of the agreed period to see
if symptoms recur or in fact have resolved and
treatment has become unnecessary

57
• Any preschool child with acute episodes of episodic
viral induced wheeze who is well enough to stay in
the community should not be prescribed oral
prednisolone
• it is likely that prednisolone will continue to be
prescribed in this small subgroup of children in
hospital. really severe preschool viral wheeze

58
• Importantly, there is no evidence to support the
use of antibiotics for the treatment of episodic
viral wheeze unless the pediatrician believes a
bacterial infection is present.

59
• Treating multiple-trigger wheeze with
continuous, standard-dose ICS is more
successful than it is in episodic viral wheeze.
• Given preschool children with a history of
wheezing, cough, and other symptoms
responsive to bronchodilators who remain
symptomatic, a trial of preventive therapy is
warranted.
Treating multiple-trigger wheeze

60
• Preschool children who have wheeze or cough
responsive to bronchodilator treatment and
breathlessness on most days even when they do
not have a viral cold should be considered for a trial
of preventive drug treatment, either inhaled
corticosteroids or a leucotriene receptor antagonist
(montelukast).
• Long acting β2 agonists are not licensed for use in
preschool children.

61
Pragmatic regimen for trial of treatment
• In a recent 2014 review, researchers recommend
a 3-step approach for preschoolers with
multiple- trigger wheeze:
Step 1: Trial of inhaled corticosteroids or
montelukast in standard dose for a defined period,
usually four to eight weeks
Step 2: Stopping treatment because symptoms
have not improved or have disappeared.

62
Pragmatic regimen for trial of treatment
Stop treatment; either there has been no
improvement, in which case further escalation is not
valuable, referral for consideration of further
investigation is recommended , or symptoms have
disappeared; in the latter case, it is not possible to
know if this was spontaneous or as a result of
treatment.
Step 3: Restart treatment only if symptoms recur;
then reduce treatment to the lowest level that

65
 Wheezing episodes in young children should be
treated initially with inhaled short-acting beta2-
agonists, regardless
of whether the diagnosis of asthma has been made.
 A trial of controller therapy should be given if the
symptom pattern suggests asthma & respiratory
symptoms are uncontrolled and/or wheezing
episodes are frequent or severe.
.

66
Therapeutic trial
A trial of treatment for at least 2–3 months with as-
needed short-acting beta2-agonist (SABA) and regular
low dose inhaled corticosteroids (ICS) may provide
some guidance about the diagnosis of asthma
(Evidence D).
Response should be evaluated by symptom control
(daytime and night-time), and the frequency of
wheezing episodes and exacerbations.

67
Therapeutic trial
Marked clinical improvement during treatment, and
deterioration when treatment is stopped, support a
diagnosis of asthma.
Due to the variable nature of asthma in young
children, a therapeutic trial may need to be
repeated in order to be certain of the diagnosis

69
 Preschool wheeze should be divided into
“episodic viral” and “multiple trigger” according to
the history, and these categories, which can change
over time, should be used to guide treatment
 No treatment has been shown to prevent
progression of preschool wheeze to school age
asthma, so treatment is driven solely by current
symptoms

70
 In all but the most severe cases, episodic
symptoms should be treated with episodic treatment
 If trials of prophylactic treatment are
contemplated, they should be discontinued at the
end of a strictly defined time period because many
respiratory symptoms remit spontaneously in
preschool children

71
• Young children who present with symptoms of
cough, wheeze, and shortness of breath may have
either viral-associated respiratory problems that
may not persist into later childhood or may have
an asthmatic pattern of airway inflammation that
may subsequently develop into asthma
• Further, the younger the child the less likely true
inflammation will be present

72
• In preschool children many will no longer have
symptoms when becoming school aged, it is
important to remember that not all children with
multiple-trigger wheeze have asthma
pathophysiology.
• Both phenotypes are lacking, however, in that they
will not identify children who will go on to develop
asthma, children who will outgrow their symptoms

73
Does preschool wheezing lead to
asthma?

77
Diagnosis of asthma in children
5 years and younger

78
• Spirometric lung function are difficult to perform
in young children, because active cooperation is
a prerequisite for successful measurements.
• In preschool children, therefore, the diagnosis is
usually purely clinical.

79
The diagnosis of asthma in preschool children is
based on recognising a characteristic pattern
of episodic respiratory symptoms and signs in
the absence of an alternative
explanation, the diagnosis is
usually purely clinical.

80
Does wheezing mean that I have
asthma?

81
What is Asthma?
A clinical diagnosis
Diagnosing Asthma-Not Easy

82
• 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.
Clinical Diagnosis of Asthma

83
• It may be difficult to make a confident diagnosis
of asthma in children 5 years and younger,
because episodic respiratory symptoms such as
wheezing and cough are also common in
children without asthma, particularly in those 0–2
years old.

• Furthermore, it is not possible to routinely
assess airflow limitation in this age group.
Clinical Diagnosis of Asthma

85
Probability of asthma
diagnosis

86
• Many young children wheeze with viral infections, and
deciding when a child should be given controller
treatment is difficult.
• A diagnosis of asthma in young children is therefore
based largely on symptom patterns combined with a
careful clinical assessment of family history and
physical findings.

87
• A positive family history of allergic disorders or the
presence of atopy or allergic sensitization provide
additional predictive support .
• Early allergic sensitization increases the likelihood
that a wheezing child will develop persistent asthma .

88
Symptoms suggestive of asthma in
children 5 years and younger
1. Episodic Symptom patterns (wheeze, cough,
breathlessness typically manifested by activity
limitation, and nocturnal symptoms or awakenings) .
2. Presence of risk factors for development of asthma-
history of other allergic disease (eczema or allergic
rhinitis) or asthma in first-degree relatives .
3. Therapeutic response to controller treatment.
(Clinical improvement during 2–3 months of
controller treatment, and worsening after cessation).

89
• A probability-based approach, based on the
pattern of symptoms during and between viral
respiratory infections, may be helpful for
discussion with parents/carers .
• This approach allows individual decisions to be
made about whether to give a trial of controller
treatment.
• It is important to make decisions for each child
individually, to avoid either over- or under-

Diagnosis
*BTS/SIGN (May 2008). British Guideline on the Management of Asthma
• Clinical features that increase the
probability of asthma:
– More than one of the following
symptoms especially if frequent,
worse at night/early morning/after
exercise/exposure to triggers etc.
• Wheeze
• Cough
• difficulty breathing,
• chest tightness
• Atopic disorder
• FH of atopic disorder/asthma
• Improvement in symptoms or lung
function with adequate therapy
• Clinical features that lowerthe
probability of asthma:
– Symptoms with URTI only
– no interval symptoms
– isolated cough in the absence of
wheeze or difficulty breathing
– history of moist cough
– prominent dizziness, light-
headedness, peripheral tingling
– repeatedly normal physical
examination of chest when
symptomatic
– normal PEFR/spirometry when
symptomatic
– no response to a trial of asthma
therapy
– clinical features pointing to
alternative diagnosis

Diagnosis II
high probability of asthma:
– start a trial of treatment
– review and assess response
• reserve further testing for
those with a poor response

• low probability of asthma
– consider more detailed
investigation and specialist
referral
intermediate probability of
asthma
• In children with an intermediate
probability of asthma who cannot
perform spirometry, offer a trial of
treatment for a specified period:
― if treatment is beneficial, treat as
asthma and arrange a review
― if treatment is not beneficial, stop
asthma treatment, and consider
tests for alternative conditionsm
and specialist referral.

101
Pharmacological
Management
of Asthma in Children 5 Years and
Younger Based on Different Global
Guidelines

105
• Delivers medication directly to the airways
• Minimizes systemic side effects
• Faster onset of action
– Rescue medications
• Recommended by asthma guidelines
Advantages of Inhaled Therapy
in Patients With Asthma

106
Pharmacokinetics of Inhaled Drugs

107
Inhaled therapy constitutes the cornerstone of asthma
treatment in this young age group.

Asthma therapy
Controllers
 Inhaled corticosteroids
 Inhaled long-acting b2-
agonists
 Oral anti-leukotrienes
 Oral theophyllines
Relievers
 Inhaled fast-acting b2-agonists

Beclomethasone
Budesonide
Fluticasone
Inhaled corticosteroids

110
Controller medication
• Daily medications for all persistent asthma
Long term control
Anti-inflammatory
Reliever or Quick-relief medication
• Bronchodilators - As needed for all asthma severity
levels
Used PRN and preventative for EIA
Bronchodilators
Oral corticosteroid bursts
Controller vs. Reliever Meds

112
o Relaxes muscles in the airways to help relieve
asthma symptoms
o Should be taken as needed for symptoms
o Need to wait 1-2 minutes between puffs for best
deposition of medication in the lungs
o Overuse is a big warning sign indicating the
child’s asthma may not be well controlled
“Relievers” (Bronchodilators)

Guidelines from around the world

Clinical Control of Asthma in
Children 5 Years and Younger
Asthma is controlled (all of the following):
1)No (or minimal) daytime symptoms
2)No limitations of activity (Child is fully active, plays
and runs without limitations of symptoms)
3)No nocturnal symptoms (including no nocturnal
coughing during sleep)
4)No (or minimal) need for rescue medication

118
A. Symptom control
In the past 4 weeks, has the child had:
Well-
controlled
Partly
controlled
Uncontrolled
• Daytime asthma symptoms for more than
few minutes, more than once/week?
Yes No
None of
these
1-2 of
these
3-4 of
these
• Any activity limitation due to asthma?
(runs/plays less than other children,
tires easily during walks/playing)
Yes No
• Reliever needed* more than once a
week?
Yes No
• Any night waking or night coughing
due to asthma?
GINA assessment of asthma control in
children ≤5 years
Level of asthma symptom control

Pharmacotherapy Recommendations for Children 0 to
2 Years
Intermittent βIntermittent β22-agonists-agonists First choice despite conflicting evidenceFirst choice despite conflicting evidence
LTRALTRA Daily controller therapy for viral wheezing (long- orDaily controller therapy for viral wheezing (long- or
short-term treatment)short-term treatment)
Nebulized or inhaledNebulized or inhaled
corticosteroidscorticosteroids
Daily controller therapy for persistent asthmaDaily controller therapy for persistent asthmaaa
First-line treatment when there is evidenceFirst-line treatment when there is evidence
of atopy/allergyof atopy/allergy
Oral corticosteroidsOral corticosteroidsbb
Acute and frequently recurrent obstructive episodesAcute and frequently recurrent obstructive episodes
a
Especially if severe or requiring frequent oral corticosteroid therapy; b
eg, 1 to 2
mg/kg/day prednisone for 3 to 5 days during acute and frequently recurrent obstructive
episodes.
.
PRACTALL EAACI / AAAAI Consensus Report
Asthma diagnosis: >3 episodes of reversible bronchial obstruction
within 6 months

122
• Consider a diagnosis of asthma if >3 episodes of
reversible bronchial obstruction have been
documented within the previous 6 months
• Intermittent β2 agonists are first choice (inhaled, jet
nebulizers in the US and oral in Europe)
• LTRA daily controller therapy for viral wheezing
(long- or short-term treatment)
Asthma treatment in children aged
0–2 years

126
• Nebulized or inhaled (metered-dose inhaler and
spacer) corticosteroids as daily controller therapy for
persistent asthma, especially if severe or requiring
frequent oral corticosteroid therapy
• Evidence of atopy/allergy lowers the threshold for use
of ICS and they may be used as first-line treatment in
such cases
• Use oral corticosteroids (e.g. 1–2 mg/kg prednisone)
for 3–5 days during acute and frequently
recurrent obstructive episodes
0–2 years

INSUFFICIENT CONTROLb
Pharmacologic Treatment (Children >2 Years)
ICS
(200µg BDP equivalent)
LTRAa
(Dose depends on age)
INSUFFICIENT CONTROLc
Increase ICS dose (800 µg BDP equivalent)
OR
Add LTRA to ICS
OR
Add LABA
INSUFFICIENT CONTROLc
StepUpTherapytoGainControl
Stepdownif
appropriate
Stepdownif
appropriate
Consider other options
•Theophylline
•Oral corticosteroids
a
LTRA may be particularly useful if the patient has concomitant rhinitis; b
Check compliance, allergy avoidance, and reevaluate diagnosis;
c
Check compliance and consider referring to specialist.
ICS=inhaled corticosteroids; LTRA=leukotriene receptor antagonist; BDP=beclomethasone dipropionate; LABA=long-acting β2-agonist.
Increase ICS dose (400 µg BDP equivalent)
OR
Add ICS to LTRA
PRACTALL EAACI / AAAAI Consensus Report
OR

130
>2 years - 5 years
• ICS are the first choice, budesonide 100–
200 μg × 2 or fluticasone 50–125 μg × 2 by MDI
• Short-acting β2 agonists,
salbutamol 0.1 mg/dose or terbutaline 0.25 mg/dose
1–2 puffs at 4-h intervals as needed
• LTRA
can be used as monotherapy instead of ICS if
symptoms are intermittent or mild persistent
• If full control is not achieved with
ICS, add LTRA montelukast 4 mg granules or 4 mg
chewing tablet

131
>2 years - 5 years
• If control still not achieved consider the following
(nonsequential) options:
1.Add LABA at least intermittently (although note
lack of published evidence supporting use in this
age group)
2.Increase ICS dose
3.Add theophylline

132
PRACTALL consensus report advocates montelukast
as an initial controller therapy for mild persistent
asthma at an age-dependent dose in pediatric
patients
Promotes its use in viral-induced wheezing in children
0-5 years.
Some studies have shown that montelukast may be
used as short course therapy for viral-induced asthma
exacerbations or ‘episodic asthma’.

133
LTRA may be an especially appropriate choice in
patients with concomitant asthma and rhinitis.
•Another indication for LTRAs is as an alternative
agent for exercise-induced asthma due to its quick
onset and prolonged duration of action.

135
May 2009
Global Strategy for the
Diagnosis and
Management of
Asthma in Children 5
Years and Younger
May, 2009

Environmental control
As needed rapid-acting β2-agonists
Controlled on as
needed
rapid-acting β2-
agonists
Partly controlled on as
needed rapid-acting β2-
agonists
Uncontrolled on β2-agonists
prn. or partly controlled on a
low-dose inhaled
glucocorticosteroid
Controller options
Leukotriene modifier
Low-dose inhaled
glucocorticosteroid
plus leukotriene modifier
Low-dose
inhaled
glucocorticosteroid
Double low-dose
inhaled glucocorticosteroid
Continue as needed
rapid-acting β2-agonists
Asthma Management Approach Based on
Control for Children 5 Years and Younger
Oral glucocorticosteroids should be used only for treatment of acute severe exacerbations of asthma.
Green shaded boxes represent the preferred treatment options.

137
A pressurized metered dose inhaler with a valved
spacer (with or without a face mask depending on the
child’s age) is the preferred delivery system
(Evidence A).
A low-dose inhaled glucocorticosteroid is
recommended as the preferred initial treatment to
control asthma (Evidence A).

138
If low-dose inhaled glucocorticosteroid does not
control symptoms, and the child is using optimal
technique and is adherent to therapy,
doubling the initial dose of ICS may be the
best option (Evidence C).
(….continued)

139
 When doubling the initial dose of ICS fails to achieve
and maintain asthma control, the child’s inhalation
technique and compliance with the medication
regimen should be carefully assessed and monitored.
 Use of oral glucocorticosteroids should be restricted
to the treatment of acute severe exacerbations,
whether viral-induced or otherwise (Evidence D).

141
• Inhaled corticosteroids are the most effective
preventer drug for adults and older children for
achieving overall treatment goals.
• There is an increasing body of evidence
demonstrating that, at recommended doses, they
are also safe and effective in children under five
with asthma.

Dose, drug, &Dose, drug, &
route dependentroute dependent
Corticosteroids for Asthma: Benefits and
Risks
ReducesReduces
inflammationinflammation
Most effectiveMost effective
long-term controllong-term control
medication formedication for
asthma*asthma*
DecreasesDecreases
morbidity / mortalitymorbidity / mortality
Generally knownGenerally known
and can beand can be
monitoredmonitored
BenefitsBenefits
RisksRisks

143
Placebo-controlled studies of inhaled gluco-
corticosteroids in children 5 years and younger with
asthma provide statistically significant clinical effects
on (Evidence A):
1. Number of symptom-free days
2. Reduced symptoms
3. Need for additional medication
4. Caregiver burden
5. Systemic glucocorticosteroid use
6. Exacerbations

–This is not a table of equivalence
–A low daily dose is defined as the dose that has not been
associated
with clinically adverse effects in trials that included measures of
safety
‘Low dose’ inhaled corticosteroids (mcg/day)
for children ≤5 years
GINA 2015, Box 6-6
Inhaled corticosteroid Low daily dose (mcg)
Beclometasone dipropionate (HFA) 100
Budesonide (pMDI + spacer) 200
Budesonide (nebulizer) 500
Fluticasone propionate (HFA) 100
Ciclesonide 160
Mometasone furoate Not studied below age 4 years
Triamcinolone acetonide Not studied in this age group
GINA 2015, Box 6-6

145
Frequency of dosing of inhaled corticosteroids
• Give inhaled corticosteroids initially twice daily
(except ciclesonide which is given once daily).
• 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

Lower ICS Doses Are Associated With Fewer
Risks
Response
Pedersen et al. Allergy. 1997;52:1-34.
Dose
Therapeutic
Effects
Favorable
Benefit:Risk
Ratio
Undesirabl
e Effects

147
• Although dose–response curves have not been
established for every ICS formulation and for all
age-groups, efficacy appears to reach a plateau for
most patients and outcomes around or below
medium dose range .

148
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
and budesonide at half the dosage.

149
• Administration of ICS at or above 400
micrograms BDP a day or equivalent may be
associated with systemic side effects.
• Monitor growth (height and weight centile) of
children with asthma on an annual basis.

150
• The clinical benefit of ICS must be balanced
against potential risks, with linear growth
remaining the dominant concern.
• Several studies in older children have consistently
demonstrated a modest but significant effect (~1
cm in the first year)
• Risks for subcapsular cataracts or bone mineral
density reduction in childhood are very low.

151
• 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.
• The lowest dose of inhaled corticosteroids
compatible with maintaining disease control
should be used.

Choosing an Inhaler Device
A pressurized metered-dose inhaler (MDI) with a valved
spacer (with or without a face mask, depending on the
child’s age) is the preferred delivery system
Choosing an Inhaler Device
Age group Preferred device Alternative device
Younger than 4 years
Pressurized metered-dose
inhaler plus dedicated
spacer with face mask
Nebulized with face mask
4-5 years
spacer with mouth piece
spacer with mouth piece,
or
Nebulizer with
mouthpiece or face mask

153
• Candidiasis of the throat and mouth may occur,
particularly with higher doses of inhaled
corticosteroids.
• Strategies to reduce the risk include use of a
spacer and rinsing the mouth with water or
cleaning the teeth following inhalation .

Children’s Healthcare of Atlanta 155

Management <5Year
Step 1
• SABA
Step 2
• Inhaled steroids if:
– exacerbation of asthma in the last 2 years requiring oral
steroids
– using inhaled β2 agonists three times a week or more
– symptomatic three times a week or more
– waking one night a week
*Titrate steroid dose to lowest dose at which effective treatment maintained
• Leukotriene agonists if inhaled steroids not tolerated

Management <5
Step 3
• If taking inhaled steroid, add in leukotriene antagonist
• If taking leukotriene antagonist, add inhaled steroid
• If <2 year proceed to Step 4
Step 4
• Refer to respiratory paediatrician

Children < 5 years BTS 2014
• Step 1: Short acting Beta agonist
• Step 2: Inhaled Steroid (200-400mcg/day)
or
Leukotriene receptor antagonist
• Step 3: ICS or LRA
• Step 4: Refer to paeds
British Thoracic guidelines recommend the use of LTRAs
for children aged less than 5 years, they are indicated as
either monotherapy or add on therapy.

© Global Initiative for Asthma
GINA Global Strategy for Asthma
Management and Prevention 2015
This slide set is restricted for academic and educational purposes
only. Use of the slide set, or of individual slides, for commercial or
promotional purposes requires approval from GINA.
Diagnosis and management
of asthma in children
5 years and younger
GINA 2015

• Over the past 20 years, the Global Initiative for
Asthma (GINA) has regularly published and
annually updated a global strategy for asthma
management and prevention that has formed
the basis for many national guidelines.
• A probability-based approach to diagnosis and
treatment for wheezing children replaces
previous classifications by wheezing phenotype
162

Children’s Healthcare of AtlantaGINA 2015, Box 6-5 (3/8)
Infrequent
viral wheezing
and no or
few interval
symptoms
Symptom pattern consistent with asthma
and asthma symptoms not well-controlled, or
≥3 exacerbations per year
Symptom pattern not consistent with asthma but
wheezing episodes occur frequently, e.g. every
6–8 weeks.
Give diagnostic trial for 3 months.
Asthma diagnosis, and
not well-controlled on
low dose ICS
Not well-
controlled
on double
ICS
First check diagnosis, inhaler skills,
adherence, exposures
CONSIDER
THIS STEP FOR
CHILDREN WITH:
RELIEVER
Other
controller
options
PREFERRED
CONTROLLER
CHOICE
As-needed short-acting beta2-agonist (all children)
Leukotriene receptor antagonist (LTRA)
Intermittent ICS
Low dose ICS + LTRA Add LTRA
Inc. ICS
frequency
Add intermitt ICS
Daily low dose ICS
Double
‘low dose’
ICS
Continue
controller
& refer for
specialist
assessment
STEP 1 STEP 2
STEP 3
STEP 4
Stepwise approach – pharmacotherapy
(children ≤5 years)

For initiating treatment, asthma severity
should be classified
The initial treatment should correspond to
the appropriate severity category.

165
Make an initial assessment of the pattern of
asthma (infrequent intermittent, frequent
intermittent, or persistent) in children aged 0-5
years not taking regular preventers

INTERMITTENT
Step 1
PERSISTENT
Step 2
(Mild)
Step 3
(Moderate)
Step 4
(Severe)
Severity is classified before
therapy begins

167
Category
Pattern and intensity of symptoms (when
not taking regulartreatment)
Infrequent intermittent asthma Symptom-free for at least 6
weeks at a time (flare-ups up to
once every 6 weeks on average
but no symptoms between flare-
ups)
Frequent intermittent asthma Flare-ups more than once every
6 weeks on average but no
symptoms between flare-ups
Persistent
asthma
Mild At least one of:
•Daytime symptoms†
more than
once per week but not every day
•Night-time symptoms†
more
than twice per month but not
every week
Moderate Any of:
daily
more than
once per week
•Symptoms sometimes restrict
activity or sleep
Severe Any of:
continual
frequent
•Flare-ups frequent
•Symptoms frequently restrict

168
Asthma Severity Assessment
1. Intermittent vs. Persistent asthma:
a. Persistent asthma is diagnosed if the child has any of
the following:
o Symptoms more than twice per week during the day
o Symptoms twice per month at night
o Any exercise limitation
o FEV1 less than 80% predicted (for children over 5
years)
o Two or more steroid bursts for asthma in 12 months
2. Treat Persistent asthma with a daily controller
medication such as inhaled corticosteroids

Diagnosis
Symptom control & risk factors
Inhaler technique & adherence
Parent preference
Asthma medications
Non-pharmacological strategies
Treat modifiable risk factors
Symptoms
Exacerbations
Side-effects
Parent satisfaction
Control-based asthma
management cycle in children ≤5
years
GINA 2015, Box 6-5 (1/8)

170
A. Symptom control
In the past 4 weeks, has the child had:
Well-
controlled
Partly
controlled
Uncontrolled
• Daytime asthma symptoms for more than
few minutes, more than once/week?
Yes No
None of
these
1-2 of
these
3-4 of
these
• Any activity limitation due to asthma?
(runs/plays less than other children,
tires easily during walks/playing)
Yes No
• Reliever needed* more than once a
week?
Yes No
• Any night waking or night coughing
due to asthma?
GINA assessment of asthma control in
children ≤5 years
Level of asthma symptom control

Once treatment is established, the emphasis
is on assessing asthma control to determine
if the goals for therapy have been met and if
adjustments in therapy (step up or step
down) would be appropriate.

Stepwise Approach to Therapy:
Gaining Control
STEP4STEP4
Severe PersistentSevere Persistent
STEP3STEP3
Moderate PersistentModerate Persistent
STEP2STEP2
Mild PersistentMild Persistent
STEP1STEP1
IntermittentIntermittent
11 22
11.. Start high andStart high and
step down.step down.
2. Start at initial2. Start at initial
level of severity;level of severity;
gradually stepgradually step up.up.

Guidelines recommend a stepwise
approach

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.

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

Stepwise approach – pharmacotherapy
(children ≤5 years)
GINA 2015, Box 6-5 (3/8)
Infrequent
viral wheezing
and no or
few interval
symptoms
6–8 weeks.
low dose ICS
Not well-
controlled
on double
ICS
CONSIDER
THIS STEP FOR
CHILDREN WITH:
RELIEVER
Other
controller
options
PREFERRED
CONTROLLER
CHOICE
Intermittent ICS
Inc. ICS
frequency
Add intermitt ICS
Daily low dose ICS
Double
‘low dose’
ICS
Continue
controller
& refer for
specialist
assessment
STEP 1 STEP 2
STEP 3
STEP 4

Step 1 (children ≤5 years) –
as needed inhaled
SABA
GINA 2015, Box 6-5 (5/8)
Infrequent
viral wheezing
and no or
few interval
symptoms
6–8 weeks.
low dose ICS
Not well-
controlled
on double
ICS
CONSIDER
THIS STEP FOR
CHILDREN WITH:
RELIEVER
Other
controller
options
PREFERRED
CONTROLLER
CHOICE
Intermittent ICS
Inc. ICS
frequency
Add intermitt ICS
Daily low dose ICS
Double
‘low dose’
ICS
Continue
controller
& refer for
specialist
assessment
STEP 1 STEP 2
STEP 3
STEP 4

initial controller + as-needed
SABA
GINA 2015, Box 6-5 (6/8)
Infrequent
viral wheezing
and no or
few interval
symptoms
6–8 weeks.
low dose ICS
Not well-
controlled
on double
ICS
CONSIDER
THIS STEP FOR
CHILDREN WITH:
RELIEVER
Other
controller
options
PREFERRED
CONTROLLER
CHOICE
Intermittent ICS
Inc. ICS
frequency
Add intermitt ICS
Daily low dose ICS
Double
‘low dose’
ICS
Continue
controller
& refer for
specialist
assessment
STEP 1 STEP 2
STEP 3
STEP 4

medium dose ICS + as-needed
inhaled SABA
GINA 2015, Box 6-5 (7/8)
Infrequent
viral wheezing
and no or
few interval
symptoms
6–8 weeks.
low dose ICS
Not well-
controlled
on double
ICS
CONSIDER
THIS STEP FOR
CHILDREN WITH:
RELIEVER
Other
controller
options
PREFERRED
CONTROLLER
CHOICE
Intermittent ICS
Inc. ICS
frequency
Add intermitt
ICS
Daily low dose ICS
Double
‘low dose’
ICS
Continue
controller
& refer for
specialist
assessment
STEP 1 STEP 2
STEP 3
STEP 4

Step 4 (children ≤5 years) – refer
for expert assessment
GINA 2015, Box 6-5 (8/8)
Infrequent
viral wheezing
and no or
few interval
symptoms
6–8 weeks.
low dose ICS
Not well-
controlled
on double
ICS
CONSIDER
THIS STEP FOR
CHILDREN WITH:
RELIEVER
Other
controller
options
PREFERRED
CONTROLLER
CHOICE
Intermittent ICS
Inc. ICS
frequency
Add intermitt
ICS
Daily low dose ICS
Double
‘low dose’
ICS
Continue
controller
& refer for
specialist
assessment
STEP 1 STEP 2
STEP 3
STEP 4

• Preferred option: as-needed inhaled SABA
– Provide inhaled SABA to all children who experience
wheezing episodes
– Not effective in all children
• Other options
– Oral bronchodilator therapy is not recommended
(slower onset of action, more side-effects)
– For children with intermittent viral-induced wheeze and
no interval symptoms, if as-needed SABA is not
sufficient, consider intermittent ICS..
Step 1 (children ≤5 years) – as-needed inhaled
SABA
GINA 2015

184
• Oral preparations of beta2 agonists have been
used extensively in the past with children but are
less effective than inhaled preparations and
have more side-effects

185
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

186
• Salbutamol is the commonly used inhaled
bronchodilator therapy in children.
• 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.

187
• Prescribe an inhaled short-acting β2 agonist as
short term reliever therapy for all patients with
symptomatic asthma.
• No benefits have been shown from regular dosing.
• Good asthma control is associated with little or no
need for short-acting β2 agonist.

188
• 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.

189
• It is important that while reviewing a patient with
asthma, the practitioner establishes how often
the child 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.

190
• 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.
• Thus, patients overusing inhaled short-acting beta2
agonists should have their asthma management
reviewed

• Indication
– Child with symptom pattern consistent with asthma,
and symptoms not well-controlled, or ≥3
exacerbations per year
– May also be used as a diagnostic trial for children
with frequent wheezing episodes
• Preferred option: regular daily low dose ICS + as-
needed inhaled SABA
– Give for ≥3 months to establish effectiveness, and
review response
Step 2 (children ≤5 years) – initial controller
+ as-needed SABA
GINA 2015

STEP 2: Initial controller treatment plus as-needed
SABA
• Preferred option: regular daily low dose ICS plus
as-needed SABA
• Regular daily, low dose ICS is recommended as the
preferred initial treatment to control asthma in
children 5 years and younger (Evidence A).
• This initial treatment should be given for at least 3
months to establish its effectiveness in achieving
good asthma control.
193

• Other options depend on symptom pattern
– Persistent asthma – regular leukotriene receptor
antagonist (LTRA) leads to modest reduction in
symptoms and need for OCS compared with
placebo
– Intermittent viral-induced wheeze – regular LTRA
improves some outcomes but does not reduce
risk of exacerbations
– Frequent viral-induced wheeze with interval
symptoms – consider episodic or as-needed ICS,194
Step 2 (children ≤5 years) – initial controller
+ as-needed SABA

• An ICS at low dose is the preferred option
• Generally ICS are more effective than LTRA in direct
comparisons
• LTRA are recommended as second option (GINA <
5, NAEPP, SIGN < 5 years)
195
STEP 2: Initial controller treatment plus as-needed
SABA

• Add inhaled corticosteroid 200-40
micrograms/day*†
or leukotriene receptor antagonist if inhaled
corticosteroid cannot be used.
• Start at dose of inhaled corticosteroid appropriate to
severity of disease
196
Step 2: Regular preventer therapy
BTS

• In most guidelines , LTRA are recommended as
second choice after low-dose ICS, or
occasionally as ‘alternative first-line treatment’
(PRACTALL), for the initial step of chronic
treatment.
• In the context of the next treatment steps, they
are also effective as add-on medications .

STEP 3: Additional controller treatment,
plus as-needed SABA
• If 3 months of initial therapy with a low dose ICS
fails to control symptoms, or if exacerbations persist,
check the following before any step up in treatment
is considered.
1)Confirm that the symptoms are due to asthma rather
than a concomitant or alternative condition .
2)Check and correct inhaler technique.
3)Confirm good adherence with the prescribed dose.
4)Enquire about risk factors such as allergen or
tobacco smoke exposure
199

• Indication
– Asthma diagnosis, and symptoms not well-controlled on
low dose ICS
– First check symptoms are due to asthma, and check
adherence, inhaler technique and environmental
exposures
• Preferred option: medium dose ICS with as-needed
inhaled SABA
• Other options
– Consider adding LTRA to low dose ICS
Step 3 (children ≤5 years) – medium dose
ICS
+ as-needed inhaled SABA GINA 2015
GINA 2015

Step 3:
• ICS can be increased to a medium dose, or a
second medication can be added.
• For children younger than 5 years, increasing ICS
is the commonest approach (GINA < 5, and
NAEPP); SIGN suggests ICS + LTRA, while
PRACTALL suggests either doubling ICS or ICS
+LTRA.

• Indication
– Asthma diagnosis, and symptoms not well-
controlled on medium dose ICS
– First check symptoms are due to asthma, and
check adherence, inhaler technique and
environmental exposures
• Preferred option: continue controller treatment and
refer for expert assessment
Step 4 (children ≤5 years) – Continue
controller treatment and refer for expert
assessment
GINA 2015

• Other options (preferably with specialist advice)
– Higher dose ICS and/or more frequent dosing (for a
few weeks)
– Add LTRA, theophylline or low dose OCS (for a few
weeks only)
– Add intermittent ICS to regular daily ICS if
exacerbations are the main problem
– ICS/LABA not recommended in this age group
204
Step 4 (children ≤5 years) – refer for expert
assessment

205
• GINA <5 does not recommend LABA for children
<5 years because of the lack of data.
• In the absence of data of safety and efficacy in
children younger than 5 years, it is probably better
to be cautious, until such data are produced.
• All documents agree that LABA should only be
prescribed in combination with ICS and are
therefore relevant as add on treatment.

• The need for additional controller treatment should
be re-evaluated at each visit and maintained for as
short a period as possible, taking into account
potential risks and benefits.
• There are insufficient data about the efficacy and
safety of inhaled combination ICS/long-acting beta2-
agonist (LABA) products in this age group to
recommend their use.

-- There is no clear evidence of benefit with
sodium cromoglicate in children aged <5
-- Theophyllines have some beneficial effect
-- Antihistamines and ketotifen are ineffective.

208
Actions to consider:
1. Assess whether the medications are being
taken as prescribed.
2. Assess whether the medications are being
inhaled with correct technique.
1. Adjust medications, as needed; either step up if
control is inadequate or step down if control is
maximized, to achieve the best control with the
lowest dose of medication.

209
REVIEWING RESPONSE AND ADJUSTING
TREATMENT
• Asthma-like symptoms remit in a substantial
proportion of children of 5 years or younger, so
the need for continued controller treatment
should be regularly assessed (e.g. every 3–6
months) .
• If therapy is discontinued, schedule a follow-up
visit 3–6 weeks later to check whether
symptoms have recurred .

210
• In practice, we have no drug strategies to reduce
future risk of asthma; neither early use of continuous
nor intermittent inhaled corticosteroids reduces the
risk of progression to school age asthma
• If inhaled drugs are prescribed, repeated education
of the parents in the correct use of spacers is
essential.
• If inhaled drugs in particular do not seem to be
working, check that they are being properly
administered rather than escalate treatment.

212
• Inhaled medications is a waste of money if
not used properly
• Poor technique is a barrier to good control
• Check at each visit
• Don’t rely on patient’s knowledge – ask them
to demonstrate

220
Spacers/Holding Chambers
• Recommended with all medium to high dose ICS
• Enhance delivery, especially with children
• Improves coordination and medication delivery
– some provide auditory feedback
• Minimize adverse effects from ICS
– decrease oral bioavailability
– reduce oral candidias (thrush)
– dysphonia, and bad taste

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

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