Pediatric Asthma Management

Pediatric Asthma
Management:
Bridging the Gaps Between
Knowledge and Practice
Welcome to Pediatric Asthma Management: Bridging the Gaps Between Knowledge

and Practice. This program is presented by Applied Clinical Education and is
accredited by Medical Education Resources. Educational support for this activity
has been provided by an educational grant from Teva Pharmaceuticals.
1
Part I:
Pediatric Asthma:
Criteria for Diagnosis
Girish D. Sharma, MD
Associate Professor
Rush Medical College
Chicago, Illinois
PART I: PEDIATRIC ASTHMA: CRITERIA FOR DIAGNOSIS

By Girish D. Sharma, MD
2
Definition
Asthma is a chronic inflammatory disorder of the airways

in which various cells and cellular elements play a role—in
particular, mast cells, eosinophils, T lymphocytes,
macrophages, neutrophils, and epithelial cells
This inflammation causes recurrent episodes of wheezing,
breathless chest tightness, and coughing, particularly at
night or in the early morning, in susceptible individuals.
These episodes are usually associated with widespread
but variable airflow obstruction, which is often reversible
either spontaneously or with treatment. The inflammation
also causes an associated increase in the existing
bronchial hyperresponsiveness to a variety of stimuli
National Asthma Education and Prevention Program Expert Panel Report 2007.
The definition of asthma developed by the National Asthma Education and

Prevention Program Expert Panel Report1 highlights the importance of chronic
inflammation in the development of asthma, in addition to episodic bronchospastic
symptoms, which are usually associated with widespread but variable airway
obstruction. Airway inflammation contributes to airway hyperresponsiveness, airflow
limitation, respiratory symptoms, and chronicity of disease. Thus, the key features
for the diagnosis are (1) the presence of episodic bronchospastic symptoms or
evidence of obstruction that is at least partially reversible spontaneously or with
treatment and (2) the exclusion of alternative diagnoses.
3
Specific Objective Criteria For The
Diagnosis Of Pediatric Asthma
Episodic lower airway obstruction is present

Airflow obstruction or symptoms (wheeze or
cough) are at least partially reversible
Alternative diagnoses are excluded
Lower airway obstruction results in wheezing
Specific objective criteria for the diagnosis of asthma include the following:
• episodic lower airway obstruction;
• airflow obstruction or symptoms (wheeze or cough); and
• exclusion of alternative diagnoses.
Lower airway obstruction results in wheezing. Among all children, 20% have
at least 1 episode of lower respiratory tract infection associated with
wheezing during first year of life, and 70% of these episodes are associated
with viral infections. Recurrent wheezing is suggestive of asthma.
4
Recommended Diagnostic
Methods For Asthma
The recommended methods for the diagnosis of

asthma are the following
– Detailed medical history
– physical examination focusing on upper respiratory
tract, chest, and skin
– Spirometry to demonstrate obstruction and assess
reversibility in children older than 4 years. The
reversibility is determined by an increase in FEV1 of
either >12% from baseline or >10% after a dose of
inhaled short-acting bronchodilator
FEV1, forced expiratory volume in 1 second
The recommended methods for the diagnosis of asthma are the following:
• detailed medical history;
• physical examination focusing on upper respiratory tract, chest, and
skin; and
• spirometry to demonstrate obstruction and assess reversibility in
children older than 4 years. The reversibility is determined by an
increase in forced expiratory volume in 1 second (FEV1) of either more
than 12% from baseline or more than 10% after a dose of inhaled short-
acting bronchodilator.
5
Wheezing In Children
Wheezing in young children is most commonly

associated with viral infections
– children younger than 2 years of age – predominantly
respiratory syncytial virus
– Older preschool children – other viruses such as
rhinovirus and parainfluenza virus
The diagnosis of asthma in young children may be difficult because episodic

wheeze and cough are also common in children who do not have asthma.1
Wheezing in children is usually associated with viral respiratory illness. Respiratory
syncytial virus is the most common cause of wheezing in children younger than 2
years, whereas other viruses can cause wheezing in older children. Other viruses,
such as rhinovirus, parainfluenza virus, and human metapneumovirus, are also
associated with wheezing in children.
6
Wheezing In Children
Key indicators for considering diagnosis of asthma include

the following
– wheezing (note that lack of wheezing or normal physical
examination findings do not exclude asthma)
– cough (especially cough that is worse during night, early hours
of morning)
– recurrent wheezing, difficulty in breathing, or chest tightness
– onset or exacerbation of symptoms caused by exercise; viral
infections; exposure to animals with fur, house dust mites,
molds, smoke, pollen; change in weather; strong emotional
expressions; airborne chemicals, dust; menses
– symptoms occur or worsen at night (early hours of morning)
Key indicators for considering a diagnosis of asthma include the following:

• wheezing (note that lack of wheezing or normal physical examination
findings do not exclude asthma);
• cough (especially cough that is worse during night, early hours of
morning);
• recurrent wheezing, difficulty in breathing, or chest tightness;
• onset or exacerbation of symptoms caused by exercise; viral infections;
exposure to animals with fur, house dust mites, molds, smoke, pollen,
airborne chemicals, dust; change in weather; strong emotional
expressions; menses; and
• onset or exacerbation of symptoms at night (early hours of morning).
7
Wheezing In Children (Cont’d)
Three Categories of wheezing in children

younger than 5 years of age
– transient early wheezing
– persistent early-onset wheezing
– Late-onset wheezing
Three categories of wheezing have been noted in children younger than 5 years of
age. These include the following:
Transient early wheezing: This is often outgrown in first 3 years of life.
Persistent early-onset wheezing: These children tend to have recurrent wheezing
associated with episodes of upper respiratory viral infections, with no evidence of
atopy and no family history of atopy. The symptoms tend to persist during preschool
age and in some until age 12.
Late-onset wheezing: These children have asthma that tends to persist during
childhood and into adult life. They are likely to have a background of atopy, often
with eczema.
8
Wheezing In Children (Cont’d)
Alternative causes of wheezing

– chronic rhinosinusitis
– gastroesophageal reflux
– recurrent viral respiratory infections
– cystic fibrosis
– bronchopulmonary dysplasia
– tuberculosis
– congenital narrowing of intrathoracic airways
– foreign body aspiration
– primary ciliary dyskinesia
– immune deficiency
– congenital heart disease
Alternative causes of wheezing include the following:

• chronic rhinosinusitis;
• gastroesophageal reflux;
• recurrent viral respiratory infections;
• cystic fibrosis;
• bronchopulmonary dysplasia;
• tuberculosis;
• congenital narrowing of intrathoracic airways;
• foreign body aspiration;
• primary ciliary dyskinesia;
• immune deficiency; and
• congenital heart disease.
It should be noted that neonatal onset of wheeze with failure to thrive and
focal lung and heart signs suggests alternative causes of wheeze.
9
Diagnosis Of Asthma
Symptoms
– frequent episodes of wheezing
– activity-induced cough or wheezing
– nocturnal cough
– absence of seasonal variation
– persistence of symptoms beyond 3 years
– other symptoms
The key to successful diagnosis of asthma is to differentiate its symptoms from

those of the aforementioned conditions. Common symptoms of asthma in
children include the following:
• frequent episodes of wheezing (more than once a week);
• activity-induced cough or wheezing;
• nocturnal cough (especially during early hours of morning and
periods without viral infection);
• absence of seasonal variation;
• persistence of symptoms beyond age of 3 years;
• chest tightness; and
• chest pain.
10
Diagnosis Of Asthma (Cont’d)
Physical findings
– increased anteroposterior diameter of chest
– prolonged expiration, expiratory wheezing,
coarse crackles
– unequal breathing sounds
Physical findings vary according to whether an acute episode is present and how
severe it is. During an outpatient visit between acute episodes, a child with mild
asthma may have normal findings on physical examination. There may be signs of
chronic respiratory distress or chronic hyperinflation, atopy, or allergic rhinitis (eg,
conjunctival congestion, ocular shiners, transverse crease over the nose due to
constant nose rubbing associated with allergic rhinitis, and pale violaceous nasal
mucosa due to allergic rhinitis). In chronic cases, the anteroposterior diameter of the
larynx may be increased, and lung examination may reveal prolongation of the
expiratory phase, expiratory wheeze, coarse crackles, and unequal breath sounds.
Once the diagnosis has been established, effort should be made to identify
precipitating factors (eg, exposure at home, day care, or school to inhalant
allergens, irritants like tobacco smoke, or viral respiratory infections) and to identify
comorbidities that may aggravate asthma (eg, sinusitis, rhinitis, gastoesophageal
reflux, obstructive sleep apnea, and allergic bronchopulmonary aspergillosis).
11
Severity Classification
of Asthma in Children
Classification of Severity of Asthma in Children
12
Classification Of Asthma Severity By
Clinical Features Before Treatment
Moderate Severe
Intermittent Mild Persistent
Persistent Persistent
Symptom >1/wk but
<1/wk Daily Daily
frequency <1/d
Exacerbation May affect May affect
Brief Frequent
characteristics activity or sleep activity or sleep
Nocturnal
≤2/mo >2/mo >2/wk Frequent
symptoms
Short-acting β2 >1/wk but
>1/wk Daily Daily
agonist use <1/d
≥80% 60%-80%
FEV1 or PEF ≥80% predicted ≤60% predicted
predicted predicted
FEV1 or PEF
<20% <20%-30% >30% >30%
variability
PEF, peak expiratory flow

Global strategy for asthma management and prevention. The GINA report 2006. Available at: www.ginasthma.com.
Spirometry is recommended for assessing the severity of asthma. The severity (intrinsic intensity of the disease
process), control (degree to which asthmatic symptoms, functional impairment, and risks for untoward events are
minimized and the goals of therapy are met), and responsiveness (the ease with which asthma control is achieved
by therapy) should be assessed.
Asthma can be classified as follows (Table):

In intermittent asthma, symptoms occur less than once a week—hence, an inhaled short-acting β2 agonist can be
used. Exacerbations are brief, and nocturnal symptoms occur less than twice a month. FEV1 and peak expiratory
flow (PEF) are greater than 80% of the predicted value, and FEV1 or PEF variability is less than 20%.
In mild persistent asthma, symptoms occur more than once a week but less than once a day. Inhaled short-acting
β2 agonists may be used accordingly. The exacerbations may affect activity or sleep, and nocturnal symptoms
occur more than twice a month. FEV1 and PEF are greater than 80% of predicted value, and FEV1 or PEF
variability is less than 20% to 30%.
In moderate persistent asthma, symptoms occur daily, and inhaled short-acting β2 agonists must be used
accordingly. Here, the exacerbations may affect activity or sleep, and nocturnal symptoms occur more than twice a
week. FEV1 and PEF are 60% to 80% of predicted value, and FEV1 or PEF variability is greater than 30%.
Finally, in severe persistent asthma, symptoms occur daily, and inhaled short-acting β2 agonists should be used
accordingly. The exacerbations appear daily, and nocturnal symptoms are frequent. FEV1 and PEF are less than
60% of predicted value, and FEV1 or PEF variability is greater than 30%.
It should be noted that because the severity of asthma depends on both the severity of the underlying disease and
its responsiveness to treatment, classification is limited in terms of value in predicting what treatment may be
required and what the response to that treatment will be. For example, a patient can present with severe symptoms
and be classified as having severe persistent asthma at initial presentation but respond fully to the initial treatment
and then be classified as having moderate persistent asthma. Hence, a periodic assessment of asthma control is
relevant and useful.
13
Physical Findings During
An Acute Episode
Mild Moderate Severe Status

Episode Episode Episode Asthmaticus
Increased,
often Imminent
Respiratory rate Increased Increased
respiratory arrest
>30/min
Bradycardia may be
Heart rate <100/min 100-120/min >120/min
present
Accessory Yes; may be Yes; respiratory
respiratory None Yes suprasternal muscles may be
muscle use retractions fatigued
Chest Moderate Loud expiratory Biphasic
May be absent
auscultation wheeze wheeze wheeze
May be present Often present Heard earlier, may

Pulsus paradoxus Absent
(10-20 mm Hg) (20-40 mm Hg) be absent
Normal, <91% in room air,
Oxyhemoglobin 91%-95% in <91% in room
>95% in with or without
saturation room air air
room air cyanosis
Physical examination during an acute episode may reveal different findings in mild, moderately
severe, and severe episodes and in status asthmaticus with imminent respiratory arrest.
During a mild episode, the respiratory rate is increased. The accessory muscles of respiration are
not used. The heart rate is less than 100 beats per minute. Pulsus paradoxus is not present.
Auscultation of the chest reveals moderate wheezing, which is often end-expiratory. The
oxyhemoglobin saturation in room air is greater than 95%.
In a moderately severe episode, the respiratory rate is increased. Typically, the accessory
muscles of respiration are used, and suprasternal retractions are present. The heart rate is 100 to
120 beats per minute. Loud expiratory wheezing can be heard. Pulsus paradoxus may be present
(10-20 mm Hg). The oxyhemoglobin saturation in room air is 91% to 95%.
During a severe episode, the respiratory rate is often greater than 30 breaths per minute. The
accessory muscles of respiration are usually used, and suprasternal retractions are commonly
present. The heart rate is more than 120 beats per minute. Loud biphasic (expiratory and
inspiratory) wheezing can be heard. Pulsus paradoxus is often present (20-40 mm Hg). The
oxyhemoglobin saturation in room air is less than 91%.
In status asthmaticus with imminent respiratory arrest, paradoxical thoracoabdominal movement

occurs. Wheezing may be absent (associated with the most severe airway obstruction). Severe
hypoxemia may manifest as bradycardia. Pulsus paradoxus noted earlier may be absent; this
finding suggests respiratory muscle fatigue.
14
Risk For Asthma In Young Children
With Recurrent Wheezing
A Clinical Index to Define Asthma Risk
Major Criteria Minor Criteria

Parental asthma Allergic rhinitis
Eczema Wheezing without colds
Eosinophilia
Castro-Rodriguez JA, et al. Am J Respir Crit Care Med. 2000;162:1403-1406.
Castro-Rodreguez et al3 proposed a simple clinical index to predict the presence of

asthma in late childhood.
The index includes 2 major criteria (physician-diagnosed asthma in a parent and
physician-diagnosed eczema in the child) and 3 minor criteria (physician-diagnosed
allergic rhinitis, wheeze without cold, and eosinophilia).
15
Risk For Asthma In Young Children
With Recurrent Wheezing (Cont’d)
The presence of asthma in later childhood

is associated with the following
– frequent wheezing during first 3 years+
– 1 major OR 2 minor risk factors.
The presence of 1 major risk factor or 2 of 3 minor risk factors has been shown to
predict the presence of asthma in later childhood.1
16
Pediatric Asthma Management
Regular assessment and monitoring

– control of factors that contribute to symptoms and
disease severity
– pharmacologic therapy
– educating the child, family, and other caregivers about
how to adhere to the asthma management plan
Based on these risk factors, successful pediatric asthma management should

include the following:
1. Regular assessment and monitoring.

2. Control of factors that contribute to symptoms and severity of disease.
3. Pharmacologic therapy.
4. Educating the child, the family, and other caregivers on how to adhere to
the asthma management plan, which includes daily management, and how to
handle episodes of asthma.
17
Goals Of Therapy
Prevent chronic symptoms

Prevent asthmatic exacerbations
Maintain normal activity levels
Maintain normal pulmonary function
Optimize pharmacotherapy, minimize side effects
Satisfy the child’s and family’s expectations/goals
The goals of therapy for the child with asthma are to:
• prevent chronic symptoms;
• prevent exacerbations of asthma;
• maintain normal levels of activity;
• maintain normal pulmonary function;
• optimize pharmacotherapy, minimize side effects; and
• satisfy the child’s and family’s expectations/goals for asthma
care.
18
Ongoing Assessment And Monitoring
Signs and symptoms of asthma

Pulmonary function
– spirometry
– PEF monitoring
Quality of life/functional status
History of asthma exacerbations
Pharmacotherapy
Patient–provider communication
Ongoing assessment includes monitoring in the following areas:

• signs and symptoms of asthma;
• pulmonary function
• spirometry
• peak flow monitoring;
• quality of life/functional status;
• history of asthma exacerbations;
• pharmacotherapy; and
• patient–provider communication.
19
Asthma Control
Partly Controlled
Controlled
Characteristic (Any Measure Uncontrolled
(Any of the
Present in
Following)
Any Week)
≥3 features of partly
Daytime symptoms None (≤2/wk) >2/wk controlled asthma
present in any week
Limitation of activities None Any Same as above
Nocturnal
None Any Same as above
symptom/awakening
Need for reliever/rescue
None (≤2/wk) >2/wk Same as above
treatment
<80% predicted or
Lung function
Normal personal best (if Same as above
(FEV1 or PEF)
known)
Exacerbations None ≥1/y 1 in any wk
Asthma is defined as controlled when there are no daytime symptoms or they are
reported to occur less than twice a week, the patient reports no limitation of
activities and/or nocturnal symptoms, there is little or no need for reliever or rescue
treatment, lung function is normal, and there are no exacerbations.
Asthma is defined as partially controlled if any of the following are present in any
week: Daytime symptoms are reported more than twice a week, activities are limited
or the patient reports nocturnal symptoms, there is need for reliever or rescue
treatment more than twice a week, lung function is affected, and 1 or more
exacerbations are reported over the course of a year.
Asthma is considered uncontrolled if 3 or more features of partly controlled asthma

are present in any given week.
It should be noted that any exacerbation should prompt a review of maintenance

therapy to ensure that it is adequate. Also, by definition, an exacerbation in any
week makes that an uncontrolled asthma week. Finally, lung function is not a
reliable test for children 5 years old or younger.
20
Ongoing Assessment And Monitoring
The Asthma Control Test (ACT) includes the

following questions
– In the past 4 weeks, how much of the time did your asthma
keep you from getting as much done at work, school, or home?
– During the past 4 weeks, how often have you had shortness
of breath?
– During the past 4 weeks, how often did your asthma symptoms
(wheezing, coughing, shortness of breath, chest tightness or
pain) wake you up at night or earlier than usual in the
morning?
– During the past 4 weeks, how often have you used your rescue
inhaler or nebulizer medication?
– How would you rate your asthma control during the past
4 weeks?
Because asthma control5 refers to control of the manifestations of the disease, it is recommended that
the treatment be aimed at controlling the clinical features of the disease, including abnormalities of
lung function.
Ideal asthma control in children will mean the following:
• no coughing;
• no difficulty in breathing;
• no nocturnal symptoms;
• normal activity, including no limitation of play, activity, sports, exercise, and school or
day care activities;
• no acute episodes and requirement for rescue medications;
• no school absences; and
• normal lung function.
As you can see from this slide, the asthma control test (ACT) has been used for assessing clinical
control as a continuous variable and provides numeric values to distinguish different levels of control.
The ACT includes responses to the following questions:
In the past 4 weeks, how much of the time did your asthma keep you from getting as much as usual
done at work, school, or home?
During the past 4 weeks, how often have you had shortness of breath?
During the past 4 weeks, how often did your asthma symptoms (wheezing, coughing, shortness of
breath, chest tightness or pain) wake you up at night or earlier than usual in the morning?
During the past 4 weeks, how often have you used your rescue inhaler or nebulizer medication?
How would you rate your asthma control during past 4 weeks?
21
Initial Evaluation In Outpatient Clinic
Ask about symptom patterns over the past

2 weeks
– daytime symptoms
– nocturnal symptoms
– school absences
– limitation of daily activities
– use of rescue medications and regular medications
During initial evaluation in an outpatient clinic, ask about symptom patterns over
the past 2 weeks:
• daytime symptoms (coughing, wheezing, shortness of breath,
rapid breathing, chest tightness);
• nocturnal symptoms (nighttime or early morning cough, wheeze,
breathlessness);
• school absences;
• limitation of daily activities; and
• use of rescue medications and regular medications.
22
Initial Evaluation
In Outpatient Clinic (Cont’d)
For infants ask about

– difficulty in feeding
– changes in respiratory rate
– altered sleep patterns
– retractions
– irritability, lethargy
– decreased appetite, weight loss
For infants ask about:

• difficulty in feeding (feeding with interruptions, poor sucking,
grunting sounds);
• changes in respiratory rate;
• altered sleep patterns;
• retractions;
• irritability, lethargy; and
• decreased appetite, weight loss.
23
Initial Evaluation
In Outpatient Clinic (Cont’d)
For older children ask about

– fatigue
– increased irritability
– complaints about not feeling well
– avoidance of certain activities
– poor school performance
For older children ask about:

• fatigue (slows down, stops playing),
• increased irritability;
• complaints about not feeling well;
• avoidance of certain activities (eg, sports, gym class); and
• poor school performance.
24
Spirometry
Use of spirometry is recommended

– at the initial visit
– after treatment has been initiated and symptoms have
stabilized, to document normal lung function
– in case of change in symptom pattern or severity
– at least once yearly to assess maintenance airway
function regardless of changes in medication
– to evaluate response to change in therapy
Use of spirometry is recommended:

• at the initial visit;
• after treatment has been initiated and symptoms have stabilized, to
document normal lung function;
• in case of change in symptom pattern or severity;
• at least once yearly to assess maintenance of airway function
regardless of changes in medication; and
• to evaluate response to change in therapy.
25
Assessment During Follow-up Visits
Has child’s asthma been better or worse since

the last visit?
In the past 2 weeks, how many days has the
child had symptoms
– during the day
– at night
– upon waking up in the morning
– during physical activity or sport activities
Since the last visit, how many times has the child
missed school because of asthma?
To assess symptoms, ask parents:

• Has the child’s asthma been better or worse since the last
visit?
• In the past 2 weeks, how many days has the child had
symptoms
• during the day, at night (during early part of night or
after midnight during early hours of morning),
• on waking up in the morning,
• during physical activity or sport activities?
• Since the last visit, how many times has the child missed
school because of asthmatic problems?
26
Assessment During
Follow-up Visits (Cont’d)
Exacerbations
– Since the last visit, has the child had any episodes
when asthmatic symptoms were a lot worse
than usual?
– What caused symptoms to worsen?
What did the child (or caregiver) do?
– Has the child had unscheduled visits to the doctor or
emergency room, or hospital admissions?
– Details of PEF – highest, lowest, any unusual fall
To assess whether any exacerbations have occurred, ask parents:

• Since the last visit, has the child had any episodes when
asthmatic symptoms were lot worse than usual?
• What caused symptoms to worsen? What did the child (or
caregiver) do?
• Has the child had unscheduled visits to the doctor or
emergency department, or has the child been admitted to a
hospital?
To assess PEF, ask:

• What are the highest and lowest PEF measurements at home
and at school since the last visit?
• Has the child’s PEF dropped below 80% of personal best
since the last visit?
Also, check the technique of administering treatment.
27
Assessment During
Medications
– Medications being used, dose and frequency?
– Medication missed, stopped or changed? If yes, why?
– Dose of short-acting β2-agonists?
– Use of β2-agonists using before exercise?
– Meter-dosed inhaler (MDI) with a space/holding
chamber/dry powder inhaler (DPI)/nebulizer?
– Is an appropriate size mask being used appropriately?
Check the technique at each visit
– Check for drug side effects
To assess what treatments have been used, ask parents:

• What medications are being used, including dose and frequency?
• Has any regular medication been missed, stopped, or changed? If
yes, why?
• How many puffs of short-acting β2 agonists is the child using daily?
How many weekly?
• How much short-acting β2 agonist medication is the child using
before exercise?
• Is the child using a metered-dose inhaler (MDI) with a spacer/holding
chamber, a dry powder inhaler (DPI), or a nebulizer? Is a mask of the
appropriate size being used appropriately? Check the technique at
each visit.
• Does the asthma medication have side effects (eg, cough, stomach
upset, bad taste, or shakiness)?
Also, periodically check the child’s/family’s technique for cleaning the device,
counting doses, replacing the nebulizer and spacers/holding chambers.
28
Assessment During
Following the care plan

– What questions do you have?
– Is the plan useful?
– Have there been any problems following the daily
management plan or the action plan?
– Always review after-hours phone numbers and the
rescue plan and steps for emergency care
Finally, to determine if children and their families are following the care plan,
ask:
• What questions do you have?
• Is the plan useful?
• Have there been any problems following the daily
management plan or the action plan?
Always review after-hours phone numbers and the rescue plan and steps for
emergency care.
29
Part II:
Diagnosing and
Assessing Asthma in
Children
David Skoner, MD
Director, Division of Allergy, Asthma and Immunology
Professor, Pediatrics
Drexel University College of Medicine
Vice Chair of Clinical Research
Division of Allergy and Immunology
Allegheny Medical Center
Pittsburgh, Pennsylvania
PART II: THE CURRENT UNDERSTANDING OF ASTHMA CONTROL

By David Skoner, MD
30
Strategies For Asthma Control
1. Identify and control environmental triggers – smoke, allergens

2. Address effect of exercise on asthma symptoms
3. Educate patients/parents about disease, need for treatment,
available treatments, environmental avoidance
4. Identify and treat concomitant diseases (allergic rhinitis, sinusitis,
gastroesophageal reflux disease)
5. Provide written maintenance and action plans
6. Use anti-inflammatory treatments and develop strategies to
promote long-term adherence
7. Fulfill the goals of asthma treatment
National Institutes of Health. National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program
Expert Panel. Clinical Practice Guidelines. Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma.
Update on Selected Topics 2007. Bethesda, MD: National Institutes of Health National Heart, Lung, and Blood Institute; 2007.
Strategies for gaining control of asthma include the following:
1. Identify and control environmental triggers: smoke, allergens.

2. Address the effect of exercise on asthma symptoms.
3. Educate patients and their parents about disease, need for treatment,
available treatments, environmental avoidance.
4. Identify and treat concomitant diseases (allergic rhinitis, sinusitis,
gastroesophageal reflux disease).
5. Provide written maintenance and action plans.
6. Use anti-inflammatory treatments and develop strategies to promote long-
term adherence.
7. Fulfill the goals of asthma treatment.
31
Classifying Asthma Severity And
Assessing Asthma Control
In patients not on controller medications

– severity based on domains of impairment and risk
– level of severity based on most severe category in which
feature appears
In patients on controller medications
– severity based on lowest step required to maintain clinical
control
– control of asthma based on domains of impairment and risk
level of control based on most severe impairment of risk category
validated questionnaires may be used in patients aged ≥12 years
National Institutes of Health. National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program
Expert Panel. Clinical Practice Guidelines. Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma.
Update on Selected Topics 2007. Publication No. 02-5075. Bethesda, MD: National Institutes of Health National Heart, Lung, and
Blood Institute; 2007.
In patients not on controller medications, the severity of asthma is based on

domains of impairment and risk and the most severe category in which a feature
appears. In patients on controller medications, severity is based on the lowest step
required to maintain clinical control.
32
Stepwise Approach For Managing
Asthma In Children Aged 0 To 4 Years
Mild
Intermittent Moderate to Severe Persistent
Persistent
Step 6
Step 5 Preferred:
Step 4 Preferred: high-
high-dose ICS
high-dose and either
Step 2 Preferred: medium-
medium-dose ICS montelukast
medium-dose ICS and either or LABA
Preferred: low-
low-dose ICS ICS and either montelukast and oral
SABA as montelukast or LABA corticosteroid
needed Alternative: or LABA s
montelukastor
cromolyn
ICS, inhaled corticosteroid; LABA, long-acting β2 agonist; SABA, short-acting β2 agonist
According to the recently revised National Asthma Education and Prevention

Program (NAEPP) guidelines for the treatment of pediatric asthma, short-acting β2
agonists are the preferred treatment for children aged 4 years and younger with
intermittent asthma. For those with mild persistent asthma, low-dose inhaled
corticosteroids (ICSs) are the preferred treatment. Finally, for those with moderate
to severe persistent asthma, medium- or high-dose ICSs monotherapy or
combination therapy with ICSs and long-acting β2 agonists or montelukast is
preferred.
33
Asthma In Children Aged 5 To 11 Years
Mild
Mild Persistent
Intermittent
Persistent
Severe Persistent
Step 6
Step 5 Preferred:
high-dose ICS
high-dose + LABA + oral
Preferred: medium-
medium-dose ICS + LABA corticosteroid
Step 2
medium-
medium-dose ICS + LABA Alternative: Alternative:
Step 1 Preferred:
ICS Alternative: high-
high-dose high-
high-dose
Preferred: low-
low-dose ICS
or medium-
medium- ICS ICS and
SABA as and either either LTRA
needed Alternative: low-
low-dose ICS dose ICS
and either and either LTRA or or
LTRA,
LABA, LTRA, LTRA theophylline theophylline +
cromolyn,
cromolyn,
or or and oral
nedocromil,
nedocromil,
theophylline theophylline omalizumab corticosteroid
or
may be and
theophylline
considered omalizumab
for patients may be
who have considered for
allergies patients who
have allergies
LTRA, leukotriene receptor antagonist.
According to the recently revised NAEPP guidelines for the treatment of pediatric
asthma, short-acting β2 agonists are the preferred treatment for children between
the ages of 5 and 11 years with intermittent asthma. For those with mild persistent
asthma, low-dose ICSs or medium-dose or low-dose ICSs with either long-acting β2
agonists or leukotriene receptor antagonists are preferred. For those with severe
persistent asthma, medium-dose ICSs plus long-acting β2 agonists or high-dose
ICSs plus long-acting β2 agonists and oral corticosteroids are preferred.
34
Asthma In Patients Aged ≥12 Years
Mild Moderate
Intermittent Severe Persistent
Persistent Persistent
Step 6
Step 5 Preferred:
high-dose ICS
high-dose + LABA
medium-dose ICS + LABA + oral
medium-dose ICS + LABA and corticosteroid
Preferred: low-
low-dose ICS ICS Alternative: consider and
SABA as Alternative: or medium-
medium-dose omalizumab consider
needed cromolyn,
cromolyn, low-
low-dose ICS ICS for patients omalizumab
nedocromil,
nedocromil, + LABA and either who have for patients
LTRA, Alternative: LTRA, allergies who have
or low-
low-dose ICS theophylline,
theophylline, allergies
theophylline and either or zileuton
LTRA,
theophylline,
theophylline,
or zileuton
ICS, inhaled corticosteroid; LABA, long-acting β2 agonist; SABA, short-acting β2 agonist
According to the recently revised NAEPP guidelines for the treatment of pediatric
asthma, short-acting β2 agonists are the preferred treatment for children older than
12 years with intermittent asthma. For those with mild persistent asthma, low-dose
ICSs are the preferred option. For those with moderate persistent asthma, medium-
dose or low-dose ICSs with long-acting β2 agonists are preferred. Finally, for those
with severe persistent asthma, high-dose ICSs plus long-acting β2 agonists or high-
dose ICSs plus long-actiing β2 agonists and oral corticosteroids are preferred.
35
Inhaled Corticosteroids
ICSs are recommended as first-line therapy and are the

most effective therapy for the treatment of persistent
asthma in both adults and children
Benefits of daily use 2.5
Rate Ratio for Death From Asthma

– fewer symptoms 2
– fewer severe exacerbations
1.5
– reduced use of
quick-relief medicine 1
– improved lung function 0.5

– reduced airway inflammation 0
0 1 2 3 4 5 6 7 8 9 10 11 12
National Asthma Education and Prevention Program (NAEPP) Expert Panel
Report 2, 1997. Number of Canisters of ICSs per Year
NAEPP Update, 2007.
Barnes PJ et al. Am J Respir Crit Care Med. 1998;157:S1–S53.
Suissa S et al. N Engl J Med. 2000;343:332-336.
The NAEPP recommends ICS as the preferred long-term controller medication for
children of all ages with persistent asthma. ICS are FDA-approved for the treatment
of asthma in children as young as 1 year of age. Although clearly effective at
achieving asthma control in children, ICSs pose important challenges in this
population. These include issues of long-term adherence, delivery of drug to large
and small airways, and the potential for systemic adverse effects. Regarding the
latter, the most frequently addressed and clinically relevant systemic adverse effect
in children is growth suppression. Benefits of the daily use of ICSs include fewer
symptoms, fewer severe exacerbations, reduced use of quick-relief medicine,
improved lung function, and reduced airway inflammation.
36
Effect Of ICSs On Inflammation
E
E
BM
BM
Before and after 3-months of treatment

with 600 mcg of BUD twice daily
BUD, budesonide
Laitinen LA et al. J Allergy Clin Immunol. 1992;90:32-42.
ICSs act on a variety of inflammatory and structural cells, including eosinophils, T

lymphocytes, dendritic cells, mast cells, macrophages, epithelial cells, airway smooth muscle
cells, endothelial cells, and mucus glands, to reduce cytokine and mediator production, vessel
leakage, and mucus production and to increase β2 receptors on airway smooth muscle cells.
For ICSs to be effective, adherence is clinically important, as evidenced by studies evaluating

asthma control in children who do and do not adhere to ICS use. However, studies evaluating
rates of adherence to ICS therapy indicate that they are very low. Therefore, the well-
described benefits provided by the long-term use of ICSs may not be attainable. Adherence to
long-term controller therapy is influenced by many factors, including ease of use, frequency of
dosing, and fear of side effects. The latter has been cited as a major barrier to the long-term
use of ICSs. Thus, adherence may be improved when the benefits and risks of ICS use in
children are fully understood. Topically deposited corticosteroids eventually appear in the
systemic circulation, with systemic bioavailability resulting from either the inhaled fraction of
drug, which enters the airways (10%-60%), or the remaining portion, which is swallowed
(40%-90%). The swallowed portion is absorbed from the gastrointestinal tract and subject to
variable first-pass metabolism in the liver. All ICSs cause dose-related systemic adverse
effects, although these are substantially less than those caused by a comparable dose of oral
corticosteroids. No first-pass metabolism occurs in the lungs, and most of the drug in the
blood enters via the lungs. Interestingly, the very source of efficacy (airway delivery) is also
the major source of concern about any systemic side effects.
37
Analysis Of Inhaled Corticosteroids
How Patients Respond
40 Malmstrom et al* (n=895)

35 Adult Study* (n=470)
30
CAMP* (n=311)
Patients, %
ACRN* (n=336)
25
20
15
10
5
0
<–20 –20 to –10 –10 to 0 0 to 10 10 to 20 20 to 30 30 to 40 >40
FEV1 Change from Baseline, %
Data include only patients who received ICS. Study of Malmstrom et al included 895 patients 15 to 85 years of age with chronic asthma; Adult
study included 470 adults with asthma; CAMP study included 311 children with asthma; ACRN study included 336 adults with asthma.
ACRN, Asthma Clinical Research Network; CAMP, Childhood Asthma Management Program
Malmstrom K et al. Arch Intern Med. 1999;130:487-495. Tantisira KG et al. Hum Mol Genet. 2004;13:1353-1359.
An important concept to understand in the appropriate use of ICSs is dose

responsiveness.
8.16
38
Dose–response Relationship In Children
With Moderate And Severe Asthma
Percentage of Maximum
100
90
80
70
Improvement
60
50
Symptoms
40 FEV1
30 Exercise (FEV1)
20 NO
10 FEF25%-75%
0
0 100 200 300 400 500 600 700 800
Daily Dose of BUD, mcg
FEF25%-75%, forced expiratory flow rate; NO, nitric oxide

Barnes PJ. N Engl J Med. 1995;332:868-875. Barnes PJ et al. Am J Respir Crit Care Med. 1998;157:S1-53.
Studies have shown that the dose–response curve for benefits of ICSs is
steep at low doses, and that relatively little benefit is gained when a low dose
is doubled or tripled. Furthermore, because the dose–response curve for
adverse events is shifted to the right at higher ICS doses, doubled and
tripled ICS doses are much more likely than low doses to produce systemic
side effects.
39
Children’s Responsiveness To ICS
And LTRA Is Highly Variable
FEV1 (Change With Montelukast, %) 40

Montelukast alone Both 22% of
30 (5%) meds patients
(17%) respond to
20 montelukast
10
0 40% of
–10 patients
respond to
–20 y fluticasone
tit Fluticasone
–30 en alone
f id
o (23%)
ne Neither medication
–40 Li
(55%)
–50
–50 –40 –30 –20 –10 0 10 20 30 40
FEV1 (Change With Fluticasone, %)
Szefler SJ et al. J Allergy Clin Immunol. 2005;115:233-242.
Another important concept is the heterogeneity of responses to ICSs, at

least some of which may be genetically and environmentally determined. In
the study of Szefler et al,16 55% of children with asthma failed to achieve an
improvement in FEV1 of 7.5% or more with either montelukast or an ICS. In
that same study, 17% responded to both medications, 23% responded only
to an ICS, and 5% responded only to montelukast. In all, 22% responded to
montelukast and 40% responded to an ICS.
40
Effect Of ICS Dosage On Therapeutic
And Systemic Corticosteroid Effects
Benefit/risk
fit
ne
be
th cts
tic
ow ffe
eu
)
gr e
ap
↓ ic
er
g, em
Th
(e yst
S
Adverse effect
clinical relevance
Drug inhaler Rx, ~mcg/day
BDP without spacer 200 350 500 1,000
BDP with spacer 200 400 600 1,200
BUD MDI 200 400 800 1,600
BUD dry powder 100 200 400 800
FP 100 200 400 800
BDP, beclomethasone diproprionate; FP, fluticasone propionate
If sufficient amounts of a corticosteroid enter the systemic circulation,

systemic side effects may develop. These include cataracts and glaucoma,
thinning and bruising of the skin, suppression of the hypothalamic–pituitary–
adrenal axis, and suppression of growth. With the exception of growth
suppression, a risk has been reported mainly with the use of high ICS doses
(eg, beclomethasone dipropionate equivalent [BDP] of >400 mcg/d). In
contrast, a small degree of growth suppression has been observed at lower,
more frequently used ICS doses.
41
Safety Considerations
With ICS Therapy
Local effects
– Oropharyngeal effects
oral candidiasis
pharyngitis
hoarseness/dysphonia
Systemic effects
– adrenocortical suppression
– changes in bone mineral density (BMD) and bone metabolism
– growth suppression
– ophthalmologic effects: cataracts and glaucoma
– skin thinning and bruising
Lipworth BJ. Arch Intern Med. 1999;159:941−955.
Of the systemic adverse effects that have been observed with ICS therapy, the
potential for growth suppression remains the greatest concern in pediatric patients.
This concern prompted the FDA to require class labeling for ICS agents in 1998, which
garnered extensive media coverage and fueled the well-known “steroid phobia” so
prominent in the United States. Although numerous studies have reported relevant
data on ICSs and growth, many do not meet the criteria for well-designed prospective
randomized controlled trials. Additional difficulties encountered in interpreting the
results of these trials include the variable growth rates occurring throughout childhood
and the variable methods (eg, stadiometry, knemometry) and end points (growth
velocity, height percentiles, final adult height, markers of bone formation/absorption)
used to assess growth effects in studies.
Despite these limitations, several prospective randomized controlled studies showed

that conventional doses of ICSs were associated with mean reductions in growth
velocity of about 1 cm per year. The growth-retarding effects of ICSs are more
pronounced at the beginning of treatment, and prepubescent children with mild asthma
appear most susceptible to these effects. Growth retardation of from 0.9 to 1.5 cm per
year has been observed with beclomethasone diproprionate and of about 0.5 cm per
year with fluticasone proprionate. Dose-responsiveness of the growth effect has been
observed.
42
Growth Suppression
Growth supression can be assessed as a short-, intermediate-,

or long-term effect
ICSs, as a class, can affect growth in childhood
– START study showed BUD causing growth retardation over
3-year period
Year 1, 0.58 cm; year 2, 0.43 cm; year 3, 0.33 cm
– Effect is small and may not be sustained with long-term therapy
Adult height attained by children treated with ICSs is not
different from that of nontreated individuals
– However, steroid phobia may still affect the use of ICSs
START, Inhaled Steroid Treatment as Regular Therapy in Early Asthma

Pederson S, O’Byrne P. Allergy. 1997;52:1-34. Leone FT et al. Chest. 2003;124:2329-2340.
Sheffer AL et al. Ann Allergy Asthma Immunol. 2005;94:48-54. Pauwels RA et al. Lancet. 2003;361(9363):1071-1076.
Growth suppression can be assessed as a short-, intermediate-, or long-term

effect. ICSs can affect short-term growth in childhood. In the START (Steroid
Treatment as Regular Therapy in Early Asthma) study, budesonide caused
growth retardation over a 3-year period. However, the effect was small and
may not be sustained with long-term therapy. Data indicate that the adult
height attained by children treated with ICSs is no different from that of
untreated individuals. However, steroid phobia may still affect the use of
ICSs
43
CAMP Study
Growth Velocity With Budesonide—
Lower In Year 1, Similar To Placebo In Years 2-4
6.5 Budesonide 200 mcg twice daily (n=311)

Standing Height Velocity, cm/y
Nedocromil 8 mg twice daily (n=312)

Placebo (n=418)
6.0
5.5
5.0
4.5
0
0 1 2 3 4
Time, year
All groups had similar growth velocity by the end of the treatment period.
Adapted from The Childhood Asthma Management Program Research Group. N Engl J Med. 2000;343:1054-1063.
Allen DB et al J AllergyClin Immunol 2003;112:S1-S40.
Although the long-term CAMP (Childhood Asthma Management Program) study

showed only transient effects of inhaled budesonide on growth velocity throughout 4 to
6 years of follow-up, it has been proposed that the return to normal growth velocity in
this and other long-term studies of ICSs may be due to waning compliance over time.
In the START study, a significant but waning effect on growth was observed in all 3
years of the study. Limited data support a lack of effect of long-term ICS use on final
adult height, and this important information can be used in an office setting to illustrate
safety and promote long-term adherence.
Following the 1998 FDA meeting to review the growth effects of ICSs, a draft guidance
was published regarding the conduct of future growth studies. Recommendations
included the following characteristics:
1. a population that is prepubertal and has mild, persistent asthma;
2. a study design with at least a 1-year treatment period that includes an untreated
control group, the collection of baseline growth velocity data, a follow-up period, and
repeat stadiometer measurements; and finally
3. a study design that uses a regression analysis of growth velocity and total length with
a 95% confidence interval of 0.5 cm or less as the primary outcome.
44
Linear Growth Stadiometry Study In Prepubertal Asthmatic
Children
Effect Of Montelukast Versus Beclomethasone
On Linear Growth Velocity
7 Montelukast 5 mg (n=120)
Change in Height Velocity, cm ± SE
Beclomethasone 400 mcg

6
(n=119)
5 Placebo (n=121)
4
3
2
1
0
–1
–2
–3
–19–16 –8 0 8 16 24 32 40 48 56
Run-in period
Weeks on Treatment
Adapted from Becker AB et al. Ann Allergy Asthma Immunol. 2006;96:800-807.
Two growth studies that followed these recommendations were subsequently

conducted. The published manuscript showed, not surprisingly, that
beclomethasone did have an expected effect on growth and that montelukast did
not affect growth. The other study, published as yet only in abstract form, showed
no growth effect with ciclesonide, a new ICS. However, in a published short-term
knemometry study, ciclesonide had no effect on the short-term lower leg growth
rate in children with mild asthma.
45
The Risk Pyramid
Safety of Inhaled Corticosteroids for Persistent Asthma in Children
STEPPED-DOWN ICS DOSES
RECOMMENDED ICS DOSES
> RECOMMENDED ICS DOSES
ORAL CORTICOSTEROIDS
(DAILY OR EVERY OTHER DAY)
UNTREATED POORLY
CONTROLLED DISEASE
QUOTE: J.Z., a 14-year-old asthmatic patient with growth delay, told a local pediatric endocrinologist trying to change ICS to every other
day: “I would rather be short than unable to play soccer.”
This slide shows the importance of evaluating risks versus rewards in the treatment
of asthma with ICS.
46
Importance Of Small
Airways In Asthma
Percentage of Peripheral to Total Airway Resistance

% Peripheral Airway Resistance to
* *
60
Total Airway Resistance, %
50 Inspiration *P<.01 vs normals

Expiration
40
30
20
10
0
Normal Group A Group B
FEV1 >80% FEV1<70%
Patients in Group A were asymptomatic (FEV1 >80% predicted without apparent airflow obstruction in preceding month and without
therapy). Patients in Group B had FEV1 <70% predicted during a 12-month observation period, irrespective of treatment. Range of age at
onset of asthma: 19 to 30 years. Duration: >20 years.
Yanai M. J Appl Physiology. 1992;72:1016-1023.
As you can see from this slide, small airways contribute significantly to total airway
resistance in many patients with asthma. Newer ICS formulations using
hydrofluoroalkane (HFA) rather than chlorofluoroalkane (CFC) as a propellant have
improved the delivery of drug to peripheral airways because of smaller particle size.
Two newer ICS formulations have been developed: BDP and ciclesonide
(mentioned previously, not yet available in the United States). With HFA solution
inhalers, both lung deposition (55% for HFA vs 4% for CFC BDP) and
oropharyngeal deposition (29% for HFA vs 94% for CFC BDP) are better. A recently
published growth study comparing CFC and HFA BDP demonstrated comparable
safety profiles. A growth study of HFA flunisolide has also been published. Clinical
studies indicate that ICSs may reduce bone mass in adults and children, potentially
increasing the risk for fracture later in life. However, long-term ICS use had no effect
on bone mineral density in the CAMP study.
47
Novel ICS Strategies
Use of biomarkers to adjust ICS dose

ICS dosing as needed
Single inhaler
Several novel strategies for the management of asthma with ICSs have
been developed, including the following: the use of biomarkers (sputum
eosinophils, level of airway hyperreactivity, fraction of exhaled nitric oxide
[FENO]) to adjust the ICS dose, as-needed dosing of ICS therapy, single-
inhaler therapy (including an ICS and a long-acting β2 agonist), and a new
ICS (ciclesonide).
48
Asthma Management (ICS) Guided
By Sputum Eosinophils
BTS management group
120
Severe exacerbations, No.

Patients with moderate to Sputum eosinophil management group
severe asthma (N=74) 100
ICS treatment titrated 80
according to British
Thoracic Society (BTS) 60
guidelines or sputum
eosinophils 40
Sputum eosinophils– 20
guided therapy: 48%
reduction in ICS therapy 0
0 1 2 3 4 5 6 7 8 9 10 11 12
Time, mo
Overall ICS use similar: sputum eosinophilia identified

subjects who needed ICS therapy and those who did
Green RH et al. Lancet. 2002;360:1715-1721. not.
Deykin Aet al. J Allergy Clin Immunol. 2005;115:720-727.
This slide summarizes a study showing the benefit of using sputum

eosinophils to adjust ICS dose. In 74 patients with moderate to severe
asthma, the ICS dose was titrated according to British Thoracic Society
guidelines or sputum eosinophils. The result was a 48% reduction in the
use of ICS therapy.
49
Monitoring Of FENO May
Reduce Exacerbations
40 Control group
35
Exacerbations, No.
30
25
20
15
10 FENO Group
5
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Time, mo
FENO, fraction of exhaled nitric oxide
Smith AD, et al. N Engl J Med. 2005;352:2163-2173.
In a single-blind, placebo-controlled trial, 97 patients with asthma who had

been regularly receiving treatment with ICSs were assigned to have their
corticosteroid dose adjusted according to either FENO measurements or
an algorithm based on conventional guidelines. The rates of exacerbation
were 0.49 episode per patient per year in the FENO group and 0.90
episode per patient in the control group. With the use of FENO
measurements, maintenance doses of ICSs may be significantly reduced
without compromising asthma control.
50
Role Of Intermittent Therapy Versus Standard
Therapy In Mild Persistent Asthma IMPACT
Outcome Regular As Needed Regular

Budesonide Budesonide Zafirlukast
Morning PEF + + +
Asthma exacerbation rates + + +
FEV1 before β2 agonist + O O
FEV1 after β2 agonist O O O
Inflammation
Degree of asthma control + O O

Markers of
Number of symptom-free days + O O

Quality of life O O O
Nitric oxide (exhaled) + O O
Sputum eosinophils + O O
Bronchial hyperactivity (MCH PC20) + O O
IMPACT, Improving Asthma Control Trial; MCH PC20, 20% fall in FEV1 on methacholine challenge; +, positive outcome; O, no significant
change from baseline
•Boushey HA et al. N Engl J Med. 2005;352:1519-1528.
• Rationale: Pharmacy records indicate that most patients use their medications less than
recommended.
• Study observed 225 adults with mild persistent asthma for 1 year.
• Included individuals aged 18 to 65 years with physician-diagnosed mild persistent asthma
and an FEV1 at least 70% of the predicted value (measured more than 4 hours after the most
recent use of a bronchodilator).
• Excluded patients smoked cigarettes, had had a respiratory tract infection or used
corticosteroids in the previous 6 weeks, or had been hospitalized or made 2 or more visits to
an emergency department for asthma treatment in the previous year.
• Primary outcome of efficacy selected before the study was morning peak flow.
Treating mild persistent asthma intermittently is effective if the morning peak flow is used as
the efficacy end point. However, other clinical outcomes of asthma control demonstrate that
regular budesonide is more effective than as-needed budesonide or regular zafirlukast. Other
factors to consider are the following:
• The patients in the study were adults.
• The setting was rigid (ie, the patients were followed closely).
51
As Needed ICS For
Mild Persistent Asthma IMPACT
Kaplan-Meier Estimates of Time to a First
Exacerbation of Asthma
100
Percentage Without
80
Exacerbation
Daily BUD P=NS

60 Daily zafirlukast
Intermittent therapy
40
20
P=0.39
0
0 100 200 300 400
Days Since Randomization
There were no significant differences among the groups (P=0.39).
Boushey HA et al. N Engl J Med. 2005;1519-1528.
Boushey et al conducted a double-blind trial in which 225 adults were

randomized to symptom-based, as-needed administration of ICS
monotherapy or to daily treatment with budesonide or zafirlukast. The
primary outcome was morning peak expiratory flow PEF; other outcome
measures included pulmonary function test results before and following
bronchodilator treatment, degree of disease control, exacerbations,
symptom-free days, and quality of life.
52
Single-Inhaler Therapy
Poor control may be partly due to overreliance

on
β2-agonist reliever at expense of regular ICS
Twelve-month randomized, double-blind,
parallel-group study
– BUD/FORM 80 mcg bid/4.5 mcg bid plus 80 mcg
prn/4.5 mcg prn (BUD/FORM maintenance + relief)
– BUD/FORM 80 mcg bid/4.5 mcg bid plus terbutaline 0.4
mcg prn (BUD/FORM + SABA)
– BUD 320 mcg bid plus terbutaline 0.4 mcg prn
(BUD + SABA)
O’Byrne PM et al. Am J Respir Crit Care Med. 2005;171:129-136.
O’Byrne et al tested the hypothesis that in children and adults treated with
a low maintenance dose of budesonide-formoterol, replacing a short-
acting β2 agonist reliever with as-needed budesonide-formoterol would
provide rapid symptom relief and a simultaneous adjustment in anti-
inflammatory therapy, thereby reducing exacerbations. They conducted a
double-blind randomized parallel-group study in 2,760 patients with
asthma who were treated with the scheme shown on the slide. Outcome
measures included time to first exacerbation, pulmonary function test
results, use of daily control measures, and safety.
53
CHALLENGES
Real-World Effectiveness
Oral Dose Onset

vs inhaled frequency of action
Effectiveness = Efficacy x Compliance

“Does it work?” “Can it work?”
(eg, controlled
clinical trial data)
Inhaler Side Perceived

technique effects safety
The physician must choose from a wide array of medications that are
recommended in the NAEPP guidelines and have been shown to be
efficacious in clinical trials. However, the efficacy of a medication in the
ideal setting of a controlled clinical trial, where compliance may be
enhanced by high levels of patient and parent education and follow-up,
may not translate into effectiveness in the real world. In clinical practice,
compliance with medical therapy is complicated by a variety of issues,
including route of administration (eg, oral vs inhaled therapy), side
effects, cost, perception of safety, frequency of dosing, patient
education, onset of action, and inhaler technique. An otherwise
efficacious drug may not be fully effective if the patient does not take it
in a compliant manner.
54
Compliance Is An Essential
Component Of Asthma Control
Poor compliance can lead to poor outcomes
100 P=0.008
80
Compliance, %
68.2%
60
40
20 13.7%
0
Children With Stable Children Requiring Oral
Asthma (n=16) Corticosteroid Rescue (n=8)
Adapted from Milgrom H et al. J Allergy Clin Immunol. 1996;98:1051-1057.
Poor compliance in this 13-week study was strongly correlated with loss
of asthma control. Among the children who required oral corticosteroid
rescue, only 13.7% adhered to their regimen, compared with a
compliance rate of 68.2% among the children with stable asthma—that
is, the children who did not require corticosteroid rescue (P=0.008). Of 8
children who required courses of oral corticosteroid during the study, 5
were among the least compliant, including 2 who were hospitalized.
These findings suggest that inadequate control of asthma may reflect
noncompliance, a problem that is widespread and not confined to
obviously uncooperative patients.
55
Reported Adherence Rates
(Outside Clinical Trials)
Medication adherence rates for asthma patients

range from 30% to 70%
– For inhaled corticosteroids
rates range from 63% to 93%
underuse (about 40%) is more common than overuse
(about 10%)
– In high-risk, inner-city adults by self-report
among those prescribed inhaled corticosteroids—51%
β2-agonists for quick relief—100%
β2-agonists for long-term control—25%
Bender B et al. Ann Allergy Asthma Immunol. 1997;79:177-186. Cochrane MG et al. Chest. 2000;117:542-550.
Hyland ME. Drugs. 1999;58(suppl 4):1-6. Collier MC et al. Am J Respir Crit Care Med. 2001;163:A314. Abstract.
In asthma studies, adherence varies widely depending on the population being

studied and the measures being analyzed. Most studies have focused only on
medication use; very few have addressed monitoring of peak flow or avoidance
of triggering factors. Bender and colleagues found that rates of adherence to
asthma medications in general ranged from 30% to 70%. Among patients using
ICSs, adherence rates are somewhat higher, but underuse is still more
common than overuse. A recent study of high-risk, inner-city adults found that
self-reported adherence to long-term controllers was very limited, although
virtually all patients used short-acting β2 agonists.
56
Adherence To Inhaled Asthma
Therapy Decreases Over Time
75 Adults with moderate to severe asthma (N=50)

treated with twice daily ICS
Actuation of inhaler monitored electronically
70
Adherence, %
65
60
55
50
0 1 2 3 4 5 6
Week of Study
Apter AJ et al. Am J Respir Crit Care Med. 1998;157:1810-1817.
Adherence to twice-daily ICS therapy in 50 adults with moderate to severe

asthma was monitored electronically for 42 days. The mean adherence rate was
63%; 54% of patients recorded at least 70% of the prescribed number of ICS
actuations.
Factors associated with poor adherence included the following:

• less than 12 years of formal education;
• poor patient–clinician communication;
• household income of less than $20,000;
• non–English-speaking patient; and
• minority status.
57
Correlates Of Adherence
Patient/Parent Factors Disease/Treatment Factors

– Monitoring of lung function – Treatment satisfaction
– Willingness to use drug in – Moderate or severe symptoms
daily practice – Written instructions on correct
– Belief in active participation use of inhalers
with physician
– Belief that asthma is serious
– Perception that asthma is not
well controlled
– Good communication with
caregiver and understanding
of medical instructions
There are many barriers to adherence, but also many intervention points at which
the healthcare team can enhance the likelihood of success. Because adherence
varies across people and treatment components, and because intensive efforts to
promote adherence involve a great deal of time, money, and special expertise, such
efforts should concentrate on the patients who are likely to need them most. Special
attention should be given to patients with psychological comorbidities, those with
chaotic or dysfunctional lives, and those who feel unable to control their disease.
Efficacious strategies of adherence promotion include simplifying the treatment
regimen, tailoring therapy to patients’ needs and preferences, and achieving a
balance between providing ongoing medical support and helping patients make
appropriate decisions about their own care. Patient action plans that are
straightforward and easy to follow promote concordance in a therapeutic
relationship.
The factors that drive adherence are complex and interdependent, involving not only
the beliefs and attitudes of patients and their families but also the disease
characteristics and treatment properties. In general, adherence is better when
patients and their families view the disease as serious, when they trust that the
intervention will help them, and when the treatments are relatively simple and
convenient to use. Good communication with the caregiver and a clear
understanding of medical directions also are correlates of adherence. These are
enhanced by the use of written instructions.
58
Correlates Of Nonadherence
Patient/Parent Factors Disease/Treatment Factors

– No routine for medication use – High cost or complexity of regimen
– Younger age, non-white ethnicity, – Dislike of medications
low socioeconomic status – Mild or no symptoms
– Belief that adherence is difficult – Difficulty or inconvenience of
– Lack of healthcare insurance using inhalers
– Skepticism about – Adverse effects or failure of
treatment efficacy previous treatments
– Fear of adverse effects
– Denial or underestimation of
disease severity
– Shame, anger, or rebellion
– Forgetfulness or complacency
Correlates or predictors of nonadherence include a lack of routine times for

administration of drug, a belief that adherence is difficult or unlikely to control
the disease, and a fear of adverse effects—including steroid phobia. Past
experience with drugs that were ineffective or intolerable also tends to limit a
patient’s willingness to comply fully with a new therapy. A patient with mild or
no symptoms is less likely to adhere to the prescribed treatment regimen,
especially if it is complex or costly. This is particularly relevant among patients
without healthcare coverage. However, many patients may deny or
underestimate the true severity of their disease. Among children and
adolescents, this is often a consequence of embarrassment or anger regarding
the disease or to simple forgetfulness. Before a medication is prescribed,
patients should be asked explicitly about their willingness to use it on a daily
basis. Many will admit that they expect it to be difficult or impossible.
59
Conclusions
ICSs are much safer than systemic steroids but continue to carry
small, dose-related, manageable risks for some children (especially
those with mild disease)
ICSs are the guideline-preferred monotherapy for asthma of all
degrees of severity, but LTRAs are viable alternatives for some
children with mild asthma
ICSs (at high doses) may have a role in addressing airway
remodeling, but more human studies are needed
LABAs are preferred adjunctive agents in patients aged ≥12 years
whose disease cannot be controlled with ICS monotherapy
None of the currently available therapies have been shown to
change the natural history of asthma, even when started early
Novel approaches to using ICSs have recently been described, the
generalizability of which to children is unknown
• ICSs are much safer than systemic steroids but continue to carry small, dose-
related, manageable risks for some children (especially those with mild
disease).
• ICSs are the guideline-preferred therapy for asthma of all severities, but
leukotriene receptor antagonists are viable alternatives for some children with
mild asthma.
• ICSs (at high doses) may have a role in addressing airway remodeling, but more
studies in humans are needed.
• None of the currently available therapies have been shown to change the
natural history of asthma, even when started early.
• Novel approaches to using ICS therapy have recently been described, but their
generalizability to children is unknown.
60
Part III:
Benefits and Limitations
of Available Therapies
and Devices in Pediatrics
Nemr S. Eid, MD
Professor of Pediatrics
University of Louisville School of Medicine
Louisville, Kentucky
PART III: BENEFITS AND LIMITATIONS OF AVAILABLE THERAPIES

AND DEVICES IN PEDIATRICS
By Nemr S. Eid, MD
61
Introduction
Inhaled route is preferable

It is a very complex process
Challenges are great in pediatrics
– pharmacokinetics
– pharmacodynamics
– Patient’s physical and cognitive abilities
– parental acceptance
The inhaled route of administration is accepted as the optimal means of drug

delivery in the treatment of asthma. The choice of delivery device and inhaler
technique are key factors that influence the effectiveness of inhaled medications.
The delivery of nebulized medications to the lungs is a complex process that can be
affected by many factors. Studies have shown that inhaled therapy in adult patients
is associated with many mishaps and difficulties, and in infants and young children
the challenges are far greater because of their anatomy, physiology, and cognition
are not fully developed. Besides the pharmacokinetic and pharmacodynamic
complexities, the patient’s physical and cognitive abilities and the parents’
understanding and willingness to use a particular inhalation device should be
considered when asthma therapy is prescribed to children. Pressurized MDIs
(metered dose inhalers) are by far the most commonly prescribed inhalers in the
United States, yet nearly half of patients do not use them properly, resulting in poor
therapeutic benefit. Clearly, therefore, new devices are urgently needed to address
these deficiencies. This presentation reviews the devices available in the US
marketplace and introduces a few that are in development.
62
Available Therapies And Devices
Metered-dose Inhalers
MDIs were introduced in 1956

Performance depends on inhalation technique
Use difficult because of poor inhalation-actuation
coordination
Misuse affects drug delivery
Spacers and holding chambers alleviate, but do
not eliminate, problems
The traditional MDI, which was approved by the FDA and marketed in 1956,
remains the most commonly prescribed device for inhalation therapy. The primary
factor influencing the clinical response to medications administered with an MDI is
inhalation technique. However, this technique is difficult to execute properly, and
research has shown that nearly 50% of patients who use an MDI do it incorrectly
because they are unable to coordinate inhalation with device actuation. Observers
first commented on the issue of poor inhalation–actuation coordination as far back
as 1971, yet the MDIs have remained largely unchanged.
63
Evaluation Of MDI Technique
54 >1 error
No error
447
Larsen JS et al. Asthma. 1994;31:193-199.
In a large study involving a total of 500 patients from different medical specialties,
Larsen et al evaluated the patients’ technique in each step of MDI use that is
needed for optimum delivery. Only 54 patients (10.7%) used their MDI correctly.
The percentage of errors was staggering and occurred in almost every step.
Pediatric patients are frequently prescribed an MDI in combination with a spacer or
a holding chamber; for children younger than 5 years of age, a mask is usually
attached to these devices. But with or without spacer devices, improper technique in
the use of MDIs has been demonstrated in many adults and children.
64
Error Summary By Device
80
Aerolizer
70
Autohaler
60 Diskus
50 pMDI
40 TBH
30
20
10
0
1 Error Critical
Error
PMDI, pressurized MDI; TBH, turbuhaler
Molimard M et al. J Aerosol Med. 2003;16:249-254.
In a large real-life observational study, Molimard and colleagues evaluated inhaler

handling in 3,811 patients for at least 1 month. The patients used an Aerolizer,
Autohaler, Diskus pressurized MDI (pMDI) or a Turbuhaler device. Inhalation errors
were considered critical if they could have substantially affected drug delivery to the
lung. Of the patients using a pMDI, 76% made at least 1 error, compared to 49% to
55% of patients using a breath-actuated inhaler. Critical errors were made by 28%
of patients treated with a pMDI.
65
Improper Use Of MDI And
Holding Chambers
60
pMDI
50 pMDI+HC
40
30
20
10
0
Shake Exhale Actuate Inhale Hold
Steps were performed improperly in both groups: those using an MDI

and those using a pMDI+ HC
HC, holding chamber
Scarfone RJ et al. Arch Pediatr Adolesc Med. 2002;156:378-383.
Scarfone et al showed that similar percentages of children performed multiple steps

improperly whether they used an MDI with (60/135, 44.4%) or without (33/73,
45.2%) a holding chamber. The steps performed improperly in the 2 groups were
similar.
66
Jet Nebulizers
Can be used with all classes of

asthma medications
Advantageous for young children and the elderly
Suited for the administration of doses of drugs
Can be used with supplemental oxygen
Less portable than inhalers, require a
power source
Longer treatment time and substantial variability
A jet nebulizer delivery system consists of a nebulizer and a source of compressed

air. Airflow to the nebulizer changes the liquid medication to a mist, which can be
inhaled by the patient over 5 to 10 minutes through a mask or mouthpiece. Jet
nebulizers can be used with all classes of asthma medications. They are particularly
advantageous for young children and for the elderly because no hand–breath
coordination is required. Furthermore, nebulizers are suitable for the administration
of high doses of drugs, as in continuous albuterol nebulization, which is commonly
used in emergency settings and intensive care units for patients with status
asthmaticus. Nebulizers can also be used with supplemental oxygen. Jet nebulizers
are less portable than inhalers and require a power source. Contamination is
possible if the nebulizer components are not routinely cleaned according to the
manufacturer’s recommendations. Other disadvantages of nebulizers include a
longer treatment time than is required with inhalers and substantial variability
between nebulizers due to output variance.
67
Dry Powder Inhalers
The powder contains micronized drug particles

Requires 30 to 120 L of inspiratory flow per minute, which
affects particle size and velocity
May be difficult for patients with severe
bronchoconstriction and/or young children
No need to coordinate device actuation with inhalation
Environmentally friendly and relatively easy and
convenient to use
Studies continue to report countless critical mistakes
with DPIs
Molimard M et al. J Aerosol Med. 2003;16:249-254.
DPIs have been available for more than 30 years. In general, they create aerosols
by drawing air through an aliquot of dry powder. The powder contains micronized
drug particles that either form loose aggregates or are loosely bound to carrier
particles (such as, lactose or glucose). Aggregates of drug particles are broken up
or drug particles are stripped from carrier particles by the energy of inhalation. The
inspiratory flow rate required to provide sufficient energy for this process ranges
from 30 to 120 L/min. Patients with severe bronchoconstriction and/or young
children may find it difficult to inhale “hard” enough to achieve optimal lung
deposition when they use devices requiring a high inspiratory flow rate. The ban on
CFC propellants in MDIs, along with an increasing recognition of the limitations
associated with MDI use, has resulted in an increased development of DPIs during
the past decade. DPIs preclude the need to coordinate device actuation with
inhalation. They are environmentally friendly, and are relatively easy and convenient
to use.
68
Error Summary By Device
80
70 Aerolizer
Autohaler
60
Diskus
50 pMDI
40 TBH
30
20
10
0
1 Error Critical
Error
Molimard M. J Aerosol Med. 2003;16:249-254.
However, despite these developments, studies continue to report countless critical

mistakes with DPIs. In a large, real-life clinical study previously mentioned,
Molimard et al showed the error rate in adults using a DPI to be about 50%.
69
New Nebulizers
Offer a marked improvement in pulmonary drug targeting

Generate aerosol only during inhalation
Shorter time required for drug delivery
Relatively quiet
No need to add diluents to the active drug solution
Three major categories are used
– modified piezoelectric (vibrating mesh or aperture
plate technology)
– high-pressure microspray technology
– electrohydrodynamic or electrostatic spray technology
Rau JL. Respir Care. 2005;50:367-382.
Nebulizer technology continues to evolve, as evidenced by several models that are

being or have been developed. These new devices are more portable and offer a
marked improvement in the efficiency of pulmonary drug targeting. Most of the new
and efficient nebulizers are breath-actuated “dosimeters” that generate aerosol and
make it available only during inhalation. These devices nebulize drug at a higher
rate (0.3-0.6 mL/min), so that a shorter time is required for drug delivery. They are
relatively quiet, and very little, if any, drug remains within them at the end of
treatment, so that the need to add diluents to the active drug is eliminated.The
newer nebulizers fall into 3 major technologic categories: (1) In the modified
piezoelectric (sometimes referred to as vibrating mesh or aperture plate)
technology, a low-velocity aerosol of fine particles is generated with low-frequency
(180-KHz) vibration; a horn or crystal transducer pushes medication through a metal
alloy mesh plate with more than 6,000 holes. (2) In high-pressure microspray
technology, liquid is forced through a nozzle to form aerosol clouds. (3) In
electrohydrodynamic or electrostatic spray atomization, the dispersion of liquid relies
solely on its electric charges.
70
New MDI Aerosols
New technology fostered by the elimination of

CFC propellent and the advent of HFA
HFA drug formulations in solution are emitted as
extrafine aerosols
Fine particles of ≤2 mcg have been shown to
penetrate more effectively into the peripheral
regions of the lung
CFC, chlorofluoroalkane; HFA, hydrofluoroalkane propellant
The elimination of chlorofluroalkane CFC propellant from MDIs and the advent of
HFA propellant have made it possible to more optimally target ICSs directly at all
inflammatory sites of the asthmatic lung. This shift of pulmonary deposition occurred
because HFA drug formulations that are in solution are emitted as extra-fine
aerosols. Fine particles of 2 micron have been shown to penetrate more effectively
into the peripheral regions of the lung.
71
Distribution Of BDP Particle Size In
CFC Suspension And HFA Solution
70
Pulmonary Oropharyngeal
Total Delivered 60
50
Percentage
40 HFA BDP
30 CFC BDP
20
10
0
65 1.1 3 .7 .8 .0 .0 0 at
.
- 0 .65 - - 2.1 - 3. -4 7-5 8-9 10 >1 ro
3 1 3 - h
0.4 0 1.1 2. 3. 4. 5. 9.
0 T
Particle Size, µm
Data from Andersen Cascade Impactor.
Leach CL. Respir Med. 1998;92:3-8.
The HFA BDP inhaler reverses the pattern of deposition of the old CFC BDP
product. The HFA BDP inhaler delivers approximately 60% of drug to the lungs,
compared with less than 10% of the CFC BDP counterpart.
72
Deposition As A Function Of HFA BDP
Inhaler Coordination
On time Early Late
70
60 58 57
50
43
Deposition, %
40 34 32
31
30 26 24 26 24
20
13
8
10
0
Lung* Oropharynx Exhaled Relative
Peripheral*
* Lung was divided into central, intermediate, and peripheral regions.
Leach CL et al. Aerosol Med. 2005;18:379-385.
Even with suboptimal coordination of the patient in using the inhaler, more than 30%
of BDP is deposited within the lungs, and and distribution is even within the lungs.
The HFA BDP inhaler is FDA-approved for the treatment of asthma in children 5
years of age and older. Inhalers in development administer other drugs that have
similar aerosol characteristics in HFA solution: triamcinolone acetonide, flunisolide,
and ciclesonide. None has yet been approved by the FDA.
73
New Dry Powder Inhalers
Reduce dosing variability and are not dependent

on inspiratory flow rate
Two types
– reservoir DPI containing an active-metering cyclone-
separator technology system
– aerosolization chamber with inspiration-actuated,
battery-powered, twin blade impeller to generate
aerosol cloud
Newman SP. Expert Opin Biol Ther. 2004;4:23-33. Hirst RH et al. Respir Med. 2002;96:389-396.
Keating GM et al. Drugs. 2002;62:1887-1895. Nelson H et al. Chest. 1999;115:329-335.
Most of the DPIs available today are “reservoir” devices—that is, the dry powder is
contained within a cartridge and measured at the time of dosing; in other types of
DPIs, the powder is contained within capsules or blister packs. Some of the new
reservoir DPIs in development promise to be more practical and cost-effective
systems for asthma therapy because they reduce the dosing variability seen with
other DPI systems and are not so dependent on inspiratory flow rates. For example,
a new DPI—not currently on the market in the United States—is a reservoir DPI that
contains an active-meter cyclone separator technology system. An internal pump
measures the drug dose by means of controlled air pressure. Inhalation transports
the drug into the cyclone separator, where it is removed from the lactose carrier,
and then into the airway. Studies have shown that deposition of BDP in the lungs
with this DPI is relatively independent of the inhalation efforts of patients, and that
dosing variability is reduced. Another, similar DPI, designed to function more
independently of the patient’s inspiratory effort, features an aerosolization chamber
containing an inspiration-actuated, battery-powered, twin-blade impeller to generate
the aerosol cloud. This design is being studied with micronized albuterol sulfate and
is still under development.
74
New Breath-operated Inhalers
Improved ease of use

Breath-actuated
Facilitating the use of inhalation devices, specifically MDIs, through technologic

advances was the primary reason for the development of breath-operated inhalers
(BOIs). A BOI obviates the need for hand–breath coordination because it
automatically releases a spray of medication when the patient begins to inhale
through the mouthpiece at a low inspiratory rate (about 20 L/min). Two breath-
operated inhaler devices are available, although only 1 has been approved in the
United States. The introduction of this device in the United States for the delivery of
CFC-free albuterol will address several of the issues associated with currently
available asthma therapies: ease of use and efficacy, patient and physician
preferences, and cost-effectiveness. Furthermore, Phase III clinical trials are
currently under way in the United States to assess the safety and efficacy of
administering CFC-free BCP in a new delivery system. If approved, this product will
have the added advantage of offering rescue and maintenance medications in 1
type of device.
75
Cost-effectiveness Of New Devices
Direct and indirect costs associated with asthma

– poor control of asthma
– underuse or incorrect use of available therapies
Preferred devices by patients and
medical providers
– increase compliance
Newer devices tend to be more expensive than traditional MDIs. However, most of
the direct and indirect costs associated with asthma are the result of poor control of
the disease, indicating that currently available therapies are either underused or
used incorrectly. If the new devices are cost-effective and are preferred by patients
and medical providers, as some of the recent studies have clearly shown, then the
benefit would outweigh the cost. An ideal inhaler would be well accepted by
patients, and this might facilitate compliance.
76
Inhaler Use Assessment In Patients
With Airflow Obstruction
MDIs used by 100 patients (22-88 years old)

Referred from inside and outside hospital
Seven devices assessed in random order
Pre-established criteria
Assessment of inhaler technique and
inhaler preference
Lenney J et al. Respir Med. 2000;94:496-500.
In 1 study designed to assess patients’ preferences regarding different inhaler

devices, 100 patients were instructed, in randomized order, in the use of 7 different
inhaler devices. After instruction, they were graded (with predetermined criteria) on
their inhaler technique. After the assessment, patients were asked which 3 inhalers
they most preferred and which, if any, they currently used.
77
Inhaler Use Assessment In Patients
With Airflow Obstruction
Optimal Poor Very Poor

Device
Technique, % Technique, % Technique, %
pMDI 79 6 15
pMDI+spacer 87 6 7
EasiBreathe 91 5 4
Autohaler 91 3 6
Turbuhaler 87 3 10
Accuhaler/Diskus 90 4 6
Clickhaler 90 4 6
Lenney J et al. Respir Med. 2000;94:496-500.
Easi-Breathe, a new BOI, was by far the most popular device with the patients; 91%
of patients demonstrated good technique with a BOI versus 79% with an MDI. This
was despite the fact that 55% of the patients in the study had been using an MDI
before study enrollment and had received further instruction on proper technique at
enrollment in the study. Moreover, approximately 65% of the patients in this study
preferred the Easi-Breathe inhaler to all other devices studied.
78
Aerosol Delivery Device
Selection Criteria
Drug availability, delivery mechanism

Patient age, clinical setting, compliance
Reimbursement/cost
Patient/clinician preferences
Dolovich MB et al. Chest. 2005;127:335-371.
Choosing an aerosol system from among the many newer systems as they become
available will require careful selection. Healthcare providers who are treating
children with asthma often encounter difficulties in devising effective management
plans. Indeed, the challenges that these healthcare providers face is that few drugs
and devices are approved for the very young. Often, they have to use their
imagination and translate the findings of adult studies into pediatric practice. At
other times, they must apply the knowledge gained in administering 1 drug in a
certain way to the administration of another, totally different class of medication
given in a different way. A recently published evidence-based review of inhalation
devices recommended an algorithm, which can be helpful in making a selection.
The clinician should consider the following questions when selecting the appropriate
device:
79
Selecting An Aerosol Delivery Device
In what device(s) is the desired drug available?

Keeping in mind the age of the patient and the clinical
setting, what device(s) is the patient likely to be able to
use properly?
For which device(s) is reimbursement available?
Which device(s) is least costly?
Can all types of inhaled asthma drugs prescribed for the
patient be delivered with the same type of device?
Does the patient or clinician have any specific device
preferences?
Dolovich MB et al. Chest. 2005;127:335-371.
1. In what device(s) is the desired drug available?

2. Keeping in mind the age of the patient and the clinical setting, what
device(s) is the patient likely to be able to use properly?
3. For which device(s) is reimbursement available?
4. Which device(s) is least costly?
5. Can all types of inhaled asthma drugs prescribed for the patient be
delivered with the same type of device?
6. Does the patient or clinician have any specific preferences regarding
devices?
80
Selecting An Aerosol Delivery Device
Healthcare providers caring for children with

asthma should continue to challenge industry to
make devices whose use in the young age group
is more intuitive
They should also continue to lobby industry to
study drug safety and efficacy in the very young
Healthcare providers caring for children with asthma should continue to challenge
industry to make devices whose use in the very young is more intuitive. They should
continue also to lobby industry to study drug safety and efficacy in the very young.
81

Pediatric Asthma Management

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Pediatric Asthma

Welcome to Pediatric Asthma Management: Bridging the Gaps Between Knowledge

PART I: PEDIATRIC ASTHMA: CRITERIA FOR DIAGNOSIS

 Asthma is a chronic inflammatory disorder of the airways

The definition of asthma developed by the National Asthma Education and

 Episodic lower airway obstruction is present

 The recommended methods for the diagnosis of

FEV1, forced expiratory volume in 1 second

 Wheezing in young children is most commonly

The diagnosis of asthma in young children may be difficult because episodic

 Key indicators for considering diagnosis of asthma include

Key indicators for considering a diagnosis of asthma include the following:

 Three Categories of wheezing in children

 Alternative causes of wheezing

Alternative causes of wheezing include the following:

The key to successful diagnosis of asthma is to differentiate its symptoms from

Classification of Severity of Asthma in Children

PEF, peak expiratory flow

Asthma can be classified as follows (Table):

Mild Moderate Severe Status

May be present Often present Heard earlier, may

In status asthmaticus with imminent respiratory arrest, paradoxical thoracoabdominal movement

A Clinical Index to Define Asthma Risk

Major Criteria Minor Criteria

Castro-Rodriguez JA, et al. Am J Respir Crit Care Med. 2000;162:1403-1406.

Castro-Rodreguez et al3 proposed a simple clinical index to predict the presence of

 The presence of asthma in later childhood

 Regular assessment and monitoring

Based on these risk factors, successful pediatric asthma management should

1. Regular assessment and monitoring.

 Prevent chronic symptoms

 Signs and symptoms of asthma

Ongoing assessment includes monitoring in the following areas:

Asthma is considered uncontrolled if 3 or more features of partly controlled asthma

It should be noted that any exacerbation should prompt a review of maintenance

 The Asthma Control Test (ACT) includes the

 Ask about symptom patterns over the past

 For infants ask about

For infants ask about:

 For older children ask about

For older children ask about:

 Use of spirometry is recommended

Use of spirometry is recommended:

 Has child’s asthma been better or worse since

To assess symptoms, ask parents:

To assess whether any exacerbations have occurred, ask parents:

To assess PEF, ask:

Also, check the technique of administering treatment.

To assess what treatments have been used, ask parents:

 Following the care plan

PART II: THE CURRENT UNDERSTANDING OF ASTHMA CONTROL

1. Identify and control environmental triggers – smoke, allergens

Strategies for gaining control of asthma include the following:

1. Identify and control environmental triggers: smoke, allergens.

 In patients not on controller medications

In patients not on controller medications, the severity of asthma is based on

ICS, inhaled corticosteroid; LABA, long-acting β2 agonist; SABA, short-acting β2 agonist

According to the recently revised National Asthma Education and Prevention

ICS, inhaled corticosteroid; LABA, long-acting β2 agonist; SABA, short-acting β2 agonist

 ICSs are recommended as first-line therapy and are the

Rate Ratio for Death From Asthma

– improved lung function 0.5

Before and after 3-months of treatment

ICSs act on a variety of inflammatory and structural cells, including eosinophils, T

Asthma is a chronic inflammatory disorder of the airways

Episodic lower airway obstruction is present

The recommended methods for the diagnosis of

Wheezing in young children is most commonly

Key indicators for considering diagnosis of asthma include

Three Categories of wheezing in children

Alternative causes of wheezing

The presence of asthma in later childhood

Regular assessment and monitoring

Prevent chronic symptoms

Signs and symptoms of asthma

The Asthma Control Test (ACT) includes the

Ask about symptom patterns over the past

For infants ask about

For older children ask about

Use of spirometry is recommended

Has child’s asthma been better or worse since

Following the care plan

In patients not on controller medications

ICSs are recommended as first-line therapy and are the

Growth supression can be assessed as a short-, intermediate-,

Use of biomarkers to adjust ICS dose

Poor control may be partly due to overreliance

Medication adherence rates for asthma patients

Inhaled route is preferable

MDIs were introduced in 1956

Can be used with all classes of

The powder contains micronized drug particles

Offer a marked improvement in pulmonary drug targeting

New technology fostered by the elimination of

Reduce dosing variability and are not dependent

Improved ease of use