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Pediatric Asthma
Evaluation & Management
Bradley E. Chipps, MD, FAAP
Capital Allergy & Respiratory Disease Center
Sacramento, CA
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Definition of Asthma
A chronic inflammatory disease of the airways with the
following clinical features:
 Episodic and/or chronic symptoms of airway obstruction
 Bronchial hyperresponsiveness to triggers
 Evidence of at least partial reversibility of the airway
obstruction
 Alternative diagnoses are excluded
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Diagnosis
1. History
2. Pulmonary function tests (PFTs)
3. Challenge studies
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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.
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Cough—Asthma?
Consider asthma in children with:




Recurrent episodes of cough with or without wheezing
Nocturnal awakening because of cough
Cough that is associated with exercise/play
Cough without wheeze is often not asthma
Cough may be the only symptom
present in patients with asthma.
Goldsobel AB, Chipps BE. Cough in the pediatric population. J Pediatr. 2010;156(3):352–358
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Asthma Predictive Index
 Identify high risk children (2 and 3 years of age):
• ≥4 wheezing episodes in the past year
(at least one must be MD diagnosed)
PLUS
 One major criterion
• Parent with asthma
• Atopic dermatitis
• Aero-allergen
sensitivity
OR
 Two minor criteria
• Food sensitivity
• Peripheral
eosinophilia (≥4%)
• Wheezing not
related to infection
Modified from: Castro-Rodriguez JA, Holberg CJ, Wright AL, et al. A clinical index to define risk of asthma in young children with recurrent
wheezing. Am J Respir Crit Care Med. 2000;162(4 Pt 1):1403–1406
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Objective Evaluation of Asthma
 Physical examination
 Pulmonary function
 Bronchoprovocation
 Validated control tools
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Defining Asthma Severity and Control
1) 0–4 years
2) 5–11 years
3) 12 years and older
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How Can Asthma Control Be Measured?
Inflammation?
Direct or indirect?
Lung
function?
Daytime
symptoms?
Utilization of
healthcare
resources?
Functional
status?
Nighttime
awakenings?
Asthma
Control
Missed work
and/or school?
Patient self-report
of control?
Asthma control test is a trademark of QualityMetric Incorporated.
Use of “quick
relief” inhaler
and/or
nebulizer?
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35
Asthma Control Cannot be Assessed
at a Single Time Point
% of Patients
30
25
20
15
10
5
0
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15-19 20-24 25+
Number of Changes Over Weeks 1–12
Approximately one-third of both adult and pediatric subjects had 15 or more changes in their
asthma severity classification based upon peak expiratory flow (PEF) during the 12-week studies.
Chipps BE, Span JD, Sorkness CA, et al. Variability in asthma severity in pediatric subjects with asthma previously receiving short-acting beta2agonists. J Pediatr. 2006;148(4):517–521; Calhoun WJ, Sutton LB, Emmett A, et al. Asthma variability in patients previously treated with beta2agonists alone. J Allergy Clin Immunol. 2003;112(6):1088–1094
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Classifying Asthma Severity and Initiating
Treatment in Children 0 to 4 Years of Age
Adapted from: National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and
Management of Asthma. US Department of Health and Human Services. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
Accessed July 5, 2012
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Assessing Asthma Control and Adjusting
Therapy in Children 0 to 4 Years of Age
Adapted from: National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and
Management of Asthma. US Department of Health and Human Services. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
Accessed July 5, 2012
Test for Respiratory and Asthma Control in Kids
(TRACK)
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Stepwise Approach for Managing Asthma
in Children 0 to 4 Years of Age
Adapted from: National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and
Management of Asthma. US Department of Health and Human Services. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
Accessed July 5, 2012
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Classifying Asthma Severity and Initiating
Treatment in Children 5 to 11 Years of Age
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Assessing Asthma Control and Adjusting
Therapy in Children 5 to 11 Years of Age
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Childhood Asthma Control Test™
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Stepwise Approach for Managing Asthma
in Children 5 to 11 Years of Age
Adapted from: National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and
Management of Asthma. US Department of Health and Human Services. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
Accessed July 5, 2012
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Classifying Asthma Severity and Initiating
Treatment in Youth ≥12 Years of Age and Adults
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Assessing Asthma Control in Children
≥12 Years of Age and Adults
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Asthma Control Test™ (ACT)
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Stepwise Approach for Managing Asthma
in Children 12 Years of Age and Adults
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Infants and Young Children—
When to Start Controllers
 >3 episodes of wheezing in the last year, and
 Parental history of asthma or physician diagnosis of
eczema
Or 2 of the following:
 Physician diagnosis of allergic rhinitis, wheezing apart
from colds, peripheral eosinophilia
 Courses of oral steroids more often than every 6 weeks
 Symptoms >2 times per week, nocturnal symptoms >2
times per month
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Step-down Therapy
Step down once control is achieved:
 After 2–3 months
 25% reduction over 2–3 months
Follow-up monitoring:





Every 1–6 months
Assess symptoms.
Review medication use.
Objective monitoring (PEF or spirometry)
Review medication.
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Step-up Therapy
 Indications: Symptoms, need for quick-relief
medication, exercise intolerance, decreased lung
function
• May need a short course of oral steroids.
 Continue to monitor.
• Follow and reassess every 1–6 months
• Step down when appropriate.
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Phenotypic Expressions of Childhood
Wheezing Disorders
1. Viral induced wheezing
2. Severe intermittent wheezing
3. Exercise bronchospasm/asthma
4. Persistent asthma
5. Severe asthma
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Viral Induced Wheezing
1. Triggered by viral infections
2. Non-atopic
3. Remission in childhood
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Infants
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

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
Intermittent Inhaled Corticosteroids (ICS)
in Infants with Episodic Wheezing
Single randomized double-blind study
N=411 infants with a 3-day history of wheezing
Infants treated with budesonide 400 µg/d or placebo
for 2 weeks
Primary outcome variables were:
•
•
•
•
Number of symptom free days
Number of days free from rescue medication use
Number of episodes
Number of treatments with open label budesonide
Bigaard H, Hermansen MN, Loland L, et al. Intermittent inhaled corticosteroids in infants with episodic wheezing. N Eng J Med.
2006;354(19):1998–2005
Intermittent ICS in Infants:
Withdrawal Due to Persistent Wheezing
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Percentage of Children Withdrawn
Because of Persistent Wheezing
50
40
30
Budesonide
20
Placebo
10
P=0.41
0
0
100 200 300 400 500 600 700 800 900
Days after Randomization
No. at Risk
Budesonide
149
115
78
27
Placebo
145
114
92
27
Progression from episodic to persistent wheezing. Results were not significant.
Bigaard H, Hermansen MN, Loland L, et al. Intermittent inhaled corticosteroids in infants with episodic wheezing. N Eng J Med. 2006;354(19):1998–
2005
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Role of Viral Infections
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Rhinovirus (RV) Wheezing versus
Respiratory Syncytial Virus (RSV) Wheezing in
First 3 Years of Life and Asthma at 6 Years of Age
Jackson DJ, Gangnon RE, Evans MD, et al. Wheezing rhinovirus illnesses in early life
predict asthma development in high-risk children. Am J Respir Crit Care Med. 2008;
178(7):667–672
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Forced Expiratory Volume in 1 Second (FEV1)
Percent Predicted
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RV Infections and the Development of Asthma
 RV infections can produce more than upper airway
illnesses during infancy.
 Children who develop asthma by 6 years of age have a
significantly increased burden of viral wheezing illnesses
in early life.
 Pulmonary function abnormalities at 6 years of age are
most significantly associated with early childhood
wheezing illnesses due to RV (not RSV).
 Of all outpatient wheezing viral illnesses in early life,
those due to RV are most significant.
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Oral Prednisolone for Preschool Children
with Acute Virus-induced Wheezing

Randomized, double-blind, placebo-controlled trial comparing a 5-day course of oral
prednisolone (10 mg daily for children 10–24 months and 20 mg daily for older children)
versus placebo in 700 children between the ages of 10 and 60 months.


No difference in 7-day symptom scores, albuterol use, or readmission
Primarily non-atopic and 60% first time wheezers
Panickar J, Lakhanpaul M, Lambert PC, et al. Oral prednisolone for preschool
children with acute virus-induced wheezing. N Engl J Med. 2009;360(4):329–338
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Severe Intermittent
Wheezing
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Acute Intermittent Management Strategies
(AIMS)—Primary Hypothesis
In young children with recurrent severe wheezing,
intervention with an ICS or leukotriene receptor
antagonist (LTRA) at the onset of respiratory tract illness
(RTI)-associated symptoms will increase the proportion
of episode-free days over a 12-month period compared
with conventional therapy.*
*Conventional therapy—inhaled bronchodilator followed by the sequential addition of systemic
corticosteroids
Episodic Use of an ICS or LTRA in Preschool Children
with Moderate-to-Severe Intermittent Wheezing
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Acute Intermittent Management Strategies (AIMS)
Study Overview
At first sign of RTI symptoms x 7 days
Budesonide 1 mg bid + Placebo LTRA + b-agonist
Run in
Randomization
Montelukast 4 mg daily + Placebo ICS + b-agonist
Placebo LTRA + Placebo ICS + b-agonist
 Randomized, multicenter, double-blind, placebo-controlled 1 year trial
 238 children, 12–59 months, with recurrent episodes of intermittent wheezing
• 2 episodes in the previous year
• 2 urgent care visits, 2 oral steroid courses, or 1 of each
 Primary outcome = episode free days
 Secondary outcomes = symptoms scores during illnesses and oral corticosteroids (OCS)
use
Bacharier LB, Phillips BR, Zeiger RS, et al. Episodic use of an inhaled corticosteroid or leukotriene receptor antagonist in preschool children with
moderate-to-severe intermittent wheezing. J Allergy Clin Immunol. 2008;122(6):1127–1135
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1° Outcome—Mean Proportion of
Episode Free Days
Proportion of episode free days adjusted for age group, API status, center
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Maintenance versus Intermittent Inhaled
Steroids in Wheezing Toddlers (MIST) Study
1. 12 month R, DB, active control: 278 children
(12–53 months)
2. 4 episodes of wheezing last year: Positive mAPI
 1 episode: OCS, emergency department,
urgent care or hospital
3. Primary outcome: Exacerbation with OCS
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Run-in: 2 weeks
Treatment Phase: 52 weeks
Randomized
Pbo run-in
nightly +
Albuterol PRN
Treatment Group
Daily low dose
budesonide
Nightly, except During RTIs
during RTI
only for 7
days
0.5 mg PM
Pbo AM
0.5 mg PM
Intermittent high dose
budesonide
Pbo PM
1.0 mg AM
1.0 mg PM
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MIST Study
1. Exacerbations 0.95/patient year; p=0.6
2. Similar time to first exacerbation; p=0.87
3. No difference in treatment failures or episode free
days
4. Height=0.26 cm average difference; weight=0.16 Kg
average difference
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Diagnosis of Exercise-induced
Bronchospasm (EIB) / Exerciseinduced Asthma (EIA)
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EIA Therapy—General Principles
 EIA may reflect suboptimally controlled asthma,
which may require adjustment of overall therapy of
asthma.
 Goal: Facilitate normal activity levels, including
competitive sports.
 Individualize therapy.
 Child needs to understand and be a partner in
therapy.
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Diagnosis of EIB
 Normal PFT at rest
 No other stimulus for bronchospasm
 Most common in allergic rhinitis patients
 Dx: 10% decrease FEV1 after 8 minutes of exercise
at 90% maximum predicted heart rate
 Rx: B-agonist before exercise, LTRA daily
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Diagnosis of EIA
 Normal or obstructive PFT at rest
 Patient has other stimuli for asthma symptoms.
 Patient has both inflammatory and bronchospasm
component.
 Dx: Same criteria
 Rx: ICS, LTRA, ICS/long-acting beta antagonist (LABA)
daily, B-agonist before exercise
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Persistent Asthma
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Multicentre Allergy Study (MAS)
1. Birth cohort: 1314
• 13-year follow up: 441 (33.6% all visits)
• No wheeze 1st year: 315 (74%)
2. Early wheezers: 126
• No wheeze (4–13 years): 79 (68%)
• Initial wheeze: 43 (34%)
• Persistent wheeze: 4 (3%)
3. Wheeze 3–6 years: 40 (13%)
4. Wheeze 6–13 years: 42 (13%)
Matricardi PM, Illi S, Grüber C, et al. Wheezing in childhood: incidence, longitudinal patterns and factors predicting persistence. Eur Respir J.
2008;32(3):585–392
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The Prevalence of Wheezing Varies
Depending on Age and Atopic Status
Prevalence (%)
Atopic (n=94)
Non-atopic (n=59)
80
70
60
50
40
30
20
10
0
1
2
3
4
5
6
7
8
9 10 11 12 13
Age (years)
Illi S, von Mutius E, Lau S, et al. Perennial allergen sensitisation early in life and chronic asthma in children: a birth cohort study. Lancet.
2006;368(9537):763–770
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Time of Sensitization and Degree of Exposure to Indoor
Allergens and Lung Function Impairment at 7 Years of Age
120
115
110
105
100
95
90
85
115
p=0.009
p=0.003
110
105
100
95
90
85
80
80
75
70
0
75
NS S/LE S/HE NS S/LE S/HE
FEV1
(% pred)
MEF50
(% pred)
70
0
NS S/LE S/HE
NS S/LE S/HE
FEV1
(% pred)
MEF50
(% pred)
Illi S, von Mutius E, Lau S, et al. Perennial allergen sensitisation early in life and chronic asthma in children: a birth cohort
study. Lancet. 2006;368(9537):763–770
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Melbourne Epidemiological Study
Phelan PD, Robertson CF, Olinsky A. The Melbourne Asthma Study: 1964-1999. J Allergy Clin Immunol. 2002;109(2):189–194
A Longitudinal, Population-based, Cohort Study
of Childhood Asthma Followed to Adulthood
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Sears MR, Greene JM, Willan AR, et al. A longitudinal population-based, cohort study of childhood asthma followed to adulthood. N Engl J Med.
2003;349(15):1414–1422
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ICS Therapy in Preschool Children
 Multicenter, double-blind, randomized placebo controlled
study designed to determine if ICS therapy can modify the
subsequent development of asthma in high risk children
 Children with a positive asthma predictive index (2–3
years of age, N=285) treated with either fluticasone 88 µg
BID or placebo for 2 years followed by a year of
observation
 Primary outcome variable: Proportion of episode free
days
Guilbert TW, Morgan WJ, Zeiger RS, et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med.
2006; 354(19):1985–1997
Fluticasone Had No Carryover Effect
During the Observation Period
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Proportion of Episode-free Days
p=0.78
p=0.006
1.00
0.95
Fluticasone
Placebo
0.90
0.85
0.80
0.75
0.00
0
2
4
6
8
10
12
14
16
18
20
22
24
26
28
30
32
34
36
Months
Treatment Period
Observation Period
The increase in symptom free days in the fluticasone cohort during the treatment period was
lost in the 12 months subsequent during the observation period.
Guilbert TW, Morgan WJ, Zeiger RS, et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med.
2006;354(19):1985–1997
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The Need for Oral Corticosteroids
Children Not Receiving
Supplementary Medication
All Children
No Need for a First course
of Prednisolone (% of children)
Observation
Treatment
100
100
Fluticasone
75
Observation
75
50
Placebo
50
Placebo
25
25
0
0
0
6
Fluticasone
12 18 24 30 36
Months
0 24 26 28 30 32 34 36
Months
No. at Risk
No. at Risk
Fluticasone
143
102
80
66
57
42
Fluticasone
132
88
Placebo
142
87
62
57
50
41
Placebo
130
85
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No Need for Supplementary
Asthma-Controller Medication
(% of children)
The Need for Supplementary Controller Meds:
No Difference at 36 months
100
100
Fluticasone
Fluticasone
75
75
Placebo
Placebo
50
50
25
25
0
0
0
6
12 18 24 30 36
0
Months
No. at Risk
No. at Risk
Fluticasone
143
131
118
116
113
99
Placebo
142
125
103
99
93
86
24 26 28 30 32 34 36
Months
Fluticasone
132
111
Placebo
130
105
The fluticasone group had less of a need for supplementary medications during the
treatment period (p<0.01). By the end of the observation period (36 months), the
groups were indistinguishable (P=0.99)
Guilbert TW, Morgan WJ, Zeiger RS, et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med. 2006;
354(19):1985–1997
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20
15
10
5
0
0
10
20
Months
30
Difference in Height Change
between Fluticasone and
Placebo Groups (cm)
Change in Height from
Baseline (cm)
Changes in Height from Baseline and Between Groups
0
-0.5
-1.0
-1.5
Month
0
1 4
10
20
30
8 12 16 20 24 28 32 36
P value
Change in height from baseline represented by the panel on the left. The difference between
groups with associated p-values represented on the right. At the end of 24 months the fluticasone
group averaged 1.1 cm less than the placebo group. At the end of the observation period
(36 months) the difference between groups was 0.7 cm.
Guilbert TW, Morgan WJ, Zeiger RS, et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med. 2006;
354(19):1985–1997
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Summary and Clinical Implications
Based on the results of the Prevention of Early Asthma
in Kids (PEAK) study:
 ICS are effective in improving asthma-like symptom
burden, exacerbations, and lung function in high
risk toddlers.
 Continuous ICS therapy for 2 years once
discontinued does not modify the natural history of
asthma in early childhood.
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START
INHALED STEROID TREATMENT
AS REGULAR THERAPY
IN EARLY ASTHMA
The World’s Largest Study
in Asthma Therapy
Pauwels RA, Pedersen S, Busse WW, et al. Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial.
Lancet. 2003;361(9363):1071–1076
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Primary Study Objective and Primary Variables
 Examines effect of early intervention with ICS on
evolution of newly diagnosed asthma
 Primary outcome:
• Time to first severe asthma-related event (SARE) during
first 3 years of study
• A severe event requiring hospitalization or emergency
treatment due to worsening of asthma or death due to
asthma
 Secondary outcome:
• Change in postbronchodilator FEV1
 Intent to treat analysis
Pauwels RA, Busse WW, O’Byrne PM, et al. The inhaled Steroid Treatment as Regular Therapy in early asthma (START) study: rationale and design.
Control Clin Trials. 2001;22(4):405–419
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Double-blind (Part A) and
Open-label (Part B) Design
Part A – Pulmicort therapy
Adults
Pulmicort 400 g once daily
+ usual asthma therapy
Children (6–10 y of age)
Part B: Open-label
Adults
Pulmicort 400 g once daily
+ usual asthma therapy
Pulmicort 200 g once daily
+ usual asthma therapy
Part A – Reference therapy
Children (6–10 y of age)
Pulmicort 200 g once daily
+ usual asthma therapy
Adults and Children
Placebo once daily
+ usual asthma therapy
Year 0
1
2
3
4
5
Visit 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
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Time to First SARE
Cumulative Probability
44% (95% CI, 29–55%) reduced risk of first SARE*
0.10
Budesonide therapy
Reference therapy
0.08
0.06
0.04
0.02
0.00
0
1
2
3
*Hazard ratio = 0.56; P<.0001.
Pauwels RA, Pedersen S, Busse WW, et al. Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial.
Lancet. 2003;361(9363):1071–1076
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Patients Requiring Additional Corticosteroids*
60
% of Patients
50
40
30
20
10
0
Budesonide Therapy
Reference Therapy
*Inhaled, oral, or systemic
Pauwels RA, Pedersen S, Busse WW, et al. Early intervention with budesonide in mild persistent asthma: a randomised, double-blind
trial. Lancet. 2003;361(9363):1071–1076
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Changes in Postbronchodilator FEV1 Over 3 Years
Pauwels RA, Pedersen S, Busse WW, et al. Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial.
Lancet. 2003;361(9363):1071–1076
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Early Intervention with Budesonide in
Mild Persistent Asthma
Sullivan SD. Early intervention with budesonide in mild persistent asthma—the
START study. Presented at the European Respiratory Society (ERS). Stockholm,
Sweden, 2002
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Early Intervention with Budesonide in
Mild Persistent Asthma
 Budesonide therapy reduces the risk of a severe
asthma exacerbation by 44% in patients with mild
persistent asthma.
 Daily treatment with low dose budesonide decreases
the need for oral corticosteroids in mild persistent
asthma.
 Budesonide daily improves asthma control
• More symptom free days
• Less additional asthma medication
Pauwels RA, Pedersen S, Busse WW, et al. Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial. Lancet.
2003;361(9363):1071–1076
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BADGER Trial
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BADGER Trial
1. 182 children (6–17 years of age), uncontrolled
asthma, FP 100 µg BID, triple crossover design,
16-week period
2. FP 250 µg BID
FP 100 µg + SALM 50 µg BID
FP 100 µg BID + MTL 5 or 10 mg daily
3. 3 outcomes
• Exacerbations
• Symptom free days
• FEV1 (Pre)
Lemanske RF, Mauger DT, Sorkness CA, et al. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. N Engl
J Med. 2010;362:975–985
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Primary Predictors of a Differential
Response to Step-up Therapy
Lemanske RF, Mauger DT, Sorkness CA, et al. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. N Engl J Med.
2010;362:975–985
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Primary Predictors of a Differential
Response to Step-up Therapy
Lemanske RF, Mauger DT, Sorkness CA, et al. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. N Engl J Med.
2010;362:975–985
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Secondary Predictors of a Differential
Response to Step-up Therapy
Lemanske RF, Mauger DT, Sorkness CA, et al. Step-up therapy for children with uncontrolled
asthma receiving inhaled corticosteroids. N Engl J Med. 2010;362:975–985
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Enrollment, Outcomes, and Schedule of Evaluations
Lemanske RF, Mauger DT, Sorkness CA, et al. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. N Engl J Med.
2010;362:975–985
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Pairwise Comparisons
Lemanske RF, Mauger DT, Sorkness CA, et al. Step-up therapy for children with uncontrolled asthma receiving inhaled
corticosteroids. N Engl J Med. 2010;362:975–985
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Probability of Best Response
Lemanske RF, Mauger DT, Sorkness CA, et al. Step-up therapy for children with uncontrolled asthma receiving inhaled
corticosteroids. N Engl J Med. 2010;362:975–985
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Severe Asthma
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Severe Asthma
 Refractory
 Difficult to control asthma
 Uncontrolled asthma refractory to conventional
treatment
 Frequent exacerbations
 ? Distinct phenotype or subgroup
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Reasons for Failure to Achieve Control
 Compliance
 Asthma heterogeneity
 Wrong diagnosis
 Wrong target
 Failure to deliver drug to the target site
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Demographic and clinical
characteristics of children
and adolescents with severe or
difficult-to-treat asthma
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TENOR Study Design
 3-year, multi-center, observational study
• Patients continued to receive medications and
treatments administered for their asthma as
indicated by their physician.
 4,756 patients enrolled between January and
October 2001
• 6 years of age or older
• 283 sites across the US
Dolan CM, Fraher KE, Bleecker ER, et al. Design and baseline characteristics of The Epidemiology and Natural History of Asthma: Outcomes
and Treatment Regimens (TENOR) study: a large cohort of patients with severe or difficult-to-treat asthma. Ann Allergy Asthma Immunol.
2004; 92(1):32–39
TM
Objectives
 Primary objective
• Describe the natural history of patients considered
by physicians to have “severe” or “difficult-to-treat”
asthma.
 Secondary objectives
• Examine relationship between features of asthma,
treatments, and outcomes.
• Observe frequency of comorbid conditions.
• Examine the relationship between immunoglobulin
and disease.
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Methods
 Cross-sectional baseline data analyzed
 TENOR patients between 6 and 17 years of age included
(N=1,261)
 Patients categorized into 4 age groups by gender:
Age group (years)
6-8
9-11
12-14
15-17
Males
(N=791)
n (%)
145 (18)
282 (36)
240 (30)
124 (16)
Females
(N=470)
n (%)
88 (19)
120 (26)
171 (36)
91 (19)
Total
(N=1,261)
n (%)
233 (18)
402 (32)
411 (33)
215 (17)
Chipps BE, Szefler SJ, Simons FE, et al. Demographic and clinical characteristics of children and adolescents with severe or difficult-to-treat asthma.
J Allergy Clin Immunol. 2007;119(5):1156–1163
TM
Spirometry by Age and Gender
Chipps BE, Szefler SJ, Simons FE, et al. Demographic and clinical characteristics of
children and adolescents with severe or difficult-to-treat asthma. J Allergy Clin
Immunol. 2007;119(5):1156–1163
TM
Medication Use by Age
*Based on test for linear trend, a statistically significant age trend (P <.05) was seen for methylxanthines and long-acting b-agonists.
Chipps BE, Szefler SJ, Simons FE, et al. Demographic and clinical characteristics
of children and adolescents with severe or difficult-to-treat asthma. J Allergy
Clin Immunol. 2007;119(5):1156–1163
TM
Healthcare Utilization by Long-term Controller Use:
6–11 and 12–17 Years of Age
Chipps BE, Szefler SJ, Simons FE, et al. Demographic and clinical characteristics
of children and adolescents with severe or difficult-to-treat asthma. J Allergy
Clin Immunol. 2007;119(5):1156–1163
TM
Summary―Predicting Persistence of Wheezing
1. Family history of asthma
2. Recurrent lower airway symptoms in infancy
3. Absence of nasal symptoms at 1 year
4. Atopic sensitization before 4 years and early exposure
5. Eczema
6. Exposure to ETS
7. Females
8. Acetaminophen ?
9. Vitamin D ?
TM
Thank You
TM
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