Download Pediatric Asthma Update

Pediatric Asthma
Update
Thomas Flaim, M.D.
Key Differences from 1997
and 2002 Expert Panel
Reports
 Clearly defined the level of evidence used to support
recommendations
 Categories A, B, C and D
 Strength of recommendation
 Severity vs Control
 Impairment vs Risk Domains
 Stepwise Approach for Managing Asthma
 Six treatment steps
 Three age categories (0-4 years, 5-11 years, ≥ 12 years)
 Inclusion of validated questionnaires
 ACT, Childhood Asthma Control Test, ACQ, ATAQ
 Peak flow monitoring vs symptom-based monitoring
Guidelines for the Diagnosis and Management of Asthma (EPR-3) 2007. NIH, NHLBI. August 2007.
NIH publication no. 08-4051.
Key Differences from 1997
and 2002 EPR
Assessment and Monitoring
 Separate but related concepts of severity,
control and responsiveness to treatment
 Classify severity to initiate therapy
 Assess control to monitor and adjust therapy
 Both severity and control have 2 domains:
 Impairment
 Risk
Guidelines for the Diagnosis and Management of Asthma (EPR-3) 2007. NIH, NHLBI. August 2007.
NIH publication no. 08-4051.
Assessment and
Monitoring
 Impairment
 frequency and intensity of symptoms and
functional limitations the patient is
experiencing or has recently experienced
 Risk
 likelihood of either asthma exacerbations,
progressive decline in lung function or risk of
adverse effects from medications
Guidelines for the Diagnosis and Management of Asthma (EPR-3) 2007. NIH, NHLBI. August 2007.
NIH publication no. 08-4051.
Assessment and
Monitoring
 Severity
 The intrinsic intensity of the disease process
 Measured most easily and directly in a patient not
receiving long-term control therapy
 Assessed to guide clinical decisions on appropriate
medications and interventions
 Control
 The degree to which the manifestations of asthma
(symptoms, functional impairments and risks of
untoward events) are minimized and the goals of
therapy are met
 Guide decisions to maintain or adjust therapy
 Responsiveness
 The ease with which asthma control is achieved by
therapy
Guidelines for the Diagnosis and Management of Asthma (EPR-3) 2007. NIH, NHLBI. August 2007.
NIH publication no. 08-4051.
Mismatch Between Symptoms,
Medication Use, and FEV1
Study Design
 Objective: To determine if lung function measures in children are
consistent with levels of asthma severity
as defined by the NAEPP guidelines
 Prospective study in 219 children aged 5-18 years attending 2 asthma
subspecialty clinics
 Parents completed questionnaires regarding their child’s asthma
symptom frequency over the last month and medication use over the
last week
 All children performed spirometry
 Differences in lung function were assessed in children of different
asthma severities
. Bacharier et al. Am J Respir Crit Care Med. 2004;170:426-432
FEV1 Values Were Similar
Regardless of Asthma Severity
FEV1 80%
100%
FEV1 60% – <80%
FEV1 <60%
% of Patients
80%
60%
40%
20%
0%
Mild
Intermittent
(n=14)
Mild
Persistent
(n=58)
P=0.3, Chi-square test.
Bacharier et al. Am J Respir Crit Care Med. 2004;170:426-432.
Moderate
Persistent
(n=46)
Severe
Persistent
(n=85)
Classifying Asthma Severity and
Initiating Treatment in Children 0-4
Years of Age
Classification of Asthma Severity
(0-4 years of age)
Components of
Severity
Impairment
Persistent
Intermittent
Mild
Moderate
Severe
Symptoms
≤2 days/week
>2 days/week but
not daily
Daily
Throughout
the day
Nighttime awakenings
0
1-2x/month
3-4x/month
>1x/week
Short-acting beta2-agonist use
for symptom control (not
prevention of EIB)
≤2 days/week
>2 days/week but
not daily
Daily
Several times
per day
Interference with
normal activity
None
Minor limitation
Some limitation
Extremely limited
0-1/year
Risk
Exacerbations
requiring oral
systemic corticosteroids
≥2 exacerbations in 6 months requiring oral systemic corticosteroids, or
≥4 wheezing episodes/1 year lasting >1 day AND risk factors for persistent
asthma
Consider severity and interval since last exacerbation.
Frequency and severity may fluctuate over time.
Exacerbations of any severity may occur in patients in any severity category
Recommended Step for
Initiating Therapy
(See figure 4-1a for
treatment steps.)
Step 1
Step 2
Step 3 and consider short course of
systemic oral corticosteroids
In 2-6 weeks, depending on severity, evaluate level of asthma control that is achieved. If no clear
benefit is observed in 4-6 weeks, consider adjusting therapy or alternative diagnoses.
Guidelines for the Diagnosis and Management of Asthma (EPR-3) 2007. NIH, NHLBI. August 2007.
NIH publication no. 08-4051.
Assessing Asthma Control and
Adjusting Therapy in Children 0-4
Years of Age
Classification of Asthma Control (0-4 years of age)
Components of
Control
Impairment
Risk
Well Controlled
Not Well Controlled
Symptoms
≤2 days/week
>2 days/week
Nighttime awakenings
≤1x/month
>1x/month
>1x/week
None
Some limitation
Extremely limited
≤2 days/week
>2 days/week
Several times per day
0-1 per year
2-3 per year
>3 per year
Interference with
normal activity
Short-acting beta2-agonist
use for symptom control
(not prevention of EIB)
Exacerbations requiring
oral systemic
corticosteroids
Treatment-related
adverse effects
Recommended Action for
Treatment
(See figure 4-1a for
treatment steps.)
Very Poorly Controlled
Throughout
the day
Medication side effects can vary in intensity from none to very troublesome and worrisome.
The level of intensity does not correlate to specific levels of control but should be considered
in the overall assessment of risk.
 Maintain current treatment.
 Step up (1 step) and
 Regular followup every 1-6
months.
 Reevaluate in 2-6 weeks.
 Consider step down if well
controlled for at least 3
months
 If no clear benefit in 4-6
weeks, consider alternative
diagnoses or adjusting
therapy.
 For side effects, consider
alternative treatment
options.
Guidelines for the Diagnosis and Management of Asthma (EPR-3) 2007. NIH, NHLBI. August 2007.
NIH publication no. 08-4051.
 Consider short course of oral
systemic corticosteroids,
 Step up (1-2 steps) and
 Reevaluate in 2 weeks.
 If no clear benefit in 4-6
weeks, consider alternative
diagnoses or adjusting
therapy.
 For side effects, consider
alternative treatment options
Categories of Evidence Used
to Support NAEPP
Recommendations
Evidence
Category
Description
A
Randomized, controlled trials (rich body of
data)
B
Randomized, controlled trials (limited
body of data)
C
Nonrandomized trials and observational
studies
D
Panel consensus judgment
Stepwise Approach for Managing Asthma in
Children 0-4 Years of Age
Intermittent
Asthma
Persistent Asthma: Daily Medication
Consult with asthma specialist if step 3 care or higher is required.
Consider consultation at step 2.
Step 6
Step 5
Step 4
Step 3
Step 1
Step 2
Preferred:
Preferred:
Medium-dose
ICS
Preferred:
Low-dose ICS
SABA PRN
Alternative:
Preferred:
Medium-dose
ICS + either
LABA or
Montelukast
Preferred:
High-dose ICS
+ either LABA
or Montelukast
Preferred:
High-dose ICS
+ either LABA
or Montelukast
Oral systemic
corticosteroids
Cromolyn or
Montelukast
Patient Education and Environmental Control at Each Step
Step up if
needed
(first, check
adherence,
inhaler
technique and
environmental
control)
Assess
control
Step down if
possible
(and asthma is
well controlled
at least 3
months)
Quick-Relief Medication for All Patients
• SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms.
• With viral respiratory infection: SABA q 4-6 hours up to 24 hours (longer with physician consult). Consider short course of
systemic oral corticosteroids if exacerbation is severe or patient has history of previous severe exacerbations.
• Caution: Frequent use of SABA may indicate the need to step up treatment. See text for recommendations on initiating
daily long-term-control therapy.
Key: ICS, inhaled corticosteroid; LABA, inhaled long-acting beta2-agonist; SABA, inhaled short-acting beta2-agonist
Guidelines for the Diagnosis and Management of Asthma (EPR-3) 2007. NIH, NHLBI. August 2007.
NIH publication no. 08-4051.
11
Evidence Supporting ICS Use
in Children Aged 0 to 4 Years
Recommendation
Evidence
Category
ICS, especially at low doses even for extended periods of time,
is generally safe
A
When initiating long-term controller therapy, daily ICS is preferred
A
Step 2:
Preferred treatment is low-dose, daily ICS
Step 3:
Preferred treatment is medium-dose ICS
Step 4:
Preferred treatment is medium-dose ICS and either
montelukast or LABA
A
D
D
Step 5:
Preferred treatment is high-dose ICS and either
montelukast or LABA
D
Step 6:
High-dose ICS and either montelukast or LABA and
oral systemic corticosteroids may be given
D
Stepwise Approach for Managing Asthma in
Children 5-11 Years of Age
Intermittent
Asthma
Persistent Asthma: Daily Medication
Consult with asthma specialist if step 4 care or higher is required.
Consider consultation at step 3.
Step 6
Step 5
Step 4
Step 2
Step 1
Preferred:
SABA PRN
Preferred:
Low-dose ICS
Alternative:
Cromolyn,
LTRA
Nedocromil, or
Theophylline
Step 3
Preferred:
Preferred:
Medium-dose
ICS + LABA
Low-dose ICS
+ either LABA,
LTRA, or
Theophylline
OR
Alternative:
Medium-dose
ICS + either
LTRA or
Theophylline
Preferred:
High-dose ICS
+ LABA
Alternative:
High-dose ICS
+ either LTRA
or Theophylline
Preferred:
High-dose ICS
+ LABA + oral
corticosteroid
Alternative:
High-dose ICS
+ either LTRA
or Theophylline
+ oral systemic
corticosteroid
Medium-dose
ICS
Each step: Patient education, environmental control, and management of comorbidities.
Step up if
needed
(first, check
adherence,
inhaler
technique,
environmental
control and
comorbid
conditions)
Assess
control
Step down if
possible
(and asthma is
well controlled
at least 3
months)
Steps 2-4: Consider subcutaneous allergen immunotherapy for patients who have allergic asthma.
Quick-Relief Medication for All Patients
• SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-minute
intervals as needed. Short course of oral systemic corticosteroids may be needed.
• Caution: Increasing use of SABA or use >2 days a week for symptom relief (not prevention of EIB) generally indicates
inadequate control and the need to step up treatment.
Key: ICS, inhaled corticosteroid; LABA, inhaled long-acting beta2-agonist; SABA, inhaled short-acting beta2-agonist
Guidelines for the Diagnosis and Management of Asthma (EPR-3) 2007. NIH, NHLBI. August 2007.
NIH publication no. 08-4051.
13
Evidence Supporting ICS Use in
Children Aged 5 to 11 Years
Recommendation
Step 2:
Daily low-dose ICS is preferred
Evidence
Category
A
Step 3: Medium-dose ICS or low-dose
ICS plus the addition of some form of
adjunctive therapy are equivalent option
B
Step 4: Medium-dose ICS and LABA
are preferred Step 4 treatment
B
Step 5: High-dose ICS and LABA are
preferred
B
Step 6: High-dose ICS and LABA and
oral corticosteroids long term are
preferred
D
CAMP: Trial Design
Experimental Design
1041 mild-to-moderate asthmatic children (5-12 y)
311
Budesonide
200 µg BID
208
Matching placebo
312
Nedocromil sodium
8 mg BID
210
Matching placebo
 Albuterol as needed for symptoms of asthma
 Oral prednisone for exacerbations of asthma
 Beclomethasone if asthma control was
inadequate
Childhood Asthma Management Research Group. N Engl J Med. 2000;343:1054-1063.
Asthma Control in CAMP
Continuous daily treatment with inhaled
budesonide leads to better control of asthma
than symptomatic treatment





43% lower rate of hospitalizations (P=0.04)
45% lower urgent care visits (P<0.001)
43% lower rate and use of prednisone (P<0.001)
Lower airway responsiveness to methacholine
Greater reduction in the need for albuterol for
symptoms (P<0.001)
 More episode-free days (P=0.01)
Childhood Asthma Management Research Group. N Engl J Med. 2000;343:1054-1063.
CAMP: Reduction in Urgent Care
Visits and Hospitalizations
Greater Reductions in the Need for Emergency Care
P<0.001
No./100 person-years
30
P=0.02
25
Budesonide
Nedocromil
22
20
16
15
P=0.04
12
10
5
2.5
4.3
4.4
0
Urgent care visits
Hospitalizations
Childhood Asthma Management Research Group. N Engl J Med. 2000;343:1054-1063.
Placebo
CAMP: Reduction in
Prednisone Courses
Fewer Courses of Oral Prednisone With Budesonide
Budesonide
Nedocromil
Placebo
No./100 person-years
P<0.001
P=0.01
122
125
102
100
75
70
50
25
0
Prednisone courses
Childhood Asthma Management Research Group. N Engl J Med. 2000;343:1054-1063.
CAMP – Safety Data
 Mean increase in height was1.1 cm less in
Budesonide group vs. placebo group
 No differences in bone density, bone age,
projected final height, and Tanner stage
between Budesonide and placebo
 No posterior subcapsular cataracts
 Greater improvement in Children’s Depression
Inventory (less depression) in Budesonide vs.
placebo group!
Childhood Asthma Management Research Group. N Engl J Med. 2000;343:1054-1063.
Steroid Response Rate
Bates CA, et al. J Allergy Clin Immunol
2003;111:256-62.
Viral Infections and
Asthma
 Rhinovirus accounts for 30-50% of all acute
respiratory infections and children are infected
several times a year
 Viral infection is detected in 85% of reported
episodes of a decrease in PEF, upper
respiratory symptoms, cough, and wheezing
 Atopic asthmatics response to rhinovirus
infection is defective ( suboptimal TH1
response )
Johnston SL, et al. BMJ 1995;310:1225-1229.
Papadopoulos NG, et al. Thorax 2002;57:328-332.
PC20 Restoration with URI
The duration of increased AHR in children
after a single cold was 5-11 weeks
An increased rate of symptomatic cold
and asthma episodes in atopic children
was associated with prolongation of AHR
After multiple colds, AHR remained
elevated more than 6 months in some
cases
Xepapadaki et al. J Allergy Clin Immunol. 2005;116:299-304.
PC20 Restoration with URI
Xepapadaki et al. J Allergy Clin Immunol 2005;116:299-304.
Episodic use of Inhaled Steroid or
Leukotriene Receptor Antagonist in
Pre-School Children
 Methods
 Randomized DBPC 12-month trial
 238 children aged 12-69 months with
moderate-to-severe intermittent wheezing
 Received 7 days of budesonide (1 mg BID),
montelukast (4 mg qhs), or placebo in
addition to Albuterol with respiratory tract
infection (RTI)
Bacharier LB, et al. J Allergy Clin Immunol 2008;122:1127-35.
Episodic use of Inhaled Steroid or
Leukotriene Receptor Antagonist in
Pre-School Children
 Primary outcome measure
 Proportion of episode-free days (EFD)
 Results
 3 treatment groups did not differ in proportions of
EFDs
 3 groups did not differ in oral corticosteroid use,
health care use, quality of life, or linear growth
 Modest reductions in symptom severity with RTIs in
Budesonide and Montelukast treated groups
Bacharier LB, et al. J Allergy Clin Immunol 2008;122:1127-35.
Episodic use of Inhaled Steroid or
Leukotriene Receptor Antagonist in
Pre-School Children
Bacharier LB, et al. J Allergy Clin Immunol 2008;122:1127-35.
Episodic use of Inhaled Steroid or
Leukotriene Receptor Antagonist in
Pre-School Children
Bacharier LB, et al. J Allergy Clin Immunol 2008;122:1127-35.
Episodic use of Inhaled Steroid or
Leukotriene Receptor Antagonist in
Pre-School Children
Bacharier LB, et al. J Allergy Clin Immunol 2008;122:1127-35.
Allergy and Asthma
 Patients with allergic rhinitis are 3x more
likely to develop asthma
 80-90% of patients with asthma have
allergy
 Allergens are potential triggers for
asthma
 Presence of allergy is single greatest risk
factor for not outgrowing asthma
Indirect Exposure to Cat in School
Almquist et al. Am J Respir Crit Care Med 2001;163:694-698.
RHINITIS
When to Consider Immunotherapy
Moderate ±
conjunctivitis
Mild
Severe ±
conjunctivitis
Allergen avoidance when possible
Pharmacotherapy
Consider immunotherapy
Intermittent
Mild persistent
Pharmacotherapy
Consider immunotherapy
Moderate
persistent
Severe
persistent
Immunotherapy in Asthma
 Treats both upper and lower airways
simultaneously
 long-term immunomodulatory effects
(Durham)
 May prevent new sensitivities (DesRoches)
 Risk of anaphylaxis, time commitment
Allergen Immunotherapy in Asthma
 Meta-analysis of 75 randomized
controlled trials of allergen-specific
immunotherapy (SIT) in asthma
involving more than 3,500 patients
 decreased symptoms scores
 decreased medication requirements
 improved allergen and non-specific
bronchial hyperresponsivelness
Abramson MJ, et al. The Cochrane Library,2003;issue 4.
Immunotherapy ( IT ) in Allergic
Rhinitis - Effects on Bronchial
Hyperresponsiveness
 50% of patients on
IT had negative
methacholine
challenges
 9% of control
patients developed
asthma vs. 0% in IT
group
Grembiale RD, et al. Am J Respir Crit Care Med 2000;162:2048-52.
Methods ( PAT Study )
 208 children aged 6-14 years from 6 European
pediatric clinics
 Clinical history of rhinoconjunctivitis symptoms
caused by allergy to birch and/or grass pollen
 Positive prick test and conjunctival provocation
test results
Moller C,et al. J Allergy Clin Immunol 2002;109:251-6.
Preventative Asthma Treatment
(PAT) Study
60
50
40
asthma
no asthma
30
20
10
0
SIT
Moller C,et al. J Allergy Clin Immunol 2002;109:251-6.
control
Vocal Cord Dysfunction
 Definition: paradoxical adduction of the
vocal cords during inspiration +/expiration
 Etiology: unknown but potential triggers
include rhinitis ( post-nasal drip ), GERD,
exercise, stress, exposure to strong
odors
 Oftentimes co-exists with asthma
 Female preponderance
Vocal Cord Dysfunction –
Clinical Cues
 Lack of response to asthma
medications
 Sudden onset and resolution of
symptoms
 Lack of nocturnal symptoms
Vocal Cord Dysfunction
 Spirometry
 Abnormal inspiratory loop
 Normal expiratory loop
 Rhinolaryngoscopy demonstrating
frequent adduction or “posterior chink” of
vocal cords is gold standard
Vocal Cord Dysfunction
Wood RP, Milgrom H. JACI 1996;98:481-5.
Conclusions
 NHLBI asthma guidelines stress need to
evaluate rate/severity of exacerbations
as indicators of severity of disease and
control
 Inhaled corticosteroids are safe and
effective first line therapy
 Potential role of allergy in persistent
disease should be evaluated