Transcript asthma - Lafayette Medical Education Foundation

Update on Asthma: 2012
Ketan K Sheth MD, MBA
Lafayette Allergy and Asthma Clinic
Important Asthma Statistics
 In 2008, an estimated 23.3 million Americans suffered from asthma1
―
In comparison, in 2007, approximately:
• 27 million had heart disease2*
• 18 million had diabetes3†
• 12 million had cancer4‡
 Asthma prevalence was1
― 10.6% in African Americans
― 7.8% in Caucasians
― 5.8% in Hispanics
 The estimated annual direct healthcare cost of asthma was approximately $15.6 billion; indirect
costs (eg, lost productivity) added another $5.1 billion, for a total of $20.7 billion1
― Prescription drugs represented the largest single direct cost, at $5.6 billion
*Heart disease includes coronary heart disease, angina pectoris, heart attack, or any other heart condition or disease in patients aged 18 and older.
†Diagnosed patients in 2007.
‡Includes any person alive before 2007 who had been diagnosed at any sites with active disease and those who were cured.
1. American Lung Association. www.lungusa.org/finding-cures/our-research/trend-reports/asthma-trend-report.pdf. Accessed November 30, 2010.
2. Pleis JR et al. Vital Health Stat. 10(242). 2009. ww.cdc.gov/nchs/data/series/sr_10/sr10_242.pdf. Accessed November 30, 2010. 3. US Centers for
Disease Control and Prevention. www.cdc.gov/diabetes/pubs/pdf/ndfs_2007.pdf. Accessed November 30, 2010. 4. National Cancer Institute
Surveillance Epidemiology and End Results. http://seer.cancer.gov/statfacts/html/all.html#prevalence. Accessed November 3, 2010.
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Asthma Remains a Serious
Health Risk in the United States
Every day in America approximately …
78,000 people miss school or work due to asthma
35,000 people have an asthma attack
4600 people visit the emergency room due to asthma
1200 people are admitted to the hospital due to asthma
10 people die from asthma
American Lung Association. www.lungusa.org/finding-cures/our-research/trend-reports/asthma-trend-report.pdf. Accessed March 29, 2010.
3
Annual Hospitalizations for Asthma
Compared to Other Chronic Diseases
Hospital discharges
per 10,000
Annual Hospitalizations by Disease State*
Discharges of inpatients from nonfederal hospitals; excludes newborns.
*Rates were calculated using postcensal estimates of the civilian population as of July 1, 2004 that were based on
the 2000 US Census Bureau.
NCHS. National Hospital Discharge Survey. http://www.cdc.gov/nchs/data/series/sr_13/sr13_162.pdf#table9.
Accessed January 3, 2008.
4
Asthma Is Associated With Significant
Direct and Indirect Costs
 Total annual costs of asthma in the United States in 2007 estimated
to be more than $19.7 billion, of which $14.7 billion were direct
medical expenses1
 10.1 million lost workdays and 12.8 million missed school days in
2003 due to asthma1
DIRECT COSTS:
$14.7 BILLION1
 Hospital care ($4.7 billion)
 Physician and other
professional healthcare
services ($3.8 billion)
 Prescription medications
($6.2 billion)
INDIRECT COSTS:
$5 BILLION1
 Lost productivity at work
 School days lost*
 Mortality
“Although . . . the cost to control asthma seems high, the cost of
not treating asthma correctly is even higher.”2
*Number of school days lost was not used in calculating total indirect cost.
1. American Lung Association. Trends in Asthma Morbidity and Mortality. 2007; 2. GINA. Global Strategy for Asthma
Management and Prevention. Revised 2007. http://www.ginasthma.org. Accessed January 3, 2008.
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Number of Asthma Deaths
Number of Asthma Deaths*
in US Has Been Declining
6000
5000
4000
3000
2000
1000
2003
2001
1999
1997
1995
1993
1991
1989
1987
1985
1983
1981
1979
0
* 1979-1998 rates reflect the International Classification of Disease (ICD) 9th Revision Code 493.
1999-2003 rates reflect the ICD 10th Revision Codes.
American Lung Association Epidemiology & Statistics Unit Research Program Services. Trends in
Asthma Morbidity and Mortality. July 2006. Available at: www.lungusa.org. Accessed November 2, 2006.
Our Understanding of Asthma
Has Evolved Since the 1970s
2010Cytokines
Target Therapy
Symptoms
Relieve Symptoms
Bronchial
Hyperreactivity
Fixed
Obstruction
Prevent Symptoms
Prevent Attacks
Prevent Symptoms
Prevent Attacks
Prevent Remodeling
Are Patients in the United States
Achieving Asthma Control
on Their Current Therapy?
Patients, %
58% of Adults With Asthma Visiting a Primary
Care Physician (PCP) for Any Reason Had
Uncontrolled Asthma
Weighted prevalence.
Results are from a cross-sectional epidemiological survey conducted between January 25 and May 2, 2008, among patients in primary care
physician (PCP) offices, regardless of reason for visit. Data are presented for 2238 adults with a self-reported physician diagnosis of asthma .
Patient asthma was classified as uncontrolled if Asthma Control Test™ score was ≤19. Asthma Control Test is a trademark of QualityMetric
Incorporated.
Mintz M et al. Curr Med Res Opin. 2009;25(10):2523-2531.
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Of Patients Whose Asthma Tested “Uncontrolled” Based on an
Asthma Control Test™ Score of ≤19, 79% Considered Their
Asthma Somewhat to Completely Controlled*
Not Well/Uncontrolled
Patients, %
Somewhat/Well/Completely Controlled
Patient Perception of Control
Results are from a cross-sectional epidemiological survey conducted between January 25 and May 2, 2008, among patients in primary care
physician (PCP) offices, regardless of reason for visit. Data are presented for 2238 adults with a self-reported physician diagnosis of asthma.
Patient asthma was classified as uncontrolled if Asthma Control Test™ score was ≤19. Asthma Control Test is a trademark of QualityMetric
Incorporated.
*Results based on the last item of the test, which is a global assessment of asthma control. This item was evaluated separately and compared
with overall score.
Data on file, GlaxoSmithKline.
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Using Too Much Albuterol May Signal a Lack
of Asthma Control
 Frequency of short-acting beta2-agonist (SABA) use may be a useful
barometer of lack of asthma control
 Excessive SABA use may be associated with an increased risk of
exacerbation1
 How much albuterol are your patients using?
― Most albuterol inhalers have 200 puffs per canister,
equaling 100 doses
― One 200-puff canister may last a patient approximately
1 year when taking <2 doses a week on average*
*Calculations are for a canister containing 200 inhalations with patient using 2 inhalations per dose.
Additional puffs may be required for priming of canister after 2 weeks of nonuse.
1. Schatz M et al. J Allergy Clin Immunol. 2006;117(5):995-1000.
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2007 National Heart, Lung, and Blood
Institute Asthma Guidelines
Advantages and Limitations of Treatment
Guidelines
 Advantages for patients and providers1
― Improve quality of patient care
― Decrease unnecessary variation in care
― Provide evidence-based recommendations for improving clinical
decisions
― Highlight gaps in knowledge
 Current limitations
― Familiarity with guideline recommendations2,3
― Implementation of guidelines2,3
― Limited information as to whether management has changed in
response to guidelines
1. Woolf SH et al. BMJ. 1999;318(7182):527-530. 2. Cabana MD et al. Arch Ped Adol Med. 2001;155(9):1057-1062. 3. Wisnivesky JP et al. Ann
Allergy Asthma Immunol. 2008;101(3):264-270.
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Definitions: Severity, Control,
and Responsiveness
 Assessment and monitoring of asthma are closely linked
to the concepts of severity, control, and responsiveness
Severity
Control
The intrinsic intensity of
the disease process;
most easily and directly
measured in a patient
who is not currently
receiving long-term
control treatment
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
Responsiveness
The ease with which
control is achieved by
therapy
National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm.
Accessed September 10, 2010.
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The Goals of Asthma Therapy
Reduce Impairment
 Prevent chronic and
troublesome symptoms
(eg, coughing)
 Require infrequent use
(≤2 days/week) of SABAs for
symptom relief
 Maintain (near) normal
pulmonary function
 Maintain normal activity levels
 Meet patients’ and families’
expectation of and satisfaction
with asthma care
Reduce Risk
 Prevent recurrent exacerbations
of asthma and minimize the
need for emergency department
visits or hospitalizations
 Prevent progressive loss of
lung function
 Provide optimal
pharmacotherapy with minimal
or no adverse effects
SABA=short-acting beta2-agonist .
National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm.
Accessed September 10, 2010.
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NIH Recommendations Guide
Patients not on a controller*
Patients on therapy
(including controller)
Assess asthma severity
Assess asthma control
Initiate/adjust
asthma therapy
*Long-term daily maintenance medication used to achieve and maintain asthma control (eg, inhaled corticosteroid).
National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm.
Accessed September 10, 2010.
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Assessing Severity
Assess
 Impairment (based on
patient’s/caregiver’s recall of
previous 2 to 4 weeks and
spirometry)
― Symptoms
― Nighttime awakenings
― SABA use for symptom control (not
prevention of exercise-induced
bronchospasm [EIB])
― Interference with normal activity
― Lung function*
− FEV1, FEV1/FVC
Assign Severity
 To most severe category
in which any feature
occurs
Intermittent
Mild Persistent
Moderate Persistent
 Risk
― Exacerbations requiring oral systemic
corticosteroids
Severe Persistent
SABA=short-acting beta2-agonist .
*Not a severity component in the guidelines for children aged 0 to 4 years.
National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program.
www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed September 10, 2010.
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Assessing Asthma Control in
Youths Aged ≥12 Years and Adults
Criteria for Well-Controlled Asthma: Impairment Domain
Symptoms
≤2 days/week
Nighttime awakening
≤2 times/month (adults and adolescents)
Interference with normal activity
None
SABA use for symptom control (not prevention of EIB)
≤2 days/week
FEV1 or peak flow
>80% predicted/personal best
Validated questionnaires (adults and adolescents only)
Asthma Therapy Assessment Questionnaire
Asthma Control Questionnaire
Asthma Control Test™†
0
≤0.75*
≥20
Patients with asthma need to meet all criteria
to be considered well controlled
* Values
of 0.76 to 1.4 are indeterminate regarding well-controlled asthma.
Control Test is a trademark of QualityMetric Incorporated.
EIB=exercise-induced bronchospasm; SABA=short-acting beta2-agonist .
†Asthma
National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm.
Accessed September 10, 2010.
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Assessing Asthma Control In
Youths Aged ≥12 Years and Adults
Criteria for Well-Controlled Asthma: Risk Domain
Exacerbations requiring oral systemic
corticosteroids
0 to 1/year. Consider severity and interval
since last exacerbation
Progressive loss of lung function (adults and
adolescents) or reduction in lung growth (children
aged 5 to 11 years)
Evaluation requires long-term follow-up care
Treatment-related adverse effects
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
 NIH Asthma Guidelines’ recommended actions for well-controlled asthma include the following:
–Schedule regular follow-ups every 1 to 6 months to maintain control
–Consider step down if well controlled for at least 3 months
Your clinical judgment is important
in considering whether patients’ asthma is well controlled;
consider both impairment and risk domains.
National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm.
Accessed September 10, 2010.
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Guidelines Recommendations on Stepping Up
and Stepping Down Asthma Therapy
3 months
 Step up to gain control
 Consider step down if well controlled
for at least 3 months
 Gradually step down and closely monitor
to determine the minimal amount of
medication required to maintain control
and/or reduce the risk of side effects
National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program.
www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed September 10, 2010.
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Clinical Assessments Before Stepping Up or
Stepping Down Asthma Therapy
 Regular follow-up contacts at 1- to 6-month intervals, depending on
the level of control
 Consider 3-month intervals if a step down in therapy is anticipated
 Step up if necessary; step down if possible
Stepping Up
Stepping Down
Review
adherence,
inhaler technique,
environmental control,
and comorbid conditions.
If alternate treatment
option used in a step,
and asthma is still
uncontrolled,
discontinue and use
preferred
medication
before stepping up
If a clear and
positive response
for ≥3 months:
Attempt a careful
step down to
identify the
minimum medication
required to
maintain control
National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program.
www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed September 10, 2010.
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Guidance on the Treatment of Asthma
 Goal is to achieve and maintain control
― Provide optimal pharmacotherapy with minimal or
no adverse events
 Timely and effective adjustment of treatment
― Assess patients at regular intervals
― Step up to achieve control
― Step down if possible without loss of asthma control
National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program.
www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed September 10, 2010.
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Asthma Control Test™ (ACT)
1. In the past 4 weeks, how much of the time did your asthma keep you from getting
as much done at work, school or at home?
SCORE
2. During the past 4 weeks, how often have you had shortness of breath?
3. 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?
4. During the past 4 weeks, how often have you used your rescue inhaler or nebulizer
medication (such as albuterol)?
5. How would you rate your asthma control during the past 4 weeks?
A score of ≤19 means your patient’s asthma may not be under control.
ACT is for patients with asthma 12 years and older.
Asthma Control Test is a trademark of QualityMetric Incorporated.
Copyright 2002, by QualityMetric Incorporated.
TOTAL
Childhood Asthma Control Test: Questions Completed by Child
Have your child complete these questions.
1. How is your asthma today?
0
Very bad
1
Bad
SCORE
2
Good
3
Very Good
2. How much of a problem is your asthma when you run, exercise or play sports?
0
It’s a big problem, I can’t do what I want to do.
1
2
It’s a problem and I don’t like it. It’s a little problem but it’s okay.
3
It’s not a problem.
3. Do you cough because of your asthma?
0
Yes, all of the time.
1
Yes, most of the time.
2
Yes, some of the time.
3
No, none of the time.
4. Do you wake up during the night because of your asthma?
0
Yes, all of the time.
1
Yes, most of the time.
2
Yes, some of the time.
3
No, none of the time.
Childhood Asthma Control Test:
Questions Completed by Parent/Caregiver
Please complete the following questions on your own.
5. During the last 4 weeks, how many days did your child have any daytime asthma symptoms?
5
4
3
2
1
0
Not at all
1-3 days
4-10 days
11-18 days
19-24 days
Everyday
6. During the last 4 weeks, how many days did your child wheeze during the day because of asthma?
5
4
3
2
1
0
Not at all
1-3 days
4-10 days
11-18 days
19-24 days
Everyday
7. During the last 4 weeks, how many days did your child wake up during the night because of asthma?
5
4
3
2
1
0
Not at all
1-3 days
4-10 days
11-18 days
19-24 days
Everyday
TOTAL
A score of ≤19 means your patient’s asthma may not be under control.
Recently Revised NIH Asthma Guidelines Identify
Prevention of Exacerbations as a Key Goal of
Therapy
 The 2007 NIH Guidelines state that a key goal for therapy is to
“prevent recurrent exacerbations of asthma and minimize the
need for ED visits or hospitalizations.”
NIH, National Heart, Lung and Blood Institute. Expert Panel Report 3: Guidelines for the Diagnosis and Management of
Asthma (EPR–3 2007). Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed September 10,
2007.
Classifying Asthma Severity:
Youths Aged ≥12 Years and Adults
Persistent
Components of Severity
Impairment
Normal
FEV1/FVC:
8−19 y 85%
20−39 y 80%
40−59 y 75%
60−80 y 70%
Intermittent
Mild
Moderate
Severe
Symptoms
≤2 days/week
>2 days/week
(not daily)
Daily
Throughout day
Nighttime awakening
≤2 times/month
3 to 4 times/month
>1 time/week
(not nightly)
Often 7 times/week
SABA use for symptom
control (not prevention
of EIB)
≤2 days/week
>2 days/week
(not daily and not
>1 daily)
Daily
Several times daily
Interference with normal activity
None
Minor limitation
Some limitation
Extremely limited
Lung function
Normal FEV1 between
exacerbations
FEV1 >80% predicted
FEV1/FVC normal
FEV1 >80% predicted
FEV1/FVC normal
FEV1 >60 but <80%
predicted
FEV1/FVC reduced 5%
FEV1 <60%
predicted
FEV1/FVC
reduced >5%
0 to 1/year*
Risk
Exacerbations
requiring oral systemic
corticosteroids
≥2 /year*
Consider severity and interval since last exacerbation
Frequency and severity may fluctuate over time
Relative annual risk of exacerbations maybe related to FEV 1
Level of severity is determined by both impairment and risk. Assess impairment domain by patient’s/caregiver’s recall of the previous 2 to 4 weeks and
spirometry. Assign severity to the most severe category in which any feature occurs.
Adapted from the NIH guidelines.
*At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma severity. In general, more frequent and
intense exacerbations (eg, requiring urgent, unscheduled care, hospitalization, or ICU admission) indicate greater underlying disease severity. For
treatment purposes, patients who had ≥2 exacerbations requiring oral systemic corticosteroids in the past year may be considered the same as patients
who have persistent asthma, even in the absence of impairment levels consistent with persistent asthma.
National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm.
Accessed September 10, 2010.
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Classifying Asthma Control:
Youths Aged ≥12 Years and Adults
Components of Control
Well
WellControlled
Controlled
Not Well Controlled
Very Poorly Controlled
more than
≤2notdays/week
>2 days/week
Throughout the day
Nighttime awakening
times/month
≤2≤2times/month
1 to 3 times/week
>4x/week
Interference with normal activity
None
None
Some limitation
Extremely limited
SABA use for symptom
control (not prevention of EIB)
days/week
≤2≤2days/week
>2 days/week
Several times per day
FEV1 or peak flow
>80%
predicted/
personal
best
personal
80% best
60% to 80% predicted/
personal best
<60% predicted/
personal best
Validated questionnaires
Asthma Therapy Assessment Questionnaire
Asthma Control Questionnaire
Asthma Control TestTM†
00
≤0.75
≤0.75*
≥20
1 to 2
≥1.5
16 to 19
3 to 4
NA
≤15
≤2 days/week but
Symptoms
once on each day
Impairment
>80% predicted/
≥20
0 to 1/year
0 to 1/year
Exacerbations
requiring oral systemic corticosteroids
Risk
Progressive loss of lung function
Treatment-related
adverse effects
≥2/year
≥2/year
Consider
severity
and
interval since
since last
Consider
severity
and
interval
lastexacerbation
exacerbation
Evaluation
requires
follow-up
care
Evaluation
requireslong-term
long-term follow-up
care
Medication side effects can vary in intensity from none to
Medication
side effects
vary in intensity
to very troublesome
very
troublesome
andcan
worrisome.
The from
levelnone
of intensity
does not
and
worrisome.
The
level
of
intensity
does
not
correlate
to
specific
levels of
correlate to specific levels of control but should be considered
control but should be considered in the overall assessment of risk.
in the overall assessment of risk.
* Values
of 0.76 to 1.4 are indeterminate regarding well-controlled asthma.
Control Test is a trademark of QualityMetric Incorporated.
Adapted from the NIH guidelines.
†Asthma
National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm.
Accessed September 10, 2010.
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Evidence-based Medicine Helps Identify
Preferred Therapies for Patients ≥ 12 Years of
Age Uncontrolled on A Controller Medication
Step 6
Step 5
Step 3
Preferred
Step 2
Low-dose
ICS + LABA
Preferred:
Step 1
Preferred:
SABA PRN
Intermittent
Low-dose ICS
OR
Alternative:Cr
Medium-dose
ICS
omolyn,
nedocromil,
LTRA, or
theophylline
Alternative:L
ow-dose ICS +
either LTRA,
theophylline, or
zileuton
Step 4
Preferred:
Preferred:
High-dose
ICS + LABA
Medium-dose
ICS + LABA
Alternative:M
edium-dose
ICS + either
LTRA,
theophylline, or
zileuton
AND
Consider
omalizumab for
patients who
have allergies
Preferred:
High-dose
ICS + LABA +
oral
corticosteroid
AND
Consider
omalizumab for
patients who
have allergies
Persistent
Continually assess control
SABA=short-acting beta2-agonist; ICS=inhaled corticosteroid; LTRA=leukotriene receptor antagonist; LABA=long-acting
beta2-agonist.
NIH, National Heart, Lung and Blood Institute. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma (EPR–3 2007).
NIH Item No. 08–4051. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed September 10, 2007.
The Epidemiology and Natural History of Asthma:
Outcomes and Treatment Regimen (TENOR)
Basic Study Design
TENOR is a three-year, multi-center, observational study
 Patients will continue to receive medications and treatments
administered for their asthma as indicated by their physician
4,756 patients aged 6 years or older, from 283 sites
 Managed care, HMO, Community physicians, Academic centers
TENOR is a cohort study
 Natural history study
 Patients who represent greatest unmet medical need
 Collect information on factors related to treatment practices and
outcomes of interest
 Can control for potential risk factors and confounding variables
in the analyses
Hayden ML et al for the TENOR Study Group. Presented at ATS 2002 A42 Poster J1.
Objectives of TENOR
Primary objective
 To describe the natural history of patients who
are considered by physicians to have ‘severe’
or ‘difficult-to-treat’ asthma
Secondary objectives
 To examine the relationship between features
of asthma, treatments and outcome
 To observe the frequency of comorbid
conditions
Healthcare Utilization and Missing
Work/School Days By Asthma Severity
12
13
Missed 1+ Days of Work /
School in Past 2 Weeks*
19
32
Unscheduled Office Visit in
Past 3 Months*
40
51
63
Regular Office Visit in
Past 3 Months*
30
Steroid Burst in
Past 3 Months*
1
3
Hospitalization in
Past 3 Months*
0
57
Mild
11
6
8
Ever Intubated
81
10
6
ER Visit in Past 3 Months*
40
72
10
Moderate
21
Severe
17
20
30
40
50
60
70
Patients (%)
*P Value for chi-square test of difference between severity groups  0.05.
80
90
100
IgE and Asthma
Features of Asthma
 A chronic inflammatory disorder of the airways
 Immunohistopathologic features of asthma include:
― Infiltration of inflammatory cells (neutrophils, eosinophils,
and T lymphocytes)
― Mast cell activation
― Epithelial cell injury
 Airway inflammation contributes to:
― Airway hyperresponsiveness
― Airflow limitation
― Respiratory symptoms
― Disease chronicity
NHLBI. J Allergy Clin Immunol. 2007;120:S94.
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Potential Causes of Asthma
 Interactions between genetic and environmental factors
at key stages during immune system development
contribute to asthma
 Environmental factors:
―Allergens
―Viruses
―Other irritants
 Atopy, the genetic predisposition for the development of
an IgE-mediated response to common aeroallergens, is
the strongest identifiable predisposing factor for
developing asthma
NHLBI. J Allergy Clin Immunol. 2007;120:S94.
35
Relationship Between Asthma
and Serum IgE Level
Asthma Risk Versus Total
Serum IgE Concentration*
40
Odds ratio
20
10
5
2.5
1
0
0.32
1
3.2
10
32
100
320 1000 3200
Serum IgE level (IU/mL)
The risk for allergic asthma starts with relatively low IgE levels.
Data from several population-based studies indicate that the overall geometric mean levels of IgE in the
general population range from 20 IU/mL to 40 IU/mL.1
*Results of a random, stratified cluster sample of 2657 patients that investigated the association of selfreported asthma with serum IgE levels and skin-test reactivity to allergens.
Adapted from Burrows et al. N Engl J Med. 1989;320:271.
1. Dolan et al. In: IgE and Anti-IgE Therapy in Asthma and Allergic Disease. 2002.
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Overview of IgE-Mediated Asthma
Inflammatory Cascade
B cell
IL-4,
IL-13
lgE
production
Mast cell
T cell
Antigenpresenting
cell
Mediator
release
Activated
B cell
(plasma cell)
Allergen
cross-linking
Allergen
IgE
Storms. Am J Respir Med. 2002:1:361.
MacGlashan et al. J Immunol. 1997;158:1438.
Airway
wall
FcRI
Safety and efficacy have not been
established in other allergic conditions.
37
Xolair (Omalizumab)
Biological Characteristics
 Humanized monoclonal
antibody against IgE
 Binds circulating IgE
regardless of specificity
 Forms small, biologically
inert Xolair:IgE
complexes
 Does not activate
complement
Murine CDRs
(5% of molecule)
IgG1 kappa
human
framework
(95% of molecule)
CDR = complementarity-determining region.
Adapted from Boushey. J Allergy Clin Immunol. 2001;108:S77.
Please refer to the full Prescribing Information, including Boxed WARNING and Medication Guide.
38
Xolair Mechanism of Action
IgE
Xolair acts early in the
allergic cascade to
selectively target lgE
Xolair
Mast cell
Xolair binds serum-free lgE to
inhibit mediators of inflammation
Storms. Am J Respir Med. 2002:1:361.
MacGlashan et al. J Immunol. 1997;158:1438.
Please refer to the full Prescribing Information, including Boxed WARNING and Medication Guide.
Safety and efficacy have not been
established in other allergic conditions.
39
Xolair Mechanism of Action (cont’d)
Xolair
limits the
release of
inflammatory
mediators
Xolair
inhibits mast-cell
degranulation
Xolair
down-regulates
high-affinity
receptors
Mediator
release
Mast cell
Allergen
crosslinking
Xolair
helps prevent
exacerbations and
improve symptoms
IgE
Airway
wall
Other drugs
Storms Am J Respir Med. 2002:1:361.
MacGlashan et al. J Immunol. 1997;158:1438.
Please refer to the full Prescribing Information, including Boxed WARNING and Medication Guide.
Safety and efficacy have not been
established in other allergic conditions.
40
IgE and Asthma: Summary
 Interactions between genetic and environmental factors at
key stages during immune system development may
contribute to asthma1
― IgE plays a key role in the inflammatory cascade
― IgE, together with antigen, stimulates the release of
cytokines and other inflammatory mediators from mast cells
 A relationship between the risk of asthma and serum IgE
levels has been observed2
 Approximately 60% of patients with asthma have IgEmediated asthma3
1. NHLBI. J Allergy Clin Immunol. 2007;120:S94.
2. Burrows et al. N Engl J Med. 1989;320:271.
3. American Academy of Allergy Asthma and Immunology. Understanding allergic asthma.
http://www.aaaai.org/patients/allergic_asthma/qanda.stm. Accessed May 8, 2008.
41
IgE and Asthma: Summary
“The development of monoclonal antibodies
against IgE has shown that reduction of IgE is
effective in asthma treatment. These clinical
observations further support the importance of
IgE to asthma.”
—2007 NHLBI Guidelines for Managing Asthma
NHLBI. J Allergy Clin Immunol. 2007;120:S94.
42
IgE-Dependent Release of Inflammatory
Mediators
Allergens
IgE
FcRI
FcRII
Over Hours
Immediate Release
Granule contents:
Histamine, TNF-,
Proteases, Heparin
Sneezing
Nasal
congestion
Itchy, runny
nose
Watery eyes
Over Minutes
Cytokine production:
Specifically IL-4, IL-5 and IL-13
Lipid mediators:
Prostaglandins
Leukotrienes
Mucus production
Eosinophil recruitment
Wheezing
Bronchoconstriction
Anti IL-5 reduces blood eosinophils
Flood-page. AJRCCM, 2007
44
Anti IL-5 Therapy Does Not Improve Lung
Function
Flood-page AJRCCM. 2007
45
Anti IL- 5
Therapy
Decreases
Asthma
Exacerbations
Halder, NEJM 2009
46
Anti IL-5 Therapy reduces asthma
exacerbations
Nair, NEJM 2009
47
Periostin and Asthma
48
Anti IL-13 in periostin asthma subgroups
49
Summary
 Asthma affects 23.3 million Americans.1 The prevalence of asthma exceeds or is
comparable with that of other high-profile disease states (heart disease,2 diabetes,3 and
cancer4)
 The majority of adults with asthma visiting a PCP for any reason demonstrated
uncontrolled asthma5
 Excessive SABA use is a key barometer of lack of asthma control6
 Treatment guidelines can help improve quality of patient care, improve clinical decisions,
and offer evidence-based recommendations7
 Severity, control, and responsiveness are evaluated based on parameters of impairment
and risk8
 Asthma therapy is stepped up to gain control, and it is stepped down for patients who
have maintained control for a sufficient length of time to determine the minimal amount
of medication required to maintain control and/or reduce the risk of side effects8
― This highlights the need to assess patients at regular intervals and accomplish
timely and effective adjustments to treatment8
1. American Lung Association, Epidemiology and Statistics Unit, Research and Program Services Division. www.lungusa.org/finding-cures/ourresearch/trend-reports/asthma-trend-report.pdf. Accessed September 24, 2010; 2. Pleis JR et al. Vital Health Stat 10(242). 2009.
www.cdc.gov/nchs/data/series/sr_10/sr10_242.pdf. Accessed November 30, 2010; 3. US Centers for Disease Control and Prevention.
www.cdc.gov/diabetes/pubs/pdf/ndfs_2007.pdf. Accessed November 30, 2010; 4. National Cancer Institute Surveillance Epidemiology and End
Results. http://seer.cancer.gov/statfacts/html/all.html#prevalence. Accessed November 3, 2010; 5. Mintz M et al. Curr Med Res Opin.
2009;25(10):2523-2531; 6. Schatz et al. J Allergy Clin Immunol. 2006;117:995-1000; 7. Woolf SH et al. BMJ. 1999;318(7182):527-530; 8. National
Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed
September 10, 2010.
50
NEJM. 2001;344:30–37.