Transcript 1-21 Amherst- Ilowite - Update on Asthma

Asthma 2006 Update
Jonathan Ilowite
Put these artists in order of popularity according
to Yahoo for 2005
A
B
1. A, B, C, D
2. B, A, C, D
3. C, D, B, A
4. I hate all of them!
C
D
Put These Asthmatics in Order of Prevalence
(greatest to least)
1. 0-14
2. 15-35
3. > 35
1. 1, 2, 3
2. 2, 3, 1
3. 3, 2, 1
Prevalence of Asthma By Age and Gender (Jan-June 2004)
Schiller JS, Coriaty Nelson Z, Hao C, et al. Early release of selected estimates based on data from January-June 2004
National Health Interview Survey. National Center for Health Statistics. http://www.cdc.gov/nchs/nhis.htm. December 2004.
Put these ethnic groups in order of asthma
attacks over the last year (least to greatest)
1.
2.
3.
4.
Blacks, Whites, Hispanics
Hispanics, Blacks, Whites
Whites, Blacks, Hispanics
Hispanic, White, Black
Asthma Attack (Within 12 Months)
Prevalence by Age Group and Ethnicity (Jan-June 2004)
Schiller JS, Coriaty Nelson Z, Hao C, et al. Early release of selected estimates based on data from January-June 2004
National Health Interview Survey. National Center for Health Statistics. http://www.cdc.gov/nchs/nhis.htm. December 2004.
Economic Impact of Asthma in the United States
Total estimated economic cost: $13 billion
• Direct medical expenditures: 58% of total
• Hospital care (inpatient, emergency, outpatient)
• Physicians’ services
• Prescriptions: 43% of direct medical expenditures
• Indirect costs: 42% of total
• Lost school days
• Lost workdays
Weiss KB, et al. J Allergy Clin Immunol. 2001;107:3–8.
Number of Visits to Hospitals and Physicians (2002)
1. Woodwell DA, et al. National Ambulatory Medical Care Survey: 2002 summary. Advance data from Vital Health
Statistics; no 346. National Center for Health Statistics. 2004.
2. Hing E, et al. National Hospital Ambulatory Medical Care Survey: 2002 outpatient department summary. Advance data from Vital Health
Statistics; no 345. National Center for Health Statistics. 2004.
3. McCaig LF, et al. National Hospital Ambulatory Medical Care Survey: 2002 emergency department summary. Advance data from Vital
Health Statistics; no 340. National Center for Health Statistics. 2004.
Asthma Facts:
Morbidity and Mortality
•
•
•
•
Asthma prevalence: 17 million Americans1
Asthma deaths: 4261 deaths in 20022
Asthma-related hospitalizations: 465,000 in 20002
Emergency department visits for asthma:
1.9 million in 20022
• Total annual costs of asthma in the US estimated to be $14
billion, of which $9.4 billion were direct medical expenses3
• 14.5 million lost workdays and 14 million missed school days
in the US per year3
1. National Institute of Allergy and Infectious Diseases. National Institutes of Health. Focus On:
Asthma. Available at: http://www2.niaid.nih.gov/newsroom/focuson/Asthma01/basics.htm#stats.
Accessed March 3, 2005.
2. Kochanek KD, et al. Nat Vital Stat Rep. 2004;53:1-116.
3. American Lung Association. Asthma & Adults: Asthma Trends. American Lung Association Epidemiology & Statistics Unit
Research and Scientific Affairs. April 2004. Trends in Asthma Morbidity and Mortality. Available at:
http://www.kintera.org/atf/cf/%7B7A8D42C2-FCCA-4604-8ADE-7F5D5E762256%7D/ASTHMA1.PDF. Accessed May 2, 2005.
Asthma hospitalizations per 10,000
Estimated Annual Rate of AsthmaRelated Hospitalizations
20
18
16
14
12
10
8
6
4
2
0
19.0
19.7
19.2
19.5
Mannino DM et al. MMWR Surveill Summ. 2002;51:1-13.
17.9
18.1
17.6
15.7
17.2
17.0
Hospital admissions per 10,000
Annual Hospitalizations for Asthma
Compared with Other Conditions
40
37.4
35
30
25
19.8
20
16.0
15
10
5
0
Coronary
atherosclerosis
Diabetes
Asthma
National Hospital Discharge Survey. Available at: http://www.cdc.gov/nchs/data/hdasd/sr13_156t9.pdf.
Accessed April 13, 2005.
Economic Burden of Asthma
in the United States
Direct Costs: $7.4
billion
• Hospital care
• Physician and other
healthcare
professional services
• Over the counter
and prescription
medications
Indirect Costs: $5.3
billion
 Lost productivity at
work
 School days lost
 Mortality
Sullivan SD, Weiss KB. J Allergy Clin Immunol. 2001; 107: 203-210
Cost to Patient
Quality of Life
 Activity avoidance
 Absenteeism
 Presenteeism
 Lifestyle disruptions
Healthcare Utilization and Missed Work/School
Days By Asthma Severity
Data From the TENOR Study
57%
Steroid burst*
40%
30%
51%
Unscheduled
office visit*
40%
32%
21%
Emergency department
visit*
11%
8%
19%
Missed 1 day
school or work†
Ever intubated
Hospitalization*
13%
12%
17%
Severe
Moderate
Mild
8%
6%
3%
1%
10%
0
20
40
* In past 3 months.
† In past 2 weeks.
Patients (%)
TENOR=The Epidemiology and natural History of Asthma: Outcomes and Treatment Regimens.
Dolan CM, et al. Ann Allergy Asthma Immunol. 2004;92:32-39.
60
Asthma Worldwide
• Around 8% of the Swiss population suffers from asthma as
against only 2% some 25-30 years ago.
• In Germany, there are an estimated 4 million asthmatics.
• In Western Europe as a whole, asthma has doubled in ten years,
according to the Institute of Allergy in Belgium.
• In the United States, the number of asthmatics has leapt by over
60% since the early 1980s and deaths have doubled to 5,000 a
year.
• There are about 3 million asthmatics in Japan of whom 7%
have severe and 30% have moderate asthma.
• In Australia, one child in six under the age of 16 is affected
Asthma Worldwide
• India has an estimated 15-20 million asthmatics.
• In the Western Pacific Region of WHO, the incidence
varies from over 50% among children in the Caroline
Islands to virtually zero in Papua New Guinea.
• In Brazil, Costa Rica, Panama, Peru and Uruguay,
prevalence of asthma symptoms in children varies
from 20% to 30%.
• In Kenya, it approaches 20%.
• In India, rough estimates indicate a prevalence of
between 10% and 15% in 5-11 year old children.
Achievement of Goals vs Reality
Goal
Reality
No missed work or school
49% of children and 25% of adults missed school or
work due to asthma
No sleep disruption
30% of patients reported nocturnal awakenings at least
once a week
Maintenance of normal activity levels
48% report that asthma interferes with recreation;
36% with normal physical exertion; 25% with social
activities
No (or minimal) need for emergency
department visits, hospitalizations, or
other unscheduled office visits
32% of children and 19% of adults required
emergency department visits; 55% of children and
36% of adults had unscheduled office visits
Normal or near-normal lung function
35% report having had a lung-function test in the past
year; 28% have peak flow meters; 9% report using
them at least once a week
Athma in America: A Landmark survey. National Survey Data.
Available at: http://www.asthmainamerica.com/cities/national.html.
Asthma Burden Worldwide
• World-wide, the economic costs associated with
asthma are estimated to exceed those of TB and
HIV/AIDS combined.
• At present Britain spends about US$1.8 billion on
health care for asthma and because of days lost
through illness.
• In Australia, annual direct and indirect medical costs
associated with asthma reach almost US$460 million
Global Burden of Asthma
• Asthma effects 300 million people worldwide,
making it one of the most common chronic
diseases
• Asthma has become more common in both
children and adults around the world in recent
decades, paralleling an increase in allergic
diseases in general
Global Burden of Asthma
• Asthma increases in prevalence with increasing
urbanization. By 2025, there will be an increase
in urbanization from 45% to 59%, which may
lead to an additional 100 million asthmatics
worldwide
• Asthma accounts for one out of every 250 deaths
worldwide
GINA guidelines 2003
Asthma Definition
• Asthma is a chronic inflammatory disease of the airways in which many
inflammatory cell types play a role, in particular mast cells, eosinophils,
T-lymphocytes, neutrophils, and epithelial cells
• In susceptible individuals, the inflammation causes recurrent episodes
of wheezing, breathlessness, chest tightness, and cough—particularly
at night and/or in the early morning
• These symptoms are usually associated with widespread but variable
airflow obstruction that is at least partly reversible either spontaneously
or with treatment
• This inflammation also causes an associated increase in airway
responsiveness to a variety of stimuli
Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma Update on Selected Topics—2002. J Allergy Clin
Immunol. 2002;110(5 suppl):S141-S219.
Asthma Pathophysiology
Asthma: Pathophysiologic Features and
Changes in Airway Morphology
Airway lumen narrowing
Mucous gland
hypertrophy and
hyperplasia
Edema
Mucus
hypersecretion
Thickening of
basement membrane
Epithelial
damage
Airway smooth-muscle
hypertrophy, hyperplasia,
and bronchoconstriction
Inflammatory
cell infiltration
Vascular
dilation
Goblet
cell hyperplasia
Adapted from National Heart, Lung, and Blood Institute. Expert Panel Report: Guidelines for the Diagnosis and
Management of Asthma. 1991. NIH publication 91-3042.
Asthma: epidemiology / pathology
Asthma images by Peter Jeffery
© AstraZeneca
The Importance of Establishing a Balance between Th1-Type and Th2-Type Cytokine Responses
Busse, W. W. et al. N Engl J Med 2001;344:350-362
Specimen of Bronchial Mucosa from a Subject without Asthma (Panel A) and a Patient with Mild
Asthma (Panel B) (Hematoxylin and Eosin, x40)
Busse, W. W. et al. N Engl J Med 2001;344:350-362
Asthma images by Peter Jeffery
© AstraZeneca
Asthma images by Peter Jeffery
© AstraZeneca
Evolution of Asthma Paradigms
Symptoms
Relieve Symptoms
Bronchial
Hyperreactivity
Fixed
Obstruction
Prevent Symptoms
Prevent Attacks
Prevent Symptoms
Prevent Attacks
Prevent Remodeling
What is Remodeling?
1. Irreversible loss of lung function in all asthmatics
2. Irreversible loss of lung function in some
asthmatics
3. Scarring and subepithelial deposition of collagen
4. Scarring as a result of chronic inflammation of the
airways in asthma
5. Asthma that turns into COPD
Rate of Decline in FEV1
1.0
0.8
FEV1/Ht3
(L/m3)
0.6
0.4
Normal
Asthma
0.2
0
20
40
60
Age (yrs)
Adapted from Peat. Eur J Respir Dis. 1987; 70:171-179.
80
Asthma: epidemiology / pathology
Potential interactions in the setting of severe asthma between eosinophils and fibroblasts involving
transforming growth factor ß (TGF-ß1 and 2), which could (1) contribute to perpetuating the
eosinophilia and (2) lead to increased deposition of matrix associated with eosinophilic
inflammation. IL = interleukin; TIMPs = tissue inhibitors of matrix metalloproteinases.
Asthma images by Peter Jeffery
© AstraZeneca
Time Course of Achieving Control
No night symptoms
100
FEV1
AM PEF
No “rescue” SABA use
% Improvement
AHR
Days
Weeks
Months
Woolcock et al. Presented at: 10th Annual ERS Congress; Florence, Italy; August 30-September 3, 2000.
Years
Change in FEV1 and PD20
Over Time With FP Therapy
FP MDI 750 mcg b.i.d.
Placebo
P<0.001 12 vs 3 months
1
P<0.01
110
105
*
100
95
Baseline
P<0.01
P=0.30
log10 PD20 (mg)
FEV1.0 (% baseline)
P<0.01
0
†
P<0.001
†
†
†
-1
-2
3
6
Time (months)
n=35
* P<0.05 vs placebo.
† P<0.001 vs placebo.
Ward et al. Thorax. 2002;57:309-316.
12 1 Month
After
Treatment
Baseline
3
6
Time (months)
12 1 Month After
Treatment
Changes in the Asthmatic Airway
Inflammation
Smooth Muscle
Changes
Expiration
Flow
Volume
Inspiration
Expiration
Flow
Volume
Inspiration
Asthma images by Peter Jeffery
© AstraZeneca
Airway Inflammation During Clinical
Remission*: Subject Characteristics
Asthmatic
(n=19)
Remission
(n=18)
Control
(n=17)
Age (yrs)
22 ± 2
21 ± 2
24 ± 1
Sex (M:F)
13:6
15:3
9:8
FEV1 (% predicted)
88 ± 12
93 ± 15
105 ± 13
FEV1 reversibility†
11 ± 1
7±1
4±1
* Clinical remission defined as reported complete absence of asthmatic symptoms in subjects not taking
any asthma medication for at least 12 months prior to the study.
† Change in FEV , expressed as increase in % of predicted normal value after administration of 1 mg
1
terbutaline.
Van den Toorn et al. Am J Respir Crit Care Med. 2001;164:2107-2113.
Airway Remodeling Occurs Even
in Patients With Mild Asthma
30
P<0.003
P<0.01
25
Subepithelial
Layer
Thickness (µm)
20
15
10
*
5
0
Severe
(n=6)
Moderate
(n=14)
* P<0.001, healthy subjects vs patients with asthma.
Chetta et al. Chest. 1997;111:852-857.
Mild
(n=14)
Healthy
(n=8)
Evolution of Asthma Paradigms
Symptoms
Relieve Symptoms
Bronchial
Hyperreactivity
Fixed
Obstruction
Prevent Symptoms
Prevent Attacks
Prevent Symptoms
Prevent Attacks
Prevent Remodeling
Asthma: epidemiology / pathology
G lobal
IN itiative for
A sthma
Corticosteroids in the
Management of Allergic Asthma




Mechanisms1
– Suppress generation of cytokines, recruitment of airway eosinophils,
release of inflammatory mediators
Clinical effects1
– Reduction in airway hyperresponsiveness, severity of symptoms,
exacerbations
– Improvement in peak expiratory flow and spirometry
Adverse Effects2
– Slowed growth in children, oropharyngeal candidiasis, adrenocortical
insufficiency, ocular complications, osteoporosis
Place in therapy
– Inhaled first-line agents for the long-term control of asthma1,2
1. NIH/NHLBI: Guidelines for the Diagnosis and Management of Asthma, 1997.
2. Boulet LP, et al: Can Respir J 2001; 8 Suppl A:5A-27A.
Proposed Mechanism of Action
of Inhaled Corticosteroids
ICS molecules
Cell membrane
Inactive steroid
receptor
Active steroid - receptor
complex
Dimer formation
DNA strand
Gene binding
Anti-inflammatory
activity
Long-acting β2-agonists in the Management of
Allergic Asthma


Indication
– For patients on optimal corticosteroid doses experiencing regular or frequent
breakthrough symptoms requiring rescue medication
Mechanisms
– Stimulate β2 receptors, increase cyclic AMP
– Relax airway smooth muscle, produce functional antagonism to
bronchoconstriction


Clinical effects
– Reduce bronchoconstriction
– Long-term control of symptoms (especially nocturnal)
Limitations
– May mask deteriorating asthmaespecially if corticosteroid is withdrawn
1. NIH/NHLBI: Guidelines for the Diagnosis and Management of Asthma, 1997.
2. Boulet LP, et al: CMAJ 1999; 161(11 Suppl):S1-61.
Leukotriene Receptor Antagonists in the
Management of Allergic Asthma



Mechanisms
– Inhibit contraction of airway smooth muscle
– Decrease vascular permeability
– Decrease mucus secretions
– Suppress attraction and activation of inflammatory cells
Clinical effects
– Minor bronchodilator effect
– Reductions in allergen-, exercise-, and sulfur-dioxide-induced
bronchoconstriction
– Reduce symptoms
– Improve lung function
Place in therapy
– Can be used as oral adjunct to corticosteroids (less effective as
adjunct than long-acting β2-agonists)2
Global Initiative for Asthma (GINA). WHO/NHLBI 2002
Classification of Severity
CLASSIFY SEVERITY
Clinical Features Before Treatment
Symptoms
STEP 4
Severe
Persistent
STEP 3
Moderate
Persistent
STEP 2
Mild
Persistent
Nocturnal
Symptoms
Continuous
Limited physical
activity
Frequent
Daily
Attacks affect activity
> 1 time week
> 1 time a week
but < 1 time a day
 60% predicted
Asymptomatic and
normal PEF between
attacks
Variability > 30%
60 - 80% predicted
> 2 times a month
Variability > 30%
 80% predicted
Variability 20 - 30%
< 1 time a week
STEP 1
Intermittent
FEV1 or PEF
 2 times a month
 80% predicted
Variability < 20%
The presence of one feature of severity is sufficient to place patient in that category.
Six-Part Asthma Management
Program
1. Educate Patients
2. Assess and Monitor Severity
3. Avoid Exposure to Risk Factors
4. Establish Medication Plans for Chronic
Management: Adults and Children
5. Establish Plans for Managing
Exacerbations
6. Provide Regular Follow-up Care
Six-part Asthma Management Program
Goals of Long-term Management







Achieve and maintain control of symptoms
Prevent asthma episodes or attacks
Maintain pulmonary function as close to normal levels
as possible
Maintain normal activity levels, including exercise
Avoid adverse effects from asthma medications
Prevent development of irreversible airflow limitation
Prevent asthma mortality
Six-part Asthma Management Program
Control of Asthma

Minimal (ideally no) chronic symptoms

Minimal (infrequent) exacerbations

No emergency visits

Minimal (ideally no) need for “as needed” use of
β2-agonist

No limitations on activities, including exercise

PEF circadian variation of less than 20 percent

(Near) normal PEF

Minimal (or no) adverse effects from medicine
Six-Part Asthma Management
Program

Any asthma more severe than intermittent
asthma is more effectively controlled by
treatment to suppress and reverse airway
inflammation than by treatment only of acute
bronchoconstriction and symptoms
Six-part Asthma Management Program
Factors Associated with
Non-Compliance in Asthma Care
Medication Usage
Patient/Physician
Misunderstanding/lack of
information

Difficulties associated with
inhalers


Complicated regimens

Underestimation of severity

Fears about, or actual side
effects

Attitudes toward ill health

Cultural factors

Poor communication

Cost
Typical Spirometric (FEV1)
Tracings
Volume
FEV1
Normal Subject
Asthmatic (After Bronchodilator)
Asthmatic (Before Bronchodilator)
1
2
3
4
Time (sec)
Note: Each FEV1 curve represents the highest of three repeat measurements
5
Six-part Asthma Management Program
Part 3: Avoid Exposure to Risk
Factors
 Methods to prevent onset of asthma are not
yet available but this remains an important
goal
 Measures to reduce exposure to causes of
asthma exacerbations (e.g. allergens,
pollutants, foods and medications) should be
implemented whenever possible
Six-part Asthma Management Program
Part 3: Avoid Exposure to Risk
Factors

Reduce exposure to indoor allergens

Avoid tobacco smoke

Avoid vehicle emission

Identify irritants in the workplace

Explore role of infections on asthma
development, especially in children and
young infants
Six-part Asthma Management Program
Part 4: Establish Medication Plans for LongTerm Asthma Management in Infants and
Children
 At present, inhaled glucocorticosteroids are the
most effective controller medications and are
recommended for persistent asthma at any step
of severity
 Long-term treatment with inhaled
glucocorticosteroids markedly reduces the
frequency and severity of exacerbations
Six-part Asthma Management Program
Part 4: Establish Medication Plans for
Long-Term Asthma Management

A stepwise approach to pharmacological therapy
is recommended

The aim is to accomplish the goals of therapy
with the least possible medication

Although in many countries traditional methods
of healing are used, their efficacy has not yet
been established and their use can therefore not
be recommended
Part 4: Long-term Asthma Management
Stepwise Approach to Asthma Therapy
The choice of treatment should be guided by:

Severity of the patient’s asthma

Patient’s current treatment

Pharmacological properties and availability of the
various forms of asthma treatment

Economic considerations
Cultural preferences and differing health care
systems need to be considered
Part 4: Long-term Asthma Management
Pharmacologic Therapy
Controller Medications:
Inhaled glucocorticosteroids
 Systemic glucocorticosteroids
 Cromones
 Methylxanthines
 Long-acting inhaled β2-agonists
 Long-acting oral β2-agonists
 Leukotriene modifiers
 Anti-IgE

Part 4: Long-term Asthma Management
Pharmacologic Therapy
Reliever Medications:

Rapid-acting inhaled β2-agonists

Systemic glucocorticosteroids

Anticholinergics

Methylxanthines

Short-acting oral β2-agonists
Part 4: Long-term Asthma Management
Stepwise Approach to Asthma Therapy
Adults/Children Older Than 5 yrs
Outcome: Best
Possible Results
Outcome: Asthma Control
Controller:

Controller:
Controller:
None
Controller:

Low-dose inhaled
corticosteroid

High-dose inhaled
corticosteroid plus
long –acting
inhaled β2-agonist
plus (if needed)
Low to medium- 
dose inhaled
corticosteroid plus
long-acting inhaled -Theophylline-SR
β2-agonist
-Leukotriene

When asthma
is controlled,
reduce therapy

Monitor
-Long-acting inhaled
β2- agonist
-Oral corticosteroid
Reliever:
STEP 1:
Intermittent
Rapid-acting inhaled β2-agonist prn
STEP 2:
Mild Persistent
STEP 3:
Moderate
Persistent
STEP 4:
Severe
Persistent
Alternative controller and reliever medications may be considered (see text).
STEP Down
Stepwise Approach to Asthma Therapy: Adults and Children >5 yr
Step 1: Intermittent Asthma
Daily Controller
Medications
None required
Reliever
Medications
Rapid-acting inhaled 2-agonist
for symptoms (but < once a week)
Rapid-acting inhaled 2-agonist,
or cromone before exercise or
exposure to allergen




Continuously review medication technique, compliance and environmental control
Review treatment every three months.
Step up if control is not achieved; step down if control is sustained for at least 3 months
Preferred treatments are in bold print
Stepwise Approach to Asthma Therapy: Adults and Children >5yr
Step 2: Mild Persistent Asthma
Daily Controller
Medications
Reliever
Medications
Low-dose inhaled
glucocorticosteroid
Rapid-acting inhaled 2-agonist
for symptoms (but < 3-4 times/day)
Other options (order by cost):
 sustained-release theophylline, or
 Cromone, or
 leukotriene modifier
Other options:
 inhaled anticholinergic, or
 short-acting oral 2-agonist, or
 short-acting theophylline




Continuously review medication technique, compliance and environmental control.
Review treatment every three months
Step up if control is not achieved; Step down if control is sustained for at least 3 months
Preferred treatments are in bold print
Stepwise Approach to Asthma Therapy: Adults and Children >5 yr
Step 3: Moderate Persistent Asthma
Daily Controller
Medications
Low- to medium-dose inhaled glucocorticosteroid, plus long-acting inhaled β2-agonist
Other options (order by cost):
 Medium-dose inhaled glucocorticosteroid plus sustainedrelease theophylline, or
 Medium-dose inhaled glucocorticosteroid plus long-acting
inhaled β2- agonist, or
 High-dose inhaled glucocorticosteroid, or
 Medium-dose inhaled glucocorticosteroid plus leukotriene
modifier




Reliever
Medications
Rapid-acting inhaled
β2 -agonist for symptoms
(but < 3 - 4 times/day)
Other options:
 inhaled anticholinergic or
 short-acting oral
β2-agonist or
 short-acting theophylline
Continuously review medication technique, compliance and environmental control.
Review treatment every three months.
Step up if control is not achieved; Step down if control is sustained for at least 3 months.
Preferred treatments are in bold print.
Stepwise Approach to Asthma Therapy: Adults and Children >5 yr
Step 4: Severe Persistent Asthma
Daily Controller
Medications
High-dose inhaled glucocorticosteroid, plus long-acting inhaled
β2-agonist plus one or more of the
following, if needed (order by cost):
 sustained-release theophylline, or
 leukotriene modifier or
 oral glucocorticosteroid




Reliever
Medications
Rapid-acting inhaled
β2-agonist for symptoms
(but < 3-4 times/day)
Other options:
 inhaled anticholinergic or
 short-acting oral
β2-agonist or
 short-acting theophylline
Continuously review medication technique, compliance and environmental control.
Review treatment every three months.
Step up if control is not achieved; Step down if control is sustained for at least 3 months.
Preferred treatments are in bold print.
Part 4: Long-term Asthma Management
Allergen-specific Immunotherapy
Greatest benefit of specific immunotherapy using allergen
extracts has been obtained in the treatment of allergic rhinitis

A number of questions must be addressed regarding the role of
specific immunotherapy in asthma therapy

Specific immunotherapy should be considered only after strict
environmental avoidance and pharmacologic intervention,
including inhaled glucocorticosteroids, have failed to control
asthma


Perform only by trained physician
Six-part Asthma Management Program
Part 4: Establish Medication Plans for LongTerm Asthma Management in Infants and
Children
 Long-term treatment with inhaled
glucocorticosteroids has not been shown to be
associated with any increase in osteoporosis or
bone fracture
 Studies including a total of over 3,500 children
treated for periods of 1 – 13 years have found no
sustained adverse effect of inhaled
glucocorticosteroids on growth
http://www.ginasthma.org
Audience Response: How Can We
Measure Asthma Control?
How Can Asthma Control Be Measured?(Audience
Response: Pick One Best Answer)
2.Lung
function?
1.Inflammation?
Direct or indirect?
3.Daytime
symptoms?
9.Utilization of
healthcare
resources?
4.Nighttime
awakenings?
Asthma
Control
8.Functional
status?
7.Missed work
and/or school?
5.Use of “quick
relief” inhaler
and/or
nebulizer?
6.Patient self-report
of control?
ACT Results: Item Selection
Item
Number
Entered
Odds Ratio (CI)
ChiSquare
P Value
Shortness of Breath
1
1.25 (1.02-1.61)
54.4273
0.0000
Patient Rating of Control
2
0.68 (0.48-0.95)
14.1044
0.0002
Use of Rescue Medication
3
1.30 (1.02-1.66)
7.1375
–0.0075
Activity Limitations
4
1.66 (1.15-2.40)
5.8535
0.0155
Nighttime Awakenings
5
1.22 (1.04-1.56)
4.1618
–0.0413
•
Items most predictive of uncontrolled asthma as assessed by specialists
•
Items selected based on forward step-wise logistic regression
Nathan et al. J Allergy Clin Immunol. 2004;113:59-65.
Paradigm Shift in Asthma
Asthma
Uncontrolled
Adjust
therapy
Difficult
to control
Controlled
Case Presentation 2
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
2.
During the past 4 weeks, how often have you had shortness
of breath?
1
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?
2
4.
During the past 4 weeks, how often have you used your rescue
inhaler or nebulizer medication (such as albuterol)?
1
5.
How would you rate your asthma control during the past
4 weeks?
4
Copyright 2002, by QualityMetric Incorporated.
Patient Total Score
10
How Can We Improve
Compliance With Inhaled
Therapy?
Poor Adherence to Therapy: Nearly 70% of
Patients Fail to Refill Their ICS
Adherence as Determined By Prescription Refills After First Prescription
70
61%
60
Adherence (%)
50
40%
40
31%
30
20
10
0
Leukotriene
antagonists
LABA
Drazen JM, et al. Am J Respir Crit Care Med. 2000;161:A402.
ICS
Adherence to Inhaled Asthma
Therapy Decreases Over Time
 Adults with moderate-to-severe asthma (N=50)
 Treated with BID ICS
 Actuation of inhaler monitored electronically
75
Adherence (%)
70
65
60
55
50
0
1
2
3
4
Week of study
Apter AJ, et al. Am J Respir Crit Care Med. 1998;157:1810-1817.
5
6
Conclusions
• Asthma is a common worldwide disease with a high
medical and economic burden
• Inflammation is prominent and a direct cause of airway
hyperresponsiveness and symptoms
• Remodeling is a less well characterized but important
component of asthma
• Asthma control is essential for optimal outcomes
• Compliance to inhaled therapy is a major determinant of
good outcome