ASTHMA
PATHOPHYSIOLOGY
ASTHMA OVERVIEW
Presented by:
Michelle Harkins, MD
University of New Mexico
This session will cover
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Review asthma statistics
Define asthma
Outline key pathophysiologic features
Review signs and symptoms of asthma
Reference to NAEPP – EPR-3: asthma severity
classification system-including impairment and
risk domains
• Diagnosing asthma
Prevalence vs Incidence
• Prevalence - the proportion or percentage of a
population that has disease at a specific point or
period of time
• Incidence – the number of new cases of
disease that develop in a population of
individuals at risk during a specific point or
period of time
• 1980-1996 prevalence of asthma in US
increased
• Since 1999, mortality and hospitalization due to
asthma have decreased
Asthma – Current Prevalence by Age, 2011
120
CURRENT PREVALENCE RATE PER 1,000
105.5
94.9
100
79.9
80
86.7
79.4
68.5
60
40
20
0
Under 5
5-17
<18
18-44
Trends in Asthma Morbidity and Mortality. American Lung Association,
Epidemiology and Statistics Unit, Research and Program Services Division.
September, 2012.
45-64
65+
Asthma – Current Prevalence by Sex and Age, 2011
Male
Female
CURRENT PREVALENCE PER 1,000
120
97.3
100
101.7
100.1
87.8
80
71.9
61.8
60
40
20
0
Total
Under 18
Trends in Asthma Morbidity and Mortality. American Lung Association,
Epidemiology and Statistics Unit, Research and Program Services Division.
September, 2012.
18 and Over
Asthma – Current Prevalence by Race, 2011
Whites
Blacks
350
CURRENT PREVALENCE PER 1,000
314.2
287.9
300
238
250
200
147.3
150
100
118
80.4
50
0
Total
Under 18
Trends in Asthma Morbidity and Mortality. American Lung Association,
Epidemiology and Statistics Unit, Research and Program Services Division.
September, 2012.
18 and Over
New Mexico BRFSS Results for 2010: Current
Prevalence: Percent of New Mexico Children who
Currently Have Asthma by Various Demographic
Characteristics
Race/Ethnicity:
White, Non-Hispanic
Hispanic
Native American
8.1%
7.4%
13.1%
SOURCE: Centers for Disease Control and Prevention (CDC).
Behavioral Risk Factor Surveillance System Survey Data. Atlanta,
Georgia: U.S. Department of Health and Human Services, Centers
for Disease Control and Prevention, 2009
Asthma – Attack Prevalence by Age and Race, 2011
White
Black
100
ATTACK PREVALENCE PER 1,000
90
80
70
60
50
40
30
20
10
0
Total
<5
5-17
18-44
Trends in Asthma Morbidity and Mortality. American Lung Association,
Epidemiology and Statistics Unit, Research and Program Services Division.
September, 2012.
45-64
65+
Asthma – First-Listed Hospital Discharges by Race, 2010
Total
White
Black
All Other
28.5
30
DISCHARGES PER 10,000
25
20
15
14.3
11.6
10
9
5
0
Trends in Asthma Morbidity and Mortality. American Lung Association,
Epidemiology and Statistics Unit, Research and Program Services Division.
September, 2012.
Asthma age-adjusted hospitalization rates per 10,000 standard population
by county, New Mexico, 2007-2011 average
Legend
Rate per 10,000 population
State Rate: 8.8
2.5 - 5.9
5.9 - 7.2
7.2- 10.0
10.0 - 12.2
12.2- 21.6
Asthma hospitalization rates per 10,000 standard population among youth (0-14 years)
by county, New Mexico, 2007-2011 average
Rate per 10,000 population
State Rate: 16.9
0.0- 6.9
6.9 - 11.4
11.4 - 15.1
15.1- 18.1
18.1 - 57.1
Asthma – Crude Death Rate by Age Group, 2009
CRUDE DEATH RATE PER 100,000
12
10
8
6
4
2
0
1-4
5-14
15-24
25-34
35-44
45-54
Trends in Asthma Morbidity and Mortality. American Lung Association,
Epidemiology and Statistics Unit, Research and Program Services Division.
September, 2012.
55-64
65-74
75-84
85+
Asthma – Age-Adjusted Death Rates by Sex and Race, 2009
Male
Female
AGE-ADJUSTED DEATH RATE PER 100,000
3
2.5
2
1.5
1
0.5
0
Total
White
Trends in Asthma Morbidity and Mortality. American Lung Association,
Epidemiology and Statistics Unit, Research and Program Services Division.
September, 2012.
Black
Hispanic
Asthma Age-Adjusted Death Rates Based on the
1940 and 2000 Standard populations, 1979-2005
1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
1940 0.9 1.0 1.0 1.0 1.2 1.1 1.2 1.2 1.3 1.4 1.4 1.4 1.5 1.4 1.4 1.5 1.5 1.5 1.4 1.4 1.2 1.1 1.0 1.0 1.0 0.9 0.9
2000 1.3 1.4 1.5 1.5 1.7 1.6 1.8 1.8 1.9 2.0 2.1 2.1 2.2 2.0 2.1 2.2 2.2 2.2 2.1 2.0 1.7 1.6 1.5 1.5 1.4 1.3 1.3
Asthma Impact – Economic Burden
• Childhood asthma accounts
for 14.4 million days missed
from school annually
– The number-one chronic
condition causing children to be
absent from school and the
third highest ranked cause of
pediatric hospitalizations in the
United States
– On average, a child with
asthma will miss one full week
of school each year due to the
disease
Asthma Impact – Economic Burden
• Adult asthma accounts for
14.2 million missed
workdays annually
• 4th leading cause of
missed work days
National Burden of Asthma
$19.7 billion annually
• $14.7 billion in direct costs
(prescription medications,
hospital care, and physician
services)
• $5 billion in indirect costs
(lost productivity due to
missed work or school and
premature mortality)
DEFINE ASTHMA
Develop a collaborative working definition of asthma
Evolution of the Definition of Asthma
1962
American Thoracic Society, 1962.
• Episodic disease
characterized by:
– Reversible airway
constriction
– Increased airway
responsiveness
2007
NAEPP, EPR3, 2007.
• Chronic disease
characterized by:
– Chronic airway
inflammation
– At least partially
reversible airway
obstruction
– Increased airway
responsiveness
3M Resource Cards
Doctors Designers
11-96
3M Resource Cards
Doctors Designers
11/96
3M Resource Cards
Doctors Designers
11-96
Pathophysiology of Asthma
Epithelial Damage in Asthma
Normal
Asthmatic
Asthma: Pathophysiology
• Inflammatory cell infiltrate consists of mainly of
eosinophils and lymphocytes
• “Sudden death” asthma associated with an
infiltrate of neutrophils
• Denudation of airway epithelium
• Mucus gland hyperplasia and hypersecretion
• Smooth muscle cell hyperplasia
• Submucosal edema and vascular dilatation
• Fibrin deposition/airway remodeling
Multiple Mechanisms Contribute to Asthma:
Inflammatory Mediators
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Mast Cells
Macrophages
Eosinophils
T-Lymphocytes
Epithelial Cells
Platelets
Neutrophils
Myofibroblasts
Basophils
Bronchoconstriction
Mediator
Soup
Histamine
Lipid Mediators*
Peptides†
Cytokines‡
Growth Factors
*For example, prostaglandins and leukotrienes.
†For example, bradykinin and tachykinin.
‡For example, tumor necrosis factor (TNF).
Adapted with permission from Barnes PJ. In: Barnes PJ et al, eds. Asthma: Basic Mechanisms
and Clinical Management. 3rd ed. Academic Press; 1998:487-506.
Microvascular Leakage
Mucus Hypersecretion
Airway
Hyperresponsiveness
FACTORS LIMITING AIRFLOW IN ACUTE AND PERSISTENT ASTHMA
NAEPP, EPR-3, pg. 15.
Inflammation in Asthma
Allergen/Trigger
Mast cell
T-cell
Macrophage
Histamine
Cytokines
Eosinophil
Airway Inflammation
IgE = immunoglobulin E.
National Asthma Education and Prevention Program Guidelines, 1997.
Busse WW et al. N Engl J Med. 2001;344:350-362.
Bousquet J et al. Am J Resp Crit Care Med. 2000;161:1720-1745.
B-cell
IgE
Aftermath of Inflammation
• Reversibility
– Occurs in most
asthma episodes
– Airway returns to
normal caliber
– Flow of air through
airways returns to
normal “speed”
• Remodeling
– Airway lining builds up
persistent fibrotic
changes
– Airway caliber remains
abnormal
– Air flow is decreased
– Permanent changes
appear to begin in
childhood, but become
recognizable in adults
Asthma is a Chronic Inflammatory Disease:
Pathophysiologic Changes
Normal Architecture
Disrupted Architecture
Bronchial Mucosa From a
Subject Without Asthma
Bronchial Mucosa From a
Subject With Mild Asthma
Hematoxylin and eosin stain.
Photographs courtesy of Nizar N. Jarjour, MD, University of Wisconsin.
Consequences of Persistent Asthma:
Subepithelial Collagen Deposition
Lumen
Epithelium
Subepithelial Collagen
Deposition
Reprinted with permission from Holloway L et al. In: Busse WW, Holgate ST, eds. Asthma and
Rhinitis. Blackwell Scientific Publications; 1995:109-118.
Consequences of Persistent Asthma:
Progressive Decline in FEV1
FEV1 % Predicted
120
100
80
60
40
n = 89
r = -0.47
P<.001
20
0
10
20
30
Duration of Asthma (years)
FEV1 = forced expiratory volume in 1 second.
Adapted with permission from Brown PJ et al. Thorax. 1984;39:131-136.
40
50
Asthma is. . .
1. Chronic inflammatory disorder of the airways
– Mast cells, eosinophils and lymphocytes infiltrate into
airway lining
– Airway hyperresponsiveness develops
2. Excessive reaction to “minor” irritants results in
a host of deleterious airway changes
– Bronchial wall edema
– Smooth muscle contraction
– Excess mucus production
3. Patchy, mostly reversible regions of airway
narrowing cause asthma symptoms
Acute Reaction to Triggers
1. Irritated airways become
more inflamed after
exposure to stimuli
2. Muscle layers around
airway constrict
3. Airway lining swells
4. Excess mucus builds up
in lumen
5. Result: symptoms of
cough, wheeze,
shortness of breath,
chest tightness
Risk Factors for Developing Asthma
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Genetic predisposition
Atopy
Airway hyperresponsiveness
Gender
Race/Ethnicity
What Parameters Affect Disease ?
• Intrinsic factors
– Genetics
– Duration of asthma
– Severity of childhood
asthma
– Gender
– Response to therapy
• Extrinsic factors
– Viral infections
– Allergen exposure
– Airway irritants
– Exercise
– Compliance
– Season
– Time of day
– Occupational—1015% of adult asthma
– Western Lifestyle-obesity
Environmental Risk Factors for
Development of Asthma
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Indoor allergens
Outdoor allergens
Occupational sensitizers
Tobacco smoke
Air Pollution
Respiratory Infections
• Parasitic infections
• Socioeconomic
factors
• Family size
• Diet and drugs
• Obesity
• Hygiene hypothesis
Asthma & Airway Inflammation
Genetic
Risk Factors
Environmental
(for development of asthma)
INFLAMMATION
Bronchial
Hyperresponsiveness
Airflow Obstruction
Symptoms
Risk Factors
(for exacerbations)
Multiple Triggers Can Stimulate
Acute Reaction
• Upper Respiratory Infections (URI’s)
– Viral Respiratory infections are the #1 trigger behind asthma hospitalizations
– Influenza vaccines are recommended for people with asthma
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Allergens
Irritants
Sudden or extreme changes of weather
Exercise
Intense emotions
Exercise Induced Bronchospasm
• Bronchospasm caused by activity
– Some activity more likely than others to trigger it
• Cold environment: skiing, ice hockey
• Heavy exertion: Soccer, long distance running
• Exercising when you have a viral cold
Exercise Induced Bronchospasm
• Symptoms include
– Coughing
– Wheezing
– Chest tightness
• Symptoms may begin during activity and peak in
severity 10-20 minutes after stopping
• Can spontaneously resolve 20-30 minutes after
its onset
Epidemiology
• Prevalence 7-20% of the general population
• 80% of patients with asthma have some degree
of EIB
• Exercise is not a risk factor for asthma, rather a
trigger
• ?Exercise may help prevent onset of asthma in
children
– Decrease in physical activity may play a role in
increased in asthma prevalence
• JACI 2005 Lucas SR, Platts-Mills TA
Prevention of EIB
• Use bronchodilator 10-15 minutes before
onset of activity
• Do warm-up/cool down exercises
• Check ozone/allergy warnings
• Never encourage anyone to “tough it out”
Management
• Increasing fitness: decreases minute ventilation needs
with exercise
• Less severe if inspired air is warmer, more humid (Evidence
Class C)
– Scarf or mask if cold weather
– Warm-up period before exercise
• Good asthma control: EIB more frequent in patients with
poorly controlled disease (Class A)
– Check for asthma control
– Treating appropriately will reduce frequency and severity of EIB
Impairment and Risk Domains
• Impairment-frequency and intensity of
symptoms and functional limitations the patient
is experiencing or has experienced
• Risk-the likelihood of either asthma
exacerbations, progressive decline in lung
function or risk of adverse effects from
medication
NIH. NAEPP Expert Panel Report 3: Guidelines for the Diagnosis and Management
of Asthma, October 2007.
Risk Factors for Death from Asthma
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History of severe exacerbations
Prior intubation for asthma
Prior admission to Intensive Care Unit
2 or more hospital admissions in the past year
3 or more emergency room visits in the past
year
• Hospital or emergency room visit past month
• Use of >2 canisters per month of inhaled shortacting beta2 –agonist
Risk Factors for Death from Asthma
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Chronic use of systemic corticosteroids
Poor perception of airflow obstruction or its severity
Co-morbid conditions (other diseases)
Serious psychiatric disease or psychosocial
problems
Low socioeconomic status and urban residence
Illicit drug use
Sensitivity to alternaria-mold
Lack of written asthma action plan
Diagnosing Asthma
• Recurrent episodes of coughing or wheeze
• Asthma may be present without a wheeze cough may be the sole symptom
• Shortness of breath or difficulty breathing
• Chest Tightness
• Wheezing does not always mean asthma
• Absence of symptoms and physical findings at
the time of the examination does not exclude
asthma
Asthma
• Diagnosis by history of wheeze, shortness of
breath, cough, chest tightness
• Spirometry can help define the severity of the
disease, however may be normal if asthma is
under control
• Lack of bronchodilator response does not rule
out asthma
• Following Peak Flows may be useful
Measures of Assessment & Monitoring
• Spirometry should be performed:
– at initial assessment
– after treatment is initiated and symptoms and PEFs
have stabilized
– at least every 1-2 years to assess maintenance of
airway function if well controlled
– More often if poor asthma control
Measures of Assessment & Monitoring
• Peak Flows may be performed:
– In all moderate and severe persistent asthmatics
• establish a personal best
• useful in exacerbations and maintenance/ changes of
therapy,
• Can be helpful with ‘poor perceivers’
< 2 Years Old: When Is It Asthma?
Risk
Factors for
Developing
Asthma
• Family history of asthma
• Atopy, eczema
• Perinatal exposure to
aeroallergens and irritants
(e.g., passive smoke)
• Wheezing triggered by
factors other than upper
respiratory infections
< 2 Years Old: When Is It Asthma?
TWO GROUPS
OF INFANTS
WHEEZE
ASTHMA
NOT ASTHMA
Asthma Predictive Index
In an infant or young child with > 3 episodes
of wheezing in the past year
1 of 2 major criteria or 2 minor criteria
• MAJOR CRITERIA
– Atopic dermatitis
– Parental Asthma
• MINOR CRITERIA
– Wheezing apart
from colds
– Allergic rhinitis
– Blood eosinophilia
> ¾ of children with a positive index had some active
asthma symptoms between 6 and 13 years of age
• Present with
symptoms of
cough ± noisy or
rapid breathing,
usually before 5
years of age
Adults
Children
Asthma: Children vs. Adults
• Present with
symptoms of
cough,
shortness of
breath, chest
pain, wheezing,
often intermittent
or nocturnal
Asthma Misdiagnosis
Commonly
Misdiagnosed in
Children as:
Commonly
Misdiagnosed in
Adults as:
CHRONIC/WHEEZY
BRONCHITIS
RECURRENT CROUP
RECURRENT UPPER
RESPIRATORY INFECTION
RECURRENT PNEUMONIA
RECURRENT
BRONCHITIS
Asthma Severity Assessments
• < 6 year old often cannot perform
reliable Pulmonary Function
Test’s (PFT’s) or peak flow
measurements
• Older children with even severe
symptoms often have fairly
normal PFT’s between episodes
• Severity assessment often
focuses on symptoms more than
lung function measurements
• PFTs play more important role in
assessment
• PFT’s performed at diagnosis
and routinely at least every 1-2
years
CHILDREN
ADULTS
Long-Term Management of Asthma in Children:
Initiation of Control Therapy
• Symptoms > 2 x week
• Severe exacerbations < 6 weeks apart
• 2 or more burst of prednisone in 6 months for
ages 0-4
• 2 or more burst of prednisone in 1 year for ages
5-11
• Positive Asthma Predictive Index
Questions?