ASTHMA PATHOPHYSIOLOGYASTHMA OVERVIEW
Presented by:Michelle Harkins, MD
University of New Mexico
This session will cover
• 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
Under 5 5-17 <18 18-44 45-64 65+0
20
40
60
80
100
120
68.5
105.594.9
79.986.7
79.4
Asthma – Current Prevalence by Age, 2011CU
RREN
T PR
EVAL
ENCE
RAT
E PE
R 1,
000
Trends in Asthma Morbidity and Mortality. American Lung Association, Epidemiology and Statistics Unit, Research and Program Services Division. September, 2012.
Total Under 18 18 and Over0
20
40
60
80
100
120
71.9
101.7
61.8
97.387.8
100.1
Asthma – Current Prevalence by Sex and Age, 2011
Male Female
Curr
ent P
reva
lenc
e pe
r 1,0
00
Trends in Asthma Morbidity and Mortality. American Lung Association, Epidemiology and Statistics Unit, Research and Program Services Division. September, 2012.
Total Under 18 18 and Over0
50
100
150
200
250
300
350
80.4
147.3
238
118
314.2287.9
Asthma – Current Prevalence by Race, 2011
Whites Blacks
Curr
ent P
reva
lenc
e pe
r 1,0
00
Trends in Asthma Morbidity and Mortality. American Lung Association, Epidemiology and Statistics Unit, Research and Program Services Division. September, 2012.
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 8.1%Hispanic 7.4%Native American 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
Total <5 5-17 18-44 45-64 65+0
10
20
30
40
50
60
70
80
90
100
Asthma – Attack Prevalence by Age and Race, 2011
White Black
ATTA
CK P
REVA
LEN
CE p
er 1
,000
Trends in Asthma Morbidity and Mortality. American Lung Association, Epidemiology and Statistics Unit, Research and Program Services Division. September, 2012.
0
5
10
15
20
25
30
14.3
9
28.5
11.6
Asthma – First-Listed Hospital Discharges by Race, 2010Total White Black All Other
DISC
HARG
ES P
ER 1
0,00
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
LegendRate per 10,000 populationState 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 populationState Rate: 16.9
0.0- 6.9
6.9 - 11.4
11.4 - 15.1
15.1- 18.1
18.1 - 57.1
Series10
2
4
6
8
10
12
Asthma – Crude Death Rate by Age Group, 2009
1-4 5-14 15-24 25-34 35-44 45-54 55-64 65-74 75-84 85+
CRU
DE D
EATH
RAT
E PE
R 10
0,00
0
Trends in Asthma Morbidity and Mortality. American Lung Association, Epidemiology and Statistics Unit, Research and Program Services Division. September, 2012.
Total White Black Hispanic0
0.5
1
1.5
2
2.5
3
Asthma – Age-Adjusted Death Rates by Sex and Race, 2009
Male Female
AGE-
ADJU
STED
DEA
TH R
ATE
PER
100,
000
Trends in Asthma Morbidity and Mortality. American Lung Association, Epidemiology and Statistics Unit, Research and Program Services Division. September, 2012.
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 20051940 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 0.92000 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
• Episodic disease characterized by:– Reversible airway
constriction– Increased airway
responsiveness
• Chronic disease characterized by:– Chronic airway
inflammation– At least partially
reversible airway obstruction
– Increased airway responsiveness
1962 2007American Thoracic Society, 1962. NAEPP, EPR3, 2007.
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
AsthmaticNormal
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
• Mast Cells• Macrophages• Eosinophils• T-Lymphocytes• Epithelial Cells• Platelets• Neutrophils• Myofibroblasts• Basophils
Multiple Mechanisms Contribute to Asthma: Inflammatory Mediators
HistamineLipid Mediators*
Peptides†
Cytokines‡
Growth Factors
MediatorSoup
Bronchoconstriction
Microvascular Leakage
Mucus Hypersecretion
AirwayHyperresponsiveness
*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.
NAEPP, EPR-3, pg. 15.
FACTORS LIMITING AIRFLOW IN ACUTE AND PERSISTENT ASTHMA
Inflammation in Asthma
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.
Airway Inflammation
Allergen/Trigger
T-cell
B-cell
IgEEosinophil
Mast cell
CytokinesHistamine
Macrophage
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
Hematoxylin and eosin stain.Photographs courtesy of Nizar N. Jarjour, MD, University of Wisconsin.
Bronchial Mucosa From a Subject Without Asthma
Bronchial Mucosa From a Subject With Mild Asthma
Normal Architecture Disrupted Architecture
Lumen
Epithelium
Subepithelial Collagen Deposition
Consequences of Persistent Asthma: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.
FEV 1
% P
redi
cted
Duration of Asthma (years)
80
40
120
10 20 5040300
r = -0.47n = 89
P<.001
60
20
100
Consequences of Persistent Asthma: Progressive Decline in FEV1
FEV1 = forced expiratory volume in 1 second.Adapted with permission from Brown PJ et al. Thorax. 1984;39:131-136.
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
Asthma is. . .
Acute Reaction to Triggers
1. Irritated airways become more inflamed after exposure to stimuli
2. Muscle layers around airway constrict
3. Airway lining swells4. Excess mucus builds up
in lumen5. Result: symptoms of
cough, wheeze, shortness of breath, chest tightness
• Genetic predisposition• Atopy• Airway hyperresponsiveness• Gender• Race/Ethnicity
Risk Factors for Developing Asthma
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—10-
15% of adult asthma– Western Lifestyle--
obesity
Environmental Risk Factors for Development of Asthma
• Indoor allergens• Outdoor allergens• Occupational sensitizers• Tobacco smoke• Air Pollution• Respiratory Infections
• Parasitic infections• Socioeconomic
factors• Family size• Diet and drugs• Obesity• Hygiene hypothesis
INFLAMMATION
Risk Factors(for development of asthma)
BronchialHyperresponsiveness
Airflow Obstruction
Risk Factors(for exacerbations)
Symptoms
Genetic Environmental
Asthma & Airway Inflammation
Multiple Triggers Can StimulateAcute Reaction
• Upper Respiratory Infections (URI’s)– Viral Respiratory infections are the #1 trigger behind asthma hospitalizations– Influenza vaccines are recommended for people with asthma
• 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.
• 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 short-
acting beta2 –agonist
Risk Factors for Death from Asthma
• 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
Risk Factors for Death from 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
Diagnosing 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
• 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’
Measures of Assessment & Monitoring
< 2 Years Old: When Is It 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
Risk Factors
for Develo
ping Asthma
< 2 Years Old: When Is It Asthma?
TWO GROUPS OF INFANTS WHEEZE
ASTHMA NOT ASTHMA
Asthma Predictive Index
• MAJOR CRITERIA– Atopic dermatitis– Parental Asthma
• MINOR CRITERIA– Wheezing apart
from colds– Allergic rhinitis– Blood eosinophilia
1 of 2 major criteria or 2 minor criteria
> ¾ of children with a positive index had some active asthma symptoms between 6 and 13 years of age
In an infant or young child with > 3 episodes of wheezing in the past year
Asthma: Children vs. Adults
Children
•Present with symptoms of cough ± noisy or rapid breathing, usually before 5 years of age
Adults
•Present with symptoms of cough, shortness of breath, chest pain, wheezing, often intermittent or nocturnal
Asthma Misdiagnosis
Commonly Misdiagnosed in
Children as:CHRONIC/WHEEZY
BRONCHITIS
RECURRENT CROUP
RECURRENT UPPER RESPIRATORY INFECTION
RECURRENT PNEUMONIA
Commonly Misdiagnosed in Adults as:
RECURRENTBRONCHITIS
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
CHILDREN
•PFTs play more important role in assessment•PFT’s performed at diagnosis and routinely at least every 1-2 years
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?