AsthmaAsthma

What is Asthma ?

What is Asthma?

1952 Definition:

“The presence of widespread narrowing of the airways which alters in severity either spontaneously or as a result of treatment”

Asthma

Chronic inflammatory disorder of the airways

Inflammation associated with Airways hyperresponsiveness Airflow limitation (at least partially reversible) Respiratory symptoms (wheeze, cough, tight chest)

Airway inflammation can be present even in mild disease

National Asthma Education and Prevention Panel, Expert Panel Report II “NAEPP Guidelines”, National Institutes of Health, 1997

What is Asthma?

Asthma

The “Tip” of the Iceberg

Airway inflammation

Airflow obstruction

Bronchial hyperresponsiveness

TITANIC Symptoms

Asthma

Symptoms of Asthma

Wheeze, cough, chest tightness (“dyspnea”)

Nocturnal awakenings

Recurrent attacks related to specific triggers

Asthma

Special Aspects of Asthma• Allergic (or extrinsic) asthma

• Nocturnal asthma

• Exercise-induced bronchoconstriction (EIB)

• Aspirin-sensitive

• Cough-variant

• Occupational

Asthma

Asthma Prevalence by Age37%

30%

21%

12%

15-19y

6-14y

< 6y

10%

19%

8%0%

0-19y 20-39y 40-59y 60+y

5%

10%

15%

20%

25%

30%

35%

40%

AGE (years)

Per

cen

tag

e o

f

Ast

hm

atic

Po

pu

lati

on

Asthma

AsthmaAsthmaBurden of Asthma

…on society

Asthma in the United States -- a growing problem

17.4 million Americans have asthma– Prevalence rose 75% 1980-1994– Prevalence rose more in children (160% in 0–4 y.o.’s)

1.9 million ER visits (in 1995) and466,000 hospitalizations (in 1993)– Office Visits doubled (from 1975 to 1995)

3 per 10,000 asthmatic patients die (1994)– Deaths doubled (for 5–24 y.o.’s from 1980 to 1993)

from National Center for Health StatisticsAsthma

Asthma is the Most Common Chronic Illness of Childhood

13 million physician visits/year 87% of asthmatic children had unscheduled physician visits in the prior

year

Third-ranking cause of hospitalization in children <15 and the highest-ranking cause among chronic conditions

200,000 hospitalizations/yearMost common chronic illness resulting in school absences

10.1 million lost school days a year On average: 1 week absent per asthmatic child

Asthma

Asthma Mortality

Higher risk of death from asthma– African Americans– Males

0

5

10

15

20

25

30

35

40

45

'79-'80 '81-'83 '84-'86 '87-'89 '90-'92 '93-'95

Caucasian

African AmericanRate of Asthma

Deaths(per 1,000,000)

Asthma

Pediatric Asthma Mortality Asthma deaths have more than doubled

for 0- to 14-year-olds from 1979 to 19951

Number of Asthma Deaths

0

20

40

60

80

100

120

140

160

'79-'80 '81-'83 '84-'86 '87-'89 '90-'92 '93-'95

0-4 yo

5-14 yo

Most patients who died – not seen as “high risk”2

Some patients who died had mild diseaseAsthma

AsthmaAsthmaBurden of Asthma

…on the patient

Asthma’s Impact

The highest-ranking chronic condition causing hospitalization in children

The most common chronic illness of childhood

Children with asthma have 3x the school absences of children without asthma

40% of children with asthma have sleep disturbances, 1 to 2 nights/week even if the child is not absent from school, he or she may

have reduced school performance due to sleep disturbances

Asthma

Asthma’s Impact

23% of adults with asthma missed work during the prior year due to asthma

36% of parents of asthmatics missed work in the prior year

50% of parents and 49% of patients say asthma limits the range of activities a family can do together

78% of parents of asthmatics report that asthma has a negative impact on the family

Asthma

AsthmaAsthma

Diagnosis

Diagnosis of AsthmaSymptoms

Wheeze, cough, chest tightness (“dyspnea”)

Nocturnal awakenings

Recurrent attacks related to specific triggers

Response to asthma-specific therapy

Asthma

Diagnosis of AsthmaLung Function Measurements

• Changes in lung function over time (Spontaneously or in response to therapy)

- Spirometry (FEV1)

- Peak expiratory flow rate(PEFR or “peak flow”)

• Airway hyperresponsiveness to stimuli

- Methacholine challenge test

- Exercise challenge test

Asthma

Bronchial Provocation

20

0

Low PD20 High BHR

High PD20 Low BHR

FEV1 %

fall from

baseline

A

B

C

Increasing dose of methacholine

Asthma

The Early and Late Asthmatic Response

50

25

1 2 3 4 5 6 7 8 9 10 11 12

75

100

Time (hours)Inhaled allergen

AAR

AAR = Acute asthmatic response LAR = Late asthmatic response

FE

V1 (

% p

red

icte

d)

LAR

Asthma

Spirometry

1

1

2

2

3

3

4

4

5 6

Time (seconds)

FEV1 post-bronchodilator

FEV1 pre-bronchodilator

Before bronchodilator

After bronchodilator

FVC

Exh

aled

vo

lum

e (L

)

Asthma

Uses of Daily Peak Flow Monitoring

Acutely:

• Assess severity of exacerbations

Short term:

• Evaluate therapy

• Establish temporal relationship to triggers

Long-term:

• Detect changes in disease status

• Evaluate treatment

• Provide patient with a written action plan

Asthma

Normal Asthma

Circadian Changes in PEFR

Morning peak flowEvening peak flow

PE

FR

(%

Pre

dic

ted

)

100%

50%

100%

50%

PEFR recorded twice-daily over 2 weeks

Asthma

AsthmaAsthmaDiagnosis

…per the guidelines

Asthma Guidelines: Recent evolution

NAEPP Guidelines 1997• National Asthma Education and Prevention Panel,

Expert Panel Report II, National Institutes of Health (“NIH”), National Heart, Lung, and Blood Institute (NHLBI))

GINA Guidelines 1998• Global INitiative for Asthma,

Asthma Management and Prevention Report, NHLBI and World Health Organization (WHO)

Pediatric Asthma: Promoting Best Practices 1999• American Academy of Allergy, Asthma & Immunology (AAAAI),

American Academy of Pediatrics (AAP), National Heart, Lung, and Blood Institute (NHLBI), NAEPP, etc

Asthma

NAEPP and GINA GuidelinesAsthma severity: Classified the same

3344

2211

Severe PersistentSevere Persistent

Moderate PersistentModerate Persistent

Mild PersistentMild Persistent

Mild IntermittentMild Intermittent

Severity is classified before therapy begins

• Symptoms

• Activity levels

• Exacerbations

• FEV1/PEFR

• PEFR variability

Classified by:

Severity is classified before therapy beginsAsthma

Asthma GuidelinesSeverity: Mild Intermittent

Mild Mild IntermittentIntermittent

Clinical features before treatment• Symptoms < 2x per week

• Brief exacerbations

• Nighttime symptoms < 2x per

month

• Asymptomatic with normal lung

function between exacerbations

• FEV1 and PEF > 80% predicted

• PEF variability < 20%

11

Asthma

Clinical features before treatment

• Symptoms > 2x per week but

<1x

per day

• Exacerbations may affect

activity

• Nighttime asthma symptoms >

2x

per month

• FEV1 and PEF > 80%

predicted

• PEF variability 20 - 30%

22Mild Mild PersistentPersistent

Asthma GuidelinesSeverity: Mild Persistent

Asthma

Clinical features before treatment

• Daily symptoms

• Exacerbations > 2x per week

affect activity

• Nighttime asthma symptoms >

1x

per week

• Daily use of short-acting ß

agonist

• FEV1 and PEF > 60% and <

80%

predicted

• PEF variability > 30%

33Moderate Moderate PersistentPersistent

Asthma GuidelinesSeverity: Moderate Persistent

Asthma

Clinical features before treatment

• Continuous symptoms

• Frequent exacerbations

• Frequent nighttime symptoms

• Limited activity

• FEV1 and PEF < 60% predicted

• PEF variability > 30%

44Severe Severe PersistentPersistent

Asthma GuidelinesSeverity: Severe Persistent

Asthma

Management of Asthma

Assessment and monitoringControl of factors contributing to

asthma severityPharmacotherapyEducation

Asthma

Eosinophils

MediatorsMediators

Histamine Histamine

Leukotrienes Leukotrienes

Prostaglandins Prostaglandins

Mast cell tryptase Mast cell tryptase

Eosinophil cationic proteinEosinophil cationic protein

Cytokines (IL-4, IL-5)Cytokines (IL-4, IL-5)

Mast cells

T lymphocytes

manyother cells

Inflammatory Cell-Derived Mediators

Asthma

Asthma

Asthma