1. Asthma
What is Asthma ?
V1.0
1997 Merck & .

2. 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

3. What is 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
Asthma is a chronic inflammatory disease of the airways. Airway inflammation in patients with asthma is associated with airway hyperresponsiveness, airflow limitation which is partly reversible, and respiratory symptoms including wheezing, breathlessness, cough, chest tightness and nocturnal awakenings. Studies have also demonstrated that airway inflammation can be present even in mild disease, suggesting that controller therapy should be used in patients with mild persistent disease even when they are asymptomatic.
Beasley et al., Am Rev Respir Dis 1989;139: Airway inflammation exists in patients with mild disease
Asthma
National Asthma Education and Prevention Panel, Expert Panel Report II
“NAEPP Guidelines”, National Institutes of Health, 1997

4. The “Tip” of the Iceberg
TITANIC
Symptoms
Airflow
obstruction
Bronchial
hyperresponsiveness
With asthma, what we see is the tip of the iceberg, the symptoms.
At the base of the iceberg is the airway inflammation.
This inflammation underlies the bronchial hyperresponsiveness of asthma.
Airflow obstruction results from bronchoconstriction, bronchial edema, mucus hypersecretion and inflammatory cell recruitment including eosinophils, a key inflammatory cell.
The culmination of the inflammatory process is the tip of the iceberg, the symptoms.
Airway
inflammation
Asthma

5. Symptoms of Asthma Wheeze, cough, chest tightness (“dyspnea”)
Nocturnal awakenings
Recurrent attacks related to specific triggers
Asthma 24

6. Special Aspects of Asthma
• Allergic (or extrinsic) asthma
• Nocturnal asthma
• Exercise-induced bronchoconstriction (EIB)
• Aspirin-sensitive
• Cough-variant
• Occupational
Asthma

7. Asthma Prevalence by Age
37%
40%
30%
35%
10%
15-19y
30%
21%
25%
Asthmatic Population
Percentage of
20%
12%
19%
6-14y
15%
10% 5% 8%
< 6y 0%
0-19y
20-39y
40-59y
60+y
AGE (years)
Asthma

8. Burden of Asthma …on society
V1.0
1997 Merck & .

9. Asthma in the United States -- a growing problem
17.4 million Americans have asthma
Prevalence rose 75%
Prevalence rose more in children (160% in 0–4 y.o.’s)
1.9 million ER visits (in 1995) and 466,000 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)
Asthma
from National Center for Health Statistics 4

10. 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/year
Most common chronic illness resulting in school absences
10.1 million lost school days a year
On average: 1 week absent per asthmatic child
Asthma is the Most Common Chronic Illness of Childhood. The prevalence in the U.S. ranges from 3 to 7%, resulting in 13 million physician visits per year (Lozano et al., Pediatrics 1997;99: ). It is the third-ranking cause of hospitalization in children under the age of 15 and highest-ranking cause among chronic conditions, with 200,000 hospitalizations per year (Lozano et al., Pediatrics 1997;99: ). Asthma is the most common chronic illness resulting in school absences. Over ten million school days are lost each year , this is an average of 1 week per child asthmatic child (Weiss KB et al. N Engl J of Med 1992;326: ). It is not surprising that children with asthma have 3 times the school absences of children without asthma (Lozano et al., Pediatrics 1997;99: ).
Total direct cost for asthma in 1994 were 1.9 billion dollars, with hospitalization and outpatient treatment accounting for 54% and 21% of that total, respectively (Weiss KB et al. N Engl J of Med 1992;326: ).
Asthma

11. Asthma Mortality Higher risk of death from asthma African Americans
Males
Rate of Asthma Deaths
(per 1,000,000)
African Americans and males are at higher risk of death from asthma.
This graph illustrates data from the CDC showing the asthma death rate for African Americans versus Caucasian Americans (categorized in the CDC data as “Black” and “White”, respectively). As shown, the rate is considerably higher for African Americans, and has risen more quickly over the past 20 years than in Caucasians.
CDC. Surveillance for Asthma--United States, (CDC Surveillance Summaries). MMWR. 1998;47(SS-1):1-26
Asthma

12. Pediatric Asthma Mortality
Asthma deaths have more than doubled for 0- to 14-year-olds from 1979 to 19951
Number of Asthma Deaths
Asthma deaths have doubled for 0- to 14-year-olds from 1979 to 1995, with the 5 to 14 year olds driving the rise in mortality1.
In a population-based study by Robertson and colleagues2, the majority of patients aged 0 to 20 years who died due to asthma could not be classified as “high risk”: Of 51 deaths:
33% were judged to have had a history of trivial or mild asthma
32% had no previous hospital admission for asthma.
Death occurred outside the hospital in 78% of subjects.
Thus, some of the patients who died had apparently mild disease, though many were felt in retrospect to have had inadequate assessment or therapy of prior asthma.
1CDC. Surveillance for Asthma--United States, (CDC Surveillance Summaries). MMWR. 1998;47(SS-1):1-26
2Robertson et al., Pediatric asthma deaths in Victoria: The mild are at risk. Pediatr Pulmonol 1992;13:
Most patients who died – not seen as “high risk”2
Some patients who died had mild disease
Asthma

13. Burden of Asthma …on the patient
V1.0
1997 Merck & .

14. 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

15. 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

16. Asthma
Diagnosis
V1.0
1997 Merck & .

17. Diagnosis of Asthma Symptoms
Wheeze, cough, chest tightness (“dyspnea”)
Nocturnal awakenings
Recurrent attacks related to specific triggers
Response to asthma-specific therapy
Asthma 24

18. Diagnosis of Asthma Lung 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

19. Bronchial ProvocationA 20 B
FEV1 %
fall from
baseline C
Low PD20
High PD20
High BHR
Low BHR
Increasing dose of methacholine
Asthma

20. The Early and Late Asthmatic Response
100
LAR 75
FEV1 (% predicted) 50
AAR 25
AAR = Acute asthmatic response
LAR = Late asthmatic response 1 2 3 4 5 6 7 8 9 10 11 12
Inhaled
Time (hours)
allergen
Asthma

21. Spirometry FEV1 post-bronchodilator FEV1 pre-bronchodilator 4 3
Exhaled volume (L) 2
FVC
After bronchodilator 1
Before bronchodilator 1 2 3 4 5 6
Time (seconds)
Asthma

22. 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

23. PEFR recorded twice-daily over 2 weeks
Circadian Changes in PEFR
PEFR recorded twice-daily over 2 weeks
Normal
Asthma
100%
100%
PEFR (%Predicted)
50%
50%
Evening peak flow
Morning peak flow
Asthma

24. Diagnosis …per the guidelines
Asthma
Diagnosis …per the guidelines
V1.0
1997 Merck & .

25. Asthma Guidelines: Recent evolution
NAEPP Guidelines
National Asthma Education and Prevention Panel, Expert Panel Report II, National Institutes of Health (“NIH”), National Heart, Lung, and Blood Institute (NHLBI))
GINA Guidelines
Global INitiative for Asthma, Asthma Management and Prevention Report, NHLBI and World Health Organization (WHO)
Pediatric Asthma: Promoting Best Practices
American Academy of Allergy, Asthma & Immunology (AAAAI), American Academy of Pediatrics (AAP), National Heart, Lung, and Blood Institute (NHLBI), NAEPP, etc
The pediatric asthma guidelines establish a four-step classification system for asthma severity: mild intermittent, mild persistent, moderate persistent, and severe persistent. The severity is classified before therapy begins.
Pediatric Asthma: Promoting Best Practice, Guide for Managing Asthma in Children. Milwaukee, WI: American Academy of Allergy, Asthma and Immunology (with AAP, NAEPP / NHLBI / NIH), 1999.
Asthma

26. NAEPP and GINA Guidelines Asthma severity: Classified the same
Classified by: 3 4 2 1
Severe Persistent
Moderate Persistent
Mild Persistent
Mild Intermittent
Symptoms
• Activity levels
• Exacerbations
• FEV1/PEFR
• PEFR variability
The pediatric asthma guidelines establish a four-step classification system for asthma severity: mild intermittent, mild persistent, moderate persistent, and severe persistent. The severity is classified before therapy begins.
Pediatric Asthma: Promoting Best Practice, Guide for Managing Asthma in Children. Milwaukee, WI: American Academy of Allergy, Asthma and Immunology (with AAP, NAEPP / NHLBI / NIH), 1999.
Severity is classified before therapy begins
Severity is classified before therapy begins
Asthma

27. Asthma Guidelines Severity: Mild Intermittent
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% 1
Mild Intermittent
Asthma

28. Asthma Guidelines Severity: Mild Persistent
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 % 2
Mild Persistent
Asthma

29. Asthma Guidelines Severity: Moderate Persistent
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% 3
Moderate Persistent
Asthma

30. Asthma Guidelines Severity: Severe Persistent4
Clinical features before treatment
Continuous symptoms
Frequent exacerbations
Frequent nighttime symptoms
Limited activity
FEV1 and PEF < 60% predicted
PEF variability > 30%
Asthma

31. Management of Asthma Assessment and monitoring
Control of factors contributing to asthma severity
Pharmacotherapy
Education
Asthma

32. Inflammatory Cell-Derived Mediators
Mast cells
Eosinophils
Histamine
Leukotrienes
Mediators
Prostaglandins
Mast cell tryptase
Eosinophil cationic protein
Cytokines (IL-4, IL-5)
many other cells
T lymphocytes
Asthma

33. Asthma

34. Asthma