1. Eileen G. Holland, Pharm.D., BCPS Associate Professor
Management of Asthma
Eileen G. Holland, Pharm.D., BCPS Associate Professor

2. Guidelines
gov/guidelines/
asthma/asthgdln.
htm

3. Outline epidemiology pathophysiology diagnosis pharmacotherapy
disease management recommendations

4. Asthma: affects 14 to 15 million Americans 5 million children
most common chronic disease of childhood

5. Asthma: annual statistics
more than100 million days of restricted activity
more than 470,000 hospitalizations
more than 5,000 die from asthma
highest rate is among blacks aged 15 to 24 years

6. Asthma: definition
“A chronic inflammatory disorder of the airways associated with recurrent episodes of wheezing, breathlessness and cough, variable airflow obstruction and bronchial hyperresponsiveness.”

7. Asthma: definition
“A chronic inflammatory disorder of the airways associated with recurrent episodes of:
wheezing,
breathlessness,
cough,
variable airflow obstruction, and
bronchial hyperresponsiveness.”

8. Asthma: pathophysiology
chronic inflammation makes the airways hypersensitive to certain triggers:
allergens, chemicals, smoke, cold, exercise, food additives, aspirin, extreme emotional expressions

9. Asthma: pathophysiology
upon exposure to these stimuli, airways:
swell, constrict, fill with mucus
become hyperresponsive to stimuli
in most, airflow limitation is reversible, either spontaneously or with medication

10. Asthma: triggers exposure to: tobacco smoke
indoor allergens (domestic mites in bedding, carpets, stuffed furniture, cat, cockroach)
chemical irritants

11. Asthma: triggers
avoidance of these triggers should be strongly encouraged in infants with FH of asthma or atopy (familial tendency for allergic reactions)
tobacco smoke
indoor allergens
chemical irritants

12. Asthma: acute symptoms
dyspnea
wheezing (especially upon expiration)
absent, if severe obstruction
flaring of nostrils
interrupted talking
agitation
hyperinflation
chronic or recurring cough

13. Asthma: diagnosis episodic breathlessness wheezing chest tightness
cough

14. Asthma: diagnosis asthma is the likely diagnosis if:
symptoms occur at night or in early morning
episodes recur following one or more triggers
relief of symptoms occurs with a bronchodilator

15. Objective measurements
typically, asthmatics have poor recognition of their symptoms and poor perception of their severity
use of peak flow meters provides direct assessment of airflow limitation, variability and reversibility
essential for accurate diagnosis and monitoring of therapy

16. Peak flow meters small, portable, convenient, cheap
measure peak expiratory flow (PEF):
the fastest rate at which air can move through the airways during a forced expiration starting with fully inflated lungs
correlates well with FEV1

17. Use of patient’s PEF compare to predicted PEF values
based on height, race, sex, and age
measure response to drug therapy
evaluate variability, by measuring:
PEF in am (usually lowest)
PEF 12 hours later (usually highest)

18. Disease assessment based on PEF
patient’s PEF is lower than predicted
> 15% increase in PEF 15 minutes after inhalation of a short acting 2 agonist
> 10% PEF variability (AM:PM)
> 20% PEF variability (AM:PM) if taking bronchodilator
> 15% decrease in PEF after 6 minutes of exercise

19. Goals of management minimal or no symptoms
minimal asthma episodes / attacks
no emergency visits to MD or hospital
minimal need for as needed 2 agonist
no limitations on physical activities
nearly normal lung function
minimal or no side effects from medication

20. Treatment options Relievers: Controllers: short-acting 2 agonist
anticholinergics
systemic steroids
Controllers:
inhaled steroids
mast cell stabilizers
long-acting 2 agonist
methylxanthines

21. Relievers: short-acting 2 agonist
MDI with a spacer or nebulizer
onset in 5 minutes, lasts 3-8 hours
equally effective
tablets / syrup available for pediatrics
onset in 30 minutes, lasts 4-8 hrs
side effects are bothersome, but transient

22. Relievers: anticholinergic
ipratropium bromide
not indicated for asthma, but does provide bronchodilation
may provide added benefit to 2 agonist
few side effects

23. Ipratropium in adults Am J Med 1999;107:363-370
10 studies; 1453 adults in ER
during the first 90 minutes, supplementary ipratropium showed a pooled effect "...equivalent to a 10%...increase in PEF”
data available from 5 reports showed that ipratropium "...reduced admission rates significantly"

24. Ipratropium in adults Am J Med 1999;107:363-370
researchers concluded: addition of ipratropium to beta-agonist treatment "...offers a statistically significant, albeit modest, improvement in pulmonary function, as well as a reduction in the rate of hospital admissions."

25. Ipratropium in children NEJM1998;339:1030-5
randomized, double-blind, placebo-controlled study in ERs
434 children (2 to18 yo)
acute exacerbation of moderate to severe asthma

26. Ipratropium in children NEJM1998;339:1030-5
all children received:
nebulized albuterol ( mg per dose every 20 min x 3, then prn)
prednisone (2 mg/kg) with 2nd dose
treatment group:
500 mcg (2.5 mL) ipratropium with the 2nd and 3rd doses of albuterol
control group: 2.5 mL of NS

27. Ipratropium in children: hospitalization rates
overall
ipratropium = 59 of 215 (27.4%)
control = 80 of 219 (36.5%)
p = 0.05

28. Ipratropium in children hospitalization rates
if moderate dx (50-70% predicted)
ipratropium: 8 of 79 (10.1%)
control: 9 of 84 (10.7%)
if severe dx (<50% predicted)
ipratropium 51 of 136 (37.5%)
control = 71 of 135 (52.6%)
p = 0.02

29. Ipratropium in children NEJM1998;339:1030-5
conclusions: among children with a severe exacerbation of asthma, the addition of ipratropium bromide to albuterol and corticosteroid therapy significantly decreases the hospitalization rate

30. Relievers: systemic steroids
prednisone or prednisolone:
2 mg/kg/d (maximum of 60 mg/d)
split daily doses??
IV = PO
generally continue for 5 days
simultaneously initiate inhaled steroid
no need to taper systemic steroids

31. Controllers: inhaled steroids
must be scheduled ATC
takes 4 to 5 days to see benefit
minimal systemic adverse effects
dosing based on LD, MD, and HD

32. Controllers: mast cell stabilizer
cromolyn or nedocromil
must be scheduled ATC
most useful in patients with:
exercise induced
associated allergies
few side effects (cough)

33. Controllers: long-acting 2 agonist
salmeterol or
albuterol extended release tablets
must be scheduled ATC

34. Controllers: methylxanthines
sustained release theophylline
numerous adverse effects and interactions

35. Controllers: systemic steroids
2 mg/kg/d (max 60 mg/d)
numerous adverse effects
including growth retardation

36. Controllers: leukotriene modulators
montelukast, zafirlukast, zileuton
unknown place in therapy
may decrease need for MD or HD inhaled steroids in select patients

37. Management plan for asthma
classify the severity of the illness
identify the appropriate regimen that will maintain control of the illness
review classification and management plan every 1 to 6 months
gain control as quickly as possible, then adjust

38. Mild intermittent disease
symptoms < 1 / week
nocturnal symptoms < 2 / month
PEF > 80% predicted
PEF variability < 20%
reliever: short-acting 2 agonist PRN
controller: none

39. Mild persistent disease
symptoms > 1 / week (but not daily)
symptoms may affect activity
nocturnal symptoms > 2 / month
PEF > 80% predicted
PEF variability = 20% - 30%
reliever: short-acting 2 agonist PRN
controller: LD inhaled steroid or mast cell stabilizer

40. Moderate persistent disease
symptoms daily
symptoms affect activity
nocturnal symptoms > 1 / week
require short-acting 2 agonist daily
PEF 60% - 80% predicted
PEF variability > 30%
reliever: short-acting 2 agonist PRN
controller: MD inhaled steroid plus long-acting bronchodilator

41. Severe persistent disease
continuous symptoms
frequent exacerbations
frequent nocturnal symptoms
physical activities limited by asthma
PEF < 60% predicted
PEF variability > 30%
reliever: short-acting 2 agonist PRN
controller: HD inhaled steroid plus long-acting bronchodilator plus systemic steroids

42. Patient education use of MDIs use of spacers use of nebulizers
use of peak flow meters
avoidance of triggers
action plan

43. Comments??
Questions??