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

Guidelines http://www.nhlbi.nih. gov/guidelines/ asthma/asthgdln. htm

Outline epidemiology pathophysiology diagnosis pharmacotherapy disease management recommendations

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

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

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

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

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

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

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

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

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

Asthma: diagnosis episodic breathlessness wheezing chest tightness cough

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

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

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

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)

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

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

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

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

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

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"

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."

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

Ipratropium in children NEJM1998;339:1030-5 all children received: nebulized albuterol (2.5 - 5 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

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

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

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

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

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

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

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

Controllers: methylxanthines sustained release theophylline numerous adverse effects and interactions

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

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

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

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

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

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

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

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

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