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Asthma

David Stevenson, MD

 

Asthma is the most common chronic disease among children. At least 75 percent of asthmatic patients demonstrate immediate hypersensitivity to common aeroallergens. Asthma triggers include viral infections; environmental pollutants, such as tobacco smoke; certain medications, (aspirin, nonsteroidal anti-inflammatory drugs), and sustained exercise, particularly in cold environments.

Diagnosis

History

Symptoms of episodic complaints of breathing difficulties, seasonal or nighttime cough, prolonged shortness of breath after a respiratory infection, or difficulty sustaining exercise.

Reversible airways disease does not always represent asthma. Wheezing may persist for weeks after an acute bronchitis episode. Patients with chronic obstructive pulmonary disease may have a reversible component superimposed on their fixed obstruction. Etiologic clues include a personal history of allergic disease, such as rhinitis or atopic dermatitis, and a family history of allergic disease.

The frequency of daytime and nighttime symptoms, duration of exacerbations and asthma triggers should be assessed.

Asthma Triggers

Sources of inhaled allergens

House dust mites

Animal danders from house pets

Pollen

Fungal spores

Cockroaches

Animal urine from laboratory animals

Infections

Viral respiratory infections

Sinusitis

Gastroesophageal reflux

Sulfites (used as preservatives in food, beer and wine)

Environmental irritants/precipitants

Tobacco smoke

Cold air

Exercise

Particulates from wood stoves

Air pollution

Chemical gases or fumes

Drugs

Aspirin

Nonsteroidal anti-inflammatory drugs

Angiotensin converting enzyme inhibitors

Beta blockers

Physical examination. Hyperventilation, use of accessory muscles of respiration, audible wheezing, and a prolonged expiratory phase are common. Increased nasal secretions or congestion, polyps, and eczema may be present. The chest and lungs should be assessed for wheezing.

Measurement of lung function. An increase in the forced expiratory volume in one second (FEV1) of 12 percent after treatment with an inhaled beta2 agonist is sufficient to make the diagnosis of reversible airways disease. A similar change in peak expiratory flow rate (PEFR) measured on a peak flow meter is also diagnostic.

Asthma Classification

Symptoms

Classification

Daytime

Nighttime

Lung function

Mild intermittent

Symptoms occur up to 2 times/week; exacerbations are brief (hours to days), with normal PEFR and no symptoms between exacerbations

Symptoms occur up to 2 times/month

PEFR or FEV1 $80% of predicted; <20% variability in PEFR

Mild persistent

Symptoms occur more than 2 times/week but less than one time/day; exacerbations may affect normal activity

Symptoms occur more than 2 times/month

PEFR or FEV, $80% of predicted; PEFR variability 20-30%

Moderate persistent

Symptoms occur daily; daily need for inhaled short-acting beta2 agonist; exacerbations affect normal activity; exacerbations occur more than 2 times/week and may last for days

Symptoms occur more than one time/week

PEFR or FEV1 >60 but <80% of predicted; PEFR variability >30%

Severe persistent

Symptoms are continual; physical activity is limited; exacerbations are frequent

Symptoms are frequent

PEFR or FEV1 <60% of predicted; PEFR variability >30%

Treatment

Allergen avoidance. Patients should avoid opening windows and using unfiltered window fans. Elimination of allergens from house dust mites and cats also will reduce symptoms.

Long-term control medications

Corticosteroids

Glucocorticoids provide anti-inflammatory effects and reduce bronchial hyperactivity. Inhaled corticosteroids are first-line agents in patients who require daily asthma therapy. No specific inhaled corticosteroid preparation is superior to another. Primary adverse effects of these medications are cough, oral thrush and hoarseness. In high doses, a potential exists for significant systemic absorption. Patients with severe persistent asthma may require daily systemic steroid therapy when other medications have failed.

Prednisone, prednisolone or methylprednisolone ( Solu-Medrol), 40 to 60 mg qd; for children, 1 to 2 mg/kg/day to a maximum of 60 mg/day. Therapy is continued for 3-10 days. The oral steroid dosage does not have to be tapered after short-course "burst" therapy if the patient is receiving inhaled steroid therapy.

Pharmacotherapy for Asthma Based on Disease Classification

Classification

Long-term control medications

Quick-relief medications

Mild intermittent

Short-acting beta2 agonist as needed

Mild persistent

Low-dose inhaled corticosteroid or cromolyn sodium (Intal) or nedocromil (Tilade); alternatively, a leukotriene modifier may be used

Short-acting beta2 agonist as needed

Moderate persistent

Medium-dose inhaled corticosteroid plus a long-acting bronchodilator (long-acting beta2 agonist) if needed

Short-acting beta2 agonist as needed

Severe persistent

High-dose inhaled corticosteroid plus a long-acting bronchodilator and systemic corticosteroid if needed

Short-acting beta2 agonist as needed

Inhaled Corticosteroids and Mast Cell Stabilizers

     

Dose range (total puffs/day)

Drug

Trade name

Dose (Fg/puff)

Low

Intermediate

High

Beclomethasone

Beclovent

Vanceril

Vanceril Double Strength

42

42

84

4 to 12

4 to 12

2 to 6

12 to 20

12 to 20

6 to 10

>20

>20

>10

Triamcinolone

Azmacort

100

4 to 10

10 to 20

>20

Flunisolide

AeroBid

250

2 to 4

4 to 8

>8

Fluticasone

Flovent 44

Flovent 110

Flovent 220

44

110

220

2 to 6

2

 

2 to 6

 

>6

>3

 

Mast cell stabilizers

Cromolyn sodium MDI

Intal

800 mg/puff

nebulizer, 20 mg/2-mL ampule

Adults: 6 puffs or 3 ampules in three divided doses

Children: 3 puffs or 3 ampules in three divided doses

Adults: 9 to 12 puffs in three divided doses

Children: 6 puffs in three divided doses

Adults: 16 puffs in three divided doses or 4 ampules in four divided doses

Children: 8 puffs or 4 ampules in four divided doses

Nedocromil

Tilade

1.75 mg/puff

Adults: 4 to 6 puffs in two to three divided doses

Children: 2 to 3 puffs in two to three divided doses

Adults: 9 to 12 puffs in two to three divided doses

Children: 4 to 6 puffs in two to three divided doses

Adults: 16 puffs in four divided doses

Children: 8 puffs in four divided doses

 

Cromolyn sodium (Intal, Nasalcrom) and nedocromil sodium (Tilade) are anti-inflammatory medications. They lack the systemic side effects associated with corticosteroids. Cromolyn, available in a metered-dose inhaler or as inhaler solution, requires dosing four times per day. Nedocromil is designed for twice-daily dosing. Maximal benefit may not be achieved for four to six weeks. Cromolyn and nedocromil are first-line agents in children.

Leukotriene modifiers

Zafirlukast ( Accolate), montelukast ( Singulair) and zileuton ( Zyflo) interfere with the actions of leukotriene inflammatory mediators, preventing bronchoconstriction. Zileuton is a 5-lipoxygenase inhibitor. Zafirlukast is a leukotriene receptor antagonist. Montelukast is similar to zafirlukast but is taken only once per day at night. Zafirlukast must be taken on an empty stomach.

Zafirlukast and zileuton may interfere with the metabolism of warfarin (Coumadin).

Zileuton has been associated with elevated levels of liver enzymes; thus, periodic monitoring of alanine transaminase is required. Zafirlukast (Accolate, 20 mg bid, on an empty stomach), montelukast ( Singular, 10 mg PO qhs) and zileuton (Zyflo, 600 mg PO qid) are alternatives for patients with mild persistent asthma who are not candidates for inhaled anti-inflammatory medications.

Long-acting beta2 agonists. If inhaled anti-inflammatory medications do not prevent asthma symptoms, an inhaled long-acting beta2 agonist may be added. Long-acting beta2 agonists relax bronchial smooth muscle. Salmeterol (Serevent, 2 puffs bid), a long-acting beta2 agonist, has a slower onset of action (up to 30 minutes) but a longer duration (at least 12 hours) than short-acting beta2 agonists. Salmeterol improves nighttime and exercise-associated symptoms. Patients should not use salmeterol for acute asthma attacks.

Methylxanthines use has declined with the arrival of safer and more effective medications. However, they still have a role in asthma therapy when newer anti-inflammatory medications fail to provide relief. Theophylline produces smooth muscle relaxation resulting in bronchodilation but also improves diaphragmatic contractility and increases mucociliary clearance. It may also have some anti-inflammatory effects. Selected patients may benefit from a sustained-action theophylline preparation in the evening, with the drug titrated to a serum concentration ranging from 5 to 15 g/mL. Theop hylline sustained release ( Theo- Dur, 100-400 mg PO bid).

Beta2 Agonists and Dosing

Drug

Trade name

Dosage

Long-Acting Agent

Salmeterol

Serevent

2 puffs bid

Short-Acting Agents

Albuterol

Ventolin Rotacaps

Proventil

Ventolin

One inhaled capsule every four to eight hours prn

2-4 puffs q4-8h prn

Albuterol HTA

Proventil HFA

2-4 puffs q4-8h prn

Bitolterol

Tornalate

2-4 puffs q4-8h prn

Pirbuterol

Maxair

2-4 puffs q4-8h prn

Quick-relief medications

Short-acting beta2 agonists are rescue medications which should only be used as monotherapy in patients with mild and intermittent asthma. These potent bronchodilators provide quick relief of acute symptoms.

Anticholinergics. Ipratropium (Atrovent) reverses bronchospasm and may have an additive effect when used with inhaled short-acting beta2 agonists.

Systemic corticosteroids. In patients with moderate to severe exacerbations of asthma, use of systemic corticosteroids during an attack can prevent further progression of the episode. Seven to 10 days is usually sufficient. Prednisone, prednisolone or methylprednisolone, 40 to 60 mg qd. The oral steroid does not have to be tapered after a short-course of therapy if the patient is on an inhaled steroid.

Management of acute exacerbations

High-dose, short-acting beta2 agonists delivered by a metered-dose inhaler with a volume spacer or via a nebulizer remain the mainstays of urgent treatment. Nebulized ipratropium bromide may enhance the bronchodilation provided by a short-acting beta2 agonist. Supplemental oxygen should be used to maintain the oxygen saturation at greater than 90 percent.

Most patients require therapy with systemic corticosteroids to resolve symptoms and prevent relapse.

Hospitalization should be considered if the PEFR remains less than 70% of predicted. Patients with a PEFR less than 50% of predicted who exhibit an increasing pCO2 level and declining mental status are candidates for intubation.