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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.

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.

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.

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 µg/mL. Theop hylline sustained release ( Theo- Dur, 100-400 mg PO bid).

_{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.