2. β2 Agonists Albuterol and other inhaled short-acting selective β2 agonists are indicated for treatment of intermittent episodes of bronchospasm and are the first treatment of choice for acute severe asthma. Formoterol and salmeterol are inhaled long-acting β2 agonists indicated as adjunctive long-term control for patients with symptoms who are already on low to medium doses of inhaled corticosteroids prior to advancing to medium- or high-dose inhaled corticosteroids.

3. Corticosteroids Corticosteroids increase the number of β2-adrenergic receptors and improve receptor responsiveness to β2- adrenergic stimulation, thereby reducing mucus production and hypersecretion, reducing BHR, and preventing and reversing airway remodeling. Inhaled corticosteroids are the most effective long-term control therapy for persistent asthma, regardless of severity, and the only therapy shown to reduce the risk of death from asthma even in relatively low doses. Systemic toxicity is minimal with low to moderate inhaled doses, but the risk of systemic effects increases with high doses. Local adverse effects include dose-dependent oropharyngeal candidiasis and dysphonia, which can be reduced by the use of a spacer device.

4. Corticosteroids Systemic corticosteroids are indicated in all patients with acute severe asthma not responding completely to aggressive inhaled β2 agonists. Intravenous therapy offers no advantage over oral administration. It may take 6 to 8 hours for improvement in pulmonary function to occur after initiation of systemic therapy. Many patients require only 3- to 5-day courses of systemic corticosteroids. Tapering the steroid dosage after short courses is unnecessary. Prednisone, 1 to 2 mg/kg/day (up to 40 to 60 mg/day), is administered orally in two divided doses for 3 to 10 days.

5. Methylxanthines Theophylline appears to produce bronchodilation by inhibiting phosphodiesterases (PDEs), which may also result in anti- inflammatory and other nonbronchodilator activity through decreased mast cell mediator release, decreased eosinophil basic protein release, decreased T-lymphocyte proliferation, decreased T-cell cytokine release, and decreased plasma exudation. Theophylline also inhibits vascular permeability, enhances mucociliary clearance, and strengthens contractions of a fatigued diaphragm. Methylxanthines are ineffective by aerosol and must be taken systemically (orally or IV). Sustained-release theophylline is the preferred oral preparation, whereas its complex with ethylenediamine (aminophylline) is the preferred parenteral product due to increased solubility.

6. Anticholinergics Ipratropium bromide and tiotropium bromide are competitive inhibitors of muscarinic receptors; they produce bronchodilation only in cholinergic-mediated bronchoconstriction. Anticholinergics are effective bronchodilators but are not as potent as β2 agonists. They attenuate, but do not block, allergen- or exercise-induced asthma in a dose-dependent fashion. Inhaled ipratropium bromide is only indicated as adjunctive therapy in severe acute asthma not completely responsive to β2 agonists alone.