Drug Treatment of Asthma

Beta2-adrenergic receptor agonists and beta agonists relax bronchial smooth muscle, decrease mast cell degranulation and histamine release, inhibit microvascular leakage into the airways, and increase mucociliary clearance. Beta-2 agonist preparations may be short-acting, long-acting, or ultra–long-acting (see tables Drug Treatment of Chronic Asthma and Drug Treatment of Asthma Exacerbations).

Short-actinghypokalemiaR

Long-acting

Ultra-long-acting beta agonists (eg, indacaterol) are active for up to 24 hours and as with long-acting beta agonists are used for moderate to severe asthma, and should never be used as a monotherapy. They interact synergistically with inhaled corticosteroids and permit lower dosing of corticosteroids.

The safety of regular long-term use of beta agonists has been confirmed by multiple randomized, controlled trials and meta-analyses, including a large international safety study that was followed by removal of a black box warning by the Food and Drug Administration (1). Because the safety and efficacy of long-acting beta agonists have been demonstrated only when used in combination with an inhaled corticosteroid, all long-acting and ultra-long beta agonists should be used only in combination with an inhaled corticosteroid for patients whose condition is not adequately controlled with other asthma controllers (eg, low- to medium-dose inhaled corticosteroids) or whose disease severity clearly warrants additional maintenance therapies. Daily use or diminishing effects of short-acting beta agonists or use of ≥ 1 canister per month suggests inadequate control and the need to begin or intensify other therapies.

Corticosteroids inhibit airway inflammation, reverse beta-receptor down-regulation, and inhibit cytokine production and adhesion protein activation. They block the late response (but not the early response) to inhaled allergens. Routes of administration include oral, IV, and inhaled. In acute asthma exacerbations, early use of systemic corticosteroids often aborts the exacerbation, decreases the need for hospitalization, prevents relapse, and speeds recovery. Oral and IV routes are equally effective.

Inhaled corticosteroids have no role in acute exacerbations but are indicated for long-term suppression, control, and reversal of inflammation and symptoms. They substantially reduce the need for maintenance oral corticosteroid therapy. Adverse local effects of inhaled corticosteroids include dysphonia and oral candidiasis, which can be prevented or minimized by having the patient use a spacer, gargle with water after corticosteroid inhalation, or both. Systemic effects are all dose related, can occur with oral or inhaled forms, and when due to inhaled forms, occur mainly with doses > 800 mcg/day. They include suppression of the adrenal-pituitary axis, osteoporosis, cataracts, skin atrophy, hyperphagia, and easy bruisability. Whether inhaled corticosteroids suppress growth in children is unclear. Most children treated with inhaled corticosteroids eventually reach their predicted adult height. Latent tuberculosis may be reactivated by systemic corticosteroid use.

Mast cell stabilizers inhibit histamine release from mast cells, reduce airway hyperresponsiveness, and block the early and late responses to allergens. They are given by inhalation prophylactically to patients with exercise-induced or allergen-induced asthma. They are ineffective once symptoms have occurred. They are the safest of all antiasthmatic drugs but the least effective.

eosinophilic granulomatosis with polyangiitis.

Methylxanthines relax bronchial smooth muscle (probably by inhibiting phosphodiesterase) and may improve myocardial and diaphragmatic contractility through unknown mechanisms. Methylxanthines appear to inhibit intracellular release of calcium, decrease microvascular leakage into the airway mucosa, and inhibit the late response to allergens. They decrease the infiltration of eosinophils into bronchial mucosa and of T cells into epithelium.

gastroesophageal reflux (by reducing lower esophageal sphincter pressure).

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Clinicians who give any of these immunomodulators should be prepared to identify and treat anaphylaxis or allergic hypersensitivity reactionsherpes zoster infection; therefore, zoster vaccination is recommend prior to initiation of therapy unless contraindicated.

Other drugs are used in asthma treatment uncommonly and in specific circumstances. Magnesium is often used in the emergency department, but it is not recommended in the management of chronic asthma.

Immunotherapy may be indicated when symptoms are triggered by allergy, as suggested by history and confirmed by allergy testing. Immunotherapy is generally more effective in children than adults. If symptoms are not significantly relieved after 24 months, then therapy is stopped. If symptoms are relieved, therapy should continue for ≥ 3 years, although the optimum duration is unknown.

1. 1. US Food and Drug Administration: FDA Drug Safety Communication: FDA review finds no significant increase in risk of serious asthma outcomes with long-acting beta agonists (LABAs) used in combination with inhaled corticosteroids (ICS).April 15, 2011. Updated December 20, 2017. Accessed January 21, 2022.