A special problem caused by inhaled topical corticosteroids is the occurrence of oropharyngeal candidiasis. This is easily treated with topical clotrimazole, and the risk of this complication can be reduced by having patients gargle water and expectorate after each inhaled treatment. Ciclesonide, a prodrug activated by bronchial esterases, is comparably effective to other inhaled corticosteroids and is associated with less frequent candidiasis. Hoarseness can also result from a direct local effect of ICS on the vocal cords. Although a majority of the inhaled dose is deposited in the oropharynx and swallowed, inhaled corticosteroids are subject to first-pass metabolism in the liver and thus are remarkably free of other short-term complications in adults. Nonetheless, chronic use may increase the risks of osteoporosis and cataracts. In children, ICS therapy has been shown to slow the rate of growth by about 1 cm over the first year of treatment, but not the rate of growth thereafter, so that the effect on adult height is minimal.
Because of the efficacy and safety of inhaled corticosteroids, national and international guidelines for asthma management recommend their prescription for patients with persistent asthma who require more than occasional inhalations of a β agonist for relief of symptoms. This therapy is continued for 10–12 weeks and then withdrawn to determine whether more prolonged therapy is needed; inhaled corticosteroids are not curative. In most patients, the manifestations of asthma return within a few weeks after stopping therapy even if they have been taken in high doses for 2 or more years. A prospective, placebo-controlled study of the early, sustained use of inhaled corticosteroids in young children with asthma showed significantly greater improvement in asthma symptoms, pulmonary function, and frequency of asthma exacerbations over the 2 years of treatment, but no difference in overall asthma control 3 months after the end of the trial. inhaled corticosteroids are thus properly labeled as “controllers.” They are effective only so long as they are taken.
Another approach to reducing the risk of long-term, twice-daily use of ICS is to administer them only intermittently, when symptoms of asthma flare. Taking a single inhalation of an ICS with each inhalation of a short-acting β-agonist reliever (eg, an inhalation of beclomethasone for each inhalation of albuterol) or taking a 5to 10-day course of twice-daily high-dose budesonide or beclomethasone when asthma symptoms worsen has been found to be nearly as effective as regular daily therapy in adults and children with mild to moderate asthma, although these approaches to treatment are neither endorsed by guidelines for asthma management nor approved by the FDA.
Cromolyn sodium (disodium cromoglycate) and nedocromil sodium were once widely used for asthma management, especially in children, but have now been supplanted so completely by other therapies that they are mostly of historic interest as asthma treatments. These drugs are thought to act by inhibiting mast cell degranulation and, as such, have no direct bronchodilator action, but inhibit both antigenand exercise-induced bronchospasm in asthmatic patients.
When taken regularly (2–4 puffs 2–4 times daily), these agents modestly but significantly reduce symptomatic severity and the need for bronchodilator medications, particularly in young patients with allergic asthma. These drugs are poorly absorbed into the systemic circulation and have little toxicity, but are not as
FIGURE 20–7 Structures of leukotriene receptor antagonists potent or as predictably effective as ICS.
(montelukast, zafirlukast) and of the 5-lipoxygenase inhibitor