Antiinflammatory therapy with glucocorticoids in intrinsic asthma

The pioneering study by Bordley et al. (John Hopkins Hosp. 1949) contains information on glucocorticoids in asthma that has stood the test of time: These drugs do not distinguish between intrinsic and extrinsic asthma. The beneficial effect can be seen in 4-48 h. The full effect is obtained in a week or longer. After stopping therapy in "cured" patients, symptoms may gradually return. Studies carried out by Swedish, English and German workers in the mid-1950s appear to be the first successful uses of topical glucocorticoids in asthma. As shown with beclomethasone dipropionate during the 1970s, and expanded during the 1980s with the more lung-selective drug, budesonide, inhaled glucocorticoids have a broad clinical efficacy in mild and severe asthma and are very safe to use. They improve baseline airway resistance and reduce "non-specific" hyperreactivity. They inhibit not only late phase responses but also immediate type reactions in the airways including exercise-induced asthma. It has been suggested that long-term treatment with glucocorticoids may have significant effects on the progression of the disease. Clinical efficacy, increased lung selectivity, and improved delivery (a breath-actuated multi-dose pure drug powder device will soon be available for inhalational glucocorticoid therapy) would speed up the current trend towards using glucocorticoids as primary and prophylactic treatment of asthma. Bordley et al. (1949) also gave factual hints about the mode of action of glucocorticoids in asthma: Sputum (eosinophilic) production ceased entirely; paleoedematous airway mucosa covered with thick purulent mucus turned into a pink normal mucosa with a clear mucus. Glucocorticoids have taught us about asthma and taken the attention away from smooth muscle and single inflammatory mediator or cell hypotheses to a focus on complex inflammatory mucosal/submucosal events involving many target cells. Of particular interest is the ability of glucocorticoids to reduce plasma exudation into airway wall and lumen. Exuded plasma is a multipotential pathogenetic factor in asthma and anti-plasma leakage actions may contribute significantly to the general clinical efficacy of glucocorticoids in this disease.