Page 37 - Comprehensive treatment of patients with glucocorticoid-dependent severe asthma

Pharmacological treatment options for severe refractory asthma
After separating all true severe asthma by revisiting the diagnosis, ongoing exposures and treatment adherence [3], optimization of therapy is the major objective. There are rapid developments in the pharmacological as well as non-pharmacological treatment of severe asthma.
High or ultra high doses of inhaled corticosteroids?
In severe asthma, doses of inhaled corticosteroids higher than that recommended in international guidelines (> 2000 mcg of fluticasone equivalent) are sometimes prescribed but there are many reasons not to do so. Firstly, there is no evidence that such high doses would give better control of asthma, improve lung function or asthma related quality of life [59;60]. More importantly, there are strong data indicating that the incidence of local adverse effects increases with increasing doses [59;61] and cause adrenal suppression [62-66]. High doses of inhaled corticosteroids are associated with substantial systemic bioavailability leading to adverse effects comparable to those of oral corticosteroids. A meta-analysis of 13 studies evaluating dose-related adrenal suppression showed that oral prednisolone and inhaled fluticasone were systematically equivalent on a 10:1 milligram base [62]. Therefore, the prescription of ultra high doses of inhaled corticosteroids should not be encouraged.
Short acting beta-2-agonists
Short-acting beta-2-agonists form a fundamental part of asthma treatment. Nevertheless, excessive doses of these short acting bronchodilators may be associated with unfavorable asthma outcomes [67;68], including higher asthma morbidity and mortality [69;70]. Regular use of short acting beta-2-agonists has been shown to lead to partial loss of effectiveness [71] and increases in airway responsiveness [72], while sudden cessation of regular beta-2-agonists may lead to rebound bronchoconstriction, and thereby pharmacological dependence. The basis for the unfavourable effects of short acting beta-2- agonists is still unclear, but could be related to a pharmacogenetic-related adverse effect [73;74]. Fortunately, careful gradual reduction of beta-2-agonist overuse can result in substantial improvements in asthma control, as was
Current treatment of severe asthma
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