Page 40 - Comprehensive treatment of patients with glucocorticoid-dependent severe asthma

Chapter 2
Early onset severe atopic asthma
In this phenotype of severe asthma, immune globulin E (IgE) plays an important role. The relevance of IgE in severe atopic asthma has been recognized for many decades in epidemiologic studies [95-97]. High levels of IgE increase the surface expression of the high-affinity IgE receptor on mast cells and basophils, and recently it has been shown that airway tissue from patients who died in an asthmatic attack shows a high expression of this receptor [98], indicating that patients with severe atopic asthma have an increased capacity to mount IgE- mediated reactions and exacerbations.
Monoclonal antibodies against IgE are the optimal targeted treatment for patients with this phenotype of severe asthma. Many studies have confirmed the beneficial effects of anti-IgE therapy in patients with severe allergic asthma despite treatment with inhaled corticosteroids and rescue medication [99]. Omalizumab reduces the frequency and occurrence of exacerbations [100;101] and improves symptom control while allowing for a reduction in the use of corticosteroids and beta-2-agonists [100-102].
Patients with the early onset severe allergic asthma phenotype are often sensitized to fungi [27;103-105], which has been shown to be associated with reduced lung function, increased sputum neutrophils and bronchiectasis [106]. Antifungal therapy has shown some beneficial effects in patients who are sensitized to fungi of the genus Trichophyton or Aspergillus. In a small pilot study Ward and colleagues showed a beneficial effect of 5 months treatment with fluconazole in patients sensitized to Trichophyton [107], whereas Denning and colleagues showed an improvement in asthma related quality of life after 8 months treatment with itraconazole in a randomized controlled trial [108]. They also demonstrated a fall in IgE levels and a modest improvement in rhinitis and morning peak flow, but no improvement in FEV1 [108]. More studies are necessary to address the questions of patient selection, optimum duration of therapy and prediction and management of azole-corticosteroid drug interactions before recommending this treatment to all sensitized patients with colonized airways [109].
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