Page 39 - Comprehensive treatment of patients with glucocorticoid-dependent severe asthma

long-acting beta-2-agonists [92]. Whether anticholinergic agents could be as effective in severe asthma as in COPD, especially in the subgroup with fixed airflow limitation, has still to be investigated.
Targeted, phenotype-driven treatment
Apart from specific considerations regarding standard inhaled medications, there are exciting new possibilities for a more targeted, phenotype-driven approach. Severe refractory asthma is a heterogeneous condition, and over the last few years several clinical phenotypes have been defined by the use of unsupervised cluster analysis [93;94]. These phenotypes appear to have different clinical, physiological and inflammatory markers of severity, which may be used to target treatment.
The severe asthma research program (SARP) investigators [93] defined 5 phenotypes of asthma, of which 3 with severe asthma. One cluster of severe asthma constituted mainly of patients with early onset severe allergic asthma with very low FEV1, a second cluster of patients with late onset non-atopic steroid dependent asthma with fixed airways obstruction and a third cluster of mainly older, obese women with late onset asthma and reduced lung function.
Haldar and colleagues [94] used sputum eosinophil data in their model, which led to slightly different clusters. Also in their analysis there was a cluster of patients with early onset severe atopic asthma, a second cluster of mainly male patients with late onset asthma, characterized by severe persistent eosinophilic airway inflammation and a cluster of obese women with late onset asthma, who did not show eosinophilia in sputum.
Although these studies were performed in different settings and used different dimensions to define the phenotypes, it is interesting to notice that the 3 subtypes of severe asthma in each study have many characteristics in common. In the following paragraphs we will discuss targeted treatment approaches that could be applied to each of these 3 adult phenotypes of severe, refractory asthma.
Current treatment of severe asthma
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