Severe asthma: novel advances in the pathogenesis and therapy

Severe asthma: novel advances in the pathogenesis and therapy 247Whether treatment of comorbidities modulates asthma severity directly or indirectly, through improving asthma control, remains controversial.Intriguingly, recent evidence has suggested that in obese asthmatics with severe disease, there is increased eosinophilic infiltration of the airway wall, perhaps suggesting, in this example, a direct effect upon the underlying pathogenesis. 2ess controversial is the increasing recognition that asthma, particularly severe asthma, is a complex heterogeneous condition encompassing several underlying pathologies that develop as a consequence of a variety of gene-environment interactions that give rise to a clinical phenotype.This review will first consider our current understanding of the pathogenesis of severe asthma across the temporal and spatial scales of the disease from genes to cells, cells to tissue, and tissue to organ.Second, we shall describe how current therapies affect different aspects or domains of the disease.Finally, we shall describe how current and future treatments are changing to go beyond target specificity to also become phenotype-and outcome -specific as we move towards stratified medicine.