More options for managing severe asthma in adults

Abstract

reduction in exacerbation frequency is not trivial, although it is lower than that anticipated in a population of patients with type 2-high allergic asthma when compared with the effects seen with biologics. In less selected severe asthma populations, such improvements in exacerbation frequency and FEV 1 have formed the basis for the registration of new, long-acting inhaled drugs for asthma. 7,8 Similarly, in chronic obstructive pulmonary disease, such reductions of 15-25% in exacerbation frequency are deemed worthwhile, and led to guideline recommendations for these drugs.Why does the overall effect seem to be as good in noneosinophilic populations as in those with eosinophilia (>250 cells per μL)? Prostaglandin D 2 has broader chemoattractant activity, activating human Th2 cells and macrophages to secrete neutrophil chemokines, and contributes to neutrophilic inflammation in animal models. 9,10 Not all cases of severe asthma or severe exacerbations are eosinophilic, as there are probably multiple pathways towards eosinophilia, and it is conceivable that the activity in the neutrophil pathway at least partially explains the 22% overall exacerbation rate reduction observed in the LUSTER trials. Unfortunately, sputum cell eosinophils and neutrophils were not measured at baseline or during exacerbations in the LUSTER trials. Such information could have proven useful to understanding the results observed.Perhaps, we should not yet close the book on prostaglandin D 2 antagonism, but instead consider adding a new chapter.HAMK reports grants and fees for consultancy or advisory board participation from Novartis, as well as grants and fees for consultancy or advisory board participation from GlaxoSmithKline and Boehringer Ingelheim, and a grant from Chiesi, all outside of the submitted work and all paid to his institution. RG reports grants from Boehringer Ingelheim, Aquilo, Chiesi, and Novartis, outside of the submitted work.

Triple therapy in uncontrolled asthma: a network meta-analysis of phase III studies

“…Adding tiotropium bromide (TIO) to dual inhaled corticosteroid (ICS)/long-acting β 2 -adrenoceptor agonist (LABA) fixed-dose combination (FDC) is currently recommended to treat asthmatic patients suffering from the most severe forms of disease [1]. Nevertheless, conflicting data are currently available concerning the real efficacy of triple ICS/LABA/long-acting muscarinic receptor antagonist (LAMA) FDCs in asthma, especially with respect to their effect against the risk of exacerbation in symptomatic patients with uncontrolled asthma [2][3][4].…”

Disease-modifying anti-asthmatic drugs

“…Even the choice of inhaled therapies has become more and more individualised, given the large spectrum of inhaled corticosteroid molecules, inhaled corticosteroid doses, inhaled corticosteroid fixed combination inhalers, applica tion schemes (maintenance therapy or inhalation on an asneeded basis) and devices. [27][28][29] Thus, today there is an armamentarium of effective, safe, phenotype-specific immunomodulatory drugs aimed at preventing symptoms and exacerbations by targeting the underlying inflammatory cascade, with the advantage of improving control of co-existing co-morbidities (figure). Notably, these drugs do not only successfully modulate inflammation, 19 but can improve the function of structural cells, such as epithelial cells, smooth muscle cells, fibroblasts, and nerves, and consequently reduce airway remodelling.…”