Editors' ChoiceAsthma

Treating Asthma: Divide and Conquer

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Science Translational Medicine  22 Oct 2014:
Vol. 6, Issue 259, pp. 259ec181
DOI: 10.1126/scitranslmed.aaa0591

Asthma is a chronic lung disease characterized by inflamed and narrowed airways. Recently, asthma has been reported to actually represent a group of heterogenic disorders, which can be further subclassified on the basis of clinical, pathologic, and molecular features. Responsiveness to specific therapeutics could differ drastically among those different asthma subtypes. For instance, asthma patients with high levels of type 2 T helper cytokines (TH2-high asthma) respond to inhaled corticosteroid (ICS) treatment, but asthma patients with low levels of TH2 cytokines (TH2-low asthma) usually do not. Currently, the molecular mechanisms that differentiate the development of TH2-high and TH2-low asthma are largely unknown.

Mouse studies have indicated that epithelial cell-derived cytokines including interleukin-25 (IL-25), IL-33, and thymic stromal lymphopoietin (TSLP) are the leading factors that drive the development of asthma. Now, Cheng et al. have analyzed bronchoalveolar lavage, endobronchial biopsy, and airway brushing samples in a cohort of Chinese subjects including 21 healthy controls and 43 asthma patients. They found that epithelial cell-derived IL-25, rather than IL-33 or TSLP, was highly increased in a subset of asthma subjects compared with control subjects. Subsequent analysis on the clinical, pathological, and molecular features of this IL-25–high subset of patients revealed that they had greater airway hyperresponsiveness, elevated numbers of airway and blood eosinophils, higher levels of serum immunoglobulin E (IgE), increased subepithelial thickening, and higher expression of TH2 signature genes, which are the characteristics of TH2-high asthma. Furthermore, the authors found that this IL-25–high subgroup of patients showed improved lung function after ICS treatment compared with the IL-25–low subgroup of patients. Importantly, plasma IL-25 levels also correlated with airway eosinophilia and beneficial responses to ICS treatment, suggesting that IL-25 could be a useful blood marker defining TH2-high subset of asthma patients.

Although the data need to be replicated in other ethnic cohorts, this paper suggests that epithelial and plasma IL-25 levels could distinguish TH2-high and TH2-low asthma phenotypes and their differential responses to ICS treatment. Furthermore, this paper indicates that epithelial IL-25 expression is a key igniter of the type 2 inflammation in TH2-high asthma subjects, and targeting IL-25 and its downstream pathways may offer a “cure” for this subset of asthma.

D. Cheng et al., Epithelial interleukin-25 is a key mediator in Th2-high, corticosteroid-responsive asthma. Am. J. Respir. Crit. Care Med. 190, 639–648. (2014). [Abstract]

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