Mechanism of Macrolide Treatment in Patients with Severe Asthma---Role of Th17/IL-17 Neutrophilic Phenotype and Airway Biofilm

Severe asthma is a heterogeneous disease. Cytokine profiles have been useful in classifying severe asthma. The interleukin (IL)-4/IL-13 signaling pathway accounts for the subset of severe asthmatics with allergen-associated symptoms and high serum immunoglobulin E (IgE) levels. The IL-5/IL-33 signaling pathway is likely to play an important role in the disease pathogenesis of those who are resistant to high doses of inhaled corticosteroid but responsive to systemic corticosteroids and anti-IL5 therapy. The IL-17 signaling pathway is thought to contribute to 'neutrophilic asthma'. Mounting evidence supports a role for Th1 cytokines such as IL-18 and interferon (IFN)-γ in severe asthma pathogenesis. It has been well established that the eosinophils, mast cells, and Th2 cells mediate the pathologic features of asthma. However, some patients with severe asthma exhibit sputum neutrophilia without eosinophilia, suggesting the possible involvement of IL-17. Biofilm diseases that characteristically involve the respiratory system include cystic fibrosis (CF), diffuse panbronchiolitis (DPB), and bronchiectasia with Pseudomonas aeruginosa (P. aeruginosa) infection. Macrolides, such as clarithromycin and azithromycin, have been shown to have anti-inflammatory and/or immunomodulatory effects in addition to their antimicrobial properties. However, the mechanism of macrolides on severe asthma is still not well investigated. Whether macrolides could affect Th17/IL17 neutrophilic asthma or biofilm is still not well known. The aims of the 3-year project are: 1. To investigate whether macrolide therapy may decrease the amount of neutrophil in induced sputum and lamina propria from severe asthma. 2. To determine whether macrolide therapy may decrease the neutrophil-derived elastase and IL-17 in induced sputum and lamina propria from severe asthma. 3. To study whether patients with severe asthma with good response to macrolides are associated with increased numbers of neutrophils and higher levels of IL-17, IL-25 and elastase in induced sputum and within the lamina propria of airways. To investigate whether oral macrolides significantly reduced the number of bacteria in biofilm of patients with severe asthma.

Project ID:PC10208-0386
External Project ID:NSC102-2314-B182-036