Abstract
Rationale: Severe adult-onset asthma is clinically identified as a distinct phenotype and associated with absence of atopy and eosinophilic airway inflammation [Amelink et al JACI 2013]. The aim of this study was to investigate airway transcriptomic profiles associated with adult-onset severe asthma.
Methods: Microarray analysis (Affymetrix HG-U133+PM) was performed on RNA from endobronchial biopsies (52) and brushings (65), nasal brushings (41) and sputum (83) in a cross-sectional design. Enrichment of 105 inflammation and leukocyte lineage gene signatures was evaluated by Gene Set Variation Analysis. Associations with adult-onset asthma (first diagnosis of asthma or onset of symptoms at age ≥18) was tested in General Linear Models adjusted for systemic steroid use and smoking.
Results: Significantly enriched signatures (p<0.05, enrichment score ±>0.2) were found in bronchial brushings, sputum and nasal brushings. Adult-onset patients expressed Type2 and mast cell signatures in bronchial brushings and sputum and an eosinophil signature in bronchial brushings (Table 1).
Conclusion: This study shows selective enrichment of Type2, mast cell, and eosinophil signatures in adult-onset severe asthma, which strengthens the concept of this being a distinct asthma phenotype. These transcriptomic profiles provide a first step towards elucidating the underlying mechanisms of this phenotype.
- Copyright ©ERS 2015