Isolated BAL Neutrophilia and Unimodal Airway Epithelial IL-13 Inducible Gene Signatures Characterize Children with Treatment-Resistant Asthma
Sunday, March 5, 2017: 2:45 PM
Rooms B303-B304 (Georgia World Congress Center, Building B)
Larry Borish, MD FAAAAI, , , , , , ,
Rationale: Assessment of lung fluid inflammatory markers and infectious species is indicated to inform treatment decisions in children with problematic asthma. The purpose of this study was to examine prevailing granulocyte patterns, potential pathogens, and bronchial epithelial IL-13-inducible gene signatures in 119 children with poor asthma control despite high-dose ICS treatment.  

Methods: Children underwent bronchoscopy with BAL for granulocyte counts, PCR for respiratory viruses, bacterial cultures, and bronchial brush (n=54) for epithelial IL13- inducible signature gene expression by qPCR. 

Results: Asthma severity spanned mild/moderate (34%), severe (41%), and very severe (25%). Isolated neutrophilia was the prevailing granulocyte pattern (43.7%), followed by pauci-granulocytic (35.3%), mixed granulocytic (17.6%), and isolated eosinophilia (3.4%). Children with BAL neutrophilia were younger, less allergen sensitized, but had an 8-fold greater detection of potential bacterial pathogens (40.0%) compared to other granulocyte patterns (p=0.0001). Enterovirus detection was common (26%) and evenly distributed among the four patterns. The IL13-inducible three gene mean signature was unimodal, did not have a clearTh2HIGH versus LOW cut point, and was highest in children with mixed granuloyctes (p=0.08). 

Conclusions: Isolated BAL neutrophilia is common in young children with poorly-controlled asthma, in an age group with less allergen sensitization but abundant potential bacterial and viral pathogens in the airspaces. Unlike studies of adults with milder asthma on low-dose ICS, we could not identify a bimodal pattern of Th2HIGH and LOW gene expression profiles, likely due to the suppressive effects of high-dose corticosteroid treatment in our sample.