INFLAMMATORY BIOMARKERS IN INDUCED SPUTUM FROM YOUNG CHILDREN WITH CYSTIC FIBROSIS

Background: In adults with cystic fibrosis (CF), induced sputum (IS) is a minimally invasive alternative to bronchoalveolar lavage (BAL) to monitor airway inflammation. Here, we investigated whether IS could yield biomarkers of early disease in young children with CF. Methods: We collected IS, BAL (right middle lobe and lingula) and blood, and performed chest computed tomography (CT) scans from 2-year-olds with CF (N=11) within a single visit. Molecular biomarkers included 20 immune mediators and soluble neutrophil elastase (NE). Cellular biomarkers consisted in frequency and phenotype (including surface NE) of T cells, monocytes / macrophages and neutrophils. Results: Six mediators were correlated between IS and BAL. Eight mediators showed similar levels in IS and BAL, including GRO-alpha, IL-1alpha, IL-6, IL-8, IP-10, M-CSF and VEGF. Four mediators were higher in IS than in both BAL fractions, including ENA-78, IL-1beta, I-TAC and TRAIL. IL-10 and IFN-gamma were present in IS samples but largely undetectable in BAL. At the cellular level, T-cell frequency was lower in IS than in BAL. Monocytes / macrophages were dominant in IS and BAL with similar frequencies but differing expression of CD16 (lower in IS), CD115 and surface-associated NE (higher in IS). Meanwhile, soluble NE had lower activity in IS than in BAL. Neutrophil frequency and phenotype did not differ between IS and BAL. Importantly however, neutrophil frequency in IS correlated measures of lung damage by chest CT. Conclusions: IS collected from young children with CF yields molecular and cellular biomarkers of early airway inflammation and structural lung damage.