PILOT STUDY OF INFLAMMATORY BIOMARKERS IN MATCHED INDUCED SPUTUM AND BRONCHOALVEOLAR LAVAGE FROM 2-YEAR-OLDS 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: Eight mediators were correlated between IS and BAL. Nine mediators showed similar levels in IS and BAL, including CXCL1, CXCL8, IL-1alpha, IL-1RA, IL-6, CCL2, CXCL10, M-CSF and VEGF-A. Four mediators were higher in IS than in both BAL fractions, including CXCL5, IL-1beta, CXCL11 and TNFSF10. 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.

Conclusions: IS collected from young children with CF yields molecular and cellular biomarkers of early airway inflammation and structural lung damage.