LAUSR

RATIONALE Biomarker signatures are needed in children with interstitial and diffuse lung disease (chILD) to improve diagnostic approaches, increase our understanding of disease pathogenesis, monitor disease progression, and develop new treatment strategies. Proteomic technology using SOMAmer® (Slow Off-rate Modified Aptamer) nucleic acid-based protein binding reagents allow for biomarker discovery. OBJECTIVES We hypothesized that proteins and protein pathways in bronchoalveolar lavage fluid (BALF) would distinguish children with neuroendocrine cell hyperplasia of infancy (NEHI), surfactant dysfunction mutations, other chILD diagnoses, and controls. METHODS BALF was collected for clinical indications and banked in patients with chILD and disease controls using standardized protocols over 10 years. BALF supernatant was analyzed using an aptamer assay to measure 1129 protein levels. Protein levels were compared between groups using an analysis of variance and adjusted for multiple comparisons using false discovery rate. Proteins were classified into pathways. Hierarchical clustering was used to define endotypes in the group of children with NEHI. RESULTS After correcting for multiple testing, children with NEHI (n=22) had 202 aptamers that were significantly different (p<0.05) in BALF compared to controls (n=9). Children with surfactant mutation (n=8) had 51 aptamers significantly different (p<0.05) in BALF compared to controls (n=9). Proteins associated with pulmonary fibrosis and inflammation were associated with the surfactant dysfunction group, but not in the NEHI group. Using hierarchical clustering analysis, two distinct NEHI endotypes were identified. CONCLUSIONS Distinct proteins and protein pathways can be determined from BALF of children with chILD, and these hold promise to further our understanding of chILD.