Biomarker analysis of bronchoalveolar lavage (BAL), bronchoabsorption (BA) and serum in Idiopathic Pulmonary Fibrosis (IPF) and healthy volunteers (HV)

Background: BA enables sampling of bronchial epithelial lining fluid through application of a synthetic absorptive matrix to the bronchial wall via bronchoscope. Eluted fluid can be assayed for potential biomarkers. Aims: To determine comparative biomarker expression in BAL, BA and serum in subjects with IPF and HV. Materials and methods: BAL, BA and serum samples from IPF (n=6) and HV (n=6) were assayed for 61 analytes of interest by multiplex Luminex assay. These analytes were derived from a proteomic array study (for 167 proteins) with pooled BA samples from the same cohort. Analytes expression in the three compartments was compared (IPF vs HV) where p<0.05 was defined as significance without adjustment for multiple comparisons. Results: In IPF subjects, most analytes were above the lower limit of detection in BAL (59/61), BA (55/61) and serum (59/61) compartments respectively. In BAL compartment chitinase-3 like-protein-1 (CHI3L1) and TIMP-1 were significantly differentially expressed in IPF vs HV. In BA compartment, 6 analytes were significantly differentially expressed in IPF vs HV: SpD, CCL18, angiopoietin-2, CD23, leptin and amyloid precursor protein (APP). In serum, 6 analytes were significantly differentially expressed in IPF vs HV: CHI3L1, SpD, galectin-3, osteopontin, periostin and midkine. Conclusion: BA can be used to detect proteins of interest that are differentially expressed in IPF vs HV. BAL, BA and serum compartments differ in the expression of selected analytes that are relevant to IPF. Assaying BA-expressed proteins may aid exploratory analysis in early phase clinical trials in IPF. The clinical utility is still unknown.