Late Breaking Abstract - Proteomic changes in respiratory tract lining fluid associated with smoking

Abstract

Smoking is the main risk factor for chronic obstructive pulmonary disease (COPD). The aim of this study was to identify dysregulation of specific proteins and pathways associated with smoking in samples from small airways obtained non-invasively with PExA method. 21 healthy controls, 48 ex-smokers and 38 current smokers were examined with the PExA method. 120 ng of samples were collected from individual subjects and analysed with the SOMAscan proteomics platform (SomaLogic Inc). Statistical analyses were performed using Qlucore Omics Explorer and pathway enrichment analysis was performed using the tool Gorilla. 203 proteins were detected in at least 50% of the total set of 107 samples. Smoking exerted a significant impact on the composition of respiratory tract lining fluid (RTLF), with 112 proteins altered due to smoking (p < 0.05, pFDR < 0.089). One of the proteins whose abundance was significantly lower in current smokers compared to ex- and never-smokers was sRAGE (soluble receptor for advanced glycation end products). Gene set enrichment analysis (GSEA) showed that proteins altered by smoking were mainly associated with the vesicle-mediated transport pathway, the protein activation cascade pathway with emphasis on complement activation, and enriched in extracellular exosomes. Our data show the PExA sampling is an efficient tool for studying surfactant changes in small airways, especially given its non-invasive nature. We observed changes in sRAGE in RTLF in connection with smoking, a protein that has previously been proposed as a potential biomarker for COPD. Furthermore, we show a significant effect of smoking on proteins associated with exosomes as well as complement activation.