Non-Invasive Distal Airway Proteomics by Particles in Exhaled Air (PExA) Sampling Demonstrates Shared Proteomic Features with Matched Bronchoalveolar Lavage

Repeated molecular sampling of the distal airways is constrained by the invasive nature of bronchoalveolar lavage (BAL), limiting its use in healthy control populations, longitudinal studies, clinical trials and occupational screening. Particles in exhaled air (PExA) sampling offers a non-invasive approach to distal-airway sampling, although whether it captures the same proteins and relative protein abundance as BAL has not been established. We performed the first proof-of-principle high-dimensional proteomic comparison of matched BAL and PExA samples collected from three individuals with silicosis using the SomaScan 11K platform. Within individuals, PExA and BAL shared a substantial subset of detectable proteins and showed similar cross-protein signal patterns, with Pearson correlation coefficients ranging from 0.48 to 0.71. Analytes recurrently detected across all three PExA samples were strongly enriched among those consistently detected in BAL and included pulmonary surfactant proteins and mediators associated with epithelial injury, alveolar macrophage function, inflammation and fibrosis. The PExA findings also showed substantial overlap with an independent published PExA-only proteomic dataset. These proof-of-principle findings show that non-invasive PExA sampling can capture a biologically meaningful subset of the matched BAL proteome. PExA may therefore offer a practical approach for repeated molecular profiling of the distal airways and warrants further evaluation for respiratory biomarker discovery and disease monitoring.