Segmental lipopolysaccharide (LPS) challenge is a well-established method to induce airway inflammation in human lungs. Bronchoalveolar lavage (BAL) is typically used to capture molecular and cellular changes, allowing investigation of pulmonary inflammation and assessing drug efficacy. This study aimed to describe the proteomic profile of human BAL in the segmental LPS challenge model. Pre-challenge BAL was collected from ten healthy non-smoking participants, followed by segmental instillation of LPS (40 EU/kg) and saline in the contralateral lung as control. After 24 h, BAL was sampled from the challenged lung segments. Using the SomaScan platform, 1,500 proteins were analysed. As expected, no significant differences were found between pre-challenge and saline-challenged BAL. After LPS compared to saline challenge, 599 proteins such as IL-6, IL-8, MPO, MMP9, CRP, VWF, G-CSF and Eotaxin, were significantly upregulated and 4 proteins were downregulated in BAL. The most significant biological processes associated with upregulated proteins were “immune system process”, “response to external stimulus” and “response to chemical”. As expected, the LPS challenge triggered a strong pro-inflammatory response including proteome changes seen in acute exacerbations (AEs). Overall, this study provides a comprehensive analysis of the proteomic profile in BAL following LPS challenge and its similarities with AEs, contributing to a deeper understanding of this model. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-39528-x.
