ClusterVAP: Multicentre Proteomic Endotyping of Ventilator-associated Pneumonia

ClusterVAP is an exploratory, observational, prospective, multicentre cross-sectional study designed to identify biologically and clinically distinct subgroups ("pneumoclusters") among patients with suspected ventilator-associated pneumonia (VAP). The study will enroll approximately 400 adult patients admitted to intensive care units in Sweden, France, Portugal, Denmark, and the United Kingdom who are receiving mechanical ventilation and undergo bronchoalveolar lavage (BAL) or mini-BAL for clinical reasons. Residual BAL supernatant will be processed for proteomic analysis using liquid chromatography tandem mass spectrometry (LC-MS/MS). Unsupervised consensus clustering will be applied to proteomic data, alone and in combination with clinical and microbiological variables, to define pneumoclusters. These clusters will be characterized by clinical features, microbiology, and radiology, and compared for 30-day outcomes including mortality, ventilator-free days, antibiotic-free days, ICU-free days, and hospital-free days. Differential protein abundance analysis will be used to identify candidate biomarkers for pragmatic cluster assignment. Data will be collected in electronic case report forms hosted in REDCap, with built-in quality checks. All data will be pseudonymized, and biological samples will be stored under controlled conditions for up to ten years for confirmatory analyses. No experimental interventions are administered; all patients receive standard care. The study has been approved by the Swedish Ethical Review Authority (Dnr 2025-04564-01) and equivalent bodies in participating countries. Results will be disseminated through peer-reviewed publications and scientific conferences, with statistical code shared for transparency.