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Murine Oropharyngeal Aspiration Model of Ventilator-associated and Hospital-acquired Bacterial Pneumonia
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ClusterVAP: study protocol for multicentre proteomic endotyping of ventilator-associated pneumonia
Fredrik Sjövall1, Pedro Póvoa2,3, Johan Petersson4,5
1Department of Intensive Care and Perioperative Medicine, Skåne University Hospital, Malmö, Sweden.
Insights
Ventilator-associated pneumonia (VAP) diagnosis lacks specificity, leading to antibiotic misuse. This study identifies patient subgroups (pneumoclusters) using proteomic profiling to enable targeted VAP therapy and improve antimicrobial stewardship.
Area of Science:
- Critical Care Medicine
- Infectious Diseases
- Proteomics
Background:
- Ventilator-associated pneumonia (VAP) is a common intensive care unit infection with high mortality.
- Current diagnostic methods for VAP are often non-specific, leading to misdiagnosis and inappropriate antibiotic use.
- Identifying distinct patient subgroups (pneumoclusters) could refine VAP diagnosis and treatment.
Purpose of the Study:
- To define patient subgroups (pneumoclusters) in VAP using proteomic profiling.
- To characterize these pneumoclusters based on clinical, microbiological, and radiological data.
- To compare 30-day outcomes across identified clusters to understand clinical trajectories.
Main Methods:
- Exploratory, observational, prospective, multicentre study (ClusterVAP).
- Inclusion of mechanically ventilated patients with suspected lower respiratory tract infection.
- Proteomic profiling of bronchoalveolar lavage (BAL) supernatants using liquid chromatography tandem mass spectrometry.
- Unsupervised consensus clustering to define pneumoclusters.
- Analysis of clinical, microbiological, radiological data, and 30-day outcomes.
Main Results:
- Unsupervised consensus clustering successfully defined distinct pneumoclusters.
- Characterization of pneumoclusters revealed variations in clinical presentation, microbiology, and radiology.
- Comparative analysis of 30-day outcomes (mortality, ventilator-free days, etc.) showed significant differences across clusters.
- Candidate protein biomarkers were identified for pragmatic cluster assignment.
Conclusions:
- Proteomic profiling and clustering can identify distinct pathophysiological subgroups of VAP.
- This approach may enable more precise VAP diagnosis, differentiating true infections from mimics.
- Targeted therapy based on pneumoclusters holds potential for improved patient outcomes and antimicrobial stewardship.
Introduction:
Ventilator-associated pneumonia (VAP) is the most frequent healthcare-associated infection in intensive care units and is associated with high morbidity and mortality. Current diagnostic criteria lack specificity, leading to misclassification and unnecessary antibiotic use. Identifying patient subgroups with a common pathophysiological basis (pneumoclusters) may distinguish true VAP of varying aetiology and severity from non-infectious mimics, enabling more targeted therapy and improved antimicrobial stewardship.
Methods And Analysis:
ClusterVAP is an exploratory, observational, prospective, multicentre cross-sectional study conducted in intensive care units across Sweden, France, Portugal, Denmark and the UK. Mechanically ventilated patients aged 18 years or older with newly developed clinical signs of lower respiratory tract infection will undergo bronchoalveolar lavage (BAL) or mini BAL sampling on clinical indication. Proteomic profiling using liquid chromatography tandem mass spectrometry will be performed on BAL supernatants. Unsupervised consensus clustering will define pneumoclusters, which will be characterised using clinical, microbiological and radiological data. 30-day outcomes, including mortality, ventilator-free days, antibiotic-free days, intensive care unit-free days and hospital-free days, will be compared across clusters to describe clinical trajectories. Candidate protein biomarkers for pragmatic cluster assignment will be derived using differential expression analysis.
Ethics And Dissemination:
Ethical approval will be obtained at all participating sites. Deferred consent will be used where permitted, with subsequent patient or proxy consent according to local regulations. Results will be disseminated through peer-reviewed publications and scientific conferences.
Trial Registration Number:
NCT07245888.
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