Hétérogénéité des pneumonies acquises à l’hôpital : nouveaux sous-phénotypes associés à la réponse clinique et une signature immuno-microbiologique

Hospital-acquired pneumonia (HAP) are one of the frequent causes of nosocomial infections and respiratory complications in intensive care units (ICU). HAP is associated with a prolonged mechanical ventilation, an attributable mortality of 13% and a long-term decrease of the quality of life of survivors. Despite a high adherence rate to expert guidelines and treatment optimisation, treatment failure rate is at 40%, suggesting an incomplete understanding of the disease. We first used an unsupervised approach on clinical data to identify two subphenotypes of HAP both robust and clinically relevant.Those subphenotypes have been validated on more than 3000 HAP patients and are associated with 28-day mortality and HAP treatment failure. Second, we used multiomic data integration from respiratory fluids of HAP patients to characterise immuno-microbial mechanisms of the two HAP subphenotypes. We showed that monocytes, macrophages, neutrophils and microbiota were interconnected in subphenotype-specific dynamics and we confirmed the hyperinflammatory state associated with the most unfavourable subphenotype, suggesting therapeutic targets to reduce the local inflammation. These results plead for a personalised medicine stratified on subphenotypes.