Pneumonia Pathogenesis, biomarkers and clinical implications

Pneumonia, an acute lower respiratory tract infection, has high morbidity and mortality rates, with progression to sepsis posing a life-threatening challenge. This thesis explores the pathogenesis, host immune response, and clinical management of pneumonia to advance individualized treatment for severe pneumonia and sepsis.
Part I focuses on the pathogenesis of pneumonia and the host immune response. Biomarkers like ferritin show promise for diagnostic and therapeutic applications in specific pneumonia subgroups. A study across 30 European Intensive Care Units (ICUs) linked ICU-acquired pneumonia to increased inflammation and disrupted endothelial barriers, both at enrollment and along the path to diagnosis.
Part II investigates the gut microbiome’s role in pneumonia and sepsis. While antibiotics are essential in treatment, they can disrupt the microbiome, with long-term consequences for immune function. A proof-of-concept trial showed short-term antibiotic-induced microbiome disruption does not influence pulmonary inflammation in allergic asthma patients.
Part III addresses diagnostic challenges in the emergency department. The OPTIMACT trial found ultra-low-dose chest CT scans yield similar outcomes to conventional X-rays for patients suspected of community-acquired pneumonia, suggesting limited routine use but potential value in complex cases.
The thesis underscores the potential of precision medicine, advocating for biomarker-driven stratification and multi-omics approaches for tailoring treatments. Standardizing biomarker assays and developing real-time decision-support tools are critical for integrating these advancements into clinical care, aiming to improve outcomes for critically ill patients with pneumonia and sepsis.