Innate Immune Immunoparalysis and Ventilator-Associated Pneumonia in Critically Ill Elderly Patients

This prospective observational cohort study aims to evaluate the role of innate immune immunoparalysis in the development of ventilator-associated pneumonia (VAP) in critically ill mechanically ventilated patients. Immunoparalysis will be assessed through monocyte HLA-DR expression and ex vivo lipopolysaccharide (LPS)-stimulated TNF-α production. The study will include three cohorts: elderly patients (≥65 years), younger adults (\<65 years), and healthy controls. The primary objective is to determine whether the presence, duration, intensity, and trend of immunoparalysis are associated with the incidence of VAP and other ICU-acquired infections. Secondary objectives include characterization of immunoparalysis dynamics, comparison of measurement methods, and evaluation of clinical outcomes.

Inclusion Criteria: * ≥18 years * Mechanical ventilation expected \>48h * Intubation between 24h pre- and 48h post- ICU admission * Informed consent Exclusion Criteria: * Known severe immunosuppression, including primary immunodeficiency disorders, advanced HIV infection (AIDS), active hematological malignancy under treatment, recent chemotherapy or immunosuppressive therapy * High dose steroids at immunosuppressive doses * Active autoimmune disease * Pregnancy * End-of-life situation