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

Hospital Universitari de Bellvitge170 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

170

Conditions

Intubated ICU Patients Ventilator Associated Pneumonia ( VAP)Immunoparalysis

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Incidence of ventilator-associated pneumonia (VAP)

Occurrence of ventilator-associated pneumonia in critically ill mechanically ventilated patients, defined according to standard clinical, radiological, and microbiological criteria.

Time frame: Up to 28 days after intubation

Secondary Outcomes

Incidence of ICU-acquired infections

Occurrence of secondary infections acquired during ICU stay, including device-related infections and other nosocomial infections diagnosed according to standard clinical, microbiological, and radiological criteria.

Time frame: Up to 28 days after intubation

Duration of invasive mechanical ventilation

Total number of days under invasive mechanical ventilation during ICU stay.

Time frame: Up to 28 Days after intubation

All-cause mortality at 28 days

Death from any cause within 28 days after ICU admission.

Time frame: 28 days after intubation

Evolution of Sequential Organ Failure Assessment (SOFA) score

Change in SOFA score over time during ICU stay as a measure of organ dysfunction trajectory.

Time frame: From ICU admission to day 15 or ICU discharge, whichever occurs first.

Prevalence of innate immune immunoparalysis at ICU admission

Proportion of patients presenting innate immune immunoparalysis at ICU admission, defined by reduced monocyte HLA-DR expression (\<5000 antibodies bound per cell \[AB/C\]) and/or decreased TNF-α production after ex vivo lipopolysaccharide (LPS) stimulation (\<200 pg/mL), based on previously reported thresholds.

Time frame: At ICU admission (baseline)

Temporal evolution of innate immune immunoparalysis

Changes over time in innate immune immunoparalysis assessed by serial measurements of monocyte HLA-DR expression and ex vivo LPS-stimulated TNF-α production, including intensity, duration, and trends.

Time frame: Baseline, 24 hours, day 3, and day 5 after intubation

Agreement between HLA-DR expression and LPS-stimulated TNF-α production

Concordance between monocyte HLA-DR expression and ex vivo LPS-stimulated TNF-α production as methods to assess innate immune immunoparalysis.

Time frame: From baseline to day 5 after intubation.

Identification of immunoparalysis thresholds associated with clinical outcomes

Determination of threshold values of monocyte HLA-DR expression and TNF-α production after LPS stimulation associated with increased risk of ventilator-associated pneumonia and other ICU-acquired infections.

Time frame: Up to 28 days after intubation.

Correlation between immunoparalysis and clinical outcomes

Correlation between the presence, duration, intensity, and trends of immunoparalysis and clinical outcomes, including ICU-acquired infections, duration of mechanical ventilation, vasopressor support, organ dysfunction (SOFA score), ICU and hospital length of stay, and survival status.

Time frame: From ICU admission to day 90, depending on the clinical outcome assessed

Effect of macrolide therapy on immunoparalysis and infection outcomes

Correlation between macrolide treatment (e.g., clarithromycin) and changes in immunoparalysis parameters, as well as its correlation with the incidence of ventilator-associated pneumonia and ICU-acquired infections.