Immunoparalysis, Intubated ICU Patients, Ventilator Associated Pneumonia ( VAP)
Conditions
Keywords
invasive mechanical ventilation, LPS stimulation, HLA-DR, innate immunity, ICU-acquired infections
Brief summary
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.
Interventions
None listed
Sponsors
Hospital Universitari de Bellvitge
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of ventilator-associated pneumonia (VAP) | Up to 28 days after intubation | Occurrence of ventilator-associated pneumonia in critically ill mechanically ventilated patients, defined according to standard clinical, radiological, and microbiological criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of ICU-acquired infections | Up to 28 days after intubation | 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. |
| Duration of invasive mechanical ventilation | Up to 28 Days after intubation | Total number of days under invasive mechanical ventilation during ICU stay. |
| All-cause mortality at 28 days | 28 days after intubation | Death from any cause within 28 days after ICU admission. |
| Evolution of Sequential Organ Failure Assessment (SOFA) score | From ICU admission to day 15 or ICU discharge, whichever occurs first. | Change in SOFA score over time during ICU stay as a measure of organ dysfunction trajectory. |
| Prevalence of innate immune immunoparalysis at ICU admission | At ICU admission (baseline) | 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. |
| Temporal evolution of innate immune immunoparalysis | Baseline, 24 hours, day 3, and day 5 after intubation | 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. |
| Agreement between HLA-DR expression and LPS-stimulated TNF-α production | From baseline to day 5 after intubation. | Concordance between monocyte HLA-DR expression and ex vivo LPS-stimulated TNF-α production as methods to assess innate immune immunoparalysis. |
| Identification of immunoparalysis thresholds associated with clinical outcomes | Up to 28 days after intubation. | 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. |
| Correlation between immunoparalysis and clinical outcomes | From ICU admission to day 90, depending on the clinical outcome assessed | 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. |
| Effect of macrolide therapy on immunoparalysis and infection outcomes | Up to 28 days after intubation. | 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. |
Countries
Spain
Outcome results
None listed