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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Elderly Mechanically Ventilated Patients (≥65 years) | Critically ill patients aged 65 years or older requiring invasive mechanical ventilation for more than 48 hours. This is the primary study cohort in which innate immune immunoparalysis will be assessed and its association with ventilator-associated pneumonia will be analyzed. | ||
| Adult Mechanically Ventilated Patients (<65 years) | Critically ill patients aged 18 to 64 years requiring invasive mechanical ventilation for more than 48 hours, included as a comparison cohort to evaluate age-related differences in immunoparalysis. | ||
| Healthy Non-Intubated Controls | Healthy adult volunteers without acute illness and not requiring mechanical ventilation. This group, assessed at a single time point, will serve as a reference population for baseline immunological parameters. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 28 days after intubation |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 28 days after intubation |
| Duration of invasive mechanical ventilation |
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Inclusion Criteria:
Exclusion Criteria:
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Critically ill adult patients requiring invasive mechanical ventilation for more than 48 hours and admitted to the Intensive Care Unit will be consecutively screened for inclusion. The study will include two patient cohorts (≥65 years and 18-64 years), as well as a cohort of healthy adult volunteers serving as controls.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Servei de medicina intensiva, Hospital Universitari de Bellvitge | Recruiting | L'Hospitalet de Llobregat | Barcelona | 08907 | Spain |
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| ID | Term |
|---|---|
| D053717 | Pneumonia, Ventilator-Associated |
| ID | Term |
|---|---|
| D000077299 | Healthcare-Associated Pneumonia |
| D003428 | Cross Infection |
| D007239 | Infections |
| D011014 | Pneumonia |
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Blood samples (plasma) will be stored for the assessment of immunological parameters. Although plasma may contain cell-free DNA (cfDNA) and mitochondrial DNA (mtDNA), no genetic analyses are planned in this study.
Total number of days under invasive mechanical ventilation during ICU stay. |
| Up to 28 Days after intubation |
| All-cause mortality at 28 days | Death from any cause within 28 days after ICU admission. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | Up to 28 days after intubation. |
| D012141 |
| Respiratory Tract Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D007049 | Iatrogenic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |