Innate Immune Immunoparalysis and Ventilator-Associated Pneumonia in Critically Ill Elderly Patients (IMP-VM)

Intensity and Duration of Innate Immune System Immunoparalysis in the Pathophysiology of Ventilator-Associated Pneumonia in Mechanically Ventilated 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.

Study Overview

• Status: Recruiting
• Conditions: Intubated ICU Patients; Ventilator Associated Pneumonia ( VAP); Immunoparalysis

• Study Type: Observational
• Enrollment (Estimated): 170

Contacts and Locations

Study Locations

• Spain
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Recruiting
      • Servei de medicina intensiva, Hospital Universitari de Bellvitge
      • Contact: Joan Sabater Riera, MD, PhD; Phone Number: +34 932607646; Email: jsabater@bellvitgehospital.cat
      • Contact: Arnau Ulsamer, PhD; Phone Number: 3068 +34 936073800; Email: aulsamer@idibell.cat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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.

Collaborators and Investigators

• Sponsor: Hospital Universitari de Bellvitge

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): May 28, 2028
• Study Completion (Estimated): July 31, 2028

Study Registration Dates

• First Submitted: April 19, 2026
• First Submitted That Met QC Criteria: April 19, 2026
• First Posted (Actual): April 24, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 17, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: invasive mechanical ventilation; innate immunity; HLA-DR; ICU-acquired infections; LPS stimulation
• Additional Relevant MeSH Terms: Healthcare-Associated Pneumonia; Pathologic Processes; Disease Attributes; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Cross Infection; Iatrogenic Disease; Pathological Conditions, Signs and Symptoms; Pneumonia, Ventilator-Associated
• Other Study ID Numbers: IMP-VM

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No