Intensity and Duration of Innate Immune System Immunoparalysis in the Pathophysiology of Ventilator-Associated Pneumonia in Mechanically Ventilated Elderly Patients
概览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- Hospital Universitari de Bellvitge
- 入组人数
- 170
- 试验地点
- 1
- 主要终点
- Incidence of ventilator-associated pneumonia (VAP)
概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •≥18 years
- •Mechanical ventilation expected \>48h
- •Intubation between 24h pre- and 48h post- ICU admission
- •Informed consent
排除标准
- •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
研究组 & 干预措施
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.
结局指标
主要结局
Incidence of ventilator-associated pneumonia (VAP)
时间窗: 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.
次要结局
- Incidence of ICU-acquired infections(Up to 28 days after intubation)
- Duration of invasive mechanical ventilation(Up to 28 Days after intubation)
- All-cause mortality at 28 days(28 days after intubation)
- Evolution of Sequential Organ Failure Assessment (SOFA) score(From ICU admission to day 15 or ICU discharge, whichever occurs first.)
- Prevalence of innate immune immunoparalysis at ICU admission(At ICU admission (baseline))
- Temporal evolution of innate immune immunoparalysis(Baseline, 24 hours, day 3, and day 5 after intubation)
- Agreement between HLA-DR expression and LPS-stimulated TNF-α production(From baseline to day 5 after intubation.)
- Identification of immunoparalysis thresholds associated with clinical outcomes(Up to 28 days after intubation.)
- Association between immunoparalysis and clinical outcomes(From ICU admission to day 90, depending on the clinical outcome assessed)
- Effect of macrolide therapy on immunoparalysis and infection outcomes(Up to 28 days after intubation.)
研究者
Joan Sabater-Riera
MD, PhD
Hospital Universitari de Bellvitge