Characterization of Early Biological and Mechanical Profiles in Sepsis-Associated ARDS for Studying Compartmentalization (Serial Bronchoalveolar Lavage and Plasma Biomarkers) to Identify Inflammatory and Hybrid Subphenotypes
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 145
- 试验地点
- 2
- 主要终点
- Early lung injury trajectory within 96 hours of sepsis onset
研究概览
简要总结
Sepsis-associated acute respiratory distress syndrome (ARDS) remains a major cause of respiratory failure and mortality in critically ill patients. Although only a proportion of patients with sepsis develop ARDS, early identification of those at highest risk remains a major unmet clinical need. Current prediction relies largely on clinical deterioration and oxygenation impairment, which often occur when lung injury has already developed. Increasing evidence suggests that biological responses to sepsis are compartmentalized between the systemic circulation and the alveolar space, while early abnormalities in respiratory mechanics and ventilatory efficiency may provide complementary information on evolving lung injury. However, no prospective study has integrated serial systemic and alveolar biomarkers with bedside respiratory physiology during the earliest phase of sepsis-associated respiratory failure.
EARLY-SARDS is a prospective observational cohort study designed to characterize the early biological and physiological trajectories of invasively ventilated patients with sepsis or septic shock. Serial bronchoalveolar lavage (BAL) and plasma samples, together with standardized measurements of respiratory mechanics and gas exchange, will be collected during the first 96 hours after enrollment. The primary objective is to develop an integrated biological-physiological model capable of predicting ARDS development and subsequent peak ARDS severity. Secondary objectives include characterizing biological compartmentalization, identifying integrated biological-physiological subphenotypes, and evaluating their association with clinically relevant outcomes, including duration of mechanical ventilation, ventilator-free days, need for extracorporeal respiratory support, ICU length of stay, and mortality.
详细描述
Acute respiratory distress syndrome (ARDS) secondary to sepsis is a biologically heterogeneous syndrome that reflects multiple interacting mechanisms of lung injury rather than a single pathological process. Current clinical definitions rely on physiological manifestations of established lung injury and therefore provide limited insight into the underlying biological processes responsible for disease initiation and progression.
Experimental and translational studies indicate that the earliest phase of sepsis-associated lung injury is characterized by dynamic interactions between inflammatory activation, epithelial injury, endothelial dysfunction, disruption of the alveolar-capillary barrier, and alterations in pulmonary permeability. These processes evolve rapidly during the first days after sepsis onset and may precede the clinical diagnosis of ARDS by several hours or days. Longitudinal characterization is therefore essential to understand the temporal evolution of lung injury.
Because the primary site of injury is the alveolar compartment, circulating biomarkers incompletely reflect the biological events occurring within the lung. Inflammatory mediators, epithelial injury markers, and endothelial activation frequently demonstrate compartmentalization between bronchoalveolar lavage (BAL) fluid and plasma, suggesting that simultaneous assessment of both compartments may provide a more comprehensive characterization of early lung injury than either compartment alone.
Respiratory physiology represents a complementary dimension of ARDS pathophysiology. Parameters including respiratory system compliance, driving pressure, plateau pressure, ventilatory ratio, and gas exchange describe the functional consequences of biological injury and the mechanical environment to which the lung is exposed during invasive mechanical ventilation. Mechanical stress and biological injury are closely interconnected and likely contribute jointly to disease progression.
By combining repeated assessment of alveolar biology, systemic host response, and respiratory physiology during the earliest phase of sepsis-associated respiratory failure, this study is designed to characterize the temporal evolution of lung injury and provide an integrated description of the biological and physiological mechanisms underlying progression to ARDS.
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
- 否
入选标准
- •Age ≥18 years.
- •Sepsis or septic shock according to Sepsis-3 criteria.
- •Requirement for invasive mechanical ventilation within 72 hours of sepsis diagnosis.
- •Written informed consent provided by the participant or a legally authorized representative.
排除标准
- •Pregnancy.
- •Previous lung transplantation.
- •Contraindication to bronchoscopy or bronchoalveolar lavage (BAL).Inability to complete at least two BAL procedures during the 96-hour study period.
- •Expected death within 24 hours or limitation of life-sustaining treatment at enrollment.
- •Written informed consent not obtained.
研究组 & 干预措施
Sepsis or Septic shock requiring mechanical ventilation
Adult ICU patients with sepsis or septic shock requiring invasive mechanical ventilation within 72 hours from sepsis diagnosis will be consecutively enrolled and followed for 96 hours after sepsis diagnosis.
干预措施: Serial bronchoalveolar lavage and biological-physiological assessment (Diagnostic Test)
结局指标
主要结局
Early lung injury trajectory within 96 hours of sepsis onset
时间窗: Baseline to 96 hours
Early lung injury trajectory, assessed as an ordinal composite endpoint integrating: 1. occurrence of ARDS according to the Berlin Definition, 2. time from sepsis diagnosis to ARDS onset, 3. the highest Berlin ARDS severity stage (mild, moderate, or severe) reached during the 96-hour observation period. This endpoint will serve as the outcome for development and internal validation of an integrated biological-physiological prediction model combining alveolar and systemic biomarkers with respiratory physiological variables.
Early hybrid biological-mechanical subphenotypes
时间窗: From enrollment to 72 hours
Identification of early alveolar inflammatory subphenotypes, defined by trajectories of BAL biomarkers (IL-6, IL-8, IL-10, TNF-α, sRAGE, KL-6, SP-D, Ang-2, vWF, total protein, albumin) and Mechanical Profiles in Sepsis-Associated ARDS.
次要结局
- Alveolar-systemic biological compartmentalization(Baseline to 96 hours)
- Incremental predictive performance of integrated biological-physiological models(Baseline to 96 hours)
- Reproducibility and external validation of biological-physiological models(Once study is completed, avarage 2 years)