Lung and Systemic Inflammation in the Critically Ill Patient

Study Overview
=================
Brief Summary
-----------------
Acute respiratory distress syndrome (ARDS) is a devastating form of acute lung inflammation, that may be caused by a variety of insults with pulmonary and systemic infectious disease being the most common predisposing factor. Sepsis, on the other hand, represents the systemic inflammatory response to an invading pathogen, which may inflict damage upon the host through organ dysfunction. ARDS and sepsis are heterogenous clinical conditions that have a high mortality, and both diseases involve a complex interplay of different inflammatory mediators and cell types. It has been suggested that locally released inflammatory mediators pass from the lungs into the bloodstream following ARDS, triggering systemic inflammation. Conversely, it is possible that severe systemic inflammation may lead to ARDS by an influx of inflammatory mediators from the bloodstream to the lungs. However, the time course and the possible pathways for this transmission of disease have yet to be established. Investigators hypothesize that: Primary systemic inflammation is followed by a secondary pulmonary inflammatory response Primary pulmonary inflammation is followed by a secondary systemic inflammatory response Both primary and secondary inflammatory responses are characterized by the appearance of pro-inflammatory cytokines, inflammatory cells and production of collagen-like proteins (termed 'lectins') The inflammatory response is most pronounced in the primary afflicted compartment.

Official Title
-----------------
Acute Pulmonary and Systemic Inflammation in Mechanically Ventilated Intensive Care Patients

Conditions
-----------------
Acute Respiratory Distress Syndrome (ARDS), Systemic Inflammatory Response Syndrome (SIRS), Sepsis

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: General: Age >18 years Mechanically ventilated < 48 hours after admission to the Intensive Care Unit Specific: -ARDS: acute (< 1 week) respiratory failure, characterized by hypoxemia (PaO2/FiO2 < 300 mmHg/40kPa), and bilateral infiltrates on x-ray or CT of thorax, that can not be explained by heart failure og overhydration. OR - SIRS (two of the following): Temperature > 38°C or < 36°C, heart rate > 90/min, respiratory frequency > 20 or PaCO2 < 4.2 kPa, leukocytosis (> 12x10^9/L) or leukopenia (< 4x10^9/L) OR ARDS + SIRS Exclusion Criteria: One lung ventilation; Tube size < 8.0 mm; INR > 1.5 or thrombocytes < 40x10^9/L; Intracranial hypertension; Malignant arrythmias

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Acute respiratory distress syndrome (ARDS)<br> | |
| Systemic inflammatory response syndrome (SIRS)<br> | |
| ARDS+SIRS<br> | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor necrosis factor alpha (TNF-a) bioactivity |  | Day one | 
| Tumor necrosis factor alpha (TNF-a) bioactivity |  | Day three | 
| Tumor necrosis factor alpha (TNF-a) bioactivity |  | Day seven | 
| Tumor necrosis factor alpha (TNF-a) bioactivity |  | Day fourteen | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interleukin (IL)-6 |  | Day one | 
| Mannose binding lectin (MBL) |  | Day one | 
| Ficolin-1,2,3 |  | Day one |