Netosis in Determination of Respiratory Infection Severity

Study Overview
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Brief Summary
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The study aims to evaluate the prognostic value of alveolar and blood NETosis in patients under mechanical ventilation and treated for an acute low-respiratory tract infection. The main outcome is the occurrence of an acute respiratory distress syndrome (ARDS) according to the Berlin definition.

Detailed Description
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Neutrophils are the first line of defense against infectious injury. Among the numerous mechanisms involving the immune system, neutrophil extracellular traps (NETs) have been recently described as an additional way neutrophils are able to use to fight against bacteria. NETs are made of DNA and antimicrobial proteins. In the other hand, NETs promote coagulation and may contribute to evolution of severe pneumonia into acute respiratory distress syndrome. The secondary objectives of the study include the research of the relation between blood NETosis and alveolar NETosis with: the documentation of invasive pulmonary infection based on microbiological analysis criteria (which would be bacteria or viral) of LBA at admission to ICU; the diagnosis value of usually used biomarkers: procalcitonin and C-reactive protein; marbrure score at admission to ICU; arterial lactatemia; scores of gravity at admission IGSII and SOFA; all-cause mortality at day-28; duration of mechanical ventilation at day-28; duration of amines at day-28; developement of hemodynamic failure; developement of pulmonary circulatory failure. The study will include 1) 60 patients under mechanical ventilation admitted to the intensive care unit for acute respiratory failure, 2) 10 control patients admitted to the ICU after a planned vascular surgery and 3) 10 healthy subjects.

Official Title
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Netosis in Mechanically Ventilated ICU Patients in Determination of Respiratory Infection Severity

Conditions
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Respiratory Infection

Intervention / Treatment
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* Biological: Blood sampling
* Procedure: Bronchoalveolar lavage


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: A/ For all subjets: Be >/= 18 years of age on day of signing informed consent; Affiliated to the french social security - welfare system in France. B/ Inclusion criteria for acute respiratory failure patients: admitted to the ICU for acute respiratory failure requiring mechanical ventilation within the first 24 hours after admission and suspected to suffer from an infectious pneumonia, according to the following criteria: recent fever; acute respiratory failure signs (dyspnea, polypnea > 30 cycles/min, hypoxemia PaO2<65 mmHg); pulmonary focal signs of auscultation; evocative signs in chest radiography or chest TDM. C/ Inclusion criteria for control patients: - admitted to the ICU for post-operative management of vascular surgery. Exclusion Criteria: A/ For all subjets: pregnancy, nosocomial pneumonia, no social health insurance, neutropenia of any cause; patient refusal. B/ Exclusion criteria for acute respiratory failure patients: - no mechanical ventilation within the first 24 hours after admission to the ICU.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| acute respiratory failure group<br>60 patients under mechanical ventilation admitted to the intensive care unit for acute respiratory failure | Biological: Blood sampling<br>* Blood sampling at baseline and at day-3 (10 ml, EDTA tube), test of NETs.<br>Procedure: Bronchoalveolar lavage<br>* Bronchoalveolar lavage at admission to the ICU with analysis of cytological, bacteriological, viral and anatomopathological, and test of NETs.<br>|
| vascular surgery control group<br>10 control patients admitted to the ICU after a planned vascular surgery | Biological: Blood sampling<br>* Blood sampling at baseline and at day-3 (10 ml, EDTA tube), test of NETs.<br>|
| Healthy volunteers group<br>10 healthy subjects. | Biological: Blood sampling<br>* Blood sampling at baseline and at day-3 (10 ml, EDTA tube), test of NETs.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute respiratory distress syndrome occurrence | Acute respiratory distress syndrome occurrence according to the Berlin definition within the first 7 days after ICU admission | at day-7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Vital statue of patient | At day-28 | 
| Duration of mechanical ventilation | Duration of mechanical ventilation: number of days without mechanical ventilation. | At day-28 | 
| IGSII score | IGSII score | At admission to ICU | 
| SOFA score | SOFA score | At admission to ICU | 
| Hemodynamic failure | Development of a hemodynamic failure | At day-28 | 
| Pulmonary circulation failure | Development of a pulmonary circulation failure (acute pulmonary heart disease, right ventricle failure) | At day-28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute respiratory distress syndrome, adult ICU, neutrophil extracellular traps (NETs), Netosis, neutrophils, mechanical ventilation, pneumonia