lung injury
Conditions
Interventions
Subjects will visit the Intensive Care research department on three occasions 
(screening (± 45 minutes), LPS study day (6-8 hours), follow-up (30 minutes)). Subjects will receive 
an arterial catheter in the radial artery and a catheter will be placed in 
either the antecubital vein or the dorsal metacarpal vein for continuous 
hemodynamic monitoring and blood sampling. An esophageal pressure catheter and 
electrical impedance tomography (EIT) will be initiated for continuous 
respiratory mechanics monitoring. Pulmonary LPS instillation (via bronchoscopy) 
will be used to generate a local lung inflammatory response at baseline. 
Subjects will then receive either normal or high imposed levels of breathing 
effort (via inspiratory loading tasks) for 2-hours, during which continuous 
monitoring of respiratory mechanics and sequential blood sampling is performed. 
At the end of 2-hour inspiratory loading task, bronchoalveolar lavage is 
performed for the measurement of cytokines. Then, all monitoring equipment and 
catheters will be removed and subjects will go to the Medical Imaging 
department to undergo a PET/CT scan for the assessment of the magnitude and 
regional distribution of lung inflammatory metabolic activity. A follow-up CT scan will be performed after 6 months.
Sponsors
Radboud Universitair Medisch Centrum
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: - Male subjects aged >=18 and =18 and
Exclusion criteria
Exclusion criteria: - Use of any prescription medication or over-the-counter non-steroidal anti-inflammatory drugs - History or signs of severe atopic syndrome (asthma, rhinitis with medication and/or eczema) - History of any disease associated with immune deficiency - History of cancer in the last 5 years (excluding localised skin cancer or carcinoma in situ) - History or signs of haematological disease - History or signs of thromboembolic disorders - History of peptic / gastric ulcer disease - History of psychiatric disorders - History of respiratory disorders (asthma, chronic obstructive pulmonary disease) - Known diabetes - Upper airway or oesophageal pathology - Smoking/vaping/cannabis use - Thrombocytopenia (<150x109/mL) or anaemia (<8.0 mmol/L) - History, signs or symptoms of cardiovascular disease, in particular: • Prone to vagal collapse • History of atrial or ventricular arrhythmia • Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrio-ventricular block or a complete left bundle branch block • Hypertension (defined as systolic pressure > 160 or diastolic pressure > 90 mmHg) • Hypotension (defined as systolic pressure < 100 or diastolic pressure < 50 mmHg) - Renal impairment (defined as plasma creatinine >120 µmol/L) - Liver enzyme abnormalities (above 2x the upper limit of normal) - Signs of infection (CRP > 20 mg/L, white blood cells > 12x109/L or < 4x109/L) - Clinically significant acute illness, including infections or trauma, within 1 month prior to the LPS challenge - Previous (participation in a study with) endotoxin (LPS) administration - Known allergy to any of the used medication (lidocaine, xylocaine) - Participation in an experimental intervention or drug trial less than 3 months ago - Any vaccination or blood donation less than 1 month ago - Recent hospital admission or surgery with general anaesthesia less than 3 months ago - Use of recreational drugs less than 2 weeks ago - Suspected of not being able to comply with the trial protocol - Inability to personally provide written informed consent (e.g. for linguistic or mental reasons) and/or take part in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoint is the between-group difference in alveolar to arterial difference of oxygen, (A-a)DO2, after a 2-hour inspiratory loading task. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints are within and between-group differences in cytokines, respiratory mechanics (minute ventilation, lung stress, lung compliance, regional ventilation distribution and pendelluft), gas exchange (PaO2, PaO2/FiO2 ratio, PaCO2, saturation, pH and ventilatory ratio), the magnitude and regional distribution of lung inflammatory metabolic activity (2*-deoxy-2*- [18F]fluoroglucose uptake rate in the lungs) and blood and BAL cell composition and transcriptome (cellular composition and RNA profiles of leukocytes and BAL cells). | — |
Countries
Netherlands
Contacts
Public ContactA.H. Jonkman
Radboud Universitair Medisch Centrum
Outcome results
None listed