Experimental Lung Inflammation Injury, Occupational Diseases, Poisoning Injury of other and unspecified intrathoracic organs
Conditions
Interventions
Study A:
To characterise the relationship between blood neutrophil/monocyte accumulation and lung inflammation after inhalation of LPS.
Duration of nebulised LPS intervention: 30 - 60 minutes
Duratio
Sponsors
University of Edinburgh (UK)
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Healthy male volunteers aged 18 - 40 years
Exclusion criteria
Exclusion criteria: 1. Aged less than 18 years 2. History of any chronic or ongoing acute illness (with particular reference to asthma, upper respiratory tract infection, lower respiratory tract infection, bronchiectasis, congenital heart disease, ischaemic heart disease, valvular heart disease, diabetes mellitus, chronic renal impairment, urinary tract infection) 3. Current history of smoking 4. Past smoking history amounting to greater than two pack-years 5. Any history of smoking in the last 12 months 6. Reported alcohol intake greater than 21 units per week 7. Any current medication 8. Abnormal physical signs detected at cardiorespiratory examination 9. Temperature greater than 37.3°C 10. Oxygen saturation less than 95% breathing room air 11. Haemoglobin, white cell count or platelet count outside the laboratory reference range 12. Blood sodium, potassium, urea, creatinine, bilirubin, alanine aminotransferase, random glucose or C-reactive protein outside the laboratory reference range 13. Forced expiratory volume in one second (FEV1) or forced vital capacity (FVC) less than 80% predicted 14. FEV1:FVC ratio less than 70% 15. Any cardiorespiratory abnormality detected on chest x-ray 16. Peripheral venous access insufficient to support bilateral 16 gauge cannulae
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Magnitude of LPS-induced neutrophilia after treatment assessed by selective mononuclear leukapheresis, sample taken at 8 hours. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Alveolar pulmonary neutrophil accumulation and injury assessed by bronchoscopy, sample retrieved at 8.5 hours 2. Global pulmonary neutrophil accumulation and injury assessed by positron emission tomography (PET), sample retrieved at 8.5 hours 3. Cytokines in BAL fluid, sample retrieved at 8.5 hours 4. Protein and albumin in BAL fluid, sample retrieved at 8.5 hours 5. Change in oxygen saturation, recordings made every 1 hour (0 - 8 hours, 24 hours and as indicated) 6. Change in serum markers of inflammation, blood drawn 0, 2, 4, 6 and 8 hours (where 0 hours is time just before nebulised LPS) 7. Serial profile of blood neutrophils and monocytes, blood drawn at 0, 2, 4, 6 and 8 hours 8. PET values, scan is at 11 hours 9. Safety and tolerablility, measured throughout | — |
Countries
United Kingdom
Outcome results
None listed