Inflammatory Markers in Sputum After LPS Inhalation

Study Overview
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Brief Summary
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The purpose of the study is to measure inflammatory biomarkers in sputum and peripheral blood in healthy volunteers after inhalation of single doses of LPS (20 mcg) administered as particles of different sizes.

Detailed Description
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Endotoxins are inflammatory substances present in the environment. In man, the inhalation of the lipopolysaccharride moiety (LPS) induces measurable immune responses. With an inhaled single dose of 20 micron, the inflammatory response in man is sub-clinical. During bronchoprovocation tests with allergens, the particle size determines to a large extent the intensity of the response. the response to LPS as a function of particle size is not known and will be studied in this study.

Official Title
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The Role of Inhaled Particle Size on the Inflammatory Response Induced by Endotoxin Inhalation

Conditions
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Inflammation

Intervention / Treatment
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* Biological: LPS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy volunteer, non-smoking or ex-smoker >1mth and <10packs/year normal ECG normal lab values for hematology, ionogram, AST, ALT, alk phosphatases, urea, creatinine and CRP FEV1/forced vital capacity >0.7 and FEV1>80% of predicted value able to produce valid sputum following induction (>=50% viable cells, <50% squamous cells and <60% neutrophils) females must be using contraception written informed consent Exclusion Criteria: infection within 14 days history of bronchial asthma obstructive respiratory condition with FEV1 <70% of theoretical value

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LPS sequence 1<br>Nebulizers A then B then C | Biological: LPS<br>* LPS 20mcg sd inhaled via nebulizer, 3 periods<br>|
| Experimental: LPS sequence 2<br>Nebulizers B then C then A | Biological: LPS<br>* LPS 20mcg sd inhaled via nebulizer, 3 periods<br>|
| Experimental: LPS sequence 3<br>Nebulizers C then A then B | Biological: LPS<br>* LPS 20mcg sd inhaled via nebulizer, 3 periods<br>|
| Experimental: LPS sequence 4<br>Nebulizers A then C then B | Biological: LPS<br>* LPS 20mcg sd inhaled via nebulizer, 3 periods<br>|
| Experimental: LPS sequence 5<br>Nebulizers C then B then A | Biological: LPS<br>* LPS 20mcg sd inhaled via nebulizer, 3 periods<br>|
| Experimental: LPS sequence 6<br>Nebulizers B then A then C | Biological: LPS<br>* LPS 20mcg sd inhaled via nebulizer, 3 periods<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute neutrophil count in sputum |  | 24hrs after LPS inhalation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| white blood cells and differential in peripheral blood |  | 0, 6 and 24 hrs after LPS inhalation | 
| CC16 in peripheral blood |  | 0, 6 and 24hrs after LPS inhalation | 
| Calgranulin A/B |  | 0, 6 and 24hrs after LPS inhalation | 
| CRP in peripheral blood |  | 0, 6 and 24hrs after LPS inhalation | 
| Spirometry (FEV1 and FEV1/FEV) |  | 0, 1, 6 and 24hrs after LPS inhalation | 
| Alveolo-capillary diffusion |  | 0, 6 and 24hrs after LPS inhalation | 
| 12-lead ECG |  | Screening Visit 1 and final Visit 5 | 
| Physical exam | A complete physical exam at screening and at the final Visits, and an abbreviated physical exam at the three Visits during which LPS will be administered | At the Screening Visit 1, at the three Visits with LPS inhalation and at the Final Visit | 
| Safety labs from peripheral blood | hematology, blood chemistry (ionogram, AST, ALT, alkaline phosphatases, urea, creatinine) | At the Screening Visit 1 and the Final Visit 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LPS, endotoxin, inflammatory markers, healthy volunteers, neutrophils in sputum