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| Name | Class |
|---|---|
| Barnes-Jewish Hospital | OTHER |
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The overall purpose of this research is to gain understanding of the basic responses of the lung to inflammation. Inflammation is the way our bodies react to irritation or injury, and involves red, warm, and often painful swelling of the affected tissue. "Acute lung injury" involves a generalized inflammation to the lung that is activated by any of several conditions: infection, trauma, inhalation of toxic substances, etc. When lung injury is severe, not enough oxygen can get into the body; this can lead to the need for mechanical support of breathing (mechanical ventilation), problems with brain, heart or other organ function, and in some cases, death. Inducible nitric oxide synthase (iNOS) contributes to the development of lung inflammation.
The investigators plan to use [18F](+/-)NOS (the F stands for fluorine and NOS stands for Nitric Oxide Synthase, the name for the investigational radioactive drug that targets iNOS) and positron emission tomography (PET) imaging as a measure of lung inflammation. PET is a machine that detects radiation and generates pictures using a donut shaped scanner similar in appearance to an x-ray "CAT" scan.
In order to show that [18F](+/-)NOS-PET is related to the amount of inflammation, the investigators first need to create a state of controlled lung inflammation that can be measured and quantified. "Controlled lung inflammation" means a reaction in the lungs that is similar to that which occurs during lung infection (increased respiratory secretions, and cough). It is "controlled" because the investigators will not be using anything alive or contagious (it will not spread from one part of your body to another, and cannot spread to another person) and a small area in only one lung will be affected. In order to create this state of controlled lung inflammation, the investigators plan to put a small amount of endotoxin into a single small section of the lung using a bronchoscope (a long, flexible, narrow tube that is passed through the nose or the mouth into the airways of the lung). This use of endotoxin is considered investigational. The investigators have received permission from the FDA to use endotoxin in this research study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Endotoxin and [18F](+/-)NOS | Experimental | All volunteers in this study will receive endotoxin in a single segment of the lung to induce mild, self-limited inflammation. They will also be imaged before and after endotoxin instillation with the novel PET tracer F-18 (+/-) NOS |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Endotoxin (E. coli O:113, Reference Endotoxin) | Drug |
|
| |
| Measure | Description | Time Frame |
|---|---|---|
| Distribution volume ratio (DVR), determined by Logan plot analysis, in the right middle lobe. | Change in DVR on post-endotoxin scan (Day 2) from baseline (Day 1). |
| Measure | Description | Time Frame |
|---|---|---|
| Bronchoalveolar lavage (BAL) fluid cell counts. | Total nucleated and neutrophil cell counts obtained by BAL after endotoxin instillation. | 24 hours after endotoxin instillation. |
| Number and percent of iNOS-stained BAL cells. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Delphine L. Chen, MD | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicne | St Louis | Missouri | 63110 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25525182 | Derived | Huang HJ, Isakow W, Byers DE, Engle JT, Griffin EA, Kemp D, Brody SL, Gropler RJ, Miller JP, Chu W, Zhou D, Pierce RA, Castro M, Mach RH, Chen DL. Imaging pulmonary inducible nitric oxide synthase expression with PET. J Nucl Med. 2015 Jan;56(1):76-81. doi: 10.2967/jnumed.114.146381. Epub 2014 Dec 18. |
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| ID | Term |
|---|---|
| D011014 | Pneumonia |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D004731 | Endotoxins |
| D008070 | Lipopolysaccharides |
| C000615276 | Fluorine-18 |
| ID | Term |
|---|---|
| D001427 | Bacterial Toxins |
| D014118 | Toxins, Biological |
| D001685 | Biological Factors |
| D006001 | Glycoconjugates |
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| [18F](+/-)NOS |
| Drug |
|
| 24 hours after endotoxin instillation. |
| D002241 |
| Carbohydrates |
| D011135 | Polysaccharides, Bacterial |
| D011134 | Polysaccharides |
| D008055 | Lipids |
| D000942 | Antigens, Bacterial |
| D000941 | Antigens |