Protocol Number: 05-CC-0012

Title:

Effects of Inhaled Carbon Monoxide on Pulmonary Inflammatory Responses Following Endotoxin Instillation

Number:

05-CC-0012

Summary:

This study will examine in healthy volunteers how breathing carbon monoxide (CO) affects lung inflammation. Severe lung inflammation sometimes develops in patients with pneumonia or patients who develop serious blood stream infections. Studies in the laboratory and in animals show that CO can decrease lung inflammation.

Healthy volunteers between 18 and 40 years of age who do not smoke, are not taking any medications, do not have asthma, are not allergic to sulfa- and penicillin-based drugs, and are not pregnant may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, electrocardiogram (EKG), and chest x-ray. Subjects are enrolled in either a pilot study or the main study.

Participants undergo bronchoscopy and bronchoalveolar lavage to study the effects of endotoxin (a component of bacteria that causes inflammation similar to that in patients with lung infections) on lung function. Before the procedure, a small plastic tube (catheter) is placed in a vein to collect blood samples and another is placed in an artery to check blood pressure. For the bronchoscopy, the mouth and nasal airways are numbed with lidocaine, and a bronchoscope (thin flexible tube) is passed through the nose into the airways of the lung. A small amount of salt water is squirted through the bronchoscope into one lung and then salt water containing endotoxin is squirted into the other lung.

Following the bronchoscopy, subjects are treated with either CO or room air (placebo) for 6 hours. (Subjects in the pilot study receive treatment for only 3 hours). The gas is delivered through a cushioned mask placed over the nose and mouth. The amount of exhaled CO is measured before, during, and after inhalation of the gas. For this measurement, subjects take a deep breath to fill up their lungs and slowly exhale into a mouthpiece connected to a measuring device until they feel their lungs are empty.

After the CO treatment, a second bronchoscopy is done to examine how the lung responded to the CO or room air. This is studied in two ways. To sample the air, a large needle is used to withdraw air through the bronchoscope over about 3 seconds. Then the areas of the lung that were squirted with salt water alone and with endotoxin and salt water and are rinsed (lavage) and cells and secretions are collected.

Sponsoring Institute:

National Institutes of Health Clinical Center (CC)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

All volunteer subjects, employees and non-employees, must 18 to 40 years of age and must be able to provide informed, written consent for participation in this study. We will not directly advertise the study to employees to avoid the potential for coercion. Eligibility in the study is determined prior to enrollment on the basis of the following inclusion and exclusion criteria.

Normal screening examination including:

1. medical history and physical examination, nonsmoker, no concurrent medications including aspirin or nonsteroidal anti-inflammatory drugs, no active medical problems

2. complete blood count with differential and platelet counts

3. serum chemistries including creatinine, blood urea nitrogen, glucose, liver enzymes and function tests, electrolytes, prothrombin time, partial thromboplastin time, carboxyhemoglobin measured by venous co-oxymetry.

4. urinalysis

5. female subjects must have negative urine pregnancy test within one week of participation (this will be repeated immediately prior to beginning the screening procedures due to radiation exposure from the chest x-ray)

6. electrocardiogram

7. chest radiograph

Sexually active females not using contraceptive methods will be instructed to abstain from sexual activity or use barrier contraception methods from the time of last negative pregnancy test to 24 hours after completion of the study.

EXCLUSION CRITERIA:

1. active tobacco use

2. baseline caroxyhemoglobin greater than 2%

3. pregnancy

4. lactation

5. medical history of recent clinically significant asthma allergy to both sulfa- and penicillin-based drugs

6. Allergy to both sulfa- and penicillin-based drugs.

Special Instructions:

Currently Not Provided

Keywords:

Lung Permeability

Endotoxin Tolerance

Bronchoscopy

Carbon Monoxide Inhalation

Recruitment Keyword(s):

None

Condition(s):

Respiratory Distress Syndrome, Adult

Investigational Drug(s):

Endotoxin

Carbon Monoxide

Investigational Device(s):

None

Intervention(s):

Procedure/Surgery: Bronchoscopy

Procedure/Surgery: Bronchoalveolar lavage

Drug: Endotoxin

Drug: Carbon Monoxide

Supporting Site:

Warren G. Magnuson Clinical Center

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Hudson LD, Milberg JA, Anardi D, Maunder RJ. Clinical risks for development of the acute respiratory distress syndrome. Am J Respir Crit Care Med. 1995 Feb;151(2 Pt 1):293-301.

Baumann WR, et al. Incidence and mortality of adult respiratory distress syndrome: a prospective analysis from a large metropolitan hospital. Crit Care Med. 1986 Jan;14(1):1-4.

Milberg JA, Davis DR, Steinberg KP, Hudson LD. Improved survival of patients with acute respiratory distress syndrome (ARDS): 1983-1993. JAMA. 1995 Jan 25;273(4):306-9.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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