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.
Acute respiratory distress syndrome (ARDS) is a major cause of morbidity and mortality. Of
the many potential predisposing factors, sepsis and pneumonia represent the two main causes
of ARDS. In spite of an increase in survival in recent years mortality in patients with ARDS
is still estimated around 30 to 40%. In this context, development of effective preventive
strategies in patients at high risk of development of ARDS is of paramount importance.
Unfortunately, the results of studies evaluating prophylactic regimens for ARDS have been
The gaseous molecule carbon monoxide (CO) has been traditionally viewed as a toxic metabolic
and industrial waste. However, recent studies have demonstrated an important physiologic role
of CO in many biological systems. Specifically, strong anti-inflammatory, anti-oxidant and
anti-thrombotic effects of CO gas administration and heme oxygenase activation (the enzyme
that generates endogenous CO gas) have been demonstrated in several animal models.
Previous studies conducted in our department have demonstrated that bronchoscopic
instillation of endotoxin (LPS) in healthy volunteers elicits a compartmentalized pulmonary
inflammatory response, serving as an excellent model to evaluate interventions directed
towards suppression of lung inflammation at its earliest stages.
In the current single blinded, randomized, placebo controlled study, we are planning to
evaluate the effects of inhaled carbon monoxide on local pulmonary inflammatory responses
following endotoxin administration. Healthy subjects will undergo local endotoxin
instillation, breathe CO or room air through a mask for 6 hours, and then a repeat
bronchoscopy with lavage will be done at 6 hours to assess the ability of CO to suppress
local inflammation in the lung.
- 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
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.
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)
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.
1. active tobacco use
2. baseline caroxyhemoglobin greater than 2%
5. medical history of recent clinically significant asthma allergy to both sulfa- and
6. Allergy to both sulfa- and penicillin-based drugs.