Effects of Bronchial Segmental Endotoxin Instillation in Humans

  • End date
    Jun 8, 2023
  • participants needed
  • sponsor
    National Institutes of Health Clinical Center (CC)
Updated on 20 June 2021


  • When bacteria enter the lungs, serious infections can occur. Researchers want to learn more about the process of inflammation in the lungs by studying lung cells and the products that they make. Lung cells are influenced by infections, smoking, and molecules made within the body. Researchers also want to learn more about one of these molecules, called microRNA (or micro ribonucleic acid).
  • To better how the body responds to infection. Also, to understand which cells in the lung secrete microRNA and how they may influence other lung cells.
  • Healthy, non-smoking adults ages 18-45.
  • Participants will be screened with a medical history and physical exam. They will have blood and urine tests and an electrocardiogram.
  • Participants will have blood drawn from an arm vein. They will have an intravenous catheter (small plastic tube) placed in a vein.
  • All participants will have bronchoscopy with bronchoalveolar lavage. They will be numbed with medicine. A thin flexible tube will be placed through the nasal passages or the mouth into the airways of the lung.
  • Some participants will have bronchoscopy with bronchoalveolar lavage (rinsing the airways with salt water) in order to obtain cells from lung. The water will then be suctioned out.
  • Some participants will have two bronchoscopies; during the first procedure, endotoxin, a molecule found in bacteria is squirted into a small portion of the lung. Endotoxin is a molecule that acts like an infection but isn t one. After 6 to 48 hours, bronchoscopy with with bronchoalveolar lavage will be done to look at the lung s response to endotoxin.
  • Participants heart rhythm and rate, temperature and blood oxygen level will be monitored during the procedures.
  • Participants will be called the next day to see how they are feeling.


Defining the mechanisms that limit tissue injury during acute inflammation may provide the basis for preventing secondary organ dysfunction during serious infections. We plan to use the human endotoxin lung challenge model to study mechanisms associated with the initiation and resolution of lung inflammation.

Endotoxin (LPS), an outer membrane component of Gram-negative bacteria, is a major microbial factor that mediates inflammation associated with serious infections. For over fifty years, endotoxin has been administered to humans as a challenge agent in order to understand basic mechanisms of inflammation, to provide a proof of principle for pharmacologic interventions (e.g., anti-cytokines, corticosteroids), or as an adjuvant for immunotherapy of malignancies.

We previously developed a human model to study the initiation and resolution of inflammation in a lung segment following endotoxin bronchial instillation. The inflammatory response was limited to the challenged segment and had minimal associated systemic responses. After direct instillation into a lung segment, endotoxin elicits an inflammatory response characterized by the local production of inflammatory mediators, proteins and increases in cellularity. The predominate cell species found in the bronchoalveolar lavage (BAL) of the challenged segment changes from a neutrophil influx at 2 - 6 hours to an influx of monocytes and lymphocytes at 24 and 48 hours following endotoxin challenge. At 6 hours, BAL pro-inflammatory activity (i.e., tumor necrosis factor bioactivity and induction of intercellular adhesion molecule-1 on reporter cells) is present and absent at 24 and 48 hours post endotoxin. In addition, unique subsets of lymphocytes are present in the lung during this inflammatory response.

We have recently shown that non-cellular microRNAs (miRNAs) are present in archived BAL from normal healthy volunteer airways and are differentially expressed 6 hours after endotoxin-induced acute lung inflammation. miRNA are single stranded non-coding RNA that mediate posttranscriptional regulation of gene expression. Some extracellular miRNA species may modulate local and distant cell processes. miRNA can activate Toll-like receptors (TLRs) and have been described as blood biomarkers of different disease states. However, the specific role of extracellular or secreted miRNAs in the lung is poorly defined. Our research plan is designed to study the roles of miRNA in acute lung inflammation by investigating the changes in miRNA signatures found in BAL and lung cells from healthy volunteers at baseline and at 6, 24, or 48 hours after endotoxin segmental lung challenge. A panel of flow cytometry cell surface markers will be performed on blood and BAL cells and intracellular and secreted miRNA will be isolated from specific cell species (i.e., neutrophils, monocytes, macrophages, and lymphocytes). We hypothesize that miRNA will have a role in modulating the initiation and resolution of inflammation.

Condition Acute Lung Inflammation
Treatment Saline, Endotoxin, Endotoxin
Clinical Study IdentifierNCT02392442
SponsorNational Institutes of Health Clinical Center (CC)
Last Modified on20 June 2021


Yes No Not Sure

Inclusion Criteria

Healthy 18 to 45 year old, nonsmoking subjects based on screening examination and laboratory tests
No significant active medical problems. This would include but not be limited to any cardiac disorder (e.g. arrhythmia, valvular heart disease), pulmonary disease (e.g. asthma requiring chronic medications, chronic bronchitis, emphysema), neurologic disorder (e.g
epilepsy), kidney disease (e.g. nephritis, nephrosis), rheumatologic disorder
(e.g. inflammatory arthritis), endocrine disorder (e.g. diabetes, thyroid
disease), liver disease (e.g. hepatitis), gastrointestinal disorder (e.g
inflammatory bowel disease) or infectious
disease (e.g. human immunodeficiency virus)
\. No concurrent medications including aspirin or non-steroidal anti-
inflammatory drugs or have not taken these for at least 7 days prior to study
\. Previous smokers would have to have abstained from cigarettes for at least
one year and have no greater than a 10-pack year smoking history. If you use a
hookah, e-cigarette, or vaping more than once a week, you must abstain for at
least 6 weeks prior to participating in the study
\. Females must be practicing active method of birth control or abstinence of
sexual activity
\. Must be willing to have samples stored

Exclusion Criteria

Any serious active medical problem as defined above
Pregnancy and/or lactation
BMI >30
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Phone Email

Preferred Language
Other Language
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note