| Study summary: |
|
This research protocol involves bronchoscopy with sampling of bronchoalveolar lavage fluid
and epithelial cells and/or nasal mucosal biopsies in healthy adult volunteers and patients
with known or suspected predisposition to respiratory infection who are enrolled in National
Institutes of Health (NIH) protocols. The cellular and acellular samples will be separated,
and stored or transferred to the appropriate laboratories investigating these diseases.
Alveolar macrophages are the predominant (greater than 95%) cell type present in the lavage
of normal subjects. Alveolar macrophages play a central role in the initiation and
propagation of lung inflammation by releasing cytokines (i.e., interleukin-1, tumor necrosis
factor) and chemokines (i.e., interleukin-8, monocyte chemotactic protein, macrophage
inflammatory protein) that activate other resident cells and recruit inflammatory cells to a
local nidus of inflammation. Airway epithelial cells are known to release a variety of
mediators as well. Thus, the interaction of cells with mediators generated by alveolar cells
and bronchial epithelial cells during acute inflammation is a key element in the initiation
of pulmonary inflammatory responses.
Bronchoalveolar lavage (BAL), bronchial brushings, and mucosal biopsies are standard
diagnostic techniques done through the bronchoscope to obtain samples of alveolar and
bronchial specimens for diagnosis of infection, malignancy, or non-infectious inflammation.
Nasal mucosal scrape biopsy is a minimally invasive method of obtaining airway epithelial
cells to diagnose disorders of airway clearance associated with abnormal cilia (hair-like
structures on airway lining cells).
The objective of this protocol is to analyze bronchoalveolar lavage fluid and airway
epithelial cells from healthy volunteers and from patients who acquire respiratory
infections to look for differences in immune function and to discover new pathways of
infectious disease susceptibility. We hypothesize that studying cellular responses to
infection and inflammatory markers released from these cells will further our understanding
of human susceptibility to respiratory tract infections.
Five hundred and fifty subjects (250 healthy volunteers and 300 patients) will undergo
bronchoalveolar lavage, bronchial brushings, endobronchial biopsies, and/or nasal mucosal
scrape biopsies to obtain bronchoalveolar lavage fluid and airway epithelial cells for in
vitro investigations and comparisons of both the cellular and acellular components. |
| Criteria: |
|
- HEALTHY VOLUNTEER INCLUSION CRITERIA FOR BRONCHOSCOPY PROCEDURES:
- 18 to 75 years of age
- Enrolled without regard to gender, race, or ethnicity
- NIH employees or non-employees eligible
- Able to provide proof of identity
- Able and willing to complete the informed consent process
- Able and willing to arrange to have another person drive them home after the
procedure
- Able and willing not to eat or drink anything for 6 hours prior and 2 hours after the
procedure
- Willing to donate blood and respiratory tract samples for storage to be used for
future research
- In good general health without clinically significant medical history
- Physical examination without clinically significant findings
- Screening laboratory tests without clinically significant abnormalities:
1. Complete blood count
2. Serum chemistries
3. HIV test and hepatitis serologies (HBsAg; HCV) if status is unknown
4. Prothrombin time, partial thromboplastin time
5. Urinalysis
6. Female subjects must have negative urine pregnancy test within 1 week of
participation and continue birth control practices prior to participation
7. Chest radiograph (CXR)
8. Pulse oximetry
9. Electrocardiogram (ECG)
10. Treadmill exercise stress test (as indicated)
HEALTHY VOLUNTEER EXCLUSION CRITERIA FOR BRONCHOSCOPY AND BRONCHOSCOPIC PROCEDURES:
- Less than 18 or greater than 75 years old
- A smoking history of 10 pack-years or more, a current smoker, or tobacco free for
less than a year.
- Positive HIV status. Subjects must have a negative FDA-approved HIV blood test.
- Acute or chronic hepatitis based on viral hepatitis serologies
- Pregnancy or breastfeeding
- Any active medical problems especially bleeding disorders, significant bruising or
bleeding difficulties with intramuscular (IM) injections or blood draws, use of
anticoagulants, or pulmonary disorders including asthma
- History of allergic reaction to lidocaine, sedative medications like Valium Trademark
or Versed Trademark, or narcotic medications like morphine or fentanyl
- Immunosuppressive medications, cytotoxic medications, inhaled corticosteroids, or
long-acting beta-agonists within the past three months. (Note that use of
corticosteroid nasal spray for allergic rhinitis, topical corticosteroids for an
acute uncomplicated dermatitis, or short-acting beta-agonists in controlled
asthmatics is not excluded).
- Use of platelet inhibitors including aspirin and nonsteroidal anti-inflammatory drugs
(NSAIDs) within 7 days of procedure
- Any medical, psychiatric, social condition, occupational reason or other
responsibility that, in the judgment of the investigator, is a contraindication to
protocol participation or impairs a volunteer's ability to give informed consent
PATIENT INCLUSION CRITERIA FOR BRONCHOSCOPY AND BRONCHOSCOPIC PROCEDURES
1. 18 to 75 years of age inclusive
2. Known or suspected respiratory infections or infection susceptibility
3. Enrolled without regard to gender, race, or ethnicity
4. Must be enrolled in a concurrent NIH protocol and under the care of a primary
physician outside of the NIH
5. Able and willing to complete informed consent process
6. Able and willing to arrange to have another person drive them home after the
procedure
7. Able and willing not to eat or drink anything for 6 hours prior and 2 hours after the
procedure
8. Willing to donate blood and respiratory tract samples for storage to be used for
future research
PATIENT EXCLUSION CRITERIA FOR BRONCHOSCOPY AND BRONCHOSCOPIC PROCEDURES
1. Less than 18 or greater than 75 years old
2. History of recent/acute clinically significant pulmonary compromise.
----This will be defined by the following criteria:
1. New lung infection or change in status of chronic lung infection or significant
new findings on chest x-ray or CT scan
2. Asthma that is unstable or required emergent care, urgent care, hospitalization,
or intubation during the past two years, or that required the use of oral or
parenteral corticosteroids during the past two years
3. Clinically significant reactive airway disease that does not respond to
bronchodilators
4. Unstable chronic lung disease such as Chronic Obstructive Pulmonary Disease
(COPD) or pulmonary fibrosis
5. History of pulmonary hypertension
6. Requirement of supplemental oxygen at rest
3. Unstable angina or uncontrolled heart failure or rhythm disturbance
4. Significant kidney or liver disease
5. Significant anemia with a hemoglobin of less than 7.5 grams/dl.
6. Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or
platelet disorder requiring special precautions), significant bruising or bleeding
difficulties with IM injections or blood draws, or use of anticoagulant medications
7. Use of platelet inhibitors including aspirin and NSAIDs within 7 days of procedure or
clopidogrel (Plavix TM) within 14 days of procedure or the inability to safely stop
platelet inhibitors for 7-14 days prior to procedures
8. History of allergic reaction to lidocaine, sedative medications like Valium TM or
Versed TM, or narcotic medications like morphine or fentanyl
9. Pregnancy or breastfeeding
10. Any medical, psychiatric, social condition, occupational reason or other
responsibility that, in the judgment of the investigator, is a contraindication to
protocol participation or impairs a volunteer's ability to give informed consent
HEALTHY VOLUNTEER INCLUSION CRITERIA FOR NASAL MUCOSAL BIOPSY:
- Greater than or equal to 2 years old
- Enrolled without regard to gender, race, or ethnicity
- NIH employees or non-employees eligible
- Able to provide proof of identity
- Able and willing to complete the informed consent process
- Willing to donate blood and respiratory tract samples for storage to be used for
future research
- Stable vital signs
HEALTHY VOLUNTEER EXCLUSION CRITERIA FOR NASAL MUCOSAL BIOPSY:
- Less than 2 years old
- History of frequent colds or significant uncontrolled hay fever symptoms, recent
or active upper respiratory tract infection, such as a cold or sinusitis, or
chronic sinus infection or congestion
- History of turbinectomy or significant nasal pathology that would preclude
obtaining mucosal scrape biopsies
- Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy,
or platelet disorder requiring special precautions), significant bruising or
bleeding difficulties with IM injections or blood draws, or use of anticoagulant
medications
- The use of nasal steroids in the past 6 weeks is an exclusion to protocol
participation.
- Any medical, psychiatric, social condition, occupational reason, or other
responsibility that, in the judgment of the investigator, is a contraindication
to protocol participation or impairs a volunteer's ability to give informed
consent
PATIENT INCLUSION CRITERIA FOR NASAL MUCOSAL BIOPSY
- Greater than or equal to 2 years old
- Known or suspected infections or infection susceptibility
- Enrolled without regard to gender, race, or ethnicity
- Must be enrolled in a concurrent NIH protocol and under the care of a primary
physician outside of the NIH
- Able and willing to complete informed consent process
- Willing to donate blood and respiratory tract samples for storage to be used for
future research
PATIENT EXCLUSION CRITERIA FOR NASAL MUCOSAL BIOPSY:
- Less than 2 years old
- Significant uncontrolled hay fever symptoms or recent or active upper
respiratory tract infection, such as a cold or sinusitis
- History of turbinectomy or significant nasal pathology that would preclude
obtaining mucosal scrape biopsies
- Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy,
or platelet disorder requiring special precautions), significant bruising or
bleeding difficulties with IM injections or blood draws, or use of anticoagulant
medications
- Any medical, psychiatric, social condition, occupational reason, or other
responsibility that, in the judgment of the investigator, is a contraindication
to protocol participation or impairs a volunteer's ability to give informed
consent. |