Collection of Lung Fluid and Tissue Samples for Research

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00471250
First received: May 8, 2007
Last updated: July 19, 2014
Last verified: July 2014
  Purpose

This study will collect fluid and tissue specimens from the lungs and nose of healthy people and people with a history of lung infections. The specimens will be examined for differences between the two groups that may be associated with susceptibility to certain infections.

Healthy normal volunteers and people with a history of lung infections between 18 and 75 years of age who are followed at NIH may be eligible for this study.

Participants undergo the following procedures:

Medical history and physical examination.

Blood and urine tests.

Electrocardiogram (ECG) and chest x-ray.

Treadmill exercise stress test (for people over 45 years old with a history of chest pain or ECG abnormalities).

Bronchoscopy: The subject s nose and throat are numbed with lidocaine and a sedative is given for comfort. A thin flexible tube called a bronchoscope is advanced through the nose or mouth into the lung airways to examine the airways carefully.

Fluid collection during the bronchoscopy using one of the following methods:

  • Bronchoalveolar lavage: Salt water is injected through the bronchoscope into the lung and immediately suctioned out, washing off cells lining the airways.
  • Bronchial brushings: A brush-tipped wire enclosed in a sheath is passed through the bronchoscope and a small area of the airway tissue is gently brushed. The brush is withdrawn with some tissue adhering to it.
  • Endobronchial biopsies: Small pinchers on a wire are passed through the bronchoscope and about 1 to 2 millimeters of tissue is removed.
  • Nasal scrape: A small device is used to scrape along the inside of the nose to collect some cells.

Condition
Mycobacterium Infections, Atypical
Granulomatous Disease, Chronic
Job's Syndrome
Influenza, Human

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Research Respiratory Tract Procedures

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 550
Study Start Date: May 2007
Detailed Description:

This research protocol involves one or more of the following procedures in healthy volunteers and patients with known or suspected predisposition to respiratory infection who are enrolled in National Institutes of Health (NIH) protocols: 1) Adults only: bronchoscopy with sampling of bronchoalveolar lavage fluid and epithelial cells in healthy adult volunteers and patients; 2) Adults and Children: sputum induction for collection of sputum specimens; 3) Adults and Children: nasal mucosal biopsies and brushings for sampling of epithelial cells. 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). Sputum induction is a routinely performed procedure to facilitate the collection of respiratory secretions (mucus) through stimulation of cough with inhalation of an aerosolized concentrated salt-water solution.

The objective of this protocol is to analyze bronchoalveolar lavage fluid, airway epithelial cells, and sputum specimens 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 one or more of the following: 1) bronchoscopy with bronchoalveolar lavage, bronchial brushings, endobronchial biopsies; 2) nasal mucosal scrape and/or brush biopsies; 3) sputum inductions to obtain specimens for in vitro investigations and comparisons of both the cellular and acellular components.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.

PATIENT INCLUSION CRITERIA FOR SPUTUM INDUCTION:

  1. greater than or equal to 10 years old
  2. Known or suspected 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. Willing to donate blood and respiratory tract samples for storage to be used for future research

PATIENT EXCLUSION CRITERIA FOR SPUTUM:

  1. < 10 years old
  2. Significant uncontrolled asthma or reactive airways disease
  3. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00471250

Contacts
Contact: Cathleen Frein, R.N. (301) 402-1006 freinc@mail.nih.gov
Contact: Kenneth N Olivier, M.D. (301) 496-5673 kenneth.olivier@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Kenneth N Olivier, M.D. National Heart, Lung, and Blood Institute (NHLBI)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00471250     History of Changes
Other Study ID Numbers: 070142, 07-I-0142
Study First Received: May 8, 2007
Last Updated: July 19, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Bronchoscopy
Bronchoalveolar Lavage
Nasal Mucosal Biopsy
Research Procedures
Infection Susceptibility
Lung Infection Susceptibility
Healthy Volunteer
HV

Additional relevant MeSH terms:
Granulomatous Disease, Chronic
Chronic Disease
Influenza, Human
Job Syndrome
Mycobacterium Infections
Mycobacterium Infections, Nontuberculous
Granuloma
Disease Attributes
Pathologic Processes
Phagocyte Bactericidal Dysfunction
Leukocyte Disorders
Hematologic Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes
Immune System Diseases
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lymphoproliferative Disorders
Lymphatic Diseases

ClinicalTrials.gov processed this record on August 19, 2014