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:
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; 4) Adults and Children: measurement of nasal nitric oxide production; 5) Adults and children: collection of exhaled breath condensate; 6) Adults and children: measurement of nasal potential difference; 7) Adults and children: exhaled aerosol mask sample collection; Adults and children: 8) cough aerosol collection. 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. Exhaled breath condensate is simply collected by breathing normally through a plastic tube inserted into a chilled cylinder. Nasal potential difference is performed by placing a small needle under the skin of the forearm that is connected to a salt solution bridge and resting a small catheter on the surface of the nose through which various salt solutions are dripped.
The objective of this protocol is to analyze bronchoalveolar lavage fluid, airway epithelial cells, sputum, and exhaled breath specimens and bedside physiologic measurements 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 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 4) exhaled breath condensate to obtain specimens for in vitro investigations and comparisons of both the cellular and acellular components. Bedside measurements 5) nasal nitric oxide production and 6) nasal potential difference 7) exhaled aerosol mask sample collection 8) cough aerosol collection may be done to assess airway infection and epithelial cell functions in real-time.
Condition | Leukocyte Disorders, Respiratory Tract Diseases, Bronchoscopy |
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Clinical Study Identifier | NCT00471250 |
Sponsor | National Heart, Lung, and Blood Institute (NHLBI) |
Last Modified on | 21 October 2022 |
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