Archive for the ‘Pulmonary Fibrosis’ Category

Association of Activated Cytolytic Lung Lymphocytes with Response to Prednisone Therapy: Discussion

Numerous studies of cell-mediated immune phenomena in interstitial lung diseases have been reported. The role of activated cytolytic lymphocytes has not been previously investigated, despite the importance of these as major effector components of the immune response. Ours is the first report, to our knowledge, demonstrating the presence of activated cytolytic cells in the BAL fluid of some patients with IPF. Longitudinal studies indicated that this subgroup of IPF patients responded to prednisone therapy with improved pulmonary function, and, significantly, clinical improvement was associated with decreased lectin-dependent cytolytic lymphocyte activity in BAL fluid. Patients with cytolytic activity in peripheral blood but not in BAL fluid and patients without cytolytic activity from either source did not respond to prednisone therapy. Patients with IPF who had lectin-dependent activity in BAL fluid may constitute a subgroup who have more active inflammation or are in an earlier stage of disease then IPF patients without initial cytolytic activity. Read the rest of this entry »

Association of Activated Cytolytic Lung Lymphocytes with Response to Prednisone Therapy: Initial Cell Counts

Association of Activated Cytolytic Lung Lymphocytes with Response to Prednisone Therapy: Initial Cell CountsInitial Cell Counts
The median total and median differential initial cell counts of IPF patients and of normal subjects are shown in Table 1. These data demonstrate increased total cell numbers and percentages of polymorphonuclear lymphocytes in BAL fluid of patients with IPF. Some patients with IPF also had increased percentages of lymphocytes. The above findings are consistent with previous reports of IPF alveolitis. Read the rest of this entry »

Association of Activated Cytolytic Lung Lymphocytes with Response to Prednisone Therapy: Results

Concanavalin A-Dependent Cell-mediated Cytotoxicity Assay: The CDCMC assay was used to measure activated lymphocyte killing, as published elsewhere. In brief, the murine mastocytoma cell line P815 (1-2×10 cells/ml) was suspended in 0.3 ml of medium; 0.3 ml of Tris phosphate buffer, ph 7.4; and 100 to 200 μCi of sodium 5ICr chromate (Amersham Corp). The P815 target cells were then incubated for 30 min at 37°C, washed three times and resuspended in medium at 1.25 x 104 viable cells/ml. Con A, 80 n-g/ml, was added to the target cells to give a 2 x concentration relative to the final concentration in the assay. One hundred microliters of 5lCr-labeled P815 cells was then dispensed into triplicate wells of a 96 well V-bottom microtiter plate (Nunc). Read the rest of this entry »

Association of Activated Cytolytic Lung Lymphocytes with Response to Prednisone Therapy: Clinical Laboratory Tests

Association of Activated Cytolytic Lung Lymphocytes with Response to Prednisone Therapy: Clinical Laboratory TestsBronchoscopy and Lymphocyte Isolation: Following topical lidocaine anesthesia, an Olympus BF-10 bronchoscope was passed into the airways transnasally and, after inspection of the airways, the bronchoscope was wedged into a segmental orifice of an affected lobe (as assessed by chest roentgenogram). BAL was performed by infusing approximately 150 ml of sterile 0.9 percent NaCl solution in 20- to 30-ml aliquots, with gentle aspiration until a 100-ml fluid return was achieved. At initial bronchoscopy, transbronchial biopsies were obtained from segments different from those used for BAL using standard techniques. Read the rest of this entry »

Association of Activated Cytolytic Lung Lymphocytes with Response to Prednisone Therapy: Materials and Methods

Patients
Ten consecutive patients with a diagnosis of IPF were recruited from Montefiore-North Central Bronx Hospital Center on initial presentation to enter this study. All subjects gave informed consent for the procedures, which were approved by the Institutional Review Board. The diagnosis of IPF was established by a combination of medical history, physical examination, laboratory tests, chest roentgenograms, pulmonary function tests (PFTs), arterial blood gas analyses, and the results of lung biopsies according to previously described criteria. Histologic confirmation of the diagnosis was obtained by transbronchial lung biopsy in four patients and by open lung biopsy in six patients. Here
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Association of Activated Cytolytic Lung Lymphocytes with Response to Prednisone Therapy

Association of Activated Cytolytic Lung Lymphocytes with Response to Prednisone TherapyPrevious studies have suggested that immune mechanisms may participate in the pathogenesis of certain interstitial lung diseases (eg, IPF, sarcoidosis, and hypersensitivity pneumonitis). While these diseases may have different initiating events and intermediate phases, they share a common final pathway leading to fibrosis and pulmonary insufficiency. IPF is characterized by accumulation of inflammatory cells in the lung, destruction of normal alveoli, and fibrosis. In contrast to sarcoidosis and hypersensitivity pneumonitis, IPF has not been thought to involve a local cell-mediated response. For example, sarcoidosis and hypersensitivity pneumonitis patients are known to have T-cell alveolitis with an altered distribution of lymphocyte subsets, but in IPF, lymphocyte subset ratios have been reported to be normal by Hunninghake and Crystal and to be decreased by Izumi et al. Link
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