bromochloroacetic-acid and Lung-Diseases--Interstitial

Pulmonary manifestations contribute significantly to the morbidity and mortality of the idiopathic inflammatory myopathies, ranging from intrinsic lung disease to secondary complications that include aspiration pneumonia, opportunistic infection, congestive heart failure, and hypoventilation. Newer classification schemes for interstitial lung disease have permitted closer correlation between histologic subtype and clinical outcome, while diagnostic techniques such as bronchoalveolar lavage have begun to define the cellular elements responsible for immune-mediated pulmonary dysfunction. Investigators have identified several serum markers correlating with inflammatory disease activity in the lung that should enhance noninvasive monitoring of therapeutic responses to newer regimens involving agents such as cyclosporine and tacrolimus. Taken together, these advances have contributed to better understanding of the immunopathogenesis of myositis-associated interstitial lung disease that should ultimately translate into more effective treatment.

Topics: Bronchoalveolar Lavage; Dermatomyositis; Humans; Keratins; Lung; Lung Diseases, Interstitial; Polymyositis; Tomography, X-Ray Computed

The serum concentration of several markers in patients with collagen disease was studied to evaluate the useful indices for the diagnosis of interstitial pneumonia/pulmonary fibroses (pneumonitis). Procollagen N-terminal type III peptides, type IV collagen and monoamine oxidase were measured as the fibrosing markers. Squamous cell related antigen (SCC) and soluble cytokeratin 19 fragments (CYFRA21-1) were measured as the tumor markers. Hyaluronic acid, ESR and CRP were measured as the inflammation markers. The 119 patients with collagen disease (71 patients with RA, 16 with SSc, 9 with SLE, 8 with PM/DM, 6 with MCTI) and 9 with other collagen diseases) who have been followed in our hospital were studied. Of 119 patients, 23 patients (RA14, SSc7, PM/DM2) were complicated with pneumonitis. The results were as follows. 1. All the serum markers except CYFRA21-1 had no significantly difference between with and without pneumonitis. The serum CYFRA21-1 level in the pneumonitis group was higher than that of the non pneumonitis group (1.38 vs 0.66 ng/ml, P < 0.001). 2. The cut-off value was set at 2.0 ng/ml, corresponding to 26.1% sensitivity and 97.9% specificity for pneumonitis complicated with collagen disease. 3. The CYFRA21-1 level in early stage of pneumonitis group (from onset to measurement < 1 year) was significantly higher than that of late stage group (from onset to measurement > 1 year). And there are 75.0% sensitivity in early stage of pneumonitis group. 4. Case study was suggested that CYFRA21-1 had a potential as a diagnostic and monitoring marker for pneumonitis.

Topics: Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Collagen Diseases; Female; Humans; Keratin-19; Keratins; Lung Diseases, Interstitial; Male; Middle Aged; Pulmonary Fibrosis; Sensitivity and Specificity

Interstitial pneumonia (IP) may occur with the chest radiographic abnormality at the bilateral, predominantly basal and subpleural area of the lower lobe. And the incidence of lung cancer are markedly increased among patients with IP. From 1993 to 2003, 15 cases (male 14, female 1; average age 65.9-year-old), who were complicated IP, underwent surgical treatment in our hospital. Concerning detective tumor markers of lung cancers with IP, CYFRA showed very high sensitivity (92.3%) for any type of carcinoma. There were no case of perioperative death, however, 3 cases occurred severe deterioration of IP within 1 month and 6 cases died of respiratory failure. The risk factors, which aggravated IP at the postoperative period, were administration of prednisolone or immunosuppressive drugs from pre-operation and resection of the relatively non-fibrotic and non-honeycomb lobe which was affected with cancer. If it is possible to prognosticate the postoperative deterioration of IP, segmentectomy should be considered.

Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Female; Humans; Keratin-19; Keratins; Lung Diseases, Interstitial; Lung Neoplasms; Lymph Node Excision; Male; Middle Aged; Neoplasm Staging; Pneumonectomy; Prognosis; Survival Rate

The epithelial alteration in interstitial pneumonias is one of the repair processes at the sites of disease activity. Regenerative epithelial cells may participate in remodeling of the lung. To determine the phenotype of regenerative epithelial cells in usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP), the expression of Clara cell 10KD protein (CC10), cytokeratin (CK) 14 and 17, surfactant apoprotein (SP)-A, KL-6/MUC1, transforming growth factor (TGF) beta2 were examined in 25 patients with UIP, 9 patients with NSIP and normal lung tissues from 10 patients with lung cancer. In honeycomb lesions of UIP, non-ciliated columnar cells mainly expressed CC10, cuboidal cells expressed CC10, CK17, CK14 and SP-A in descending order. Fibroblastic foci are covered by CK17, CK14, CC10, and a few SP-A positive flattened or cuboidal cells. Regenerative epithelium in NSIP mainly comprised cuboidal cells expressing SP-A, CC10 and CK17. KL-6 was more remarkably expressed in cuboidal and non-ciliated columnar cells both in UIP and NSIP. Expression of TGFbeta2 was observed in cuboidal and flattened epithelium. In severe fibrotic areas, CC10 expressing cells were more prominent, while SP-A positive cells were more prominent in less fibrotic areas. Regenerative epithelial cells in remodeling area in UIP may be derived from bronchiolar basal cells and Clara cells, while most of those in NSIP may be derived from type II pneumocytes. The different origin of regenerative epithelium may reflect the severity and extent of the injury and the degree of consequent fibrosis in UIP and NSIP.

Topics: Antigens; Antigens, Neoplasm; Apoproteins; Bronchi; Enzyme Inhibitors; Epithelial Cells; Female; Fibroblasts; Fibrosis; Glycoproteins; Humans; Keratins; Lung; Lung Diseases, Interstitial; Lung Neoplasms; Male; Middle Aged; Mucin-1; Mucins; Phenotype; Phospholipases; Proteins; Pulmonary Surfactant-Associated Proteins; Regeneration; Transforming Growth Factor beta; Transforming Growth Factor beta2; Uteroglobin

A 76-year-old woman presented with non-productive cough and progressive dyspnea, and was admitted to Oita Medical University Hospital. Arterial blood gas values obtained on admission indicated severe hypoxemia. Chest roentgenograms and computed tomography disclosed diffuse interstitial infiltrates in both lungs. Transbronchial lung biopsy specimens demonstrated thickened alveolar walls with lymphocyte infiltration and swollen type II pneumocyte proliferation. Eosinophils were observed mainly around bronchioles. For approximately 6 months prior to hospitalization, the patient had been given misoprostol, sodium aurothiomalate, prednisolone, and loxoprofen sodium for the treatment of rheumatoid arthritis. Based on the clinical history and findings, drug-induced interstitial pneumonia was suspected. All medications were discontinued, and the patient was then placed on corticosteroids. After treatment, arterial blood gas values improved and the findings on chest roentgenograms cleared up. Positive lymphocyte stimulation tests and positive dermal reaction patch tests implicated misoprostol as an etiologic factor in the patient's interstitial pneumonia. High serum levels of KL-6 and cytokeratin subunit 19 fragment had been detected on admission. These values returned to normal after the interstitial infiltrates had disappeared. To our knowledge, this is the first reported case of misoprostol-induced interstitial pneumonia.

Topics: Aged; Anti-Ulcer Agents; Antigens; Antigens, Neoplasm; Female; Glycoproteins; Humans; Keratins; Lung Diseases, Interstitial; Lymphocyte Activation; Misoprostol; Mucin-1; Mucins; Peptide Fragments; Procollagen

CYFRA 21-1 and ProGRP have recently been established as new tumor markers for lung cancer. However, there are few reports evaluating concentrations in their bronchoalveolar lavage (BAL) fluid. In this study, we examined 81 patients with benign lung disease. The mean values of CYFRA 21-1 in the BAL fluid of each lung disease were as follows: bronchiolitis obliterans organizing pneumonia (BOOP), 3.9 +/- 2.1 ng/ml (positive rate 50%); collagen vascular disease associated interstitial pneumonia (CVD-IP), 10.7 +/- 15.7 ng/ml (positive rate 50%); diffuse panbronchiolitis (DPB), 4.2 +/- 6.4 ng/ml (positive rate 29%); idiopathic pulmonary fibrosis (IPF), 1.5 +/- 2.1 ng/ml (positive rate 17%); pulmonary infiltration with eosinophilia, 6.3 +/- 7.1 ng/ml (positive rate 44%); sarcoidosis, 4.6 +/- 6.2 ng/ml (positive rate 27%); and healthy volunteer (HV), 0.6 +/- 0.6 ng/ml; and total, 4.4 +/- 5.6 ng/ml (positive rate 32%). The mean values of ProGRP in the BAL fluid were as follows: DPB, 5.0 +/- 7.6 pg/ml (positive rate 0%); IPF, 6.4 +/- 10.6 pg/ml (positive rate 0%); HV, 12.4 +/- 8.3 pg/ml; and total, 5.6 +/- 8.7 pg/ml (positive rate 0%). These results indicate that the two tumor markers have no disease specificity in benign lung disease.

Topics: Antigens, Neoplasm; Bronchoalveolar Lavage Fluid; Cryptogenic Organizing Pneumonia; Humans; Keratin-19; Keratins; Lung Diseases; Lung Diseases, Interstitial; Peptide Fragments; Peptides; Pulmonary Eosinophilia; Recombinant Proteins

Cytokeratin 19 fragment (CK19) levels in serum have already been documented as a useful tumour marker for lung cancer. In the present study, it was hypothesized that CK19 may be increased in the serum and epithelial lining fluid of the respiratory tract from patients with pulmonary fibrosis. CK19 was measured in the serum and bronchoalveolar lavage fluid (BALF) of patients with pulmonary fibrosis and the correlation between CK19 levels and clinical parameters evaluated. Nineteen patients diagnosed with idiopathic pulmonary fibrosis (IPF), eight with pulmonary fibrosis associated with a collagen vascular disorder (PF-CVD), seven patients with acute interstitial pneumonia (AIP), and 10 normal smokers as a control group were studied. CK19 levels in sera of patients with IPF and patients with PF-CVD were significantly increased compared to those of normal smokers. CK19 levels in sera of patients with AIP were significantly increased compared to those of other groups. CK19 values in the BALF of patients with pulmonary fibrosis were significantly elevated compared to those of normal smokers. CK19 values in sera charged according to the progression or improvement of the acute lung injury. Immunohistochemical study using pulmonary tissues obtained from patients with AIP demonstrated that the hyaline membrane and proliferating type II pneumocytes were stained by anti-human cytokeratin 19 antibody. These data demonstrated that the measurement of cytokeratin 19 fragment is a useful parameter to evaluate the activity of lung epithelial cell damage and repair.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Biomarkers; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Collagen Diseases; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Female; Humans; Immunoenzyme Techniques; Keratins; Lung Diseases, Interstitial; Male; Middle Aged; Pulmonary Fibrosis; Vascular Diseases

Cytokeratin 19 fragment (CK19) levels in serum have been documented as a useful tumor marker for lung cancer. We hypothesize that CK19 may increase in serum in patients with interstitial pneumonia associated with polymyositis/dermatomyositis (PM/DM) and CK19 might be a useful variable to evaluate the activity of lung injury.. 1. We measured CK19 in sera in 15 patients diagnosed with PM/DM; 6 had nonspecific interstitial pneumonia (NIP), 4 had acute interstitial pneumonia (AIP), and 5 had no pulmonary involvement. We also measured CK19 in 10 healthy nonsmokers serving as a control group. 2. We evaluated the correlation between CK19 level and individual clinical course in patients with pulmonary involvement associated with PM/DM.. CK19 levels in sera of patients with NIP associated with PM/DM were significantly higher versus patients with PM/DM without interstitial pneumonia and healthy nonsmokers. CK19 levels in sera in patients with AIP associated with PM/DM were significantly higher compared with the other groups. CK19 values in sera changed according to the progression or improvement of interstitial pneumonia. Immunohistochemical studies using pulmonary tissues obtained at autopsy from patients with AIP associated with PM/DM revealed that the hyaline membrane was mostly stained by anti-human cytokeratin 19 monoclonal antibody as well as the strong positivity of proliferating type II pneumocytes.. These results suggest that the measurement of CK19 was a useful variable to evaluate the activity of lung injury in interstitial pneumonia associated with PM/DM.

Topics: Adult; Aged; Dermatomyositis; Female; Humans; Immunohistochemistry; Keratins; Lung Diseases, Interstitial; Male; Middle Aged; Peptide Fragments

Topics: Aged; Antibodies, Neoplasm; Humans; Keratins; Lung Diseases, Interstitial; Lung Neoplasms; Male

1. It has been suggested that CYFRA21-1, a cytokeratin subunit 19 fragment, is potentially useful for diagnosis and monitoring of lung carcinoma. However, serum levels of CYFRA21-1 are also increased in a high proportion of patients with interstitial lung disease. In this study we measured CYFRA21-1 levels in bronchoalveolar lavage fluid from 10 normal subjects, 18 patients with idiopathic pulmonary fibrosis and 14 patients with sarcoidosis, and determined whether any relationship exists between CYFRA21-1 levels in bronchoalveolar lavage fluid and clinical parameters. 2. CYFRA21-1 levels in bronchoalveolar lavage fluid were significantly higher in patients with sarcoidosis (mean value 8.3 ng/ml, P < 0.01) and idiopathic pulmonary fibrosis (42.5 ng/ml, P < 0.005) than in normal controls (1.0 ng/ml). Moreover, higher CYFRA21-1 levels in bronchoalveolar lavage fluid were found in sarcoidosis patients in radiological stage 2 or 3 than in those in stage 1. In patients with idiopathic pulmonary fibrosis, there was a significant correlation between CYFRA21-1 levels, and percentage of inflammatory cells in bronchoalveolar lavage fluid (r = 0.56, P < 0.05) and the magnitude of the alveolar--arterial oxygen pressure difference [P(A-a)O2] gradient (r = 0.66, P < 0.01). 3. Serial bronchoalveolar lavage samples were obtained from six patients with clinically active pneumonitis after they had undergone systemic corticosteroid therapy. CYFRA21-1 levels were significantly lower after these patients exhibited clinical improvement (P < 0.05). 4. These findings suggest that the level of CYFRA21-1 in bronchoalveolar lavage fluid is a useful marker for the clinical diagnosis of pneumonitis, and is also adequate for the evaluation of disease activity, especially over the course of treatment.

Topics: Adrenal Cortex Hormones; Antigens, Neoplasm; Biomarkers; Bronchoalveolar Lavage Fluid; Female; Humans; Keratin-19; Keratins; Lung Diseases, Interstitial; Male; Middle Aged; Prospective Studies; Pulmonary Fibrosis; Sarcoidosis; Statistics, Nonparametric

The two main reactive pulmonary lymphoid disorders are lymphoid interstitial pneumonia and follicular bronchitis/bronchiolitis, both pathological entities with a variety of aetiologies. We reviewed the morphological and immunohistochemical features of 26 cases with one or other of these two diagnoses, to explore the possibility that they represented overlapping patterns of hyperplasia of the bronchopulmonary immune system. The polymerase chain reaction was used to determine the clonality of the infiltrates. Histologically, there was a spectrum of changes with two main components. An interstitial infiltrate of mainly T lymphocytes, plasma cells and histiocytes predominated in lymphoid interstitial pneumonia, whilst lymphoid follicles predominated around airways in follicular bronchitis/bronchiolitis. Classification of the disorder rested on which component the pathologists believed to be dominant. In two cases, histology and immunohistochemistry suggested lymphoma, and in one of these cases this diagnosis was confirmed by the polymerase chain reaction. One case of lymphoid interstitial pneumonia produced three bands. The remainder produced polyclonal patterns when samples were adequate. Clinically, there was no clear difference between patients with the two disorders, or patients with pathological features of both.

Topics: Adolescent; Adult; Aged; Antigens, CD; B-Lymphocytes; Bronchiolitis; Cell Movement; Child; Child, Preschool; DNA; Female; Histiocytes; Humans; Immunoglobulin G; Immunoglobulin Heavy Chains; Infant; Keratins; Lung; Lung Diseases, Interstitial; Lymphoproliferative Disorders; Male; Middle Aged; Plasma Cells; T-Lymphocytes