bromochloroacetic-acid and Bronchitis

Cytokeratin 19 (CK19) is a specific cytoskeletal structure of simple epithelia, including bronchial epithelial cells (BEC). Since CK19 is released from injured bronchial epithelium, we investigated the levels of CK19 fragments in the bronchoalveolar lavage fluid (BALF) of eight patients with chronic airway inflammatory diseases (CAID) using an enzyme-linked immunosorbent assay (ELISA). Included in our test group were four cases of chronic bronchitis, three cases of bronchiectasis, and one case of diffuse panbronchiolitis. There were also 15 control subjects (five asymptomatic smokers and 10 nonsmokers). BALF from the nonsmokers as well as from the asymptomatic smokers contained few CK19 fragments (0.2 +/- 0.2 and 1.9 +/- 0.8 pg/ml, respectively). In contrast, significantly high levels of CK19 were present in the BALF of patients with CAID (21.7 +/- 5.7 pg/ml; p < 0.01 versus nonsmoking controls). In addition, CK19 fragment concentrations in BALF correlated significantly with the number of neutrophils (r = 0.722, p < 0.01) but not with the numbers of macrophages or lymphocytes in BALF. BALF from patients with CAID contained high levels of neutrophil elastase (NE) activity, suggesting that NE might be an important stimulus for the release of CK19 from BEC. To prove this, we incubated BET-1A cells, a human immortalized bronchial epithelial cell line, both in the absence and the presence of inflammatory mediators (including NE, tumor necrosis factor-alpha [TNF-alpha], and hydrogen peroxide). We then measured the concentration of CK19 fragments in the culture supernatants with ELISA. BET-1A cells released CK19 fragments into their culture supernatants after treatment with NE but not after treatment with TNF or hydrogen peroxide. Further, we demonstrated that CK19 cleaved by NE could not be detected by ELISA. Our results suggest that CK19 measurement in BALF is useful for assessing the presence of bronchial epithelial injuries.

Topics: Adult; Aged; Biomarkers; Bronchi; Bronchiectasis; Bronchiolitis; Bronchitis; Bronchoalveolar Lavage Fluid; Case-Control Studies; Cells, Cultured; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation Mediators; Keratins; Male; Middle Aged; Smoking

The monitoring of serum concentrations of Cyfra 21-1, tumor polypeptide antigen (TPA), and tissue polypeptide specific antigen (TPS) has been demonstrated to be useful in the clinical treatment of patients with lung cancer. This study was planned to evaluate the clinical usefulness of the assay of these tumor markers on bronchial washing (BW) fluid and to compare it with serum assay in patients with neoplastic and nonneoplastic disease.. Serum and BW fluid levels of Cyfra 21-1, TPA, and TPS were measured in 40 subjects (10 control subjects, 11 with chronic bronchitis, 10 with squamous cell lung cancer, and 9 with nonsquamous cell lung cancer) undergoing diagnostic bronchoscopy. BW was performed using 25 mL of pyrogen-free saline solution instilled through the working channel of the bronchoscope, and successively aspirated. The quantity of the fluid recovered was measured and used for the assay of albumin, Cyfra 21-1, TPA, and TPS.. Mean BW concentrations of Cyfra 21-1, TPA, and TPS concentrations were significantly higher than serum concentrations (p < 0.01). Serum Cyfra 21-1, TPA, and TPS concentrations were significantly lower in controls and in those with chronic bronchitis than in patients with epidermoid and nonepidermoid carcinoma (p < 0.01). No difference in serum concentrations of the three markers was observed between controls and patients with chronic bronchitis. On the contrary, BW Cyfra 21-1 and TPA concentrations were significantly higher in those with chronic bronchitis and in cancer patients than in controls (p < 0.01), whereas they did not differ between patients with chronic bronchitis and cancer patients. No significant difference in BW TPS concentration was observed among the four groups. Sensitivity and specificity of the BW markers in diagnosing lung cancer were as follows: 68.4% and 61.9% for Cyfra 21-1; 68.4% and 66.6% for TPA; and 57.9% and 66.6% for TPS.. BW fluid concentrations of Cyfra 21-1 and TPA are increased in patients with chronic bronchitis and in patients with lung cancer. Being unable to distinguish malignant from nonmalignant inflammatory conditions, the measurement of airway concentrations of such markers has a too-low specificity to be considered useful in diagnosing malignant abnormalities of the lung.

Topics: Adult; Aged; Albumins; Antigens; Antigens, Neoplasm; Biomarkers, Tumor; Bronchitis; Bronchoalveolar Lavage Fluid; Bronchoscopy; Carcinoma; Carcinoma, Squamous Cell; Chronic Disease; Female; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Peptides; Sensitivity and Specificity; Tissue Polypeptide Antigen