title: Pulmonary epithelial cell injury and alveolar-capillary permeability in berylliosis.
abstract: Inhaled beryllium induces specific sensitization and nonspecific effects leading to chronic beryllium disease (CBD). It is not known whether beryllium induces epithelial cell injury and increases alveolar-capillary leak. We hypothesize that lung injury is an early event in this disease and that markers of lung injury reflect severity of CBD. We measured serum and bronchoalveolar lavage fluid (BALF) KL-6 level, a marker of epithelial cell injury, and BALF/serum albumin, a marker of alveolar-capillary permeability, in 26 patients with CBD, 15 beryllium-sensitized subjects without disease (BeS), and 32 control subjects (Ctrl). We examined the association of these markers, BAL cellularity, pulmonary function, gas exchange, serum angiotensin-converting enzyme, chest radiograph, the effects of glucocorticoid therapy, and clinical course. BALF/serum albumin and serum KL-6 increased in CBD and were discriminative markers for CBD. BALF KL-6 and BALF/serum albumin reflected mainly lung cellular and granulomatous inflammation. Serum KL-6, like and BALF KL-6, was associated with permeability change and reflected functional and radiologic abnormalities. Serum KL-6 detected early lung injury in BeS. Epithelial injury and permeability changes occur early in CBD, indicating disease severity. Monitoring of these events with serum KL-6 may be useful for management of CBD.
authors.affiliation: Pulmonary Division, National Jewish Medical and Research Center, Denver, CO 80206, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: E
authors.initials: E
authors.lastname: Barker
authors.forename: E
authors.initials: E
authors.lastname: Daniloff
authors.forename: N
authors.initials: N
authors.lastname: Kohno
authors.forename: K
authors.initials: K
authors.lastname: Hiwada
authors.forename: L S
authors.initials: LS
authors.lastname: Newman
mesh_terms: D000328:Adult; D000368:Aged; D000941:Antigens / Q000032:analysis* / Q000097:blood; D000951:Antigens, Neoplasm; D001607:Berylliosis / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis* / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D002199:Capillary Permeability; D016022:Case-Control Studies; D004848:Epithelium / Q000473:pathology; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006023:Glycoproteins / Q000032:analysis* / Q000097:blood; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018396:Mucin-1; D009077:Mucins; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011659:Pulmonary Gas Exchange; D011859:Radiography; D012709:Serum Albumin / Q000032:analysis*
chemical_list: D000941:Antigens; D000951:Antigens, Neoplasm; D015415:Biomarkers; D005938:Glucocorticoids; D006023:Glycoproteins; C060192:MUC1 protein, human; D018396:Mucin-1; D009077:Mucins; D012709:Serum Albumin; D007703:Peptidyl-Dipeptidase A