title: Serum heat shock protein 47 levels in patients with drug-induced lung disease.
abstract: BACKGROUND
  Heat shock protein (HSP) 47 is a collagen-specific molecular chaperone that is required for molecular maturation of various types of collagens. We recently reported that HSP47 serum levels were markedly higher in patients with acute exacerbations of idiopathic pulmonary fibrosis (IPF) when compared with patients with stable IPF, suggesting that serum HSP47 levels correlate with interstitial pneumonia activity. The aim of this study was to evaluate serum HSP47 levels in patients with drug-induced lung disease (DILD).
  
  
  METHODS
  Findings from high-resolution computed tomographic chest scans of 47 patients with DILD were classified into one of four predominant patterns: organizing pneumonia (OP) (n = 4), nonspecific interstitial pneumonia (NSIP) (n = 24), hypersensitivity pneumonitis (HP) (n = 11), and diffuse alveolar damage (DAD) (n = 8). Serum levels of HSP47, Krebs von den Lungen-6 (KL-6), surfactant protein (SP)-A, and SP-D were measured in these patients.
  
  
  RESULTS
  The PaO2/fraction of inspired oxygen (FiO2) (P/F) ratios were significantly lower and the alveolar-arterial difference of oxygen (A-a DO2) was significantly higher in the DAD group than in the other groups. Patients with DAD had the worst outcomes among the different subgroups. Patients in the DAD group had significantly higher serum HSP47 levels than those in other groups. Receiver operating characteristic curves revealed that HSP47 was superior to KL-6, SP-A, and SP-D for discriminating between the DAD group and the other groups. The cut-off level for HSP47 that resulted in the highest diagnostic accuracy was 1711.5 pg/mL. The sensitivity, specificity, and diagnostic accuracy were 87.5%, 97.4%, and 95.7%, respectively. Serum levels of HSP47 in the group of patients requiring glucocorticoids were significantly higher than those in patients who experienced clinical improvement without glucocorticoid administration. Serum HSP47 levels also significantly correlated with various respiratory parameters.
  
  
  CONCLUSIONS
  This study demonstrated that serum HSP47 levels were elevated in patients with DILD with a DAD pattern who had the worst outcomes among the different subgroups, and that this was correlated with P/F ratio and A-a DO2.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan. kakugawa@nagasaki-u.ac.jp.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kakugawa
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Yokota
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishimatsu
authors.forename: Tomayoshi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Shota
authors.initials: S
authors.lastname: Nakashima
authors.forename: Shintaro
authors.initials: S
authors.lastname: Hara
authors.forename: Noriho
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsuoka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kubota
authors.forename: Mariko
authors.initials: M
authors.lastname: Mine
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mukae
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nagata
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000542:Alveolitis, Extrinsic Allergic / Q000097:blood / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D018549:Cryptogenic Organizing Pneumonia / Q000097:blood / Q000175:diagnosis*; D003937:Diagnosis, Differential; D005260:Female; D050958:HSP47 Heat-Shock Proteins / Q000097:blood*; D006801:Humans; D008171:Lung Diseases / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis*; D017563:Lung Diseases, Interstitial / Q000097:blood / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood; D011379:Prognosis; D037662:Pulmonary Surfactant-Associated Protein A / Q000097:blood; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D050958:HSP47 Heat-Shock Proteins; C060192:MUC1 protein, human; D018396:Mucin-1; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D