Serum heat shock protein 47 levels in patients with drug-induced lung disease

Respiratory Research

Shigeru Kohno¹  Kazuhiro Nagata⁴  Hiroshi Mukae⁵  Mariko Mine²  Hiroshi Kubota⁸  Yasuhiro Matsuoka⁶  Noriho Sakamoto¹  Shintaro Hara¹  Shota Nakashima¹  Tomayoshi Hayashi⁷  Yuji Ishimatsu¹  Shin-ichi Yokota³  Tomoyuki Kakugawa¹ 

[1] Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan;Biostatistics Section, Division of Scientific Data Registry, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan;Department of Microbiology, Sapporo Medical University School of Medicine, Sapporo, Japan;Laboratory of Molecular and Cellular Biology, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto, Japan;Department of Respiratory Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan;Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan;Department of Pathology, Nagasaki University Hospital, Nagasaki, Japan;Department of Life Science, Faculty and Graduate School of Engineering and Resource Science, Akita University, Akita, Japan

关键词: Surfactant protein D;    Surfactant protein A;    Serum marker;    Krebs von den Lungen-6;    Drug-induced lung disease;   

Others  :  792274
DOI  :  10.1186/1465-9921-14-133

 received in 2013-08-05, accepted in 2013-11-07,  发布年份 2013

【 摘 要 】

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.

Conclusion

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.

【 授权许可】

   
2013 Kakugawa et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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Figure 3.

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