Abstract
BackgroundHeat 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).MethodsFindings 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.ResultsThe 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.ConclusionThis 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.
Highlights
Heat shock protein (HSP) 47 is a collagen-specific molecular chaperone that is required for molecular maturation of various types of collagens
Serum HSP47 levels are superior to those of Krebs von den Lungen-6 (KL-6), surfactant protein (SP)-A, and SP-D for discriminating between acute exacerbations of idiopathic pulmonary fibrosis (IPF) and stable IPF [19]. These findings suggest that serum HSP47 levels correlate with interstitial pneumonia activity
In the diffuse alveolar damage (DAD) group, none of the patients improved without glucocorticoid administration, whereas 75.0% of the organizing pneumonia (OP) group, 45.8% (11 of 24 patients) of the nonspecific interstitial pneumonia (NSIP) group, and 36.4% of the hypersensitivity pneumonitis (HP) group improved without glucocorticoid administration
Summary
Heat shock protein (HSP) 47 is a collagen-specific molecular chaperone that is required for molecular maturation of various types of collagens. Radiographic appearance was assessed in 70 patients with confirmed gefitinib-induced lung toxicity [2]; the mortality rate was significantly higher in patients with a pattern of extensive bilateral ground-glass attenuation or airspace consolidations with traction bronchiectasis in HRCT chest scans (a finding that is thought to reflect DAD) when compared with patients with other patterns of lung injury [2]. This finding is consistent with observations by Ichikado et al, who reported that traction bronchiectasis is an important prognostic CT finding in patients with acute interstitial pneumonia [3]. The identification of other noninvasive markers that identify DAD and correlate with respiratory status, disease severity, and outcomes would be of benefit
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