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Objective: The purpose was to identify distinguishing CT features of pathologically diagnosed asbestosis, and correlate diagnostic confidence with asbestos body burden., Methods: Thirty-three workers (mean age at CT: 73 years) with clinical diagnoses of asbestosis, who were autopsied (n = 30) or underwent lobectomy (n = 3), were collected. Two radiologists independently scored high-resolution CT images for various CT findings and the likelihood of asbestosis was scored. Two pathologists reviewed the pathology specimens and scored the confidence of their diagnoses. Asbestos body count was correlated with CT and pathology scores., Results: Pathologically, 15 cases were diagnosed as asbestosis and 18 cases with various lung fibroses other than asbestosis. On CT, only the score of the subpleural curvilinear lines was significantly higher in asbestosis (p = 0.03). Accuracy of CT diagnosis of asbestosis with a high confidence ranged from 0.73 to 0.79. Asbestos body count positively correlated with CT likelihood of asbestosis (r = 0.503, p = 0.003), and with the confidence level of pathological diagnosis (r = 0.637, p < 0.001)., Conclusions: Subpleural curvilinear lines were the only clue for the diagnosis of asbestosis. However, this was complicated by other lung fibrosis, especially at low asbestos body burden., Key Points: • Various patterns of pulmonary fibrosis occurred in asbestos-exposed workers. • The fibre burden in lungs paralleled confident CT diagnosis of asbestosis. • The fibre burden in lungs paralleled confident pathological diagnosis of asbestosis. • Subpleural curvilinear lines were an important CT finding favouring asbestosis.

Lung epithelial cells have an integral role in the maintenance of lung homeostasis; however, the regulatory mechanism thereof has not been fully clarified. Recently, hepatoma-derived growth factor (HDGF) was reported to be involved in organ development and remodeling through its mitogenic effect. We investigated the biological role of HDGF in lung remodeling. HDGF was more highly expressed in the lungs of idiopathic pulmonary fibrosis, chiefly in the epithelial cells, than in control nonfibrotic lungs. We also confirmed the expression of HDGF protein and mRNA in the lungs of bleomycin-instilled mice, mainly in the bronchial and alveolar epithelial cells, by immunohistochemical analysis and in situ hybridization. We found that recombinant HDGF promoted DNA synthesis in rat alveolar epithelial cells and A549 cells in vitro. Endogenous HDGF overexpressed by gene transfer was translocated into the nucleus and promoted the proliferation of A549 cells. In vivo intratracheal instillation of recombinant HDGF induced the proliferation of bronchial and alveolar epithelial cells without causing marked interstitial inflammation. These findings suggest that HDGF may be involved in lung remodeling after injury by promoting the proliferation of lung epithelial cells, probably in an autocrine manner.

To elucidate the biological significance of selectin for idiopathic pulmonary fibrosis, we titrated the serum soluble E-selectin. From 31 cases of idiopathic pulmonary fibrosis patients without signs or symptoms of infection, the serum was obtained and the concentration was titrated by enzyme-linked immunosorbent assay. The serum soluble E-selectin titer was significantly higher than that of healthy controls. However, significant elevation was not observed in the sera from the patients with other pulmonary diseases, such as pulmonary emphysema, sarcoidosis, or bronchiectasis. In the patients with idiopathic pulmonary fibrosis, the number of white blood cells, C-reactive protein or lactate dehydrogenase activity did not show a significant relationship with the soluble E-selectin titer. About 16 out of the 31 idiopathic fibrosis patients, the serum surfactant apoprotein-A titer, which is a parameter of the disease activity of idiopathic pulmonary fibrosis, was also tested. The surfactant apoprotein-A titer was loosely correlated with the soluble E-selectin titer. These observations suggest that E-selectin may be relevant to the pathogenesis of idiopathic pulmonary fibrosis, and it may be a novel clinical parameter for idiopathic pulmonary fibrosis.

To elucidate the pathophysiology of pulmonary fibrosis, we investigated the involvement of p38 mitogen-activated protein kinase (MAPK), which is one of the major signal transduction pathways of proinflammatory cytokines, in a murine model of bleomycin-induced lung fibrosis. p38 MAPK and its substrate, activating transcription factor (ATF)-2, in bronchoalveolar lavage fluid cells were phosphorylated by intratracheal exposure of bleomycin, and the phosphorylation of ATF-2 was inhibited by subcutaneous administration of a specific inhibitor of p38 MAPK, FR-167653. FR-167653 also inhibited augmented expression of tumor necrosis factor -alpha, connective tissue growth factor, and apoptosis of lung cells induced by bleomycin administration. Moreover, daily subcutaneous administration of FR-167653 (from 1 day before to 14 days after bleomycin administration) ameliorated pulmonary fibrosis and pulmonary cachexia induced by bleomycin. These findings demonstrated that p38 MAPK is involved in bleomycin-induced pulmonary fibrosis, and its inhibitor, FR-167653, may be a feasible therapeutic agent.

ABSTRACT Background and objective Acute exacerbation ( AE) of idiopathic pulmonary fibrosis ( IPF) ( AE-IPF) is a poor prognostic disorder. AE is also reported to occur in other idiopathic interstitial pneumonias ( IIPs). There are limited data available regarding the effectiveness of treatment for AE-IIPs. The objective of this study was to clarify the prognostic impact of the initial dose of prednisolone ( PSL) for treating AE-IIPs. Methods Eighty-five patients with AE-IIPs, diagnosed according to the criteria of the Japanese Respiratory Society, were enrolled in this study ( IPF/non- IPF: 63/22 patients) from 2004 to 2013. We performed multivariate Cox proportional hazard regression analysis to identify poor prognostic factors. HRCT patterns at the onset of AE-IIPs were classified as diffuse or non-diffuse. We evaluated the prognostic significance of the initial dose of PSL by adjusting for other prognostic factors. Results Median survival time ( MST) after AE-IIPs diagnosis was 49 days. MST of AE-IPF and AE-non- IPF was 39 and 49 days, respectively. A diffuse HRCT pattern, lower serum IgG and higher serum surfactant protein-D at AE diagnosis, long-term oxygen therapy ( LTOT) before AE and positive pressure ventilation ( PPV) use for AE were significant poor prognostic factors for all patients, as were LTOT before AE and lower serum IgG for no- PPV patients. High-dose PSL ≥ 0.6 mg/kg was a significant prognostic factor for no- PPV patients after adjusting for other prognostic factors. Conclusion We concluded that a dose of PSL ≥ 0.6 mg/kg after i.v. high-dose methylprednisolone therapy should be recommended for the treatment of AE-IIPs. [ABSTRACT FROM AUTHOR]