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Objective We aimed to clarify the clinical significance of serum levels of MMPs in interstitial lung disease (ILD) complicated with PM/DM (PM/DM-ILD). Methods We retrospectively analysed serum levels of seven subsets of MMPs in 52 PM/DM-ILD patients diagnosed at Kyoto University Hospital or Tenri Hospital from January 2005 to December 2014. The patients were sub-grouped based on the presence of anti-amimoacyl-tRNA synthetase antibody (anti-ARS antibody), anti-melanoma differentiation-associated protein 5 antibody (anti-MDA5 antibody) or lack of the antibodies (ARS-ILD, MDA5-ILD and other-ILD groups, respectively) and independently analysed. Eighteen PM/DM patients without ILD and 55 healthy control were also analysed. Associations between serum levels of MMPs and clinical findings including mortality were analysed. Results Among the MMPs analysed, MMP-7 serum levels in the ARS-ILD group were significantly higher compared with those in any of the other groups of PM/DM patients or in healthy controls. On the other hand, in the MDA5-ILD group, serum MMP-7 levels >5.08 ng/ml were associated with worse overall survival both in univariate (P = 0.017; odds ratio 18.0; 95% CI 1.69, 192.00) and multivariate (P = 0.027; odds ratio 14.60; 95% CI 1.11, 192.00) analyses. Immunohistochemical analysis suggested that MMP-7 was expressed in type II alveolar epithelial cells adjacent to the fibrotic lesions. Conclusion Serum MMP-7 levels were higher in anti-ARS antibody-positive PM/DM-ILD patients, while higher serum MMP-7 levels among anti-MDA5 antibody-positive PM/DM-ILD patients were associated with a worse prognosis. Fibrotic processes may be associated with the elevation of serum MMP-7 levels. [ABSTRACT FROM AUTHOR]

Objective: Young patients with advanced interstitial lung disease (ILD) are potential candidates for cadaveric lung transplantation. This study aimed to examine clinical features, outcomes, and prognostic factors in Japanese ILD patients awaiting lung transplantation. Methods: We investigated the clinical features and outcomes of 77 consecutive candidates with ILD who were referred to Kyoto University Hospital and subsequently actively listed for lung transplant in the Japan Organ Transplant Network between 2010 and 2014. Results: Of the 77 candidates, 33 had idiopathic pulmonary fibrosis (IPF) and 15 had unclassifiable ILD. During the observational period, 23 patients (30%) received lung transplantations and 49 patients (64%) died before transplantation. Of the 33 patients with IPF, 13 (39%) had a family history of ILD and 13 (39%) had an “inconsistent with usual interstitial pneumonia pattern” on high-resolution computed tomography (HRCT). The median survival time from registration was 16.7 months, and mortality was similar among patients with IPF, unclassifiable ILD, and other ILDs. Using a multivariate stepwise Cox proportional hazards model, 6-min walking distance was shown to be an independent prognostic factor in candidates with ILD (per 10 m, hazard ratio (HR): 0.97; 95% confidence interval (CI): 0.95–0.99, p<0.01), while lower body mass index (HR: 0.83; 95% CI: 0.72–0.95, p < 0.01) independently contributed to mortality in patients with IPF. Conclusions: Japanese patients with ILD awaiting transplantation had very poor outcomes regardless of their specific diagnosis. A substantial percentage of IPF patients had an atypical HRCT pattern. 6-min walking distance in ILD patients and body mass index in IPF patients were independent predictors of mortality. [ABSTRACT FROM AUTHOR]

Background Lung perfusions after single lung transplantation ( SLT) have not been fully clarified in patients with interstitial lung disease ( ILD). The present study aimed to investigate temporal changes in native lung perfusion and their associated clinical factors in patients with ILD who have undergone SLT. Methods Eleven patients were enrolled. Perfusion scintigraphy was serially performed up to 12 months after SLT. Correlations between the post-operative perfusion ratio in the native lung and clinical parameters, including pre-operative perfusion ratio and computed tomography ( CT) volumetric parameters, were evaluated. Results On average, the perfusion ratio of the native lung was maintained at approximately 30% until 12 months after SLT. However, the ratio declined more significantly in idiopathic pulmonary fibrosis ( IPF) than in other ILDs (p = 0.014). The perfusion ratio before SLT was significantly correlated with that at three months after SLT (ρ = 0.64, p = 0.048). The temporal change of the perfusion ratio in the native lung did not correlate with those of the CT parameters. Conclusion The pre-operative perfusion ratio may predict the post-operative perfusion ratio of the native lung shortly after SLT in ILD. Perfusion of the native lung may decline faster in IPF compared with other ILDs. [ABSTRACT FROM AUTHOR]

Background: Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown etiology with few current treatment options. Recently, we determined an important role of prostaglandin F2α (PGF2α) in pulmonary fibrosis by using a bleomycin-induced pulmonary fibrosis model and found an abundance of PGF2α in bronchoalveolar lavage fluid of IPF patients. We investigated the role of PGF2α in human IPF by assessing plasma concentrations of 15-keto-dihydro PGF2α, a stable metabolite of PGF2α. Methods: We measured plasma concentrations of 15-keto-dihydro PGF2α in 91 IPF patients and compared these values with those of controls (n = 25). We further investigated the relationships of plasma 15-keto-dihydro PGF2α concentrations with disease severity and mortality. Results: Plasma concentrations of 15-keto-dihydro PGF2α were significantly higher in IPF patients than controls (p<0.001). Plasma concentrations of this metabolite were significantly correlated with forced expiratory volume in 1 second (Rs [correlation coefficient] = −0.34, p = 0.004), forced vital capacity (Rs = −0.33, p = 0.005), diffusing capacity for carbon monoxide (Rs = −0.36, p = 0.003), the composite physiologic index (Rs = 0.40, p = 0.001), 6-minute walk distance (Rs = −0.24, p = 0.04) and end-exercise oxygen saturation (Rs = −0.25, p = 0.04) when patients with emphysema were excluded. Multivariate analysis using stepwise Cox proportional hazards model showed that a higher composite physiologic index (relative risk = 1.049, p = 0.002) and plasma 15-keto-dihydro PGF2α concentrations (relative risk = 1.005, p = 0.002) were independently associated with an increased risk of mortality. Conclusions: We demonstrated significant associations of plasma concentrations of PGF2α metabolites with disease severity and prognosis, which support a potential pathogenic role for PGF2α in human IPF. [ABSTRACT FROM AUTHOR]

This article discusses findings of a study, which identified patients with anti-asparaginyl-transfer RNA synthetase (AsnRS) autoantibodies. It also studied the link of AsnRS with the syndrome of myositis, interstitial lung disease, arthritis and other features that had been associated with other anti-aminoacyl-trNA synthetase autoantibodies. Several clinical features that have been found in patients with anti-HisRS include myositis, interstitial lung disease, arthritis, Raynaud's phenomenon, fever and skin lesion of the fingers.

In the treatment of polymyositis and dermatomyositis (PM/DM), the complication of interstitial lung disease (ILD) is an important prognostic factor. It has been reported that autoantibodies against aminoacyl-tRNA synthetases (ARS) are strongly associated with ILD. The aim of this study is to examine the correlation between anti-ARS and the clinical course of ILD. We investigated 41 cases of PM/DM with ILD. The response of ILD to corticosteroids (CS) was determined according to the change in respiratory symptoms, image findings, and pulmonary function between, before and 2 months after the treatment. Anti-ARS (anti-Jo-1, PL-7, PL-12, EJ, OJ and KS) antibodies were screened with the RNA immunoprecipitation assay. In the stratification into ILD-preceding, simultaneous and myopathy-preceding types, anti-ARS antibodies were significantly frequent in the ILD-preceding type (p < 0.05). In the stratification into anti-ARS-positive and negative groups, the response of ILD to CS was significantly better in the positive group (p < 0.05). However, recurrence of ILD was significantly more frequent in the positive group (p < 0.01), and 2 year prognoses of pulmonary function (%VC and %DLCO) were not different between the two groups. In conclusion, screening of anti-ARS may be useful to predict late-onset myopathy in ILD-preceding patients and to predict the clinical course of ILD in PM/DM patients. [ABSTRACT FROM AUTHOR]

Background: Radiological pleuroparenchymal fibroelastosis (PPFE) lesion is characterized by pleural thickening with associated signs of subpleural fibrosis on high-resolution computed tomography (HRCT). This study evaluated the clinical significance of radiological PPFE as an isolated finding or associated with other interstitial lung diseases (ILDs) in patients having fibrotic ILDs and registered for cadaveric lung transplantation (LT).Methods: This retrospective study included 118 fibrotic ILD patients registered for LT. Radiological PPFE on HRCT was assessed. The impact of radiological PPFE on clinical features and transplantation-censored survival were evaluated.Results: Radiological PPFE was observed in 30/118 cases (25%): definite PPFE (PPFE concentrated in the upper lobes, with involvement of lower lobes being less marked) in 12 (10%) and consistent PPFE (PPFE not concentrated in the upper lobes, or PPFE with features of coexistent disease present elsewhere) in 18 (15%). Of these, 12 had late-onset non-infectious pulmonary complications after hematopoietic stem-cell transplantation and/or chemotherapy (LONIPCs), 9 idiopathic PPFE, and 9 other fibrotic ILDs (idiopathic pulmonary fibrosis, IPF; other idiopathic interstitial pneumonias, other IIPs; connective tissue disease-associated ILD, CTD-ILD, and hypersensitivity pneumonia, HP). Radiological PPFE was associated with previous history of pneumothorax, lower body mass index, lower percentage of predicted forced vital capacity (%FVC), higher percentage of predicted diffusion capacity of carbon monoxide, less desaturation on six-minute walk test, and hypercapnia. The median survival time of all study cases was 449 days. Thirty-seven (28%) received LTs: cadaveric in 31 and living-donor lobar in six. Of 93 patients who did not receive LT, 66 (71%) died. Radiological PPFE was marginally associated with better survival after adjustment for age, sex, %FVC, and six-minute walk distance < 250 m (hazard ratio 0.51 [0.25-1.05], p = 0.07). After adjustment for covariates, idiopathic PPFE and LONIPC with radiological PPFE was associated with better survival than fibrotic ILDs without radiological PPFE (hazard ratio 0.38 [0.16-0.90], p = 0.03), and marginally better survival than other fibrotic ILDs with radiological PPFE (hazard ratio, 0.20 [0.04-1.11], p = 0.07).Conclusions: idiopathic PPFE and LONIPC with radiological PPFE has better survival on the wait list for LT than fibrotic ILDs without radiological PPFE, after adjustment for age, sex, %FVC, and six-minute walk distance. [ABSTRACT FROM AUTHOR]