Sakae Homma

An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline

BACKGROUND This document updates the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guideline on idiopathic pulmonary fibrosis treatment. METHODS Systematic reviews and, when appropriate, meta-analyses were performed to summarize all available evidence pertinent to our questions. The evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and then discussed by a multidisciplinary panel. Predetermined conflict-of-interest management strategies were applied, and recommendations were formulated, written, and graded exclusively by the nonconflicted panelists. RESULTS After considering the confidence in effect estimates, the importance of outcomes studied, desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention, and implications to health equity, recommendations were made for or against specific treatment interventions. CONCLUSIONS The panel formulated and provided the rationale for recommendations in favor of or against treatment interventions for idiopathic pulmonary fibrosis.

Pulmonary fibrosis in an individual occupationally exposed to inhaled indium-tin oxide

Despite the increasing industrial use of indium-tin oxide (ITO) to manufacture flat-panel displays, such as liquid-crystal displays or plasma display panels for televisions, little is known about the potential health hazard induced by occupational exposure to indium compounds. The current study describes a case of fibrotic lung disease that developed after a 4-yr exposure to ITO. The pathology of the lung demonstrated pulmonary fibrosis with the presence of cholesterol granulomas. In conclusion, more attention needs to be paid to the possible toxic effects of indium compounds, and maximum healthcare measures should be taken to protect industry workers from these toxicities.

Pulmonary fibrosis in myeloperoxidase antineutrophil cytoplasmic antibody‐associated vasculitides

Objective:  The association of pulmonary fibrosis (PF) with myeloperoxidase antineutrophil cytoplasmic antibody (MPO‐ANCA)‐associated vasculitides has not been well documented. The aim of this study was to assess the clinicopathological characteristics of PF in patients who tested positive for MPO‐ANCA.

Efficacy of inhaled N-acetylcysteine monotherapy in patients with early stage idiopathic pulmonary fibrosis

Background and objective:  Idiopathic pulmonary fibrosis (IPF) is a fatal disorder for which there are currently no specific or effective medical treatments. A multicentre, prospective, randomized, controlled clinical trial was conducted to assess the efficacy of inhaled N‐acetylcysteine (NAC) monotherapy in Japanese patients with early stage IPF.

High-resolution computed tomography findings of lung cancer associated with idiopathic pulmonary fibrosis.

Objective: The purpose of this study was to evaluate high-resolution computed tomography (HRCT) findings of lung cancer associated with idiopathic pulmonary fibrosis (IPF). Methods: Thirty patients with lung cancer who had preceding IPF and were receiving regular follow-up between 1993 and 2002 were examined. Medical records, radiographs (including HRCT scans), and histologic slides were reviewed. Results: In 28 of the 30 patients, the most common HRCT pattern of lung cancer was a nodular lesion with soft tissue attenuation. Nodule margins were well defined in 23 lesions (82.1%), associated with lobulation in 24 (85.7%), or characterized by spiculation in 14 (50%). Air bronchogram was observed in 16 lesions (57.1%). All nodules were located in the peripheral area of fibrotic lesions. Squamous cell carcinoma and adenocarcinoma were the most frequent histologic types. Conclusions: The typical HRCT findings of lung cancer were well-defined nodular lesions with lobulation in peripheral areas of the lung.

Comparison of clinical characteristics and prognostic factors of combined pulmonary fibrosis and emphysema versus idiopathic pulmonary fibrosis alone

The results of studies examining the outcome and the factors predicting prognosis in combined pulmonary fibrosis and emphysema (CPFE) have so far been contradictory. Our objective was to determine prognosis and the prognostic factors for CPFE.

Bronchiolitis in Kartagener's syndrome

The association of diffuse bronchiolitis in patients with Kartageners syndrome (KS) has not been reported previously. The aim of this study was to present the morphological characteristics of bronchiolitis in patients with KS. Eight patients (four males, four females; mean age 37.9+/-18.7 yrs), clinically diagnosed as KS with the classical triad of chronic pansinusitis, bronchiectasis and situs in versus with dextrocardia, were evaluated. Routine chest radiography showed bronchiectasis and dextrocardia in all patients. Chest computed tomography (CT) showed diffuse centrilobular small nodules up to 2 mm in diameter throughout both lungs in six out of eight patients. Pulmonary function tests revealed marked obstructive impairment in all patients (forced expiratory volume in one second 57.0+/-11.3%, residual volume/total lung capacity 45.+/-12.7%, maximum midexpiratory flow 0.92+/-0.72 L x s(-1), forced vital capacity 74.1+/-12.2% (all mean +/- SD)). The examination of cilial movement of the bronchus revealed immotility in all of the five patients examined. The ultrastructure showed ciliary dynein arm defects in all patients. Histopathological examination of lung specimens obtained at autopsy or by video-assisted thoracoscopic surgery showed obliterative thickening of the walls of the membranous bronchioli with infiltration of lymphocytes, plasma cells and neutrophils, but most of the distal respiratory bronchioli were spared and alveolar spaces were overinflated. Pathologically, the diffuse centrilobular small nodules on the chest CT mainly corresponded to membranous bronchiolitis. This is the first report demonstrating that the association of diffuse bronchiolitis might be one of the characteristic features of the lung in Kartageners syndrome.

Clinical significance of BIM deletion polymorphism in non-small-cell lung cancer with epidermal growth factor receptor mutation.

Background: Germline alterations in the proapoptotic protein Bcl-2–like 11 (BIM) can have a crucial role in tumor response to treatment. To determine the clinical utility of detecting BIM deletion polymorphism in non–small-cell lung cancer positive for epidermal growth factor receptor (EGFR) mutation, we examined outcomes of patients with and without BIM alterations. Methods: We studied 70 patients with EGFR mutation-positive non–small-cell lung cancer who were treated with an EGFR tyrosine kinase inhibitor between January 2008 and January 2013. BIM deletion was analyzed by polymerase chain reaction in 58 samples of peripheral blood and 24 formalin-fixed paraffin-embedded slides of surgical specimens (20 of lung tissue and four of brain tissue); both blood and tissue specimens were available for 12 patients. We retrospectively analyzed clinical characteristics, response rate, toxicity, and outcomes among patients with and without BIM deletion. Results: BIM deletion was present in 13 of 70 patients (18.6%). There were no significant differences between patients with and without BIM deletion in clinical characteristics, rate of response to EGFR tyrosine kinase inhibitor, or incidence of adverse events. Patients with BIM deletion had significantly shorter progression-free survival (PFS) than those without BIM deletion (median, 227 versus 533 days; p < 0.001). Multivariate Cox regression analysis showed that BIM deletion was an independent indicator of shorter PFS (hazard ratio, 3.99; 95% confidence interval, 1.864–8.547; p < 0.001). Conclusions: Polymerase chain reaction successfully detected BIM deletion in samples of peripheral blood and formalin-fixed paraffin-embedded slides of surgical specimens. BIM deletion was the most important independent prognostic factor in shorter PFS.

Chaperonin TRiC/CCT participates in replication of hepatitis C virus genome via interaction with the viral NS5B protein.

To identify the host factors implicated in the regulation of hepatitis C virus (HCV) genome replication, we performed comparative proteome analyses of HCV replication complex (RC)-rich membrane fractions prepared from cells harboring genome-length bicistronic HCV RNA at the exponential and stationary growth phases. We found that the eukaryotic chaperonin T-complex polypeptide 1 (TCP1)-ring complex/chaperonin-containing TCP1 (TRiC/CCT) plays a role in the replication possibly through an interaction between subunit CCT5 and the viral RNA polymerase NS5B. siRNA-mediated knockdown of CCT5 suppressed RNA replication and production of the infectious virus. Gain-of-function activity was shown following co-transfection with whole eight TRiC/CCT subunits. HCV RNA synthesis was inhibited by an anti-CCT5 antibody in a cell-free assay. These suggest that recruitment of the chaperonin by the viral nonstructural proteins to the RC, which potentially facilitate folding of the RC component(s) into the mature active form, may be important for efficient replication of the HCV genome.

Diffuse panbronchiolitis in rheumatoid arthritis

The association of progressive obliterative bronchiolitis (OB) with rheumatoid arthritis (RA) is uncommon but has been reported previously. Diffuse panbronchiolitis (DPB) is a unique inflammation principally affecting the respiratory bronchioli and has been reported mainly in Japanese adults. Recently, DPB has also been noted in patients with RA in Japan. Therefore, there might be considerable overlap in clinical features between DPB and OB associated with RA in Japan. The aim of this study was to evaluate the clinicopathological characteristics of bronchiolitis in patients with RA. Three RA patients clinically diagnosed as having DPB were evaluated. All patients underwent chest radiographs, pulmonary function tests (PFT) and post mortem examination. Clinical features in all patients were a history of productive cough, exertional dyspnoea, wheezing and/or coarse crackles. Chest radiographs showed small nodular shadows up to 2 mm in diameter with bronchiolectasis throughout both lungs in all patients. The PFT revealed marked obstructive impairment in all patients. All patients died of progressive respiratory failure. Pathologically, two out of the three cases were confirmed as DPB, while the remaining one case was confirmed as OB, because the primary obstructive lesions were in the respiratory bronchioli in the former and in the membranous bronchioli and the proximal small bronchi in the latter. Thus, the clinical features of DPB and OB were strikingly similar, but the histopathological features revealed distinct differences. This study demonstrated that there was considerable overlap in clinical features between diffuse panbronchiolitis and obliterative bronchiolitis associated with rheumatoid arthritis, suggesting that diffuse panbronchiolitis might be a new manifestation of rheumatoid arthritis. The differentiation of these two disease entities is significant in making decisions on their therapeutic modality and is possible by analysing the precise histopathological findings of the lung.