Keishi Oda

High-resolution CT scoring system-based grading scale predicts the clinical outcomes in patients with idiopathic pulmonary fibrosis.

BackgroundThe 2011 idiopathic pulmonary fibrosis (IPF) guidelines are based on the diagnosis of IPF using only high-resolution computed tomography (HRCT). However, few studies have thus far reviewed the usefulness of the HRCT scoring system based on the grading scale provided in the guidelines. We retrospectively studied 98 patients with respect to assess the prognostic value of changes in HRCT findings using a new HRCT scoring system based on the grading scale published in the guidelines.MethodsConsecutive patients with IPF who were diagnosed using HRCT alone between January 2008 and January 2012 were evaluated. HRCT examinations and pulmonary function tests were performed at six-month intervals for the first year after diagnosis. The HRCT findings were evaluated using the new HRCT scoring system (HRCT fibrosis score) over time. The findings and survival rates were analyzed using a Kaplan-Meier analysis.ResultsThe HRCT fibrosis scores at six and 12 months after diagnosis were significantly increased compared to those observed at the initial diagnosis (p < 0.001). The patients with an elevated HRCT fibrosis score at six months based on a receiver operating characteristic (ROC) curves analysis had a poor prognosis (log-rank, hazard ratio [HR] 2.435, 95% CI 1.196-4.962; p = 0.0142). Furthermore, among the patients without marked changes in %FVC, those with an elevated score above the cut-off value had a poor prognosis (HR 2.192, 95% CI 1.003-4.791; p = 0.0491).ConclusionsOur data demonstrate that the HRCT scoring system based on the grading scale is useful for predicting the clinical outcomes of IPF and identifying patients with an adverse prognosis when used in combination with spirometry.

Assessment of Pathologically Diagnosed Patients with Castleman’s Disease associated with Diffuse Parenchymal Lung Involvement Using the Diagnostic Criteria for IgG4-Related Disease

BackgroundIgG4-related disease (IgG4RD) is a recently recognized disease entity. Differentiating IgG4RD from plasma cell type Castleman’s disease (PCD) is important but also difficult using only pathological findings. In addition, little is known about the association between these two diseases with diffuse parenchymal lung involvement.MethodsWe analyzed the serum IgG4 levels and the ratio of IgG4/IgG-positive plasmacytes in the lung and lymph node specimens of eight patients previously pathologically diagnosed of PCD with diffuse parenchymal lung involvement (DL-PCD). We also compared the clinical and laboratory findings observed in these patients.ResultsSix of the eight patients exhibited abundant IgG4-positive plasmacytes in the lung and lymph node tissues and elevated serum IgG4 levels, thereby fulfilling the diagnostic criteria of IgG4RD with DL (DL-IgG4RD) in addition to having obstructive phlebitis and massive lymphoplasmacytic infiltration with fibrosis. However, three of these six patients exhibited higher levels of serum interleukin-6 and were still diagnosed with DL-PCD. Accordingly, three of these eight patients were considered as IgG4RD with DL (DL-IgG4RD), and the other five patients were ultimately given a diagnosis of DL-PCD. These two diseases have different characteristics in terms of age, symptoms, serum levels of C-reactive protein, and IgA, complicating allergic disorders, response to corticosteroids, and prognosis.ConclusionsThis is the first report to show a high prevalence of DL-IgG4RD in DL-PCD patients, although additional large investigations are necessary. Clinical and laboratory findings are important for distinguishing between these two diseases in other organs, as previously described.

Profibrotic role of WNT10A via TGF-β signaling in idiopathic pulmonary fibrosis

BackgroundWNT/β-catenin signaling plays an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF); however, the role of WNT10A via transforming growth factor (TGF)-β signaling remains unclear.MethodsWe evaluated the expression of WNT10A and TGF-β in bleomycin (BLM)-treated mice and the interactions between TGF-β or BLM and WNT10A in vitro. Additionally, we investigated IPF patients who underwent video-assisted thoracoscopic surgery to determine whether the WNT10A expression is related to the survival.ResultsIncreased WNT10A and TGF-β expressions were noted in the BLM-treated mice. Real-time PCR and luciferase reporter assays demonstrated the levels of WNT10A and collagen in the fibroblasts cells to increase after TGF-β administration. Conversely, WNT10A siRNA treatment inhibited the synthesis of collagen in the transfected fibroblasts cells. A Kaplan-Meier survival analysis demonstrated a tendency toward a poor survival among the IPF patients with a WNT10A-positive expression compared to those with a negative expression (Hazard ratio 5.351, 95 % CI 1.703-16.82; p = 0.0041). An overexpression of WNT10A was found to be significantly predictive of an acute exacerbation of IPF (AE-IPF) (Odds ratio 13.69, 95 % CI 1.728-108.5; p = 0.013).ConclusionsWNT10A plays an important role in the pathogenesis of IPF via TGF-β activation and it may also be a sensitive predictor for the onset of an AE-IPF.

Relationship between the ratios of CD4/CD8 T-lymphocytes in the bronchoalveolar lavage fluid and lymph nodes in patients with sarcoidosis

BACKGROUND Evaluating the ratio of CD4/CD8 T-lymphocytes in the bronchoalveolar lavage fluid (BALF) is important for understanding the clinical and pathological conditions of patients with sarcoidosis. However, few studies have thus far demonstrated the usefulness of evaluating the relationship between the ratios of CD4/CD8 T-lymphocytes in the mediastinal lymph nodes and BALF. This study aimed to investigate and identify the relationships between CD4/CD8 T-lymphocyte ratio in the mediastinal lymph nodes and BALF in patients with sarcoidosis. METHODS Thirty-three consecutive patients with sarcoidosis with enlarged mediastinal and/or hilar lymphadenopathy were enrolled in the study, and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and bronchoalveolar lavage (BAL) were simultaneously performed. The CD4/CD8 T-lymphocyte ratios in the mediastinal lymph nodes and BALF were evaluated using immunohistochemistry and flow cytometry, respectively. RESULTS The interobserver variability in the CD4/CD8 ratio in the mediastinal lymph nodes as determined by immunostaining was low, and the pathological and cytological profiles of T-lymphocytes in the mediastinal and/or hilar lymph nodes and BALF were correlated in patients with sarcoidosis. Additionally, the CD4/CD8 T-lymphocyte ratios in BALF were significantly higher than those in the mediastinal lymph nodes. Importantly, non-caseating granulomas were detected at a high rate by using EBUS-TBNA. CONCLUSIONS Performing EBUS-TBNA in patients with sarcoidosis allows correct diagnosis as well as the estimation of the ratio of CD4/CD8 T-lymphocytes in BALF.

Prognostic value of serial serum KL-6 measurements in patients with idiopathic pulmonary fibrosis

BACKGROUND The prognostic significance of serial measurements of serum KL-6 levels in patients with idiopathic pulmonary fibrosis (IPF) is unclear; hence, it was assessed in this study. METHODS Medical records of 66 patients with IPF, who were not treated with pirfenidone prior to enrollment, were retrospectively reviewed for information on clinical progress, forced vital capacity (FVC), survival, and serum KL-6 levels. We assessed initial serum levels of KL-6, serial changes in serum KL-6 levels, yearly decline in FVC (ΔFVC), and the rate of decline (%ΔFVC). RESULTS Patients with increased serum KL-6 levels during follow-up had a significantly steeper decline in ΔFVC than those with no KL-6 increase (-201 vs. -50.7ml/year; p=0.0001). Patients with both initial serum KL-6 ≥1000U/ml and serial increases in serum KL-6 had the steepest decline, while those with both initial serum KL-6 <1000ml and no serial increases in KL-6 had the least decline in ΔFVC and %ΔFVC. Relative to the non-increased KL-6 group, survival in the increased KL-6 group tended to be poorer (p=0.0530). Patients with both initial serum KL-6 values <1000U/ml and no serial increase in KL-6 had more favorable prognoses than those with serial increases in KL-6 or initial serum KL-6 values ≥1000U/ml (p<0.0044). Prognosis was significantly poorer in patients with serial KL-6 changes >51.8U/ml/year than in those with serial KL-6 changes <51.8U/ml/year (p=0.0009). CONCLUSION Thus, serial serum KL-6 measurements can be useful for assessing prognosis in patients with IPF.

Possible role of anaerobes in the pathogenesis of nontuberculous mycobacterial infection

Recent advances in cultivation‐independent molecular biological modalities for detecting bacterial species have indicated that several bacterial species may play a role in the pathogenesis of certain infectious diseases. The aim of this study was to evaluate the role of bacterial flora in the pathogenesis of nontuberculous mycobacteriosis (NTM) using a bacterial floral analysis of bronchoalveolar lavage fluid (BALF) with 16S rRNA gene sequencing in patients with bronchiectasis.

A serious mediastinum abscess induced by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA): a case report and review of the literature.

A 75-year-old man with interstitial pneumonia and enlarged mediastinal lymph nodes underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). He developed a high-grade fever seven days after EBUS-TBNA was performed; laboratory and radiologic findings showed intense inflammatory reactions, with swelling of the mediastinal lymph nodes on chest computed tomography. Mediastinal lymph node abscess was diagnosed, and it worsened in spite of systemic antibacterial treatment. Surgical treatment using a median sternotomy was performed, and the cultivation of surgically obtained mediastinal lymph node abscess fluid revealed Streptococcus intermedius. Combined treatment with antibiotics and surgical treatment was effective, leading to remission.

Prevalence of sinusitis and efficacy of intranasal corticosteroid treatment on asthmatic symptoms in asthmatic patients with rhinosinusitis: a pilot study.

Prevalence of sinusitis on sinus computed tomography (CT) in asthmatic patients and efficacy of intranasal corticosteroid treatment on asthmatic symptoms in asthmatic patients with rhinosinusitis on sinus CT is unclear.

Incidence and outcomes of bepridil-induced interstitial pneumonia

BACKGROUND The incidence of bepridil-induced pulmonary toxicity, such as interstitial pneumonia, is still unknown. The aim of the present study was to evaluate the incidence of bepridil-induced pulmonary toxicity. METHODS AND RESULTS A total of 253 patients treated with bepridil between January 2009 and January 2011 were retrospectively evaluated. Eight out of the 222 evaluable patients (male/female: 5/3, age range: 64-97 years, average age: 80.5 years, median age: 81.0 years) showed bepridil-induced pulmonary toxicity. CONCLUSIONS The incidence of bepridil-induced pulmonary toxicity was 3.60% in our study population.

Protective Role of Myelocytic Nitric Oxide Synthases against Hypoxic Pulmonary Hypertension in Mice

&NA; Rationale: Nitric oxide (NO), synthesized by NOSs (NO synthases), plays a role in the development of pulmonary hypertension (PH). However, the role of NO/NOSs in bone marrow (BM) cells in PH remains elusive. Objectives: To determine the role of NOSs in BM cells in PH. Methods: Experiments were performed on 36 patients with idiopathic pulmonary fibrosis and on wild‐type (WT), nNOS (neuronal NOS)−/−, iNOS (inducible NOS)−/−, eNOS (endothelial NOS)−/−, and n/i/eNOSs−/− mice. Measurements and Main Results: In the patients, there was a significant correlation between higher pulmonary artery systolic pressure and lower nitrite plus nitrate levels in the BAL fluid. In the mice, hypoxia‐induced PH deteriorated significantly in the n/i/eNOSs−/− genotype and, to a lesser extent, in the eNOS−/− genotype as compared with the WT genotype. In the n/i/eNOSs−/− genotype exposed to hypoxia, the number of circulating BM‐derived vascular smooth muscle progenitor cells was significantly larger, and transplantation of green fluorescent protein‐transgenic BM cells revealed the contribution of BM cells to pulmonary vascular remodeling. Importantly, n/i/eNOSs−/−‐BM transplantation significantly aggravated hypoxia‐induced PH in the WT genotype, and WT‐BM transplantation significantly ameliorated hypoxia‐induced PH in the n/i/eNOSs−/− genotype. A total of 69 and 49 mRNAs related to immunity and inflammation, respectively, were significantly upregulated in the lungs of WT genotype mice transplanted with n/i/eNOSs−/−‐BM compared with those with WT‐BM, suggesting the involvement of immune and inflammatory mechanisms in the exacerbation of hypoxia‐induced PH caused by n/i/eNOSs−/−‐BM transplantation. Conclusions: These results demonstrate that myelocytic n/i/eNOSs play an important protective role in the pathogenesis of PH.