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Hideki Kusagaya,
Yutaro Nakamura, Masato Kono,
Yusuke Kaida,
Shigeki Kuroishi,
Noriyuki Enomoto,
Tomoyuki Fujisawa,
Naoki Koshimizu,
Koshi Yokomura,
Naoki Inui,
Takafumi Suda,
Thomas V Colby,
Kingo Chida
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ABSTRACT: BACKGROUND: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a recently reported group of disorders characterized by fibrotic thickening of the pleural and subpleural parenchyma predominantly in the upper lobes. We report five Japanese cases fulfilling the criteria of IPPFE and address whether it should be considered a separate clinicopathologic entity. And this study was an attempt to identify features in common between IPPFE and previously described idiopathic upper lobe fibrosis (IPUF), allowing IPPFE to be considered as a distinct entity in our Japanese series. METHODS: Five consecutive cases of idiopathic interstitial lung disease confirmed as IPPFE by surgical lung biopsy were studied. RESULTS: There were four males and one female, aged 70+/-2.76 yr. No associated disorder or presumed cause was found in any case. Lung function tests found a restrictive ventilatory defect (4/5) and/or impairment of DLco (4/5). Chest X-ray showed marked apical pleural thickening in all cases. Computed tomography of the chest in all cases mainly showed intense pleural thickening and volume loss associated with evidence of fibrosis, predominantly in the upper lobes. In all cases in this study, markedly thickened visceral pleura and prominent subpleural fibrosis characterized by both elastic tissue and dense collagen were clearly shown. All cases were alive at the last follow-up, 17.6+/-13.59 months after diagnosis; however, all had deteriorated both clinically and radiologically. CONCLUSIONS: IPPFE deserves to be defined as a separate, original clinicopathologic entity owing to its uniformity and IPPFE has some features in common with previously described idiopathic upper lobe fibrosis (IPUF). Our limited experience with a cohort of 5 subjects suggests that IPPFE can be rapidly progressive.
BMC Pulmonary Medicine 12/2012; 12(1):72. · 1.33 Impact Factor
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Yutaro Nakamura,
Takafumi Suda,
Yusuke Kaida, Masato Kono,
Hironao Hozumi,
Dai Hashimoto,
Noriyuki Enomoto,
Tomoyuki Fujisawa,
Naoki Inui,
Shiro Imokawa,
Kazumasa Yasuda,
Toshihiro Shirai,
Hideki Suganuma,
Satoru Morita,
Hiroshi Hayakawa,
Yasuo Takehara,
Thomas V Colby,
Kingo Chida
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ABSTRACT: To investigate the prognostic significance of histopathological characteristics in patients with biopsy-proven rheumatoid lung disease (RLD).
Retrospective analysis was conducted on samples from 54 RLD patients who underwent surgical lung biopsies (SLBs) at Hamamatsu University Hospital and affiliated hospitals between 1980 and 2009. The overall survival rate, the spectrum of histopathological diagnosis and their associated prognostic significance were investigated.
The study group consisted of 30 men and 24 women with a median age of 60.3 years. Histopathological analysis revealed the following: usual interstitial pneumonia (UIP), 15 cases; nonspecific interstitial pneumonia/fibrosis, 16 cases; organizing pneumonia, 4 cases; unclassifiable, 2 cases; desquamative interstitial pneumonia, 1 case; and bronchiolar disease, 16 cases. In survival outcome, 10 yr survival rate was 76.6%. Patients with UIP had significantly worse prognosis than those with non-UIP (RLD cases except those with UIP) (p = 0.0452).
RLD includes several histopathological groups. Patients with UIP have worse survival than those with other types of RLD. Histopathological diagnosis may have a major impact on prognostication in patients with RLD.
Respiratory medicine 05/2012; 106(8):1164-9. · 2.33 Impact Factor
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ABSTRACT: The development of effective vaccine strategies for intracellular bacteria, including tuberculosis, is one of the major frontiers of medical research. Our previous studies showed that dendritic cell (DC) vaccine is a promising approach for eliciting protective immunity against intracellular bacteria. However, it has been reported that standard fully mature DCs show reduced ability to produce IL-12p70 upon subsequent interaction with antigen (Ag)-specific T cells, limiting their in vivo performance for vaccines. Recently, we found that such "DC exhaustion" could be prevented by the presence of IL-4 and IFN-γ during the maturation of mouse DCs (type-1 polarization), resulting in improved induction of anti-tumor immunity in cancer. Here we show that such type-1 polarized DCs promote dramatic enhancement of protective immunity against an intracellular bacterium, Listeria monocytogenes. Murine bone marrow-derived DCs were cultured and matured with LPS, IL-4 and IFN-γ (type-1 polarized DCs), and with LPS alone (non-polarized DCs). DCs were loaded with listeriolysin O (LLO) 91-99, H2-K(d)-restricted epitope of L. monocytogenes, and were injected into naïve BALB/c mice intravenously. Type-1 polarized DCs produced significantly higher levels of IL-12p70 than non-polarized DCs in vitro, and this vaccine strongly enhanced LLO 91-99-specific CD8(+) T cells exhibiting epitope-specific cytotoxic activity and IFN-γ production, leading to significant induction of protective immunity against L. monocytogenes. Type-1 polarized DCs are potential candidates for enhancing protective immunity in the design of effective vaccination strategies against intracellular bacteria.
Vaccine 02/2012; 30(16):2633-9. · 3.77 Impact Factor
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Masato Kono,
Yutaro Nakamura,
Takafumi Suda,
Masato Kato,
Yusuke Kaida,
Dai Hashimoto,
Naoki Inui,
Etsuko Hamada,
Osamu Miyazaki,
Syunsuke Kurashita,
Isamu Fukamachi,
Koki Endo,
Poh-Sing Ng,
Kazuhiko Takehara,
Hirotoshi Nakamura,
Masato Maekawa,
Kingo Chida
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ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal pulmonary fibrotic disease and useful biomarkers are required to diagnose and predict disease activity. CCN2 (connective tissue growth factor; CTGF) has been reported as one of the key profibrotic factors associated with transforming growth factor-β (TGF-β), and its assay has potential as a non-invasive measure in various fibrotic diseases. Recently, we developed a new subtraction method for determination of plasma CCN2 levels. We examined the utility of plasma CCN2 levels as a surrogate marker in IPF.
Plasma CCN2 levels were calculated in 33 patients with IPF, 14 patients with non-IPF idiopathic interstitial pneumonias (IIPs) and 101 healthy volunteers by sandwich enzyme-linked immunosorbent assay (ELISA) using specific monoclonal antibodies for two distinct epitopes of human CCN2. We evaluated the utility of plasma CCN2 levels by comparison with clinical parameters.
Plasma CCN2 levels were significantly higher in patients with IPF than in those with non-IPF IIPs and healthy volunteers. Importantly, plasma CCN2 levels showed significantly negative correlation with 6-month change of forced vital capacity (FVC) in patients with IPF.
Plasma CCN2 is a potential biomarker for IPF.
Clinica chimica acta; international journal of clinical chemistry 08/2011; 412(23-24):2211-5. · 2.54 Impact Factor
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Masato Kono,
Takafumi Suda,
Noriyuki Enomoto,
Yutaro Nakamura,
Yusuke Kaida,
Dai Hashimoto,
Naoki Inui,
Tomoaki Mizuguchi,
Akihiko Kato,
Toshihiro Shirai,
Hirotoshi Nakamura,
Kingo Chida
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ABSTRACT: Recently, the potential therapeutic effect of direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) has been reported for acute exacerbation of interstitial pneumonia (AE-IP), a highly morbid clinical event; however, there is no consensus on the appropriate procedure for PMX-DHP. We examined the appropriate perfusion duration of PMX-DHP for AE-IP.
AE-IP patients receiving PMX-DHP were divided into two groups: short-duration group (≤6 h) (n = 5) and long-duration group (12 h) (n = 12).
ThePaO(2)/FiO(2) (P/F) ratio increased immediately after PMX-DHP in the two groups. In the long-duration group, the P/F ratio continued to increase over the following 7 days, while, in the short-duration group, the P/F ratio declined again 3 days after therapy. The survival rate 30 days after PMX-DHP was significantly higher in the long-duration group than in the short-duration group.
A long perfusion duration of PMX-DHP is more efficacious for AE-IP than a short perfusion duration.
Blood Purification 03/2011; 32(2):75-81. · 2.10 Impact Factor
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Takafumi Suda, Masato Kono,
Yutaro Nakamura,
Noriyuki Enomoto,
Yusuke Kaida,
Tomoyuki Fujisawa,
Shiro Imokawa,
Kazumasa Yasuda,
Hideo Hashizume,
Koushi Yokomura,
Mikio Toyoshima,
Naoki Koshimizu,
Hideki Suganuma,
Toshihiro Shirai,
Dai Hashimoto,
Naoki Inui,
Thomas V Colby,
Kingo Chida
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ABSTRACT: Although idiopathic nonspecific interstitial pneumonia (NSIP) was initially identified as a provisional diagnosis, the 2008 American Thoracic Society Project concluded that idiopathic NSIP is a distinct form of idiopathic interstitial pneumonia. However, an association between idiopathic NSIP and autoimmune diseases still attracts interest. In this context, a recent study proposed an intriguing concept that idiopathic NSIP is the pulmonary manifestation of undifferentiated connective tissue disease (UCTD). However, this has not been confirmed in a large number of patients with idiopathic NSIP. The present study was conducted to investigate the proportion and characteristics of patients with idiopathic NSIP who meet the criteria for UCTD.
We reviewed 47 consecutive patients with idiopathic NSIP and examined whether they met prespecified criteria for UCTD. Furthermore, we compared the clinical characteristics between patients fulfilling the UCTD criteria (UCTD-NSIP) and those not meeting them (Non-UCTD-NSIP).
Of 47 patients with idiopathic NSIP, 22 (47%) met the UCTD criteria. Common symptoms associated with connective tissue diseases (CTDs) were skin change (50%) and Raynaud's phenomenon (41%) in UCTD-NSIP. UCTD-NSIP showed a female predominance and significantly higher percentages of lymphocytes with a lower CD4/CD8 ratio in bronchoalveolar lavage than Non-UCTD-NSIP. Interestingly, UCTD-NSIP had a significantly better survival than Non-UCTD-NSIP.
Idiopathic NSIP included subjects who fulfilled the UCTD criteria, and these subjects had different clinical characteristics with significantly better outcome than those who did not meet the criteria. These data suggest that a part, but not all, of patients with idiopathic NSIP show CTD-like features with a distinct prognosis.
Respiratory medicine 10/2010; 104(10):1527-34. · 2.33 Impact Factor
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ABSTRACT: A 49-year-old-man was admitted to our hospital because of cough, wheezing, and dyspnea. Chest CT showed bilateral bronchocentric nodules and increased bronchial thickness. And he was given a diagnosis of bronchial asthma. However, another small airway disease, such as diffuse panbronchiolitis (DPB) was also suspected, and surgical lung biopsy was performed. The biopsy specimens showed a prominent peribronchial lymphoplasmacytic and eosinophilic infiltration with IgG4-positive plasma cells. IgG4-positive plasma cells may play a role in the pathogenesis of bronchiolar diseases associated with allergic airway inflammation.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 04/2010; 48(4):317-21.
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ABSTRACT: A case of IgG4-related lung disease in a worker who had been exposed to asbestos is described. The patient had nocturnal cough and wheeze that responded to inhaled corticosteroid, and the radioallergosorbent test was positive against common allergens, suggesting an association with atopic asthma. IgE elevation is reported in asbestos-exposed workers, and asbestos exposure may cause atopic conditions. Predominance of Th2 cytokines and up-regulation of regulatory T lymphocytes have been reported in IgG4-related disease. IgG4-related disease may occur from hypersensitivity of the regulatory immune system to atopic conditions. Asbestos exposure may be a causal factor of IgG4-related disease.
Internal Medicine 01/2010; 49(12):1175-8. · 0.94 Impact Factor
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ABSTRACT: Interstitial pneumonia in a 54-year-old woman was diagnosed in April 2007, without symptoms. She was admitted to our hospital in February 2009 because chest radiography showed gradual worsening. On physical examination, she had fine crackles on chest auscultation and "mechanic's hands", without arthritis, myopathy, or Reynaud disease. On laboratory tests, antinuclear antibody (speckled and cytoplasmic pattern) and anti SS-A antibody were positive. Chest CT showed ground-glass opacities in both lower lobes with volume loss and she had a restrictive disorder on a pulmonary function test. Bronchoalveolar lavage was within almost normal limits. For a definitive diagnosis, video associated thracoscopic surgery was performed. The histopathological findings showed a fibrotic nonspecific interstitial (f-NSIP) pattern. Corticosteroid therapy (prednisolone, initially 40 mg/day) was started, and the chest radiography improved. Later, an RNA immunoprecipitation test was positive for anti-signal recognition particle (SRP) antibody. This is a rare case of interstitial pneumonia with anti-SRP antibody without myopathy.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 01/2010; 48(1):92-7.
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ABSTRACT: A 53-year-old man had received various chemotherapy and steroid treatments for malignant thymoma. He had demonstrated persistent fever since the beginning of January 2006, and chest radiograph showed consolidation in the left middle lung fields. Bacterial pneumonia was suspected, but antibiotics were not effective. He was referred and admitted to our hospital on January 16. Chest radiograph and CT scan on admission showed diffuse ground-glass opacities, consolidation with cavity, and cystic changes. Pneumocystis jiroveci Pneumonia was diagnosed by examination of alveolar lavage. This patient was regarded as immunodeficient because of steroid treatment, low counts of CD4-positive lymphocytes, and the complication of hypogammagloblinemia. We reported this case of a non-HIV patient with atypical images demonstrating Pneumocystis jiroveci pneumonia.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 05/2008; 46(4):297-301.
