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Dive into the research topics where Masayuki Hojo is active.

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Featured researches published by Masayuki Hojo.


American Journal of Respiratory and Critical Care Medicine | 2010

Inhaled granulocyte/macrophage-colony stimulating factor as therapy for pulmonary alveolar proteinosis.

Ryushi Tazawa; Bruce C. Trapnell; Yoshikazu Inoue; Toru Arai; Toshinori Takada; Yasuyuki Nasuhara; Nobuyuki Hizawa; Yasunori Kasahara; Koichiro Tatsumi; Masayuki Hojo; Haruyuki Ishii; Masanori Yokoba; Naohiko Tanaka; Etsuro Yamaguchi; Ryosuke Eda; Yoshiko Tsuchihashi; Konosuke Morimoto; Masanori Akira; Masaki Terada; Junji Otsuka; Masahito Ebina; Chinatsu Kaneko; Toshihiro Nukiwa; Jeffrey P. Krischer; Kohei Akazawa; Koh Nakata

RATIONALE Inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) is a promising therapy for pulmonary alveolar proteinosis (PAP) but has not been adequately studied. OBJECTIVES To evaluate safety and efficacy of inhaled GM-CSF in patients with unremitting or progressive PAP. METHODS We conducted a national, multicenter, self-controlled, phase II trial at nine pulmonary centers throughout Japan. Patients who had lung biopsy or cytology findings diagnostic of PAP, an elevated serum GM-CSF antibody level, and a Pa(O(2)) of less than 75 mm Hg entered a 12-week observation period. Those who improved (i.e., alveolar-arterial oxygen difference [A-aDO(2)] decreased by 10 mm Hg) during observation were excluded. The rest entered sequential periods of high-dose therapy (250 microg Days 1-8, none Days 9-14; x six cycles; 12 wk); low-dose therapy (125 microg Days 1-4, none Days 5-14; x six cycles; 12 wk), and follow-up (52 wk). MEASUREMENTS AND MAIN RESULTS Fifty patients with PAP were enrolled in the study. During observation, nine improved and two withdrew; all of these were excluded. Of 35 patients completing the high- and low-dose therapy, 24 improved, resulting in an overall response rate of 62% (24/39; intention-to-treat analysis) and reduction in A-aDO(2) of 12.3 mm Hg (95% confidence interval, 8.4-16.2; n = 35, P < 0.001). No serious adverse events occurred, and serum GM-CSF autoantibody levels were unchanged. A treatment-emergent correlation occurred between A-aDO(2) and diffusing capacity of the lung, and high-resolution CT revealed improvement of ground-glass opacity. Twenty-nine of 35 patients remained stable without further therapy for 1 year. CONCLUSIONS Inhaled GM-CSF therapy is safe, effective, and provides a sustained therapeutic effect in autoimmune PAP. Clinical trial registered with www.controlled-trials.com/isrctn (ISRCTN18931678), www.jmacct.med.or.jp/english (JMA-IIA00013).


European Respiratory Journal | 2011

Clinical features of secondary pulmonary alveolar proteinosis: pre-mortem cases in Japan

Haruyuki Ishii; Ryushi Tazawa; Chinatsu Kaneko; Takeshi Saraya; Yoshikazu Inoue; Emi Hamano; Yoshihito Kogure; Keisuke Tomii; Masaki Terada; Toshinori Takada; Masayuki Hojo; Aya Nishida; Toshio Ichiwata; Bruce C. Trapnell; Hajime Goto; Koh Nakata

To the Editors: Pulmonary alveolar proteinosis (PAP) is a rare syndrome that predominantly affects the lungs, and is characterised by the accumulation of surfactant lipids and proteins in the alveoli and terminal airways 1. In 1999, we published findings that high levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) neutralising autoantibodies were detected specifically in patients with idiopathic PAP 2. Recently, as a result of the excellent sensitivity and specificity of GM-CSF autoantibody assays in identifying this form of PAP 3, it has been proposed that the nomenclature for this condition should be changed to “autoimmune PAP” rather than “idiopathic PAP” 4. Secondary or hereditary PAP is not associated with GM-CSF autoantibodies but develops as a consequence of a separate underlying disorder or genetic background 5. Recently, we demonstrated that the characteristic high-resolution computed tomography (HRCT) findings in secondary PAP are distinct from those in autoimmune PAP 6. However, physicians may not suspect secondary PAP, even when encountering unexplained pulmonary opacities on chest radiograph or computed tomography in patients with pre-existing haematological or infectious diseases, since there is little information available on the clinical features. Here, we outline the clinical features of adult-onset secondary PAP based on our database of 40 pre-mortem cases in which serum GM-CSF autoantibodies were negative, and compare them with other cases in the literature. A total of 404 patients with pre-mortem cytologically or pathologically proven PAP were registered in our study group between 1999 and 2009. We obtained consent from all treating physicians for each identified case according to the guidelines for epidemiological studies from the Ministry of Health, Labour and Welfare 7, and all clinical data were de-identified. 360 (89%) cases were positive for serum GM-CSF autoantibody. The clinical features of 223 of the cases were previously published as …


Chest | 2014

Duration of Benefit in Patients With Autoimmune Pulmonary Alveolar Proteinosis After Inhaled Granulocyte-Macrophage Colony-Stimulating Factor Therapy

Ryushi Tazawa; Yoshikazu Inoue; Toru Arai; Toshinori Takada; Yasunori Kasahara; Masayuki Hojo; Shinya Ohkouchi; Yoshiko Tsuchihashi; Masanori Yokoba; Ryosuke Eda; Hideaki Nakayama; Haruyuki Ishii; Takahito Nei; Konosuke Morimoto; Yasuyuki Nasuhara; Masahito Ebina; Masanori Akira; Toshio Ichiwata; Koichiro Tatsumi; Etsuro Yamaguchi; Koh Nakata

BACKGROUND Treatment of autoimmune pulmonary alveolar proteinosis (aPAP) by subcutaneous injection or inhaled therapy of granulocyte-macrophage colony-stimulating factor (GM-CSF) has been demonstrated to be safe and efficacious in several reports. However, some reports of subcutaneous injection described transient benefit in most instances. The durability of response to inhaled GM-CSF therapy is not well characterized. METHODS To elucidate the risk factors for recurrence of aPAP after GM-CSF inhalation, 35 patients were followed up, monitoring for the use of any additional PAP therapies and disease severity score every 6 months. Physiologic, serologic, and radiologic features of the patients were analyzed for the findings of 30-month observation after the end of inhalation therapy. RESULTS During the observation, 23 patients remained free from additional treatments, and twelve patients required additional treatments. There were no significant differences in age, sex, symptoms, oxygenation indexes, or anti-GM-CSF antibody levels at the beginning of treatment between the two groups. Baseline vital capacity (% predicted, %VC) were higher among those who required additional treatment (P<.01). Those patients not requiring additional treatment maintained the improved disease severity score initially achieved. A significant difference in the time to additional treatment between the high %VC group (%VC≥80.5) and the low %VC group was seen by a Kaplan-Meier analysis and a log-rank test (P<.0005). CONCLUSIONS These results demonstrate that inhaled GM-CSF therapy sustained remission of aPAP in more than one-half of cases, and baseline %VC might be a prognostic factor for disease recurrence. TRIAL REGISTRY ISRCTN Register and JMACCT Clinical Trial Registry; No.: ISRCTN18931678 and JMAIIA00013; URL: http://www.isrctn.org and http://www.jmacct.med.or.jp.


BMC Pulmonary Medicine | 2014

Secondary pulmonary alveolar proteinosis complicating myelodysplastic syndrome results in worsening of prognosis: a retrospective cohort study in Japan

Haruyuki Ishii; John F. Seymour; Ryushi Tazawa; Yoshikazu Inoue; Naoyuki Uchida; Aya Nishida; Yoshihito Kogure; Takeshi Saraya; Keisuke Tomii; Toshinori Takada; Yuko Itoh; Masayuki Hojo; Toshio Ichiwata; Hajime Goto; Koh Nakata

BackgroundSecondary pulmonary alveolar proteinosis (sPAP) is a very rare lung disorder comprising approximately 10% of cases of acquired PAP. Hematological disorders are the most common underlying conditions of sPAP, of which 74% of cases demonstrate myelodysplastic syndrome (MDS). However, the impact of sPAP on the prognosis of underlying MDS remains unknown. The purpose of this study was to evaluate whether development of sPAP worsens the prognosis of MDS.MethodsThirty-one cases of sPAP and underlying MDS were retrospectively classified into mild and severe cases consisting of very low-/low-risk groups and intermediate-/high-/very high-risk groups at the time of diagnosis of MDS, according to the prognostic scoring system based on the World Health Organization classification. Next, we compared the characteristics, disease duration, cumulative survival, and prognostic factors of the groups.ResultsIn contrast to previous reports on the prognosis of MDS, we found that the cumulative survival probability for mild MDS patients was similar to that in severe MDS patients. This is likely due to the poor prognosis of patients with mild MDS, whose 2-year survival rate was 46.2%. Notably, 75% and 62.5% of patients who died developed fatal infectious diseases and exacerbation of PAP, respectively, suggesting that the progression of PAP per se and/or PAP-associated infection contributed to poor prognosis. The use of corticosteroid therapy and a diffusing capacity of the lung for carbon monoxide of less than 44% were predictive of poor prognosis.ConclusionDevelopment of sPAP during the course of MDS may be an important adverse risk factor in prognosis of patients with mild MDS.


Respiratory Medicine | 2012

Direct evidence that GM-CSF inhalation improves lung clearance in pulmonary alveolar proteinosis

Kazumasa Ohashi; Atsuyasu Sato; Toshinori Takada; Toru Arai; Takahito Nei; Yasunori Kasahara; Natsuki Motoi; Masayuki Hojo; Shinya Urano; Haruyuki Ishii; Masanori Yokoba; Ryosuke Eda; Hideaki Nakayama; Yasuyuki Nasuhara; Yoshiko Tsuchihashi; Chinatsu Kaneko; Hiroko Kanazawa; Masahito Ebina; Etsuro Yamaguchi; Jacqueline Kirchner; Yoshikazu Inoue; Koh Nakata; Ryushi Tazawa

BACKGROUND Autoimmune pulmonary alveolar proteinosis (aPAP) is caused by granulocyte/macrophage-colony stimulating factor (GM-CSF) autoantibodies in the lung. Previously, we reported that GM-CSF inhalation therapy improved alveolar-arterial oxygen difference and serum biomarkers of disease severity in these patients. It is plausible that inhaled GM-CSF improves the dysfunction of alveolar macrophages and promotes the clearance of the surfactant. However, effect of the therapy on components in bronchoalveolar lavage fluid (BALF) remains unclear. OBJECTIVES To figure out changes in surfactant clearance during GM-CSF inhalation therapy. METHODS We performed retrospective analyses of BALF obtained under a standardized protocol from the same bronchus in each of 19 aPAP patients before and after GM-CSF inhalation therapy (ISRCTN18931678, JMA-IIA00013; total dose 10.5-21 mg, duration 12-24 weeks). For evaluation, the participants were divided into two groups, high responders with improvement in alveolar-arterial oxygen difference ≥13 mmHg (n = 10) and low responders with that < 13 mmHg (n = 9). RESULTS Counts of both total cells and alveolar macrophages in BALF did not increase during the therapy. However, total protein and surfactant protein-A (SP-A) were significantly decreased in high responders, but not in low responders, suggesting that clearance of surfactant materials is correlated with the efficacy of the therapy. Among 94 biomarkers screened in bronchoalveolar lavage fluid, we found that the concentration of interleukin-17 and cancer antigen-125 were significantly increased after GM-CSF inhalation treatment. CONCLUSIONS GM-CSF inhalation decreased the concentration of total protein and SP-A in BALF, and increase interleukin-17 and cancer antigen-125 in improved lung of autoimmune pulmonary alveolar proteinosis.


European Respiratory Journal | 2012

Reduced GM-CSF autoantibody in improved lung of autoimmune pulmonary alveolar proteinosis

Kazumasa Ohashi; Atsuyasu Sato; Toshinori Takada; Toru Arai; Yasunori Kasahara; Masayuki Hojo; Takahito Nei; Hideaki Nakayama; Natsuki Motoi; Shinya Urano; Ryosuke Eda; Masanori Yokoba; Yoshiko Tsuchihashi; Yasuyuki Nasuhara; Haruyuki Ishii; Masahito Ebina; Etsuro Yamaguchi; Yoshikazu Inoue; Koh Nakata; Ryushi Tazawa

To the Editors: Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterised by excessive accumulation of surfactant materials within alveolar spaces [1]. Patients with autoimmune PAP (aPAP) present a high level of granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (GM-Ab) in the serum as well as in bronchoalveolar lavage fluid (BALF) [2]. GM-Ab neutralise the biological activity of GM-CSF in the lung [3], impairing terminal differentiation of alveolar macrophages and macrophage-mediated pulmonary surfactant clearance [4]. Based on the aetiology, clinical trials of exogenous GM-CSF supplementation have been carried out by a number of physicians with variable response rates ranging from 40 to 62% [5–9]. Previously, we reported that in three patients who received a pilot GM-CSF inhalation therapy, oxygenation was improved and the concentration of GM-Ab in BALF was reduced [7]. Bonfield et al . [8] also reported that the serum titre of GM-Ab was reduced during successful treatment of aPAP with subcutaneously injected GM-CSF. However, our recent phase II trial of GM-CSF inhalation involving 35 patients revealed that serum levels of GM-Ab remained unchanged throughout the therapy, suggesting that GM-CSF inhalation therapy did not affect the production of GM-Ab [9]. Thus, the effect of exogenous GM-CSF administration on GM-Ab levels in the serum remains controversial. This discrepancy may be due to differences in the route of administration and/or the dose of GM-CSF. Aerosolised GM-CSF reaches the lower respiratory tract and may stimulate immature alveolar macrophages directly to promote terminal differentiation and improve the local clearance of the accumulated surfactant and GM-Ab, although it does not affect the production of systemic GM-Ab. To test this hypothesis, …


Annals of the American Thoracic Society | 2017

A Semiquantitative Computed Tomographic Grading System for Evaluating Therapeutic Response in Pulmonary Alveolar Proteinosis

Sayoko Tokura; Masanori Akira; Tomohisa Okuma; Ryushi Tazawa; Toru Arai; Chikatoshi Sugimoto; Akiko Matsumuro; Masaki Hirose; Toshinori Takada; Koh Nakata; Haruyuki Ishii; Yasunori Kasahara; Masayuki Hojo; Shinya Ohkouchi; Yoshiko Tsuchihashi; Masanori Yokoba; Ryosuke Eda; Hideaki Nakayama; Takahito Nei; Konosuke Morimoto; Yasuyuki Nasuhara; Masahito Ebina; Toshio Ichiwata; Koichiro Tatsumi; Etsuro Yamaguchi; Yoshikazu Inoue

Rationale: A useful semiquantitative method of using computed tomographic (CT) images to evaluate therapeutic response in pulmonary alveolar proteinosis (PAP) has not been established, although the extent score or grading score of ground‐glass opacities has been used. Objectives: The purpose of this study was to establish a semiquantitative method for evaluating therapeutic response in PAP. Methods: CT scans were obtained within 1 month before and after therapy from 32 patients with PAP who participated in a multicenter phase II trial of granulocyte‐macrophage colony‐stimulating factor inhalation therapy. The scans were evaluated by two chest radiologists independently. Increased parenchymal opacity was evaluated on the basis of its intensity and extent (CT grade), and the severity scores were compared with CT scores based on the extent alone (CT extent), as well as on the basis of physiological and serological results. Results: CT grade score and CT extent score had significant correlation with diffusing capacity of the lung for carbon monoxide percent predicted (%DlCO), PaO2, VC percent predicted (%VC), Krebs von den Lungen (KL)‐6, and surfactant protein D. The change in CT grade score between pre‐ and post‐treatment examinations (&Dgr;CT grade) correlated better with difference of PaO2 between pre‐ and post‐treatment examinations (&Dgr;PaO2) than &Dgr;CT extent (difference of CT extent score between pre‐ and post‐treatment examinations). In univariate analysis, &Dgr;CT grade, &Dgr;CT extent, &Dgr;KL‐6, &Dgr;%DlCO, &Dgr;%VC, and change in surfactant protein D correlated significantly with &Dgr;PaO2. In multivariate analysis, &Dgr;CT grade and &Dgr;KL‐6 correlated more closely with &Dgr;PaO2. Conclusions: Although a number of CT variables were collected, the currently proposed grading system that correlates well with PaO2 should be viewed as a retrospective scoring system that needs future validation with another PAP cohort.


Chest | 2009

Comparative Study of High-Resolution CT Findings Between Autoimmune and Secondary Pulmonary Alveolar Proteinosis

Haruyuki Ishii; Bruce C. Trapnell; Ryushi Tazawa; Yoshikazu Inoue; Masanori Akira; Yoshihito Kogure; Keisuke Tomii; Toshinori Takada; Masayuki Hojo; Toshio Ichiwata; Hajime Goto; Koh Nakata


American Journal of Respiratory and Critical Care Medicine | 1998

Involvement of α -4 Integrins in Allergic Airway Responses and Mast Cell Degranulation In Vivo

Masayuki Hojo; Karim Maghni; Thomas B. Issekutz; James G. Martin


American Journal of Respiratory and Critical Care Medicine | 1998

CD4 + T Cells Can Induce Airway Hyperresponsiveness to Allergen Challenge in the Brown Norway Rat

Hideyasu Mishima; Masayuki Hojo; Azuma Watanabe; Qutayba Hamid; James G. Martin

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Yoshikazu Inoue

Cincinnati Children's Hospital Medical Center

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