M Fujimura

Kanazawa University, Kanazawa, Ishikawa, Japan

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Publications (508)1152.84 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: ABSTRACT Aims: Inflammatory mediators are involved in the pathophysiology of neutrophilic bronchial disorders presenting with chronic productive cough. Accumulating evidence indicates that prostanoids are key elements in the pathophysiology of these disorders. However, little is known about the role of prostacyclin in neutrophilic bronchial inflammation. Methods: The effect of beraprost, a chemically and biologically stable analog of prostacyclin, on cough response to inhaled capsaicin was examined in 14 patients with chronic bronchitis, a neutrophilic bronchial disorder, in a randomized, placebo-controlled crossover study. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of the airway cough reflex sensitivity. Results: After a 2-week treatment with beraprost (80 μg twice a day orally), the cough threshold was significantly (P < .05) decreased as compared with placebo [12.2 (geometric standard error of the mean [GSEM] 1.5) μM vs. 24.4 (GSEM 1.3)]. Conclusions: These findings indicate that prostacyclin is involved in the pathophysiology of cough reflex sensitivity in patients with chronic bronchitis, a frequently encountered neutrophilic bronchial disorder presenting with chronic productive cough.
    Experimental Lung Research 10/2014; · 1.47 Impact Factor
  • Allergology international : official journal of the Japanese Society of Allergology. 08/2014;
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    ABSTRACT: Asian dust, known as kosa in Japanese, is a major public health concern. In this panel study, we evaluated the effects of exposure to kosa on daily cough occurrence. The study subjects were 86 patients being treated for asthma, cough variant asthma, or atopic cough in Kanazawa University Hospital from January 2011 to June 2011. Daily mean concentrations of kosa and spherical particles were obtained from light detection and ranging (LIDAR) measurements, and were categorized from Grade 1 (0 μg/m3) to 5 (over 100 μg/m3). The association between kosa and cough was analyzed by logistic regression with a generalized estimating equation. Kosa effects on cough were seen for all Grades with potential time lag effect. Particularly at Lag 0 (the day of exposure), a dose-response relationship was observed: the odds ratios for Grades 2, 3, 4, and 5 above the referent (Grade 1) were 1.111 (95% confidence interval (CI): 0.995-1.239), 1.171 (95% CI: 1.006-1.363), 1.357 (95% CI: 1.029-1.788), and 1.414 (95% CI: 0.983-2.036), respectively. Among the patients without asthma, the association was higher: the odds ratios for Grades 2, 3, 4 and 5 were 1.223 (95% CI: 0.999-1.497), 1.309 (95% CI: 0.987-1.737), 1.738 (95% CI: 1.029-2.935) and 2.403 (95% CI: 1.158-4.985), respectively. These associations remained after adjusting for the concentration of spherical particles or particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5). Our findings demonstrate that kosa is an environmental factor which induces cough in a dose-response relationship.
  • Allergology international : official journal of the Japanese Society of Allergology. 06/2014;
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    ABSTRACT: Increasing number of patients with advanced non-small cell lung cancer are receiving outpatient maintenance chemotherapy. It is very important to maintain these patients' quality of life(QOL). Pemetrexed has been reported to be an effective maintenance chemotherapy. However, its effects on the QOL of patients with non-small cell lung cancer who are undergoing outpatient maintenance chemotherapy are unknown; therefore, we conducted this study. To investigate factors that influence the QOL of these patients, we provided a QOL questionnaire,"The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs(QOL-ACD)"to 7 patients with non-small cell lung cancer. The medical factors related to the overall QOL scores, as well as other categories indicating"activity","physical condition","psychological condition","social relationship", and"face scale", were analyzed. No significant reductions in any of the factors were observed in this study.
    Gan to kagaku ryoho. Cancer & chemotherapy 06/2014; 41(6):761-764.
  • Allergology International 04/2014;
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    ABSTRACT: In steroid-naive patients with asthma, several gene variants are associated with a short-term response to inhaled corticosteroid (ICS) treatment; this has mostly been observed in Caucasians. However, not many studies have been conducted for other ethnicities. Here, we aimed to determine the relationship between the annual decline in forced expiratory flow volume in one second (FEV1 ) and the variant of the glucocorticoid-induced transcript 1 gene (GLCCI1) in Japanese patients with asthma receiving long-term ICS treatment, taking into account the effect of high serum periostin levels, a known association factor of pulmonary function decline and a marker of refractory eosinophilic/Th2 inflammation. In this study, 224 patients with asthma receiving ICS treatment for at least 4 years were enrolled. The effects of single-nucleotide polymorphisms (SNPs) in GLCCI1, stress-induced phosphoprotein 1 (STIP1), and T gene on the decline in FEV1 of 30 ml/year or greater were determined. Besides the known contributing factors, that is, the most intensive treatment step, ex-smoking, and high serum periostin levels (≥95 ng/ml), the GG genotype of GLCCI1 rs37973, and not other SNPs, was independently associated with a decline in FEV1 of 30 ml/year or greater. When patients were stratified according to their serum periostin levels, the GG genotype of rs37973 was significantly associated with blood eosinophilia (≥250/μl) in the high serum periostin group. A GLCCI1 variant is a risk factor of pulmonary function decline in Japanese patients with asthma receiving long-term ICS treatment. Thus, GLCCI1 may be associated with response to ICS across ethnicities.
    Allergy 03/2014; · 5.88 Impact Factor
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    ABSTRACT: With regard to fungal colonization and fungal sensitization, the goals of fungus-associated asthma management are as follows: 1) to survey fungi colonizing the airways of patients repeatedly; 2) to evaluate the tendency of the colonizing fungi to sensitize patients and the influence on clinical manifestations of asthma; 3) to follow disease development to allergic bronchopulmonary mycosis or sinobronchial allergic mycosis; and 4) to determine whether fungal eradication from the airway of patients is beneficial from the viewpoints of future risk factors. Recent developments in molecular biological analyses have facilitated the identification of basidiomycetous fungi that were not previously thought to be of concern in fungal allergy. The total control of fungus-associated asthma will be accomplished by environmental management established from the viewpoint of both the ecology and life cycle of the responsible fungi.
    Expert Review of Clinical Immunology 03/2014; · 2.89 Impact Factor
  • The Journal of allergy and clinical immunology 02/2014; · 12.05 Impact Factor
  • Antimicrobial Agents and Chemotherapy 11/2013; 57(11):5783. · 4.57 Impact Factor
  • Allergology International 09/2013;
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    ABSTRACT: Among the various types of laryngeal paresthesia suffered by chronic cough patients, we often encounter "a sensation of irritation in the throat (SIT)". Our study indicated that capsaicin cough threshold was significantly (P<0.05) lower in the SIT-positive group (13.9 μM) than in the SIT-negative group (49.6 μM,). The establishment of treatment strategies for SIT would be advantageous for treating chronic cough patients suffering from this laryngeal sensation.
    Respirology 08/2013; · 2.78 Impact Factor
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    ABSTRACT: An increasing number of patients with lung cancer are undergoing outpatient chemotherapy. It is very important to maintain good quality of life(QOL)for these patients, and Japanese traditional medicine, TJ-41, has been reported to improve the QOL of patients with advanced cancer. However, the effect of TJ-41 on patients with lung cancer undergoing outpatient chemotherapy is unknown. Therefore, we conducted this study. To investigate the factors influencing the QOL of these patients, we distributed a QOL questionaire,"The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs"(QOL-ACD)to 11 patients with non-small cell lung cancer. The medical factors related to the overall QOL scores and other categories, indicating"activity","physical condition","psychological condition","social relationships","psychological condition"and"face scale"were analyzed. A significant decrease in each of the factors was not observed in this study.
    Gan to kagaku ryoho. Cancer & chemotherapy 07/2013; 40(7):913-6.
  • Pulmonary Pharmacology &amp Therapeutics 06/2013; · 2.54 Impact Factor
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    ABSTRACT: Pirfenidone, an antifibrotic drug with anti-inflammatory and antioxidant effects, delays fibrosis in idiopathic pulmonary fibrosis (IPF). Patients with IPF have a greater cough reflex sensitivity to inhaled capsaicin than healthy people, and cough is an independent predictor of IPF disease progression; however, the effects of pirfenidone on cough reflex sensitivity are unknown. After challenge with an aerosolized antigen in actively sensitized guinea pigs, pirfenidone was administered intraperitoneally, and the cough reflex sensitivity was measured at 48 h after the challenge. Bronchoalveolar lavage (BAL) was performed, and the tracheal tissue was collected. Pirfenidone suppressed the capsaicin-induced increase in cough reflex sensitivity in a dose-dependent manner. Additionally, increased levels of prostaglandin E2, substance P, and leukotriene B4, but not histamine, in the BAL fluid were dose dependently suppressed by pirfenidone. The decrease in neutral endopeptidase activity in the tracheal tissue was also alleviated by pirfenidone treatment. The total number of cells and components in the BAL fluid was not influenced. These results suggest that pirfenidone ameliorates isolated cough based on increased cough reflex sensitivity associated with allergic airway diseases, and potentially relieve chronic cough in IPF patients who often have increased cough reflex sensitivity. Prospective studies on cough-relieving effects of pirfenidone in patients with IPF are therefore warranted.
    Pulmonary Pharmacology &amp Therapeutics 06/2013; · 2.54 Impact Factor
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    ABSTRACT: Periostin, an extracellular matrix protein, contributes to subepithelial thickening in asthmatic airways, and its serum levels reflect airway eosinophilic inflammation. However, the relationship between periostin and the development of airflow limitation, a functional consequence of airway remodeling, remains unknown. We aimed to determine the relationship between serum periostin levels and pulmonary function decline in asthmatic patients on inhaled corticosteroid (ICS) treatment. Two hundred twenty-four asthmatic patients (average age, 62.3 years) treated with ICS for at least 4 years were enrolled. Annual changes in FEV1, from at least 1 year after the initiation of ICS treatment to the time of enrollment or later (average, 16.2 measurements over 8 years per individual), were assessed. At enrollment, clinical indices, biomarkers that included serum periostin, and periostin gene polymorphisms were examined. Associations between clinical indices or biomarkers and a decline in FEV1 of 30 mL or greater per year were analyzed. High serum periostin levels (≥95 ng/mL) at enrollment, the highest treatment step, higher ICS daily doses, a history of admission due to asthma exacerbation, comorbid or a history of sinusitis, and ex-smoking were associated with a decline in FEV1 of 30 mL or greater per year. Multivariate analysis showed that high serum periostin, the highest treatment step, and ex-smoking were independent risk factors for the decline. Polymorphisms of periostin gene were related to higher serum periostin levels (rs3829365) and a decline in FEV1 of 30 mL or greater per year (rs9603226). Serum periostin appears to be a useful biomarker for the development of airflow limitation in asthmatic patients on ICS.
    The Journal of allergy and clinical immunology 06/2013; · 12.05 Impact Factor
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    ABSTRACT: Abstract Objective: There is increasing interest in the association between the severity of asthma and fungal sensitization, and lung function decline in relation to mold and dampness in the home has recently been reported. This study was performed to determine the correlation between sensitization to Schizophyllum commune and decline of lung function, and to elucidate the outcomes and risk factors, especially from Schizophyllum allergy. Methods: The medical records of 50 patients with asthma who satisfied the following inclusion criteria were collected and reviewed retrospectively: (1) at least five years of follow-up with five evaluations; (2) intradermal skin tests including S. commune performed at the initial assessment; and (3) severity ranging from mild-to-moderate. Lung function decline (evaluated as adjusted delta FEV1/year) was compared in a cross-sectional manner with regard to gender, age, BMI, smoking habit, allergological characteristics, and exacerbation frequency. Results and Conclusions: There were significant differences in lung function decline between females and males (P < 0.05), positive and negative results of late-phase skin reaction to S. commune (P < 0.001), and positive and negative late-phase skin reaction to Aspergillus (P < 0.05). Lung function decline was correlated with exacerbation frequency (r = 0.428, P = 0.002). On multivariate analysis, the probability of lung function decline in asthma was found to be significantly associated with female gender and positive late-phase skin reaction against S. commune. Our results suggested that sensitization to S. commune may be one of the risk factors involved in lung function decline in asthmatic patients.
    Journal of Asthma 05/2013; · 1.85 Impact Factor
  • European Respiratory Journal 02/2013; 41(2):474-477. · 6.36 Impact Factor
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    ABSTRACT: BACKGROUND: The presence of basidiomycetous (BM) fungi in induced sputum is an important clinical finding in chronic idiopathic cough (CIC). However, the efficacy of anti-fungal therapy for CIC has not been evaluated. METHODS: We selected 10 patients with CIC and carried out allergological examinations for Bjerkandera adusta, a BM fungus that has been shown to enhance cough severity. The efficacy of low-dose itraconazole (ITCZ) therapy (50 mg/day) for 14 days as an adjunctive therapy was estimated with use of Cough Visual Analog Scale (VAS) and the Japanese version of the Leicester Cough Questionnaire (J-LCQ). We evaluated whether there was a recognizable clinical or allergological pattern that could predict the efficacy of ITCZ therapy in CIC patients. RESULTS: Significant changes in Cough VAS and minimal important difference in domains of the J-LCQ were observed in 3 and 5 CIC patients, respectively. The Delta cough scale was correlated with changes in domains of the J-LCQ (total (r = --0.73, P < 0.05), psychological (r = --0.73, P < 0.05), and social (r = --0.71, P < 0.05), respectively. There were significant differences in the change in total score (P < 0.05) and in the domain of social (P < 0.05) and Delta cough scale (P < 0.05) between positive and negative results of immediate skin test for B. adusta. Positive results for improvement of cough-related laryngeal sensation which was represented as a sensation of mucus in the throat (SMIT) were observed in 6 patients in the BM colonization-positive group (85.7%) and none in the BM colonization-negative group (0%). There was a significant difference in the positive ratio for improvement of SMIT between the two groups. CONCLUSIONS: At present, it is not possible to conclude whether ITCZ therapy provides sufficient relief in CIC patients. However, this study suggested both the possible applicability of low-dose ITCZ therapy for treatment of CIC patients with regard to BM allergy and the necessity of development of a new assessment questionnaire for cough-associated respiratory symptoms.Trial registration: UMIN-CTR (reference number R000005872; UMIN000004933).
    Cough 01/2013; 9(1):1. · 1.26 Impact Factor
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    ABSTRACT: The effects of inductive hyperthermia on lung cancer have yet to be fully investigated. Magnetic nanoparticles used in inductive hyperthermia are made-to-order and expensive. This study was performed to investigate the use of ferucarbotran in inductive hyperthermia and to clarify whether inductive hyperthermia using ferucarbotran promotes antitumor effects in vivo using a lung cancer cell line. We injected A549 cells subcutaneously into the right thighs of BALB/c nu/nu nude mice. Forty mice with A549 xenografts were then classified into three groups. Group 1 was the control group. All mice in groups 2 and 3 had ferucarbotran injected into their tumors, and mice in group 3 were then subjected to alternating magnetic field irradiation. We evaluated tumor temperature during the hyperthermic procedure, the time course of tumor growth, histologic findings in tumors after hyperthermic treatment, and adverse events. Intratumor temperature rose rapidly and was maintained at 43°C-45°C for 20 minutes in an alternating magnetic field. Tumor volumes in groups 1 and 2 increased exponentially, but tumor growth in group 3 was significantly suppressed. No severe adverse events were observed. Histologic findings for the tumors in group 3 revealed mainly necrosis. Inductive hyperthermia using ferucarbotran is a beneficial and promising approach in the treatment of lung cancer. Ferucarbotran is a novel tool for further development of inductive hyperthermia.
    OncoTargets and Therapy 01/2013; 6:237-42. · 2.07 Impact Factor

Publication Stats

3k Citations
1,152.84 Total Impact Points


  • 1985–2014
    • Kanazawa University
      • • Department of Respiratory Medicine
      • • Department of Radiological Technology
      • • Department of Cellular Transplantation Biology
      • • Department of Internal Medicine
      • • School of Medicine
      Kanazawa, Ishikawa, Japan
  • 1988–2013
    • Kanazawa Medical University
      • • Department of Respiratory Medicine
      • • Department of Internal Medicine (III)
      Kanazawa, Ishikawa, Japan
    • Iwate Medical University
      • Department of Pediatrics
      Morioka, Iwate, Japan
  • 1983–2011
    • Ishikawa Prefectural Central Hospital
      Ishiza, Okinawa, Japan
  • 2010
    • St. Marianna University School of Medicine
      Kawasaki Si, Kanagawa, Japan
  • 2003–2010
    • National Hospital Organization Minami Kyoto Hospital
      Kioto, Kyōto, Japan
  • 2009
    • Osaka City University
      Ōsaka, Ōsaka, Japan
  • 1998–2008
    • Kanazawa Municipal Hospital
      Kanazawa, Ishikawa, Japan
  • 1996–2003
    • Toyama Medical and Pharmaceutical University
      Тояма, Toyama, Japan
  • 1995–1997
    • Japan Red Cross Fukuoka Hospital
      Hukuoka, Fukuoka, Japan
    • Ehime Prefectural Central Hospital
      Matuyama, Ehime, Japan
  • 1987
    • Osaka Medical Center and Research Institute for Maternal and Child Health
      Izumi, Ōsaka, Japan
    • Seirei Hamamatsu General Hospital
      Hamamatu, Shizuoka, Japan