Michiaki Mishima

Kyoto University, Kioto, Kyōto, Japan

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Publications (428)1353.55 Total impact

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    ABSTRACT: Visceral obesity, low adiponectin, and severe obstructive sleep apnea (OSA) are associated with cardiovascular diseases, but the interactions among these factors on endothelial dysfunction are not well known.Methods and Results:Endothelial function in 133 patients after polysomnography was evaluated as reactive hyperemia index (RHI) on reactive hyperemia peripheral arterial tonometry. Visceral obesity was defined as visceral fat area ≥100 cm(2)on computed tomography. RHI was significantly correlated with apnea hypopnea index (AHI), visceral fat area, and serum adiponectin (r=-0.24, P=0.0055, r=-0.19, P=0.031, and r=0.20, P=0.019, respectively). RHI in patients with visceral obesity was significantly decreased in the presence of severe OSA (AHI ≥30; P=0.042). On multivariate regression analysis, only severe OSA remained as an independent predictive factor of RHI (P=0.024, R(2)=5.4%). RHI in patients with severe OSA (n=44) was significantly improved after 3 months of continuous positive airway pressure (CPAP) treatment (1.78±0.40 before CPAP vs. 2.00±0.53 after CPAP, P=0.013), similarly to those with AHI <30 (P=0.45). Severe OSA, but not visceral fat area or serum adiponectin, was independently associated with endothelial function according to RHI. In addition, impaired endothelial function was reversible following 3 months of CPAP treatment.
    Circulation Journal 03/2015; DOI:10.1253/circj.CJ-14-1303 · 3.69 Impact Factor
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    ABSTRACT: Toll-like receptor 3 (TLR3) may be associated with T helper 1 immune response. This study aimed to investigate the role of a functional TLR3 single nucleotide polymorphism (SNP) in sarcoidosis. We genotyped 220 Japanese patients with sarcoidosis and 140 controls for TLR3 SNP rs3775291 to analyze its association with susceptibility to sarcoidosis and assessed its relationship to clinical features in 172 patients over 2 years. The TLR3 rs3775291 genotype was not significantly associated with disease susceptibility. However, patients with cardiac sarcoidosis (CS) significantly more frequently had the TT genotype (p < 0.01) or the T allele (p < 0.05) than those patients without CS. We conclude that TLR3 SNP rs3775291 may affect cardiac involvement in Japanese patients with sarcoidosis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
    Tissue Antigens 03/2015; 85(3):204-8. DOI:10.1111/tan.12535 · 2.35 Impact Factor
  • Hitomi Ajimizu, Young Hak Kim, Michiaki Mishima
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    ABSTRACT: Crizotinib is a potent and specific small-molecule inhibitor of both anaplastic lymphoma kinase (ALK) and c-MET tyrosine kinases, and patients with ALK rearrangement tumor benefit from crizotinib treatment; however, its penetration into calculated cerebrospinal fluid (CSF) is considered to be poor. Alectinib is a highly selective, next-generation ALK inhibitor, and both preclinical and clinical studies have indicated that alectinib is also effective in crizotinib-resistant tumors. A recent in vitro study demonstrated significant antitumor activity of alectinib for brain metastases using mouse models of ALK-positive non-small-cell lung cancer. In this paper, we report a first case alectinib was highly effective against brain metastases refractory to crizotinib. Further investigation of alectinib in this setting would be particularly valuable.
    Medical Oncology 02/2015; 32(2). DOI:10.1007/s12032-014-0477-7 · 2.06 Impact Factor
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    ABSTRACT: This study was conducted to evaluate trends in the isolation of strains of nontuberculous mycobacteria (NTM) and trends in the number of patients with pulmonary Mycobacterium avium complex (MAC) disease. We retrospectively reviewed microbiological results and clinical data to identify patients who were diagnosed with pulmonary MAC disease at Kyoto University Hospital in Japan between 2000 and 2013. NTM were isolated from 6,327 of 80,285 samples (7.9%) for mycobacterial culture. The proportion of NTM isolates among all mycobacterial isolates increased from 355 of 792 samples (44.8%) in 2000 to 688 of 847 samples (81.2%) in 2013. MAC was most frequently observed (5436 isolates, 85.9%), followed by M. abscessus (175 isolates, 2.8%) and M. kansasii (74 isolates, 1.2%). A total of 592 patients with pulmonary MAC disease were identified (age, 66.0±11.5 years; females, 61.1%). Compared with the early cohort (2000-2006, 236 patients), more patients in the late cohort (2007-2013, 356 patients) had an underlying disease (157 [66.5%] vs. 284 [79.8%], P=0.0003), a Charlson comorbidity index score ≥1 (115 [48.7%] vs. 213 [59.8%], P=0.008), collagen vascular disease (18 [7.6%] vs. 60 [16.9%], P=0.001), rheumatoid arthritis (11 [4.7%] vs. 41 [11.5%], P=0.004), and used immunosuppressive drugs (22 [9.3%] vs. 63 [17.7%], P=0.004). The numbers of patients with lung disease, malignant disease and diabetes mellitus increased; however, their frequencies did not differ. The recovery rate of NTM and patients with pulmonary MAC disease increased, especially in patients with collagen vascular disease or rheumatoid arthritis or who used immunosuppressive drugs.
    Journal of Infection and Chemotherapy 01/2015; DOI:10.1016/j.jiac.2015.01.004 · 1.38 Impact Factor
  • American Journal of Respiratory and Critical Care Medicine 12/2014; 190(12):1449-52. DOI:10.1164/rccm.201407-1290LE · 11.99 Impact Factor
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    ABSTRACT: Abstract Objectives: 2-[18F]-fluoro-2-deoxy-D-glucose positron-emission tomography/-computed tomography (FDG-PET/CT) was reported useful for monitoring immunoglobulin G4-related disease (IgG4-RD); however, a quantitative FDG-PET/CT analysis such as total lesion glycolysis (TLG) has not yet been conducted. This study aimed to investigate whether TLG would correlate with serum markers in IgG4-RD, and the utility of TLG for disease monitoring. Methods: This retrospective study included 17 patients (12 men; median age, 62 years) who were followed up at Kyoto University Hospital and underwent FDG-PET/CT from April 2009 to November 2013. TLG was calculated for the involved lesions. Correlations between serum markers [IgG4, soluble IL-2 receptor (sIL-2R), lactate dehydrogenase (LDH), and C- reactive protein (CRP)] and TLG concomitant with FDG-PET/CT scans were investigated. Serial changes in TLG were assessed in patients who underwent follow-up FDG-PET/CT (n=6). Results: The calculated median (interquartile range) TLG value was 154.8 (63.7-324.4). A significant correlation was found between the sIL-2R level and TLG (P= 0.001, rs = 0.763). In contrast, no correlations were found between the IgG4, LDH or CRP levels and TLG. Increased or decreased TLG corresponded with clinical disease improvement or worsening. Conclusions: TLG correlated significantly with the serum sIL-2R level and may be useful for disease monitoring in IgG4-RD.
    Modern Rheumatology 12/2014; DOI:10.3109/14397595.2014.990674 · 2.21 Impact Factor
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    ABSTRACT: Introduction: To investigate the impact of pre-existing radiological interstitial lung disease (ILD) findings on the incidence of radiation pneumonitis (RP) and clinical outcomes after stereotactic body radiation therapy (SBRT) for stage I non-small-cell lung cancer. Methods: We included 157 consecutive patients who underwent SBRT alone for stage I non-small-cell lung cancer and whose pretreatment lung computed tomography images were available for retrospective review. The pretreatment computed tomography images were evaluated retrospectively for the presence of ILD. The incidence of RP, overall survival (OS) rate, and the incidence of disease progression and local progression were evaluated between patients with ILD (ILD[+]) and without ILD (ILD[-]). Results: Pre-existing ILD was identified in 20 patients. The median follow-up period was 39.5 months. The incidences of RP worse than grade 2 (>= Gr2 RP) and worse than grade 3 (>= Gr3 RP) were significantly higher in ILD(+) than ILD(-) (1 year >= Gr2 RP rate, 55.0% versus 13.3%; p < 0.001 and 1year >= Gr3 RP rate 10.0% versus 1.5%; p = 0.020). Multivariate analysis also indicated that ILD(+) was a risk factor for >= Gr2 and >= Gr3 RP, and the volume of the irradiated lung. The OS rate tended to be worse in ILD(+) than ILD(-) (3-year OS, 53.8% versus 70.8%; p = 0.28). No difference was observed in the disease progression or local progression rates. Conclusions: Pre-existing ILD was a significant risk factor for symptomatic and severe RP. Prescreening for ILD findings is important for determining the radiation pneumonitis risk when planning SBRT.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 11/2014; 10(1). DOI:10.1097/JTO.0000000000000359 · 4.55 Impact Factor
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    ABSTRACT: http://www.journalsleep.org/AcceptedPapers/SP-854-13.pdf
    Sleep 10/2014; · 5.06 Impact Factor
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    ABSTRACT: Background: Environmental exposure is a likely risk factor for the development of pulmonary Mycobacterium avium complex (MAC) disease. The influence of environmental exposure on the response to antimicrobial treatment and relapse is unknown. Methods: We recruited 72 patients with pulmonary MAC disease (male [female], 18 [54]; age, 61.7 +/- 10.3 years) who initiated and completed standard three-drug regimens for more than 12 months between January 2007 and December 2011. The factors associated with sputum conversion, relapse and treatment success without relapse were retrospectively evaluated after adjustments for confounding predictors. Results: Fifty-two patients (72.2%) demonstrated sputum conversion, and 15 patients (28.8%) relapsed. A total of 37 patients (51.4%) demonstrated treatment success. Sputum conversion was associated with negative smears (odds ratio [OR], 3.89; 95% confidence interval [CI], 1.27-12.60; P = 0.02). A relapse occurred in patients with low soil exposure after the start of treatment less frequently than in patients with high soil exposure (7/42 [16.7%] vs. 8/10 [80.0%], P = 0.0003). Treatment success was associated with low soil exposure after the beginning of treatment (OR, 13.46; 95% CI, 3.24-93.43; P = 0.0001) and a negative smear (OR, 2.97; 95% CI, 1.02-9.13; P = 0.047). Conclusion: Low soil exposure was independently associated with better microbiological outcomes in patients with pulmonary MAC disease after adjusting for confounding clinical, microbiological and radiographic findings.
    BMC Infectious Diseases 09/2014; 14(1):522. DOI:10.1186/1471-2334-14-522 · 2.56 Impact Factor
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    ABSTRACT: Background and objectiveObesity hypoventilation syndrome (OHS) prevalence was previously estimated at 9% in patients with obstructive sleep apnoea (OSA) in Japan. However, the definition of OSA in that study was based on an apnoea-hypopnoea index (AHI) of 20/h rather than 5/h. Therefore, the prevalence of OHS in OSA was not measured in the same way as for Western countries. Our study objectives were to investigate the characteristics of Japanese patients with OHS. Methods Nine hundred eighty-one consecutive patients investigated for suspected OSA were enrolled. At least 90% of them were from urban areas, including 162 with obese OSA (body mass index (BMI)30kg/m(2) and AHI5/h). ResultsThe prevalence of OHS (BMI 36.74.9kg/m(2)) in OSA and that in obese OSA were 2.3% and 12.3%, respectively. Multiple regression analysis revealed that independent of age and BMI, arterial oxygen pressure (contribution rate (R-2)=7.7%), 4% oxygen desaturation index (R-2=8.9%), carbon monoxide diffusing capacity/alveolar volume (R-2=8.3%), haemoglobin concentration (R-2=4.9%) and waist circumference (R-2=4.9%) were independently associated with arterial carbon dioxide pressure. After 12.34.6 months of CPAP treatment, more than 60% of OHS patients no longer had hypercapnia. Conclusions The prevalence of OHS in OSA in Japan was 2.3%. The mean BMI of patients with OHS in Japan was lower than that in Western countries (36.7kg/m(2) vs 44.0kg/m(2)). The prevalence of OHS in obese OSA Japanese patients is approximately the same as in Western patients despite a much lower BMI. Moreover, DLCO/V-A, reported in this study for the first time, was independently associated with PaCO2 levels.
    Respirology 09/2014; 19(8). DOI:10.1111/resp.12367 · 3.50 Impact Factor
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    ABSTRACT: No methods for isolating induced alveolar epithelial progenitor cells (AEPCs) from human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) have been reported. Based on a study of the stepwise induction of alveolar epithelial cells (AECs), we identified carboxypeptidase M (CPM) as a surface marker of NKX2-1(+) "ventralized" anterior foregut endoderm cells (VAFECs) in vitro and in fetal human and murine lungs. Using SFTPC-GFP reporter hPSCs and a 3D coculture system with fetal human lung fibroblasts, we showed that CPM(+) cells isolated from VAFECs differentiate into AECs, demonstrating that CPM is a marker of AEPCs. Moreover, 3D coculture differentiation of CPM(+) cells formed spheroids with lamellar-body-like structures and an increased expression of surfactant proteins compared with 2D differentiation. Methods to induce and isolate AEPCs using CPM and consequently generate alveolar epithelial spheroids would aid human pulmonary disease modeling and regenerative medicine.
    09/2014; 3(3). DOI:10.1016/j.stemcr.2014.07.005
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    ABSTRACT: Background Comprehensive studies of the pathophysiologic characteristics of elderly asthma, including predominant site of disease, airway inflammation profiles, and airway hyperresponsiveness, are scarce despite their clinical importance. Objective To clarify the pathophysiologic characteristics of elderly patients with asthma. Methods Patients older than 65 years (elderly; n = 45) vs those no older than 65 years (nonelderly; n = 67) were retrospectively analyzed by spirometry, computed tomographic indices of large airway wall thickness and small airway involvement (air trapping), impulse oscillation measurements, exhaled nitric oxide levels, blood and induced sputum cell differentials, methacholine airway responsiveness, and total and specific serum IgE levels. Results Elderly patients with asthma had significantly lower values for forced expiration volume in 1 second, mid-forced expiratory flow (percentage predicted), and ratio of forced expiration volume in 1 second to forced vital capacity than nonelderly patients with asthma (median 81.2% vs 88.8%, P = .02; 50.9% vs 78.6%, P = .03; 0.72 vs 0.78, P = .001, respectively). In computed tomographic measurements, elderly patients with asthma had significantly greater airway wall thickening and air trapping than nonelderly patients. Impulse oscillation measurements indicated that elderly patients with asthma showed significantly greater resistance at 5 Hz (used as an index of total airway resistance), greater decrease in resistance from 5 to 20 Hz, a higher ratio of decrease in resistance from 5 to 20 Hz to resistance at 5 Hz, higher integrated area between 5 Hz and frequency of resonance, greater frequency of resonance, and lower reactance at a frequency of 5 Hz (potential markers of small airway disease) than nonelderly patients. There were no significant differences in blood or sputum cell differentials, exhaled nitric oxide, or methacholine airway responsiveness between the 2 groups. Total serum IgE levels and positive rates of specific IgE antibodies against several allergens were significantly lower in elderly than in nonelderly patients with asthma. Conclusion Based on spirometric, computed tomographic, and impulse oscillation analyses, elderly patients with asthma have greater involvement of small and large airways than nonelderly patients with asthma.
    Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 09/2014; DOI:10.1016/j.anai.2014.08.002 · 2.75 Impact Factor
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    ABSTRACT: Although obesity has been reported to be a potential risk factor for abdominal aortic dilatation, the impact of obstructive sleep apnea (OSA) on the abdominal aortic diameter remains unknown. We retrospectively reviewed 427 patients aged >45 years who underwent polysomnography and abdominal computed tomography from November 2008 to February 2012. Aortic diameters were measured at 3 locations: upper, infrarenal, and lower abdominal aorta. OSA was defined as non-OSA (apnea-hypopnea index [AHI] <10, n = 58), mild to moderate (AHI 10 to 30, n = 167), and severe (AHI ≥30, n = 202). Adjusted diameter was not significantly different among OSA severity categories at the upper (21.0, 21.3, and 21.4 mm, respectively) and infrarenal aorta (19.5, 20.2, and 19.9 mm, respectively) but was significantly different at the lower abdominal aorta (17.3, 18.2, and 18.2 mm, respectively, p = 0.006) with larger diameters in patients with OSA. Multivariate linear regression analyses revealed that risk profiles for aortic dilatation varied according to the location and gender and that OSA (AHI ≥10) was an independent risk factor for infrarenal and lower abdominal aortic dilatation only in men (β = 0.10 and 0.18, p = 0.049 and 0.001, respectively). In conclusion, OSA may enhance dilatation of the distal abdominal aorta in men.
    The American Journal of Cardiology 08/2014; 114(4):618–623. DOI:10.1016/j.amjcard.2014.05.044 · 3.43 Impact Factor
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    American Journal of Respiratory and Critical Care Medicine 08/2014; 190(4):472-4. DOI:10.1164/rccm.201403-0562LE · 11.04 Impact Factor
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    ABSTRACT: Since commercial forced oscillation technique (FOT) devices became available, they have been widely used for physiological assessments, mainly of obstructive lung diseases. However, it is not known whether the impedance values measured with different devices are identical. In this study, two FOT devices-the impulse oscillometry system (IOS) and the MostGraph (MG)-were compared using phantom models. The resistance values varied up to 10 % from estimated values in both devices. Additionally, there was a difference in frequency dependence for the resistance between the devices. The reactance values measured with MG were higher than those measured with IOS. The effects of ventilation on the measured impedance values were higher for IOS than for MG, especially at lower frequencies. We concluded that the devices do not always generate identical impedance values. Thus, differences between the devices should be taken into consideration when evaluating clinical data.
    The Journal of Physiological Sciences 07/2014; DOI:10.1007/s12576-014-0329-4 · 1.25 Impact Factor
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    ABSTRACT: Background: Preclinical data indicated that the combination of erlotinib and pemetrexed is synergistic when erlotinib is administered after pemetrexed. Patients and Methods: This was a phase II study of pemetrexed and erlotinib in patients with pretreated advanced non-squamous non-small-cell lung cancer (NSCLC) with wild-type epidermal growth factor receptor (EGFR). Chemotherapy consisted of pemetrexed (500 mg/m(2)) on day 1 and erlotinib (150 mg/body) on days 2-15 every 3 weeks. The protocol treatment was repeated until disease progression or intolerable toxicities occurred. Results: Seventeen patients were enrolled between January 2010 and January 2013, and 15 patients were evaluable for both safety and efficacy. The study was terminated due to slow patient accrual. There was 1 complete response. There was a partial response in 3 patients, stable disease in 4 and progressive disease in 7. The response rate was 27% and disease control rate was 53%. The median progression-free survival and overall survival were 2.5 months and 6.7 months, respectively. Conclusions: Statistical interpretation could not been made due to the early termination of the study. Further studies are needed to clarify the efficacy of this regimen in NSCLC patients without EGFR mutation (UMIN-CTR No. 0000024531). © 2014 S. Karger AG, Basel.
    Chemotherapy 07/2014; 59(6):414-419. DOI:10.1159/000363731 · 1.55 Impact Factor
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    ABSTRACT: Background: Omalizumab, a humanized anti-IgE monoclonal antibody, is reportedly an effective treatment for severe allergic asthma. However, there have been few comprehensive analyses of its efficacy, including assessments of small airways or airway remodeling. Objective: To comprehensively evaluate the efficacy of omalizumab, including its effects on small airways and airway remodeling, in adult patients with severe refractory asthma. Methods: In this prospective, time-series, single-arm observational study, 31 adult patients with severe refractory asthma despite the use of multiple controller medications, including high-dose inhaled corticosteroids (1,432 +/- 581 mu g/d of fluticasone propionate equivalent), were enrolled. Clinical variables, including Asthma Quality of Life Questionnaire, asthma exacerbations, exhaled nitric oxide, pulmonary function, methacholine airway responsiveness, induced sputum, and chest computed tomogram, were assessed at baseline and after 16 and 48 weeks of treatment with omalizumab. Results: Twenty-six of the 31 patients completed 48 weeks of treatment. For these patients, Asthma Quality of Life Questionnaire scores and peak expiratory flow values significantly and continuously improved throughout the 48 weeks (P < .001 for all comparisons). Unscheduled physician visits, asthma exacerbations requiring systemic corticosteroids, fractional exhaled nitric oxide at 50 mL/s and alveolar nitric oxide levels, sputum eosinophil proportions, and airway-wall thickness as assessed by computed tomography significantly decreased at 48 weeks (P < .05 for all comparisons). Conclusion: Omalizumab was effective for adult patients with severe refractory asthma. Omalizumab may have anti-inflammatory effects on small airways and reverse airway remodeling.
    Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 07/2014; 113(4). DOI:10.1016/j.anai.2014.06.004 · 2.75 Impact Factor
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    ABSTRACT: Bacteria and viruses are major causes of COPD exacerbations. Molecular components of these pathogens are recognized by pattern-recognition receptors (PRRs) expressed by various cells in the airway, which leads to initiation of inflammatory processes. Expression levels of PRRs in airway inflammatory cells are expected to affect susceptibility to COPD exacerbation.
    The Clinical Respiratory Journal 06/2014; DOI:10.1111/crj.12171 · 2.20 Impact Factor
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    ABSTRACT: There is a need for agents that suppress inflammation and progression of chronic obstructive pulmonary disease. p38 mitogen-activated protein kinase (p38 MAPK) has been associated with this disorder, and several inhibitors of this cascade are in clinical trials for its treatment, but their efficacy and utility are unknown. This study evaluated the relationship between p38 MAPK activation and susceptibility to cigarette smoke (CS)-induced emphysema, and whether its inhibition ameliorated the lung inflammation and injury in murine models of cigarette smoke exposure.
    BMC Pulmonary Medicine 05/2014; 14(1):79. DOI:10.1186/1471-2466-14-79 · 2.49 Impact Factor
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    ABSTRACT: Patients with pulmonary Mycobacterium avium complex (MAC) disease are often co-infected with various pathogenic microorganisms. This study aimed to determine the prevalence of co-infection with non-MAC pathogens and the risk factors associated with co-infection in patients with pulmonary MAC disease. We retrospectively reviewed the patient characteristics, microbiological results and chest CT findings in 275 patients with pulmonary MAC who visited the Kyoto University Hospital from January 2001 to May 2013. We defined chronic pathogenic co-infection as the isolation of non-MAC pathogens from sputum samples taken on more than two visits that occurred at least 3 months apart. The participants were predominantly female (74.5%) and infected with M. avium (75.6%). Chronic co-infection with any pathogen was observed in 124 patients (45.1%). Methicillin-sensitive Staphylococcus aureus (MSSA; n=64), Pseudomonas aeruginosa (n=35) and Aspergillus spp (n=18) were the most prevalent pathogens. The adjusted factors were chronic obstructive pulmonary disease (COPD; OR=4.2, 95% CI 1.6 to 13.1) and pulmonary M. intracellulare disease (OR=2.2, 95% CI 1.1 to 4.4) in chronic co-infections; COPD (OR=4.2, 95% CI 2.1 to 31.4), long duration of MAC disease (OR=2.2, 95% CI 1.2 to 4.4) and nodules (OR=3.5, 95% CI 1.2 to 13.2) in chronic MSSA co-infection; COPD (OR=7.5, 95% CI 2.1 to 31.4) and lower lobe involvement (OR=9.9, 95% CI 2.0 to 90.6) in chronic P. aeruginosa co-infection; and use of systemic corticosteroids (OR=7.1, 95% CI 1.2 to 50.9) and pulmonary M. intracellulare disease (OR=4.0, 95% CI 1.1 to 14.5) in chronic Aspergillus spp co-infection. Patients with pulmonary MAC disease frequently had chronic co-infections with pathogenic microorganisms such as MSSA, P. aeruginosa and Aspergillus. The risk factors for chronic co-infection were COPD and pulmonary M. intracellulare disease.
    05/2014; 1(1):e000050. DOI:10.1136/bmjresp-2014-000050

Publication Stats

6k Citations
1,353.55 Total Impact Points

Institutions

  • 1993–2015
    • Kyoto University
      • • Department of Respiratory Medicine
      • • Primate Research Institute
      Kioto, Kyōto, Japan
  • 2013
    • Khon Kaen University
      • Centre for Research and Development of Medical Diagnostic Laboratories
      Kawn Ken, Khon Kaen, Thailand
  • 2011
    • Hospital Universitari Germans Trias i Pujol
      Badalona, Catalonia, Spain
  • 2010
    • Chiba University
      • Department of Respirology
      Chiba-shi, Chiba-ken, Japan
  • 2007
    • Shiga University of Medical Science
      Ōtu, Shiga Prefecture, Japan
  • 2006
    • Nagai Internal Medicine Clinic
      Okayama, Okayama, Japan
  • 2005
    • Kyoto Sangyo University
      Kioto, Kyōto, Japan
  • 1992
    • Hyogo Prefectural Amagasaki Hospital
      Amagasaki, Hyōgo, Japan