Michiaki Mishima

Kyoto University, Kioto, Kyōto, Japan

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Publications (441)1425.63 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Airway remodelling in bronchial asthma (BA) and COPD has been quantitatively assessed by analysing the airway wall area and the luminal area on cross-sectional CT images. To date, there have been no reports on assessment of the longitudinal structure of the airway lumen. Quantitative airway analysis using CT was performed on three groups consisting of 29 patients with BA, 58 patients with COPD and 59 healthy controls. To assess the longitudinal shape irregularity of the airway lumen, new quantitative CT parameters, validated by a phantom study, were established. The internal radii of imaginary inscribed spheres in the airway lumen were measured as a function of distance from the level of the carina to the fifth-order branches of the right posterior basal bronchus. The gaps of these radii from the regression line were calculated as parameters to reflect the longitudinal airway lumen shape irregularity. These new parameters were compared among the study groups as well as with the conventional parameters of airway wall thickening and luminal area. Longitudinal airway lumen shape irregularity was significantly greater in patients with COPD than in those with BA and healthy controls. Wall thickening was significantly greater, and luminal area smaller, in patients with BA than in those with COPD and healthy controls. These results were consistent even among the BA and COPD subgroups with similar airflow limitation. The combination of cross-sectional and longitudinal airway structure analyses using CT images may suggest differences in the characteristics of airway remodelling between COPD and asthma. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Thorax 05/2015; DOI:10.1136/thoraxjnl-2014-206651 · 8.56 Impact Factor
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    ABSTRACT: Pulmonary spindle cell carcinoma (SpCC) is a rare subtype of non-small-cell lung cancer (NSCLC) and, in general, is chemoresistance.
    05/2015; 30. DOI:10.1016/j.rmcr.2015.05.003
  • Young Hak Kim, Michiaki Mishima
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 05/2015; 10(5):e35. DOI:10.1097/JTO.0000000000000513 · 5.80 Impact Factor
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    ABSTRACT: Computed tomography (CT) assessment of air trapping has been considered useful as a measure of small airway disease. Mean lung density (MLD) and the percentage of the lung field occupied by low attenuation area (LAA%) can be evaluated automatically, and their expiratory/inspiratory (E/I) ratios correlate with asthma severity and spirometry parameters. However, mosaic attenuation, another indicator of air trapping, has been assessed visually, and its functional relevance remains controversial. This retrospective study was conducted to correlate mosaic attenuation, which was assessed visually and automatically, and the E/I ratios of MLD and LAA% (defined as areas <-960 Hounsfield units) with clinical and physiological variables, including impulse oscillometry (IOS) indices. In 36 nonsmoking patients with stable asthma, the lungs were scanned at full inspiration and full expiration. Mosaic attenuation was measured visually and automatically, by counting areas with CT values higher than the surrounding areas. MLD and LAA% were measured using our validated method. Spirometry, IOS, exhaled NO and the sputum eosinophil count were evaluated. The automatic results and visual scores of mosaic attenuation correlated well on expiratory scans (r = 0.894) and to a lesser degree on inspiratory scans (r = 0.629; p < 0.0001 for both). However, only the E/I ratios of MLD and LAA% correlated with forced expiratory volume in 1 s/forced vital capacity of spirometry and the IOS indices of resistance from 5 to 20 Hz and the integrated area of low-frequency reactance. Our automatic method for analysis of mosaic attenuation is likely useful, but the results themselves may not be reflecting small airway involvement of asthma, unlike the E/I ratios of MLD and LAA%. © 2015 S. Karger AG, Basel.
    Respiration 04/2015; DOI:10.1159/000381553 · 2.92 Impact Factor
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    ABSTRACT: No studies have addressed the relationship between obstructive sleep apnea (OSA) and abdominal aortic calcification (AAC), a marker for subclinical atherosclerosis and future cardiovascular events. To investigate 1) the association between OSA severity and AAC, and 2) whether OSA can impact the extent of AAC independent of comorbid atherogenic risk factors. 390 participants aged 40-70 years underwent polysomnography and abdominal computed tomography. AAC was separately quantified in the upper and lower abdominal aorta using the modified Agatston scoring method, and the total AAC score was calculated as a sum of the two scores. OSA was defined as none/mild (apnea-hypopnea index [AHI] <15, n = 87), moderate (AHI 15-30, n = 129), and severe (AHI ≥30, n = 174). Log-transformed total AAC score adjusted for age and body mass index (BMI) was greater in participants with an elevated AHI (3.4 for none/mild OSA, 3.7 for moderate OSA, and 4.2 for severe OSA, p = 0.04). Multivariate linear regression analysis including age and BMI as covariates showed that severe OSA was associated with higher scores for the lower and total AAC (β = 0.15 and 0.14, p = 0.01 and 0.01, respectively). The association did not persist after additionally adjusting for traditional atherogenic risk factors including visceral fat, smoking, hypertension, dyslipidemia, and diabetes. Severe OSA was associated with a greater extent of AAC, which was dependent on coexisting atherogenic risk factors. Comorbid cardiometabolic disorders may largely mediate the association of OSA with subclinical atherosclerosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Atherosclerosis 04/2015; 241(1):6-11. DOI:10.1016/j.atherosclerosis.2015.04.801 · 3.97 Impact Factor
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    ABSTRACT: Chronic obstructive pulmonary disease (COPD) is characterized by a mixture of emphysema and airway disease. The forced oscillation technique (FOT) has been applied to COPD patients to clarify changes in respiratory mechanics; dynamic changes in respiratory resistance (Rrs) during breathing (within-breath changes in Rrs, ΔRrs) are characteristic of COPD. However, the pathophysiological significance of these changes is unknown. The aim of this study was to assess how emphysema and airway disease influence ΔRrs in COPD patients. In this cross-sectional study, stable COPD patients were recruited and underwent respiratory impedance measurements with a commercially available FOT device. Rrs was recorded during tidal breathing and then analyzed as whole-breath Rrs (Rrs at 5 Hz, R5; Rrs at 20 Hz, R20; and their difference, R5-R20) or as ΔRrs, the difference between the expiratory and inspiratory Rrs (ΔR5, ΔR20 and ΔR5-R20). The percentage of the low attenuation area (LAA%) and airway wall area (WA%) was quantified by computed tomography analysis, and their contributions to ΔRrs were examined. Seventy-five COPD patients were recruited. LAA% was negatively correlated with ΔR5 and ΔR5-R20 (P = 0.0002 and P = 0.0033, respectively); meanwhile, WA% in B(10) was positively correlated with ΔR5 and ΔR5-R20 (P = 0.0057 and P < 0.0001, respectively). Multivariate analysis revealed that the contribution of both LAA% and WA% in B(10) to ΔRrs was independent of the severity of airflow limitations. This study shows that emphysema suppresses ΔRrs in COPD patients, while airway disease increases ΔRrs in these patients. © 2015 Asian Pacific Society of Respirology.
    Respirology 03/2015; DOI:10.1111/resp.12535 · 3.50 Impact Factor
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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; 79(6). DOI:10.1253/circj.CJ-14-1303 · 3.69 Impact Factor
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    ABSTRACT: There are reports suggesting that obstructive sleep apnea (OSA) may itself cause weight gain. However, recent reports showed increases in body mass index (BMI) following continuous positive airway pressure (CPAP) treatments. When considering weight changes, changes in humoral factors that have significant effects on appetite such as acyl (AG) and desacyl ghrelin (DAG), leptin, insulin, and glucose and their interactions, examples of which are AG/ DAG and AG/ insulin, are important. The aim of this study was to test the hypothesis that some appetite-related factors had a specific profile before and after CPAP treatment. Metabolic parameters were measured cross-sectionally while fasting and 30, 60, 90, and 120 min following breakfast in no or mild OSA (apnea hypopnea index <15, n = 15) and moderate-to-severe OSA (apnea hypopnea index ≥15, n = 39) participants in a single institute. There were no differences in age, sex, BMI, or visceral fat accumulation between the two groups. Twenty-one patients with moderate-to-severe OSA who received CPAP treatment also prospectively underwent the same testing following 3 months of CPAP treatment. Although fasting and postprandial glucose, insulin, and leptin levels did not differ between no or mild OSA and moderate-to-severe OSA participants, AG and DAG, including AG/ DAG and AG/ insulin, under fasting and postprandial conditions were significantly increased in the moderate-to-severe OSA patients (p < 0.01). After 3 months of CPAP treatment in 21 of the moderate-to-severe OSA participants, AG/ DAG did not change significantly, but other ghrelin-related parameters including AG/ insulin significantly decreased compared with values before treatment but remained higher than in no or mild OSA. Among several important metabolic factors, ghrelin-related factors had the strongest associations with moderate-to-severe OSA. These results indicate that continuous changes in ghrelin secretion in OSA patients existed at least within 3 months of CPAP treatment. Methods to prevent OSA as well as treatment in its early stage may be recommended. URL:http://www.clinicaltrials.gov. Unique identifier: NCT00942110. Copyright © 2015 American Academy of Sleep Medicine. All rights reserved.
    Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine 03/2015; · 2.83 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 · 5.80 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.
    Stem Cell Reports 09/2014; 3(3). DOI:10.1016/j.stemcr.2014.07.005

Publication Stats

6k Citations
1,425.63 Total Impact Points


  • 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
    • Hikone Municipal Hospital
      Hikone, Shiga Prefecture, Japan
  • 1992
    • Hyogo Prefectural Amagasaki Hospital
      Amagasaki, Hyōgo, Japan