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Yumiko Matsuo,1,2 Emiko Ogawa,1,2 Yoko Tsunoda,1 Akio Yamazaki,1 Satoru Kawashima,1 Yasuki Uchida,1 Hiroaki Nakagawa,1 Daisuke Kinose,1 Masafumi Yamaguchi,1 Yasutaka Nakano1 1Division of Respiratory Medicine, Department of Internal Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan; 2Health Administration Center, Shiga University of Medical Science, Otsu, Shiga, JapanCorrespondence: Emiko Ogawa, Health Administration Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan, Tel/Fax +81-77-548-2212, Email eogawa@belle.shiga-med.ac.jpPurpose: Disease probability measure (DPM) is a useful voxel-wise imaging assessment of gas-trapping and emphysematous lesions in patients with chronic obstructive pulmonary disease (COPD). To elucidate the progression of COPD, we performed a cluster analysis using the following DPM parameters: normal (DPMNormal), gas-trapping (DPMGasTrap), and emphysematous lesions (DPMEmph). Our findings revealed the characteristics of each cluster and the 3-year disease progression using imaging parameters.Patients and Methods: Inspiratory and expiratory chest computed tomography (CT) images of 131 patients with COPD were examined, of which 84 were followed up for 3 years. The percentage of low attenuation volume (LAV%) and the square root of the wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) were quantitatively measured using inspiratory chest CT. A hierarchical cluster analysis was performed using the DPM parameters at baseline. Five clusters were named according to the dominant DPM parameters: normal (NL), normal-GasTrap (NL-GT), GasTrap (GT), GasTrap-Emphysema (GT-EM), and Emphysema (EM).Results: Women were predominantly diagnosed with GT. Forced expiratory volume in 1 s gradually decreased in the following order: NL, NL-GT, GT, GT-EM, and EM. DPMEmph correlated well with LAV%. Four clusters other than NL showed significantly higher values of √Aaw at Pi10 than NL; however, no significant differences were observed among them. In all clusters, DPMEmph increased after 3 years. DPMNormal only increased in the GT cluster.Conclusion: Clusters using DPM parameters may reflect the characteristics of COPD and help understand the pathophysiology of the disease.Keywords: cluster analysis, computed tomography, COPD, DPM, gas-trapping, emphysema

Yumiko Matsuo,1 Emiko Ogawa,1,2 Ruriko Seto-Yukimura,1 Yasushi Ryujin,1,3 Daisuke Kinose,1 Masafumi Yamaguchi,1 Makoto Osawa,1 Taishi Nagao,1 Hajime Kurosawa,4 Yasutaka Nakano1 1Division of Respiratory Medicine, Department of Internal Medicine, Shiga University of Medical Science, Shiga, Japan; 2Health Administration Center, Shiga University of Medical Science, Shiga, Japan; 3Ryujin Medical Clinic, Osaka, Japan; 4Center for Environmental Conservation and Research Safety, Department of Occupation Health, Tohoku University, Miyagi, JapanCorrespondence: Emiko OgawaHealth Administration Center, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga 520-2192, JapanTel/Fax +81-77-548-2212Email eogawa@belle.shiga-med.ac.jpPurpose: The forced oscillation technique (FOT) is a non-invasive method to measure respiratory impedance, the respiratory resistance (Rrs) and reactance (Xrs). The disease probability measure (DPM) is a useful computed tomography (CT) imaging variable for the assessment of gas trapping and emphysema in patients with chronic obstructive pulmonary disease (COPD) using pairs of inspiratory and expiratory CT images. We aimed to develop FOT-based phenotypes and determine whether the phenotypes and their imaging characteristics could facilitate the understanding of COPD pathophysiology.Patients and methods: FOT and spirometry were examined in 164 COPD patients and 22 non-COPD smokers. COPD patients were divided into four FOT-based phenotypes (NL, normal group; RD, resistance-dominant group; XD, reactance-dominant group; and MIX, mixed group) based on the 3rd quartile values of R5 (Rrs at 5Hz) and X5 (Xrs at 5Hz) in the non-COPD group. The emphysematous lesions and the airway lesions were quantitatively assessed in CT images by low attenuation volume and the square root of the wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10), respectively. DPM imaging analysis was also performed in 131 COPD patients. We investigated the differences in COPD parameters between the FOT-based phenotypes.Results: √Aaw at Pi10 were significantly higher in the RD, XD, and MIX groups than in the NL group. The XD group showed lower pulmonary function and higher dyspnea scores than the RD group. No significant changes in DPM values were observed between the RD and the NL groups. The gas-trapping area was significantly higher in the XD group than in the NL group. The MIX group showed the highest dyspnea score, most emphysematous lesions, and the lowest forced expiratory volume in 1 s % predicted value.Conclusion: The FOT-based phenotyping may be useful to assess pathophysiological changes of COPD with CT assessments.Keywords: oscillometry, emphysema, exhalation, quantitative evaluation, COPD

Kenichi Goto,1,2 Emiko Ogawa,1,3 Kaoruko Shimizu,4 Hironi Makita,4 Hidenobu Suzuki,5 Yoshiki Kawata,5 Noboru Niki,5 Masaharu Nishimura,4 Yasutaka Nakano1 1Division of Respiratory Medicine, Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, 2Department of Pulmonary Medicine, Takatsuki Red Cross Hospital, Takatsuki, Osaka, 3Health Administration Center, Shiga University of Medical Science, Otsu, Shiga, 4First Department of Medicine, Hokkaido University Hospital, Sapporo, Hokkaido, 5Institute of Technology and Science, Tokushima University, Tokushima, Tokushima, Japan Background: Osteoporosis is a well-known comorbidity in COPD. It is associated with poor health status and prognosis. Although the exact pathomechanisms are unclear, osteoporosis is suggested to be either a comorbidity due to shared risk factors with COPD or a systematic effect of COPD with a cause–effect relationship. This study aimed to evaluate whether progression of osteoporosis is synchronized with that of COPD. Materials and methods: Data from 103 patients with COPD included in the Hokkaido COPD cohort study were analyzed. Computed tomography (CT) attenuation values of thoracic vertebrae 4, 7, and 10 were measured using custom software, and the average value (average bone density; ABD4,7,10) was calculated. The percentage of low attenuation volume (LAV%) for each patient was also calculated for evaluation of emphysematous lesions. Annual change in thoracic vertebral CT attenuation, which is strongly correlated with dual-energy X-ray absorptiometry-measured bone mineral density, was compared with that in FEV1.0 or emphysematous lesions. Results: In the first CT data set, ABD4,7,10 was significantly correlated with age (ρ=–0.331; p=0.0006), body mass index (BMI; ρ=0.246; p=0.0136), St George’s Respiratory Questionnaire (SGRQ) activity score (ρ=–0.248; p=0.0115), eosinophil count (ρ=0.229; p=0.0198), and LAV% (ρ=–0.372; p=0.0001). However, ABD4,7,10 was not associated with FEV1.0. After adjustment for age, BMI, SGRQ activity score, and eosinophil count, no significant relationship was found between ABD4,7,10 and LAV%. Annual change in ABD4,7,10 was not associated with annual change in LAV% or FEV1.0. Conclusion: Progression of osteoporosis and that of COPD are not directly related or synchronized with each other. Keywords: osteoporosis, quantitative CT analysis, FEV1.0, low attenuation volume, automatic analysis, systemic effect

Eiichi Ogawa,1 Norihiro Furusyo,1 Mindie H Nguyen2 1Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan; 2Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA Abstract: Tenofovir alafenamide (TAF), a novel prodrug of tenofovir (TFV), has been approved for the treatment of chronic hepatitis B virus (HBV) infection. TAF has been shown to be a potent inhibitor of HBV replication at a low dose, with high intracellular concentration and more than 90% lower systemic TFV concentration than tenofovir disoproxil fumarate (TDF). In two randomized, double-blind, multinational, Phase 3, non-inferiority trials for hepatitis B e antigen (HBeAg)-positive and -negative patients (primary analysis: 48 weeks), TAF 25 mg orally once-daily was not inferior to TDF 300 mg in achieving an HBV DNA level