Sakurai, Kaori

写真a

Affiliation

School of Medicine, Center for Preventive Medicine ( Shinanomachi )

Position

Instructor
Scopus Paper Info  
Paper Count: 26 Citation Count: 253 h-index: 10

Click to view the Scopus page. The data was downloaded from Scopus API in August 23, 2026, via http://api.elsevier.com and http://www.scopus.com .

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Academic Background 【 Display / hide 】

  • 2007.04
    -
    2013.03

    Keio University, 医学部

  • 2018.04
    -
    2023.03

    Keio University, 医学部医学研究科博士課程

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Academic Degrees 【 Display / hide 】

  • 博士（医学）, Keio University, 2025.08

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Papers 【 Display / hide 】

  • Determinants of high chronic obstructive pulmonary disease assessment test scores according to airflow limitation severity: a three-year prospective study

    Iizuka H., Irie H., Chubachi S., Nishikawa K., Nishizawa T., Fukuzawa K., Arai T., Shimada T., Otake S., Sakurai K., Iijima H., Tanabe N., Tanimura K., Shimizu K., Sato S., Nakamura H., Asano K., Fukunaga K.

    BMC Pulmonary Medicine 26 ( 1 )  2026.04

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    BACKGROUND: The determinants of chronic obstructive pulmonary disease (COPD) assessment test (CAT) scores according to airflow limitation severity are not fully understood. METHODS: We aimed to elucidate this by analyzing data from 378 patients with COPD, categorized into two groups based on airflow limitation severity (FEV1 > 50% [GOLD-mild] and ≤ 50% [GOLD-severe]). Within each severity group, patients were further sub-stratified by CAT score (≥ 10 vs. <10). RESULTS: Patients with CAT scores ≥ 10 in the GOLD-mild group were older, with more severe airflow limitation and higher prevalence of gastroesophageal reflux disease (GERD), anxiety, depression, and diabetes, whereas those in the GOLD-severe group showed higher GERD and asthma prevalences. GERD and asthma contributed predominantly to respiratory-specific items. Airflow limitation and GERD were strong determinants in both severity groups. Key determinants were anxiety and depression in the GOLD-mild group and asthma in the GOLD-severe group. These associations remained consistent over 3 years. CONCLUSIONS: These findings offer valuable insights for managing patients with pronounced subjective symptoms in COPD.

  • Adipose–Muscle Crosstalk in COPD Cachexia: Early Adipose Atrophy Drives Subsequent Muscle Wasting

    Shimada T., Chubachi S., Nishikawa K., Arai T., Iizuka H., Otake S., Sakurai K., Hamamoto J., Sasaki M., Maetani T., Tanabe N., Masaki K., Kabata H., Miyata J., Yamada Y., Jinzaki M., Nakamura H., Asano K., Fukunaga K.

    Journal of Cachexia Sarcopenia and Muscle 16 ( 6 )  2025.12

    ISSN  21905991

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    Background: Chronic obstructive pulmonary disease (COPD) is frequently associated with cachexia, leading to poor prognoses and reduced quality of life. However, the mechanisms underlying adipose tissue atrophy, its pathological significance and its interaction with skeletal muscle remain poorly understood. We hypothesised that adipose tissue atrophy precedes muscle wasting in COPD-associated cachexia, and muscle atrophy progresses through adipose–muscle crosstalk. Methods: We analysed chest computed tomography scans of 185 patients with COPD to quantify the cross-sectional areas of the pectoralis muscle (PM), subcutaneous adipose tissue (SAT) and epicardial adipose tissue (EAT), and the percentage of low attenuation area (LAA%) as an index of emphysema. To elucidate the pathophysiological mechanisms underlying cachexia in COPD, we performed histological and molecular analyses of the lung, muscle and adipose tissues over time in a cigarette smoke–induced emphysema mouse model. Further, we used an in vitro culture system of differentiated adipocytes (3T3-L1) and myotubes (C2C12) to study the effects of cigarette smoke extract (CSE) on adipose–muscle interaction. Results: In patients with COPD, the areas of PM, SAT and EAT all demonstrated significant negative correlations with LAA%; notably, PM and EAT were independently associated with the extent of emphysematous changes. In the smoke-exposed murine model, adipose tissue atrophy was observed after 1 month of exposure, accompanied by increased expressions of IL-6 and IL-1β, macrophage infiltration and the upregulation of the lipolytic enzymes ATGL and HSL. The adipose atrophy had further progressed after 3 months of exposure, and the high expression of UCP1 was sustained, which suggested the browning of adipose tissue. Conversely, muscle atrophy was not evident at 1 month but became apparent after 3 months, coinciding with emphysema development. This was associated with the downregulation of the myogenic markers MyoD and Myogenin and the upregulation of the muscle degradation marker Atrogin-1. In vitro experiments revealed that CSE exposure reduced lipid droplet content and induced IL-6 and IL-1β expressions in adipocytes. Conditioned media from CSE-treated adipocytes triggered myotube atrophy and downregulated MyoD and Myogenin but upregulated Atrogin-1. Conclusions: Our findings indicate that cigarette smoke-induced adipose tissue atrophy precedes muscle wasting, and alterations in adipose tissue may contribute to muscle atrophy progression. Adipose tissue dysfunction may be implicated in the development of cachexia in patients with COPD, highlighting its potential as a therapeutic target.

  • Roflumilast reduces the number of lung adenocarcinomas, inflammation, and emphysema in a smoking-induced mouse model

    Sakurai K., Nakayama S., Chubachi S., Otake S., Shimada T., Irie H., Tsutsumi A., Kameyama N., Hegab A.E., Shimoda M., Hamamoto J., Terai H., Yasuda H., Kanai Y., Fukunaga K.

    BMC Pulmonary Medicine 25 ( 1 )  2025.12

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    Background: The prognosis of lung cancer complicated by chronic obstructive pulmonary disease is poor, and effective prophylactic agents have not been established. Given that inflammation is a shared pathogenic mechanism of both diseases, we aimed to evaluate the efficacy of roflumilast, a novel anti-inflammatory drug, in preventing emphysema and lung cancer using a smoking-induced lung cancer mouse model. Methods: Male A/J mice were exposed to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a potent carcinogen, and intermittent mainstream cigarette smoke for 20 weeks. Roflumilast or vehicle was administered via intragastric gavage once daily. Lung tissues were assessed for tumor nodules and emphysema, and bronchoalveolar lavage fluid was collected for cell counting. Emphysema severity and concentrations of inflammatory cytokines (IL-6, IL-1β, and TNF-α) were assessed. RAW 264.7 macrophage cells were used to assess cellular responses to cigarette smoke extract. Results: Roflumilast attenuated the increase in total cells and macrophages in bronchoalveolar lavage fluid induced by intermittent smoking exposure and significantly suppressed smoking-induced expressions of IL-6, IL-1β, and TNF-α. Roflumilast also reduced emphysematous changes and the number of lung tumors. In vitro, roflumilast attenuated cigarette smoke extract-induced expression of IL-6, IL-1β, and TNF-α in RAW 264.7 cells. Conclusions: This study highlights the potential use of roflumilast as a chemopreventive agent for patients with chronic obstructive pulmonary disease who are at risk of lung cancer and underscores its relevance for future clinical application and research on phosphodiesterase-4 inhibitors.

  • Exploring the pathophysiology of anemia in COPD: Insights from chest CT and longitudinal clinical data

    Takizawa A., Shimada T., Chubachi S., Arai T., Miyakawa A., Iizuka H., Otake S., Sakurai K., Tanabe N., Yamada Y., Jinzaki M., Nakamura H., Asano K., Fukunaga K.

    Respiratory Medicine 240 2025.04

    ISSN  09546111

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    Background: Although anemia has been associated with chronic obstructive pulmonary disease (COPD) severity, the underlying risk factors, such as chest imaging indicators, remain poorly understood. In this study, we aimed to investigate the relationship between anemia and clinical features, including pulmonary and extrapulmonary indicators on chest computed tomography (CT), and to clarify the pathophysiology of anemia in COPD. Methods: A total of 400 patients with COPD were prospectively followed for 3 years. Anemia was defined as hemoglobin <13 g/dl in males and <12 g/dl in females. Patients were categorized into the anemia and non-anemia groups, and their clinical characteristics were compared. Results: The anemia group exhibited lower percentage of predicted forced expiratory volume in 1 s (%FEV<inf>1</inf>) and body mass index (BMI) measurements, worse COPD assessment test (CAT) scores, and more frequent exacerbations. Imaging revealed more severe emphysema, lower cross-sectional areas of the pectoralis and erector spinae muscles, decreased subcutaneous fat, and more severe coronary artery calcification in this group. Additionally, echocardiography demonstrated a higher prevalence of pulmonary hypertension and reduced left ventricular ejection fraction in patients with anemia. Three-year longitudinal data analysis further showed that declining hemoglobin levels correlated with the worsening of nutritional status, a deterioration in bone mineral density (BMD), and an increase in CAT scores. Conclusion: Anemia in COPD is a multifactorial comorbidity resulting in emphysema, decreased fat and muscle mass, and reduced BMD.

  • Impact of smoking on gut microbiota and short-chain fatty acids in human and mice: Implications for COPD

    Otake S., Chubachi S., Miyamoto J., Haneishi Y., Arai T., Iizuka H., Shimada T., Sakurai K., Okuzumi S., Kabata H., Asakura T., Miyata J., Irie J., Asano K., Nakamura H., Kimura I., Fukunaga K.

    Mucosal Immunology 18 ( 2 ) 353 - 365 2025.04

    ISSN  19330219

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    We aimed to elucidate the dynamic changes in short-chain fatty acids (SCFA) produced by the gut microbiota following smoking exposure and their role in chronic obstructive pulmonary disease (COPD) pathogenesis. SCFA concentrations were measured in human plasma, comparing non-smokers (n = 6) and smokers (n = 12). Using a mouse COPD model induced by cigarette smoke exposure or elastase-induced emphysema, we modulated SCFA levels through dietary interventions and antibiotics to evaluate their effects on inflammation and alveolar destruction. Human smokers showed lower plasma SCFA concentrations than non-smokers, with plasma propionic acid positively correlating with forced expiratory volume in 1 s/forced vital capacity. Three-month smoking-exposed mice demonstrated altered gut microbiota and significantly reduced fecal SCFA concentrations compared to air-exposed controls. In these mice, a high-fiber diet increased fecal SCFAs and mitigated inflammation and alveolar destruction, while antibiotics decreased fecal SCFAs and exacerbated disease features. However, in the elastase-induced model, fecal SCFA concentration remained unchanged, and high-fiber diet or antibiotic interventions had no significant effect. These findings suggest that smoking exposure alters gut microbiota and SCFA production through its systemic effects. The anti-inflammatory properties of SCFAs may play a role in COPD pathogenesis, highlighting their potential as therapeutic targets.

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