Fukunaga, Koichi

写真a

Affiliation

School of Medicine, Department of Internal Medicine (Pulmonary Medicine) (Shinanomachi)

Position

Professor
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Other Affiliation 【 Display / hide 】

  • School of Medicine, 内科学(呼吸器), Associate Professor

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Career 【 Display / hide 】

  • 1994.04
    -
    Present

    慶應義塾大学医学部, 内科学教室, 研修医

  • 2000.01
    -
    Present

    東京大学大学院, 生化学分子細胞生物学講座, 研究員

  • 2001.07
    -
    Present

    独立行政法人国立病院機構南横浜病院, 内科, 医員

  • 2002.08
    -
    Present

    ハーバード大学医学部Brigham Women’s Hospital, Post Doctoral fellow

  • 2005.11
    -
    Present

    慶應義塾大学医学部, 内科学呼吸器内科, 臨床助手

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Academic Background 【 Display / hide 】

  • 1994.03

    慶應義塾大学, 医学部

    University, Graduated

  • 2002.04

    慶應義塾大学, 臨床系呼吸循環器内科学

    Graduate School, Completed, Doctoral course

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Academic Degrees 【 Display / hide 】

  • 博士（医学）, 慶應義塾大学, Coursework, 2002.04

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Licenses and Qualifications 【 Display / hide 】

  • 日本医師会産業認定医

  • 臨床研修指導医

  • 日本感染症学会　ICD（インフェクション・コントロールドクター）

  • 日本がん治療認定医機構　認定医

  • 日本アレルギー学会　専門医・指導医

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Research Areas 【 Display / hide 】

  • Life Science / Respiratory medicine

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Research Keywords 【 Display / hide 】

  • アレルギー

  • 喘息

  • 睡眠時無呼吸症候群

  • 脂質メディエーター

  • 自然免疫

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Research Themes 【 Display / hide 】

  • 睡眠時無呼吸症候群における合併症と新たな診断法の解明, 

    2010.04
    -
    Present

  • 難治性喘息における病態解明, 

    2000.04
    -
    Present

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Books 【 Display / hide 】

  • 進行性非小細胞肺癌に対する併用化学療法におけるDocetaxel投与量の影響

    YAMAGUCHI KAZUHIRO, 2003.12

  • ヒト気管支平滑筋細胞におけるトロンボキサンA2の作用

    Suzuki Yuusuke, Asano Kouichirou, Nakajima Takeshi, Yamaguchi Kazuhiro, Fukunaga Kouichi, Shiomi Tetsuya, 2003.02

  • ヒト気管支平滑筋細胞におけるトロンボキサンA2の作用

    YAMAGUCHI KAZUHIRO, 2003

  • 喘息の薬理遺伝学，副腎皮質ステロイド薬―グルココルチコイド受容体遺伝子変異と喘息治療の可能性―

    Fukunaga Kouichi, Yamaguchi Kazuhiro, 2002.04

  • ロイコトリエンC4合成酵素遺伝子多型とロイコトリエン受容体拮抗薬pranlukastの臨床効果

    Asano Kouichirou，Hasegawa Naoki，Nakamura Hidetoshi，Fukunaga Kouichi，Shiomi Tetsuya，Suzuki Yuusuke，Kanazawa Minoru，Yamaguchi Kazuhiro, 2002.02

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Papers 【 Display / hide 】

  • Prognostic significance of chronic kidney disease and impaired renal function in Japanese patients with COVID-19

    Tanaka H., Chubachi S., Asakura T., Namkoong H., Azekawa S., Otake S., Nakagawara K., Fukushima T., Lee H., Watase M., Sakurai K., Kusumoto T., Masaki K., Kamata H., Ishii M., Hasegawa N., Okada Y., Koike R., Kitagawa Y., Kimura A., Imoto S., Miyano S., Ogawa S., Kanai T., Fukunaga K.

    BMC Infectious Diseases 24 ( 1 )  2024.12

    　View Summary

    Background: Renal impairment is a predictor of coronavirus disease (COVID-19) severity. No studies have compared COVID-19 outcomes in patients with chronic kidney disease (CKD) and patients with impaired renal function without a prior diagnosis of CKD. This study aimed to identify the impact of pre-existing impaired renal function without CKD on COVID-19 outcomes. Methods: This retrospective study included 3,637 patients with COVID-19 classified into three groups by CKD history and estimated glomerular filtration rate (eGFR) on referral: Group 1 (n = 2,460), normal renal function without a CKD history; Group 2 (n = 905), impaired renal function without a CKD history; and Group 3 (n = 272), history of CKD. We compared the clinical characteristics of these groups and assessed the effect of CKD and impaired renal function on critical outcomes (requirement for respiratory support with high-flow oxygen devices, invasive mechanical ventilation, or extracorporeal membrane oxygen, and death during hospitalization) using multivariable logistic regression. Results: The prevalence of comorbidities (hypertension, diabetes, and cardiovascular disease) and incidence of inflammatory responses (white blood counts, and C-reactive protein, procalcitonin, and D-dimer levels) and complications (bacterial infection and heart failure) were higher in Groups 2 and 3 than that in Group 1. The incidence of critical outcomes was 10.8%, 17.7%, and 26.8% in Groups 1, 2, and 3, respectively. The mortality rate and the rate of requiring IMV support was lowest in Group 1 and highest in Group 3. Compared with Group 1, the risk of critical outcomes was higher in Group 2 (adjusted odds ratio [aOR]: 1.32, 95% confidence interval [CI]: 1.03–1.70, P = 0.030) and Group 3 (aOR: 1.94, 95% CI: 1.36–2.78, P < 0.001). Additionally, the eGFR was significantly associated with critical outcomes in Groups 2 (odds ratio [OR]: 2.89, 95% CI: 1.64–4.98, P < 0.001) and 3 (OR: 1.87, 95% CI: 1.08–3.23, P = 0.025) only. Conclusions: Clinicians should consider pre-existing CKD and impaired renal function at the time of COVID-19 diagnosis for the management of COVID-19.

  • Chronic obstructive pulmonary disease, asthma, and mechanical ventilation are risk factors for dyspnea in patients with long COVID: A Japanese nationwide cohort study

    Matsuyama E., Miyata J., Terai H., Miyazaki N., Iwasaki T., Nagashima K., Watase M., Sunata K., Namkoong H., Asakura T., Masaki K., Chubachi S., Ohgino K., Kawada I., Minami K., Hagiwara R., Ueda S., Yoshiyama T., Kokuto H., Kusumoto T., Oashi A., Miyawaki M., Saito F., Tani T., Ishioka K., Takahashi S., Nakamura M., Ishii M., Sato Y., Fukunaga K.

    Respiratory Investigation 62 ( 6 ) 1094 - 1101 2024.11

    ISSN  22125345

    　View Summary

    Background: Patients often experience multiple prolonged symptoms following acute coronavirus disease 2019 (COVID-19) recovery, defined as long coronavirus disease (COVID). Patients with long COVID may experience dyspnea during acute and post-acute phases. Therefore, this study aimed to identify specific risk factors for dyspnea in patients with long COVID. Methods: Hospitalized patients with COVID-19, aged ≥18 years, were enrolled in this multicenter cohort study conducted at 26 medical institutions across Japan. Clinical data during hospitalization and patient-reported outcomes after discharge at the 3, 6, and 12-month follow-ups were retrieved from medical records and paper-based or smartphone application-based questionnaires, respectively. Results: Generalized linear mixed model (GLMM) analysis of prolonged dyspnea at each time point during follow-up showed that this symptom was associated with chronic obstructive pulmonary disease (COPD) (odds ratio [OR], 2.74; 95% confidence interval [CI], 1.31–5.74), asthma (OR, 2.21; 95%CI, 1.17–4.16), and ventilator management (OR, 3.10; 95%CI, 1.65–5.83). In addition, patients with COPD (44.4%) and ventilator management (25.0%) were more frequently associated with delayed dyspnea onset. The generalized estimating equations analysis results with multiple imputed datasets, conducted as a sensitivity analysis, confirmed the adjusted GLMM analysis results. Conclusions: Prolonged dyspnea was associated with COPD, asthma, and severe infection that required mechanical ventilation in the Japanese population with long COVID. Further investigation is needed to clarify its mechanism and develop prophylactic and therapeutic strategies for dyspnea in patients with long COVID.

  • Combined use of serum ferritin and KL-6 levels as biomarkers for predicting COVID-19 severity

    Tanaka H., Toya E., Chubachi S., Namkoong H., Asakura T., Azekawa S., Otake S., Nakagawara K., Fukushima T., Watase M., Sakurai K., Masaki K., Kamata H., Ishii M., Hasegawa N., Okada Y., Koike R., Kitagawa Y., Kimura A., Imoto S., Miyano S., Ogawa S., Kanai T., Fukunaga K.

    Respiratory Investigation 62 ( 6 ) 1132 - 1136 2024.11

    ISSN  22125345

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    Objectives: To assess the value of serum ferritin and Krebs von den Lungen-6 (KL-6) levels for predicting severe COVID-19 (death or requirement for invasive mechanical ventilation [IMV]/high-flow oxygen). Methods: Data were analyzed on 2495 patients with COVID-19 from February 2020 to November 2022 using data from a nationwide COVID-19 database. Results: Patients with high KL-6 and low ferritin levels were older with more comorbidities and higher mortality rates, whereas those with high ferritin and low KL-6 levels were younger, predominantly male, and more likely to need IMV. A high level of both markers was strongly associated with critical outcomes (adjusted odds ratio: 13.6, 95% confidence interval: 8.58–21.5). The combination of both markers had higher predictive value than either marker alone (area under the curve: 0.709, 0.745, and 0.781 for KL-6, ferritin, and KL-6 + ferritin, respectively). Conclusions: The combination of both markers accurately predicted COVID-19 severity.

  • Social impact of brain fog and analysis of risk factors: Long COVID in Japanese population

    Shigematsu L., Kimura R., Terai H., Mimura Y., Ito D., Bun S., Namkoong H., Asakura T., Chubachi S., Masaki K., Ohgino K., Miyata J., Kawada I., Ishii M., Takemura R., Ueda S., Yoshiyama T., Kokuto H., Kusumoto T., Oashi A., Miyawaki M., Saito F., Tani T., Ishioka K., Takahashi S., Nakamura M., Sato Y., Fukunaga K.

    Annals of Clinical and Translational Neurology 11 ( 8 ) 2188 - 2200 2024.08

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    Objective: To reveal the clinical features and assess risk factors linked to brain fog and its societal implications, including labor productivity, providing valuable insights for the future care of individuals who have experienced coronavirus disease 2019 (COVID-19). Methods: We analyzed a comprehensive cohort dataset comprising 1,009 patients with COVID-19 admitted to Japanese hospitals. To assess brain fog, we analyzed patients who responded to a questionnaire indicating symptoms such as memory impairment and poor concentration. Results: The prevalence of brain fog symptoms decreased 3 months posthospitalization but remained stable up to 12 months. Neurological symptoms such as taste and smell disorders and numbness at hospitalization correlated with a higher frequency of identifying brain fog as a long COVID manifestation. Our findings indicated that advanced age, female sex, a high body mass index, oxygen required during hospitalization, chronic obstructive pulmonary disease, asthma, and elevated C-reactive protein and elevated D-dimer levels were risk factors in patients exhibiting brain fog. Additionally, we demonstrated the negative impact of brain fog on labor productivity by presenteeism scores. Interpretations: This study clarified the clinical characteristics of patients experiencing brain fog as a long COVID manifestation, specifically emphasizing neurological symptoms during hospitalization and their correlation with brain fog. Additionally, the study identified associated risk factors for its onset and revealed that the emergence of brain fog was linked to a decline in labor productivity.

  • CT-derived vertebral bone mineral density is a useful biomarker to predict COVID-19 outcome

    Azekawa S., Maetani T., Chubachi S., Asakura T., Tanabe N., Shiraishi Y., Namkoong H., Tanaka H., Shimada T., Fukushima T., Otake S., Nakagawara K., Watase M., Terai H., Sasaki M., Ueda S., Kato Y., Harada N., Suzuki S., Yoshida S., Tateno H., Yamada Y., Jinzaki M., Hirai T., Okada Y., Koike R., Ishii M., Kimura A., Imoto S., Miyano S., Ogawa S., Kanai T., Fukunaga K.

    Bone 184 2024.07

    ISSN  87563282

    　View Summary

    The low vertebral bone computed tomography (CT) Hounsfield unit values measured on CT scans reflect low bone mineral density (BMD) and are known as diagnostic indicators for osteoporosis. The potential prognostic significance of low BMD defined by vertebral bone CT values for the coronavirus disease 2019 (COVID-19) remains unclear. This study aimed to assess the impact of BMD on the clinical outcome in Japanese patients with COVID-19 and evaluate the association between BMD and critical outcomes, such as high-flow nasal cannula, non-invasive and invasive positive pressure ventilation, extracorporeal membrane oxygenation, or death. We examined the effects of COVID-19 severity on the change of BMD over time. This multicenter retrospective cohort study enrolled 1132 inpatients with COVID-19 from the Japan COVID-19 Task Force database between February 2020 and September 2022. The bone CT values of the 4th, 7th, and 10th thoracic vertebrae were measured from chest CT images. The average of these values was defined as BMD. Furthermore, a comparative analysis was conducted between the BMD on admission and its value 3 months later. The low BMD group had a higher proportion of critical outcomes than did the high BMD group. In a subanalysis stratifying patients by epidemic wave according to onset time, critical outcomes were higher in the low BMD group in the 1st–4th waves. Multivariable logistic analysis of previously reported factors associated with COVID-19 severity revealed that low BMD, chronic kidney disease, and diabetes were independently associated with critical outcomes. At 3 months post-infection, patients with oxygen demand during hospitalization showed markedly decreased BMD than did those on admission. Low BMD in patients with COVID-19 may help predict severe disease after the disease onset. BMD may decrease over time in patients with severe COVID-19, and the impact on sequelae symptoms should be investigated in the future.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

  • Distinct roles of types 1 and 2 interferons in human eosinophil regulation: A multi-omics analysis

    Sasaki H., Miyata J., Kawashima Y., Konno R., Ishikawa M., Hasegawa Y., Onozato R., Otsu Y., Matsuyama E., Sunata K., Masaki K., Kabata H., Kimizuka Y., Ueki S., Asano K., Kawana A., Arita M., Fukunaga K.

    Allergy: European Journal of Allergy and Clinical Immunology 79 ( 11 ) 3141 - 3145 2024.11

    ISSN  01054538

  • A second update on mapping the human genetic architecture of COVID-19

    Kanai M., Andrews S.J., Cordioli M., Stevens C., Neale B.M., Daly M., Ganna A., Pathak G.A., Iwasaki A., Karjalainen J., Mehtonen J., Pirinen M., Chwialkowska K., Trankiem A., Balaconis M.K., Veerapen K., Wolford B.N., Ahmad H.F., von Hohenstaufen Puoti K.A., Boer C., Boua P.R., Butler-Laporte G., Cadilla C.L., Colombo F., Douillard V., Dueker N., Dutta A.K., El-Sherbiny Y.M., Eltoukhy M.M., Esmaeeli S., Faucon A., Fave M.J., Cadenas I.F., Francescatto M., Francioli L., Franke L., Fuentes M., Durán R.G., Cabrero D.G., Harry E.N., Jansen P., Szentpéteri J.L., Kaja E., Kirk C., Kousathanas A., Krieger J.E., Patel S.K., Lemaçon A., Limou S., Lió P., Marouli E., Marttila M.M., Medina-Gómez C., Michaeli Y., Migeotte I., Mondal S., Moreno-Estrada A., Moya L., Nakanishi T., Nasir J., Pasko D., Pearson N.M., Pereira A.C., Priest J., Prijatelj V., Prokic I., Teumer A., Várnai R., Romero-Gómez M., Roos C., Rosenfeld J., Ruolin L., Schulte E.C., Schurmann C., Sedaghati-khayat B., Shaheen D., Shivanathan I., Sipeky C., Sirui Z., Striano P., Tanigawa Y., Remesal A.U., Vadgama N., Vallerga C.L., van der Laan S., Verdugo R.A., Wang Q.S., Wei Z., Zainulabid U.A., Zárate R.N., Auton A., Shelton J.F., Shastri A.J., Weldon C.H., Filshtein-Sonmez T., Coker D., Symons A.

    Nature 621 ( 7977 ) E7 - E26 2023.09

    ISSN  00280836

  • Editorial: Heterogeneity of ILC2s

    Kabata H., Fukunaga K.

    Frontiers in Immunology 14 2023

  • How Can Dupilumab Cause Eosinophilic Pneumonia?

    Kurihara M., Masaki K., Matsuyama E., Fujioka M., Hayashi R., Tomiyasu S., Sasahara K., Sunata K., Asaoka M., Akiyama Y., Nishie M., Irie M., Tanosaki T., Kabata H., Fukunaga K.

    Biomolecules 12 ( 12 )  2022.12

    　View Summary

    Reports of eosinophilic pneumonia (EP) as a side effect of dupilumab administration are limited in previous studies. Herein, we report two cases in which EP developed subsequent to the administration of dupilumab for eosinophilic chronic rhinosinusitis (ECRS). Case 1: A 55-year-old woman presented with ECRS, eosinophilic otitis media, and bronchial asthma, and was treated with dupilumab for ECRS. Five weeks later, fever and dyspnea developed, and infiltration shadows were observed in her lungs. The peripheral blood eosinophil count (PBEC) was 3848/μL (26%), bronchoalveolar lavage fluid showed eosinophilic infiltration, and EP was subsequently diagnosed. Her condition improved following prednisolone treatment. Case 2: A 59-year-old man presented with fatigue and dyspnea after receiving dupilumab for ECRS. He had infiltrative shadows throughout his left lung field, and his PBEC was 4850/μL (26.5%). Prednisolone was initiated, and his condition improved. EP developed in both patients during the period of elevated PBEC after dupilumab administration, and dupilumab was suspected to be the causative agent in their EP. Hence, EP should be considered as a differential diagnosis when fever and dyspnea appear following dupilumab administration.

  • A rare case of COVID-19 infection with laryngeal involvement

    Asaoka M., Chubachi S., Yamada Y., Fukunaga K.

    BMJ Case Reports 14 ( 6 )  2021.06

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Presentations 【 Display / hide 】

  • 進行性非小細胞癌に対する併用化学療法におけるドセタキセル投与量の影響

    YAMAGUCHI KAZUHIRO

    第137回日本肺癌学会関東地方会 (東京) , 

    2003.06
    , 

    Oral presentation (general)

  • The usefulness monitoring serum concentrations of pulmonary epithelial markers KL6 and SPD during 18 months chemotherapy for patients with pulmonary Mycobacteria avium complex infection.

    YAMAGUCHI KAZUHIRO

    2003 ATS International Conference (Seattle) , 

    2003.05
    , 

    Poster presentation

  • 一次性肺MAC（Mycobacterium avium complex）症に対するクラリスロマイシン800mgを含む4剤治療の効果

    Hasegawa Naoki, Ooya Sumire, Fukunaga Kouichi, Takeshita Kei, Kou Hidefumi, Shimizu Mie, Yamada Wakako, Fujishima Seitarou, Ishizaka Akitoshi, Komatsu Hikotarou, Ishii Masamichi, Yamaguchi Kazuhiro

    43回日本呼吸器学会総会, 

    2003.03
    , 

    Oral presentation (general)

  • 血小板活性化因子（PAF）受容体遺伝子多型のヒト好中球機能に及ぼす影響

    Nakajima Takeshi, Asano Kouichirou, Fukunaga Kouichi, Suzuki Yuusuke, Shiomi Tetsuya, Yamaguchi Kazuhiro

    43回日本呼吸器学会総会, 

    2003.03
    , 

    Oral presentation (general)

  • Effects of thromboxane A2 mimetic on proliferation of human bronchial smooth muscle cells

    YAMAGUCHI KAZUHIRO

    2003 American Thoracic Society International Conference ('Seattle, Washington, USA') , 

    2003
    , 

    Poster presentation

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • Novel therapeutic strategy for refractory asthma using immunophenotyping

    2022.04
    -
    2025.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 基盤研究(B), Principal investigator

  • ヒト腸内細菌移植マウスを用いた肥満合併重症喘息の解明

    2018.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • steroid resistance of upper and lower airways

    2014.04
    -
    2017.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

    　View Summary

    In conducting our research regarding steroid resistance of upper and lower airways, we collected　eosinophils and Group 2 innate lymphoid cells (ILC 2s) from surgical specimens of chronic eosinophilic sinusitis and peripheral blood of severe asthmatic patients and examined them. First, we established a method to collect each cell stably from the specimen and blood. Especially, ILC2s with small number in blood was examined using single cell analysis method which can analyze from one cell. As a result, the difference between the healthy subjects and the patient's phenotype (proliferative ability and cytokine production capacity) has become clear. In addition, eosinophils were also examined using comprehensive analysis and revealed differences in productivity of enzymes and mediators as compared to healthy subjects. We are currently investigating the resistance of steroids of these cells and will continue to conduct current research.

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Courses Taught 【 Display / hide 】

  • SYMPTOMATOLOGY

    2024

  • PHARMACOLOGY

    2024

  • ORIENTAL MEDICINE

    2024

  • LECTURE SERIES, INTERNAL MEDICINE (PULMONOLOGY)

    2024

  • KAMPO MEDICINE: SEMINAR

    2024

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