• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Potential role of club cell secretory protein (CC16) in development of obese asthma: findings from a birth cohort and animal studies

Research Project

Project/Area Number 20K10425
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 58020:Hygiene and public health-related: including laboratory approach
Research InstitutionHokkaido University

Principal Investigator

Goudarzi Houman  北海道大学, 医学研究院, 准教授 (40713607)

Co-Investigator(Kenkyū-buntansha) 池田 敦子 (荒木 敦子)  北海道大学, 環境健康科学研究教育センター, 特任教授 (00619885)
今野 哲  北海道大学, 医学研究院, 教授 (20399835)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsAsthma / Obesity / Birth cohort / General population / Adult asthma / circulatory CC16 / Experimental studies / CC16 polymorphism / adult/childhood asthma / CC16 / prospective birth cohort / adult asthma cohort / experimental studies / T2 phebotypes / Airway inflammation / Oxidative biomarkers / birth cohort / adult asthma patients / T helper 2 biomarkers / Adults and children / Club cell protein (CC16) / In vivo study / Asthma and allergy / Obese asthma / Animal studies
Outline of Research at the Start

As clinical implications, CC16 levels could be applied for risk stratification for prevention of progressive airway inflammation, and optimization of asthma treatment in children especially obese individuals. With combination of epidemiological and animal studies, we may provide novel evidence that serial low CC16 concentration, as a risk factor, could be implemented in clinical setting for prevention of obese asthma (and other allergic diseases). Finally, CC16 may attract clinicians’ interest as a target of therapy in obese asthma phenotype in future studies.

Outline of Final Research Achievements

1) Adult asthma cohort: BMI was significantly and monotonously associated with reduced circulating CC16 levels in adults. Mediation analysis revealed that CC16 mediates effects of BMI on airway hyperresponsiveness, asthma severity, and required dose of inhaled corticosteroid. Also, serum CC16 was inversely associated with sputum eosinophils and blood periostin as T2 biomarkers. Patients with the lowest tertile of serum CC16 levels at baseline had a -14.3 mL decline in FEV1 than those with the highest tertile over 5 years of follow-up. 2) Hokkaido Birth cohort: Plasma CC16 was inversely associated with asthma prevalence, and T2 biomarkers(FeNO and blood eosinophils). 3) Experimental studies: The percentage of CC16-expressing cells was reduced in the small airways of both mice and humans with obesity. Obesity reduced circulating CC16 levels but not surfactant protein SP-A and SP-D levels in the mice.

Academic Significance and Societal Importance of the Research Achievements

We showed the effects of reduced human CC16 in development of obese asthma and Th2 inflammation in children and adults for first time. CC16 levels is useful for risk stratification for prevention of progressive airway inflammation, and optimization of asthma treatment especially obese individuals.

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (39 results)

All 2024 2023 2022 2021 2020 Other

All Int'l Joint Research (8 results) Journal Article (15 results) (of which Int'l Joint Research: 14 results,  Peer Reviewed: 15 results,  Open Access: 12 results) Presentation (12 results) (of which Int'l Joint Research: 12 results,  Invited: 1 results) Remarks (4 results)

  • [Int'l Joint Research] Icahn School of Medicine at Mount Sinai/The Murray M. Rosenberg/Department of Pulmonary Medicine(米国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Taipei Medical University/School of Medical/Laboratory Science and Biotechnology(中国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Icahn School of Medicine at Mount Sinai/New York/Prof. Monica Kraft(米国)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Johns Hopkins University/Baltimore/Prof. Shau-ku Huang(米国)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] University of Arizona/Tucson/Prof. Monica Kraft(米国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Johns Hopkins University/Baltimore, MD, USA/Prof. Shau-ku Huang(米国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] University of Arizona/Tucson/Prof. Monica Kraft(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Johns Hopkins University/Baltimore, MD, USA/Prof. Shau-ku Huang(米国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Global fertility in 204 countries and territories, 1950ー2021, with forecasts to 2100: a comprehensive demographic analysis for the Global Burden of Disease Study 20212024

    • Author(s)
      GBD 2021 Fertility and Forecasting Collaborator
    • Journal Title

      Lancet

      Volume: - Issue: 10440 Pages: 00550-6

    • DOI

      10.1016/s0140-6736(24)00550-6

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 20212024

    • Author(s)
      Mohsen Naghavi, Kanyin Liane Ong, Amirali Aali, Hazim S Ababneh, ..., Goudarzi Houman, ..., Murray Christopher J L
    • Journal Title

      The Lancet

      Volume: 403 Issue: 10440 Pages: 2100-2132

    • DOI

      10.1016/s0140-6736(24)00367-2

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Impact of the Covid-19 pandemic and ensuing online teaching on pre-clinical medical education2024

    • Author(s)
      Goudarzi Houman、Onozawa Masahiro、Takahashi Makoto
    • Journal Title

      BMC Medical Education

      Volume: 24 Issue: 1

    • DOI

      10.1186/s12909-023-04967-x

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Applicable predictive factors extracted from peak flow trajectory for the prediction of asthma exacerbation2024

    • Author(s)
      Yang Yichi、Kimura Hirokazu、Goudarzi Houman、Ishikuro Akihiko、Ohtsuka Yoshihiro、Watanabe Kazuhiko
    • Journal Title

      Annals of Allergy, Asthma & Immunology

      Volume: 132 Issue: 4 Pages: 469-476

    • DOI

      10.1016/j.anai.2023.11.015

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Association of serum CC16 levels with eosinophilic inflammation and respiratory dysfunction in severe asthma2023

    • Author(s)
      Goudarzi Houman、Kimura Hirokazu、Kimura Hiroki、Makita Hironi、Takimoto-Sato Michiko、Abe Yuki、Oguma Akira、Matsumoto Munehiro、Takei Nozomu、Matsumoto-Sasaki Machiko、Shimizu Kaoruko、Suzuki Masaru、Shijubo Noriharu、Huang Shau-ku、Hizawa Nobuyuki、Nishimura Masaharu、Konno Satoshi
    • Journal Title

      Respiratory Medicine

      Volume: 206 Pages: 107089-107089

    • DOI

      10.1016/j.rmed.2022.107089

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Exposure to organophosphate flame retardants and plasticizers is positively associated with wheeze and FeNO and eosinophil levels among school-aged children: The Hokkaido study2023

    • Author(s)
      Zeng Yi、Goudarzi Houman、Ait Bamai Yu、Ketema Rahel Mesfin、Roggeman Maarten、den Ouden Fatima、Gys Celine、Miyashita Chihiro、Ito Sachiko、Konno Satoshi、Covaci Adrian、Kishi Reiko、Ikeda-Araki Atsuko
    • Journal Title

      Environment International

      Volume: 181 Pages: 108278-108278

    • DOI

      10.1016/j.envint.2023.108278

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Potential determinants of T helper 2 markers and their distribution in school-aged children2023

    • Author(s)
      Goudarzi Houman、Ikeda-Araki Atsuko、Bamai Yu Ait、Ito Sachiko、Inao Tasuku、Yokota Isao、Miyashita Chihiro、Kishi Reiko、Konno Satoshi
    • Journal Title

      Allergology International

      Volume: 72 Issue: 1 Pages: 100-106

    • DOI

      10.1016/j.alit.2022.07.009

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of obesity on CC16 and their potential role in overweight/obese asthma2023

    • Author(s)
      Goudarzi Houman、Kimura Hirokazu、Kimura Hiroki、Nakamura Akinobu、Hizawa Nobuyuki、Atsumi Tatsuya、Huang Shau-ku、Ito Yoichi M.、Nishimura Masaharu、Konno Satoshi
    • Journal Title

      Respiratory Research

      Volume: 23 Issue: 1 Pages: 174-174

    • DOI

      10.1186/s12931-022-02038-1

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differential role of mucus plugs in asthma: Effects of smoking and association with airway inflammation2023

    • Author(s)
      Oguma Akira、Shimizu Kaoruko、Kimura Hirokazu、Tanabe Naoya、Sato Susumu、Yokota Isao、Takimoto-Sato Michiko、Matsumoto-Sasaki Machiko、Abe Yuki、Takei Nozomu、Goudarzi Houman、Suzuki Masaru、Makita Hironi、Hirai Toyohiro、Nishimura Masaharu、Konno Satoshi
    • Journal Title

      Allergology International

      Volume: 72 Issue: 2 Pages: 262-270

    • DOI

      10.1016/j.alit.2022.10.007

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Blood eosinophil count variability in chronic obstructive pulmonary disease and severe asthma2023

    • Author(s)
      Abe Yuki、Suzuki Masaru、Kimura Hirokazu、Shimizu Kaoruko、Takei Nozomu、Oguma Akira、Matsumoto-Sasaki Machiko、Goudarzi Houman、Makita Hironi、Nishimura Masaharu、Konno Satoshi
    • Journal Title

      Allergology International

      Volume: 72 Issue: 3 Pages: 402-410

    • DOI

      10.1016/j.alit.2022.11.012

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Further evidence for association of YKL-40 with severe asthma airway remodeling2022

    • Author(s)
      Kimura H, Shimizu K, Tanabe N, Makita H, Taniguchi N, Kimura H, Suzuki M, Abe Y, Matsumoto-Sasaki M, Oguma A, Takimoto-Sato M, Takei N, Matsumoto M, Goudarzi H, Sato S, Ono J, Izuhara K, Hirai T, Nishimura M, Konno S
    • Journal Title

      Annals of Allergy, Asthma & Immunology

      Volume: - Issue: 6 Pages: 682-688

    • DOI

      10.1016/j.anai.2022.03.016

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Future career plans of medical students and the COVID‐19 pandemic: Time to recover?2022

    • Author(s)
      Goudarzi Houman、Onozawa Masahiro、Takahashi Makoto
    • Journal Title

      Journal of General and Family Medicine

      Volume: 24 Issue: 2 Pages: 139-140

    • DOI

      10.1002/jgf2.591

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Association of abdominal visceral adiposity with sputum IL-5 levels in asthma2022

    • Author(s)
      Goudarzi Houman、Kimura Hirokazu、Makita Hironi、Abe Yuki、Oguma Akira、Sato Michiko、Matsumoto Munehiro、Takei Nozomu、Kimura Hiroki、Shimizu Kaoruko、Suzuki Masaru、Ito Yoichi M.、Nishimura Masaharu、Konno Satoshi
    • Journal Title

      Allergology International

      Volume: 71 Issue: 1 Pages: 137-139

    • DOI

      10.1016/j.alit.2021.08.003

    • NAID

      130008145220

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Determination of the cutoff values of Th2 markers for the prediction of future exacerbation in severe asthma: An analysis from the Hokkaido Severe Asthma Cohort Study2021

    • Author(s)
      Kimura Hirokazu、Makita Hironi、Taniguchi Natsuko、Takei Nozomu、Matsumoto Munehiro、Kimura Hiroki、Goudarzi Houman、Shimizu Kaoruko、Suzuki Masaru、Nishimura Masaharu、Konno Satoshi
    • Journal Title

      Allergology International

      Volume: 70 Issue: 1 Pages: 68-73

    • DOI

      10.1016/j.alit.2020.09.001

    • NAID

      130007966772

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hokkaido birth cohort study on environment and children’s health: cohort profile 20212021

    • Author(s)
      Kishi Reiko、Ikeda-Araki Atsuko、Miyashita Chihiro、Itoh Sachiko、Kobayashi Sumitaka、Ait Bamai Yu、Yamazaki Keiko、Tamura Naomi、et al.
    • Journal Title

      Environmental Health and Preventive Medicine

      Volume: 26 Issue: 1 Pages: 1-20

    • DOI

      10.1186/s12199-021-00980-y

    • NAID

      210000159057

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Mediation effect of CC16 on the associations between urinary phosphate flame retardants and fractional exhaled nitric oxide among children: The Hokkaido Study.2024

    • Author(s)
      曾 怡, Houman Goudarzi,アイツバマイ ゆふ, 山口 健史, Rahel Mesfin Ketema, Maarten Roggeman, Fatima Den Ouden, Celine Gys, Megasari Marsela, 安田 彩夏、宮下 ちひろ, 今野 哲, Adrian Covaci, 岸 玲子, 池田 敦子
    • Organizer
      94th Annual Meeting of Japanese Society for Hygiene, Kagoshima, Japan
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Exploring individual and joint effects of phthalates on allergies among school children: The Hokkaido Study.2024

    • Author(s)
      Ketema Rahel Mesfin, Ait Bamai Yu, Miyashita Chihiro, Yamaguchi Takeshi, Zeng Yi, Yasuda Ayaka, Marsela Megasari, Goudarzi Houman, Konno Satoshi, Kishi Reiko, Ikeda Atsuko
    • Organizer
      94th Annual Meeting of Japanese Society for Hygiene, Kagoshima, Japan
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Association of circulatory CC16 with type 2 inflammation and pulmonary dysfunction: Potential role of CC16 in obese asthma.2023

    • Author(s)
      Satoshi Konno, Houman Goudarzi, Hirokazu Kimura, Masaru Suzuki, Kaoruko Shimizu, Hiroki Kimura, Noriharu Shijubo, Shau-ku Huang, Masaharu Nishimura.
    • Organizer
      65th Annual Meeting of Thomas L. Petty Aspen Lung Conference, Aspen, Colorado, USA
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Organophosphate Flame Retardants Mixture Exposure associate with Increased Levels of Urinary Oxidative Stress Biomarkers among School Children: The Hokkaido Study.2023

    • Author(s)
      Yi Zeng, Atsuko Ikeda-Araki, Houman Goudarzi, Yu Ait Bamai, Rahel Mesfin Ketema, Maarten Roggeman, Fatima Den Ouden, Celine Gys, Chihiro Miyashita, Sachiko Ito, Satoshi Konno, Adrian Covaci, Reiko Kishi.
    • Organizer
      35th Annual ISEE Conference in Kaohsiung, Taiwan,
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Blood eosinophil count variability in chronic obstructive pulmonary disease and severe asthma.2023

    • Author(s)
      Yuki Abe, Masaru Suzuki, Hirokazu Kimura, Kaoruko Shimizu, Nozomu Takei, Akira Oguma, Machiko Matsumoto-Sasaki,Houman Goudarzi, Hironi Makita, Masaharu Nishimura, Satoshi Konno.
    • Organizer
      American Thoracic Society (ATS) International Conference 2023, Washington, DC, USA
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Association of serum CC16 levels with eosinophilic inflammation and respiratory dysfunction in severe asthma.2023

    • Author(s)
      Houman Goudarzi, Hirokazu Kimura, Hiroki Kimura, Hironi Makita, Michiko Takimoto-Sato, Yuki Abe, Akira Oguma, Munehiro Matsumoto, Nozomu Takei, Machiko Matsumoto-Sasaki, Kaoruko Shimizu, Masaru Suzuki, Noriharu Shijubo, Shau-Ku Huang, Nobuyuki Hizawa, Masaharu Nishimura, Satoshi Konno
    • Organizer
      Japanese Society of Allergology (JSA) 72st Annual Meeting, Tokyo, Japan.
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Predictors of academic performance among medical students using a cluster-analytic approach.2023

    • Author(s)
      Houman Goudarzi, Masahiro Onozawa, Yoichi M. Ito, Makoto Takahashi.
    • Organizer
      The 55th Annual Meeting of the Japan Society for Medical Education (JSME), Nagasaki, Japan.
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of COVID-19 pandemic on career plans and academic performance of medical students.2023

    • Author(s)
      Houman Goudarzi, Masahiro Onozawa, Makoto Takahashi.
    • Organizer
      The 26th Academic Meeting of the JASMEE, Tokyo, Japan.
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of obesity on CC16 and their potential role in obese asthma2022

    • Author(s)
      Houman Goudarzi, Hirokazu Kimura, Hironi Makita, Mune Matsumoto, Nozomu Takei, Kaoruko Shimizu, Taku Watanabe, Masaharu Nishimura, Satoshi Konno
    • Organizer
      Japan Society for Allergology 71st Annual Meeting, 2022 October 7-9, Tokyo Japan I received the best presentation award)
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Career plans and academic performance of medical students before, during, and beyond COVID-19 pandemic: Time to recover?2022

    • Author(s)
      Houman Goudarzi, Masahiro Onozawa, Makoto Takahashi
    • Organizer
      The 54th Annual meeting of the Japan Society for Medical Education, 2022 August 5-6, Gunma, Japan
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mixture exposure to plastic-related short half-life chemicals and associations with childhood asthma and allergies: The Hokkaido Study2022

    • Author(s)
      Yu Ait Bamai, Celine Guys, Michiel Bastiaensen, Atsuko Ikeda-Araki, Rahel Mesfin Ketema, Houman Goudarzi, Chihito Miyashita, Satoshi Konno, Reiko Kishi
    • Organizer
      The 34th Annual ISEE conference, 2022 September 18-21, Athens, Greece
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Prevalence and time trends of allergic disease among Japanese children: Interpretation of T helper 2 biomarker levels for clinical applications.2020

    • Author(s)
      Houman Goudarzi, Atsuko Araki, Chihiro Miyashita, Yu Ait Bamai, Sachiko Ito, Reiko Kishi, Masaharu Nishimura, Satoshi Konno.
    • Organizer
      JSA/WAO Joint Congress 2020, 2020, Kyoto, Japan
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Remarks] https://researchmap.jp/houman

    • Related Report
      2023 Annual Research Report
  • [Remarks] https://www.cehs.hokudai.ac.jp/

    • Related Report
      2023 Annual Research Report
  • [Remarks] https://www.cehs.hokudai.ac.jp/en

    • Related Report
      2022 Research-status Report
  • [Remarks] Website of Hokkaido Study

    • URL

      https://www.cehs.hokudai.ac.jp/hokkaidostudy/

    • Related Report
      2021 Research-status Report

URL: 

Published: 2020-04-28   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi