| Project/Area Number |
20K10425
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 58020:Hygiene and public health-related: including laboratory approach
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| 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)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| 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)
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| Keywords | Asthma / 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 |
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| 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.
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| 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.
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| 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.
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