| 研究課題/領域番号 |
20K10425
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| 研究種目 |
基盤研究(C)
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| 配分区分 | 基金 |
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| 応募区分 | 一般 |
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| 審査区分 |
小区分58020:衛生学および公衆衛生学分野関連:実験系を含む
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| 研究機関 | 北海道大学 |
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研究代表者 |
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| 研究分担者 |
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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| 研究期間 (年度) |
2020-04-01 – 2024-03-31
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| 研究課題ステータス |
完了 (2023年度)
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| 配分額 *注記 |
4,420千円 (直接経費: 3,400千円、間接経費: 1,020千円)
2022年度: 910千円 (直接経費: 700千円、間接経費: 210千円)
2021年度: 1,820千円 (直接経費: 1,400千円、間接経費: 420千円)
2020年度: 1,690千円 (直接経費: 1,300千円、間接経費: 390千円)
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| キーワード | adult/childhood asthma / CC16 / prospective birth cohort / adult asthma cohort / experimental studies / T2 phebotypes / Airway inflammation / Oxidative biomarkers / Asthma / Obesity / birth cohort / adult asthma patients / T helper 2 biomarkers / Experimental studies / Adults and children / Club cell protein (CC16) / In vivo study / Asthma and allergy / Obese asthma / Animal studies |
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| 研究開始時の研究の概要 |
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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| 研究実績の概要 |
1) Adult asthma cohort: BMI was significantly and monotonically associated with lower circulating CC16 levels in adult asthma patients. Also, CC16 was inversely associated with sputum eosinophils and blood periostin. Patients in the lowest tertile of serum CC16 levels at baseline had a -14.3 mL decline in FEV1 over five years of follow-up compared to those in the highest tertile (Goudarzi et al. Respiratory Medicine, 2023). 2) Experimental study: The percentage of CC16 cells was reduced in the small airways of obese mice and humans. Serum CC16 levels, but not SP-A and D, were significantly lower in obese mice than in non-obese control mice. 3) Hokkaido birth cohort: We measured circulating CC16 in 10-year-old children from the general population. BMI at ages 7 and 10 was associated with reduced CC16 at age 10. Children with wheeze had significantly lower plasma CC16 (median 5.2, IQR 3.8-6.1) compared to children without wheeze (median 5.6, IQR 4.3-7.1). Plasma CC16 was inversely associated with wheeze and asthma prevalence, with a 1 ng/mL increase in CC16 decreasing the risk of wheeze by 20% (adjusted odds ratio: 0.80, 95% CI: 0.66-0.99). CC16 was inversely associated with T2 phenotypes, including blood eosinophils and FeNO. Finally, we examined the association of urinary oxidative and lipid peroxidation with CC16 and the obese asthma phenotype. CC16 was inversely associated with urinary HNE and HEL, which are biomarkers of oxidative stress. We also completed genotyping of CC16 and found a significant influence of genotypes on circulating CC16.
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