2023 Fiscal Year Annual Research Report
Potential role of club cell secretory protein (CC16) in development of obese asthma: findings from a birth cohort and animal studies
| Project/Area Number |
20K10425
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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 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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| Keywords | adult/childhood asthma / CC16 / prospective birth cohort / adult asthma cohort / experimental studies / T2 phebotypes / Airway inflammation / Oxidative biomarkers |
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| Outline of Annual Research Achievements |
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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| Remarks |
We completed our research plans in these 4 years and published several papers in high-impact journals. We presented the results in international conferences and disseminated the finding in society.
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