2021 Fiscal Year Research-status 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 – 2023-03-31
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| Keywords | Asthma / Obesity / Adults and children / Airway inflammation / Club cell protein (CC16) / T helper 2 biomarkers / In vivo study |
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| Outline of Annual Research Achievements |
1) Adult asthma cohort):BMI was significantly and monotonously associated with reduced circulating CC16 levels in adult asthmas patients. Also, CC16 was inversely associated with sputum eosinophils and blood periostin. 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 five years of follow-up (p for trend = 0.031).
2) Population 2 (birth cohort): Ongoing.
3) Animal study: The percentage of CC16-cells was reduced in the small airways of mice with obesity. In addition, serum CC16 levels were significantly lower in obese mice than in non-obese control mice. However, the serum levels of SP-A and SP-D, other products of club cells, did not vary between obese and non-obese control mice.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
A) Adult asthma cohort: We have enrolled patients diagnosed with asthma by pulmonologists between 2010 and 2012 at the Hokkaido University Hospital and affiliated hospitals (n=127). Several clinical parameters were evaluated in all participants such as pulmonary function tests, biomarkers.
B) Hokkaido birth cohort: For allergic condition assessment, follow-up questionnaires were distributed to children aged 1, 2, 4, 7, and 10 years old, which included questions on wheeze, rhinitis, and eczema from the ISAAC questionnaires.
C) In vivo study: C57BL/6 Wild-type mice randomly were divided into two subgroups given normal chow or a high-fat diet. Blood CC16 levels and other products of club cells (SP-A and SP-D) in control mice vs. high-fat diet mice. Small airways were immunostained for CC16.
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| Strategy for Future Research Activity |
Most of our analysis in adult asthma cohort and in vivo studies have been finished. We have measured Th2 biomarkers and circulatory CC16 in children, anthropometric measures, and assessed allergic outcomes. Therefore, we will examine association CC16 with obesity, asthma and obese asthma phenotype. We also assess association of CC16 with eosinophilic inflammatory biomarkers including blood eosinophils, FeNO and total serum IgE. In addition, I will examine early life determinant of CC16 in children within a couple of months. The results will be published in three manuscripts in international journals. Also, I will share these results with academic societies and citizens.
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| Causes of Carryover |
Because of the COVID-19 pandemic, we have faced difficulties in increasing the number of study participants. Hopefully, we will increase the number of participants and, consequently, the power of the study in the near future.
We have collected information on outcomes by ISAAC questionnaires and completed measurement of inflammatory biomarkers, club cell secretory protein (CC16) in the early stages of the current study. In addition, I could get two internal grants from Hokkaido University in FY 2020 and 2021. Therefore, we still have some budget to use in FY 2022. In future plans, I am going to finish data analysis, share the results in scientific presentations and our study participants, and publish three papers using data of the current study in FY 2022.
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