肥胖对CC16的影响及其在超重/肥胖哮喘中的潜在作用
2022/07/19
摘要
引言：CC16是一种表达于气道的主要抗炎蛋白；然而，CC16对超重/肥胖哮喘的潜在作用尚未明确。在这项研究中，我们使用实验和流行病学研究评估肥胖是否会降低气道/循环CC16水平。然后，我们探讨了CC16在超重/肥胖与临床哮喘指标之间的中介作用。
方法：通过ELISA评估三个独立人群的循环CC16水平，包括两组健康人群和普通人群以及哮喘患者。通过免疫组织化学方法测定肥胖小鼠与非肥胖小鼠和人气道中表达CC16的细胞百分比。进行因果分析，以确定循环CC16是否在超重/肥胖和临床哮喘指标之间起中介作用。
结果：在所有人群中，BMI与循环CC16水平降低显著相关。在肥胖小鼠和肥胖患者中的小气道中，CC16表达细胞的百分比均降低。最后，中介分析显示循环 CC16 在 BMI 与临床哮喘指标之间的相关性中有显著贡献；在健康受试者的体重指数与气道高反应性的相关性中，其占总效应的21.8%（p = 0.09）；其26.4% 与哮喘严重程度相关（p = 0.030），其23% 与所需剂量的吸入皮质类固醇相关（p = 0.042）。在逻辑回归分析中，哮喘患者血清 CC16 水平下降 1-SD 与87%的高剂量ICS需求增加相关（p < 0.001）。
结论：我们证明，与体重指数呈负相关的气道/循环CC16可能参与超重/肥胖哮喘的发展并与其严重程度相关。
Effects of obesity on CC16 and their potential role in overweight/obese asthma.
Houman Goudarzi, Hirokazu Kimura, Hiroki Kimura,
Abstrast
Introduction：Club cell secretory protein-16 (CC16) is a major anti-inflammatory protein expressed in the airway; however, the potential role of CC16 on overweight/obese asthma has not been assessed. In this study, we examined whether obesity reduces airway/circulatory CC16 levels using experimental and epidemiological studies. Then, we explored the mediatory role of CC16 in the relationship of overweight/obesity with clinical asthma measures.
Methods：Circulating CC16 levels were assessed by ELISA in three independent human populations, including two groups of healthy and general populations and asthma patients. The percentage of cells expressing club markers in obese vs. non-obese mice and human airways was determined by immunohistochemistry. A causal mediation analysis was conducted to determine whether circulatory CC16 acted as a mediator between overweight/obesity and clinical asthma measures.
Results：BMI was significantly and monotonously associated with reduced circulating CC16 levels in all populations. The percentage of CC16-expressing cells was reduced in the small airways of both mice and humans with obesity. Finally, mediation analysis revealed significant contributions of circulatory CC16 in the association between BMI and clinical asthma measures; 21.8% of its total effect in BMI’s association with airway hyperresponsiveness of healthy subjects (p = 0.09), 26.4% with asthma severity (p = 0.030), and 23% with the required dose of inhaled corticosteroid (p = 0.042). In logistic regression analysis, 1-SD decrease in serum CC16 levels of asthma patients was associated with 87% increased odds for high dose ICS requirement (p < 0.001).
Conclusions：We demonstrate that airway/circulating CC16, which is inversely associated with BMI, may mediate development and severity in overweight/obese asthma.
引言：CC16是一种表达于气道的主要抗炎蛋白；然而，CC16对超重/肥胖哮喘的潜在作用尚未明确。在这项研究中，我们使用实验和流行病学研究评估肥胖是否会降低气道/循环CC16水平。然后，我们探讨了CC16在超重/肥胖与临床哮喘指标之间的中介作用。
方法：通过ELISA评估三个独立人群的循环CC16水平，包括两组健康人群和普通人群以及哮喘患者。通过免疫组织化学方法测定肥胖小鼠与非肥胖小鼠和人气道中表达CC16的细胞百分比。进行因果分析，以确定循环CC16是否在超重/肥胖和临床哮喘指标之间起中介作用。
结果：在所有人群中，BMI与循环CC16水平降低显著相关。在肥胖小鼠和肥胖患者中的小气道中，CC16表达细胞的百分比均降低。最后，中介分析显示循环 CC16 在 BMI 与临床哮喘指标之间的相关性中有显著贡献；在健康受试者的体重指数与气道高反应性的相关性中，其占总效应的21.8%（p = 0.09）；其26.4% 与哮喘严重程度相关（p = 0.030），其23% 与所需剂量的吸入皮质类固醇相关（p = 0.042）。在逻辑回归分析中，哮喘患者血清 CC16 水平下降 1-SD 与87%的高剂量ICS需求增加相关（p < 0.001）。
结论：我们证明，与体重指数呈负相关的气道/循环CC16可能参与超重/肥胖哮喘的发展并与其严重程度相关。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校)
(Respiratory research 2022 Jun 29;23(1):174 doi:10.1186/s12931-022-02038-1)
(Respiratory research 2022 Jun 29;23(1):174 doi:10.1186/s12931-022-02038-1)
Effects of obesity on CC16 and their potential role in overweight/obese asthma.
Houman Goudarzi, Hirokazu Kimura, Hiroki Kimura,
Abstrast
Introduction：Club cell secretory protein-16 (CC16) is a major anti-inflammatory protein expressed in the airway; however, the potential role of CC16 on overweight/obese asthma has not been assessed. In this study, we examined whether obesity reduces airway/circulatory CC16 levels using experimental and epidemiological studies. Then, we explored the mediatory role of CC16 in the relationship of overweight/obesity with clinical asthma measures.
Methods：Circulating CC16 levels were assessed by ELISA in three independent human populations, including two groups of healthy and general populations and asthma patients. The percentage of cells expressing club markers in obese vs. non-obese mice and human airways was determined by immunohistochemistry. A causal mediation analysis was conducted to determine whether circulatory CC16 acted as a mediator between overweight/obesity and clinical asthma measures.
Results：BMI was significantly and monotonously associated with reduced circulating CC16 levels in all populations. The percentage of CC16-expressing cells was reduced in the small airways of both mice and humans with obesity. Finally, mediation analysis revealed significant contributions of circulatory CC16 in the association between BMI and clinical asthma measures; 21.8% of its total effect in BMI’s association with airway hyperresponsiveness of healthy subjects (p = 0.09), 26.4% with asthma severity (p = 0.030), and 23% with the required dose of inhaled corticosteroid (p = 0.042). In logistic regression analysis, 1-SD decrease in serum CC16 levels of asthma patients was associated with 87% increased odds for high dose ICS requirement (p < 0.001).
Conclusions：We demonstrate that airway/circulating CC16, which is inversely associated with BMI, may mediate development and severity in overweight/obese asthma.
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重症哮喘的生物学特性与气道重塑
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