哮喘发展中的细胞和全身能量代谢失调——一种假说生成方法
2021/11/24
摘要
背景：系统性和气道特异性上皮能量代谢在改变早期气道上皮细胞（AEC）发育程序中的作用尚不清楚。
目的：评估患有和不患有喘息的儿童发生AEC时的碳水化合物代谢，并测试婴儿血浆能量生物标记物与随后复发的喘息和哮喘结局的相关性。
方法：我们测量了15名有或无喘息史的男性受试者在2岁时收集的在体鼻AEC中的细胞碳水化合物代谢，并进行主成分分析，以直观地评估糖醛酸代谢物和单糖AEC代谢数据的聚类。在237名有1年血浆样本的儿童中，我们使用广义估计方程和logistic回归测试了1年血浆能量生物标记物与反复喘息和哮喘的相关性。
结果：有喘息史的儿童鼻AEC葡萄糖利用率低于无喘息史的儿童。从系统角度来看，第1年血糖浓度升高（在正常范围内）与5岁时哮喘发病率降低相关（调整后的比值比[aOR]0.56，95%可信区间[CI]0.35-0.90）。1岁时的胰岛素、葡萄糖/胰岛素比率、c肽和瘦素与2-5岁时的反复喘息有关。
结论：这些研究表明，生命早期存在明显的能量代谢失调可能影响AEC的发展。婴儿期上皮细胞代谢的这些干扰可能对肺发育有持久的影响，这可能使气道更容易过敏。
Cellular and systemic energy metabolic dysregulation in asthma development- a hypothesis-generating approach
Sergejs Berdnikovs, Dawn C Newcomb, Tebeb Gebretsadik, Brittney M Snyder, Derek A Wiggins, Kadijah S Poleon, Tina V Hartert
Abstract
Background: The roles of systemic and airway-specific epithelial energy metabolism in altering the developmental programming of airway epithelial cells (AECs) in early life are poorly understood.
Objective: To assess carbohydrate metabolism in developing AECs among children with and without wheeze and test the association of infant plasma energy biomarkers with subsequent recurrent wheeze and asthma outcomes.
Methods: We measured cellular carbohydrate metabolism in live nasal AECs collected at age 2-years from 15 male subjects with and without wheeze history and performed a principal component analysis to visually assess clustering of data on AEC metabolism of glycolitic metabolites and simple sugars. Among 237 children with available 1-year plasma samples, we tested the associations of 1-year plasma energy biomarkers and recurrent wheeze and asthma using generalized estimating equations and logistic regression.
Results: Children with a history of wheeze had lower utilization of glucose in nasal AECs than children with no wheeze. Systemically, higher plasma glucose concentration at year 1 (within the normal range) was associated with decreased odds of asthma at age 5-years (adjusted odds ratio [aOR] 0.56, 95% confidence interval [CI] 0.35-0.90). Insulin, glucose/insulin ratio, c-peptide, and leptin at year 1 were associated with recurrent wheeze from age 2-5 years.
Conclusion: These studies suggest that there is significant energy metabolism dysregulation in early life which likely impacts AEC development. These pertubations of epithelial cell metabolism in infancy may have lasting effects on lung development, which could render the airway more susceptible to allergic sensitization.
背景：系统性和气道特异性上皮能量代谢在改变早期气道上皮细胞（AEC）发育程序中的作用尚不清楚。
目的：评估患有和不患有喘息的儿童发生AEC时的碳水化合物代谢，并测试婴儿血浆能量生物标记物与随后复发的喘息和哮喘结局的相关性。
方法：我们测量了15名有或无喘息史的男性受试者在2岁时收集的在体鼻AEC中的细胞碳水化合物代谢，并进行主成分分析，以直观地评估糖醛酸代谢物和单糖AEC代谢数据的聚类。在237名有1年血浆样本的儿童中，我们使用广义估计方程和logistic回归测试了1年血浆能量生物标记物与反复喘息和哮喘的相关性。
结果：有喘息史的儿童鼻AEC葡萄糖利用率低于无喘息史的儿童。从系统角度来看，第1年血糖浓度升高（在正常范围内）与5岁时哮喘发病率降低相关（调整后的比值比[aOR]0.56，95%可信区间[CI]0.35-0.90）。1岁时的胰岛素、葡萄糖/胰岛素比率、c肽和瘦素与2-5岁时的反复喘息有关。
结论：这些研究表明，生命早期存在明显的能量代谢失调可能影响AEC的发展。婴儿期上皮细胞代谢的这些干扰可能对肺发育有持久的影响，这可能使气道更容易过敏。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2021 Nov 2;S0091-6749(21)01682-1. doi: 10.1016/j.jaci.2021.10.024.)
(J Allergy Clin Immunol. 2021 Nov 2;S0091-6749(21)01682-1. doi: 10.1016/j.jaci.2021.10.024.)
Cellular and systemic energy metabolic dysregulation in asthma development- a hypothesis-generating approach
Sergejs Berdnikovs, Dawn C Newcomb, Tebeb Gebretsadik, Brittney M Snyder, Derek A Wiggins, Kadijah S Poleon, Tina V Hartert
Abstract
Background: The roles of systemic and airway-specific epithelial energy metabolism in altering the developmental programming of airway epithelial cells (AECs) in early life are poorly understood.
Objective: To assess carbohydrate metabolism in developing AECs among children with and without wheeze and test the association of infant plasma energy biomarkers with subsequent recurrent wheeze and asthma outcomes.
Methods: We measured cellular carbohydrate metabolism in live nasal AECs collected at age 2-years from 15 male subjects with and without wheeze history and performed a principal component analysis to visually assess clustering of data on AEC metabolism of glycolitic metabolites and simple sugars. Among 237 children with available 1-year plasma samples, we tested the associations of 1-year plasma energy biomarkers and recurrent wheeze and asthma using generalized estimating equations and logistic regression.
Results: Children with a history of wheeze had lower utilization of glucose in nasal AECs than children with no wheeze. Systemically, higher plasma glucose concentration at year 1 (within the normal range) was associated with decreased odds of asthma at age 5-years (adjusted odds ratio [aOR] 0.56, 95% confidence interval [CI] 0.35-0.90). Insulin, glucose/insulin ratio, c-peptide, and leptin at year 1 were associated with recurrent wheeze from age 2-5 years.
Conclusion: These studies suggest that there is significant energy metabolism dysregulation in early life which likely impacts AEC development. These pertubations of epithelial cell metabolism in infancy may have lasting effects on lung development, which could render the airway more susceptible to allergic sensitization.
上一篇：
dTBP2通过阻断dTCTP介导的细胞炎症网络减轻严重的气道炎症
下一篇：
谷氨酰胺缺乏将哮喘状态转变为中性粒细胞气道炎症
