代谢组学分析显示哮喘患者吸入皮质类固醇治疗导致广泛的肾上腺抑制
2022/04/19
摘要
大规模代谢组学分析的应用为实现基于组学的精准治疗哮喘的潜力提供了新的机会。通过利用四个不同队列中超过14000名个体的数据，本研究确定并独立复制了17种类固醇代谢物，这些代谢物在哮喘流行个体中的水平显著降低。尽管在所有哮喘患者中，无论药物使用情况如何，类固醇水平都会降低，但最大的降低与吸入性皮质激素（ICS）治疗有关，这在一项为期4年的低剂量ICS临床试验中得到了证实。ICS治疗对类固醇水平的影响呈剂量依赖性；然而，低剂量ICS治疗也能显著降低死亡率。利用电子病历中的信息，我们发现，与未经治疗的哮喘患者和无哮喘患者相比，接受ICS治疗的哮喘患者的皮质醇水平在每天24小时内显著降低。此外，与未接受ICS治疗的哮喘患者相比，接受ICS治疗的哮喘患者疲劳和贫血显著增加。因此，在接受ICS治疗的哮喘患者中，肾上腺抑制可能是一个比以前认识到的更大的公共卫生问题。需要对接受ICS治疗的哮喘患者进行定期皮质醇监测，以便在最大限度地减少肾上腺抑制的不良影响，同时利用ICS治疗的既定益处之间实现最佳平衡。
Metabolomic profiling reveals extensive adrenal suppression due to inhaled corticosteroid therapy in asthma
Priyadarshini Kachroo, Isobel D Stewart, Rachel S Kelly, Meryl Stav, Kevin Mendez, Amber Dahlin, Djøra I Soeteman, Su H Chu, Mengna Huang, Margaret Cote, Hanna M Knilhtilä, Kathleen Lee-Sarwar, Michael McGeachie, Alberta Wang, Ann Chen Wu, Yamini Virkud, Pei Zhang, Nicholas J Wareham, Elizabeth W Karlson, Craig E Wheelock, Clary Clish, Scott T Weiss, Claudia Langenberg, Jessica A Lasky-Su
Abstract
The application of large-scale metabolomic profiling provides new opportunities for realizing the potential of omics-based precision medicine for asthma. By leveraging data from over 14,000 individuals in four distinct cohorts, this study identifies and independently replicates 17 steroid metabolites whose levels were significantly reduced in individuals with prevalent asthma. Although steroid levels were reduced among all asthma cases regardless of medication use, the largest reductions were associated with inhaled corticosteroid (ICS) treatment, as confirmed in a 4-year low-dose ICS clinical trial. Effects of ICS treatment on steroid levels were dose dependent; however, significant reductions also occurred with low-dose ICS treatment. Using information from electronic medical records, we found that cortisol levels were substantially reduced throughout the entire 24-hour daily period in patients with asthma who were treated with ICS compared to those who were untreated and to patients without asthma. Moreover, patients with asthma who were treated with ICS showed significant increases in fatigue and anemia as compared to those without ICS treatment. Adrenal suppression in patients with asthma treated with ICS might, therefore, represent a larger public health problem than previously recognized. Regular cortisol monitoring of patients with asthma treated with ICS is needed to provide the optimal balance between minimizing adverse effects of adrenal suppression while capitalizing on the established benefits of ICS treatment.
大规模代谢组学分析的应用为实现基于组学的精准治疗哮喘的潜力提供了新的机会。通过利用四个不同队列中超过14000名个体的数据，本研究确定并独立复制了17种类固醇代谢物，这些代谢物在哮喘流行个体中的水平显著降低。尽管在所有哮喘患者中，无论药物使用情况如何，类固醇水平都会降低，但最大的降低与吸入性皮质激素（ICS）治疗有关，这在一项为期4年的低剂量ICS临床试验中得到了证实。ICS治疗对类固醇水平的影响呈剂量依赖性；然而，低剂量ICS治疗也能显著降低死亡率。利用电子病历中的信息，我们发现，与未经治疗的哮喘患者和无哮喘患者相比，接受ICS治疗的哮喘患者的皮质醇水平在每天24小时内显著降低。此外，与未接受ICS治疗的哮喘患者相比，接受ICS治疗的哮喘患者疲劳和贫血显著增加。因此，在接受ICS治疗的哮喘患者中，肾上腺抑制可能是一个比以前认识到的更大的公共卫生问题。需要对接受ICS治疗的哮喘患者进行定期皮质醇监测，以便在最大限度地减少肾上腺抑制的不良影响，同时利用ICS治疗的既定益处之间实现最佳平衡。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Nat Med. 2022 Mar 21. doi: 10.1038/s41591-022-01714-5. Online ahead of print.)
(Nat Med. 2022 Mar 21. doi: 10.1038/s41591-022-01714-5. Online ahead of print.)
Metabolomic profiling reveals extensive adrenal suppression due to inhaled corticosteroid therapy in asthma
Priyadarshini Kachroo, Isobel D Stewart, Rachel S Kelly, Meryl Stav, Kevin Mendez, Amber Dahlin, Djøra I Soeteman, Su H Chu, Mengna Huang, Margaret Cote, Hanna M Knilhtilä, Kathleen Lee-Sarwar, Michael McGeachie, Alberta Wang, Ann Chen Wu, Yamini Virkud, Pei Zhang, Nicholas J Wareham, Elizabeth W Karlson, Craig E Wheelock, Clary Clish, Scott T Weiss, Claudia Langenberg, Jessica A Lasky-Su
Abstract
The application of large-scale metabolomic profiling provides new opportunities for realizing the potential of omics-based precision medicine for asthma. By leveraging data from over 14,000 individuals in four distinct cohorts, this study identifies and independently replicates 17 steroid metabolites whose levels were significantly reduced in individuals with prevalent asthma. Although steroid levels were reduced among all asthma cases regardless of medication use, the largest reductions were associated with inhaled corticosteroid (ICS) treatment, as confirmed in a 4-year low-dose ICS clinical trial. Effects of ICS treatment on steroid levels were dose dependent; however, significant reductions also occurred with low-dose ICS treatment. Using information from electronic medical records, we found that cortisol levels were substantially reduced throughout the entire 24-hour daily period in patients with asthma who were treated with ICS compared to those who were untreated and to patients without asthma. Moreover, patients with asthma who were treated with ICS showed significant increases in fatigue and anemia as compared to those without ICS treatment. Adrenal suppression in patients with asthma treated with ICS might, therefore, represent a larger public health problem than previously recognized. Regular cortisol monitoring of patients with asthma treated with ICS is needed to provide the optimal balance between minimizing adverse effects of adrenal suppression while capitalizing on the established benefits of ICS treatment.
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外周血炎症表型与成人哮喘不同临床表现之间的关系：基于一项大型人群的队列研究
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短效β2受体激动剂应用与重度哮喘发作：欧洲和北美的SABINA研究结果
