Metabolomic profiling reveals extensive adrenal suppression due to inhaled corticosteroid therapy in asthma.
Metabolomic profiling reveals extensive adrenal suppression due to inhaled corticosteroid therapy in asthma.
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DOI：
10.1038/s41591-022-01714-5
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发表时间：
2022-04
期刊：
影响因子：
82.9
通讯作者：
Lasky-Su, Jessica A.
中科院分区：
文献类型：
--
作者：
Kachroo, Priyadarshini;Stewart, Isobel D.;Kelly, Rachel S.;Stav, Meryl;Mendez, Kevin;Dahlin, Amber;Soeteman, Djora I.;Chu, Su H.;Huang, Mengna;Cote, Margaret;Knilhtila, Hanna M.;Lee-Sarwar, Kathleen;McGeachie, Michael;Wang, Alberta;Wu, Ann Chen;Virkud, Yamini;Zhang, Pei;Wareham, Nicholas J.;Karlson, Elizabeth W.;Wheelock, Craig E.;Clish, Clary;Weiss, Scott T.;Langenberg, Claudia;Lasky-Su, Jessica A.
大规模代谢组学分析的应用为实现基于组学的哮喘精准医学的潜力提供了新的机会。通过利用来自四个不同队列中超过14，000名个体的数据，该研究确定并独立复制了17种类固醇代谢物，其水平在患有哮喘的个体中显著降低。尽管在所有哮喘病例中，无论药物使用情况如何，类固醇水平均降低，但最大的降低与吸入性皮质类固醇（ICS）的使用有关，这在一项为期4年的低剂量ICS临床试验中得到证实。使用ICS对类固醇水平的影响具有剂量依赖性，然而，使用低剂量ICS也会显著降低类固醇水平。使用电子病历（EMR）的信息，我们发现，与未经治疗和非哮喘患者相比，ICS治疗的哮喘患者的皮质醇水平在整个24小时的日常时间内大幅降低。此外，与未使用ICS的患者相比，使用ICS治疗的哮喘患者显示疲劳和贫血显著增加。因此，接受ICS治疗的哮喘患者的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，以在最大限度地减少肾上腺抑制的不良反应与利用ICS治疗的既定获益之间提供最佳平衡。
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 seventeen 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) use, as confirmed in a four-year low-dose ICS clinical trial. Effects of ICS use on steroid levels were dose-dependent, however, significant reductions also occurred with low-dose ICS use. Using information from electronic medical records (EMR), we found that cortisol levels were substantially reduced throughout the entire 24-hour daily period in asthma patients treated with ICS compared with those untreated and non-asthma patients. Moreover, asthma patients treated with ICS showed significant increases in fatigue and anemia as compared to those without ICS use. Adrenal suppression in asthma patients treated with ICS may therefore represent a larger public health problem than previously recognized. Regular cortisol monitoring of asthma patients 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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影响因子：
11.1
作者：
Gurnell M;Heaney LG;Price D;Menzies-Gow A
通讯作者：
Menzies-Gow A
影响因子：
4.6
作者：
Akbaraly T;Würtz P;Singh-Manoux A;Shipley MJ;Haapakoski R;Lehto M;Desrumaux C;Kähönen M;Lehtimäki T;Mikkilä V;Hingorani A;Humphries SE;Kangas AJ;Soininen P;Raitakari O;Ala-Korpela M;Kivimäki M
通讯作者：
Kivimäki M
影响因子：
9.6
作者：
Adamko, Darryl J.;Sykes, Brian D.;Rowe, Brian H.
通讯作者：
Rowe, Brian H.
影响因子：
5.6
作者：
Figueiredo RG;Costa RS;Figueiredo CA;Cruz AA
通讯作者：
Cruz AA
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y