Endotype of allergic asthma with airway obstruction in urban children.
Endotype of allergic asthma with airway obstruction in urban children.
复制标题
DOI：
10.1016/j.jaci.2021.02.040
复制
发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Inner City Asthma Consortium
中科院分区：
文献类型：
--
作者：
Altman MC;Calatroni A;Ramratnam S;Jackson DJ;Presnell S;Rosasco MG;Gergen PJ;Bacharier LB;O'Connor GT;Sandel MT;Kattan M;Wood RA;Visness CM;Gern JE;Inner City Asthma Consortium
在美国，在贫困城市社区长大的黑人和西班牙裔儿童的哮喘及相关发病率最高。旨在确定该人群健康和疾病的特定呼吸表型、与生命早期暴露的关系以及临床疾病背后的鼻上皮细胞基因表达的分子模式。研究人群包括 442 名高危城市儿童，他们在 10 岁时反复评估了喘息、过敏原特异性 IgE 和肺功能。通过为这些数据开发时间轨迹来确定表型，然后与早期生活暴露和 11 岁时鼻上皮基因表达模式进行比较。在 6 种确定的呼吸表型中，高喘息高过敏性低肺功能 (HW-HA-LF) 组的呼吸系统发病率最高。在生命早期，这一群体对常见过敏原的接触程度较低，而对室内灰尘中的麦角甾醇的接触程度较高。虽然所有高特应性组均与鼻上皮样本中 2 型炎症基因模块表达增加相关，但上皮 IL-13 反应模块与肺功能受损密切相关，并且 MUC5AC 分泌过多模块在 HW-HA-LF 中独特上调。相比之下，中度喘息低特应性（MW-LA）组表现出上皮完整性、上皮损伤和抗氧化途径模块表达的改变。在生命的第一个十年，高危城市儿童会出现不同的呼吸系统健康与疾病表型，这些表型将生命早期的环境暴露与儿童过敏和哮喘联系起来。此外，气道基因表达的独特模式证明了特定的分子途径如何构成不同的呼吸表型，包括过敏性和非过敏性哮喘。我们已经证明了不同的呼吸道表型（在 10 岁时形成并与哮喘发展相关）以及呼吸道上皮中的相关功能基因表达网络。
Black and Hispanic children growing up in disadvantaged urban neighborhoods have the highest rates of asthma and related morbidity in the United States. To identify specific respiratory phenotypes of health and disease in this population, associations with early-life exposures, and molecular patterns of gene expression in nasal epithelial cells that underlie clinical disease. The study population consisted of 442 high-risk urban children who had repeated assessments of wheezing, allergen-specific IgE, and lung function through age 10 years. Phenotypes were identified by developing temporal trajectories for these data, and then compared to early life exposures and patterns of nasal epithelial gene expression at age 11. Of the 6 identified respiratory phenotypes, a high-wheeze high-atopy low-lung-function (HW-HA-LF) group had the greatest respiratory morbidity. In early life, this group had low exposure to common allergens and high exposure to ergosterol in house dust. While all high atopy groups were associated with increased expression of a type-2 inflammation gene module in nasal epithelial samples, an epithelium IL-13 response module tracked closely with impaired lung function, and a MUC5AC hypersecretion module was uniquely upregulated in HW-HA-LF. In contrast, a medium-wheeze low-atopy (MW-LA) group showed altered expression of modules of epithelial integrity, epithelial injury, and antioxidant pathways. In the first decade of life, high-risk urban children develop distinct phenotypes of respiratory health versus disease that link early-life environmental exposures to childhood allergic sensitization and asthma. Moreover, unique patterns of airway gene expression demonstrate how specific molecular pathways underlie distinct respiratory phenotypes, including allergic and non-allergic asthma. We have demonstrated both distinct respiratory phenotypes – which develop by age 10 and link to asthma development – and related functional gene expression networks in respiratory epithelium.
登录
查看更多内容
DOI：
10.1016/j.jaci.2020.02.024
发表时间：
2020-06
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Larson D;Patel P;Salapatek AM;Couroux P;Whitehouse D;Pina A;Johnson JL;Sever ML;Sanda S;Poyser J;Allio T;Scadding GW;Qin T;Shamji MH;Kwok WW;James EA;French D;Lelic A;Larché M;Altman MC;Togias A;Durham SR
通讯作者：
Durham SR
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
8
作者：
Karvonen, Anne M.;Hyvarinen, Anne;Pekkanen, Juha
通讯作者：
Pekkanen, Juha
影响因子：
6.1
作者：
Looi, K.;Buckley, A. G.;Stick, S. M.
通讯作者：
Stick, S. M.
DOI：
10.1164/rccm.201507-1493oc
发表时间：
2016-04-15
影响因子：
24.7
作者：
Loss, Georg J.;Depner, Martin;Ege, Markus J.
通讯作者：
Ege, Markus J.