Clustering-based COPD subtypes have distinct longitudinal outcomes and multi-omics biomarkers.
Clustering-based COPD subtypes have distinct longitudinal outcomes and multi-omics biomarkers.
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DOI：
10.1136/bmjresp-2021-001182
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发表时间：
2022-08
影响因子：
4.1
通讯作者：
中科院分区：
文献类型：
--
作者：
慢性阻塞性肺疾病（COPD）可在多个领域进展，使疾病进展决定因素的识别复杂化。在我们以前的工作中，我们应用k-均值聚类肺功能和胸部放射学指标，以确定四个COPD相关的亚型：“相对耐药吸烟者（RRS）”，“轻度上叶为主的肺气肿（ULE）”，“气道为主的疾病（AD）”和“严重肺气肿（SE）”。在目前的研究中，我们研究了这些亚型与纵向COPD相关健康指标以及血液转录组学和血浆蛋白质组学生物标志物的相关性。我们纳入了来自COPDGene研究的8266名非西班牙裔白色和非裔美国人吸烟者。我们使用线性回归来研究肺量测定和放射学测量的5年前瞻性变化以及基因表达和蛋白质水平的聚类关联。我们使用Cox比例风险检验来检验与前瞻性急性加重、合并症和死亡率的相关性。基线时RRS、ULE、AD和SE簇分别占研究队列的39%、15%、26%和20%。SE组的5年FEV 1（1秒用力呼气量）和肺气肿进展最大，急性加重、心血管疾病和死亡率风险最高。AD集群具有最高的糖尿病风险。经过调整后，只有SE集群的呼吸道死亡风险升高，而ULE，AD和SE集群的全因死亡风险升高。这些簇还显示了差异蛋白质和基因表达生物标志物的关联，主要与炎症和免疫过程有关。COPD k-means亚型表现出不同的疾病进展率、前瞻性合并症、死亡率以及与转录组学和蛋白质组学生物标志物的相关性。这些发现强调了这些亚型的临床和生物学相关性，这需要更多的研究转化为临床实践。NCT 00608764。
Chronic obstructive pulmonary disease (COPD) can progress across several domains, complicating the identification of the determinants of disease progression. In our previous work, we applied k-means clustering to spirometric and chest radiological measures to identify four COPD-related subtypes: ‘relatively resistant smokers (RRS)’, ‘mild upper lobe-predominant emphysema (ULE)’, ‘airway-predominant disease (AD)’ and ‘severe emphysema (SE)’. In the current study, we examined the associations of these subtypes to longitudinal COPD-related health measures as well as blood transcriptomic and plasma proteomic biomarkers. We included 8266 non-Hispanic white and African-American smokers from the COPDGene study. We used linear regression to investigate cluster associations to 5-year prospective changes in spirometric and radiological measures and to gene expression and protein levels. We used Cox-proportional hazard test to test for cluster associations to prospective exacerbations, comorbidities and mortality. The RRS, ULE, AD and SE clusters represented 39%, 15%, 26% and 20% of the studied cohort at baseline, respectively. The SE cluster had the greatest 5-year FEV1 (forced expiratory volume in 1 s) and emphysema progression, and the highest risks of exacerbations, cardiovascular disease and mortality. The AD cluster had the highest diabetes risk. After adjustments, only the SE cluster had an elevated respiratory mortality risk, while the ULE, AD and SE clusters had elevated all-cause mortality risks. These clusters also demonstrated differential protein and gene expression biomarker associations, mostly related to inflammatory and immune processes. COPD k-means subtypes demonstrate varying rates of disease progression, prospective comorbidities, mortality and associations to transcriptomic and proteomic biomarkers. These findings emphasise the clinical and biological relevance of these subtypes, which call for more study for translation into clinical practice. NCT00608764.
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影响因子：
5.8
作者：
Ford ES;Wheaton AG;Mannino DM;Presley-Cantrell L;Li C;Croft JB
通讯作者：
Croft JB
影响因子：
3.7
作者：
Arostegui I;Esteban C;García-Gutierrez S;Bare M;Fernández-de-Larrea N;Briones E;Quintana JM;IRYSS-COPD Group
通讯作者：
IRYSS-COPD Group
影响因子：
3.1
作者：
Hersh CP;Make BJ;Lynch DA;Barr RG;Bowler RP;Calverley PM;Castaldi PJ;Cho MH;Coxson HO;DeMeo DL;Foreman MG;Han MK;Harshfield BJ;Hokanson JE;Lutz S;Ramsdell JW;Regan EA;Rennard SI;Schroeder JD;Sciurba FC;Steiner RM;Tal-Singer R;van Beek E Jr;Silverman EK;Crapo JD;COPDGene and ECLIPSE Investigators
通讯作者：
COPDGene and ECLIPSE Investigators
DOI：
10.1164/ajrccm.159.3.9805067
发表时间：
1999-03-01
影响因子：
24.7
作者：
Coxson, HO;Rogers, RM;Hogg, JC
通讯作者：
Hogg, JC
DOI：
10.1164/rccm.201105-0831oc
发表时间：
2011-11-01
影响因子：
24.7
作者：
Casanova, Ciro;de Torres, Juan P.;Celli, Bartolome R.
通讯作者：
Celli, Bartolome R.