慢性疲劳综合征是否存在亚组？生物标志物的探索性聚类分析。
Are there subgroups of chronic fatigue syndrome? An exploratory cluster analysis of biological markers.
机构信息
Department of Paediatric and Adolescent Health, Akershus University Hospital, 1478, Lørenskog, Norway.
Division of Medicine and Laboratory Sciences, University of Oslo, Oslo, Norway.
出版信息
J Transl Med. 2021 Jan 30;19(1):48. doi: 10.1186/s12967-021-02713-9.
BACKGROUND
Chronic fatigue syndrome (CFS) is defined according to subjective symptoms only, and several conflicting case definition exist. Previous research has discovered certain biological alterations. The aim of the present study was to explore possible subgroups based on biological markers within a widely defined cohort of adolescent CFS patients and investigate to what extent eventual subgroups are associated with other variables.
METHODS
The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL) has previously performed detailed investigation of immunological, autonomic, neuroendocrine, cognitive and sensory processing functions in an adolescent group of CFS patients recruited according to wide diagnostic criteria. In the present study, hierarchical cluster analyses (Ward's method) were performed using representative variables from all these domains. Associations between clusters and constitutional factors (including candidate genetic markers), diagnostic criteria, subjective symptoms and prognosis were explored by standard statistical methods.
RESULTS
A total of 116 patients (26.7% males, mean age 15.4 years) were included. The final cluster analyses revealed six clusters labelled pain tolerant & good cognitions, restored HPA dynamics, orthostatic intolerance, low-grade inflammation, pain intolerant & poor cognitions, and high vagal (parasympathetic) activity, respectively. There was substantial overlap between clusters. The pain intolerant & poor cognitions-cluster was associated with low functional abilities and quality of life, and adherence to the Canada 2003 diagnostic criteria for CFS. No other statistically significant cluster associations were discovered.
CONCLUSION
Within a widely defined cohort of adolescent CFS patients, clusters could be delineated, but no distinct subgroups could be identified. Associations between clusters and constitutional factors, subjective symptoms and prognosis were scarce. These results question the clinical usefulness of searching for CFS subgroups, as well as the validity of the most "narrow" CFS diagnostic criteria.
TRIAL REGISTRATION
Clinical Trials NCT01040429.
背景
慢性疲劳综合征（CFS）仅根据主观症状定义，存在几种相互矛盾的病例定义。先前的研究已经发现了某些生物学改变。本研究的目的是在广泛定义的青少年 CFS 患者队列中，基于生物标志物探索可能的亚组，并研究最终的亚组在多大程度上与其他变量相关。
方法
挪威青少年慢性疲劳综合征的研究：病理生理学和干预试验（NorCAPITAL）先前根据广泛的诊断标准，对招募的青少年 CFS 患者群体进行了详细的免疫、自主、神经内分泌、认知和感觉处理功能研究。在本研究中，使用来自所有这些领域的代表性变量进行层次聚类分析（Ward 方法）。通过标准统计方法探索聚类与体质因素（包括候选遗传标记）、诊断标准、主观症状和预后之间的关系。
结果
共纳入 116 例患者（男性 26.7%，平均年龄 15.4 岁）。最终的聚类分析揭示了六个聚类，分别标记为耐受疼痛和良好认知、恢复的 HPA 动力学、体位不耐受、低度炎症、不耐受疼痛和认知能力差、高迷走（副交感）活动。聚类之间存在很大的重叠。不耐受疼痛和认知能力差的聚类与较低的功能能力和生活质量以及对加拿大 2003 年 CFS 诊断标准的依从性相关。没有发现其他具有统计学意义的聚类关联。
结论
在广泛定义的青少年 CFS 患者队列中，可以划定聚类，但无法确定明确的亚组。聚类与体质因素、主观症状和预后之间的关联很少。这些结果质疑寻找 CFS 亚组的临床实用性，以及最“狭义”CFS 诊断标准的有效性。
试验注册
ClinicalTrials.gov NCT01040429。
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