Mechanisms of a Symptom Cluster: Dyspnea, Fatigue and Sleep Disturbance in Chroni

描述（由申请人提供）：背景：症状集群是两个或两个以上相关症状的共同出现。评估和治疗慢性疾病的症状群可能比针对单一症状对健康结果有更有利的影响。群集性呼吸困难、疲劳和睡眠障碍是肺动脉高压（PAH）患者常见的症状，并对与健康相关的生活质量产生负面影响。确定潜在的生物学机制对于开发和测试针对这些机制和缓解症状的生物行为干预措施至关重要。参与PAH的病理生物学包括交感神经系统（SNS）和炎症途径的激活，这可能证明影响PAH的症状群。炎性细胞因子如白细胞介素-6 （IL-6）和肿瘤坏死因子- α (TNF- α)与其他疾病的症状（呼吸困难、疲劳和睡眠障碍）有关。初步证据显示疲劳与多环芳烃中的IL-6之间存在关联。研究：本次K23奖提出的项目是在慢性疾病症状管理研究项目中迈向独立的一步。在拟议的项目中，我们将确定SNS的激活[通过血浆去甲肾上腺素酶联免疫吸收试验（ELISA）测量]和炎症生物标志物水平（通过IL-6和tnf - α ELISA测量）是否与症状集群严重程度[通过美国剑桥肺动脉高压结局评价（US CAMPHOR）测量的呼吸困难，通过多重疲劳量表（MFI）测量的疲劳，通过匹兹堡睡眠质量指数（PSQI）测量的睡眠障碍，Epworth嗜睡量表（ESS）、活动记录仪和睡眠日记]。我们将招募60名患有PAH的女性，她们将完成美国CAMPHOR、MFI、PSQI、ESS和PAH症状严重程度量表。受试者还将完成为期7天的活动记录仪和睡眠日记。采集血浆去甲肾上腺素，白细胞介素-6和tnf - α水平。我们的总体假设是血浆去甲肾上腺素、IL-6和tnf - α水平的升高与PAH女性症状群的严重程度有关。这项研究将形成候选人开发有针对性的干预措施，以减轻症状集群的基础。这项研究不仅对多环芳烃有影响，而且对其他慢性、产生症状的疾病也有影响。培训：K23的这一部分由教学和指导经验组成，使候选人能够在以患者为导向的研究中作为独立的科学家发展拟议的研究计划。培训计划建立在候选人之前的经验基础上，并提供炎症生物标志物、睡眠测量、临床试验设计和高级统计方法方面的必要培训。培训活动包括课程作业、出席会议和研讨会以及一对一的指导。

DESCRIPTION (provided by applicant): Background: Symptom clusters are the co-occurrence of two or more symptoms that are related. Assessing and treating symptom clusters in chronic illness may have a more favorable impact on health outcomes than targeting single symptoms. The symptom cluster dyspnea, fatigue and sleep disturbance is common and negatively affects health-related quality of life in people with pulmonary arterial hypertension (PAH). Determining underlying biological mechanisms is essential to develop and test biobehavioral interventions to target these mechanisms and alleviate symptoms. The pathobiology involved in PAH includes activation of the sympathetic nervous system (SNS) and inflammatory pathways which may prove to impact the symptom cluster in PAH. Inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF- alpha) have been associated with symptoms (dyspnea, fatigue and sleep disturbance) in other disorders. Preliminary evidence has shown an association between fatigue and IL-6 in PAH. Research: The proposed project in this K23 award is the step toward independence in a program of research in symptom management in chronic illness. In the proposed project we will determine if activation of the SNS [measured by plasma norepinephrine enzyme-linked immunosorbent assay (ELISA)] and inflammatory biomarker levels (measured by IL-6 and TNF-alpha ELISAs) are associated with symptom cluster severity [dyspnea measured by the US Cambridge Pulmonary Hypertension Outcome Review (US CAMPHOR), fatigue measured by the Multidimensional Fatigue Inventory (MFI), sleep disturbance measured by the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), actigraphy and sleep diary]. We will enroll 60 women with PAH who will complete the US CAMPHOR, MFI, PSQI, ESS and the PAH Symptom Severity Scale. Subjects will also complete 7-days of actigraphy along with a sleep diary. We will collect plasma norepinephrine, IL-6 and TNF-alpha levels. Our overall hypothesis is increased levels of plasma norepinephrine, IL-6 and TNF-alpha levels will be associated with symptom cluster severity in women with PAH. This study will form the basis for the candidate to develop targeted interventions to alleviate symptom clusters. This study has implications not only for PAH but other chronic, symptom-producing illnesses. Training: This component of the K23 is comprised of didactic and mentored experiences to enable the candidate to develop the proposed program of research as an independent scientist in patient-oriented research. The training plan builds on the candidate's prior experiences and provides the necessary training in inflammatory biomarkers, sleep measures, clinical trial design and advanced statistical methods. Training activities include course work, attendance and presentations at conferences and workshops along with one-on- one mentoring.