EARLY TX OF ALS WITH NUTRITION AND NON-INVASIVE POSITIVE PRESSURE VENTILATION

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。目的：制定和验证提高无创正压通气(NIPPV)耐受性的策略，找出影响接受该治疗方式的因素，并评估早期呼吸功能障碍的措施。研究计划：受试者将采用分层设计，FVC为80%-95%(组1)，50%-79%(组2)。当参赛者的FVC下降到他们组的下限(第一组为80%，第二组为50%)时，将向他们提供NIPPV。这项先导性研究的结果将使美国国家神经疾病和中风研究所(NINDS)能够设计一项多中心第三阶段试验，以确定早期NIPPV和营养干预的疗效。方法：进行肺活量测定，并将FVC测量和患者分成两组。体检和非呼吸系统问卷调查：McGill生活质量、老年抑郁量表、Idler宗教信仰、家庭评估工具、Spielberg焦虑量表和Chalder疲劳量表。将进行以下呼吸系统问卷调查：医学研究理事会修订的呼吸困难量表、博格呼吸困难量表、肌萎缩侧索硬化症功能性呼吸困难、埃普沃斯嗜睡量表和匹兹堡睡眠质量指数。将进行以下肺功能测试(PFT)：肺活量、呼吸肌压、最大吸气压和最大呼气压、鼻压、最大自主通气量、呼气末二氧化碳和夜间血氧计。将进行血液测试，以评估氯化物和碳酸氢盐的水平。参与者将每隔8周接受一次评估，以确保他们的FVC不会低于提供NIPPV的设定点。第一组(预计FVC的85%-90%)和第二组(预计FVC的55%-60%)的患者在任何一次就诊期间都将被要求在4周内返回进行“监测”访问。一旦受试者达到他们的目标FVC，他们将开始夜间NIPPV，并将进行关于NIPPV耐受性的额外问卷调查，并收集有关依从性的数据。呼吸治疗师将对受试者进行评估，并在PFT之间进行比较，以确定哪种测量方法对呼吸肌功能的变化最敏感。将对NIPPV的接受者(NIPPV每天4小时)和拒绝NIPPV者进行比较。我们将寻求确定预测NIPPV延迟或不被接受的心理、社会、金融和人口因素。还将检查临床参与(球部与手臂与腿部)、照顾者可用性、ALSFRS、症状、接口和药物使用方面的差异，以确定决定成功使用和不成功使用NIPPV的因素。临床相关性：到目前为止的研究表明，NIPPV提高了ALS的存活率，即使在疾病后期引入。据推测，早期干预可能会进一步改善结果。目前尚缺乏可靠的早期呼吸功能不全指标，需要确定影响NIPPV治疗接受度和耐受性的因素以及早期呼吸功能障碍的测量方法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: To develop and validate strategies to improve tolerability of non-invasive positive pressure ventilation (NIPPV), to identify factors that influence acceptance of this treatment modality, and to evaluate measures of early respiratory dysfunction. RESEARCH PLAN: Subjects will be enrolled using a stratified design based on FVC 80-95% (Group 1) versus 50-79% (Group 2). NIPPV will be offered to participants as their FVC declines to the lower limit of their group (80% for Group 1 and 50% for Group 2). The results of this Pilot Study will allow the National Institute of Neurological Disorders and Stroke (NINDS) to design a multi-center Phase III trial to determine the efficacy of early NIPPV and nutritional intervention. METHODS: Spirometry will be performed and the FVC measures and patients will be stratified for Group 1 or 2. A physical exam will be performed and the following non-respiratory questionnaires will be administered: McGill Quality of Life, Geriatric Depression Scale, Idler Religiosity, Family Assessment Device, Spielberg Anxiety, and Chalder Fatigue Scale. The following respiratory questionnaires will be administered: Medical Research Council Modified Dyspnea Scale, Borg Dyspnea Scale, ALS Functional Dyspnea, Eppworth Sleepiness Scale, and the Pittsburgh Sleep Quality Index. The following pulmonary function tests (PFTs) will be performed: Spirometry, respiratory muscle pressures, maximum inspiratory pressures, and maximum expiratory pressures, sniff nasal pressure, maximum voluntary ventilation, end tidal CO2, and nocturnal oximetry. A blood test will be obtained to assess chloride and bicarbonate levels. Participants will be evaluated at 8 week intervals to ensure that their FVC does not dip below the set point to offer NIPPV. Patients in Group 1 (FVC between 85-90% of predicted) and Group 2 (FVC between 55 and 60% predicted) during any of their visits will be asked to return in 4 weeks for a "Surveillance" visit. Once subjects reach their goal FVC they will be started on nocturnal NIPPV and an additional questionnaire regarding NIPPV tolerance will be administered and data regarding compliance will be collected. Respiratory therapists will evaluate the subject and comparisons will be made between the PFTs to see which measure is most sensitive to changes in respiratory muscle function. Comparisons will be made between acceptors (NIPPV 4 hours/day) and refusers of NIPPV. We will seek to identify psychological, social, financial and demographic factors that predict delayed, or non-acceptance of NIPPV. Differences in clinical involvement (bulbar vs. arm vs. leg), caregiver availability, ALSFRS, symptoms, interface, and medication usage will also be examined to determine factors that determine successful use and unsuccessful NIPPV use. CLINICAL RELEVANCE: Studies to date indicate that NIPPV improves survival in ALS, even when introduced late in the disease. It is hypothesized that early intervention may improve outcome even further. There is a lack of a reliable indicator for early respiratory insufficiency and factors need to be identified that influence acceptance and tolerability of NIPPV therapy and measurements of early respiratory dysfuncti