UCSF AsthmaNet Clinical Center

加州大学旧金山分校哮喘网络临床中心

• 批准号: 8704269
• 负责人: Michael D Cabana
• 金额: $ 50.14万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8704269
• 关键词: 10 year old; Accident and Emergency department; Accounting; Address; Adrenal Cortex Hormones; Adult; Affect; African American; Aftercare; Ally; Antibiotics; Asthma; Azithromycin; Biopsy; Breathing; Bronchitis; Caring; Charge; Child; Childhood; Childhood Asthma; Chronic Disease; Climate; Clinical; Clinical Trials Network; Conduct Clinical Trials; Defense Mechanisms; Development; Direct Costs; Disease; Dose; Double-Blind Method; Elderly; Ensure; Frequencies; Goals; Health; Hospitalization; Immune; Infection; Intake; Interleukin-13; Irrigation; Life; Lower Respiratory Tract Infection; Malabsorption Syndromes; Measures; Methods; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Nature; Nose; Obesity; Observational Study; Office Visits; Organism; Outcome; Parents; Patients; Pediatric Hospitals; Pharmaceutical Preparations; Pigments; Play; Population; Premature Birth; Prevalence; Pulmonary function tests; Randomized; Reporting; Resistance; Resources; Respiratory Tract Infections; Respiratory physiology; Rest; Risk; Risk Factors; Role; Sampling; Schools; Sea; Severities; Sinusitis; Skin; Source; Sputum; Sunlight; Supplementation; Surveys; Symptoms; Testing; The Sun; United States National Institutes of Health; Viral; Virus Diseases; Visit; Vitamin D; Vitamin D Deficiency; Wheezing; airway remodeling; asthmatic patient; base; bronchial epithelium; clinical practice; control trial; cost; design; health care service utilization; improved; middle age; novel; pathogen; prenatal; prevent; primary outcome; programs; protective behavior; receptor; respiratory; response; treatment as usual; treatment effect; young adult

DESCRIPTION (provided by applicant): This proposal is for the establishment of a UCSF/Children's Hospital Oakland Clinical Center in an NIHsupported network charged with conducting clinical trials of therapies for asthma in adults and children, including patients with severe asthma. As examples ofthe Clinical Trials this network could conduct, this application describes two studies. One trial derives from evidence on the importance of vitamin D for innate defense mechanisms in the bronchial epithelium. This trial would compare the effects of two doses of vitamin D on the frequency of asthma exacerbations in children: the current recommended dose of 400 IU/ day vs. the higher but well-tolerated dose of 2000 lU/day. The second trial examines the effects of treatment of asthma exacerbations with the antibiotic, azithromycin. Use of this antibiotic is common practice in treating asthma exacerbations, but rests on an extraordinarily slender body of evidence. Only one of (only) three previous studies showed any benefit, and that study examined a different antibiotic and showed small and inconsistent effects. Given the effects of widespread use of an antibiotic on the costs of care and on the emergence of resistant organisms, we believe the actual benefit of azithromycin treatment of asthma exacerbations needs to be determined. We also believe that such a study should examine a large enough population to allow examination of differential responses in sub-groups, such as those with symptoms of purulent bronchitis or sinusitis, those with positive culture or PCR for potential bacterial pathogens, and those with evidence of respiratory viral infection by PCR testing of sputum or nasal lavage samples. This proposal also describes two "Concept" studies of mechanisms of asthma that an NIH "AsthmaNet" network could undertake: one applying a highly novel, culture-independent method, the "PhyloChip" to examine differences in the bronchial microbiota in asthmatic patients regularly using - or naive to - inhaled corticosteroid treatment, how these bacterial populations are alTected by prolonged azithromycin treatment, and whether these effects are related to the effects of such treatment on markers of asthma control. The second "concept" study will examine the effects of an 1L-4/IL-13 receptor-antagonist on markers of airway remodeling by applying Designed-Based Stereology to bronchial biopsies obtained before and after treatment. The straightforward nature of these studies, the resources of UCSF/CHRCO, and the highly diverse nature of the populations they serve, will ensure generalizability to clinical practice of the findings made.

描述（由申请人提供）：本提案旨在建立一个由NIH支持的网络中的UCSF/儿童医院奥克兰临床中心，负责在成人和儿童（包括重度哮喘患者）中进行哮喘治疗的临床试验。作为该网络可以进行的临床试验的示例，本申请描述了两项研究。一项试验来自维生素D对支气管上皮细胞先天防御机制的重要性的证据。这项试验将比较两种剂量的维生素D对儿童哮喘急性发作频率的影响：目前推荐的400 IU/天剂量与较高但耐受性良好的2000 IU/天剂量。第二项试验检查了抗生素阿奇霉素治疗哮喘急性发作的效果。使用这种抗生素是治疗哮喘急性发作的常见做法，但依赖于非常微弱的证据。之前的三项研究中只有一项显示出任何益处，该研究检查了一种不同的抗生素，并显示出小而不一致的效果。考虑到抗生素的广泛使用对护理成本和耐药微生物的出现的影响，我们认为阿奇霉素治疗哮喘急性发作的实际益处需要确定。我们还认为，这样的研究应该检查足够大的人群，以便检查亚组中的差异反应，例如具有化脓性支气管炎或鼻窦炎症状的人群，潜在细菌病原体培养或PCR阳性的人群，以及通过痰或鼻灌洗液样本PCR检测有呼吸道病毒感染证据的人群。该提案还描述了NIH“AsthmaNet”网络可以进行的两项哮喘机制的“概念”研究：一个应用高度新颖的、不依赖于培养的方法，“PhyloChip”来检查经常使用或未接受吸入性皮质类固醇治疗的哮喘患者的支气管微生物群的差异，这些细菌群体如何被长期阿奇霉素治疗改变，以及这些作用是否与这种治疗对哮喘控制标志物的作用有关。第二项“概念”研究将通过将基于设计的体视学应用于治疗前后获得的支气管活组织检查来检查IL-4/IL-13受体拮抗剂对气道重塑标志物的影响。这些研究的直接性质，UCSF/CHRCO的资源，以及他们所服务的人群的高度多样性，将确保所做研究结果的临床实践的普遍性。