UCSF AsthmaNet Clinical Center

加州大学旧金山分校哮喘网络临床中心

• 批准号: 8501645
• 负责人: Michael D Cabana
• 金额: $ 84.73万
• 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/8501645
• 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)：这项建议是为了在国立卫生研究院支持的网络中建立加州大学旧金山分校/儿童医院奥克兰临床中心，负责对成人和儿童哮喘的治疗方法进行临床试验，包括严重哮喘患者。作为该网络可以进行的临床试验的例子，本申请描述了两项研究。一项试验来自于关于维生素D对支气管上皮中天然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对儿童哮喘恶化频率的影响：目前推荐的剂量为400IU/天，而较高但耐受性良好的剂量为2000Lu/天。第二个试验检验了使用抗生素阿奇霉素治疗哮喘恶化的效果。使用这种抗生素是治疗哮喘恶化的常见做法，但依据的证据非常单薄。在之前的三项研究中，只有一项显示出任何益处，而那项研究检查了另一种抗生素，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恶化的实际益处需要确定。我们还认为，这样的研究应该调查足够多的人群，以便检查不同亚组的不同反应，例如有化脓性支气管炎或鼻窦炎症状的人，培养或聚合酶链式反应(PCR)潜在细菌病原体阳性的人，以及通过痰或鼻灌洗液样本的聚合酶链式反应(PCR)检测证明呼吸道病毒感染的人。这项建议还描述了NIH“哮喘网”网络可以进行的两项关于哮喘机制的“概念”研究：一项是应用一种高度新颖的、独立于培养的方法--“植物芯片”，以检查定期使用或单纯吸入糖皮质激素治疗的哮喘患者的支气管微生物区系的差异，延长阿奇霉素治疗对这些细菌种群的影响，以及这些影响是否与此类治疗对哮喘控制标记物的影响有关。第二个“概念”研究将通过将基于设计的体视学应用于治疗前和治疗后的支气管镜活检，来检验1L-4/IL-13受体拮抗剂对气道重塑标记物的影响。这些研究的直截了当的性质、加州大学旧金山分校/CHRCO的资源以及它们所服务的人群的高度多样化的性质，将确保所取得的结果可推广到临床实践。