Innovative Investigations and Therapies for Asthma

哮喘的创新研究和治疗

• 批准号: 6800756
• 负责人: RICHARD J MARTIN
• 金额: $ 82.82万
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6800756
• 关键词: Chlamydiaceae; Mycoplasma pneumoniae; albuterol; asthma; bacteria infection mechanism; bacterial cytopathogenic effect; beta adrenergic receptor; biomarker; bronchodilators; clinical research; combination chemotherapy; cooperative study; corticosteroids; human subject; human therapy evaluation; immunoglobulin E; inflammation; macrolide antibiotics; nitric oxide; patient oriented research; phenotype; polymerase chain reaction; respiratory disorder chemotherapy; respiratory pharmacology; spirometry; tryptase

DESCRIPTION (provided by applicant): This Asthma Clinical Research Network (ACRN) grant application involves three investigators who have extensive experience in multicenter asthma investigation. The areas of research expertise that will be brought to the ACRN include adult and pediatric investigation, allergy and immunology, pulmonology, pharmacology, chronobiology, steroid and beta-2 agonist receptor knowledge, airway inflammation, morphometrics, infection, physiology, and patient care. The two research protocols are potentially of great importance to the understanding of asthma pathophysiology and patient care. Protocol 1 will determine the link between chronic infection (Mycoplasma pneumoniae and Chlamydia pneumoniae) and chronic asthma. In a pilot study, we have shown that approximately 50% of patients with asthma exhibit evidence of M. pneumoniae or C. pneumoniae in their airways, and respond to treatment with a macrolide antibiotic. However, evaluation and extension of these observations in large multi-center trials are critical, if we are to potentially identify a new asthma phenotype, and thus affect therapy of asthma. Therefore, we propose to evaluate these patients with both a macrolide antibiotic and an inhaled corticosteroid (ICS) in subjects (+) and (-) for these bacteria. As we have been interested in corticosteroid responsiveness for many years, Protocol 2 will evaluate biomarkers to predict ICS responders (good, marginal, and poor) as well as determining why these different responses occur. This protocol is an extension of our own work, and work through ACRN with Denver as the lead center. Additive therapy, long-acting beta-2 agonists and anti-lgE, will be studied to determine if either or both improve responses to ICS. The ability to predict who will and will not respond to corticosteroids and additive therapy will greatly improve our ability to treat asthma effectively.

描述（由申请人提供）： 这项哮喘临床研究网络 (ACRN) 拨款申请涉及三名在多中心哮喘调查方面拥有丰富经验的研究人员。 ACRN 的研究专业领域包括成人和儿科研究、过敏和免疫学、肺病学、药理学、时间生物学、类固醇和 β2 激动剂受体知识、气道炎症、形态测量、感染、生理学和患者护理。这两项研究方案对于理解哮喘病理生理学和患者护理可能非常重要。 方案 1 将确定慢性感染（肺炎支原体和肺炎衣原体）与慢性哮喘之间的联系。在一项初步研究中，我们发现大约 50% 的哮喘患者气道中存在肺炎支原体或肺炎衣原体，并对大环内酯类抗生素治疗有反应。然而，如果我们要潜在地识别出一种新的哮喘表型，从而影响哮喘的治疗，那么在大型多中心试验中对这些观察结果进行评估和扩展至关重要。因此，我们建议在受试者（+）和（-）中使用大环内酯类抗生素和吸入皮质类固醇（ICS）对这些患者进行这些细菌的评估。 由于我们多年来一直对皮质类固醇反应性感兴趣，协议 2 将评估生物标志物来预测 ICS 反应者（良好、边缘和差），并确定发生这些不同反应的原因。 该协议是我们自己工作的延伸，并通过 ACRN 以丹佛为牵头中心开展工作。 将研究附加疗法、长效 β2 激动剂和抗 lgE 药物，以确定其中之一或两者是否可以改善 ICS 的反应。 预测谁会对皮质类固醇和附加疗法产生反应和不会产生反应的能力将大大提高我们有效治疗哮喘的能力。