Innovative Investigations and Therapies for Asthma

哮喘的创新研究和治疗

• 批准号: 6675046
• 负责人: RICHARD J MARTIN
• 金额: $ 86.08万
• 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/6675046
• 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）赠款涉及三名在多中心哮喘研究方面具有丰富经验的研究者。将带给ACRN的研究专业知识领域包括成人和儿科研究，过敏和免疫学，肺病学，药理学，计时生物学，类固醇和β-2激动剂受体知识，气道炎症，形态学，感染，生理学和患者护理。这两种研究方案对于理解哮喘病理生理学和患者护理至关重要。 方案1将确定慢性感染（支原体肺炎和肺炎衣原体）与慢性哮喘之间的联系。在一项试点研究中，我们已经表明，大约50％的哮喘患者在其气道中表现出肺炎支链球菌或肺炎梭菌的证据，并对大花环抗生素的治疗反应。但是，如果我们要识别新的哮喘表型，从而影响哮喘治疗，那么在大型多中心试验中对这些观察结果的评估和扩展至关重要。因此，我们建议在这些细菌的受试者（+）和（ - ）中评估这些患者患有大环内酯类抗生素和吸入的皮质类固醇（IC）。 由于我们对皮质类固醇的反应感兴趣多年，协议2将评估生物标志物以预测ICS响应者（良好，边际和穷人），并确定为什么会发生这些不同的响应。 该协议是我们自己的工作的扩展，并通过ACRN与丹佛作为领导中心进行工作。 将研究添加剂疗法，长效β-2激动剂和抗LGE，以确定或两者都可以改善对IC的反应。 预测谁将和不会对皮质类固醇和添加剂疗法反应的能力将大大提高我们有效治疗哮喘的能力。