Innovative Investigations and Therapies for Asthma

描述(由申请人提供)： 这次哮喘临床研究网络(ACRN)的拨款申请涉及三名在多中心哮喘研究方面拥有丰富经验的研究人员。将为ACRN带来的研究专长领域包括成人和儿科调查、过敏和免疫学、肺病学、药理学、时间生物学、类固醇和β-2激动剂受体知识、呼吸道炎症、形态计量学、感染、生理学和患者护理。这两个研究方案对于理解哮喘的病理生理学和患者护理具有重要的潜在意义。 方案1将确定慢性感染(肺炎支原体和肺炎衣原体)和慢性哮喘之间的联系。在一项初步研究中，我们已经表明，大约50%的哮喘患者在他们的呼吸道中表现出肺炎支原体或肺炎衣原体的证据，并对大环内酯类抗生素的治疗有反应。然而，如果我们要潜在地识别一种新的哮喘表型，从而影响哮喘的治疗，那么在大型多中心试验中评估和推广这些观察结果是至关重要的。因此，我们建议在受试者(+)和(-)中同时使用大环内酯类抗生素和吸入性皮质类固醇(ICS)来评估这些患者的细菌。 由于我们多年来一直对皮质类固醇的反应性感兴趣，议定书2将评估生物标记物以预测ICS反应者(好的、边缘的和差的)，并确定这些不同的反应发生的原因。该协议是我们自己工作的扩展，并通过以丹佛为主导中心的ACRN进行工作。将对长效β-2激动剂和抗LGE这两种附加疗法进行研究，以确定其中一种或两种都能改善ICS的反应。预测谁会对皮质类固醇和添加剂治疗有反应的能力将极大地提高我们有效治疗哮喘的能力。

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.