Fourth Annual International Pulmonary Alveolar Proteinosis Research Conference

描述(由申请人提供)：本提案寻求对题为“2006年第四届国际肺泡研究年会：世界观”的会议的支持。原发性肺泡蛋白沉积症(PAP)是一种罕见的疾病，其特征是肺内表面活性物质异常积聚，其临床病程从自然缓解到呼吸衰竭，并增加肺和肺外感染的发病率和死亡率。对PAP发病机制的认识虽然40多年来一直未知，但由于临床、基础和翻译研究以及参与PAP研究的临床医生和科学家之间日益密切的全球合作，PAP的发病机制最近取得了巨大进展。与此同时，PAP的治疗也一直很慢，与20世纪60年代初引入的原始方法S(反复在全身麻醉下溺水肺以冲洗表面活性物质)相比，治疗也没有进步。在GM-CSF缺陷小鼠中鉴定PAP提供了第一个真正的致病线索，并刺激了PAP研究，在不到十年的时间里，这种神秘但迷人的疾病从默默无闻到清晰。PAP研究的惊人进展使我们目前对PAP的认识是一种自身免疫性疾病，其中针对GM-CSF的抗体介导了临床表现。来自NHLBI/NIH和日本卫生部的资金促进了国际合作，从而极大地加速了PAP研究。我们对PAP发病机制的新认识导致了新的治疗方法，包括(1)GM-CSF免疫治疗(已完成/正在进行的研究)，(2)血浆置换(试验阶段)，(3)抗B淋巴细胞治疗(试验将于2006年开始)。在过去两年中，由NIH R13资助的国际PAP研究会议极大地促进了PAP研究工作的全球化。有强有力的证据证明有必要在2006年召开一次行动纲领研究会议。在过去的一年里，研究进展继续以惊人的速度进行，我们相信拟议中的会议将规划PAP研究的进程，促进PAP诊断、临床评估和治疗方法的协调，并为正在与我们合作进行临床研究的PAP患者带来希望。拟议会议的具体目标是：(1)回顾我们打算在2006年发表的对200名PAP患者进行的为期5年的横断面研究的数据；(2)回顾关于GM-CSF治疗PAP的总体应答率和有效性的临床研究数据；(3)宣传和审查将由RLDC进行的PAP纵向研究；(4)就(A)抗GM-CSF抗体阳性PAP的适当诊断标准、(B)PAP的疾病严重程度分级、(C)治疗的特定适应症、(D)全肺灌洗治疗的最佳做法达成协议。

DESCRIPTION (provided by applicant): This proposal seeks support for a conference entitled "Fourth Annual International Pulmonary Alveolar Research Conference: A world View in 2006." Primary pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by abnormal surfactant accumulation in the lungs, a variable clinical course ranging from spontaneous resolution to respiratory failure and an increased morbidity and mortality from pulmonary and extrapulmonary infections. Knowledge of the pathogenesis of PAP, while unknown for more than 4 decades, has recently advanced tremendously due to clinical, basic and translational research and increasing global cooperation among clinicians and scientists involved in PAP research. In parallel, therapy for PAP had also been slow and had not advanced from crude methods introduced in the early 1960's (repeated "drowning" the lungs under general anesthesia to wash out surfactant). Identification of PAP in GM-CSF deficient mice provided the first real pathogenic clue and stimulated PAP research, which has taken this enigmatic but fascinating disorder from obscurity towards clarity in less than a decade. The phenomenal progress PAP research has led to our current understanding of primary PAP as an autoimmune disease in which antibodies targeting GM-CSF mediate the clinical manifestations. Funding from the NHLBI/NIH and Japanese Ministry of Health has facilitated international collaboration that has accelerated PAP research tremendously. Our new understanding of PAP pathogenesis has led to new therapeutic approaches including (1) GM-CSF immunotherapy (completed/ongoing studies), (2) plasmapheresis (pilot stage), (3) anti-B lymphocyte therapy (trials to start in 2006). International PAP research meetings over the past 2 years supported by NIH R13 funding have helped tremendously to facilitate this globalization of the PAP research effort. Evidence documenting the need for a PAP Research Conference in 2006 is strong. Research progress over the past year has continued at a remarkable pace and we are confident the proposed conference will chart the course for PAP research, facilitate harmonization of the approaches for diagnosis, clinical assessment and treatment of PAP and provide hope for patients with PAP, who are collaborating with us in our clinical research studies. The Specific Objectives of the proposed conference are to: (1) review data from a 5-year cross-sectional study of 200 PAP patients that we intend to publish in 2006; (2) review clinical research data regarding the overall response rate and usefulness of GM-CSF therapy for PAP; (3) publicize and review the longitudinal study of PAP to be conducted by within RLDC; (4) reach agreement regarding (a) appropriate diagnostic criteria for anti-GM-CSF antibody-positive PAP, (b) a disease severity scale for PAP, (c) specific indications for therapy, (d) best practices for whole lung lavage therapy.