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. ? ? ? ?
