Clinical Trial Readiness for Rare Lung Diseases - ABSTRACT – Overall The Rare Lung Diseases Consortium (RLDC) is designed to accelerate clinical research on rare lung diseases (RLDs) by pursuing our objectives of conducting longitudinal natural history studies, developing novel diagnostics and therapeutics, providing clinical research training, and developing educational materials for patients, physicians, and public. The diseases to be studied in our application include diffuse cystic lung diseases (DCLDs) (lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis, Birt-Hogg-Dubé syndrome and follicular bronchiolitis/lymphocytic interstitial pneumonitis), pulmonary alveolar proteinosis (PAP), and familial interstitial pneumonias (FIPs) (including telomerase mutations and surfactant protein mutations). The rationale for this grouping is based on 1) the extensive experience and knowledge of these diseases among the investigators, 2) longstanding NIH-funded, collaborative clinical, translational, and basic research on these diseases by the group, 3) use of similar remote and clinic-based diagnostic/monitoring approaches for the rigorous assessment and follow-up of patients with these diseases, and 4) longstanding, close collaboration of the relevant patient advocacy groups for these diseases and these investigators. Each of the chosen diseases has been advanced by the clinical project leaders along a defined therapeutic development pathway germane to rare diseases. The proposed research is designed to move the selected RLDs along this pathway to the next step, which is different for each disease. The research focus will be on better defining the natural history, developing molecular pathway-driven novel diagnostic, prognostic and predictive biomarkers and useful remote monitoring tools and patient reported outcome instruments for RLDs. Advances from ongoing research led by the clinical project leaders will form the platform for pilot project proposals. Program component leaders have trained numerous investigators, developed diverse educational materials and mentorship opportunities, and established highly productive relationships with advocacy groups. To accomplish our goals, we will pursue the following five Specific Aims: AIM 1: Continue to support and enhance the Rare Lung Diseases Consortium (RLDC). AIM 2: Conduct clinical research studies involving patients with DCLDs, PAP, FIPs. AIM 3: Conduct a pilot clinical research program to test emerging hypotheses for rare lung diseases. AIM 4: Provide career enhancement for investigators & trainees interested in rare lung diseases. AIM 5: Develop educational materials on rare lung diseases for patients, doctors and the public. Successful completion of the aims of this proposal will facilitate clinical trial readiness for DCLDs, PAP and FIPs by defining the natural history of each disease, development of diagnostic, prognostic and predictive biomarkers, and establishing the utility of remote monitoring of lung function and exercise tolerance.
