Critical Illness Polyneuropathy/Myopathy in ALI

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DESCRIPTION (provided by applicant): This award will provide an opportunity for Dr. Lee to develop as an independent patient-oriented scientific investigator in the field of translational investigation (clinical epidemiology focused on translating basic science advances to clinical practice) and genetic epidemiology. Through an integrated curriculum with coursework in epidemiology and molecular biology, collaboration with local experts in the biology of acute lung injury (ALl), and practical experience in designing, conducting and interpreting a prospective clinical study, Dr. Lee will use this award to become a well-trained translational investigator with the skills needed to incorporate laboratory studies into clinical research. This will lead to a successful independent research career focused on the relationship between the pathobiology of ALl, including its long term complications, and patient-centered outcomes. The primary scientific goal of this proposal is to study the epidemiology, mechanism and outcomes of critical illness polyneuropathy/myopathy (CIPM) in patients with ALl. CIPM has been recently been shown to be highly prevalent in sepsis, and may be associated with important patient-centered outcomes after critical illness. CIPM has not been studied in a population of ALl patients. The overall design is a prospective cohort study. Patients with ALl will be identified, receive clinical and electrodiagnostic evaluations, and have blood and muscle samples collected for histologic, biochemical and genetic studies. Subjects will be followed and interviewed at 6 months to measure health-related quality of life. Aim One will determine prevalence of CIPM and identify its clinical risk factors. Aim Two is a study of the association of markers and mediators, including myosin metabolites and inflammatory cytokines, with diagnosis of CIPM. Aim Three is a genetic association study that examines the relationship between CIPM in ALl patients and polymorphisms that affect inflammation and muscle metabolism. Aim Four is a study of the influence of CIPM and health-related quality of life in ALl survivors. This study will provide important insights into the clinical impact of CIPM in patients with ALl, further our under-standing about the biology of neuromuscular manifestations of critical illness, and create a repository of biologic samples to be used for future investigations.