Advancing Symptom Science and Management in Cystic Fibrosis: Biological, Social, and Clinical Mechanisms - Project Summary Therapeutic advances have doubled life expectancy for many people living with cystic fibrosis (PLWCF), yet multisystem symptom burden (e.g., pain, dyspnea, fatigue) continues to impair quality of life. Evidence also suggests that quality of life and mortality in CF are influenced by social determinants of health and race. The goal of this observational study is to identify overlapping biopsychosocial drivers of symptom experience in PLWCF. Specific Aim 1: We will use patient-reported outcomes to identify clusters of co-occurring, plausibly interrelated symptoms in 140 adults with CF. We will also determine the extent to which social determinants of health interrelate with symptom clusters to form clinically meaningful phenotypes of CF symptom experience. Specific Aim 2: We will perform untargeted metabolomic analysis of plasma and exhaled breath condensate to identify metabolic signatures (e.g. inflammation and oxidative stress) and clustering techniques to propose metabolic endotypes and determine their relationships with symptom clusters and phenotypes. Specific Aim 3: We will use sequential mixed methods incorporating surveys and interviews to identify PLWCF experience of CF clinical care and relationships between symptom clusters, social determinants of health, and care experience. Cumulatively, these complementary yet independent approaches will create a robust, person- centered understanding of CF symptoms, their correlates and interactions, and their effect on quality of life. The expected outcome of this research is identification of new, actionable targets for interventions to prevent or reduce symptoms at the biological, clinical, and systems levels.
