PROJECT SUMMARY Human lung function is determined by a complex combination of both genetic and environmental factors. Climate change is an environmental factor with the potential to affect lung health on a large scale. While transient changes in local weather have been associated with increased rates of asthma and COPD exacerbations, less is known about the effects of climate on long-term respiratory outcomes. A prior retrospective cross-sectional study has shown that warmer ambient air temperatures are associated with lower lung function in a general healthy U.S. population (NHANES), which may have implications given climate change. The primary goal of our proposal is to identify associations between changes in lung function and climate over time by analyzing data from the U.S. Cystic Fibrosis (CF) Foundation Patient Registry, which includes longitudinal data from over 30,000 individuals with CF receiving care at accredited CF centers in the U.S. We are utilizing CF as a model as warmer temperatures have been associated with lower lung function in 3 separate populations of individuals with CF in the U.S. and Australia, again through retrospective cross-sectional studies. Additionally, dense demographic and clinical information is collected routinely every three months for the entire lifetime of people with CF, which will facilitate this unique longitudinal study. In addition to testing whether temperature changes are associated with changes in lung function, we also plan to assess the roles of respiratory pathogens and socioeconomic factors in this relationship as well. Our methods include several different modeling approaches to account for subject mobility over time, non-linear temperature changes, CFTR modulator therapies, and time-varying confounders. We will also test approaches for interaction models (socioeconomic factors) and mediation models (respiratory pathogens). Completion of this research will provide information on the potential effects of climate change on long-term respiratory outcomes with relevance to respiratory morbidities and mortality as well as inform analytic techniques for future climate change studies of longitudinal outcomes. Understanding the effect of climate change on longitudinal outcomes is essential in quantifying the burden of disease imposed by climate change.