PROJECT SUMMARY Cystic Fibrosis (CF) is a lethal autosomal recessive disease affecting nearly 80,000 people worldwide. Despite advances in therapy, CF remains a progressive lung disease that leads to decline in lung function and frequent pulmonary exacerbations. Higher levels of outdoor air pollution, including particulate matter (PM) with a diameter of 10µm or less (PMR10R) and 2.5µm or less (PMR2.5R), nitrogen dioxide (NOR2R), and ozone, have been shown to lead to worse CF outcomes such as decline in lung function and increased pulmonary exacerbations. Many studies have shown that higher levels of indoor air pollution increase morbidity in obstructive lung diseases such as asthma and COPD. To our knowledge, this has not been studied in individuals with CF, also an obstructive lung disease. In this proposal we aim to study how indoor air pollution affects individuals with CF. We hypothesize that higher levels of indoor air pollution are associated with worse CF outcomes, such as increased respiratory symptoms and decline in lung function. To explore our hypothesis, we will conduct a sub-analysis from data collected in the US CF Twin and Sibling Study, which includes data on exposure to sources of indoor air pollution and clinical outcomes on over 2000 CF individuals from 2000-13. Next, we will distribute a survey to our local CF cohort to gather more detailed home exposure data and follow respiratory symptoms and lung function over time. Finally, we will conduct a pilot study to measure daily PMR2.5R and weekly NOR2R and nicotineR Rlevels inside the homes of 20 patients with CF for two one-week periods, separated by season, and ask patients to answer a daily respiratory symptoms questionnaire, complete daily activity diaries, and perform daily home spirometry. We will then determine if daily variations in PMR2.5 Rand weekly levels of NOR2R and nicotine are associated with daily variation in respiratory symptoms and lung function. The research carried out in this proposal is of public health significance and will provide new information on how indoor air pollution affects CF. The results of this study may impact the entire CF community and will serve as a catalyst for a future, multi-center and interventional study which will be the basis for my K23 application.

PROJECT NARRATIVE Cystic fibrosis (CF) is a lethal autosomal recessive genetic disorder, affecting approximately 80,000 individuals worldwide and results in progressive loss of lung function, frequent pulmonary exacerbations, lung transplant, and premature death. There is increasing evidence that environmental exposures, in addition to genetic and non-genetic influences and chronic bacterial infections, such as tobacco smoke and outdoor air pollution exposures, contribute to CF morbidity and mortality. Given that many studies have shown indoor air pollution contributes to morbidity in obstructive lung diseases such as asthma and COPD, but has not been studied in CF, this proposal aims to determine how indoor air pollution affects outcomes in individuals with CF.