Cystic fibrosis patients at risk for disease progression marked by decline in FEV1% predicted: development of the cystic fibrosis risk of disease progression score

Background: Cystic fibrosis (CF) is one of the most common recessively inherited disorders diagnosed in early childhood in the United States. Determining the phenotype of CF patients likely to experience a significant drop in FEV1% predicted will help target efforts for mitigating this deleterious disorder. Methods: This retrospective cohort study evaluated potential risk variables that account for the decline in FEV1% predicted in 81 CF patients treated at Miller Children's and Women's Hospital, CA. Cystic fibrosis risk of disease progression (CF RD-Pro) score was evaluated as a tool to identify high-risk patients for accelerated disease progression (event = drop in FEV1% predicted >= 10 percentage points) based on risk variables identified as significant. Results: ROC analysis determined classification of high versus low-moderate risk of FEV1% decline during year two based on RD-Pro score. Scores >= 2 applied as threshold for high-risk revealed relatively good validity estimates: sensitivity =82.8%, specificity =66.7%, PVP =77.4%, PVN =73.7%, and correct classification =76%. Patients with CF RD-Pro scores suggestive of high (>= 2 points) vs. low-moderate (<2 points) risk were nearly 10 times more likely to experience significant disease progression (OR 9.6, 95% CI, 2.6-36.1, P=0.001). Conclusions: Identification of patients at high risk for significant decline in lung function will enable address of potential therapeutic modalities, environmental exposures, and behavioral variants that may improve outcomes in these patients. The power of the CF RD-Pro Score lies in its simplicity. Our study provides a novel readily available score, which incorporates body mass index (BMI) and Staphylococcus aureus infection, both being alterable targets for slowing CF progression.