Sinus Hypoplasia Precedes Sinus Infection in a Porcine Model of Cystic Fibrosis

OBJECTIVES/HYPOTHESIS Chronic sinusitis is nearly universal in humans with cystic fibrosis (CF) and is accompanied by sinus hypoplasia (small sinuses). However, whether impaired sinus development is a primary feature of loss of the cystic fibrosis transmembrane conductance regulator (CFTR) or a secondary consequence of chronic infection remains unknown. Our objective was to study the early pathogenesis of sinus disease in CF. STUDY DESIGN Animal/basic science research. METHODS Sinus development was studied in a porcine CF model. RESULTS Porcine sinus epithelia expressed CFTR and exhibited transepithelial anion transport. Disruption of the CFTR gene eliminated both. Sinuses of newborn CF pigs were not infected and showed no evidence of inflammation, yet were hypoplastic at birth. Older CF pigs spontaneously developed sinus disease similar to that seen in humans with CF. CONCLUSIONS These results define a role for CFTR in sinus development and suggest the potential of the CF pig as a genetic model of CF-sinus disease in which to test therapeutic strategies to minimize sinus-related CF morbidity.