Through a better understanding of CFTR biogenesis and activation, new therapeutic approaches that restore activity to mutant CFTR molecules in vitro and in vivo are being developed. Biomarkers that can detect activity of rescued CFTR are required to measure therapeutic effects of new compounds. Current methods have yet to show consistent rescue of CFTR activity, raising the importance of optimizing detection strategies, including the most effective NPD endpoint. This may be particularly important for subjects harboring the ∆F508 mutation which in addition to its cell processing abnormality, also exhibits a channel gating defect (it does not activate with the conventional NPD agonist isoproterenol) thereby reducing detection of rescued protein. The investigators have previous experience evaluating alternative CFTR activating agents, both in CF animal models, and in human subjects. By adding quercetin to the sequence of perfusion solutions for NPD, the investigators may be better suited to detect CFTR activity of rescued mutant protein. In vitro experiments show that quercetin induces activation of CFTR additive to that seen with current NPD reagents. Preliminary in vivo experiments of non-CF individuals mirrored these results and show that quercetin activates CFTR in human NPD tests (n=12). Importantly, quercetin perfusion was well-tolerated by a validated sinus questionnaire and physician assessed nasal examination rating. As preliminary data suggest perfusion of quercetin may improve defective CFTR activation in surface localized ΔF508, use of this agent within an NPD protocol is likely to improve detection of ΔF508 CFTR resident at the cell surface, representing a potential means to identify new candidates for systemic CFTR potentiator therapies.