Testing association between epithelial chloride transport and measures of clinical improvement

P.I.: Dave Nichols, MD
Associate Professor,
Pediatrics

Jason Debley, MD, MPH
Associate Professor,
Pediatrics

Drug therapies to enhance CFTR function (“modulators”) are an important therapeutic step in CF care and research. Highly effective modulator therapy is increasingly available to people with CF but individual responses to these medications can be highly variable. Furthermore, many patients have rare, poor characterized mutations and their response to modulator drugs cannot be predicted. In vitro assessment of improved ion transport after exposure to modulator compounds holds promise to help address these questions related to heterogeneity or unpredictability of clinical response. Subject cohorts in Ireland with G551D or R117H mutations have and continue to be carefully phenotyped and characterized after initiation of ivacaftor. We propose to obtain and test the in vitro response to ivacaftor in primary nasal airway epithelial cells. We will then test for association between the in vitro improvements in ion transport and clinical outcomes measured in these subjects.