M1873 TGFβ Polymorphism in Patients With Acute Pancreatitis (AP) in Association With Cytokine Level and Disease Severity

Abstract

G A A b st ra ct s may limit its utility. Aims: To evaluate the potential usefulness of electrophysiological studies, ex vivo, on rectal biopsy samples as a surrogate marker for measurement of CFTR function. These results were compared to NPD results from the same subject. Methods: Intestinal Current Measurement (ICM) and NPD were performed on healthy controls (routine colonoscopy) and CF patients (sigmoidoscopy). Median values comprising the ICM (carbachol, histamine, and forskolin responses) and NPD (basal and chloride transport responses) tests were determined. For each response, the Wilcoxon rank sum test was applied to determine the ability of each measure to distinguish between CF and healthy controls. Results: ICM measurements demonstrated a median (interquartile range) carbachol response in healthy control subjects (n=29 subjects; 40 analyzable biopsies) of 11.1 (7.9, 20.75) μA/cm2, histamine response of 8.7 (5.0, 12.9) μA/cm2, and a forskolin response of 3.9 (2.3, 7.4) μA/cm2. These responses were inverted in CF subjects (n=8, 10 analyzable biopsies) with a mean carbachol response of -2.5 (-4.8, -1.6) μA/cm2, histamine of -1.0 (-1.6, 0) μA/cm2, and no forskolin response. Each of the ICM measurements effectively distinguished between CF and controls (p < 0.0001). NPD measurements demonstrated a median basal PD response in healthy control subjects (n=7) of -12.0 mV (13.5, -8.0) and a chloride transport response of 14.0 mV (12, 20.5). In CF subjects (n=8), the median values were -49.0 mV (-51.5, -42.5) and -2.0 mV (-3.0, 0), respectively. Similar to ICM, each of the NPD measurements distinguished between healthy controls and CF (p < 0.0005). Conclusions: ICM is equivalent to NPD in the ability to distinguish CF patients from healthy controls. Rectal biopsy studies, like NPD, allow measurement of CFTR mediated chloride transport which has the potential for use as a therapeutic endpoint for studies in CF patients. This is of particular importance in evaluating young children who are less likely to tolerate NPD.