Beyond the Surface: Novel Therapy Approach for Pancreatitis in the Setting of CFTR Dysfunction

超越表面:CFTR功能障碍背景下胰腺炎的新疗法

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Abstract

OBJECTIVES: Despite cystic fibrosis transmembrane conductance regulator (CFTR) proteins being present throughout the entire body and organ systems, typical presentation of cystic fibrosis (CF) involves lung disease. We report a series of individuals that were referred to our CF clinic for evaluation following a diagnosis of chronic pancreatitis or acute recurrent pancreatitis. After evaluation, they were deemed to have CFTR dysfunction and started on highly effective modulator therapy (HEMT). METHODS: A retrospective chart review was completed for all individuals referred to the University of Iowa Health Care Cystic Fibrosis Clinic from January 1, 2012, through December 31, 2023, for follow-up evaluation of chronic or acute recurrent pancreatitis. Along with demographic data, we quantified emergency department encounters or hospitalizations due to pancreatitis pre- and post-HEMT as well as individual tolerability of therapy. RESULTS: Ten individuals met inclusion criteria. Four individuals were found to have sweat chlorides that confirmed a diagnosis of CF, and three individuals with sweat chloride values below the diagnostic threshold were further evaluated with nasal potential difference (NPD) testing and found to have results consistent with CFTR dysfunction. All 10 patients were initiated on HEMT. In the 2 years prior to HEMT initiation, there was an average of 0.33 pancreatic episodes per month (range: 0.00-1.38), compared with 0.09 pancreatic episodes per month (range: 0.00-0.50) after initiation. HEMT was generally well tolerated with one individual discontinuing due to liver function abnormalities. CONCLUSIONS: Our study highlights a panel of individuals that may have been overlooked for CFTR dysfunction due to a nonpulmonary primary presentation, such as pancreatitis. However, our use of additional diagnostic tools followed by HEMT utilization was able to describe individual-reported improvements in symptoms and quality of life in individuals with CFTR dysfunction.

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