Corresponding author
Name: Dr. Rachael Marpole
Mailing address: Respiratory and Sleep Medicine Department, Perth Children’s Hospital, 15 Hospital Avenue, Locked Bag 2010, Nedlands WA 6009, Australia.
Phone number: +61 8 6456 2222
Email: rachael.marpole@health.wa.gov.au
ORCID Rachael Marpole https://orcid.org/0000-0002-2652-0560
Key words Cystic fibrosis, Pancreatic function, CFTR modulators, residual CFTR function, child, paediatric
Running head: Reviewing pancreatic function in CF
To the Editor,
Cystic fibrosis (CF) is a common autosomal recessive disease that causes pancreatic exocrine insufficiency (PI) in 90% of cases1. Over the last decade new CF transmembrane conductance regulator (CFTR) protein modulator therapies, like ivacaftor, have become available. Ivacaftor can cause children with a gating mutation, up to 14 years of age, born with a meconium ileus to become pancreatic exocrine sufficient (PS)2. Of note, children with residual CFTR function mutations may be PI in infancy and then spontaneously become PS3.
Current recommendations from the Nutrition guidelines for CF in Australia and New Zealand suggest all children with CF have pancreatic function tested at diagnosis1. It is also suggested that repeat testing can help guide pancreatic enzymes replacement therapy (PERT) in patients on CF modulators. The aim of this study was to evaluate the benefit of reviewing pancreatic function testing and diagnosis of PS/PI of a cohort of CF patients and offering repeat testing to patients who had potential to become PS since initial testing.
Institutional ethics approval was granted prior to commencement of the study. All children with CF living in Western Australia were included. Retrospective review of the following included age, sex, birthplace, genotype, eligibility for and prescription of modulator therapy, current pancreatic function status, previous testing, meconium ileus at birth, and if prescribed PERT. After review, patients who had potential to become PS were offered testing prospectively.
There was 204 children and adolescents with CF being managed at Perth Children’s Hospital the only tertiary paediatric hospital in Western Australia, at the end of 2019. 95 (46%) were males, with an age range of 0-18 years. Exocrine pancreatic function had been tested in 177/204 (86%), with the majority having faecal pancreatic elastase testing. Out of the tested cohort 73% were diagnosed as PI (130/177).
Ivacaftor
All 12 patients eligible for ivacaftor were pancreatic insufficient, 11 were on PERT (table 1). One patient ceased ivacaftor due to poor tolerance. All taking ivacaftor were offered repeat testing. 81% (9/11) completed this. Four had become PS since starting ivacaftor (one clinically), with three stopping PERT. Two of the three patients experienced recurrent abdominal pain when taking PERT, which resolved on ceasing. Time on ivacaftor to stopping PERT varied from 14 months to 3 years. Age at stopping was 5, 9 and 10 years. One infant who tested initially as PI was not started on PERT due to lack of symptoms of malabsorption, became PS after six months of ivacaftor.
Other patients continue to be PI and on PERT despite being prescribed ivacaftor for up to 8 years. This includes an adolescent who developed pancreatitis twice after being on ivacaftor for 6 years. His pancreatic elastase has increased from <15 to 120microg/g.