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Disease severity of people with cystic fibrosis carrying residual function mutations: Data from the ECFS Patient Registry

  • Meir Mei Zahav
    Affiliations
    Kathy and Lee Graub Cystic Fibrosis Centre and Pulmonary Unit, Schneider Children's Medical Centre of Israel, Petah Tikva, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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  • Annalisa Orenti
    Affiliations
    Department of Clinical Sciences and Community Health, Laboratory of Medical Statistics, Biometry and Epidemiology “G.A. Maccacaro”, University of Milan, Italy
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  • Andreas Jung
    Affiliations
    ECFS Patient Registry, Paediatric Pulmonology, University Children`s Hospital Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland
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  • Elpis Hatziagorou
    Affiliations
    Paediatric Pulmonology and Cystic Fibrosis Unit, 3rd Paediatric Department, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
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  • Hanne Vebert Olesen
    Affiliations
    Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Denmark
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  • Eitan Kerem
    Correspondence
    Corresponding author at: Department of Paediatrics and Center for Cystic Fibrosis, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
    Affiliations
    Department of Paediatrics and Centre for Cystic Fibrosis, Hadassah University Medical Centre, Hebrew University Hadassah Medical School, Jerusalem, Israel
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  • on behalf ofECFSPR with the list of contributing authors
Published:August 04, 2022DOI:https://doi.org/10.1016/j.jcf.2022.07.015

      Abstract

      Rational

      People with cystic fibrosis carrying residual function (RF) mutations are considered to have a mild disease course. This may influence caregivers and patients on how intensive the treatments should be.

      Objectives

      Characterize disease severity of patients carrying RF mutations, using the European CF Society Patient Registry (ECFSPR) data.

      Methods

      Demographic, clinical characteristics, lung function and death probability of patients carrying at least one RF mutation were analyzed and compared to patients homozygous to minimal function mutations (MF).

      Main results

      Of the 44,594 eligible patients (median age 19.5 years, IQR 10–29.8), 6,636 (14.6%) carried RF mutations, and 37,958 (85.1%) MF mutations. Patients carrying RF mutations were older, diagnosed at a later age, had lower sweat chloride at diagnosis and better FEV1pp at each age group. However, their FEV1pp declined with age and rates of chronic Pseudomonas aeruginosa increased with age. A significant number of patients with RF had FEV1pp similar to patients with MF at each age group. 4.5% of RF patients were treated with oxygen and 2.61% had a lung transplant. With increasing age, 26.6% of RF patients were treated with pancreatic enzymes associated with a more severe lung disease. RF patients had shortened life spans, with mortality starting around the age of 20 years.

      Conclusions

      Patients carrying an RF mutations experience a decline of pulmonary function with age, leading to life-shortening. Standard of care therapies and augmenting CFTR function may improve their survival and quality of life.
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