Tanja Gonska1, Perry Choi2, Anne Stephenson3, Lynda Ellis4, Sheelagh Martin4, Melinda Solomon5, Annie Dupuis6, Ruslan Dorfman7, Julian Zielenski8, Chee Y Ooi9, William Weiser2, Peter R Durie1, Elizabeth Tullis10. 1. Department of Pediatrics, University of Toronto, Toronto, ON, Canada; Physiology and Experimental Medicine, Research Institute and Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Toronto, ON, Canada. 2. Department of Medical Imaging, St. Michael's Hospital and University of Toronto, Toronto, ON, Canada. 3. Department of Medicine, University of Toronto, Toronto, ON, Canada; Division of Respirology and Keenan Research Centre of Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada. 4. Physiology and Experimental Medicine, Research Institute and Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Toronto, ON, Canada. 5. Department of Pediatrics, University of Toronto, Toronto, ON, Canada; Department of Pediatrics, Division of Respirology, Biostatistics, Toronto, ON, Canada. 6. Design and Analysis Unit, Research Operations, Neuroscience, Toronto, ON, Canada. 7. Mental Health, Research Institute, and Genetics and Genomic Biology, Research Institute, Toronto, ON, Canada. 8. Department of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada. 9. School of Women's and Children's Health, Faculty of Medicine, University of New South Wales and Sydney Children's Hospital Randwick, Sydney, NSW, Australia. 10. Department of Medicine, University of Toronto, Toronto, ON, Canada; Division of Respirology and Keenan Research Centre of Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada. Electronic address: TULLISE@smh.ca.
Abstract
BACKGROUND: Previous studies report a high frequency of mutations in the cystic fibrosis (CF) transmembrane conductance regulator gene (CFTR) in patients with idiopathic bronchiectasis. However, most studies have based their findings on preselected patient groups or have performed limited testing for CF transmembrane conductance regulator (CFTR) dysfunction. The objective of our study was to evaluate the prevalence of CFTR gene mutations and/or CFTR-related ion channel abnormalities among subjects with idiopathic chronic sinopulmonary disease and the prevalence of CF or a CFTR-related disorder in this population. METHODS: We evaluated 72 prospectively enrolled patients from 1995 to 2005 at the Hospital for Sick Children and St. Michael’s Hospital with idiopathic chronic sinopulmonary disease for evidence of CFTR-mediated abnormalities. We performed CFTR genotyping and assessed CFTR function using sweat testing and nasal potential difference testing. The results were compared with data from healthy control subjects, CF heterozygotes, and patients with CF. RESULTS: The CFTR functional tests in idiopathic sinopulmonary patients showed a continuous spectrum, ranging from normal to values typically seen in individuals with CF. Forty-eight patients (66%) demonstrated CFTR mutations and/or abnormalities of CFTR function. Twenty-two (31%) fulfilled criteria for a diagnosis of CF and 26 (36%) for a CFTR-related disorder with a strong female preponderance. Functional tests, more than genotyping, were instrumental in establishing a CF diagnosis. Clinical features failed to distinguish subjects with CF from those with CFTR-related or idiopathic disease. CONCLUSIONS: The high prevalence of CF and CFTR dysfunction among patients with idiopathic chronic sinopulmonary disease underscores the need for extensive diagnostic evaluation for CF.
BACKGROUND: Previous studies report a high frequency of mutations in the cystic fibrosis (CF) transmembrane conductance regulator gene (CFTR) in patients with idiopathic bronchiectasis. However, most studies have based their findings on preselected patient groups or have performed limited testing for CF transmembrane conductance regulator (CFTR) dysfunction. The objective of our study was to evaluate the prevalence of CFTR gene mutations and/or CFTR-related ion channel abnormalities among subjects with idiopathic chronic sinopulmonary disease and the prevalence of CF or a CFTR-related disorder in this population. METHODS: We evaluated 72 prospectively enrolled patients from 1995 to 2005 at the Hospital for Sick Children and St. Michael’s Hospital with idiopathic chronic sinopulmonary disease for evidence of CFTR-mediated abnormalities. We performed CFTR genotyping and assessed CFTR function using sweat testing and nasal potential difference testing. The results were compared with data from healthy control subjects, CF heterozygotes, and patients with CF. RESULTS: The CFTR functional tests in idiopathic sinopulmonary patients showed a continuous spectrum, ranging from normal to values typically seen in individuals with CF. Forty-eight patients (66%) demonstrated CFTR mutations and/or abnormalities of CFTR function. Twenty-two (31%) fulfilled criteria for a diagnosis of CF and 26 (36%) for a CFTR-related disorder with a strong female preponderance. Functional tests, more than genotyping, were instrumental in establishing a CF diagnosis. Clinical features failed to distinguish subjects with CF from those with CFTR-related or idiopathic disease. CONCLUSIONS: The high prevalence of CF and CFTR dysfunction among patients with idiopathic chronic sinopulmonary disease underscores the need for extensive diagnostic evaluation for CF.
Authors: Felix Ratjen; Scott C Bell; Steven M Rowe; Christopher H Goss; Alexandra L Quittner; Andrew Bush Journal: Nat Rev Dis Primers Date: 2015-05-14 Impact factor: 52.329
Authors: Jessica E Char; Marlene H Wolfe; Hyung-Ju Cho; Il-Ho Park; Jin Hyeok Jeong; Eric Frisbee; Colleen Dunn; Zoe Davies; Carlos Milla; Richard B Moss; Ewart A C Thomas; Jeffrey J Wine Journal: PLoS One Date: 2014-02-10 Impact factor: 3.240