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Original Research: Cystic Fibrosis |

Role of Cystic Fibrosis Transmembrane Conductance Regulator in Patients With Chronic Sinopulmonary DiseaseCystic Fibrosis and Chronic Sinopulmonary Disease

Tanja Gonska, MD; Perry Choi, MD; Anne Stephenson, MD, PhD; Lynda Ellis, RN; Sheelagh Martin, RN; Melinda Solomon, MD; Annie Dupuis, PhD; Ruslan Dorfman, MBA, PhD; Julian Zielenski, PhD; Chee Y. Ooi, MBBS; William Weiser, MD; Peter R. Durie, MD; Elizabeth Tullis, MD, FCCP
Author and Funding Information

From the Department of Pediatrics (Drs Gonska, Solomon, and Durie) and Department of Medicine (Drs Stephenson and Tullis), University of Toronto, Toronto, ON, Canada; Division of Respirology and Keenan Research Centre of Li Ka Shing Knowledge Institute (Drs Stephenson and Tullis), St. Michael’s Hospital, Toronto, ON, Canada; Physiology and Experimental Medicine, Research Institute and Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition (Drs Gonska and Durie and Mss Ellis and Martin), Department of Pediatrics, Division of Respirology (Dr Solomon), Biostatistics: Design and Analysis Unit, Research Operations (Dr Dupuis), Neuroscience and Mental Health, Research Institute (Dr Dorfman), and Genetics and Genomic Biology, Research Institute, and Department of Pediatrics (Dr Zielenski), Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Imaging (Drs Choi and Weiser), St. Michael’s Hospital and University of Toronto, Toronto, ON, Canada; and School of Women’s and Children’s Health, Faculty of Medicine (Dr Ooi), University of New South Wales and Sydney Children’s Hospital Randwick, Sydney, NSW, Australia. Dr Dorfman is currently at the Office of Personalized Genomics and Innovative Medicine, Mount Sinai Hospital (Toronto, ON, Canada).

Correspondence to: Elizabeth Tullis, MD, FCCP, St. Michael’s Hospital, Rm 6-049, 30 Bond St, Toronto, ON, M5B 1W8, Canada; e-mail: TULLISE@smh.ca


Funding/Support: This study was supported by Genome Canada through the Ontario Genomics Institute as per research agreement 2004-OGI-3-05 (to Drs Durie and Zielenski), the Ontario Research Foundation (to Drs Durie and Zielenski), the Canadian Cystic Fibrosis Foundation (to Drs Durie and Zielenski). Drs Ooi and Gonska were funded by Canadian Cystic Fibrosis Foundation Fellowship awards. Dr Stephenson is supported by a Canadian Institutes of Health Research (CIHR) Postdoctoral Fellowship Award.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2012;142(4):996-1004. doi:10.1378/chest.11-2543
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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.

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