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Semin Respir Crit Care Med 2019; 40(06): 715-726
DOI: 10.1055/s-0039-1694021
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Cystic Fibrosis: Pathophysiology of Lung Disease

Christelle Bergeron
1   Respiratory Division, Department of Medicine, Faculty of Medicine and Health Sciences, University of Sherbrooke, Quebec, Canada
,
André M. Cantin
1   Respiratory Division, Department of Medicine, Faculty of Medicine and Health Sciences, University of Sherbrooke, Quebec, Canada
2   Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Quebec, Canada
› Author Affiliations Funding C.B. has been awarded a Cystic Fibrosis Canada Clinical fellowship grant for 2018–2019 and is currently enrolled in the Adult Cystic Fibrosis Fellowship program at the University of Toronto (St. Michael's Hospital).
A.M.C. is a member of the FQRS-funded Centre de Recherche Clinique du CHUS, and was supported by a grant from the Canadian Institutes of Health Research.
Further Information

Publication History

Publication Date:
28 October 2019 (online)

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Abstract

Cystic fibrosis (CF) is a common, life-threatening, multisystemic, autosomal recessive disorder. In the last few years, giant steps have been made with regard to the understanding of CF pathophysiology, allowing the scientific community to propose mechanisms that cause the myriad of CF clinical manifestations. Following the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989, the structure and function of the CFTR protein were described. Since then, more than 2,000 variants of the CFTR gene and their impact on the amount and function of the CFTR protein have been reported. The role of the CFTR protein as an ion channel transporting chloride and bicarbonate and its repercussions on different epithelial cell-lined organs and mucus are now better understood. Mechanisms behind susceptibility to infection in CF have also been proposed and include abnormalities in the composition, volume and acidity of the airway surface liquid, changes in the submucosal gland's anatomy and function, and deficiencies in the mucociliary clearance system. Numerous hypotheses explaining the excessive inflammatory response in CF are also debated and involve impaired mucociliary clearance, persistent hypoxia, lipid abnormalities, protease and antiprotease disproportion, and oxidant and antioxidant imbalance. The purpose of this review is to summarize our current knowledge of CF pathophysiology, including significant historic discoveries and most recent breakthroughs, and to improve understanding and awareness of this fatal disease.

Keywords

cystic fibrosis - pathophysiology - CFTR - infection - inflammation - proteases - oxidants - mucins
 

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