Therapeutic Approaches to Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction in Chronic Bronchitis.
Chronic obstructive pulmonary disease is a common cause of morbidity and a rising cause of mortality worldwide. Its rising impact indicates the ongoing unmet need for novel and effective therapies. Previous work has established a pathophysiological link between the chronic bronchitis phenotype of chronic obstructive pulmonary disease and cystic fibrosis as well as phenotypic similarities between these two airways diseases. An extensive body of evidence has established that cigarette smoke and its constituents contribute to acquired dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in the airways, pointing to a mechanistic link with smoking-related and chronic bronchitis. Recent interest surrounding new drugs that target both mutant and wild-type CFTR channels has paved the way for a new treatment opportunity addressing the mucus defect in chronic bronchitis. We review the clinical and pathologic evidence for modulating CFTR to address acquired CFTR dysfunction and pragmatic issues surrounding clinical trials as well as a discussion of other ion channels that may represent alternative therapeutic targets.
1 Department of Medicine.|2 Gregory Fleming James Cystic Fibrosis Research Center.
George M
GM
Solomon
1 Department of Medicine.|2 Gregory Fleming James Cystic Fibrosis Research Center.
S Vamsee
SV
Raju
1 Department of Medicine.|3 University of Alabama at Birmingham Lung Health Center.
Mark T
MT
Dransfield
1 Department of Medicine.|2 Gregory Fleming James Cystic Fibrosis Research Center.|3 University of Alabama at Birmingham Lung Health Center.|4 Department of Pediatrics, and.|5 Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama.
Steven M
SM
Rowe
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D029481:Bronchitis, Chronic / Q000378:metabolism / Q000628:therapy*; D003550:Cystic Fibrosis / Q000378:metabolism / Q000628:therapy; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D005100:Expectorants / Q000627:therapeutic use*; D006801:Humans; D026741:Physical Therapy Modalities; D012907:Smoking / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D000900:Anti-Bacterial Agents; C505032:CFTR protein, human; D005100:Expectorants; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
chronic bronchitis; chronic obstructive pulmonary disease; cystic fibrosis transmembrane conductance regulator