title: A ferret model of COPD-related chronic bronchitis.
abstract: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the US. The majority of COPD patients have symptoms of chronic bronchitis, which lacks specific therapies. A major impediment to therapeutic development has been the absence of animal models that recapitulate key clinical and pathologic features of human disease. Ferrets are well suited for the investigation of the significance of respiratory diseases, given prior data indicating similarities to human airway physiology and submucosal gland distribution. Here, we exposed ferrets to chronic cigarette smoke and found them to approximate complex clinical features of human COPD. Unlike mice, which develop solely emphysema, smoke-exposed ferrets exhibited markedly higher numbers of early-morning spontaneous coughs and sporadic infectious exacerbations as well as a higher level of airway obstruction accompanied by goblet cell metaplasia/hyperplasia and increased mucus expression in small airways, indicative of chronic bronchitis and bronchiolitis. Overall, we demonstrate the first COPD animal model exhibiting clinical and pathologic features of chronic bronchitis to our knowledge, providing a key advance that will greatly facilitate the preclinical development of novel treatments for this disease.
authors.affiliation: Department of Medicine.
authors.forename: S Vamsee
authors.initials: SV
authors.lastname: Raju
authors.affiliation: Department of Radiology.
authors.forename: Hyunki
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Medicine.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Byzek
authors.affiliation: Department of Medicine.
authors.forename: Li Ping
authors.initials: LP
authors.lastname: Tang
authors.affiliation: Department of Medicine.
authors.forename: John E
authors.initials: JE
authors.lastname: Trombley
authors.affiliation: Department of Medicine.|UAB Lung Health Center, and.
authors.forename: Patricia
authors.initials: P
authors.lastname: Jackson
authors.affiliation: Department of Medicine.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Rasmussen
authors.affiliation: Department of Medicine.|UAB Lung Health Center, and.|Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Wells
authors.affiliation: Department of Medicine.|Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Emily Falk
authors.initials: EF
authors.lastname: Libby
authors.affiliation: Animal Resources Program, Birmingham, Alabama, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Dohm
authors.affiliation: Department of Pediatrics.
authors.forename: Lindy
authors.initials: L
authors.lastname: Winter
authors.affiliation: Department of Radiology.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Samuel
authors.affiliation: Department of Radiology.
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Zinn
authors.affiliation: Department of Medicine.|UAB Lung Health Center, and.|Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: J Edwin
authors.initials: JE
authors.lastname: Blalock
authors.affiliation: Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.|Department of Genetics, and.
authors.forename: Trenton R
authors.initials: TR
authors.lastname: Schoeb
authors.affiliation: Department of Medicine.|UAB Lung Health Center, and.|Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Dransfield
authors.affiliation: Department of Medicine.|UAB Lung Health Center, and.|Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.|Department of Pediatrics.|Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Rowe
mesh_terms: D000818:Animals; D029481:Bronchitis, Chronic / Q000139:chemically induced / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D005289:Ferrets; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced / Q000503:physiopathology*; D012906:Smoke / Q000009:adverse effects
chemical_list: D012906:Smoke