Sinus hypoplasia precedes sinus infection in a porcine model of cystic fibrosis.
OBJECTIVE
Chronic sinusitis is nearly universal in humans with cystic fibrosis (CF) and is accompanied by sinus hypoplasia (small sinuses). However, whether impaired sinus development is a primary feature of loss of the cystic fibrosis transmembrane conductance regulator (CFTR) or a secondary consequence of chronic infection remains unknown. Our objective was to study the early pathogenesis of sinus disease in CF.


METHODS
Animal/basic science research.


METHODS
Sinus development was studied in a porcine CF model.


RESULTS
Porcine sinus epithelia expressed CFTR and exhibited transepithelial anion transport. Disruption of the CFTR gene eliminated both. Sinuses of newborn CF pigs were not infected and showed no evidence of inflammation, yet were hypoplastic at birth. Older CF pigs spontaneously developed sinus disease similar to that seen in humans with CF.


CONCLUSIONS
These results define a role for CFTR in sinus development and suggest the potential of the CF pig as a genetic model of CF-sinus disease in which to test therapeutic strategies to minimize sinus-related CF morbidity.
Department of Otolaryngology-Head and Neck Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA. eugene-chang@uiowa.edu
Eugene H
EH
Chang
Alejandro A
AA
Pezzulo
David K
DK
Meyerholz
Andrea E
AE
Potash
Tanner J
TJ
Wallen
Leah R
LR
Reznikov
Jessica C
JC
Sieren
Philip H
PH
Karp
Sarah
S
Ernst
Thomas O
TO
Moninger
Nicholas D
ND
Gansemer
Paul B
PB
McCray
David A
DA
Stoltz
Michael J
MJ
Welsh
Joseph
J
Zabner
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001707:Biopsy, Needle; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000235:genetics* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D007150:Immunohistochemistry; D015994:Incidence; D008297:Male; D009297:Nasal Mucosa / Q000473:pathology; D038081:Organogenesis / Q000235:genetics; D010256:Paranasal Sinuses / Q000196:embryology / Q000473:pathology*; D011897:Random Allocation; D012016:Reference Values; D018570:Risk Assessment; D012852:Sinusitis / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D013552:Swine
D019005:Cystic Fibrosis Transmembrane Conductance Regulator