• Open Access

Sinus hypoplasia precedes sinus infection in a porcine model of cystic fibrosis

Authors

  • Eugene H. Chang MD,

    Corresponding author
    1. Department of Otolaryngology–Head and Neck Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, U.S.A.
    • Department of Otolaryngology–Head and Neck Surgery, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, 21200 PFP, Iowa City, IA 52242
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  • Alejandro A. Pezzulo MD,

    1. Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, U.S.A.
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  • David K. Meyerholz DVM, PhD,

    1. Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, U.S.A.
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  • Andrea E. Potash MD,

    1. Department of Otolaryngology–Head and Neck Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, U.S.A.
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  • Tanner J. Wallen BS,

    1. Department of Otolaryngology–Head and Neck Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, U.S.A.
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  • Leah R. Reznikov PhD,

    1. Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, U.S.A.
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  • Jessica C. Sieren PhD,

    1. Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, U.S.A.
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  • Philip H. Karp BS,

    1. Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, U.S.A.
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  • Sarah Ernst BS,

    1. Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, U.S.A.
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  • Thomas O. Moninger BS,

    1. Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, U.S.A.
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  • Nicholas D. Gansemer BS,

    1. Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, U.S.A.
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  • Paul B. McCray Jr. MD,

    1. Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, U.S.A.
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  • David A. Stoltz MD, PhD,

    1. Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, U.S.A.
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  • Michael J. Welsh MD,

    1. Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, U.S.A.
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  • Joseph Zabner MD

    1. Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, U.S.A.
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  • The authors have no other funding, financial relationships, or conflicts of interest to disclose.

Abstract

Objectives/Hypothesis:

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.

Study Design:

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.

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