Animal Models of Laryngopharyngeal Reflux Disease: A Systematic Review of Mucosal Changes and Voice Disorders.

作者信息

Chen Guangjin, Lechien Jérôme R

机构信息

Department of Surgery, UMONS Research Institute for Health Sciences and Technology, University of Mons (UMons), Mons, Belgium.

Department of Surgery, UMONS Research Institute for Health Sciences and Technology, University of Mons (UMons), Mons, Belgium; Department of Otolaryngology and Head and Neck Surgery, Foch Hospital, School of Medicine, UFR Simone Veil, Université Versailles Saint-Quentin-en-Yvelines (Paris Saclay University), Paris, France; Department of Otolaryngology and Head and Neck Surgery, CHU Saint-Pierre, Brussels, Belgium; Department of Otolaryngology, Elsan Hospital of Poitiers, Poitiers, France.

出版信息

J Voice. 2025 Apr 15. doi: 10.1016/j.jvoice.2025.03.046.

BACKGROUND

Over the past decades, various animal models have been developed to elucidate the molecular pathways and tissue alterations associated with laryngopharyngeal reflux disease (LPRD). This systematic review aimed to summarize the current knowledge gained through experimental animal models in understanding LPRD pathophysiology, especially LPRD-related voice disorders.

METHODS

According to the PRISMA statements, two investigators systematically search PubMed, Embase, and Web of Science databases for experimental studies investigating mucosa injuries or modifications related to LPRD refluxate, and their potential mechanistic associations with voice quality impairments.

RESULTS

Of 326 retrieved articles, 44 studies documented reflux-induced laryngeal mucosal changes, including 19 animal model studies (canine, porcine, rat, mice, and rabbit models). The exposure of laryngeal tissue to refluxate (pepsin, bile acids, and trypsin) was associated with microscopic tissue alterations, including epithelium disruption and inflammatory infiltrate, metaplasia, erosion, and ulceration. The mucosa alterations vary according to the anatomical sublocation (vocal folds, posterior commissure, and supraglottic and subglottic regions). Several cytokines have been identified as mucosal injury mediators. The microscopic modifications of laryngeal mucosa may cause damage to tissue and changes in cell function. The experimental models were limited to supine-positioned animals exposed to liquid refluxate. No studies addressed the potential effects of elastase, bile salts, trypsin, and lipases in nonacidic (weakly acidic or alkaline) gaseous environment.

CONCLUSION

Experimental animal models of LPRD supported vocal fold and laryngeal mucosal changes in response to acidic reflux exposure. However, the translational value of these findings is limited by distinct differences in reflux pathophysiology between human subjects and animal models.