Human Vocal Fold Tissue Modifications Related to Laryngopharyngeal Reflux Disease: A Systematic Review.

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 May 5. doi: 10.1016/j.jvoice.2025.04.019.

BACKGROUND

The vocal fold tissue modifications and related dysphonia caused by laryngopharyngeal reflux disease (LPRD) remain a controversial topic in laryngology. Investigation of human vocal fold tissue exposed to reflux content can provide valuable insights. This systematic review aimed to summarize the current knowledge about LPRD-induced human vocal fold tissue modifications to better understand LPRD pathophysiology and LPRD-related voice disorders.

METHODS

A PubMed, Embase, and Web of Science database search was carried out by two investigators for studies investigating human laryngeal mucosa injuries and histological modifications related to LPRD refluxate, and their potential mechanistic associations with voice quality impairments according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses statements.

RESULTS

Of 389 retrieved articles, 24 experimental studies met the inclusion criteria. Studies demonstrate that laryngeal, particularly vocal fold, biopsies of patients with suspected LPRD reveal a substantial number of histological and functional alterations, including inflammatory cell infiltration, cell junction proteolysis, intercellular space dilatation, pepsin-induced cell DNA damage, and increases in oxidative stress mediators and tissue injuries. Functional impairment of defensive mechanisms through downregulation of carbonic anhydrases (CA III) and protective mucins (MUC2, MUC4, and MUC5AC) can consist of favoring factor of tissue injuries. Emerging studies reported evidence of tissue remodeling through matrix metalloproteinase activation and metabolic alterations included increased Glut-1 and sphingosine pathway activation, potentially linking LPRD to leukoplakia development. No studies addressed the potential effects of elastase, bile salts, trypsin, and lipases in non-acidic (weakly acidic or alkaline) gaseous environment.

CONCLUSION

This systematic review demonstrates that LPRD and pepsin induce cellular alterations in vocal fold and laryngeal tissues, highlighting potential pathogenic mechanisms and identifying biomarkers that may guide future diagnostic and therapeutic strategies.