Acute Histologic Effects of Extraesophageal Reflux on Vocal Fold Healing

Abstract

This study evaluates how extraesophageal reflux affects membranous vocal fold healing in a canine model. We created membranous vocal fold injuries in the animals and randomly assigned them to topical application of acid and pepsin at pH 2 or pH 6 or of normal saline solution every other day for 12 days. The experimental vocal folds were compared to uninjured, control vocal folds from animals painlessly sacrificed for other reasons. Hematoxylin and eosin, fibronectin, and procollagen I staining were performed for histologic analysis. The injured specimens had three times greater cellular infiltrate (p ≤ .001, analysis of variance) and twice as much fibronectin and procollagen I (p ≤ .001, analysis of variance) as did the specimens from the control animals. No significant differences or trends were identified for cellular infiltrate, fibronectin, or procollagen I within the injured groups (p > .05, Bonferroni t-test). Acute wound healing did not appear to be influenced by the presence of acid and pepsin at pH 2 or 6 as compared to saline solution.

Keywords

gastroesophageal reflux vocal fold wound healing

Get full access to this article

View all access options for this article.

References

Goldberg

Noyek

Pritzker

KPH

. Laryngeal granuloma secondary to gastro-esophageal reflux. J Otolaryngol 1978; 7: 196–202.

Loughlin

Koufman

. Paroxysmal laryngospasm secondary to gastroesophageal reflux. Laryngoscope 1996; 106: 1502–5.

Kuhn

Toohill

Ulualp

. Pharyngeal acid reflux events in patients with vocal cord nodules. Laryngoscope 1998; 108: 1146–9.

Toohill

Kuhn

. Role of refluxed acid in pathogenesis of laryngeal disorders. Am J Med 1997; 103: 100S–106S.

Koufman

. The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): A clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury. Laryngoscope 1991; 101(suppl 53).

Freije

Beatty

Campbell

Woodson

Schultz

Toohill

. Carcinoma of the larynx in patients with gastroesophageal reflux. Am J Otolaryngol 1996; 17: 386–90.

Barbero

. Gastroesophageal reflux and upper airway disease. Otolaryngol Clin North Am 1996; 29: 27–38.

Hanson

Kamel

Kahrilas

. Outcomes of antireflux therapy for the treatment of chronic laryngitis. Ann Otol Rhinol Laryngol 1995; 104: 550–5.

Little

Koufman

Kohut

Marshall

. Effect of gastric acid on the pathogenesis of subglottic stenosis. Ann Otol Rhinol Laryngol 1985; 94: 516–9.

10.

Wetmore

. Effects of acid on the larynx of the maturing rabbit and their possible significance to the sudden infant death syndrome. Laryngoscope 1993; 103: 1242–54.

11.

Johnston

Bulmer

Gill

. Cell biology of laryngeal epithelial defenses in health and disease: Further studies. Ann Otol Rhinol Laryngol 2003; 112: 481–91.

12.

Garrett

Coleman

Reinisch

. Comparative histology and vibration of the vocal folds: Implications for experimental studies in microlaryngeal surgery. Laryngoscope 2000; 110: 814–24.

13.

Cho

Kim

Lee

Kim

Park

. Influence of phonation on basement membrane zone recovery after phonomicrosurgery: A canine model. Ann Otol Rhinol Laryngol 2000; 109: 658–66.

14.

Belafsky

Postma

Koufman

. The validity and reliability of the reflux finding score (RFS). Laryngoscope 2001; 111: 1313–7.

15.

Courey

Shohet

Scott

Ossoff

. Immunohistochemical characterization of benign laryngeal lesions. Ann Otol Rhinol Laryngol 1996; 105: 525–31.

16.

Gray

Hammond

Hanson

. Benign pathologic responses of the larynx. Ann Otol Rhinol Laryngol 1995; 104: 13–8.

17.

Hirano

Bless

Rousseau

Welham

Scheidt

Ford

. Fibronectin and adhesion molecules on canine scarred vocal folds. Laryngoscope 2003; 113: 966–72.

18.

Thibeault

Gray

Bless

Chan

Ford

. Histologic and rheologic characterization of vocal fold scarring. J Voice 2002; 16: 96–104.

19.

Willems

Arends

Daemen

. Tenascin and fibronectin expression in healing human myocardial scars. J Pathol 1996; 179: 321–5.

20.

Kawahara

Mukai

Oda

Nakanishi

Iwa

. Left ventriculotomy of the heart: Tissue repair and localization of collagen types I, II, III, IV, V, VI and fibronectin. Virchows Arch A Pathol Anat Histopathol 1990; 417: 229–36.

21.

Sakai

Koibuchi

Ohtake

. Type I and type III procollagen gene expressions in the early phase of ligament healing in rabbits: An in situ hybridization study. J Orthop Res 2001; 19: 132–5.

22.

Gaynor

. Gastroesophageal reflux as an etiologic factor in laryngeal complications of intubation. Laryngoscope 1988; 98: 972–9.

23.

Borowiecki

Croft

. Experimental animal model of subglottic stenosis. Ann Otol Rhinol Laryngol 1977; 86: 835–40.

24.

Courey

Bryant

Jr Ossoff

. Posterior glottic stenosis: A canine model. Ann Otol Rhinol Laryngol 1998; 107: 839–46.

25.

Maronian

Azadeh

Waugh

Hillel

. Association of laryngopharyngeal reflux disease and subglottic stenosis. Ann Otol Rhinol Laryngol 2001; 110: 606–12.