[show abstract][hide abstract] ABSTRACT: This is the second annual report of an international collaborative research group that is examining the cellular impact of laryngopharyngeal reflux (LPR) on laryngeal epithelium. The results of clinical and experimental studies are presented. Carbonic anhydrase (CA), E-cadherin, and MUC gene expression were analyzed in patients with LPR, in controls, and in an in vitro model. In patients with LPR, we found decreased levels of CAIII in vocal fold epithelium and increased levels in posterior commissure epithelium. The experimental studies confirm that laryngeal CAIII is depleted in response to reflux. Also, cell damage does occur well above pH 4.0. In addition, E-cadherin (transmembrane cell surface molecules, which have a key function in epithelial cell adhesion) was not present in 37% of the LPR laryngeal specimens. In conclusion, the laryngeal epithelium lacks defenses comparable to those in esophageal epithelium, and these differences may contribute to the increased susceptibility of laryngeal epithelium to reflux-related injury.
The Annals of otology, rhinology, and laryngology 07/2003; 112(6):481-91. · 1.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: Otitis media with effusion is the most common cause of childhood deafness. Gastroesophageal reflux has been implicated in the disease pathogenesis; therefore, it is necessary to identify the presence or absence of gastric juice in the middle ear.
Middle ear effusions were collected from children undergoing myringotomy. If gastric reflux has occurred, effusions should contain pepsin protein.
Total pepsin/pepsinogen protein, fibrinogen, and albumin content of effusions were measured in enzyme-linked immunosorbent assays using antibodies to porcine pepsin, human albumin, and human fibrinogen. Proteolytic activity of each effusion was measured at pH 2. The pH of effusions was measured.
Fifty-nine of 65 effusion samples gave a positive result with the antipepsin antibody, which also recognized pepsinogen. Pepsin/pepsinogen levels ranged from 0.8 to 213.9 microg/mL (serum reference levels, 49.8-86.6 ng/mL). All effusions contained albumin and fibrinogen with respective ranges of 1.77 to 95.75 and 0.30 to 2.30 mg/mL (serum reference levels, 35-45 and 2.2 to 4.6 mg/mL, respectively). Acidic protease activity occurred in 19 of 65 effusion samples. The pH of effusion samples was 7 to 9.
The majority of effusion samples contained pepsin/pepsinogen protein; only 29% were active. The pepsin level in effusion samples based on activity is substantially lower than levels based on antibody detection; however, the pH present would irreversibly inhibit pepsin, which would explain the low levels of active enzyme. Pepsin/pepsinogen levels in the effusion samples were up to 1000 times higher than serum levels, whereas albumin and fibrinogen levels were of the same magnitude. The pepsin in middle ear effusions is almost certainly due to reflux of gastric contents, and there may be a role for antireflux therapy in the treatment of otitis media with effusion.
The Laryngoscope 12/2002; 112(11):1930-4. · 1.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: Otitis media with effusion (glue ear) is the most frequent cause of deafness in children. We investigated the role of gastric juice reflux in this disease. We measured pepsin concentrations in middle ear effusions from children using ELISA and enzyme activity assays. 45 (83%) of 54 effusions contained pepsin/pepsinogen at concentrations of up to 1000-fold greater than those in serum. Our data suggest that reflux of gastric juice could be a major cause of glue ear in children.
The Lancet 03/2002; 359(9305):493. · 39.06 Impact Factor