Gene expression changes of inflammatory mediators in posterior laryngitis due to laryngopharyngeal reflux and evolution with PPI treatment: a preliminary study.
OBJECTIVE
Standard of care in laryngopharyngeal reflux (LPR) is acid suppression therapy. Its treatment efficacy and mechanism of action are not well documented. No objective study investigating the molecular patterns of inflammation in LPR or in response to proton pump inhibitor (PPI) treatment has been accomplished. We hypothesized that gene expression levels of mediators of inflammation -- interleukin 6 (IL6), interleukin 8 (IL8), interleukin 1a (IL1a), interleukin 1b (IL1b), transforming growth factor beta 1 (TGFbeta1), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF2), and tumor necrosis factor alpha (TNFalpha) -- in posterior larynx tissue would be increased in those with diagnosed LPR and would be then reduced with PPI treatment.


METHODS
Prospective uncontrolled trial.


METHODS
Biopsies from the posterior larynx were taken from 25 participants with LPR before and after a 10-week period with rabeprazole (40 mg). RNA isolation and real-time PCR was used to measure gene expression levels.


RESULTS
No significant differences were measured for any of the cytokines, either for the entire participant group (n = 25) or for the subset of participants who did not have a previous history of PPI usage (n = 15). In those participants who had a history of PPI usage (n = 10), a significant increase in gene expression levels post medication was measured for TGFbeta1 (P = .0396), VEGF (P = .0216), IL8 (P = .0297), after adjusting for compliance, subjective improvement, and reflux severity.


CONCLUSIONS
Our findings are provocative and speak to the unresolved understanding of the pathophysiology of LPR, its diagnosis, and its differences from gastroesophageal reflux disease.
Thibeault
Susan L
SL
Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Wisconsin-Madison, Madison, WI 53792-7375, USA. thibeault@surgery.wisc.edu
Smith
Marshall E
ME
Peterson
Kathryn
K
Ylitalo-Moller
Riitta
R
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D050782:Esophageal pH Monitoring; D004945:Esophagoscopy; D005260:Female; D005764:Gastroesophageal Reflux / Q000150:complications* / Q000188:drug therapy; D015870:Gene Expression; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis*; D007827:Laryngitis / Q000188:drug therapy / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008365:Manometry; D008875:Middle Aged; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D064750:Rabeprazole; D020133:Reverse Transcriptase Polymerase Chain Reaction
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D018836:Inflammation Mediators; D054328:Proton Pump Inhibitors; D064750:Rabeprazole