IMPAIRMENT OF SALIVARY EPIDERMAL GROWTH-FACTOR SECRETORY RESPONSE TO ESOPHAGEAL MECHANICAL AND CHEMICAL-STIMULATION IN PATIENTS WITH REFLUXESOPHAGITIS

Objectives: It has been demonstrated recently that salivary epidermal growth factor (sEGF) output in healthy individuals is strongly and sig nificantly influenced by esophageal intraluminal mechanical and chemic al stimuli. Therefore, we have studied the impact of intraesophageal m echanical and chemical stressors on the rate of secretion of sEGF in 1 4 patients with reflux esophagitis (RE), and compared these results wi th corresponding parameters measured in 14 sex- and age-matched contro ls. Methods: EGF was assessed in saliva collected during basal conditi ons, chewing of parafilm, placement of esophageal tubing, inflation of intraesophageal balloons, and perfusion with NaCl, HCl, and HCl/pepsi n solutions. The concentration of sEGF was measured with an RIA kit fr om Amersham (Arlington Heights, IL). Results: The concentrations of sE GF were (mean +/- SEM) 2.50 +/- 0.32 ng/ml and 2.00 +/- 0.37 ng/ml in basal saliva and during stimulation by chewing the parafilm, respectiv ely. Basal sEGF value appeared to be significantly higher than in cont rols (2.50 +/- 0.32 vs. 1.90 +/- 0.22 ng/ml, p < 0.05, in one-tailed t test). Placement of intraesophageal tubing resulted in a significant decline of sEGF concentration, compared with parafilm-stimulated condi tions (1.25 +/- 0.12 vs. 2.00 +/- 0.37 ng/ml, p < 0.0001) and correspo nding tubing-stimulated sEGF value in controls (1.25 +/- 0.12 vs. 1.52 +/- 0.16 ng/ml, p < 0.05). sEGF concentrations after inflation of int raesophageal balloons and subsequent perfusion with initial saline, HC l, HCl/pepsin, and ending saline were also highly significantly lower (1.05 +/- 0.18 ng/ml, p < 0.001; 1.10 +/- 0.20 ng/ml, p < 0.001; 1.10 +/- 0.18 ng/ml, p < 0.001; 1.10 +/- 0.19 ng/ml, p < 0.001; and 1.05 +/ - 0.18 ng/ml, p < 0.001, respectively) than sEGF concentration recorde d during stimulation with parafilm. Concentrations of sEGF during esop hageal perfusion with HCl, HCl/pepsin, and ending saline were also sig nificantly lower than corresponding values in controls (1.10 +/- 0.18 vs. 1.49 +/- 0.11 ng/ml, p < 0.05; 1.10 +/- 0.19 vs. 1.59 +/- 0.11 ng/ ml, p < 0.05; and 1.05 +/- 0.18 vs. 1.65 +/- 0.13 ng/ml, p < 0.01, res pectively). The rate of sEGF output, which was 1.30 +/- 0.24 ng/min du ring basal conditions, increased significantly during stimulation with parafilm (2.30 +/- 0.38 ng/min, p < 0.05). Both basal and parafilm-st imulated sEGF outputs were somewhat higher, although nonsignificantly, than corresponding values recorded in healthy individuals. Mechanical and chemical stimulation (initial NaCl, HCl, and ending NaCl) failed to evoke a significant increase in sEGF output over the value observed during parafilm stimulation in patients with RE, although such a sign ificant increase was clearly demonstrated in healthy individuals. Ther efore, sEGF output in patients with RE remained significantly lower th an corresponding values recorded in controls during an entire mechanic al stimulation (2.65 +/- 0.35 vs. 4.60 +/- 0.85 ng/min, p < 0.001, aft er placement of intraesophageal tubing and 2.80 +/- 0.54 vs. 5.15 +/- 0.70 ng/min, p < 0.001, after inflation of balloons). sEGF output in p atients with RE remained also significantly lower than adequate contro l values during chemical stimulation (3.65 +/- 0.64 vs. 5.20 +/- 0.60 ng/min, p < 0.05, during perfusion with initial saline; 3.70 +/- 0.70 vs. 5.20 +/- 0.60 ng/min, p < 0.05, during perfusion with HCl; 3.70 +/ - 0.52 vs. 5. 55 +/- 0.72 ng/min, p < 0.01, during perfusion with HCl/ pepsin, and 3.30 +/- 0.56 vs. 5.80 +/- 0.86 ng/min, p < 0.001, during ending saline). Conclusion: Impairment in sEGF secretion during mechan ical and chemical intraesophageal stimulation, mimicking the natural s cenario occurring during gastroesophageal reflux, may facilitate the d evelopment of esophageal mucosal pathology and delay the healing of al ready developed mucosal injury.