Gastroesophageal reflux disease and patterns of reflux in patients with idiopathic pulmonary fibrosis using hypopharyngeal multichannel intraluminal impedance.

Idiopathic pulmonary fibrosis (IPF) is a diffuse fibrotic lung disease of unknown etiology. The association between IPF and gastroesophageal reflux disease (GERD) has been suggested. The objective of this study was to determine the prevalence of GERD and assess the proximity of reflux events in patients with histologically proven IPF using hypopharyngeal multichannel intraluminal impedance (HMII). This is a retrospective review of prospectively collected data from patients with histologically confirmed IPF (via lung biopsy) who underwent objective esophageal physiology testing including high-resolution manometry and HMII. Defective lower esophageal sphincter (LES) was defined as either LES pressure of <5.0 mmHg, total length of LES of <2.4 cm, or intra-abdominal length of LES of <0.9 cm. Abnormal esophageal motility was considered present when failed swallows ≥30% and/or mean wave amplitude <30 mmHg was present. HMII used a specialized impedance catheter to directly measure laryngopharyngeal reflux (LPR) and full column reflux (reflux 2 cm distal to the upper esophageal sphincter). Based on the previous study of healthy subjects, abnormal proximal exposure was considered present when LPR ≥1/day and/or full column reflux ≥5/day were present. From October 2009 to June 2011, 46 patients were identified as having pulmonary fibrosis and sufficient HMII data. Of 46, 10 patients were excluded because of concomitant connective tissue diseases, and 8 patients were excluded because they had undergone lung transplantation, which may impact the patterns of reflux. The remaining 28 patients with histologically confirmed IPF (male 16, female 12) were included in this study. Mean age and BMI were 60.4 years (range, 41-78) and 28.4 (range, 21.1-38.1), respectively. All patients except one were symptomatic; 23 (82%) patients had concomitant typical GERD symptoms such as heartburn, whereas 4 (14%) patients had isolated pulmonary symptoms such as cough. Esophageal mucosal injury such as esophagitis and Barrett's esophagus was found in 17 (71%) patients, whereas hiatal hernia was found in 19 (73%) patients. Abnormal proximal exposure, which occurred almost exclusively in the upright position, was present in 54% (15/28) of patients. There was no significant difference in clinical symptoms, objective findings of GERD, and pulmonary functions such as forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) between patients with and without abnormal proximal exposure. Although the total number of reflux events was significantly higher in patients with abnormal proximal exposure, a large number of patients had a negative DeMeester score regardless of whether abnormal proximal exposure was present (patients with, 80%; those without, 85%). Patients with abnormal proximal exposure more likely had a defective LES compared with those without (93% vs. 75%). Fourteen patients (56%) had abnormal esophageal motility including aperistaltic esophagus (n = 9). This first study of HMII in patients with IPF demonstrated that GERD is highly prevalent (>70%), and abnormal proximal reflux events such as LPR and full column reflux are common despite a frequently negative DeMeester score. HMII may be beneficial in the work-up of GERD in patients with IPF.

Recombinant vascular endothelial growth factor165 gene therapy improves anastomotic healing in an animal model of ischemic esophagogastrostomy.

Proper anastomotic healing is dependent upon many factors including adequate blood flow to healing tissue. The aim of this study was to investigate the impact of vascular endothelial growth factor (VEGF(165)) transfection on anastomotic healing in an ischemic gastrointestinal anastomosis model. Utilizing an established opossum model of esophagogastrectomy followed by esophageal-gastric anastomosis, the gastric fundus was transfected with recombinant human vascular endothelial growth factor via direct injection of a plasmid-based nonviral delivery system. Twenty-nine animals were divided into three groups: two concentrations of VEGF and a control group. Outcomes included VEGF mRNA transcript levels, neovascularization, tissue blood flow, and anastomotic bursting pressure. To determine whether local injection resulted in a systemic effect, distant tissues were evaluated for VEGF transcript levels. Successful gene transfection was demonstrated by quantitative polymerase chain reaction analysis of anastomotic tissue, with significantly higher VEGF mRNA expression in treated animals compared to controls. At the gastric side of the anastomosis, there was significantly increased neovascularization, blood flow, and bursting pressure in experimental animals compared to controls. There were no differences in outcome measures between low- and high-dose VEGF groups; however, the high-dose group demonstrated increased VEGF mRNA expression across the anastomosis. VEGF production was not increased at distant sites in treated animals. In this animal model, VEGF gene therapy increased VEGF transcription at a healing gastrointestinal anastomosis without systemic VEGF upregulation. This treatment led to improved healing and strength of the acutely ischemic anastomosis. These findings suggest that VEGF gene therapy has the potential to reduce anastomotic morbidity and improve surgical outcomes in a wide array of patients.