Gastro-oesophageal reflux, aspiration and anti-reflux surgery in a human lung transplant population

Abstract

Introduction Asymptomatic gastro-oesophageal reflux and aspiration may be associated with allograft dysfunction post lung transplant. Early anti-reflux surgery has been advocated in selected patients and may improve long-term survival. Little has been published on this topic and the current evidence supporting this is flawed. The understanding of the pathophysiology of aspiration in lung transplant recipients is currently limited. This study reports a prospective analysis of reflux/aspiration immediately post-transplantation to date and its subsequent management. Methods Lung transplant recipients were recruited over 12 months. At one and six months post-transplantation, patients completed a reflux symptom index (RSI) questionnaire for symptoms of extra-oesophageal reflux and underwent objective assessment for reflux (manometry & pH/impedance). Testing was performed with subjects on maintenance proton pump inhibitor. Bronchoalveolar lavage fluid was assessed for pepsin, bile salts, interleukin-8 and neutrophils. Laparoscopic fundoplication was performed on selected patients. Subsequent laboratory based work was performed to determine the composition of gastric juice and to assess the effects of aspiration on primary bronchial epithelial cells and HT29-MTX goblet cells. Results 18 patients with a median age of 46 years (range 22-59) were studied. Manometry was abnormal in 8/18 (44%) patients. Seventeen patients completed 24 hour pHimpedance measurements. 12 of 17 (71 %) had evidence of GORD on pH-impedance monitoring. 3 of 12 (25%) of patients had exclusively weakly-acid reflux. A statistically significant correlation existed between proximal reflux events and neutrophilia at one month (n=13)(Spearman correlation r=0.52, p=0.03). Pepsin was detected in BALF signifying aspiration. Bile salts were rarely detected using 3 separate assays [sensitivity 0.1 /lmolll]. The prevalence of reflux increased over the first six months post-transplant despite a reduction in immunosuppression and normal lung function. Nine patients have subsequently undergone fundoplication for severe Xlil or symptomatic reflux. No major complications occurred. This was associated with improved quality of life and decreased symptoms. Laboratory work gave useful background information on pepsin and bile salts. Mean levels in gastric juice were 380llg/ml (range 0-3892) for pepsin and 50llmolll (range 0-8000) for bile salts. Microaspiration may lead to primary bronchial epithelial cell damage and death. Conclusion Reflux/aspiration is prevalent early post-operatively. Pepsin but rarely bile salts were detected in the lavage fluid suggesting pepsin to be a more common biomarker of aspiration. This study suggests that the causes for reflux are not all related to adverse thoracic changes and immunosuppression as surprisingly. despite a lack of a significant increase in immunosuppression levels, reflux indices increased over the first six months. Laboratory based work provides background information on the use of biomarkers and suggests aspiration could lead to cell death. Fundoplication is safe in selected patients and improved quality of life and GORD symptoms. Further studies are required to assess the effects on lung function and survival.