Aspiration and allograft injury secondary to gastroesophageal reflux occur in the immediate post-lung transplantation period (prospective clinical trial).

OBJECTIVES: To provide novel pilot data to quantify reflux, aspiration, and allograft injury immediately post-lung transplantation. BACKGROUND: Asymptomatic reflux/aspiration, associated with allograft dysfunction, occurs in lung transplant recipients. Early fundoplication has been advocated. Indications for surgery include elevated biomarkers of aspiration (bile salts) in bronchoalveolar lavage fluid (BALF). Measurements have been mostly documented after the immediate posttransplant period. We report the first prospective study of reflux/aspiration immediately posttransplantation to date. METHODS: Lung transplant recipients were recruited over 12 months. At 1 month posttransplantation, patients completed a Reflux Symptom Index questionnaire and underwent objective assessment for reflux (manometry and pH/impedance). Testing was performed on maintenance proton pump inhibitor. BALF was assessed for pepsin, bile salts, interleukin-8 and neutrophils. RESULTS: Eighteen lung transplant recipients, median age of 46 years (range: 22-59 years), were recruited. Eight of 18 patients had abnormal esophageal peristalsis. Five of 17 patients were positive on Reflux Symptom Index questionnaire. Twelve of 17 patients had reflux. Three patients exclusively had weakly acid reflux. Median acid exposure was 4.8% (range: 1%-79.9%) and median esophageal volume exposure was 1.6% (range: 0.7-5.5). There was a median of 72 reflux events (range: 27-147) per 24 hours. A correlation existed between Reflux Symptom Index score and proximal reflux (r = 0.533, P = 0.006). Pepsin was detected in 11 of 15 BALF samples signifying aspiration (median: 18 ng/mL; range: 0-43). Bile salts were undetectable, using spectrophotometry and rarely detectable using dual mass spectrometry (2/15) (levels 0.2 and 1.2 µmol/L). Lavage interleukin-8 and neutrophil levels were elevated. A correlation existed between proximal reflux events and neutrophilia (r = 0.52, P = 0.03). CONCLUSIONS: Lung transplant recipients should be routinely assessed for reflux/aspiration within the first month posttransplant. Reflux/aspiration can be present early postoperatively. Pepsin was detected suggesting aspiration. Bile salts were rarely detected. Proximal reflux events correlated with neutrophilia, linked to allograft dysfunction and mortality. These results support the need for early assessment of reflux/aspiration, which may inform fundoplication.

Measurement of stainer bath contamination and evaluation of common mitigation strategies.

Methods relative to the staining of tissues using hematoxylin and eosin (H&E) have largely not evolved beyond linear batch staining processes. The batching of slides in the histopathology laboratory inherently leads to the sharing of the various reagents among those specimens being processed through the baths. Studies analyzing the effects of reagent sharing during the common H&E linear staining method are limited. This study assessed rates of extraneous tissue contamination found in selected stainer bath containers from the deparaffinization portion of the H&E linear staining procedure. The impact of common mitigation strategies on those rates of contamination was evaluated.

Chronic cough: relationship between microaspiration, gastroesophageal reflux, and cough frequency.

BACKGROUND: Microaspiration is often considered a potential cause of cough. The aim of this study was to investigate the relationship between microaspiration, the degree and type of gastroesophageal reflux, and the frequency of coughing in patients with chronic cough. METHODS: One hundred patients with chronic cough (mean [± SD] age, 55.8 years [± 11.0 years]; 65 women) and 32 healthy volunteers (median age, 43.5 years [interquartile range (IQR), 30-50.8 years]; 16 women) were recruited. Patients with chronic cough performed 24-h objective cough frequency with simultaneous esophageal impedance/pH monitoring and measurement of pepsin concentrations in sputum and BAL. Twelve healthy volunteers underwent bronchoscopy/BAL, and 20 underwent impedance/pH monitoring. RESULTS: Patients with chronic cough had significantly more reflux episodes than healthy volunteers (median, 63.5 reflux episodes [IQR, 52.5-80.0] vs 59.0 [IQR, 41.8-66.0]; P = .03), although the absolute difference was small, and there was no difference in numbers of events extending into the proximal esophagus (median, 17.2% [IQR, 8.0%-26.0%] vs 20.3% [IQR, 5.1%-32.1%]; P = .36). BAL pepsin levels were also similar in chronic cough to control subjects (median, 18.2 ng/mL [range, 0-56.4 ng/mL] vs 9.25 ng/mL [range, 0-46.9 ng/mL]; P = .27). Sputum but not BAL pepsin weakly correlated with the number of proximally occurring reflux events (r = 0.33, P = .045) but was inversely related to cough frequency (r = −0.52, P = .04). Sputum pepsin was, therefore, best predicted by combining the opposing influences of cough and proximal reflux (r = 0.50, P = .004). CONCLUSIONS: Proximal gastroesophageal reflux and microaspiration into the airways have limited roles in provoking chronic cough. Indeed, coughing appears to be protective, reducing pepsin concentration in the larger airways of patients with chronic cough.

Physiological parameters governing the action of pancreatic lipase.

The most widely used pharmacological therapies for obesity and weight management are based on inhibition of gastrointestinal lipases, resulting in a reduced energy yield of ingested foods by reducing dietary lipid absorption. Colipase-dependent pancreatic lipase is believed to be the major gastrointestinal enzyme involved in catalysis of lipid ester bonds. There is scant literature on the action of pancreatic lipase under the range of physiological conditions that occur within the human small intestine, and the literature that does exist is often contradictory. Due to the importance of pancreatic lipase activity to nutrition and weight management, the present review aims to assess the current body of knowledge with regards to the physiology behind the action of this unique gastrointestinal enzyme system. Existing data would suggest that pancreatic lipase activity is affected by intestinal pH, the presence of colipase and bile salts, but not by the physiological range of Ca ion concentration (as is commonly assumed). The control of secretion of pancreatic lipase and its associated factors appears to be driven by gastrointestinal luminal content, particularly the presence of acid or digested proteins and fats in the duodenal lumen. Secretion of colipase, bile acids and pancreatic lipase is driven by cholecystokinin and secretin release.

Lung transplantation, gastroesophageal reflux, and fundoplication.

Lung transplantation is an accepted treatment strategy for end-stage lung disease; however, bronchiolitis obliterans syndrome is a major cause of morbidity and mortality. This review explores the role of gastroesophageal reflux disease in bronchiolitis obliterans syndrome and the evidence suggesting the benefits of anti-reflux surgery in improving lung function and survival. There is a high prevalence of gastroesophageal reflux in patients post lung transplantation. This may be due to a high preoperative incidence, vagal damage and immunosuppression. Reflux in these patients is associated with a worse outcome, which may be due to micro-aspiration. Anti-reflux surgery is safe in selected lung transplant recipients; however there has been one report of a postoperative mortality. Evidence is conflicting but may suggest a benefit for patients undergoing anti-reflux surgery in terms of lung function and survival; there are no controlled studies. The precise indications, timing, and choice of fundoplication are yet to be defined, and further studies are required.

A call for standardization of antireflux surgery in the lung transplantation population.

Long-term survival post lung transplant is reduced significantly by Bronchiolitis Obliterans Syndrome. It is suggested that extra-esophageal reflux disease is a risk factor for Bronchiolitis Obliterans Syndrome and that antireflux surgery may be beneficial. However, practice between centers varies greatly. We suggest a need for improved evidence and standardization.

Expression of mucin gene products in laryngeal squamous cancer.

OBJECTIVE: Mucins are high-molecular-weight glycoproteins present at the outer surface of mammalian cells. The objective of this study was to examine the expression of mucin (MUC) genes 3, 4, 5AC, 5B, 6, and 7 in early and late laryngeal squamous cancer using the in situ hybridization technique. Study design Retrospective analysis of pathological archive specimens. RESULTS: While MUC 3 and 7 are expressed in a small proportion of early cancers, MUC 5AC, 5B, and 6 are not expressed in laryngeal squamous cancer. MUC 4 was expressed in 13 of the 30 patients. Ten patients and 3 patients with stage 1 and stage 4 disease respectively expressed MUC 4 gene (Fisher's exact, P = 0.02). MUC 4-positive patients had a definite trend towards better survival (log rank test, P = 0.05). In the presence of tumor stage and comorbidity grade, Cox's proportional hazards model failed to statistically confirm the survival advantage provided by MUC 4 gene expression. CONCLUSION: There is a survival advantage for patients with advanced-stage nonmetastatic cancer when the MUC 4 gene is expressed. AIMS: To study the expression of mucin (MUC) genes 3, 4, 5AC, 5B, 6, and 7 in early and advanced squamous cell cancer of the larynx; to attempt to correlate changes in gene expression with tumor stage by studying stage I and stage IV (AJCC, 1988) tumors.