Natan Feldman

Idiopathic pulmonary fibrosis is associated with increased impedance measures of reflux compared to non‐fibrotic disease among pre‐lung transplant patients

Gastroesophageal reflux (GER) has been associated with idiopathic pulmonary fibrosis (IPF), although the mechanism remains unclear. Gastroesophageal reflux/microaspiration may lead to lung fibrosis, while increased pulmonary workload may also worsen GER. Comparing the GER profile of IPF patients to chronic obstructive pulmonary disease (COPD) patients with similar lung function may help delineate the role of GER in IPF pathogenesis.

Endoscopic pH monitoring for patients with suspected or refractory gastroesophageal reflux disease

BACKGROUND Wireless pH studies can offer prolonged pH monitoring, which may potentially facilitate the diagnosis and management of patients with gastroesophageal reflux disease (GERD). The aim of the present study was to evaluate the detection rate of abnormal esophageal acid exposure using prolonged pH monitoring in patients with suspected or refractory GERD symptoms. METHODS Patients undergoing prolonged ambulatory pH studies for the evaluation of GERD-related symptoms were assessed. Patients with a known diagnosis of GERD were tested on medical therapy, while patients with suspected GERD were tested off therapy. The wireless pH capsules were placed during upper endoscopy 6 cm above the squamocolumnar junction. RESULTS One hundred ninety-one patients underwent a total of 198 pH studies. Fifty ambulatory pH studies (25%) were excluded from the analysis: 27 patients (14%) had insufficient data capture (less than 18 h on at least one day of monitoring), 15 patients had premature capsule release (7%), seven were repeat studies (3.5%) and one had intolerable pain requiring capsule removal (0.5%). There were 115 patients undergoing pH studies who were off medication, and 33 patients were on therapy. For the two groups of patients, results were as follows: 32 (28%) and 22 (67%) patients with normal studies on both days; 58 (50%) and five (15%) patients with abnormal studies on both days; 18 (16%) and three (9%) patients with abnormal studies on day 1 only; and seven (6%) and three (9%) patients with abnormal studies on day 2 only, respectively. CONCLUSIONS Prolonged 48 h pH monitoring can detect more abnormal esophageal acid exposure but is associated with a significant rate of incomplete studies.

Pre-lung transplant measures of reflux on impedance are superior to pH testing alone in predicting early allograft injury

AIM To evaluate pre-lung transplant acid reflux on pH-testing vs corresponding bolus reflux on multichannel intraluminal impedance (MII) to predict early allograft injury. METHODS This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant combined MII-pH-testing at a tertiary care center from January 2007 to November 2012. Patients with pre-transplant fundoplication were excluded. Time-to-event analysis was performed using a Cox proportional hazards model to assess associations between measures of reflux on MII-pH testing and early allograft injury. Area under the receiver operating characteristic (ROC) curve (c-statistic) of the Cox model was calculated to assess the predictive value of each reflux parameter for early allograft injury. Six pH-testing parameters and their corresponding MII measures were specified a priori. The pH parameters were upright, recumbent, and overall acid reflux exposure; elevated acid reflux exposure; total acid reflux episodes; and acid clearance time. The corresponding MII measures were upright, recumbent, and overall bolus reflux exposure; elevated bolus reflux exposure; total bolus reflux episodes; and bolus clearance time. RESULTS Thirty-two subjects (47% men, mean age: 55 years old) met the inclusion criteria of the study. Idiopathic pulmonary fibrosis (46.9%) represented the most common pulmonary diagnosis leading to transplantation. Baseline demographics, pre-transplant cardiopulmonary function, number of lungs transplanted (unilateral vs bilateral), and post-transplant proton pump inhibitor use were similar between reflux severity groups. The area under the ROC curve, or c-statistic, of each acid reflux parameter on pre-transplant pH-testing was lower than its bolus reflux counterpart on MII in the prediction of early allograft injury. In addition, the development of early allograft injury was significantly associated with three pre-transplant MII measures of bolus reflux: overall reflux exposure (HR = 1.18, 95%CI: 1.01-1.36, P = 0.03), recumbent reflux exposure (HR = 1.25, 95%CI: 1.04-1.50, P = 0.01) and bolus clearance (HR = 1.09, 95%CI: 1.01-1.17, P = 0.02), but not with any pH-testing parameter measuring acid reflux alone. CONCLUSION Pre-transplant MII measures of bolus reflux perform better than their pH-testing counterparts in predicting early allograft injury post-lung transplantation.

Lung disease severity in idiopathic pulmonary fibrosis is more strongly associated with impedance measures of bolus reflux than pH parameters of acid reflux alone

Gastroesophageal reflux (GER) has been associated with idiopathic pulmonary fibrosis (IPF). Pathogenesis may be related to chronic micro‐aspiration. We aimed to assess objective measures of GER on multichannel intraluminal impedance and pH study (MII‐pH) and their relationship with pulmonary function testing (PFT) results, and to compare the performance of pH/acid reflux parameters vs corresponding MII/bolus parameters in predicting pulmonary dysfunction in IPF.

Abnormal Bolus Reflux Is Associated With Poor Pulmonary Outcome in Patients With Idiopathic Pulmonary Fibrosis

Background/Aims Gastroesophageal reflux (GER) is postulated to play a role in idiopathic pulmonary fibrosis (IPF). However, the value of objective GER measures in predicting IPF disease progression is unclear. We aim to evaluate the association between objective GER measures on multichannel intraluminal impedance and pH (MII-pH) testing and development of poor pulmonary outcomes within 1 year in pre-lung transplant IPF patients. Methods This was a retrospective cohort study of adults with IPF who underwent pre-lung transplant evaluation with MII-pH off proton pump inhibitors (PPI) at a tertiary care center from June 2008 to November 2015. Patients were followed for 1 year from time of MII-pH for poor pulmonary outcomes, defined by hospitalization for respiratory exacerbation or death. Univariate, multivariate and time-to-event analyses were performed to assess associations between baseline GER parameters on MII-pH and poor outcomes. Results Eighty-four subjects (mean age 61.1 years, 64.3% male) were included. Subjects with increased bolus exposure time (BET) had a higher incidence of 1-year poor pulmonary outcome vs normal BET (45.7% vs 15.2%, P = 0.006). Increased BET remained an independent predictor of poor outcome after controlling for age, gender, body mass index, smoking, lung disease severity, and PPI use (OR, 4.18; P = 0.030). Increased BET was also predictive of decreased time to poor pulmonary outcome (hazard ratio [HR], 4.88; P = 0.007). Subgroup analyses showed that increased BET remained independently associated with time to pulmonary hospitalization (HR, 4.00; P = 0.020), with a trend for 1-year mortality (HR, 2.19; P = 0.380). Conclusion Increased BET on MII-pH is an independent predictor of poor pulmonary outcome over 1 year in IPF patients.

Increased proximal acid reflux is associated with early readmission following lung transplantation

Gastroesophageal reflux disease has been associated with poor outcomes following lung transplantation. However, the association between pretransplant reflux and post‐transplant readmission, an indicator of early clinical outcome, has not been previously assessed.

241 Increased Reflux Severity on Impedance Predicts One-Year Pulmonary Function Decline in Pre-Lung Transplant Patients With Idiopathic Pulmonary Fibrosis

Background: Gastroesophageal reflux (GER) has been associated with pulmonary disease in pre-lung transplant patients, especially idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). The mechanism of these associations remains controversial. Microaspiration of refluxate may lead to inflammatory changes and pulmonary fibrosis or airway disease. Worsening pulmonary function may also increase trans-diaphragmatic pressure gradient, magnifying GER. The association between GER and decline in lung function in these patients has not yet been demonstrated. Evaluating the relationship between objective reflux parameters and change in pulmonary function may help clarify pathophysiology and identify targets for treatment. Aim: To investigate the association between objective measures of reflux on multichannel intraluminal impedance and pH study (MII-pH) and change in pulmonary function testing (PFT) parameters over one year, in pre-lung transplant patients with IPF or COPD. Methods: This was a retrospective cohort study of adults with IPF or COPD who underwent pretransplant evaluation with MII-pH, off acid suppression, at a tertiary care center from 6/2010-14. Patients with fundoplication prior to MII-pH were excluded. PFT was performed within 1 month of MII-pH and at 12-month follow-up. Association between baseline reflux measures and change in PFT parameters over one year was evaluated using Students t-test for continuous variables and Fishers exact test for binary variables. Results: 57 subjects (mean age=60 yrs, 42% female, 37 IPF vs 20 COPD) met criteria for inclusion. Among IPF patients, abnormal bolus reflux on impedance was associated with a significant decline in forced expiratory volume in 1 second (FEV1) in 1 year (-0.048 L/sec vs +0.24 L/sec, p=0.041), as was increased acid exposure time (-0.195 L/sec vs +0.144 L/sec, p=0.05). Trends toward more severe decline in forced vital capacity (FVC) in 1year for both abnormal bolus reflux (-0.085 L/sec vs +0.25 L/sec, p=0.09) and increased acid exposure time (-0.28 L/sec vs +0.147 L/sec, p=0.10) were also observed. Among COPD patients, trends toward more severe decline in FEV1 in 1 year was noted for increased acid exposure time (-0.27 L/sec vs -0.035 L/sec, p=0.087). No other significant associations between change in PFT and abnormal MII-pH parameters were found (Table 1). Conclusion: Abnormal GER as measured on MII-pH predicts more severe decline in lung function in 1 year on PFT among pre-lung transplant patients with IPF. A similar association between GER and lung function decline was not found in COPD patients. GER may play a more significant role in the pathogenesis of IPF than COPD. Future long-term studies are needed to further characterize the effect of GER on severity and prognosis of pulmonary disorders. Association between measures of reflux severity and worse pulmonary function (FEV1) after 1 year in patients with IPF.

T1057 Risk Factors for Incomplete Antibiotic Treatment Response in Small Intestinal Bacterial Overgrowth

Background/Aims: Both azathioprine (AZA) and 6-mercaptopurine (6MP) have shown their efficacy in the treatment of Crohns disease (CD). However, their use is limited owing to treatment intolerance or toxicity. Among adverse effects of immunomodulato-rs (IMM), leukopenia is the most serious, and occurs in about 40% of Korean CD population. Some authors suggest that TPMT polymorphism might be the cause of leucopenia in Korea, but it remains unclear. Coadministration of IMM and 5-aminosalicylate (5-ASA) may inhibit TMPT activity, and might cause leukopenia. Based on it, we conducted this study to clarify whether leukopenia occurs more common in coadministration of IMM and 5-ASA (Co_Ad) group than in IMM only group or not retrospectively. Method: Among 1,525 CD patients registered at IBD clinic in AMC between January 1999 and September 2008, 554 CD patients, who have been on azathioprine/6MP more than 1 month, were identified. Leukopenia was defined as WBC count below 4,000/mm3 . A conversion factor of 2.08 was taken into account when calculating equivalent doses of 6-MP and AZA. Results: Of 554 CD patients (67 patients on IMM only, 487 patients on IMM and 5-ASA), baseline characteristics of both group, including mean ages (31.8±10.19 vs 29.6±8.8), ratio of male to female (1.75:1 vs 2.55:1), patients number with stricture (42 vs 311), patients number with fistula (36 vs 242), and patients number on steroids (27 vs 172) were similar in both groups. The mean dosage of AZA were 1.81mg/Kg in IMM group and 1.77mg/Kg in Co-Ad group (p= n.s). The incidence of leukopenia was 44.7 % (30/67) in IMM group and 61.6% (300/487) in Co-Ad group, and was higher in Co-Ad group than in IMM group (p= 0.011). The steroid free remission rates were similar in both groups (48.1% vs 51.9%). Conclusion: Leukopenia occurs more common in Co-Ad group. More careful monitorings is necessary if CD patients had been on combination therapy with azathiprine/6MP and 5 ASA.