AIM:To evaluate pre-lung transplant acid reflux on p H-testing vs corresponding bolus reflux on multichannel intraluminal impedance(MII) to predict early allograft injury.METHODS:This was a retrospective cohort study ...AIM:To evaluate pre-lung transplant acid reflux on p H-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 pretransplant combined MII-p H-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-p H 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 p H-testing parameters and their corresponding MIImeasures were specified a priori. The p H 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%) repres e n t e d t h e m o s t c o m m o n p u l m o n a r y d i a g n o s i s leading to transplantation. Baseline demographics,pre-transplant cardiopulmonary function,number of lungs transplanted(unilateral vs bilateral),and posttransplant 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 p H-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 p Htesting parameter measuring acid reflux alone.CONCLUSION:Pre-transplant MII measures of bolus reflux perform better than their p H-testing counterparts in predicting early allograft injury post-lung transplantation.展开更多
BACKGROUND Gastroesophageal reflux is associated with poorer outcomes after lung transplant,likely through recurrent aspiration and allograft injury.Although prior studies have demonstrated a relationship between impe...BACKGROUND Gastroesophageal reflux is associated with poorer outcomes after lung transplant,likely through recurrent aspiration and allograft injury.Although prior studies have demonstrated a relationship between impedance-pH results and transplant outcomes,the role of esophageal manometry in the assessment of lung transplant patients remains debated,and the impact of esophageal dysmotility on transplant outcomes is unclear.Of particular interest is ineffective esophageal motility(IEM)and its associated impact on esophageal clearance.AIM To assess the relationship between pre-transplant IEM diagnosis and acute rejection after lung transplantation.METHODS This was a retrospective cohort study of lung transplant recipients at a tertiary care center between 2007 and 2018.Patients with pre-transplant anti-reflux surgery were excluded.Manometric and reflux diagnoses were recorded from pre-transplant esophageal function testing.Time-to-event analysis using Cox proportional hazards model was applied to evaluate outcome of first episode of acute cellular rejection,defined histologically per International Society of Heart and Lung Transplantation guidelines.Subjects not meeting this endpoint were censored at time of post-transplant anti-reflux surgery,last clinic visit,or death.Fisher’s exact test for binary variables and student’s t-test for continuous variables were performed to assess for differences between groups.RESULTS Of 184 subjects(54%men,mean age:58,follow-up:443 person-years)met criteria for inclusion.Interstitial pulmonary fibrosis represented the predominant pulmonary diagnosis(41%).During the follow-up period,60 subjects(33.5%)developed acute rejection.The all-cause mortality was 16.3%.Time-to-event univariate analyses demonstrated significant association between IEM and acute rejection[hazard ratio(HR):1.984,95%CI:1.03-3.30,P=0.04],confirmed on Kaplan-Meier curve.On multivariable analysis,IEM remained independently associated with acute rejection,even after controlling for potential confounders such as the presence of acid and nonacid reflux(HR:2.20,95%CI:1.18-4.11,P=0.01).Nonacid reflux was also independently associated with acute rejection on both univariate(HR:2.16,95%CI:1.26-3.72,P=0.005)and multivariable analyses(HR:2.10,95%CI:1.21-3.64,P=0.009),adjusting for the presence of IEM.CONCLUSION Pre-transplant IEM was associated with acute rejection after transplantation,even after controlling for acid and nonacid reflux.Esophageal motility testing may be considered in lung transplant to predict outcomes.展开更多
BACKGROUND Gastroesophageal reflux(GER)has been associated with poor outcomes after lung transplantation for chronic lung disease,including increased risk of chronic rejection.GER is common in cystic fibrosis(CF),but ...BACKGROUND Gastroesophageal reflux(GER)has been associated with poor outcomes after lung transplantation for chronic lung disease,including increased risk of chronic rejection.GER is common in cystic fibrosis(CF),but factors influencing the likelihood of pre-transplant pH testing,and the impact of testing on clinical management and transplant outcomes in patients with CF are unknown.AIM To evaluate the role of pre-transplant reflux testing in the evaluation of lung transplant candidates with CF.METHODS This was a retrospective study from 2007-2019 at a tertiary medical center that included all patients with CF undergoing lung transplant.Patients with pretransplant anti-reflux surgery were excluded.Baseline characteristics(age at transplantation,gender,race,body mass index),self-reported GER symptoms prior to transplantation,and pre-transplant cardiopulmonary testing results,were recorded.Reflux testing consisted of either 24-h pH-or combined multichannel intraluminal impedance and pH monitoring.Post-transplant care included a standard immunosuppressive regimen,and regular surveillance bronchoscopy and pulmonary spirometry in accordance with institutional practice as well as in symptomatic patients.The primary outcome of chronic lung allograft dysfunction(CLAD)was defined clinically and histologically per International Society of Heart and Lung Transplantation criteria.Statistical analysis was performed with Fisher’s exact test to assess differences between cohorts,and time-to-event Cox proportional hazards modeling.RESULTS After applying inclusion and exclusion criteria,a total of 60 patients were included in the study.Among all CF patients,41(68.3%)completed reflux monitoring as part of pre-lung transplant evaluation.Objective evidence of pathologic reflux,defined as acid exposure time>4%,was found in 24 subjects,representing 58%of the tested group.CF patients with pre-transplant reflux testing were older(35.8 vs 30.1 years,P=0.01)and more commonly reported typical esophageal reflux symptoms(53.7%vs 26.3%,P=0.06)compared to those without reflux testing.Other patient demographics and baseline cardiopulmonary function did not significantly differ between CF subjects with and without pre-transplant reflux testing.Patients with CF were less likely to undergo pre-transplant reflux testing compared to other pulmonary diagnoses(68%vs 85%,P=0.003).There was a decreased risk of CLAD in patients with CF who underwent reflux testing compared to those who did not,after controlling for confounders(Cox Hazard Ratio 0.26;95%CI:0.08-0.92).CONCLUSION Pre-transplant reflux testing revealed high prevalence of pathologic reflux in CF patients and was associated with decreased risk of CLAD.Systematic reflux testing may enhance outcomes in this patient population.展开更多
Lung transplantation is one of the highest risk solid organ transplant modalities. Recent studies have demonstrated a relationship between gastroesophageal reflux disease(GERD) and lung transplant outcomes, including ...Lung transplantation is one of the highest risk solid organ transplant modalities. Recent studies have demonstrated a relationship between gastroesophageal reflux disease(GERD) and lung transplant outcomes, including acute and chronic rejection. The aim of this review is to discuss the pathophysiology, evaluation, and management of GERD in lung transplantation, as informed by the most recent publications in the field. The pathophysiology of reflux-induced lung injury includes the effects of aspiration and local immunomodulation in the development of pulmonary decline and histologic rejection, as reflective of allograft injury. Modalities of reflux and esophageal assessment, including ambulatory p H testing, impedance, and esophageal manometry, are discussed, as well as timing of these evaluations relative to transplantation. Finally, antireflux treatments are reviewed, including medical acid suppression and surgical fundoplication, as well as the safety, efficacy, and timing of such treatments relative to transplantation. Our review of the data supports an association between GERD and allograft injury, encouraging a strategy of early diagnosis and aggressive reflux management in lung transplant recipients to improve transplant outcomes. Further studies are needed to explore additional objective measures of reflux and aspiration, better compare medical and surgical antireflux treatment options, extend followup times to capture longer-term clinical outcomes, and investigate newer interventions including minimally invasive surgery and advanced endoscopic techniques.展开更多
文摘AIM:To evaluate pre-lung transplant acid reflux on p H-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 pretransplant combined MII-p H-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-p H 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 p H-testing parameters and their corresponding MIImeasures were specified a priori. The p H 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%) repres e n t e d t h e m o s t c o m m o n p u l m o n a r y d i a g n o s i s leading to transplantation. Baseline demographics,pre-transplant cardiopulmonary function,number of lungs transplanted(unilateral vs bilateral),and posttransplant 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 p H-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 p Htesting parameter measuring acid reflux alone.CONCLUSION:Pre-transplant MII measures of bolus reflux perform better than their p H-testing counterparts in predicting early allograft injury post-lung transplantation.
文摘BACKGROUND Gastroesophageal reflux is associated with poorer outcomes after lung transplant,likely through recurrent aspiration and allograft injury.Although prior studies have demonstrated a relationship between impedance-pH results and transplant outcomes,the role of esophageal manometry in the assessment of lung transplant patients remains debated,and the impact of esophageal dysmotility on transplant outcomes is unclear.Of particular interest is ineffective esophageal motility(IEM)and its associated impact on esophageal clearance.AIM To assess the relationship between pre-transplant IEM diagnosis and acute rejection after lung transplantation.METHODS This was a retrospective cohort study of lung transplant recipients at a tertiary care center between 2007 and 2018.Patients with pre-transplant anti-reflux surgery were excluded.Manometric and reflux diagnoses were recorded from pre-transplant esophageal function testing.Time-to-event analysis using Cox proportional hazards model was applied to evaluate outcome of first episode of acute cellular rejection,defined histologically per International Society of Heart and Lung Transplantation guidelines.Subjects not meeting this endpoint were censored at time of post-transplant anti-reflux surgery,last clinic visit,or death.Fisher’s exact test for binary variables and student’s t-test for continuous variables were performed to assess for differences between groups.RESULTS Of 184 subjects(54%men,mean age:58,follow-up:443 person-years)met criteria for inclusion.Interstitial pulmonary fibrosis represented the predominant pulmonary diagnosis(41%).During the follow-up period,60 subjects(33.5%)developed acute rejection.The all-cause mortality was 16.3%.Time-to-event univariate analyses demonstrated significant association between IEM and acute rejection[hazard ratio(HR):1.984,95%CI:1.03-3.30,P=0.04],confirmed on Kaplan-Meier curve.On multivariable analysis,IEM remained independently associated with acute rejection,even after controlling for potential confounders such as the presence of acid and nonacid reflux(HR:2.20,95%CI:1.18-4.11,P=0.01).Nonacid reflux was also independently associated with acute rejection on both univariate(HR:2.16,95%CI:1.26-3.72,P=0.005)and multivariable analyses(HR:2.10,95%CI:1.21-3.64,P=0.009),adjusting for the presence of IEM.CONCLUSION Pre-transplant IEM was associated with acute rejection after transplantation,even after controlling for acid and nonacid reflux.Esophageal motility testing may be considered in lung transplant to predict outcomes.
基金The study was reviewed and approved by the Mass General Brigham Healthcare Institutional Review Board(2011P001563).
文摘BACKGROUND Gastroesophageal reflux(GER)has been associated with poor outcomes after lung transplantation for chronic lung disease,including increased risk of chronic rejection.GER is common in cystic fibrosis(CF),but factors influencing the likelihood of pre-transplant pH testing,and the impact of testing on clinical management and transplant outcomes in patients with CF are unknown.AIM To evaluate the role of pre-transplant reflux testing in the evaluation of lung transplant candidates with CF.METHODS This was a retrospective study from 2007-2019 at a tertiary medical center that included all patients with CF undergoing lung transplant.Patients with pretransplant anti-reflux surgery were excluded.Baseline characteristics(age at transplantation,gender,race,body mass index),self-reported GER symptoms prior to transplantation,and pre-transplant cardiopulmonary testing results,were recorded.Reflux testing consisted of either 24-h pH-or combined multichannel intraluminal impedance and pH monitoring.Post-transplant care included a standard immunosuppressive regimen,and regular surveillance bronchoscopy and pulmonary spirometry in accordance with institutional practice as well as in symptomatic patients.The primary outcome of chronic lung allograft dysfunction(CLAD)was defined clinically and histologically per International Society of Heart and Lung Transplantation criteria.Statistical analysis was performed with Fisher’s exact test to assess differences between cohorts,and time-to-event Cox proportional hazards modeling.RESULTS After applying inclusion and exclusion criteria,a total of 60 patients were included in the study.Among all CF patients,41(68.3%)completed reflux monitoring as part of pre-lung transplant evaluation.Objective evidence of pathologic reflux,defined as acid exposure time>4%,was found in 24 subjects,representing 58%of the tested group.CF patients with pre-transplant reflux testing were older(35.8 vs 30.1 years,P=0.01)and more commonly reported typical esophageal reflux symptoms(53.7%vs 26.3%,P=0.06)compared to those without reflux testing.Other patient demographics and baseline cardiopulmonary function did not significantly differ between CF subjects with and without pre-transplant reflux testing.Patients with CF were less likely to undergo pre-transplant reflux testing compared to other pulmonary diagnoses(68%vs 85%,P=0.003).There was a decreased risk of CLAD in patients with CF who underwent reflux testing compared to those who did not,after controlling for confounders(Cox Hazard Ratio 0.26;95%CI:0.08-0.92).CONCLUSION Pre-transplant reflux testing revealed high prevalence of pathologic reflux in CF patients and was associated with decreased risk of CLAD.Systematic reflux testing may enhance outcomes in this patient population.
文摘Lung transplantation is one of the highest risk solid organ transplant modalities. Recent studies have demonstrated a relationship between gastroesophageal reflux disease(GERD) and lung transplant outcomes, including acute and chronic rejection. The aim of this review is to discuss the pathophysiology, evaluation, and management of GERD in lung transplantation, as informed by the most recent publications in the field. The pathophysiology of reflux-induced lung injury includes the effects of aspiration and local immunomodulation in the development of pulmonary decline and histologic rejection, as reflective of allograft injury. Modalities of reflux and esophageal assessment, including ambulatory p H testing, impedance, and esophageal manometry, are discussed, as well as timing of these evaluations relative to transplantation. Finally, antireflux treatments are reviewed, including medical acid suppression and surgical fundoplication, as well as the safety, efficacy, and timing of such treatments relative to transplantation. Our review of the data supports an association between GERD and allograft injury, encouraging a strategy of early diagnosis and aggressive reflux management in lung transplant recipients to improve transplant outcomes. Further studies are needed to explore additional objective measures of reflux and aspiration, better compare medical and surgical antireflux treatment options, extend followup times to capture longer-term clinical outcomes, and investigate newer interventions including minimally invasive surgery and advanced endoscopic techniques.
