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425: Gatroesophageal Relfux Disease Increases the Rate of Acute Rejection in Lung Transplant Allografts
The Journal of Heart and Lung Transplantation Volume 28, Number 2S
424
Abstracts
S213
A. Pelaez1,2 1Emory University School of Medicine, Atlanta, GA; Emory University School of Medicine, Atlanta, GA; 3Rollins School of Public Health, Atlanta, GA; 4Emory University School of Medicine, Atlanta, GA; 5Emory University School of Medicine, Atlanta, GA 2
Temporal Patterns of Lung Pepsin Levels in Allografts Suggest Aspiration Is an Ongoing Injury, Which Can Occur Early Following Lung Transplantation R. Stovold2, I. Forrest1, D. Murphy1, G. Johnston1, J. Lordan1, A. Fisher1, J. Dark1, P. Corris1, J. Pearson2, C. Ward1 1University of Newcastle, Newcastle upon Tyne, United Kingdom; 2University of Newcastle, Newcastle upon Tyne, United Kingdom Purpose: Aspiration may contribute to non-alloimmune lung allograft injury and eventual loss. Medical and surgical interventions have been advocated including fundoplication, but there is no consensus about when this should be carried out. Biomarker approaches, including measuring pepsin and bile salts have been proposed to document aspiration, and may potentially inform treatment, but there are few longitudinal studies. Hypothesis. Pepsin is present in serial BAL samples from lung allografts. High levels, early post lung transplant may be a practicable guide/rationale for early therapeutic intervention. Methods and Materials: Ten lung allograft recipients without BOS (3 male, median age 43, range 20-61, 2 with an episode of clinical infection 1 Aspergillus and 1 pneumococcus) underwent longitudinal bronchoscopy and standardised BAL with biopsy to assess rejection. BAL samples taken at one week, one month, three months, six months and a year were analysed for pepsin using a specific ELISA. Results: Pepsin was detectable in variable amounts in all patients including high levels early post transplant. Fig. 1 plots this, and broken lines highlight 3 patients with early elevated levels. These three patients also had clinically significant (A2) acute vascular rejection, concordant with elevated pepsin, but no evidence of clinical infection. There was a trend towards higher pepsin levels (mean ⫾SEM) in patients with early ⱖA2 rejection 26.7(⫾ 8.2) ng/ml, compared to patients with lesser grades of rejection 14.9 (⫾ 3.3) ng/ml, p⫽NS. Conclusions: Aspiration may be an early and ongoing injury to lung allografts and may cause injury previously attributed to alloimmunity.
Purpose: Gastric fundoplicaton (GF) for gastroesophageal reflux disease (GERD) may protect against the progression of chronic rejection in lung transplant (LTx) recipients. However, the association of GERD with acute rejection (AR) is unknown. This study aims to identify if AR is linked to GERD in LTx patients, and if GF is protective in those identified with GERD. Methods and Materials: In this single center retrospective observational cohort study, all consecutive patients transplanted from Jan 1st 2006 to Jun 31st 2008 were identified. Patients with GERD were determined by pH probe or barium esophagogram. The occurrence of AR (⬎ ISHLT A2) was compared among the cohort of patients with and without GERD by incidence density (number of events per patient days post LTx). Additionally, the incidence density of AR in patients with GERD alone was compared to patients with GERD treated by GF. Results: We found 53 episodes of AR among the 70 patients transplanted for a combined 25,984 patient-days. Of the 38 patients diagnosed with GERD, 7 patients underwent GF prior to LTx, 11 patients after LTx, and 20 patients had no surgical intervention. A statistically significant higher rate of AR occurred in patients with GERD than those without (2.72 vs 1.06 per 1000 pt days, p⫽0.008). In patients with GF prior to LTx a trend towards higher rate of AR occurred compared to patients with GERD alone (4.92 vs 2.72 per 1000 pt days, p⫽0.11). Conversely, patients with GF after LTx tended to have lower rate of AR compared to patients with GERD alone (0.54 vs 2.72 per 1000 pt days, p⫽0.11). In the 11 patients undergoing GF after LTx, a trend towards a higher rate of AR occurred before GF than after GF (6.86 vs 0.54 per 1000 pt days, p⫽0.06). Median time for AR and GF after LTx was 37 days and 121 days, respectively. Conclusions: In LTx recipients, GERD is associated with a higher rate of AR. GF prior to LTx may not be protective for AR. Due to the small sample size, the benefit for GF for GERD after LTx to prevent AR remains inconclusive.
426 Exhaled Breath Condensate Pepsin Correlates with BAL Pepsin: A Potential Marker of GERD Post Lung Transplantation? A. Krishnan1, S. Chow2, M.A. Malouf1, M.L. Plit1, A.R. Glanville1 1 St.Vincent’s Hospital, Sydney, New South Wales, Australia; 2 University of New South Wales, Sydney, NSW, Australia
425 Gatroesophageal Relfux Disease Increases the Rate of Acute Rejection in Lung Transplant Allografts N.S. Shah1, K.V. Leeper1, K.A. Easley3, J. Qian3, S.D. Force4, A.A. Gal5, A.M. Ramirez1,2, D.C. Neujahr1,2, E.C. Lawrence1,2,
Purpose: Gastroesophageal reflux disease (GERD) is an important risk factor for chronic allograft dysfunction in lung transplant (LTx) recipients. Diagnosis currently relies on invasive tests such as oesophageal pH probe testing. We have previously reported pepsin in exhaled breath condensate (EBC) as a potential marker of aspiration and this has also been studied in bronchoalveolar lavage (BAL) but the correlation between the two is unknown. The aim of this study was to study the correlation between EBC and BAL pepsin in the investigation of GERD post LTx. We also investigated the correlation between these measures and acid exposure on pH probe testing. Methods and Materials: 10 LTx patients, who underwent bronchoscopy for investigation of worsening lung function, were recruited. All
424
Abstracts
S213
A. Pelaez1,2 1Emory University School of Medicine, Atlanta, GA; Emory University School of Medicine, Atlanta, GA; 3Rollins School of Public Health, Atlanta, GA; 4Emory University School of Medicine, Atlanta, GA; 5Emory University School of Medicine, Atlanta, GA 2
Temporal Patterns of Lung Pepsin Levels in Allografts Suggest Aspiration Is an Ongoing Injury, Which Can Occur Early Following Lung Transplantation R. Stovold2, I. Forrest1, D. Murphy1, G. Johnston1, J. Lordan1, A. Fisher1, J. Dark1, P. Corris1, J. Pearson2, C. Ward1 1University of Newcastle, Newcastle upon Tyne, United Kingdom; 2University of Newcastle, Newcastle upon Tyne, United Kingdom Purpose: Aspiration may contribute to non-alloimmune lung allograft injury and eventual loss. Medical and surgical interventions have been advocated including fundoplication, but there is no consensus about when this should be carried out. Biomarker approaches, including measuring pepsin and bile salts have been proposed to document aspiration, and may potentially inform treatment, but there are few longitudinal studies. Hypothesis. Pepsin is present in serial BAL samples from lung allografts. High levels, early post lung transplant may be a practicable guide/rationale for early therapeutic intervention. Methods and Materials: Ten lung allograft recipients without BOS (3 male, median age 43, range 20-61, 2 with an episode of clinical infection 1 Aspergillus and 1 pneumococcus) underwent longitudinal bronchoscopy and standardised BAL with biopsy to assess rejection. BAL samples taken at one week, one month, three months, six months and a year were analysed for pepsin using a specific ELISA. Results: Pepsin was detectable in variable amounts in all patients including high levels early post transplant. Fig. 1 plots this, and broken lines highlight 3 patients with early elevated levels. These three patients also had clinically significant (A2) acute vascular rejection, concordant with elevated pepsin, but no evidence of clinical infection. There was a trend towards higher pepsin levels (mean ⫾SEM) in patients with early ⱖA2 rejection 26.7(⫾ 8.2) ng/ml, compared to patients with lesser grades of rejection 14.9 (⫾ 3.3) ng/ml, p⫽NS. Conclusions: Aspiration may be an early and ongoing injury to lung allografts and may cause injury previously attributed to alloimmunity.
Purpose: Gastric fundoplicaton (GF) for gastroesophageal reflux disease (GERD) may protect against the progression of chronic rejection in lung transplant (LTx) recipients. However, the association of GERD with acute rejection (AR) is unknown. This study aims to identify if AR is linked to GERD in LTx patients, and if GF is protective in those identified with GERD. Methods and Materials: In this single center retrospective observational cohort study, all consecutive patients transplanted from Jan 1st 2006 to Jun 31st 2008 were identified. Patients with GERD were determined by pH probe or barium esophagogram. The occurrence of AR (⬎ ISHLT A2) was compared among the cohort of patients with and without GERD by incidence density (number of events per patient days post LTx). Additionally, the incidence density of AR in patients with GERD alone was compared to patients with GERD treated by GF. Results: We found 53 episodes of AR among the 70 patients transplanted for a combined 25,984 patient-days. Of the 38 patients diagnosed with GERD, 7 patients underwent GF prior to LTx, 11 patients after LTx, and 20 patients had no surgical intervention. A statistically significant higher rate of AR occurred in patients with GERD than those without (2.72 vs 1.06 per 1000 pt days, p⫽0.008). In patients with GF prior to LTx a trend towards higher rate of AR occurred compared to patients with GERD alone (4.92 vs 2.72 per 1000 pt days, p⫽0.11). Conversely, patients with GF after LTx tended to have lower rate of AR compared to patients with GERD alone (0.54 vs 2.72 per 1000 pt days, p⫽0.11). In the 11 patients undergoing GF after LTx, a trend towards a higher rate of AR occurred before GF than after GF (6.86 vs 0.54 per 1000 pt days, p⫽0.06). Median time for AR and GF after LTx was 37 days and 121 days, respectively. Conclusions: In LTx recipients, GERD is associated with a higher rate of AR. GF prior to LTx may not be protective for AR. Due to the small sample size, the benefit for GF for GERD after LTx to prevent AR remains inconclusive.
426 Exhaled Breath Condensate Pepsin Correlates with BAL Pepsin: A Potential Marker of GERD Post Lung Transplantation? A. Krishnan1, S. Chow2, M.A. Malouf1, M.L. Plit1, A.R. Glanville1 1 St.Vincent’s Hospital, Sydney, New South Wales, Australia; 2 University of New South Wales, Sydney, NSW, Australia
425 Gatroesophageal Relfux Disease Increases the Rate of Acute Rejection in Lung Transplant Allografts N.S. Shah1, K.V. Leeper1, K.A. Easley3, J. Qian3, S.D. Force4, A.A. Gal5, A.M. Ramirez1,2, D.C. Neujahr1,2, E.C. Lawrence1,2,
Purpose: Gastroesophageal reflux disease (GERD) is an important risk factor for chronic allograft dysfunction in lung transplant (LTx) recipients. Diagnosis currently relies on invasive tests such as oesophageal pH probe testing. We have previously reported pepsin in exhaled breath condensate (EBC) as a potential marker of aspiration and this has also been studied in bronchoalveolar lavage (BAL) but the correlation between the two is unknown. The aim of this study was to study the correlation between EBC and BAL pepsin in the investigation of GERD post LTx. We also investigated the correlation between these measures and acid exposure on pH probe testing. Methods and Materials: 10 LTx patients, who underwent bronchoscopy for investigation of worsening lung function, were recruited. All