Lo WK, Fernandez AM, Feldman N, Sharma N, Goldberg HJ, Chan WW. Increased reflux burden on pre-transplant reflux testing independently predicts significant pulmonary function decline after lung transplantation. World J Transplant 2025; 15(3): 100111 [DOI: 10.5500/wjt.v15.i3.100111]
Corresponding Author of This Article
Walter W Chan, AGAF, FACG, MD, Associate Professor, Department of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, United States. wwchan@bwh.harvard.edu
Research Domain of This Article
Transplantation
Article-Type of This Article
Retrospective Cohort Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Wai-Kit Lo, Natan Feldman, Nirmal Sharma, Walter W Chan, Department of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women’s Hospital, Boston, MA 02115, United States
Annel M Fernandez, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States
Hilary J Goldberg, Department of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States
Author contributions: Lo WK and Chan WW initiated study concepts and design and performed statistical analyses; Lo WK, Feldman N, Sharma N, Goldberg HJ, and Chan WW contributed to acquisition of data; Lo WK, Sharma N, Goldberg HJ, and Chan WW performed analysis and interpretation of data; Lo WK, Fernandez AM, and Chan WW drafted the manuscript; Lo WK, Fernandez AM, Feldman N, Sharma N, Goldberg HJ, and Chan WW contributed to critical revision of manuscript for important intellectual content; Chan WW provided administrative support and overall study supervision; and all authors thoroughly reviewed and endorsed the final manuscript.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Mass General Brigham Institutional Review Board, approval No. 2011P001563.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: Technical appendix, statistical code, and dataset available upon reasonable request and approval by the Institutional Review Borad from the corresponding author at wwchan@bwh.harvard.edu.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Walter W Chan, AGAF, FACG, MD, Associate Professor, Department of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, United States. wwchan@bwh.harvard.edu
Received: August 7, 2024 Revised: January 8, 2025 Accepted: February 26, 2025 Published online: September 18, 2025 Processing time: 253 Days and 22.8 Hours
Abstract
BACKGROUND
Gastroesophageal reflux disease has been shown to contribute to allograft injury and rejection outcomes in lung transplantation through a proposed mechanism of aspiration, inflammation, and allograft injury. The value of pre-transplant reflux testing in predicting reduction in pulmonary function after lung transplantation is unclear. We hypothesized that increased reflux burden on pre-transplant reflux testing is associated with pulmonary function decline following lung transplant.
AIM
To assess the relationship between pre-transplant measures of reflux and pulmonary function decline in lung transplant recipients.
METHODS
This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant reflux testing with 24-hour pH-impedance off acid suppression at a tertiary center in 2007-2016. Patients with pre-transplant fundoplication were excluded. Time-to-event analysis was performed using Cox proportional hazards models to assess associations between reflux measures and reduction in forced expiratory volume in 1 second (FEV1) of ≥ 20% post-transplant. Patients not meeting endpoint were censored at time of post-transplant fundoplication, last clinic visit, or death, whichever was earliest.
RESULTS
Seventy subjects (58% men, mean age: 56 years) met the inclusion criteria. Interstitial lung disease represented the predominant pulmonary diagnosis (40%). Baseline demographics were similar between groups and were not associated with pulmonary decline. The clinical endpoint (≥ 20% FEV1 decline) was reached in 18 subjects (26%). In time-to-event univariate analysis, FEV1 decline was associated with increased acid exposure time (AET) [hazard ratio (HR) = 3.49, P = 0.03] and increased proximal acid reflux (HR = 3.34, P = 0.04) with confirmation on Kaplan-Meier analysis. Multivariate analysis showed persistent association between pulmonary decline and increased AET (HR = 3.37, P = 0.04) when controlling for potential confounders including age, body mass index, and sex. Sub-group analysis including only patients with FEV1 decline showed that all subjects with abnormal AET progressed to bronchiolitis obliterans syndrome.
CONCLUSION
Increased reflux burden on pre-transplant testing was associated with significant pulmonary function decline post-transplant. Pre-transplant reflux assessment may provide clinically relevant information in the prognostication and management of transplant recipients.
Core Tip: Gastroesophageal reflux has been associated with increased morbidity and mortality after lung transplantation. Abnormal objective measures of reflux on pre-transplant multichannel intraluminal impedance and pH have also been associated with early allograft injury, early rehospitalization and development of bronchiolitis obliterans syndrome and chronic lung allograft dysfunction. However, the relationship between pre-transplant reflux severity and pulmonary function decline after lung transplant remains unclear. Out study demonstrated that abnormal acid exposure time on pre-transplant reflux testing was associated with significant pulmonary function decline defined as ≥ 20% decrease in post-transplant baseline forced expiratory volume in one second. Patients with acid reflux and forced expiratory volume in one second decline are at high risk of poor lung transplant outcomes and should be aggressively managed.
Citation: Lo WK, Fernandez AM, Feldman N, Sharma N, Goldberg HJ, Chan WW. Increased reflux burden on pre-transplant reflux testing independently predicts significant pulmonary function decline after lung transplantation. World J Transplant 2025; 15(3): 100111
Numerous publications have suggested a correlation between gastroesophageal reflux disease (GERD) and poor lung transplant outcomes[1-3]. GERD is highly prevalent after lung transplant with a prevalence of 51%-69%[2], and is thought to increase the risk of post-transplant aspiration, resulting in the activation of an inflammatory process that results in allograft injury and acute rejection, which may affect as many as 55% of patients within the first year. Several studies have documented evidence of inflammatory markers and pepsin or bile acids in bronchoalveolar fluid among subjects with acute rejection, suggesting the involvement of reflux and aspiration in early allograft damage[4-7]. Repeated occurrences of acute rejection and ongoing allograft injury may precipitate chronic rejection, ultimately resulting in the failure of the graft[7]. These findings are particularly noteworthy given that lung transplantation has the lowest mean 5-year survival rate[8](53%) compared to other solid organ transplant modalities[9,10].
Our group previously demonstrated that objective measures of reflux severity on pre-transplant impedance and pH testing were associated with decreased time to early graft injury following lung transplant[4]. More recently, we investigated the relationship between pre-transplant reflux testing and the development of bronchiolitis obliterans syndrome (BOS) and chronic lung allograft dysfunction (CLAD), indicators of chronic rejection following lung transplantation[11]. Although baseline forced expiratory volume in one second (FEV1) initially improves during the first 6-12 months following lung transplantation[12], BOS is marked by persistent FEV1 decline over 30-45 days post-transplant with a subsequent decrease in survival[13]. While previous studies have shown that increased acid exposure on pre-transplant reflux testing is associated with development of BOS[14], the relationship between pre-transplant reflux severity and decline in post-transplant pulmonary function, before formal criteria for rejection are met, remains unclear. Therefore, the aim this study is to assess the relationship between pre-transplant measures of reflux and pulmonary function decline in lung transplant recipients, as an earlier indicator of allograft injury. We hypothesized that increased acid exposure on pre-transplant reflux testing is associated with pulmonary function decline following lung transplant, as suggested by the above mechanism linking reflux to aspiration, inflammation, allograft injury, and rejection outcomes with ensuing impact on clinical lung function.
MATERIALS AND METHODS
This was a retrospective cohort study of lung transplant recipients (aged older than 18 years) who underwent pre-transplant reflux testing with 24-hour pH-impedance study multichannel intraluminal impedance and pH (MII-pH) off acid suppression at a tertiary care center between 2007-2016. Only patients undergoing initial primary lung transplant were included. Patients with pre-transplant fundoplication were excluded. The study enrolled all participants who met the specified inclusion and exclusion criteria, and their baseline characteristics and outcomes data were gathered and analyzed. Baseline characteristics included age at transplantation, number of lungs transplanted, sex, race, body mass index, pulmonary diagnosis, results of standard pre-transplant cardiopulmonary testing, cytomegalovirus mismatch, increased risk donor, post-transplant acid suppression medication use, and post-transplant infection. ABO compatibility was confirmed for all donors and recipients prior to transplantation.
Pre-transplant MII-pH
All patients in the study underwent reflux monitoring with MII-pH (Sandhill Scientific Inc, Highland Ranch, CO, United States) off acid suppression for at least 7 days and following an overnight fasting period prior to transplantation. This system includes a portable electronic data collection device and a MII-pH catheter equipped with two pH electrodes (positioned at 0 cm and 15 cm) and eight impedance electrodes (positioned at -3 cm, -1 cm, 1 cm, 3 cm, 5 cm, 9 cm, 11 cm and 13 cm). The catheter is calibrated according to the manufacturer's guidelines, inserted nasally into the oesophagus, and the distal pH electrode is positioned 5 cm above the lower oesophageal sphincter (LES). The distal pH electrode is positioned above the LES to detect distal reflux, while the proximal electrode is positioned approximately 15 cm above the LES to detect proximal reflux. Patients were instructed to maintain their usual daily routines throughout the 24-hour study period, to remain upright during the day and recumbent at night. They were also instructed to document meal times separately, which were excluded from analysis. Impedance and pH data were analyzed using specialized software (Bioview Analysis, version 5.6.3.0, Sandhill Scientific Inc). Parameters of interest included one measure of reflux by pH [acid exposure time (AET)] and two measures of reflux by impedance (proximal acid episodes and total reflux episodes). In the absence of clear thresholds in lung transplantation, increased AET was defined by > 4.2% of total study time with pH < 4 at the distal pH sensor; increased total reflux episodes was defined by > 72 episodes; and increased proximal acid episodes was defined by > 28 episodes, based on previously established GERD cutoffs in normal patients[15].
Post-transplant outcomes
Following transplantation, patients were treated with a standard immunosuppressive therapy regimen of azathioprine or mycophenolate, tacrolimus, and methylprednisolone[16], and 57 patients received proton pump inhibitor medication given a prior history of GERD or new-onset heartburn symptoms. All patients included in the study also underwent routine surveillance bronchoscopy and pulmonary function testing (PFT) set by our institutional protocol. A post-transplant baseline FEV1 was obtained which was assumed to be the highest FEV1 sustained after transplant. PFTs were subsequently obtained in response to symptoms or every 2-4 weeks for the first 3-6 months post-transplant, and then spaced out over time. Primary outcomes assessed included reduction in FEV1 of ≥ 20% from highest post-transplant value. This cutoff was selected because persistent clinical decline beyond this value sustained for 2 consecutive measurements taken 3 weeks apart, occurring at least 3 months from date of transplant, would satisfy formal clinical criteria for BOS per the International Society for Heart and Lung Transplantation[17]. The time to event was calculated from the date of transplant to the date of FEV1 decline. Patients who did not meet the end point were censored at date of post-transplant fundoplication, last clinic visit, or death, whichever was earliest. A sub-group analysis was performed including only those subjects meeting the ≥ 20% FEV1 decline endpoint, in which mean AET and progression to BOS was calculated.
Statistical analysis
Fischer’s exact test was used for categorical variables, and Student’s t-test was used for continuous variables to evaluate baseline differences among patient groups. The Kaplan-Meier method was used to construct time-to-event curves, with log-rank testing to quantify differences in time-to-event relationships. Time-to-event analysis using Cox proportional hazards model was applied to assess the relationship between pre-transplant reflux measures and reduction in FEV1 of ≥ 20%. All statistical analyses were performed using SAS 9.3 software (SAS Institute Inc, Cary, NC).
RESULTS
Seventy patients (58% male, mean age at transplant 56 years) met inclusion criteria for the study, with a mean follow-up of 2.2 years (Table 1). Interstitial pulmonary fibrosis represented the predominant pulmonary diagnosis leading to transplantation (22 subjects, 31%). 36 patients underwent bilateral lung transplantation. There were 16 deaths overall, with 13 attributable to pulmonary complications including pneumonia, lung cancer, and rejection. Baseline cardiopulmonary characteristics were similar between reflux severity groups (Table 1). The clinical endpoint (≥ 20% FEV1 decline) was reached in 18 subjects (26%). 14 of these patients developed BOS, including 3 with histologic confirmation of bronchiolitis obliterans. The mean time to FEV1 decline was 1.7 years with a median time of 0.8 years. Patient baseline demographics were evaluated to identify potential confounding factors and were ultimately not associated with pulmonary function decline (Table 2).
Table 1 Baseline demographics and clinical characteristics of study cohort, n (%).
Characteristics
Total (n = 70)
Normal acid exposure (n = 52)
Increased acid exposure (n = 18)
P value
Follow up, (years), mean ± SD
2.23 ± 1.87
2.24 ± 2.03
2.22 ± 1.34
0.97
Male sex
41 (58.6)
30 (57.7)
11 (61.1)
1.00
BMI, mean ± SD
26.8 ± 4.56
27.4 ± 4.40
25.4 ± 4.80
0.11
Age at transplant, mean ± SD
56.3 ± 12.5
56.7 ± 12.5
55.0 ± 13.0
0.62
White race
67 (95.7)
51 (98.1)
16 (88.9)
0.16
Pulmonary diagnosis
ILD
40 (57.1)
28 (53.8)
12 (66.7)
0.41
IPF
22 (31.4)
14 (26.9)
8 (44.4)
0.24
COPD
15 (21.4)
13 (25.0)
2 (11.1)
0.32
Other
17 (24.3)
13 (25.0)
4 (22.2)
1.00
Cardiac function, baseline
LVEF, mean ± SD
60.9 ± 5.48
60.3 ± 5.72
62.7 ± 4.40
0.11
PaP, mean ± SD
26.6 ± 9.36
27.7 ± 10.3
23.5 ± 4.62
0.03
PCWP, (mm Hg), mean ± SD
10.3 ± 4.90
10.8 ± 5.18
8.82 ± 3.71
0.16
PVR (dynes/cm5), mean ± SD
225 ± 134
230 ± 145
212 ± 91.9
0.64
Pulmonary function, baseline
FVC, mean ± SD
2.00 ± 0.77
1.99 ± 0.67
2.03 ± 1.01
0.87
FVC, %-pred, mean ± SD
0.49 ± 0.15
0.50 ± 0.16
0.46 ± 0.12
0.29
FEV1, mean ± SD
1.36 ± 0.66
1.32 ± 0.59
1.47 ± 0.85
0.44
FEV1, %-pred, mean ± SD
0.42 ± 0.19
0.43 ± 0.20
0.40 ± 0.18
0.63
FEV1/FVC, mean ± SD
0.69 ± 0.23
0.68 ± 0.23
0.72 ± 0.22
0.62
Bilateral lung transplant
36 (51.4)
29 (55.8)
7 (38.9)
0.28
CMV mismatch
18 (25.7)
15 (28.8)
3 (16.7)
0.37
Increased risk donor
11 (15.7)
8 (15.4)
3 (16.7)
1.00
Post-transplant infection
30 (42.8)
23 (44.3)
7 (38.9)
0.79
Post-transplant PPI
54 (77.1)
38 (73.1)
16 (88.9)
0.21
≥ 20% FEV1 decline
18 (25.7)
11 (21.1)
7 (38.9)
0.21
Table 2 Baseline demographics of cohort demonstrated no association with forced expiratory volume in 1 decline on time-to-event analysis.
Characteristics
Univariate hazard ratio for pulmonary function decline (95%CI)
P value
Male sex
2.14 (0.67-6.87)
0.20
BMI
0.98 (0.87-1.09)
0.70
Age at transplant
1.00 (0.95-1.04)
0.85
White race
0.59 (0.08-4.59)
0.62
Pulmonary diagnosis
ILD
2.29 (0.71-7.39)
0.16
IPF
2.73 (0.94-7.89)
0.06
COPD
0
-
Other
0.91 (0.28-2.94)
0.87
Cardiac function, baseline
LVEF
0.19 (0-4512)
0.75
PaP (mm Hg)
1.00 (0.95-1.06)
0.85
PCWP (mm Hg)
1.00 (0.90-1.11)
0.98
PVR (dynes/cm5)
1.00 (0.99-1.00)
0.58
Pulmonary function, baseline
FVC
1.14 (0.62-2.11)
0.67
FVC, %-pred
0.30 (0.01-9.66)
0.49
FEV1
1.67 (0.84-3.32)
0.14
FEV1, %-pred
3.25 (0.24-43.9)
0.37
FEV1/FVC
6.21 (0.46-83.7)
0.17
Bilateral lung transplant
0.74 (0.25-2.16)
0.59
CMV mismatch
0.77 (0.21-2.76)
0.69
Increased risk donor
0.62 (0.08-4.84)
0.65
Post-transplant infection
1.40 (0.49-4.01)
0.53
Post-transplant PPI
1.57 (0.35-7.04)
0.55
In time-to-event univariate analysis (Table 3), FEV1 decline was associated with increased AET [hazard ratio (HR) 3.49; 95% confidence interval (CI): 1.15-10.6; P = 0.03], and increased proximal acid reflux (HR = 3.34; 95%CI: 1.02-1.0; P = 0.04) with confirmation on Kaplan-Meier analysis (Figure 1). Multivariable analyses showed persistent association between pulmonary decline and increased AET (HR = 3.37; 95%CI: 1.08-10.6; P = 0.04) when controlling for potential confounders including age, body mass index and sex. Other reflex parameters were notably not associated with pulmonary decline.
Figure 1 Kaplan-Meier analysis of time to pulmonary decline by pre-transplant.
A: Kaplan-Meier analysis of time to pulmonary decline by pre-transplant acid exposure time. Increased acid exposure time (> 4.2% of time with pH < 4) resulted in earlier development of forced expiratory volume in 1 decline in transplant recipients. These results were preserved on multivariate analysis when controlling for body-mass index and gender; B: Kaplan-Meier analysis of time to pulmonary decline by pre-transplant proximal acid reflux episodes. Increased proximal episodes > 28 resulted in earlier development of forced expiratory volume in 1 decline in transplant recipients on univariate analysis.
Table 3 Multichannel intraluminal impedance and pH measures and time to forced expiratory volume in 1 decline.
Characteristics
Univariate hazard ratio for pulmonary function decline (95%CI)
P value
Multivariate analyses (separate models controlling for age, sex, BMI)
P value
Elevated AET (> 4.2%)
3.49 (1.15-10.6)
0.03
3.37 (1.08-10.6)
0.04
Elevated total reflux episodes (> 73)
1.09 (0.34-3.48)
0.89
1.45 (0.40-5.27)
0.57
Elevated proximal acid episodes (> 28)
3.34 (1.02-11.0)
0.04
3.29 (0.90-12.1)
0.07
Sub-group analysis
A sub-group analysis was performed for all subjects with ≥ 20% FEV1 decline (n = 18, 67% male, mean age at transplant 56). Mean AET for patients that progressed to BOS was 5.54 ± 5.92 vs 1.48 ± 1.51 for patients that did not progress to BOS (P = 0.04). No other demographic differences were noted. Importantly, all patients with abnormal AET > 4.2% progressed to BOS, and the 4 subjects with recovery of pulmonary function that did not develop BOS all had normal AET.
DISCUSSION
Numerous prior studies have shown that objective assessment of reflux during pre-transplant ambulatory reflux monitoring predicts adverse outcomes soon after lung transplantation including early allograft injury[4,11] and early readmission[18]. Other studies have assessed the relationship between pre-transplant reflux measures and longer-term outcomes, particularly chronic rejection[19,20], including BOS and CLAD. However, one area of interest is whether this association holds in patients with early pulmonary decline, before a clinical diagnosis of BOS or CLAD can be made.
In the present study, we highlighted three MII-pH parameters of reflux severity as part of the pre-transplant evaluation, which have been well studied in prior literature. We demonstrated that increased AET on pre-transplant reflux testing and elevated proximal acid episodes were associated with significant pulmonary function decline defined as ≥ 20% decrease in post-transplant baseline FEV1, and the association with increased AET held on multivariable analysis. When comparing baseline demographics between groups with normal acid exposure vs groups with increased acid exposure, no statistically significant differences between groups was identified (Table 1). The general homogeneity of the cohort is not surprising, considering the meticulous selection of transplant patients aimed at reducing perioperative risks. Additionally, baseline demographics of our cohort were not associated with pulmonary function decline (Table 2).
The literature on pre-transplant acid reflux assessment and post-transplant pulmonary function decline is limited. However, studies investigating the role of antireflux surgery in preserving post-transplantation pulmonary function provides support for our findings[21]. In one study published by Abbassi-Ghadi et al[22], lung transplant recipients with abnormal reflux on MII-pH that underwent laparoscopic Nissen fundoplication showed significant improvement in rate of change in FEV1 despite initially declining FEV1 post-transplant. Another study published by Davis et al[23], found that fundoplication in lung transplant recipients was associated with significant improvement in pulmonary function. Although these studies addressed post-transplant reflux, they suggest that timely management of reflux in lung transplant patients can result in improvement in pulmonary function. Moreover, studies have found benefit for aggressive antireflux surgery or medical antireflux interventions, either prior to transplant or soon after transplant[24-27], with 6 months post-transplant being a reasonable target date of antireflux intervention to minimize rejection and maximize outcomes. Therefore, reflux may surely play a role in pulmonary function decline in lung transplant patients, leading to more severe consequences of allograft injury including rejection.
Identifying elevated pre-transplant acid exposure is clinically significant because it may indicate patients at greater risk of FEV1 decline in transplant recipients. Pre-transplant GERD has previously been associated with a 70% decrease in FEV1 over an 18-month post-transplant follow-up interval[28], but based on the above results, that timeline may be too extended to allow for timely intervention. In our sub-group analysis, all patients with ≥ 20% FEV1 decline and elevated AET progressed to BOS, implying that increased AET may also predispose to BOS in those with FEV1 decline. Recent updated criteria for BOS staging includes an early BOS stage (0-p) characterized by 81%-90% of baseline FEV1 as well as an understanding that BOS may be marked by both a rapid decline in lung function post-transplant in some patients vs a slower loss of function in others[13]. Nonetheless, BOS has been identified as one of the most significant limiting factors in long term survival of lung transplant patients impacting as many as 80% of lung transplant recipients within 5 years[2,29]. Therefore, pre-transplant reflux assessment provides clinically relevant information in the prognostication and management of transplant recipients, which may be associated with early pulmonary function decline as reflective of allograft injury and rejection risk. Despite the above findings, there remains variability in reflux testing practices across lung transplant centers[30]. Our results should encourage routine reflux testing in lung transplant candidates to identify those at risk of early pulmonary function decline, which may be an indicator of progression to early allograft injury, acute rejection, and chronic rejection outcomes, such as BOS and CLAD.
One limitation of this study is the retrospective design. Nonetheless, all patients included in this study completed MII-pH testing as part of routine pre-transplant evaluation, received a standard peri-transplant immunosuppressant regimen and underwent routine PFT and bronchoscopy, as per our institutional peri-transplant protocol. Our cohort was also small in size, although largely within range of prior publications on this population. Although the proportion of patients with interstitial pulmonary fibrosis in the study cohort was higher than the overall proportion of lung transplant patients, a variety of primary lung diseases were represented and had no impact on the results. Future studies may include a multicenter, prospective study design, with a larger study cohort to include a wide range of pulmonary diagnoses.
CONCLUSION
In conclusion, our study demonstrated that increased AET and proximal acid reflux on pre-transplant reflux testing are associated with ≥ 20% FEV1 decline post-transplant, which is a clinical risk factor for development of chronic rejection. Additionally, increased AET may predispose to BOS in those with FEV1 decline. These findings indicate that pre-transplant reflux could impact pulmonary function decline as reflective of early-phase allograft injury or rejection, and further supports the role of routine reflux assessments for prognostication and to guide timely management of lung transplant patients.
Footnotes
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Transplantation
Country of origin: United States
Peer-review report’s classification
Scientific Quality: Grade B
Novelty: Grade B
Creativity or Innovation: Grade C
Scientific Significance: Grade B
P-Reviewer: Zhang XJ S-Editor: Bai Y L-Editor: A P-Editor: Zhao YQ
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