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Journal of Current Surgery

Short Communication

Volume 13, Number 1, September 2023, pages 12-16

Impact of Gastroesophageal Reflux Disease on Patients Undergoing Lung Transplantation for COVID-19: A Single Institution Retrospective Study

Gastroesophageal reflux disease (GERD) symptoms are prevalent in up to 40% of the population, and this can increase in patients after lung transplantation [1]. The incidence is estimated to be up to 65% of patients who have undergone lung transplant [2]. The exact mechanisms for post-transplant GERD are unclear; proposed mechanisms include intra-operative vagal nerve damage, esophageal and gastric dysmotility, and underlying structural compromise with the presence of a hiatal hernia [3]. Optimizing management of GERD is important to preserve graft function after lung transplantation as patients with GERD are at higher risk of rejection [4]. With the recent coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an increasing number of patients presented with COVID-19-associated respiratory failure with lung transplantation explored for this unique cohort of patients. As such, lung transplantation is an emerging subset of transplant patients in which GERD pre- or post-transplant is not well characterized.

A retrospective review was conducted at a single academic medical center with a large multi-organ transplant program, with the aim of evaluating the prevalence of GERD pre-transplant and the incidence of GERD post-transplant in patients undergoing lung transplantation for COVID-19-associated respiratory failure. The research was conducted ethically in accordance with the Health Insurance Portability and Accountability Act and the World Medical Association Declaration of Helsinki. The analysis received approval from the Institutional Review Board (IRB) through the Houston Methodist Research Institute (ID: MOD00005383). All patients undergoing lung transplant due to COVID-19 from 2020 to 2021 were included in the study, with attention to pre- and post-operative physiological testing for GERD. Data collected included the following: age at transplant, body mass index (BMI), gender, ethnicity, time from documented COVID-19 to date of transplant, requirement of veno-venous extracorporeal membrane oxygenation (VV ECMO), reflux symptoms or GERD diagnosis reported prior to transplant, comorbidities prior to transplant (i.e., diabetes, obesity, and hiatal hernia), any completed pre-transplant reflux testing, whether the patient was on acid suppression therapy before and/or after transplant, single versus dual organ transplant, post-transplant reflux symptoms, reflux studies completed post-transplant (i.e., gastric emptying, pH-impedance, barium esophagram, and esophagogastroduodenoscopy (EGD)), and evaluation for anti-reflux surgery (ARS).

Seventeen patients were identified who had undergone lung transplant for COVID-19. All patients were male, with the following demographics: 52.9% (9/17) Hispanic, 35.3% (6/17) Caucasian and 11.8% (2/17) Black (Table 1). The median age was 50 (24 - 70 years), with median time to transplant from documented infection of 131 days. A pre-hospitalization GERD diagnosis was found in 29.4% (5/17) patients, and two of these patients (11.8%) were taking prescribed proton pump inhibitor (PPI) prior to their COVID-19-associated hospitalization. No patient underwent pre-transplant GERD testing, although three patients did undergo upper endoscopy for gastrointestinal (GI) bleeding prior to transplant. Post-transplant, all patients were immediately treated with a PPI per institutional protocol. Seventy point five percent (12/17) patients reported post-transplant foregut symptoms including heartburn, regurgitation, dysphagia, early satiety, abdominal bloating/cramping, nausea, and vomiting (Table 2). All 17 patients had at least one symptom-driven foregut study such as a barium esophagram, upper endoscopy, gastric emptying study, esophageal manometry or pH testing. Three patients were referred for ARS based on results of testing, including delayed gastric emptying, abnormal pH testing and bronchoscopy findings concerning for aspiration pneumonia. All three underwent Toupet fundoplication with or without hiatal hernia repair; one was performed early (< 3 months) post-transplant, two occurred late (> 6 months), and none had complications or symptom-based recurrence of reflux at 12 months post-transplant.

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Table 1. Clinical Characteristics in Patients Who Underwent Lung Transplant for COVID-19 Prior to Transplantation

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Table 2. Clinical Characteristics in Patients Who Underwent Lung Transplant for COVID-19 After Transplantation

In this retrospective single-center descriptive study on patients with COVID-19-associated respiratory failure and undergoing lung transplant, pre-operative reflux testing could not be performed in the unique setting of a global pandemic with acutely critically ill patients. Nevertheless, GERD symptoms were still routinely assessed and evaluated post-transplant prompting medical and surgical management with acid suppression therapy and ARS, respectively, in a small subset of patients. This was seen in both early (< 6 months) and late (> 6 months) post-transplant, with resolution of GERD symptoms reported.

Notably, the incidence of post-transplant GERD was 70.5% in our cohort, which is around the reported incidence based on prior studies [2]. The prevalence of GERD prior to transplant was seen in 29.4% of our cohort, comparable to prior reported studies [1, 2, 4]. Thus, the underlying insult causing the respiratory failure, which in our cohort was infectious and a more acute process, does not appear to affect the overall incidence of GERD post-transplant. However, this postulation is clearly limited given the retrospective nature of the study, the small number of patients in the cohort, and the fact that pre-transplant testing for GERD was unable to be pursued in this critically ill group of patients.

While this is not the largest cohort of lung transplantation for COVID-19 published, it is the largest and only cohort of such patients where an attention to GERD and therapy has been described [5]. Management of GERD has been shown to reduce the risk of rejection and improve overall transplantation outcomes [6, 7]. Evidence for the role of medical anti-reflux therapy has been limited; however, exposure to acid suppression after transplantation has been associated with reduced risk of allograft rejection [8, 9]. ARS has been suggested to better prevent allograft injury and improve survival, as acid suppression, while altering the acidity of refluxate, does not necessarily prevent volume reflux and aspiration, and therefore may only play an adjunctive role, especially when ARS cannot be immediately performed [10, 11]. However, none of these studies included a subset of patients where transplantation occurred for severe acute lung injury such as COVID-19.

The retrospective and descriptive nature of this study and the inability to evaluate the role of GERD pre-operatively restricts the assessment of the impact of GERD on allograft dysfunction. However, even in this smaller group of respiratory failure due to COVID-19, a pragmatic post-operative approach to GERD driven by either symptoms or deterioration of lung function, suggests that testing may be foregone in select cases and performed postoperatively without change in 3- or 6-month survival. Ultimately, the unique nature of this group, with acute lung injury leading to transplantation, merits further investigation in assessing the impact of GERD on allograft dysfunction and mortality.

Acknowledgments

None to declare.

Financial Disclosure

None to declare.

Conflict of Interest

The authors have no conflict of interest to declare.

Informed Consent

All subjects provided informed consents.

Author Contributions

CK wrote the paper and performed analysis on the collected data; CK, DB, EC and GE conceived the study and helped write the paper; HH, RC, AG, SY, JY, TM, ES and PC contributed to the study design and analysis and critically reviewed the manuscript. All authors approved the final version of the article, including the authorship list.

Data Availability

The data underlying this article are available in the article, and will also be shared on reasonable request to the corresponding author.

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Journal of Current Surgery is published by Elmer Press Inc.