Bronchoalveolar bile acid and inflammatory markers to identify high-risk lung transplant recipients with reflux and microaspiration

Zhang, Chen Yang Kevin; Ahmed, M.; Huszti, Ella; Levy, Liran; Hunter, Sarah; Boonstra, K.; Moshkelgosha, Sajad; Sage, A.T.; Azad, S.; Zamel, R.; Ghany, R.; Yeung, Jonathan C.; Crespin, Oscar M.; Frankel, Courtney W.; Budev, Marie; Shah, Pali D.; Reynolds, John M.; Snyder, L.D.; Belperio, John A.; Singer, L.G.; Weigt, S. Samuel; Todd, Jamie L.; Palmer, Scott M.; Keshavjee, S.; Martinu, T.

doi:10.1016/j.healun.2020.05.006

Cited by 23 publications

(43 citation statements)

References 26 publications

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“…Moreover, fundoplication has been shown to successfully decrease airway bile acid levels and proinflammatory cytokines. 32 Our study is consistent with these reports, showing a significant increased freedom from CLAD and overall survival in the fundoplication arm. The positive effect of fundoplication on survival remained independent after adjusting for other risk factors.…”

Section: Discussionsupporting

confidence: 93%

“…31 This was recently confirmed in a multicenter study in which higher levels of bile acids at 3 months after transplant were associated with increased levels of IL-1β, IL-12p70, and CCL5. 32 Whether the relationship between aspiration from GER and CLAD is a matter of direct injury or indirect insults that result in further alloimmune injury requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

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Fundoplication after lung transplantation in patients with systemic sclerosis–related end-stage lung disease

Leiva‐Juárez

Urso

Costa

et al. 2021

Journal of Scleroderma and Related Disorders

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Introduction: Gastroesophageal reflux and aspiration are risk factors for chronic lung allograft dysfunction in lung transplant recipients. Patients with systemic sclerosis are at an increased risk of aspiration due to esophageal dysmotility and an ineffective lower esophageal sphincter. The aim of this study is to understand the effect of fundoplication on outcomes in systemic sclerosis recipients. Methods: Between 2001 and 2019, 168 systemic sclerosis patients were referred for lung transplantation—51 (30.3%) were listed and 36 (21.4%) were transplanted. Recipients were stratified whether they underwent a fundoplication (n = 10, 27.8%) or not (n = 26, 72.2%). Freedom from chronic lung allograft dysfunction and survival were analyzed using log-rank test. Multivariable analysis for known risk factors was performed using a Cox-proportional hazards model. Results: Median time to fundoplication after transplantation was 16.4 months (interquartile range: 9.6–25.1) and all were laparoscopic (Dor 50%, Nissen 40%, Toupet 10%). There were no differences in acute rejection ⩾ A1 (26.9% vs 30%), or primary graft dysfunction grades 2–3 at 72 h (42.3% vs 40%) between groups. Recipients with fundoplication had an increased freedom from chronic lung allograft dysfunction (p = 0.035) and overall survival (p = 0.01). Fundoplication was associated with a reduced risk of mortality adjusting for other comorbidities (hazard ratio = 0.13; 95% confidence interval = 0.02–0.65; p = 0.014). Double and single lung transplant did not have different post-transplant survival. Conclusion: Fundoplication in systemic sclerosis lung transplant recipients is associated with greater freedom from chronic lung allograft dysfunction and overall survival. Screening for reflux and aspiration followed by early fundoplication may delay graft deterioration in this population.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Fundoplication after lung transplantation in patients with systemic sclerosis–related end-stage lung disease

Leiva‐Juárez

Urso

Costa

et al. 2021

Journal of Scleroderma and Related Disorders

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“…Conversely, 20 of 73 patients with normal prelung transplant DeMeester scores developed abnormal DeMeester scores postlung transplant. In a study of patients who had both esophageal pH-impedance monitoring and BAL performed 6–12 weeks after lung transplantation, those with GERD (diagnosed on the basis of elevated reflux events) had higher levels of bile acids in BAL at three months following transplant [44 ▪ ]. In this same cohort, elevated BAL bile acids were associated with acute lung allograft dysfunction, and BAL bile acid levels improved after antireflux operations.…”

Section: Gastroesophageal Reflux Disease and Lung Transplant Recipientsmentioning

confidence: 99%

Impact of gastroesophageal reflux disease on idiopathic pulmonary fibrosis and lung transplant recipients

Reddy¹,

Wakwaya

2022

Current Opinion in Gastroenterology

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Purpose of reviewIdiopathic pulmonary fibrosis (IPF) is a prevalent subset of interstitial lung disease (ILD) that often progresses to require lung transplantation. Gastroesophageal reflux disease (GERD) is common in the IPF population, and GER-related micro-aspiration appears to be an important risk factor for IPF pathogenesis and for the deterioration of transplanted lung function.Recent findingsMany patients with IPF have elevated esophageal acid exposure on reflux testing despite having no or minimal symptoms. Studies on the effects of medical GERD therapy on IPF-related outcomes have had mixed results. Antireflux surgery is safe in appropriately selected IPF patients, and appears to have potential for slowing the decline of lung function. GERD can persist, improve or develop after lung transplantation, and the presence of GERD is associated with allograft injury and pulmonary function decline in lung transplant recipients.SummaryClinicians should have a low threshold to assess for objective evidence of GERD in IPF patients. Antireflux surgery in IPF patients with GERD appears to improve lung function, but further studies are needed before surgical treatment can be recommended routinely in this setting. In lung transplant recipients, reflux testing after transplant is the most accurate way to guide GERD treatment decisions.

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“…101 Gastroesophageal reflux disease (GERD) has been associated with allograft injury and increased risk of ACR. 102,103 BAL bile acids, as well as pepsin, have been proposed as biomarkers of aspiration and have been associated with GERD and concurrent acute lung allograft dysfunction, 104,105 although further study is required to assess whether they directly correlate with ACR.…”

Section: Posttransplant Factorsmentioning

confidence: 99%

Acute Rejection in the Modern Lung Transplant Era

Renaud-Picard

Koutsokera

Cabanero

et al. 2021

Semin Respir Crit Care Med

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Acute cellular rejection (ACR) remains a common complication after lung transplantation. Mortality directly related to ACR is low and most patients respond to first-line immunosuppressive treatment. However, a subset of patients may develop refractory or recurrent ACR leading to an accelerated lung function decline and ultimately chronic lung allograft dysfunction. Infectious complications associated with the intensification of immunosuppression can also negatively impact long-term survival. In this review, we summarize the most recent evidence on the mechanisms, risk factors, diagnosis, treatment, and prognosis of ACR. We specifically focus on novel, promising biomarkers which are under investigation for their potential to improve the diagnostic performance of transbronchial biopsies. Finally, for each topic, we highlight current gaps in knowledge and areas for future research.

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Bronchoalveolar bile acid and inflammatory markers to identify high-risk lung transplant recipients with reflux and microaspiration

Cited by 23 publications

References 26 publications

Fundoplication after lung transplantation in patients with systemic sclerosis–related end-stage lung disease

Fundoplication after lung transplantation in patients with systemic sclerosis–related end-stage lung disease

Impact of gastroesophageal reflux disease on idiopathic pulmonary fibrosis and lung transplant recipients

Acute Rejection in the Modern Lung Transplant Era

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