Lung Transplantation: The State of the Airways

Husain, Aliya N.; Garrity, Edward R.

doi:10.5858/arpa.2015-0295-sa

Cited by 12 publications

(6 citation statements)

References 17 publications

(11 reference statements)

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“…As a form of chronic allograft rejection, OB is a serious threat to long-term survival after lung transplantation and affects up to 50-60% of patients who survive 5 years after surgery (Husain and Garrity 2016). Sustained inflammatory reactions can often lead to fibrosis or even carcinogenesis of organs (Liu et al 2018;Rieder et al 2010).…”

Section: Discussionmentioning

confidence: 99%

MiR-27a-3p downregulation contributes to the development of occlusive bronchiolitis

Dong

Wang

Guan

et al. 2019

Cell Stress and Chaperones

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The only effective clinical treatment for many end-stage lung diseases is lung transplantation. However, chronic rejection of transplanted lung affects the long-term efficacy of lung transplantation to a large extent, thereby limiting the clinical application of lung transplantation. Occlusive bronchiolitis (OB) is a major cause of chronic functional loss of the transplanted lung. However, the OB pathogenesis remains unclear. Therefore, studying the OB pathogenesis and finding effective intervention methods are highly important. This study analyzed changes in the expression profile of microRNAs and transcription factors in mice with OB after orthotopic tracheal transplantation. miR-27a-3p was upregulated in lung tissue 20 days after transplantation. Transcription factor microarray analysis revealed that Smad3 was significantly downregulated. A miRNA-mRNA interaction network was constructed, and specific regulatory effects of miR-27a-3p on Smad3 were found. Smad3 was strongly associated with tumorigenesis and organ fibrosis. Compared with the control group, miR-27a-3p inhibited the epithelial-mesenchymal transformation (EMT) of lung epithelial cells. In addition, miR-27a-3p inhibition promoted the invasion and migration of lung epithelial cells. Dual luciferase reporter gene assay showed that miR-27a-3p can regulate the promoter activity of Smad3. MiR-27a-3p also inhibited the expression of inflammatory cytokines. Western blot results showed that miR-27a-3p can upregulate the E-cadherin expression and downregulate the expression of vimentin, fibronectin, and α-SMA. By studying the OB pathogenesis, we found that inhibition or alteration of the occurrence of EMT may reduce the proportion of chronic rejection of lung transplantation. MiR-27a-3p may also be developed as a new drug for the OB therapy. This finding will provide many possibilities for OB treatment and improve the prognosis of patients with OB.

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Section: Discussionmentioning

confidence: 99%

MiR-27a-3p downregulation contributes to the development of occlusive bronchiolitis

Dong

Wang

Guan

et al. 2019

Cell Stress and Chaperones

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“…RAS manifests as progressive, restrictive physiology with an appearance of increasing fibrosis on imaging studies[20,21], and is defined as a persistent decline in total lung capacity alongside a decline in FEV1[22]. RAS is histologically characterized by diffuse alveolar damage and extensive fibrosis in the alveolar interstitium, visceral pleura, and interlobular septa, and may also contain scattered obliterative bronchiolitis lesions[21-24].…”

Section: Introductionmentioning

confidence: 99%

Role of gastroesophageal reflux disease in lung transplantation

Hathorn

Chan

2017

WJT

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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 pH 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 follow-up times to capture longer-term clinical outcomes, and investigate newer interventions including minimally invasive surgery and advanced endoscopic techniques.

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“…However, it is noteworthy to point out that large airways were significantly affected in the CR of our groups with a mean score greater than 2. Large airways are not considered in the current rejection grading system of clinical samples, even though several authors have more recently highlighted the need to reconsider the role of large airways (19,20).…”

Section: Discussionmentioning

confidence: 99%

Chronic lung allograft pathology lesions in two rat strain combinations

Pezzuto

Lunardi

Vadori³

et al. 2021

J Thorac Dis

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Background: Chronic lung allograft dysfunction remains an obstacle to long-term survival after lung transplantation. Two phenotypes have been described: obliterative bronchiolitis and restrictive allograft syndrome. Preclinical models are essential to analyze chronic lung allograft dysfunction pathophysiology. Methods: Orthotopic lung transplants from 38 Lewis into Fischer 344 (Lew→F344) and 67 Brown-Norway into Lewis (BN→Lew) rats were performed in our center in the last decade. We carefully reviewed and quantified all grafts with chronic rejection (40 cases) (18 Lew→F344, 22 BN→Lew) with the aim to investigate if histological changes of chronic lung allograft dysfunction could be also detected in rat grafts. Results: All animals showed human reminiscent histological lesions. Early chronic rejection lesions were detected in BN→Lew. End-stage chronic rejection with features of obliterative bronchiolitis was observed in 33% of Lew→F344; end-stage with restrictive allograft syndrome chronic rejection in 67% and 80% of Lew→F344 and BN→Lew, respectively. BN→Lew showed higher grades of endotheliitis, vascular fibrosis, and lower grades of lymphoid aggregates than Lew→F344 (P=0.007, P=0.043, P=0.004, respectively). Conclusions: Chronic rejection lesions in rat lung allografts mimic those in humans. The frequent occurrence of restrictive allograft syndrome-like lesions in BN→Lew may be related to a higher degree of mismatch in this strain combination. These animal models could allow future mechanistic studies to better understand chronic lung allograft dysfunction pathogenesis.

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Lung Transplantation: The State of the Airways

Cited by 12 publications

References 17 publications

MiR-27a-3p downregulation contributes to the development of occlusive bronchiolitis

MiR-27a-3p downregulation contributes to the development of occlusive bronchiolitis

Role of gastroesophageal reflux disease in lung transplantation

Chronic lung allograft pathology lesions in two rat strain combinations

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