Airway hypoxia in lung transplantation

Pasnupneti, Shravani; Nicolls, Mark R.

doi:10.1016/j.cophys.2018.12.002

Cited by 14 publications

(5 citation statements)

References 40 publications

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“…Like lung transplantations, the blood flow reverses in the bronchial arteries. 40 As a result, the hemoglobin level (OHI) was equivalent in all 3 assessed bronchus anastomosis regions. However, the anastomosis region marks the endpoints of antegrade and retrograde supply resulting in a reduced StO 2 , and NIR-index compared to the central bronchus region.…”

Section: Discussionmentioning

confidence: 90%

Intraoperative Determination of Bronchus Stump and Anastomosis Perfusion with Hyperspectral Imaging

Ellebrecht

Kügler

2023

Surg Innov

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Background The intraoperative evaluation of bronchus perfusion is limited. Hyperspectral Imaging (HSI) is a newly established intraoperative imaging technique that enables a non-invasive, real-time perfusion analysis. Therefore, the purpose of this study was to determine the intraoperative perfusion of bronchus stump and anastomosis during pulmonary resections with HSI. Methods In this prospective, IDEAL Stage 2a study (Clinicaltrials.gov: NCT04784884) HSI measurements were carried out before bronchial dissection and after bronchial stump formation or bronchial anastomosis, respectively. Tissue oxygenation (StO2; upper tissue perfusion), organ hemoglobin index (OHI), near-infrared index (NIR; deeper tissue perfusion) and tissue water index (TWI) were calculated. Results Bronchus stumps showed a reduced NIR (77.82 ± 10.27 vs 68.01 ± 8.95; P = 0,02158) and OHI (48.60 ± 1.39 vs 38.15 ± 9.74; P = <.0001), although the perfusion of the upper tissue layers was equivalent before and after resection (67.42% ± 12.53 vs 65.91% ± 10.40). In the sleeve resection group, we found both a significant decrease in StO 2 and NIR between central bronchus and anastomosis region (StO2: 65.09% ± 12.57 vs 49.45 ± 9.94; P = .044; NIR: 83.73 ± 10.92 vs 58.62 ± 3.01; P = .0063). Additionally, NIR was decreased in the re-anastomosed bronchus compared to central bronchus region (83.73 ± 10.92 vs 55.15 ± 17.56; P = .0029). Conclusions Although both bronchus stumps and anastomosis show an intraoperative reduction of tissue perfusion, there is no difference of tissue hemoglobin level in bronchus anastomosis.

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Section: Discussionmentioning

confidence: 90%

Intraoperative Determination of Bronchus Stump and Anastomosis Perfusion with Hyperspectral Imaging

Ellebrecht

Kügler

2023

Surg Innov

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“…In addition, indices of vascular regrowth were associated with survival in our cohort. This has been posited in adult LTx as important for survival 16 …”

Section: Discussionmentioning

confidence: 99%

Auto‐inflammation and auto‐immunity pathways are associated with emergence of BOS in pediatric lung transplantation

Conrad

Hedlin

Chin

et al. 2022

Pediatric Transplantation

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“…As PGD is an ischemia-reperfusion injury, hypomethylation of hypoxia-related gene promoters is perhaps the least surprising. Indeed, hypoxia following PGD could potentially persist well beyond the 72 h of the study definition secondary to organizing diffuse alveolar damage or vascular dysfunction (25). Glycolytic gene promoters, an oxygenindependent metabolic pathway, were also found to be hypomethylated in subjects that experienced PGD, as were inflammatory and cell cycle pathways.…”

Section: Discussionmentioning

confidence: 99%

Lung Allograft Epithelium DNA Methylation Age Is Associated With Graft Chronologic Age and Primary Graft Dysfunction

et al. 2021

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Advanced donor age is a risk factor for poor survival following lung transplantation. However, recent work identifying epigenetic determinants of aging has shown that biologic age may not always reflect chronologic age and that stressors can accelerate biologic aging. We hypothesized that lung allografts that experienced primary graft dysfunction (PGD), characterized by poor oxygenation in the first three post-transplant days, would have increased biologic age. We cultured airway epithelial cells isolated by transbronchial brush at 1-year bronchoscopies from 13 subjects with severe PGD and 15 controls matched on age and transplant indication. We measured epigenetic age using the Horvath epigenetic clock. Linear models were used to determine the association of airway epigenetic age with chronologic ages and PGD status, adjusted for recipient PGD risk factors. Survival models assessed the association with chronic lung allograft dysfunction (CLAD) or death. Distributions of promoter methylation within pathways were compared between groups. DNA methyltransferase (DNMT) activity was quantified in airway epithelial cells under hypoxic or normoxic conditions. Airway epigenetic age appeared younger but was strongly associated with the age of the allograft (slope 0.38 per year, 95% CI 0.27–0.48). There was no correlation between epigenetic age and recipient age (P = 0.96). Epigenetic age was 6.5 years greater (95% CI 1.7–11.2) in subjects who had experienced PGD, and this effect remained significant after adjusting for donor and recipient characteristics (P = 0.03). Epigenetic age was not associated with CLAD-free survival risk (P = 0.11). Analysis of differential methylation of promoters of key biologic pathways revealed hypomethylation in regions related to hypoxia, inflammation, and metabolism-associated pathways. Accordingly, airway epithelial cells cultured in hypoxic conditions showed suppressed DNMT activity. While airway methylation age was primarily determined by donor chronologic age, early injury in the form of PGD was associated with increased allograft epigenetic age. These data show how PGD might suppress key promoter methylation resulting in long-term impacts on the allograft.

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Airway hypoxia in lung transplantation

Cited by 14 publications

References 40 publications

Intraoperative Determination of Bronchus Stump and Anastomosis Perfusion with Hyperspectral Imaging

Intraoperative Determination of Bronchus Stump and Anastomosis Perfusion with Hyperspectral Imaging

Auto‐inflammation and auto‐immunity pathways are associated with emergence of BOS in pediatric lung transplantation

Lung Allograft Epithelium DNA Methylation Age Is Associated With Graft Chronologic Age and Primary Graft Dysfunction

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