<i>N</i>-Acetylcysteine inhalation improves pulmonary function in patients received liver transplantation

Li, Xiaoyun; Wei, Xiaoxia; Chen, Chaojin; Zhang, Zheng; Liu, Dezhao; Hei, Ziqing; Yao, Weifeng

doi:10.1042/bsr20180858

Cited by 17 publications

(13 citation statements)

References 40 publications

(41 reference statements)

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“…This specificity is supported by the clinical experience with NAC. NAC treatment clears lung secretions in several acute and chronic lung conditions (Dekhuijzen and van Beurden, 2006;Li et al, 2018). However, NAC failed to reverse liver failure in a controlled clinical trial (Squires et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Impaired Lung Development and Ciliation in Mannosidase-1-Alpha-2 (Man1a2) Mutants

et al. 2021

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BackgroundCiliary defects cause heterogenous phenotypes related to mutation burden which lead to impaired development. A previously reported homozygous deletion in the Man1a2 gene causes lethal respiratory failure in newborn pups and decreased lung ciliation compared with wild type (WT) pups. The effects of heterozygous mutation, and the potential for rescue are not known.PurposeWe hypothesized that survival and lung ciliation, (a) would decrease progressively in Man1a2+/− heterozygous and Man1a2–/– null newborn pups compared with WT, and (b) could be enhanced by gestational treatment with N-Acetyl-cysteine (NAC), an antioxidant.MethodsMan1a2+/– adult mice were fed NAC or placebo from a week before breeding through gestation. Survival of newborn pups was monitored for 24 h. Lungs, liver and tails were harvested for morphology, genotyping, and transcriptional profiling.ResultsSurvival (p = 0.0001, Kaplan-Meier) and percent lung ciliation (p = 0.0001, ANOVA) measured by frequency of Arl13b+ respiratory epithelial cells decreased progressively, as hypothesized. Compared with placebo, gestational NAC treatment enhanced (a) lung ciliation in pups with each genotype, (b) survival in heterozygous pups (p = 0.017) but not in WT or null pups. Whole transcriptome of lung but not liver demonstrated patterns of up- and down-regulated genes that were identical in living heterozygous and WT pups, and completely opposite to those in dead heterozygous and null pups. Systems biology analysis enabled reconstruction of protein interaction networks that yielded functionally relevant modules and their interactions. In these networks, the mutant Man1a2 enzyme contributes to abnormal synthesis of proteins essential for lung development. The associated unfolded protein, hypoxic and oxidative stress responses can be mitigated with NAC. Comparisons with the developing human fetal lung transcriptome show that NAC likely restores normal vascular and epithelial tube morphogenesis in Man1a2 mutant mice.ConclusionSurvival and lung ciliation in the Man1a2 mutant mouse, and its improvement with N-Acetyl cysteine is genotype-dependent. NAC-mediated rescue depends on the central role for oxidative and hypoxic stress in regulating ciliary function and organogenesis during development.

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Section: Discussionmentioning

confidence: 99%

Mechanisms of Impaired Lung Development and Ciliation in Mannosidase-1-Alpha-2 (Man1a2) Mutants

et al. 2021

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“…Several authors have also reported significant reductions in levels of pulmonary inflammation following NAC supplementation at approximately 1200 mg/day as evidenced by reduced levels of PICs, ROS, tissue damage and fibrin deposits in alveoli and interstitial tissue [ [222] , [223] , [224] ]. There is also evidence to suggest that NAC improves pulmonary function, an effect which appears to be enhanced when the thiol is inhaled [ 207 , 225 ]. NAC supplementation also exerts several other anti-inflammatory effects relevant to the pathophysiology of ARDS, most notably by decreasing levels of IL-6 [ [226] , [227] , [228] ] and NF-κB [ [229] , [230] , [231] ].…”

Section: Suggestions For Therapeutic Interventionmentioning

confidence: 99%

Preventing the development of severe COVID-19 by modifying immunothrombosis

Morris

Bortolasci

Puri³

et al. 2021

Life Sciences

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Background COVID-19-associated acute respiratory distress syndrome (ARDS) is associated with significant morbidity and high levels of mortality. This paper describes the processes involved in the pathophysiology of COVID-19 from the initial infection and subsequent destruction of type II alveolar epithelial cells by SARS-CoV-2 and culminating in the development of ARDS. Main body The activation of alveolar cells and alveolar macrophages leads to the release of large quantities of proinflammatory cytokines and chemokines and their translocation into the pulmonary vasculature. The presence of these inflammatory mediators in the vascular compartment leads to the activation of vascular endothelial cells platelets and neutrophils and the subsequent formation of platelet neutrophil complexes. These complexes in concert with activated endothelial cells interact to create a state of immunothrombosis. The consequence of immunothrombosis include hypercoagulation, accelerating inflammation, fibrin deposition, migration of NET producing neutrophils into the alveolar apace, activation of the NLRP3 inflammazome, increased alveolar macrophage destruction and massive tissue damage by pyroptosis and necroptosis Therapeutic combinations aimed at ameliorating immunothrombosis and preventing the development of severe COVID19 are discussed in detail.

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“…600 Tianhe Road, Guangzhou 10630, Guangdong, People's Republic of China. 2 Guangzhou AID Cloud Technology Co., LTD, Guangzhou, People's Republic of China. 3 Department of Information, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China.…”

Section: Supplementary Informationmentioning

confidence: 99%

“…Postoperative pulmonary complications (PPC) adversely affect the clinical course of orthotopic liver transplantation (OLT) and play an important role in poor survival [1]. Postoperative pneumonia is the most common type of PPC, contributing to morbidity, length of hospital stay, and mortality [2]. Identification of patients at high risk of developing postoperative pneumonia is the key to early implementing interventions to prevent its onset or antibiotics to treat bacterial infection [3].…”

Section: Introductionmentioning

confidence: 99%

Development and performance assessment of novel machine learning models to predict pneumonia after liver transplantation

Chen

Yang²,

Gao

et al. 2021

Respir Res

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Background Pneumonia is the most frequently encountered postoperative pulmonary complications (PPC) after orthotopic liver transplantation (OLT), which cause high morbidity and mortality rates. We aimed to develop a model to predict postoperative pneumonia in OLT patients using machine learning (ML) methods. Methods Data of 786 adult patients underwent OLT at the Third Affiliated Hospital of Sun Yat-sen University from January 2015 to September 2019 was retrospectively extracted from electronic medical records and randomly subdivided into a training set and a testing set. With the training set, six ML models including logistic regression (LR), support vector machine (SVM), random forest (RF), adaptive boosting (AdaBoost), extreme gradient boosting (XGBoost) and gradient boosting machine (GBM) were developed. These models were assessed by the area under curve (AUC) of receiver operating characteristic on the testing set. The related risk factors and outcomes of pneumonia were also probed based on the chosen model. Results 591 OLT patients were eventually included and 253 (42.81%) were diagnosed with postoperative pneumonia, which was associated with increased postoperative hospitalization and mortality (P < 0.05). Among the six ML models, XGBoost model performed best. The AUC of XGBoost model on the testing set was 0.734 (sensitivity: 52.6%; specificity: 77.5%). Pneumonia was notably associated with 14 items features: INR, HCT, PLT, ALB, ALT, FIB, WBC, PT, serum Na+, TBIL, anesthesia time, preoperative length of stay, total fluid transfusion and operation time. Conclusion Our study firstly demonstrated that the XGBoost model with 14 common variables might predict postoperative pneumonia in OLT patients.

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N-Acetylcysteine inhalation improves pulmonary function in patients received liver transplantation

Cited by 17 publications

References 40 publications

Mechanisms of Impaired Lung Development and Ciliation in Mannosidase-1-Alpha-2 (Man1a2) Mutants

Mechanisms of Impaired Lung Development and Ciliation in Mannosidase-1-Alpha-2 (Man1a2) Mutants

Preventing the development of severe COVID-19 by modifying immunothrombosis

Development and performance assessment of novel machine learning models to predict pneumonia after liver transplantation

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