Azithromycin Partially Mitigates Dysregulated Repair of Lung Allograft Small Airway Epithelium.


  • 影响因子:3.04
  • DOI:10.1097/TP.0000000000003134
  • 作者列表:"Ling KM","Garratt LW","Banerjee B","Lavender MA","Wrobel JP","Musk M","Martinovich KM","Shaw NC","Iosifidis T","Looi K","Kicic-Starcevich E","Sutanto EN","Yerkovich ST","Chambers DC","Stick SM","Kicic A
  • 发表时间:2020-01-23

BACKGROUND:Dysregulated airway epithelial repair following injury is a proposed mechanism driving posttransplant bronchiolitis obliterans (BO) and its clinical correlate bronchiolitis obliterans syndrome (BOS). This study compared gene and cellular characteristics of injury and repair in large (LAEC) and small (SAEC) airway epithelial cells of transplant patients. METHODS:Subjects were recruited at time of routine bronchoscopy posttransplantation and included patients with and without BOS. Airway epithelial cells were obtained from bronchial and bronchiolar brushing performed under radiological guidance from these patients. In addition, bronchial brushings were also obtained from heathy control subjects comprising of adolescents admitted for elective surgery for nonrespiratory related conditions. Primary cultures were established, monolayers wounded and repair assessed (+/-) azithromycin (1µg/ml). In addition, proliferative capacity as well as markers of injury and dysregulated repair were also assessed. RESULTS:SAEC had a significantly dysregulated repair process postinjury, despite having a higher proliferative capacity than LAEC. Addition of azithromycin significantly induced repair in these cells however full restitution was not achieved. Expression of several genes associated with epithelial barrier repair (MMP7, MMP3, the integrins β6 and β8, and β-catenin) were significantly different in epithelial cells obtained from patients with BOS compared to transplant patients without BOS and controls, suggesting an intrinsic defect. CONCLUSION:Chronic airway injury and dysregulated repair programs are evident in airway epithelium obtained from patients with BOS, particularly with SAEC. We also show that azithromycin partially mitigates this pathology.


背景: 损伤后气道上皮修复失调是驱动移植后闭塞性细支气管炎 (BO) 及其临床相关性闭塞性细支气管炎综合征 (BOS) 的机制。本研究比较了移植患者大 (LAEC) 和小 (SAEC) 气道上皮细胞损伤和修复的基因和细胞特征。 方法: 在移植后常规支气管镜检查时招募受试者,包括有和无 BOS 的患者。在这些患者的放射学指导下进行支气管和细支气管刷检,获得气道上皮细胞。此外,还从健康对照受试者获得了支气管刷检,这些受试者包括因非呼吸相关疾病接受择期手术的青少年。建立原代培养,单层损伤和修复评估 (+/-) 阿奇霉素 (1 µ g/ml)。此外,还评估了增殖能力以及损伤和修复失调的标志物。 结果: SAEC 损伤后修复过程明显失调,尽管增殖能力高于 LAEC。添加阿奇霉素可显著诱导这些细胞的修复,但未实现完全恢复。几种与上皮屏障修复相关的基因 (MMP7 、 MMP3 、整合素 β 6 和 β 8 以及 β-catenin) 的表达与无 BOS 的移植患者和对照组相比,从 BOS 患者获得的上皮细胞存在显著差异,提示存在内在缺陷。 结论: BOS 患者,特别是 SAEC 患者的气道上皮有明显的慢性气道损伤和修复程序失调。我们还表明阿奇霉素部分缓解了这种病理。



来源期刊:Surgical Endoscopy
作者列表:["Yang, Shun-Mao","Chen, Yi-Chang","Ko, Wei-Chun","Huang, Hsin-Chieh","Yu, Kai-Lun","Ko, Huan-Jang","Huang, Pei-Ming","Chang, Yeun-Chung"]

METHODS:Background Dye localization is a useful method for the resection of unidentifiable small pulmonary lesions. This study compares the transbronchial route with augmented fluoroscopic bronchoscopy (AFB) and conventional transthoracic CT-guided methods for preoperative dye localization in thoracoscopic surgery. Methods Between April 2015 and March 2019, a total of 231 patients with small pulmonary lesions who received preoperative dye localization via AFB or percutaneous CT-guided technique were enrolled in the study. A propensity-matched analysis, incorporating preoperative variables, was used to compare localization and surgical outcomes between the two groups. Results After matching, a total of 90 patients in the AFB group ( N  = 30) and CT-guided group ( N  = 60) were selected for analysis. No significant difference was noted in the demographic data between both the groups. Dye localization was successfully performed in 29 patients (96.7%) and 57 patients (95%) with AFB and CT-guided method, respectively. The localization duration (24.1 ± 8.3 vs. 21.4 ± 12.5 min, p  = 0.297) and equivalent dose of radiation exposure (3.1 ± 1.5 vs. 2.5 ± 2.0 mSv, p  = 0.130) were comparable in both the groups. No major procedure-related complications occurred in either group; however, a higher rate of pneumothorax (0 vs. 16.7%, p  = 0.029) and focal intrapulmonary hemorrhage (3.3 vs. 26.7%, p  = 0.008) was noted in the CT-guided group. Conclusion AFB dye marking is an effective alternative for the preoperative localization of small pulmonary lesions, with a lower risk of procedure-related complications than the conventional CT-guided method.

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作者列表:["Matava, Clyde","Pankiv, Evelina","Raisbeck, Sam","Caldeira, Monica","Alam, Fahad"]

METHODS:Background The use of artificial intelligence, including machine learning, is increasing in medicine. Use of machine learning is rising in the prediction of patient outcomes. Machine learning may also be able to enhance and augment anesthesia clinical procedures such as airway management. In this study, we sought to develop a machine learning algorithm that could classify vocal cords and tracheal airway anatomy real-time during video laryngoscopy or bronchoscopy as well as compare the performance of three novel convolutional networks for detecting vocal cords and tracheal rings. Methods Following institutional approval, a clinical dataset of 775 video laryngoscopy and bronchoscopy videos was used. The dataset was divided into two categories for use for training and testing. We used three convolutional neural networks (CNNs): ResNet, Inception and MobileNet. Backpropagation and a mean squared error loss function were used to assess accuracy as well as minimize bias and variance. Following training, we assessed transferability using the generalization error of the CNN, sensitivity and specificity, average confidence error, outliers, overall confidence percentage, and frames per second for live video feeds. After the training was complete, 22 models using 0 to 25,000 steps were generated and compared. Results The overall confidence of classification for the vocal cords and tracheal rings for ResNet, Inception and MobileNet CNNs were as follows: 0.84, 0.78, and 0.64 for vocal cords, respectively, and 0.69, 0.72, 0.54 for tracheal rings, respectively. Transfer learning following additional training resulted in improved accuracy of ResNet and Inception for identifying the vocal cords (with a confidence of 0.96 and 0.93 respectively). The two best performing CNNs, ResNet and Inception, achieved a specificity of 0.985 and 0.971, respectively, and a sensitivity of 0.865 and 0.892, respectively. Inception was able to process the live video feeds at 10 FPS while ResNet processed at 5 FPS. Both were able to pass a feasibility test of identifying vocal cords and tracheal rings in a video feed. Conclusions We report the development and evaluation of a CNN that can identify and classify airway anatomy in real time. This neural network demonstrates high performance. The availability of artificial intelligence may improve airway management and bronchoscopy by helping to identify key anatomy real time. Thus, potentially improving performance and outcomes during these procedures. Further, this technology may theoretically be extended to the settings of airway pathology or airway management in the hands of experienced providers. The researchers in this study are exploring the performance of this neural network in clinical trials.

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作者列表:["Dhooria S","Chaudhary S","Ram B","Sehgal IS","Muthu V","Prasad KT","Aggarwal AN","Agarwal R"]

METHODS:BACKGROUND:The optimal mode of delivering topical anesthesia during flexible bronchoscopy remains unknown. This article compares the efficacy and safety of nebulized lignocaine, lignocaine oropharyngeal spray, or their combination. METHODS:Consecutive subjects were randomized 1:1:1 to receive nebulized lignocaine (2.5 mL of 4% solution, group A), oropharyngeal spray (10 actuations of 10% lignocaine, group B), or nebulization (2.5 mL, 4% lignocaine) and two actuations of 10% lignocaine spray (group C). The primary outcome was the subject-rated severity of cough according to a visual analog scale. The secondary outcomes included bronchoscopist-rated severity of cough and overall procedural satisfaction on a visual analog scale, total lignocaine dose, subject's willingness to undergo a repeat procedure, adverse reactions to lignocaine, and others. RESULTS:A total of 1,050 subjects (median age, 51 years; 64.8% men) were included. The median (interquartile range) score for subject-rated cough severity was significantly lower in group B compared to group C or group A (4 [1-10] vs 11 [4-24] vs 13 [5-30], respectively; P < .001). The bronchoscopist-rated severity of cough was also the least (P < .001), and the overall satisfaction was highest in group B (P < .001). The cumulative lignocaine dose administered was the least in group B (P < .001). A significantly higher proportion of subjects (P < .001) were willing to undergo a repeat bronchoscopy in group B (73.7%) than in groups A (49.1%) and C (59.4%). No lignocaine-related adverse events were observed. CONCLUSIONS:Ten actuations of 10% lignocaine oropharyngeal spray were superior to nebulized lignocaine or their combination for topical anesthesia during diagnostic flexible bronchoscopy. TRIAL REGISTRY:ClinicalTrials.gov; No.: NCT03109392; URL: www.clinicaltrials.gov.

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