Gabriela Gonzales, Ronit Malka, Lisa M Marinelli, Christine M Lee, Stacy Cook, Solaleh Miar, Gregory R Dion, Teja Guda
{"title":"局部给药对猪上气道插管损伤后喉力学、局部炎症反应和呼吸道微生物组的影响。","authors":"Gabriela Gonzales, Ronit Malka, Lisa M Marinelli, Christine M Lee, Stacy Cook, Solaleh Miar, Gregory R Dion, Teja Guda","doi":"10.1186/s12931-024-02973-1","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Laryngeal injury associated with traumatic or prolonged intubation may lead to voice, swallow, and airway complications. The interplay between inflammation and microbial population shifts induced by intubation may relate to clinical outcomes. The objective of this study was to investigate laryngeal mechanics, tissue inflammatory response, and local microbiome changes with laryngotracheal injury and localized delivery of therapeutics via drug-eluting endotracheal tube.</p><p><strong>Methods: </strong>A simulated traumatic intubation injury was created in Yorkshire crossbreed swine under direct laryngoscopy. Endotracheal tubes electrospun with roxadustat or valacyclovir- loaded polycaprolactone (PCL) fibers were placed in the injured airway for 3, 7, or 14 days (n = 3 per group/time and ETT type). Vocal fold stiffness was then evaluated with normal indentation and laryngeal tissue sections were histologically examined. Immunohistochemistry and inflammatory marker profiling were conducted to evaluate the inflammatory response associated with injury and ETT placement. Additionally, ETT biofilm formation was visualized using scanning electron microscopy and micro-computed tomography, while changes in the airway microbiome were profiled through 16S rRNA sequencing.</p><p><strong>Results: </strong>Laryngeal tissue with roxadustat ETT placement had increasing localized stiffness outcomes over time and histological assessment indicated minimal epithelial ulceration and fibrosis, while inflammation remained severe across all timepoints. In contrast, vocal fold tissue with valacyclovir ETT placement showed no significant changes in stiffness over time; histological analysis presented a reduction in epithelial ulceration and inflammation scores along with increased fibrosis observed at 14 days. Immunohistochemistry revealed a decline in M1 and M2 macrophage markers over time for both ETT types. Among the cytokines, IL-8 levels differed significantly between the roxadustat and valacyclovir ETT groups, while no other cytokines showed statistically significant differences. Additionally, increased biofilm formation was observed in the coated ETTs with notable alterations in microbiota distinctive to each ETT type and across time.</p><p><strong>Conclusion: </strong>The injured and intubated airway resulted in increased laryngeal stiffness. Local inflammation and the type of therapeutic administered impacted the bacterial composition within the upper respiratory microbiome, which in turn mediated local tissue healing and recovery.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":null,"pages":null},"PeriodicalIF":5.8000,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439253/pdf/","citationCount":"0","resultStr":"{\"title\":\"Localized delivery of therapeutics impact laryngeal mechanics, local inflammatory response, and respiratory microbiome following upper airway intubation injury in swine.\",\"authors\":\"Gabriela Gonzales, Ronit Malka, Lisa M Marinelli, Christine M Lee, Stacy Cook, Solaleh Miar, Gregory R Dion, Teja Guda\",\"doi\":\"10.1186/s12931-024-02973-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Laryngeal injury associated with traumatic or prolonged intubation may lead to voice, swallow, and airway complications. The interplay between inflammation and microbial population shifts induced by intubation may relate to clinical outcomes. The objective of this study was to investigate laryngeal mechanics, tissue inflammatory response, and local microbiome changes with laryngotracheal injury and localized delivery of therapeutics via drug-eluting endotracheal tube.</p><p><strong>Methods: </strong>A simulated traumatic intubation injury was created in Yorkshire crossbreed swine under direct laryngoscopy. Endotracheal tubes electrospun with roxadustat or valacyclovir- loaded polycaprolactone (PCL) fibers were placed in the injured airway for 3, 7, or 14 days (n = 3 per group/time and ETT type). Vocal fold stiffness was then evaluated with normal indentation and laryngeal tissue sections were histologically examined. Immunohistochemistry and inflammatory marker profiling were conducted to evaluate the inflammatory response associated with injury and ETT placement. Additionally, ETT biofilm formation was visualized using scanning electron microscopy and micro-computed tomography, while changes in the airway microbiome were profiled through 16S rRNA sequencing.</p><p><strong>Results: </strong>Laryngeal tissue with roxadustat ETT placement had increasing localized stiffness outcomes over time and histological assessment indicated minimal epithelial ulceration and fibrosis, while inflammation remained severe across all timepoints. In contrast, vocal fold tissue with valacyclovir ETT placement showed no significant changes in stiffness over time; histological analysis presented a reduction in epithelial ulceration and inflammation scores along with increased fibrosis observed at 14 days. Immunohistochemistry revealed a decline in M1 and M2 macrophage markers over time for both ETT types. Among the cytokines, IL-8 levels differed significantly between the roxadustat and valacyclovir ETT groups, while no other cytokines showed statistically significant differences. Additionally, increased biofilm formation was observed in the coated ETTs with notable alterations in microbiota distinctive to each ETT type and across time.</p><p><strong>Conclusion: </strong>The injured and intubated airway resulted in increased laryngeal stiffness. 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引用次数: 0
摘要
背景:与创伤性或长时间插管相关的喉损伤可能会导致嗓音、吞咽和气道并发症。插管引起的炎症和微生物群变化之间的相互作用可能与临床结果有关。本研究的目的是调查喉力学、组织炎症反应以及喉气管损伤和通过药物洗脱气管导管局部给药引起的局部微生物群变化:方法:在直接喉镜检查下,对约克郡杂交猪进行模拟创伤性插管损伤。将电纺有罗沙司他(roxadustat)或伐昔洛韦(valacyclovir- loaded polycaprolactone (PCL))纤维的气管导管置于受伤气道中 3、7 或 14 天(每组/时间和 ETT 类型 n = 3)。然后用正常压痕法评估声带僵硬度,并对喉组织切片进行组织学检查。免疫组化和炎症标记物分析用于评估与损伤和 ETT 置入相关的炎症反应。此外,还使用扫描电子显微镜和微型计算机断层扫描观察了 ETT 生物膜的形成,并通过 16S rRNA 测序分析了气道微生物组的变化:结果:放置了罗沙司他 ETT 的喉组织的局部僵硬度随时间推移而增加,组织学评估显示上皮溃疡和纤维化极少,而炎症在所有时间点上都很严重。与此相反,放置了伐昔洛韦 ETT 的声带组织的僵硬度没有随着时间的推移而发生显著变化;组织学分析表明,上皮溃疡和炎症评分降低,14 天后观察到纤维化增加。免疫组化显示,两种 ETT 的 M1 和 M2 巨噬细胞标记物均随时间推移而下降。在细胞因子中,罗沙司他和伐昔洛韦 ETT 组的 IL-8 水平差异显著,而其他细胞因子则没有统计学意义上的显著差异。此外,在有涂层的 ETT 中观察到生物膜形成增加,每种 ETT 类型和不同时间段的微生物群发生了明显变化:结论:受伤和插管气道导致喉部僵硬度增加。局部炎症和治疗类型影响了上呼吸道微生物群中的细菌组成,进而促进了局部组织的愈合和恢复。
Localized delivery of therapeutics impact laryngeal mechanics, local inflammatory response, and respiratory microbiome following upper airway intubation injury in swine.
Background: Laryngeal injury associated with traumatic or prolonged intubation may lead to voice, swallow, and airway complications. The interplay between inflammation and microbial population shifts induced by intubation may relate to clinical outcomes. The objective of this study was to investigate laryngeal mechanics, tissue inflammatory response, and local microbiome changes with laryngotracheal injury and localized delivery of therapeutics via drug-eluting endotracheal tube.
Methods: A simulated traumatic intubation injury was created in Yorkshire crossbreed swine under direct laryngoscopy. Endotracheal tubes electrospun with roxadustat or valacyclovir- loaded polycaprolactone (PCL) fibers were placed in the injured airway for 3, 7, or 14 days (n = 3 per group/time and ETT type). Vocal fold stiffness was then evaluated with normal indentation and laryngeal tissue sections were histologically examined. Immunohistochemistry and inflammatory marker profiling were conducted to evaluate the inflammatory response associated with injury and ETT placement. Additionally, ETT biofilm formation was visualized using scanning electron microscopy and micro-computed tomography, while changes in the airway microbiome were profiled through 16S rRNA sequencing.
Results: Laryngeal tissue with roxadustat ETT placement had increasing localized stiffness outcomes over time and histological assessment indicated minimal epithelial ulceration and fibrosis, while inflammation remained severe across all timepoints. In contrast, vocal fold tissue with valacyclovir ETT placement showed no significant changes in stiffness over time; histological analysis presented a reduction in epithelial ulceration and inflammation scores along with increased fibrosis observed at 14 days. Immunohistochemistry revealed a decline in M1 and M2 macrophage markers over time for both ETT types. Among the cytokines, IL-8 levels differed significantly between the roxadustat and valacyclovir ETT groups, while no other cytokines showed statistically significant differences. Additionally, increased biofilm formation was observed in the coated ETTs with notable alterations in microbiota distinctive to each ETT type and across time.
Conclusion: The injured and intubated airway resulted in increased laryngeal stiffness. Local inflammation and the type of therapeutic administered impacted the bacterial composition within the upper respiratory microbiome, which in turn mediated local tissue healing and recovery.
期刊介绍:
Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases.
As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion.
Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.