Burn inhalation injury and intubation with dexamethasone-eluting endotracheal tubes modulate local microbiome and alter airway inflammation
BackgroundInhalation injuries, caused by exposure to extreme heat and chemical irritants, lead to complications with speaking, swallowing, and breathing. This study investigates the effects of thermal injury and endotracheal tube (ETT) placement on the airway microbiome and inflammatory response. A...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2025.1524013/full |
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| author | Gabriela Gonzales Ronit Malka Rena Bizios Gregory R. Dion Teja Guda Teja Guda |
| author_facet | Gabriela Gonzales Ronit Malka Rena Bizios Gregory R. Dion Teja Guda Teja Guda |
| author_sort | Gabriela Gonzales |
| collection | DOAJ |
| description | BackgroundInhalation injuries, caused by exposure to extreme heat and chemical irritants, lead to complications with speaking, swallowing, and breathing. This study investigates the effects of thermal injury and endotracheal tube (ETT) placement on the airway microbiome and inflammatory response. A secondary aim is to assess the impact of localized dexamethasone delivery via a drug-eluting ETT to reduce laryngeal scarring.MethodsInhalation injury was developed in swine by administering heated air (150°C–160°C) under endoscopic visualization. Following injury, segments of regular or dexamethasone-loaded endotracheal tubes (ETTs) were placed in the injured airways for 3 or 7 days. Computed tomography (CT) scans were used to assess airway narrowing post-injury. Biofilm formation on the ETTs was investigated using micro-CT and microscopy. The airway microbiome was analyzed via 16S rRNA sequencing. Inflammatory markers were quantified using an immunoassay and macrophage populations in laryngeal tissue were assessed with CD86 and CD206 staining. Tracheal tissues were also histologically examined for epithelial thickness, collagen area, and mucin production.ResultsCT scans confirmed airway narrowing post-injury, particularly around ETT sites. Biofilm formation was more extensive on dexamethasone-coated ETTs at later timepoints. Beta diversity analysis revealed significant shifts in microbial composition related to ETT type (R2 = 0.04, p < 0.05) and duration of placement (R2 = 0.22, p < 0.05). Differential abundance analysis demonstrated significant positive log fold changes in genera such as Bergeriella, Peptostreptococcus, and Bacteriodes with thermal injury over time. Inflammatory markers IFN-γ, IL-4, and IL-1β were elevated in dexamethasone-ETT groups at 3 days, then decreased by 7 days. Macrophage markers CD86 and CD206 were significantly greater in dexamethasone groups compared to regular ETT groups at 7 days (p = 0.002 and p = 0.0213, respectively). Epithelial thickness was significantly greater with regular ETT placement compared to dexamethasone ETT placement in the burn-injured airway at 3 days (p = 0.027).ConclusionThermal inhalation injury and ETT placement significantly impact airway inflammation, structural integrity, and microbiome composition. Dexamethasone-eluting ETTs, intended to reduce inflammation, increased biofilm formation and elevated cytokine levels, suggesting complex interactions between the drug coating and the host immune response. The airway microbiome shifted significantly with specific taxa thriving in the inflamed environment. |
| format | Article |
| id | doaj-art-22e408a2314e43c282fbdbfce50e89f4 |
| institution | DOAJ |
| issn | 2296-4185 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj-art-22e408a2314e43c282fbdbfce50e89f42025-08-20T02:45:34ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852025-02-011310.3389/fbioe.2025.15240131524013Burn inhalation injury and intubation with dexamethasone-eluting endotracheal tubes modulate local microbiome and alter airway inflammationGabriela Gonzales0Ronit Malka1Rena Bizios2Gregory R. Dion3Teja Guda4Teja Guda5Department of Biomedical Engineering and Chemical Engineering, University of Texas at San Antonio, San Antonio, TX, United StatesDepartment of Otolaryngology – Head and Neck Surgery, Brooke Army Medical Center JBSA Fort Sam Houston, San Antonio, TX, United StatesDepartment of Biomedical Engineering and Chemical Engineering, University of Texas at San Antonio, San Antonio, TX, United StatesDepartment of Otolaryngology – Head and Neck Surgery, University of Cincinnati, Cincinnati, OH, United StatesDepartment of Biomedical Engineering and Chemical Engineering, University of Texas at San Antonio, San Antonio, TX, United StatesDepartment of Cell Systems and Anatomy, University of Texas Health San Antonio, San Antonio, TX, United StatesBackgroundInhalation injuries, caused by exposure to extreme heat and chemical irritants, lead to complications with speaking, swallowing, and breathing. This study investigates the effects of thermal injury and endotracheal tube (ETT) placement on the airway microbiome and inflammatory response. A secondary aim is to assess the impact of localized dexamethasone delivery via a drug-eluting ETT to reduce laryngeal scarring.MethodsInhalation injury was developed in swine by administering heated air (150°C–160°C) under endoscopic visualization. Following injury, segments of regular or dexamethasone-loaded endotracheal tubes (ETTs) were placed in the injured airways for 3 or 7 days. Computed tomography (CT) scans were used to assess airway narrowing post-injury. Biofilm formation on the ETTs was investigated using micro-CT and microscopy. The airway microbiome was analyzed via 16S rRNA sequencing. Inflammatory markers were quantified using an immunoassay and macrophage populations in laryngeal tissue were assessed with CD86 and CD206 staining. Tracheal tissues were also histologically examined for epithelial thickness, collagen area, and mucin production.ResultsCT scans confirmed airway narrowing post-injury, particularly around ETT sites. Biofilm formation was more extensive on dexamethasone-coated ETTs at later timepoints. Beta diversity analysis revealed significant shifts in microbial composition related to ETT type (R2 = 0.04, p < 0.05) and duration of placement (R2 = 0.22, p < 0.05). Differential abundance analysis demonstrated significant positive log fold changes in genera such as Bergeriella, Peptostreptococcus, and Bacteriodes with thermal injury over time. Inflammatory markers IFN-γ, IL-4, and IL-1β were elevated in dexamethasone-ETT groups at 3 days, then decreased by 7 days. Macrophage markers CD86 and CD206 were significantly greater in dexamethasone groups compared to regular ETT groups at 7 days (p = 0.002 and p = 0.0213, respectively). Epithelial thickness was significantly greater with regular ETT placement compared to dexamethasone ETT placement in the burn-injured airway at 3 days (p = 0.027).ConclusionThermal inhalation injury and ETT placement significantly impact airway inflammation, structural integrity, and microbiome composition. Dexamethasone-eluting ETTs, intended to reduce inflammation, increased biofilm formation and elevated cytokine levels, suggesting complex interactions between the drug coating and the host immune response. The airway microbiome shifted significantly with specific taxa thriving in the inflamed environment.https://www.frontiersin.org/articles/10.3389/fbioe.2025.1524013/fullinhalation injuryupper airwaymicrobiomeinflammationendotracheal tube |
| spellingShingle | Gabriela Gonzales Ronit Malka Rena Bizios Gregory R. Dion Teja Guda Teja Guda Burn inhalation injury and intubation with dexamethasone-eluting endotracheal tubes modulate local microbiome and alter airway inflammation Frontiers in Bioengineering and Biotechnology inhalation injury upper airway microbiome inflammation endotracheal tube |
| title | Burn inhalation injury and intubation with dexamethasone-eluting endotracheal tubes modulate local microbiome and alter airway inflammation |
| title_full | Burn inhalation injury and intubation with dexamethasone-eluting endotracheal tubes modulate local microbiome and alter airway inflammation |
| title_fullStr | Burn inhalation injury and intubation with dexamethasone-eluting endotracheal tubes modulate local microbiome and alter airway inflammation |
| title_full_unstemmed | Burn inhalation injury and intubation with dexamethasone-eluting endotracheal tubes modulate local microbiome and alter airway inflammation |
| title_short | Burn inhalation injury and intubation with dexamethasone-eluting endotracheal tubes modulate local microbiome and alter airway inflammation |
| title_sort | burn inhalation injury and intubation with dexamethasone eluting endotracheal tubes modulate local microbiome and alter airway inflammation |
| topic | inhalation injury upper airway microbiome inflammation endotracheal tube |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2025.1524013/full |
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