Subglottic injury: A clinically relevant animal model

Kelly, Niall P.; Murphy, Madeline; Giles, Sally; Russell, John

doi:10.1002/lary.23515

Cited by 19 publications

(34 citation statements)

References 36 publications

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“…The pathogenic mechanism of post intubation SGS has been well established as a progression from mucosal injury to granulation tissue and subsequent scarring fibrosis [11]. Given that by definition idiopathic SGS does not have an identifiable trauma it seems reasonable to theorize that this cascade of scarring results from another initiating inflammatory event.…”

Section: Discussionmentioning

confidence: 99%

Myhre-LAPs syndrome and intubation related airway stenosis: keys to diagnosis and critical therapeutic interventions

Oldenburg

Frisch

Lindor

et al. 2015

American Journal of Otolaryngology

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Section: Discussionmentioning

confidence: 99%

Myhre-LAPs syndrome and intubation related airway stenosis: keys to diagnosis and critical therapeutic interventions

Oldenburg

Frisch

Lindor

et al. 2015

American Journal of Otolaryngology

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“…As other studies have suggested, additional contributing factors include microbiome shifts in the larynx and trachea 38 and the ensuing perichondritis after hypoxic injury caused by intubation. 39 Recent discoveries also highlight the potential for a genetic predisposition to laryngotracheal scar formation; one study found an association between a polymorphism in matrix metalloproteinase 1 (MMP1) and the formation of scar after intubation injury. 40 This discovery complements our finding of elevated MMP activity after hypoxic stimulation of normal laryngotracheal fibroblasts, suggesting that genetic predisposition may enhance the effects of hypoxia on the laryngotracheal ECM.…”

Section: Discussionmentioning

confidence: 99%

Fibroblasts in Hypoxic Conditions Mimic Laryngotracheal Stenosis

Yin

Motz²,

Samad

et al. 2017

Otolaryngol.--head neck surg.

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Objective To elucidate the role of hypoxia and inflammatory pathways in the pathogenesis of iatrogenic laryngotracheal stenosis (iLTS). Study Design 1) Examination of mucosal surface gene expression in human iLTS 2) In vitro comparison of normal and scar laryngotracheal fibroblasts under normoxic and hypoxic conditions Setting Tertiary care hospital in a research university, 2012–2016 Subjects and Methods Brush biopsies were obtained from normal laryngotracheal tissue and scar in iLTS patients; gene expression was compared. Fibroblasts were isolated from normal and scarred trachea and grown in vitro in either a 1% O2 or normoxic environment. Cell growth and gene and protein expression were compared. Statistical analysis utilized a multilevel mixed-effects model. Results Expression of IL-6 (Fold-change = 2.8, p<0.01), myofibroblast marker αSMA (Fold-change = 3.0, p=0.01), and MMP13 (Fold-change = 5.4, p=0.02) was significantly increased in scar biopsy samples compared to normal. Under hypoxic conditions in vitro, normal laryngotracheal fibroblasts proliferated significantly faster (n=8, p<0.01 each day). Expression of IL-6 (n=8, Fold-change = 2.6, p<0.01) increased significantly after 12 hours under hypoxia. Expression of αSMA (n=8, Fold-change= 2.0, p=0.03), COL1 (n=8, Fold-change = 1.1), and MMP13 (n=8, Fold-change = 1.6, p=0.01) increased significantly after 48 hours under hypoxia. Scar fibroblasts also proliferated significantly faster under hypoxic conditions, but did not display the same expression profile. Conclusion Human iLTS scar has a myofibroblast phenotype. Under hypoxic conditions in vitro, normal laryngotracheal fibroblasts can transdifferentiate into a similar phenotype. These changes may be mediated by IL-6, a fibrosis-related cytokine.

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“…A variety of animal models of subglottic stenosis exist, of which a select cohort are listed here [28–32]. However, there are few reports of in vivo OCT of subglottic stenosis models with comparative histologic analysis [24].…”

Section: Discussionmentioning

confidence: 99%

Long-range Fourier domain optical coherence tomography of the pediatric subglottis

Volgger

Sharma

Jing

et al. 2015

International Journal of Pediatric Otorhinolaryngology

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Background Acquired subglottic stenosis (SGS) most commonly results from prolonged endotracheal intubation and is a diagnostic challenge in the intubated child. At present, no imaging modality allows for in vivo characterization of subglottic microanatomy to identify early signs of acquired SGS while the child remains intubated. Fourier domain optical coherence tomography (FD-OCT) is a minimally invasive, light-based imaging modality which provides high resolution, three dimensional (3D) cross-sectional images of biological tissue. We used long-range FD-OCT to image the subglottis in intubated pediatric patients undergoing minor head and neck surgical procedures in the operating room. Methods A long-range FD-OCT system and rotary optical probes (1.2 mm and 0.7 mm outer diameters) were constructed. Forty-six pediatric patients (ages 2–16 years) undergoing minor upper airway surgery (e.g. tonsillectomy, adenoidectomy) were selected for intraoperative, trans-endotracheal tube FD-OCT of the subglottis. Images were analyzed for anatomical landmarks and subepithelial histology. Volumetric image sets were rendered into virtual 3D airway models in Mimics software. Results FD-OCT was performed on 46 patients (ages 2–16 years) with no complications. Gross airway contour was visible on all 46 data sets. Twenty (43%) high-quality data sets clearly demonstrated airway anatomy (e.g., tracheal rings, cricoid, vocal folds) and layered microanatomy of the mucosa (e.g., epithelium, basement membrane, lamina propria). The remaining 26 data sets were discarded due to artifact, high signal-to-noise ratio or missing data. 3D airway models allowed for user-controlled manipulation and multiplanar airway slicing (e.g. sagittal, coronal) for visualization of OCT data at multiple anatomic levels simultaneously. Conclusions Long-range FD-OCT produces high-resolution, 3D volumetric images of the pediatric subglottis. This technology offers a safe and practical means for in vivo evaluation of lower airway microanatomy in intubated pediatric patients. Ultimately, FD-OCT may be applied to serial monitoring of the neonatal subglottis in long-term intubated infants at risk for acquired SGS.

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Subglottic injury: A clinically relevant animal model

Cited by 19 publications

References 36 publications

Myhre-LAPs syndrome and intubation related airway stenosis: keys to diagnosis and critical therapeutic interventions

Myhre-LAPs syndrome and intubation related airway stenosis: keys to diagnosis and critical therapeutic interventions

Fibroblasts in Hypoxic Conditions Mimic Laryngotracheal Stenosis

Long-range Fourier domain optical coherence tomography of the pediatric subglottis

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