The Potential Role of Bile Acids in Acquired Laryngotracheal Stenosis

Aldhahrani, Adil; Powell, Jason; Ladak, Shameem; Ali, Mahmoud S.; Ali, Simi; Verdon, Bernard; Pearson, Jeffrey P.; Ward, Chris

doi:10.1002/lary.27105

Cited by 26 publications

(28 citation statements)

References 33 publications

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“…The present examination of the potential for pepsin to contribute to fibrosis in iSGS was therefore important for informing current treatment strategies. Whereas the findings herein do not support a role for pepsin in EMT in the larynx, previous findings suggest that acid‐targeting medical therapies may allow ongoing damage by other nonacid reflux components, warranting further investigation …”

Section: Discussioncontrasting

confidence: 86%

“…Anti‐reflux medical therapy has demonstrated success independently or as an adjunct to surgical treatment . Physiologically, relevant concentrations of bile acids induce markers of EMT in human primary tracheal epithelial cells, demonstrating a potential role for refluxed bile acids in tracheal scarring and remodeling and thus in stenosis …”

Section: Introductionmentioning

confidence: 99%

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The role of pepsin in epithelia‐mesenchymal transition in idiopathic subglottic stenosis

et al. 2019

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Objectives: Idiopathic subglottic stenosis (iSGS) is commonly characterized by laryngeal fibrosis thought to arise by epithelia-mesenchymal transition (EMT) induced by chronic inflammation. Pepsin is a potent inducer of inflammation in the airways during chronic laryngopharyngeal reflux and has been observed in the subglottic mucosa of patients with iSGS, absent in normal mucosa. The aim of this study was to examine the effect of pepsin on mechanisms of EMT in laryngeal cells with implications for iSGS.Study Design: In vitro translational research study. Methods: Human laryngeal epithelial cell cultures were exposed to 0.1 mg/mL or 1.0 mg/mL pepsin at pH7 for 24 and 48 hours, or media pH5 AE 0.1 mg/mL pepsin for 10 minutes and harvested after 24 and 48 hours. EMT marker expression was measured by qPCR and enzyme-linked immunosorbent assays. Wound-healing scratch assay was performed on immortalized human vocal fold fibroblasts pretreated with media pH5 AE 0.1 mg/mL pepsin (10 minutes) or continuously treated with media pH7 AE 0.1 to 1 mg/mL pepsin for 24 hours.Results: Pepsin yielded no effect on MMP1, MMP9, FN1, COL1A1, HAS2, or CDH1 gene expression or matrix metalloproteinase-9 or fibronectin protein expression, either alone or in the presence of weak acid. Pepsin and/or acid produced no effect on fibroblast migration.Conclusion: Whereas pepsin has been shown to be present in the subglottic mucosa of patients with iSGS, this in vitro acute exposure investigation does not provide evidence of a direct causal role for development of fibrosis in subglottic epithelial cell cultures.

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Section: Discussioncontrasting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

The role of pepsin in epithelia‐mesenchymal transition in idiopathic subglottic stenosis

et al. 2019

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“…The examination was normal, and no subglottic pathology was encountered. However, these symptoms could be due to laryngopharyngeal reflux, which has been shown to alter laryngeal cell phenotype . The samples had to be obtained during general anesthesia due to the difficulty in accessing the subglottis; therefore, it was not possible to access subglottic samples from completely asymptomatic patients (who would not be undergoing this procedure).…”

Section: Discussionmentioning

confidence: 99%

Establishment of an immortalized human subglottic epithelial cell line

et al. 2019

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Objective: Translational research into subglottic disease is restricted by the availability of primary human tissue originating from this subsite. Primary epithelial cells are also limited by their inability to survive beyond several divisions in culture outside of the body. Specific subglottic cell lines, useful for in vitro studies, have not yet been described. We therefore demonstrate what we believe to be the first immortalized subglottic epithelial cell line.Methods: Subglottic tissue was derived from a single adult patient's neoplasia-free human subglottic brushing specimen. Cells were immortalized using a lentiviral vector expressing simian virus 40 T antigen. Karyotyping was performed on the transformed cells using single nucleotide polymorphism array comparative genomic hybridization. Transformed cells were phenotypically characterized by light microscopy, immunohistochemistry, and electrophysiology studies.Results: The immortalized subglottic cell line (SG01) was able to divide successfully beyond 20 passages. Karyotyping demonstrated no significant genomic imbalance after immortalization. The cells demonstrated normal epithelial morphology and cytokeratin expression throughout. SG01 cells were also successfully cultured at air-liquid interface (ALI). At ALI cells demonstrated cilia, mucus production, and relevant ion channel expression.Conclusion: The novel SG01 subglottic epithelial cell line has been established. This cell line provides a unique resource for researchers to investigate subglottic diseases, such as subglottic stenosis.

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“…The current survey reveals similar lack of awareness of the potential role of LPR in development of laryngotracheal stenosis and chronic media otitis, despite an increasing literature which supports this relationship. 10,11,26,27 Surprisingly, non-laryngologists seem to be unaware about the role of LPR in bronchial diseases such as asthma; however, many studies have demonstrated that LPR is involved in the development of bronchial hypersensitivity conditions, such as asthma, 28,29 or chronic obstructive pulmonary disease. 30 In the current survey, the largest differences between laryngologists and non-laryngologists concern diagnostic approach towards LPR, particularly with regard to examinations such as esophagoscopy and MII-pH.…”

Section: Discussionmentioning

confidence: 99%

Do Laryngologists and General Otolaryngologists Manage Laryngopharyngeal Reflux Differently?

et al. 2020

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Objective To investigate current practices of laryngologists and non‐laryngologists in management of Laryngopharyngeal Reflux (LPR). Methods An online survey was sent to members of otolaryngology societies about LPR, and subgroup analysis was performed between laryngologists and non‐laryngologists. This survey was conducted by the LPR Study Group of Young Otolaryngologists of the International Federation of Otolaryngological Societies. Results A total of 535 otolaryngologists completed the survey. Among them, 127 were laryngologists and 408 were non‐laryngologists. Collectively, symptoms most commonly attributed to LPR are cough after lying down/meal, throat clearing, and acid brash; most common findings are thought to be arytenoid erythema and posterior commissure hypertrophy. Respectively, 12.5% and 5% of non‐laryngologists and laryngologists believe that ≥50% of LPR patients suffer from heartburn (P = .010). Non‐laryngologists are more aware about some extra‐laryngeal findings associated with LPR (eg, pharyngeal erythema) than laryngologists. Neither laryngologists nor non‐laryngologists associated development of benign lesions of the vocal folds with reflux. The management of LPR substantially differs between groups, with laryngologists indicating increased awareness of (impedance)‐pH monitoring as well as the prevalence and treatment of nonacid/mixed LPR. Conversely, non‐laryngologists are much more likely to include gastroenterology referral in their management of presumed LPR. Respectively, 44.8% and 27.6% of non‐laryngologists and laryngologists believe themselves not sufficiently knowledgeable about LPR. Conclusions Significant differences exist between laryngologists and non‐laryngologists in diagnosis and treatment of LPR. Overall only one‐third of responders believe themselves to be sufficiently educated about LPR. Level of Evidence 4 Laryngoscope, 130:E539–E547, 2020

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The Potential Role of Bile Acids in Acquired Laryngotracheal Stenosis

Abstract: NA. Laryngoscope, 128:2029-2033, 2018.

Cited by 26 publications

References 33 publications

The role of pepsin in epithelia‐mesenchymal transition in idiopathic subglottic stenosis

The role of pepsin in epithelia‐mesenchymal transition in idiopathic subglottic stenosis

Establishment of an immortalized human subglottic epithelial cell line

Do Laryngologists and General Otolaryngologists Manage Laryngopharyngeal Reflux Differently?

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