The frequency of UPSCC has increased significantly in recent calendar periods, and most cases are HPV-positive. As expected, patients with HPV-positive UPSCC tend to be male and younger.
Objective
Laryngotracheal stenosis (LTS) is a fibrotic process that narrows the upper airway and has a significant impact on breathing and phonation. Iatrogenic injury from endotracheal and/or tracheostomy tubes is the most common etiology. This study investigates differences in LTS etiologies as they relate to tracheostomy dependence and dilation interval.
Study Design
Case series with chart review
Setting
Single-center tertiary care facility
Subjects and Methods
Review of adult patients with LTS was performed between 2004–2015. The association of patient demographics, comorbidities, disease etiology, and treatment modalities with patient outcomes was assessed. Multiple logistic regression analysis and Kaplan-Meier analysis was performed to determine factors associated with tracheostomy-dependence and time to second procedure respectively.
Results
262 patients met inclusion criteria. Iatrogenic patients presented with greater stenosis (p=0.023), greater length (p=0.004), and located further from the vocal folds (p<0.001) compared with other etiologies. Iatrogenic patients were more likely to be African-American and have obstructive sleep apnea, type II diabetes, hypertension, COPD, stroke, and use tobacco. Iatrogenic LTS (OR=3.1, CI= 1.2–8.2), Cotton-Myer Grade 3–4 (OR=2.6, CI=1.1–6.4), and lack of intraoperative steroids (OR=2.9, CI=1.2–6.9) were associated with tracheostomy-dependence. Non-smokers, patients without tracheostomy, and idiopathic LTS patients had a significantly longer time to second dilation procedure.
Conclusion
Iatrogenic LTS presents with a greater disease burden and higher risk of tracheostomy dependence compared to other etiologies of LTS. Co-morbid conditions promoting microvascular injury, including smoking, COPD, and diabetes, were prevalent in the iatrogenic cohort. Changes in hospital practice patterns to promote earlier tracheostomy in high risk patients could reduce the incidence of LTS.
Objective/Purpose
Laryngotracheal stenosis (LTS) is a chronic fibrotic disease characterized by fibroblast proliferation, collagen deposition, and matrix remodeling in the lamina propria of the larynx and/or trachea. Current medical therapies are limited by a poor understanding of the effector cell’s (fibroblasts) cellular biology and metabolism. The purpose of this study is to compare cellular proliferation, function, and metabolism between normal and LTS-derived fibroblasts in vitro.
Methods
Human biopsies of normal and iatrogenic LTS tissue (n=7) were obtained and fibroblasts were isolated and cultured in vitro. Cellular proliferation, cellular histology, gene expression and metabolic analyses were performed. Statistical analyses comparing normal and scar-derived fibroblasts were performed.
Results
LTS fibroblast proliferation rate, cellular surface area, and collagen-1 expression were increased compared to normal fibroblasts. Cellular metabolic analysis of LTS-derived fibroblasts demonstrated reduced oxidative phosphorylation and increased glycolysis/oxidative phosphorylation ratio compared with normal fibroblasts.
Conclusion
Human iatrogenic LTS-derived fibroblasts demonstrated aberrant behavior when compared with normal fibroblasts. A Warburg-like effect was revealed suggesting human iatrogenic LTS fibroblasts drive their proliferation with aerobic glycolysis. The distinct metabolism suggests metabolic inhibitors could reduce fibroblast hyperplasia and hypertrophy in LTS and fibrosis in general.
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