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Tracheobronchial injuries can be difficult to diagnose and manage, especially in the presence of polytrauma. A 50-year-old woman presented as a Level I trauma activation after being struck by a motor vehicle. Initial evaluation demonstrated intracranial hemorrhage and multiple chest injuries, including multilevel bilateral rib fractures, pneumomediastinum, and concern for tracheobronchial injury. After initial stabilization, bronchoscopy was performed and demonstrated an injury to the carina. We report a novel airway and ventilation strategy in the setting of concomitant tracheobronchial injury after severe blunt chest trauma in which extracorporeal support is contraindicated.
Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
STUDY OBJECTIVE - Induction doses of etomidate during rapid sequence intubation cause transient adrenal dysfunction, but its clinical significance on trauma patients is uncertain. Ketamine has emerged as an alternative for rapid sequence intubation induction. Among adult trauma patients intubated in the emergency department, we compare clinical outcomes among those induced with etomidate and ketamine.
METHODS - The study entailed a retrospective evaluation of a 4-year (January 2011 to December 2014) period spanning an institutional protocol switch from etomidate to ketamine as the standard induction agent for adult trauma patients undergoing rapid sequence intubation in the emergency department of an academic Level I trauma center. The primary outcome was hospital mortality evaluated with multivariable logistic regression, adjusted for age, vital signs, and injury severity and mechanism. Secondary outcomes included ICU-free days and ventilator-free days evaluated with multivariable ordered logistic regression using the same covariates.
RESULTS - The analysis included 968 patients, including 526 with etomidate and 442 with ketamine. Hospital mortality was 20.4% among patients induced with ketamine compared with 17.3% among those induced with etomidate (adjusted odds ratio [OR] 1.41; 95% confidence interval [CI] 0.92 to 2.16). Patients induced with ketamine had ICU-free days (adjusted OR 0.80; 95% CI 0.63 to 1.00) and ventilator-free days (adjusted OR 0.96; 95% CI 0.76 to 1.20) similar to those of patients induced with etomidate.
CONCLUSION - In this analysis spanning an institutional protocol switch from etomidate to ketamine as the standard rapid sequence intubation induction agent for adult trauma patients, patient-centered outcomes were similar for patients who received etomidate and ketamine.
Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.
OBJECTIVES/HYPOTHESIS - Idiopathic subglottic stenosis (iSGS) is a rare and devastating extrathoracic obstruction involving the lower laryngeal and upper tracheal airway. It arises without known antecedent injury or associated disease process. Persistent mucosal inflammation and a localized fibrotic response are hallmarks of the disease. Despite the initial clinical description of iSGS more than 40 year ago, there have been no substantive investigations into the pathogenesis of this enigmatic and progressive airway obstruction. In these studies, we present the initial characterization of the molecular pathogenesis underlying the fibrosing phenotype of iSGS.
METHODS - Utilizing 20 human iSGS and healthy control specimens, we applied histologic, immunohistochemical, molecular, and immunologic techniques.
RESULTS - We demonstrate significant activation of the canonical IL-23/IL-17A pathway in the tracheal mucosa of iSGS patients, as well as identify γδ T cells as the primary cellular source of IL-17A.
CONCLUSION - Our results suggest that aberrant mucosal immune activation is a component in of the pathogenesis of iSGS. Most critically, our work offers new targets for future therapeutic intervention.
LEVEL OF EVIDENCE - NA Laryngoscope, 126:E356-E361, 2016.
© 2016 The American Laryngological, Rhinological and Otological Society, Inc.
OBJECTIVES/HYPOTHESIS - Idiopathic subglottic stenosis (iSGS) is an unexplained obstruction involving the lower laryngeal and upper tracheal airway. Persistent mucosal inflammation is a hallmark of the disease. Epithelial microbiota dysbiosis is found in other chronic inflammatory mucosal diseases; however, the relationship between tracheal microbiota composition and iSGS is unknown. Given the critical role for host defense at mucosal barriers, we analyzed tissue specimens from iSGS patients for the presence of microbial pathogens.
METHODS - Utilizing 30 human iSGS, 20 intubation-related tracheal stenosis (iLTS), and 20 healthy control specimens, we applied molecular, immunohistochemical, electron microscopic, immunologic, and Sanger-sequencing techniques.
RESULTS - With unbiased culture-independent nucleic acid, protein, and immunologic approaches, we demonstrate that Mycobacterium species are uniquely associated with iSGS. Phylogenetic analysis of the mycobacterial virulence factor rpoB suggests that, rather than Mycobacterium tuberculosis, a variant member of the Mycobacterium tuberculosis complex or a closely related novel mycobacterium is present in iSGS specimens.
CONCLUSION - These studies identify a novel pathogenic role for established large airway bacteria and provide new targets for future therapeutic intervention.
LEVEL OF EVIDENCE - NA Laryngoscope, 127:179-185, 2017.
© 2016 The American Laryngological, Rhinological and Otological Society, Inc.
We report that p73 is expressed in multiciliated cells (MCCs), is required for MCC differentiation, and directly regulates transcriptional modulators of multiciliogenesis. Loss of ciliary biogenesis provides a unifying mechanism for many phenotypes observed in p73 knockout mice including hydrocephalus; hippocampal dysgenesis; sterility; and chronic inflammation/infection of lung, middle ear, and sinus. Through p73 and p63 ChIP-seq using murine tracheal cells, we identified over 100 putative p73 target genes that regulate MCC differentiation and homeostasis. We validated Foxj1, a transcriptional regulator of multiciliogenesis, and many other cilia-associated genes as direct target genes of p73 and p63. We show p73 and p63 are co-expressed in a subset of basal cells and suggest that p73 marks these cells for MCC differentiation. In summary, p73 is essential for MCC differentiation, functions as a critical regulator of a transcriptome required for MCC differentiation, and, like p63, has an essential role in development of tissues.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
The pseudostratified epithelium of the lung contains ciliated and secretory luminal cells and basal stem/progenitor cells. To identify signals controlling basal cell behavior we screened factors that alter their self-renewal and differentiation in a clonal organoid (tracheosphere) assay. This revealed that inhibitors of the canonical BMP signaling pathway promote proliferation but do not affect lineage choice, whereas exogenous Bmp4 inhibits proliferation and differentiation. We therefore followed changes in BMP pathway components in vivo in the mouse trachea during epithelial regeneration from basal cells after injury. The findings suggest that BMP signaling normally constrains proliferation at steady state and this brake is released transiently during repair by the upregulation of endogenous BMP antagonists. Early in repair, the packing of epithelial cells along the basal lamina increases, but density is later restored by active extrusion of apoptotic cells. Systemic administration of the BMP antagonist LDN-193189 during repair initially increases epithelial cell number but, following the shedding phase, normal density is restored. Taken together, these results reveal crucial roles for both BMP signaling and cell shedding in homeostasis of the respiratory epithelium.
© 2016. Published by The Company of Biologists Ltd.
IMPORTANCE - Patients who undergo open airway reconstruction procedures are likely to experience some degree of postoperative dysphagia symptoms and delayed return to oral intake.
OBJECTIVE - To review the duration of postoperative dysphagia symptoms and outcomes in a group of adult patients.
DESIGN, SETTING, AND PARTICIPANTS - Retrospective review of the medical records of adult patients undergoing laryngotracheoplasty, posterior cricoid split laryngoplasty, tracheal resection, and cricotracheal resection in a tertiary hospital between July 2009 and September 2014.
EXPOSURES - Laryngotracheoplasty, posterior cricoid split laryngoplasty, tracheal resection, and cricotracheal resection.
MAIN OUTCOMES AND MEASURES - Demographic characteristics, etiology of airway stenosis, surgical procedure, stent type, and duration of dysphagia symptoms.
RESULTS - Thirty-eight patients (14 men, 24 women; mean [SD; range] age, 48 [14.4; 20-80] years) fitting the inclusion criteria were identified. Twenty-four (63%) patients had laryngotracheal stenosis secondary to prolonged intubation, with 3 (8%), 5 (13%), and 6 (16%) cases being due to autoimmune, idiopathic, or other etiology, respectively. Twenty-five (66%) patients underwent tracheal or cricotracheal resection, and 13 (34%) underwent laryngotracheoplasty or posterior cricoid split laryngoplasty. Of the 17 patients with stents placed, 6 (35%) patients had a suprastomal stent sewn at the top with a polypropylene suture using a horizontal mattress technique, 6 (35%) patients had a suprastomal stent capped with an extended Silastic thoracic T-tube segment, and 5 (29%) patients had either a T-tube or hood bronchial stent. Eight of 17 patients used a nasogastric feeding tube while the stent was in place (up to 5 weeks). All patients returned to their preoperative diet. The mean (SD) duration of dysphagia symptoms in all patients (both those without a stent and following stent removal) was 8 (27.2) days (median, 1.5 days). The mean (SD) duration of dysphagia symptoms in patients who did not have a stent placed was 4.8 (5.3) days (median, 4 days).
CONCLUSIONS AND RELEVANCE - In this study of adults who underwent open airway reconstruction, all returned to their preoperative diet, but those without stents had a shorter duration of dysphagia symptoms than those with stents. Approximately half as many patients with a stent had a prolonged course with dysphagia symptoms compared with those without a stent.
OBJECTIVE - To assess intrinsic and extrinsic risk factors in the development of posterior glottic stenosis (PGS) in intubated patients.
METHODS - Patients diagnosed with PGS between September 2012 and May 2014 at 3 tertiary care university hospitals were included. Patient demographics, comorbidities, duration of intubation, endotracheal tube (ETT) size, and indication for intubation were recorded. Patients with PGS were compared to control patients represented by patients intubated in intensive care units (ICU).
RESULTS - Thirty-six PGS patients were identified. After exclusion, 28 PGS patients (14 male, 14 female) and 112 (65 male, 47 female) controls were studied. Multivariate analysis demonstrated ischemia (P < .05), diabetes (P < .01), and length of intubation (P < .01) were significant risk factors for the development of PGS. Fourteen of 14 (100%) males were intubated with a size 8 or larger ETT compared to 47 of 65 (72.3%) male controls (P < .05). Posterior glottic stenosis (P < .01), length of intubation (P < .001), and obstructive sleep apnea (P < .05) were significant risk factors for tracheostomy.
CONCLUSION - Duration of intubation, ischemia, diabetes mellitus, and large ETT size (8 or greater) in males were significant risk factors for the development of PGS. Reducing the use of size 8 ETTs and earlier planned tracheostomy in high-risk patients may reduce the incidence of PGS and improve ICU safety.
© The Author(s) 2015.
OBJECTIVES/HYPOTHESIS - Laryngotracheal stenosis (LTS) is largely considered a structural entity, defined on anatomic terms (i.e., percent stenosis, distance from vocal folds, overall length). This has significant implications for identifying at-risk populations, devising systems-based preventive strategies, and promoting patient-centered treatment. The present study was undertaken to test the hypothesis that LTS is heterogeneous with regard to etiology, natural history, and clinical outcome.
STUDY DESIGN - Retrospective cohort study of consecutive adult tracheal stenosis patients from 1998 to 2013.
METHODS - Subjects diagnosed with laryngotracheal stenosis (ICD-9: 478.74, 519.19) between January 1, 1998, and January 1, 2013, were identified. Patient characteristics (age, gender, race, follow-up duration) and comorbidities were extracted. Records were reviewed for etiology of stenosis, treatment approach, and surgical dates. Stenosis morphology was derived from intraoperative measurements. The presence of tracheostomy at last follow-up was recorded.
RESULTS - One hundred and fifty patients met inclusion criteria. A total of 54.7% had an iatrogenic etiology, followed by idiopathic (18.5%), autoimmune (18.5%), and traumatic (8%). Tracheostomy dependence differed based on etiology (P < 0.001). Significantly more patients with iatrogenic (66%) and autoimmune (54%) etiologies remained tracheostomy-dependent compared to traumatic (33%) or idiopathic (0%) groups. On multivariate regression analysis, each additional point on Charlson Comorbidity Index was associated with a 67% increased odds of tracheostomy dependence (odds ratio 1.67; 95% confidence interval 1.04-2.69; P = 0.04).
CONCLUSIONS - Laryngotracheal stenosis is not a homogeneous clinical entity. It has multiple distinct etiologies that demonstrate disparate rates of long-term tracheostomy dependence. Understanding the mechanism of injury and contribution of comorbid illnesses is critical to systems-based preventive strategies and patient-centered treatment.
LEVEL OF EVIDENCE - 4.
© 2014 The American Laryngological, Rhinological and Otological Society, Inc.