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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 a rare and potentially life-threatening disease marked by recurrent and progressive airway obstruction frequently requiring repeated surgery to stabilize the airway. Unknown etiology and low disease prevalence have limited the ability to characterize the natural history of iSGS and resulted in variability in surgical management. It is uncertain how this variation relates to clinical outcomes.
STUDY DESIGN - Medical record abstraction.
METHODS - Utilizing an international, multi-institutional collaborative, we collected retrospective data on patient characteristics, treatment, and clinical outcomes. We investigated variation between and within open and endoscopic treatment approaches and assessed therapeutic outcomes; specifically, disease recurrence and need for tracheostomy at last follow-up.
RESULTS - Strikingly, 479 iSGS patients across 10 participating centers were nearly exclusively female (98%, 95% confidence interval [CI], 96.1-99.6), Caucasian (95%, 95% CI, 92.2-98.8), and otherwise healthy (mean age-adjusted Charlson Comorbidity Index 1.5; 95% CI, 1.44-1.69). The patients presented at a mean age of 50 years (95% CI, 48.8-51.1). A total of 80.2% were managed endoscopically, whereas 19.8% underwent open reconstruction. Endoscopic surgery had a significantly higher rate of disease recurrence than the open approach (chi(2) = 4.09, P = 0.043). Tracheostomy was avoided in 97% of patients irrespective of surgical approach (95% CI, 94.5-99.8). Interestingly, there were outliers in rates of disease recurrence between centers using similar treatment approaches.
CONCLUSION - Idiopathic subglottic stenosis patients are surprisingly homogeneous. The heterogeneity of treatment approaches and the observed outliers in disease recurrence rates between centers raises the potential for improved clinical outcomes through a detailed understanding of the processes of care.
LEVEL OF EVIDENCE - 4. Laryngoscope, 126:1390-1396, 2016.
© 2015 The American Laryngological, Rhinological and Otological Society, Inc.
BACKGROUND/AIMS - Rehabilitation of the bilaterally paralyzed human larynx remains a complex clinical problem. Conventional treatment generally involves surgical enlargement of the compromised airway, but often with resultant dysphonia and risk of aspiration. In this retrospective study, we compared one such treatment, posterior cordotomy, with unilateral laryngeal pacing: reanimation of vocal fold opening by functional electrical stimulation of the posterior cricoarytenoid muscle.
METHODS - Postoperative peak inspiratory flow (PIF) values and overall voice grade ratings were compared between the two surgical groups, and pre- and postoperative PIF were compared within the pacing group.
RESULTS - There were 5 patients in the unilateral pacing group and 12 patients in the unilateral cordotomy group. Within the pacing group, postoperative PIF values were significantly improved from preoperative PIF values (p = 0.04) without a significant effect on voice (grade; p = 0.62). Within the pacing group, the mean postoperative PIF value was significantly higher than that in the cordotomy group (p = 0.05). Also, the mean postoperative overall voice grade values in the pacing group were significantly lower (better) than those of the cordotomy group (p = 0.03).
CONCLUSION - Unilateral pacing appears to be an effective treatment superior to posterior cordotomy with respect to postoperative ventilation and voice outcome measures.
Copyright © 2013 S. Karger AG, Basel.
Laryngopharyngeal reflux (LPR) is associated with symptoms of laryngeal irritation such as throat pain, cough, and voice change. Currently, the two main diagnostic tools are laryngoscopy and reflux monitoring. On laryngoscopy, the signs most commonly used to diagnose LPR are erythema and edema of the larynx; however, these signs are not specific for LPR, may be associated with other causes, and may even be found in healthy individuals. In addition, pH testing has low sensitivity in diagnosing gastroesophageal reflux disease-related laryngeal findings. Proton pump inhibitor (PPI) therapy remains the cornerstone of treatment. The current management recommendation for this group of patients is empiric therapy with twice-daily PPIs for 1 to 2 months. In the majority of those who are unresponsive to such therapy, other causes of laryngeal irritation are considered. Surgical fundoplication is most effective in those who are responsive to acid-suppressive therapy.
© Springer Science+Business Media, LLC 2011
OBJECTIVES - We compare the success of different surgical options in the treatment of laryngeal webs.
METHODS - We performed a retrospective study spanning the years 1980 to 2005.
RESULTS - Eighteen patients were identified. The average age at diagnosis was 6 months (range, 1 day to 2.5 years). The presenting symptoms included weak cry, stridor, airway obstruction, and difficulty breathing. Associated cardiac defects consistent with the diagnosis of 22q-syndrome were present in 7 patients. Webs were classified as grade I (5 patients), grade II (2 patients), grade III (10 patients), or grade IV (1 patient) according to the Cohen classification. In 5 patients, only endoscopic lysis was required. The remaining 13 patients underwent open procedures; 9 patients in this group required tracheotomy. An average of 1.3 open airway procedures was necessary to achieve a decannulation rate of 89%. After operation, 34% of patients had residual webbing and 20% had a weak or aphonic voice.
CONCLUSIONS - Management of laryngeal webs is dependent on the severity of airway obstruction. Grade I and II webs can be treated endoscopically; more severe laryngeal webs usually require tracheotomy and open airway reconstruction.
A recently developed immersed-boundary method is used to model the flow-structure interaction associated with the human phonation. The glottal airflow is modeled as a two-dimensional incompressible flow driven by a constant subglottal pressure, and the vocal folds are modeled as a pair of three-layered, two-dimensional, viscoelastic structures. Both the fluid dynamics and viscoelasticity are solved on fixed Cartesian grids using a sharp-interface immersed boundary method. It is found that the vibration mode and frequency of the vocal fold model are associated with the eigenmodes of the structures, and that the transition of the vibration mode takes place during onset of the sustained vibration. The computed glottal waveforms of the volume flux, velocity, and pressure are reasonably realistic. The glottal flow features an unsteady jet whose direction is deflected by the large-scale vortices in the supraglottal region. A detailed analysis of the flow and vocal fold vibrations is conducted in order to gain insights into the biomechanics of phonation.
OBJECTIVES - We report on four cases of thyroglossal duct cyst (TGDC) excision using the Sistrunk procedure (resection of the mid-portion of the hyoid bone in continuity with a thyroglossal duct cyst tract) in which the airway was significantly injured. The patterns of injury, their treatment and outcomes as well as preventative measures are detailed.
METHODS - Retrospective analysis of four patients referred to a tertiary medical center after sustaining injury to the cricothyroid membrane and/or thyroid cartilages while undergoing a Sistrunk excision of a TGDC.
RESULTS - Three patients were repaired after a delay; one patient was immediately repaired. All four patients required application of cartilage grafts, and all ultimately required tracheotomy. Decannulation was achieved in the four patients after an average of 4.5 months, and none suffered from aspiration. Voice outcomes were poor in 3/4.
CONCLUSIONS - The Sistrunk procedure has been advocated for TGDC excision, citing a low recurrence rate. However, if the thyroid cartilage is mistaken for the hyoid bone, significant airway injury occurs. Urgent laryngotracheoplasty is indicated, but poor voice outcomes are anticipated.
SIGNIFICANCE - Surgeons employing the Sistrunk procedure to excise TGDC must remain oriented to midline cervical anatomy, particularly as the hyoid my override the thyroid notch in young children, placing the larynx at risk for significant injury.
OBJECTIVES - We describe a method for eliciting phonation in an in vivo rabbit preparation using low-frequency, bipolar pulsed stimulation of the cricothyroid muscles with airflow delivered to the glottis.
METHODS - Ten New Zealand White breeder rabbits weighing 3 to 5 kg were used in this study. The cricothyroid muscles were isolated bilaterally, and separate pairs of anode-cathode hooked-wire electrodes were inserted into each muscle. A Grass S-88 stimulator and 2 constant-current PSIU6 isolation units were used to deliver bipolar square wave pulses to each cricothyroid muscle, with airflow delivered to the glottis through a cuffed endotracheal tube.
RESULTS - Phonation was evoked with a 50-Hz, 4-mA stimulus train of 1-ms pulses delivered to each cricothyroid muscle. The pulse trains were on for 2 seconds and were repeated every 5 seconds over a period of 180 minutes. Airflow was delivered at 143 cm3/s, producing phonation measuring 71 to 85 dB sound pressure level.
CONCLUSIONS - Evoked phonation is feasible in rabbits by use of bipolar stimulation of the cricothyroid muscles with airflow delivered to the glottis. The in vivo rabbit preparation described may provide a useful small animal option for studies of evoked phonation. From the level and consistency of the adduction observed, we hypothesize that current spreading to the underlying adductor muscles and nerves resulted in neural pathway involvement beyond discrete activation of the cricothyroid muscle, providing sufficient approximation of the vocal folds for phonation.
Two adult female cynomolgus monkeys (Macaca fascicularis) that had been housed together for 4 months died within 2 weeks of each other after brief illnesses. Monkey No. 1 presented with collapse, watery stool, and hypothermia and died overnight. Monkey No. 2 presented with dyspnea, nasal discharge, leukopenia, and hypoproteinemia and was euthanized after 2 days. Both animals had peritoneal effusions, massive necrosis of pharyngeal, esophageal, and gastric mucosa, and multifocal hepatic and pancreatic necrosis. Monkey No. 2 also had lingual ulcers and locally extensive necrosis of spleen, adrenal glands, and lymph nodes. Large numbers of eosinophilic intranuclear inclusion bodies were present in epithelial and syncytial cells adjoining the necrotic foci in Monkey No. 2 but were absent in Monkey No. 1. Monkey No. 1 seroconverted to cercopithecine herpesvirus 1 (CHV-1, commonly known as herpes B) in the month before death. CHV-1 was isolated from a sample of stomach from Monkey No. 2, and electron microscopy of liver from this animal demonstrated herpesvirus particles within hepatocytes. Both animals were seropositive for simian type D retrovirus, and the virus was cultured from the liver of Monkey No. 2. A diagnosis of disseminated CHV-1 infection was made, possibly occurring secondary to immunosuppression due to infection with simian type D retrovirus. Although a high percentage of cynomolgus monkeys are apparently infected with CHV-1, disseminated disease is rare. Because infection with CHV-1 in humans is associated with a high fatality rate, familiarity with the lesions of disseminated infection with this virus is important.
A tissue-culture model has been developed for the study of fibroblasts from the canine vocal fold. Laryngeal tissue (lamina propria) obtained from euthanized dogs is rinsed, cut into 1-mm3 pieces, and incubated in 5% carbon dioxide at 37 degrees C. A confluent monolayer is established within several days. Detectable levels of elastin in the tissue culture supernatant are measured by an indirect enzyme-linked immunosorbent assay. Various external agents have been shown to affect elastin production. The effects of KTP laser irradiation, hydrocortisone (1.3 mumol/L), transforming growth factor-beta (10 ng/mL), and human leukocyte elastase have been measured. Thus the canine vocal fold fibroblast tissue culture is established as a model for further investigations to improve wound healing and to understand the wound-healing process following laryngeal microsurgery.