Publications by authors named "Alexander Gelbard"

73 Publications

Modeling Recurrence in Idiopathic Subglottic Stenosis With Mobile Peak Expiratory Flow.

Laryngoscope 2021 Jul 26. Epub 2021 Jul 26.

Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, U.S.A.

Objectives/hypothesis: We sought to establish normative peak expiratory flow (PEF) data for patients with idiopathic subglottic stenosis (iSGS), evaluate whether immediate changes in PEF after a procedure predict long-term treatment response, and test if a decline in longitudinal PEF is associated with disease recurrence.

Study Design: International, prospective, 3-year multicenter cohort study of 810 patients with untreated, newly diagnosed, or previously treated iSGS.

Methods: iSGS patients consented and enrolled in the North American Airway Collaborative (NoAAC) iSGS cohort recorded PEF data on a mobile smartphone app. Cox regression tested the associations between the magnitude of postoperative PEF improvement and longitudinal 90-day PEF decline with the risk of disease recurrence.

Results: Within the NoAAC iSGS cohort, 810 patients participated in a 3-year prospective study comparing surgical treatment efficacy and 385 had appropriate PEF measurements and follow-up data. Of those patients, 42% (161/385) required at least one operation during study follow-up. The mean PEF preceding operative intervention was 241 L/min (95% confidence interval [CI]: 120-380) corresponding to a predicted PEF of 52%. The mean increase in PEF following a procedure was 111 L/min (95% CI: 96-125 L/min). Interestingly, the magnitude of immediate PEF improvement was not predictive of disease recurrence (hazard ratio [HR] for 100 L/min increase = 0.90, 95% CI: 0.60-1.00). However, recurrence was associated with the magnitude of PEF decline over 90 days (30% vs. 10% decline, HR = 2.2, 95% CI: 1.5-3.0).

Conclusions: We provide normative PEF data on a large iSGS patient cohort. The degree of PEF improvement immediately after surgery was not associated with a longer procedure-free interval. However, a 30% decline in PEF over 90 days was associated with elevated risk of disease recurrence.

Level Of Evidence: 2 Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29760DOI Listing
July 2021

Endoscopic Resection and Mucosal Reconstitution With Epidermal Grafting: A Pilot Study in Idiopathic Subglottic Stenosis.

Otolaryngol Head Neck Surg 2021 Jul 13:1945998211028163. Epub 2021 Jul 13.

Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

Objective: To describe technical aspects and surgical outcomes of endoscopic resection and mucosal reconstitution with epidermal grafting (ie, the Maddern procedure) in the treatment of idiopathic subglottic stenosis.

Study Design: Medical record abstraction.

Setting: Johns Hopkins Hospital.

Methods: Retrospective series of 9 adults with idiopathic subglottic stenosis who underwent the Maddern procedure by a single surgeon over a 5-year period. Prespecified outcomes included (1) perioperative outcomes (Clavien-Dindo grade 4/5 complications, need for staged tracheostomy, hospital length of stay), (2) postoperative outcomes (peak expiratory flow rate [PEFR], need for subsequent airway surgery, tracheostomy at follow-up), and (3) patient-reported quality-of-life outcomes (Clinical COPD Questionnaire, Voice Handicap Index-10, Eating Assessment Tool-10, and 12-Item Short Form Version 2). Wilcoxon matched-pairs signed rank test and Kaplan-Meier analysis were performed.

Results: There were no Clavien-Dindo grade 4/5 complications; 2 patients required unplanned staged tracheostomy; and the median length of stay was 3 days. Following endoscopic resection and stent removal, a median of 2 laser resurfacing procedures were required. Two patients developed recurrent stenosis requiring cricotracheal resection (CTR). There were significant improvements in PEFR, Clinical COPD Questionnaire, and Voice Handicap Index-10, without significant difference in Eating Assessment Tool-10. The 12-Item Short Form Version 2 approximated the population norm. Kaplan-Meier analysis demonstrated significant improvement in time to surgery after the final laser resurfacing.

Conclusion: The Maddern procedure has a low complication rate and offers durable physiologic improvement in PEFR, limiting need for additional procedures. Risks included need for CTR salvage, temporary tracheostomy, phlegm accumulation, and laryngospasm. It is a surgical option for patients with short dilation intervals who prefer to avoid the risks of CTR.
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http://dx.doi.org/10.1177/01945998211028163DOI Listing
July 2021

Bilateral Vocal Fold Paralysis Following Electrocution Injury.

OTO Open 2021 Apr-Jun;5(2):2473974X211023728. Epub 2021 Jun 16.

Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

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http://dx.doi.org/10.1177/2473974X211023728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216378PMC
June 2021

Early Intervention for the Treatment of Acute Laryngeal Injury After Intubation-Excellent Outcomes With Low Risk?-Reply.

JAMA Otolaryngol Head Neck Surg 2021 Jun 17. Epub 2021 Jun 17.

Department of Otolaryngology, Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.

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http://dx.doi.org/10.1001/jamaoto.2021.1201DOI Listing
June 2021

Impact of Adjuvant Medical Therapies on Surgical Outcomes in Idiopathic Subglottic Stenosis.

Laryngoscope 2021 Jun 12. Epub 2021 Jun 12.

Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, U.S.A.

Objectives/hypothesis: Adjuvant medications including proton pump inhibitors (PPI), antibiotics (trimethoprim/sulfamethoxazole [TMP-SMX]), and inhaled corticosteroids (ICS) may be prescribed for patients with idiopathic subglottic stenosis (iSGS). We describe medication use with endoscopic dilation (ED) or endoscopic resection with medical treatment (ERMT) and evaluate impact on outcomes.

Study Design: International, prospective, 3-year multicenter cohort study of 810 patients with untreated, newly diagnosed, or previously treated iSGS.

Methods: Post hoc secondary analysis of prospectively collected North American Airway Collaborative data on outcomes linked with adjuvant medication utilization. Primary outcome was time to recurrent operation, evaluated using Kaplan-Meier curves and Cox regression analysis. Secondary outcomes of change in peak expiratory flow (PEF) and clinical chronic obstructive pulmonary disease questionnaire (CCQ) score over 12 months were compared.

Results: Sixty-one of 129 patients undergoing ED received PPI (47%), and 10/143 patients undergoing ED received ICS (7%). TMP-SMX was used by 87/115 patients (76%) undergoing EMRT. PPI use in the ED group did not affect time to recurrence (hazard ratio [HR] = 1.00, 95% confidence interval [CI]: 0.53-1.88; P = .99) or 12-month change in PEF (L/min) (median [interquartile range], 12.0 [10.7-12.2] vs. 8.7 [-5.1 to 24.9]; P = .59), but was associated with 12-month change in CCQ (-0.05 [-0.97 to 0.75] vs. -0.50 [-1.60 to 0.20]; P = .04). ICS did not affect outcome measures. TMP-SMX use in ERMT did not affect time to recurrence (HR = 0.842, 95% CI: 0.2345-3.023; P = .79), PEF at 12 months (75 [68-89] vs. 81 [68-89]; P = .92), or 12-month change in CCQ (0.20 [-1.05 to 0.47] vs. -0.30 [-1.00 to 0.10]; P = .45).

Conclusion: There is no standard practice for prescribing adjuvant medications. These data do not support that adjuvant medications prolong time to recurrence or increase PEF. Patients with iSGS and gastroesophageal reflux disease may experience some symptom benefit with PPI.

Level Of Evidence: Level 3 Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29675DOI Listing
June 2021

A Rare Laryngeal Presentation of Stevens-Johnson Syndrome.

Laryngoscope 2021 May 4. Epub 2021 May 4.

Department of Otolaryngology - Head & Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, U.S.A.

Stevens-Johnson syndrome (SJS) is a rare but severe mucocutaneous epidermolysis commonly triggered by medications. SJS is characterized by mucocutaneous lesions of the trunk, face, and limbs, as well as the oral cavity, gastrointestinal tract, and respiratory tract. Although uncommon, laryngeal involvement in SJS can lead to severe respiratory, phonatory and deglutitive complications. Providers caring for patients with SJS should maintain a high index of suspicion for laryngeal involvement and low threshold to solicit Otolaryngology consultation. Laryngeal complications can be more expediently managed when anticipated early in the course of disease. Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29598DOI Listing
May 2021

Delayed Tracheal Perforation Following Total Thyroidectomy.

Laryngoscope 2021 Mar 30. Epub 2021 Mar 30.

Department Otolaryngology Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, U.S.A.

Delayed tracheal rupture following total thyroidectomy (TT) is rare and represents a potential airway emergency. A 34-year-old female with Felty Syndrome underwent TT for Hashimoto's thyroiditis. On post-operative day 10, she presented with subcutaneous emphysema and an anterolateral tracheal perforation on CT scan. Urgent operative exploration revealed transmural tracheal necrosis and a 5 mm perforation. This was oversewn with non-absorbable suture and a strap muscle flap rotated over the defect to promote healing. Repeat direct laryngoscopy at 72 hours revealed healing tissue. Tracheal necrosis and perforation following TT constitutes a potential airway emergency and should be promptly explored and repaired. Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29534DOI Listing
March 2021

Association of Social Determinants of Health with Time to Diagnosis and Treatment Outcomes in Idiopathic Subglottic Stenosis.

Ann Otol Rhinol Laryngol 2021 Feb 25:3489421995283. Epub 2021 Feb 25.

Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles, CA, USA.

Objectives: To examine whether social determinants of health (SDH) factors are associated with time to diagnosis, treatment selection, and time to recurrent surgical intervention in idiopathic subglottic stenosis (iSGS) patients.

Methods: Adult patients with diagnosed iSGS were recruited prospectively (2015-2017) via clinical providers as part of the North American Airway Collaborative (NoAAC) and via an online iSGS support community on Facebook. Patient-specific SDH factors included highest educational attainment (self-reported), median household income (matched from home zip code via U.S. Census data), and number of close friends (self-reported) as a measure of social support. Main outcomes of interest were time to disease diagnosis (years from symptom onset), treatment selection (endoscopic dilation [ED] vs cricotracheal resection [CTR] vs endoscopic resection with adjuvant medical therapy [ERMT]), and time to recurrent surgical intervention (number of days from initial surgical procedure) as a surrogate for disease recurrence.

Results: The total 810 participants were 98.5% female, 97.2% Caucasian, and had a median age of 50 years (IQR, 43-58). The cohort had a median household income of $62 307 (IQR, $50 345-$79 773), a median of 7 close friends (IQR, 4-10), and 64.7% of patients completed college or graduate school. Education, income, and number of friends were not associated with time to diagnosis via multivariable linear regression modeling. Univariable multinominal logistic regression demonstrated an association between education and income for selecting ED versus ERMT, but no associations were noted for CTR. No associations were noted for time to recurrent surgical procedure via Kaplan Meier modeling and Cox proportional hazards regression.

Conclusions: Patient education, income, and social support were not associated with time to diagnosis or time to disease recurrence. This suggests additional patient, procedure, or disease-specific factors contribute to the observed variations in iSGS surgical outcomes.
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http://dx.doi.org/10.1177/0003489421995283DOI Listing
February 2021

Multi-Institutional Analysis of Outcomes in Supraglottic Jet Ventilation with a Team-Based Approach.

Laryngoscope 2021 Feb 20. Epub 2021 Feb 20.

Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, U.S.A.

Objectives/hypothesis: To evaluate the safety and complications of endoscopic airway surgery using supraglottic jet ventilation with a team-based approach.

Study Design: Retrospective cohort study.

Methods: Subjects at two academic institutions diagnosed with laryngotracheal stenosis who underwent endoscopic airway surgery with jet ventilation between January 2008 and December 2018 were identified. Patient characteristics (age, gender, race, follow-up duration) and comorbidities were extracted from the electronic health record. Records were reviewed for treatment approach, intraoperative data, and complications (intraoperative, acute postoperative, and delayed postoperative).

Results: Eight hundred and ninety-four patient encounters from 371 patients were identified. Intraoperative complications (unplanned tracheotomy, profound or severe hypoxic events, barotrauma, laryngospasm) occurred in fewer than 1% of patient encounters. Acute postoperative complications (postoperative recovery unit [PACU] rapid response, PACU intubation, return to the emergency department [ED] within 24 hours of surgery) were rare, occurring in fewer than 3% of patient encounters. Delayed postoperative complications (return to the ED or admission for respiratory complaints within 30 days of surgery) occurred in fewer than 1% of patient encounters. Diabetes mellitus, active smoking, and history of previous tracheotomy were independently associated with intraoperative, acute, and delayed complications.

Conclusions: Employing a team-based approach, jet ventilation during endoscopic airway surgery demonstrates a low rate of complications and provides for safe and successful surgery.

Level Of Evidence: Level 4 Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29431DOI Listing
February 2021

Early Intervention for the Treatment of Acute Laryngeal Injury After Intubation.

JAMA Otolaryngol Head Neck Surg 2021 03;147(3):232-237

Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.

Importance: Patients with laryngeal injury after endotracheal intubation often present long after initial injury with mature fibrosis compromising cricoarytenoid joint mobility and glottic function.

Objective: To compare functional outcomes between early and late intervention for intubation-related laryngeal injury.

Design, Setting, And Participants: This retrospective cohort study involved 29 patients with laryngeal injury resulting from endotracheal intubation who were evaluated at a tertiary care center between May 1, 2014, and June 1, 2018. Ten patients with intubation injury to the posterior glottis who received early treatment were compared with 19 patients presenting with posterior glottic stenosis who received late treatment. Statistical analysis was performed from May 1 to July 1, 2019.

Exposures: Early intervention, defined as a procedure performed 45 days or less after intubation, and late treatment, defined as an intervention performed greater than 45 days after intubation.

Main Outcomes And Measures: Patient-specific and intervention-specific covariates were compared between the 2 groups, absolute differences with 95% CIs were calculated, and time to tracheostomy decannulation was compared using log-rank testing.

Results: The 2 groups had similar demographic characteristics and a similar burden of comorbid disease. Ten patients who received early intervention (7 women [70%]; median age, 59.7 years [range, 31-72 years]; median, 34.7 days to presentation [IQR, 1.5-44.8 days]) were compared with 19 patients who received late intervention (11 women [58%]; median age, 53.8 years [range, 34-73 years]; median, 341.9 days to presentation [IQR, 132.7-376.3 days]). Nine of 10 patients (90%) who received early intervention and 11 of 19 patients (58%) who received late interventions were decannulated at last follow-up (absolute difference, 32%; 95% CI, -3% to 68%). Patients who received early treatment required fewer total interventions than patients with mature lesions (mean, 2.2 vs 11.5; absolute difference, 9.3; 95% CI, 6.4-12.1). In addition, none of the patients who received early treatment required an open procedure, whereas 17 patients (90%) with mature lesions required open procedures to pursue decannulation.

Conclusions And Relevance: This study suggests that early intervention for patients with postintubation laryngeal injury was associated with a decreased duration of tracheostomy dependence, a higher rate of decannulation, and fewer surgical procedures compared with late intervention. Patients who underwent early intervention also avoided open reconstruction. These findings may bear relevance to the management of patients requiring extended durations of endotracheal intubation during recovery for critical illness related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
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http://dx.doi.org/10.1001/jamaoto.2020.4517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844690PMC
March 2021

Quantitative Assessment of the Immune Microenvironment in Patients With Iatrogenic Laryngotracheal Stenosis.

Otolaryngol Head Neck Surg 2021 06 8;164(6):1257-1264. Epub 2020 Dec 8.

Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Objective: Iatrogenic laryngotracheal stenosis (iLTS) is characterized by fibroinflammatory narrowing of the upper airway and is most commonly caused by intubation injury. Evidence suggests a key role for CD4 T cells in its pathogenesis. The objective of this study is to validate emerging multiplex immunofluorescence (mIF) technology for use in the larynx and trachea while quantitatively characterizing the immune cell infiltrate in iLTS. In addition to analyzing previously unstudied immune cell subsets, this study aims to validate previously observed elevations in the immune checkpoint PD-1 and its ligand PD-L1 while exploring their spatial and cellular distributions in the iLTS microenvironment.

Study Design: Controlled ex vivo cohort study.

Setting: Tertiary care center.

Methods: mIF staining was performed with formalin-fixed, paraffin-embedded slides from 10 patients with iLTS who underwent cricotracheal resection and 10 control specimens derived from rapid autopsy for CD4, CD8, CD20, FoxP3, PD-1, PD-L1, and cytokeratin.

Results: There was greater infiltration of CD4 T cells, CD8 T cells, CD20 B cells, FoxP3CD4 Tregs, and FoxP3CD8 early effector T cells in the submucosa of iLTS specimens as compared with controls ( < .05 for all). PD-1 was primarily expressed on T cells and PD-L1 predominantly on CD4 cells and "other" cells.

Conclusion: This study leverages the power of mIF to quantify the iLTS immune infiltrate in greater detail. It confirms the highly inflammatory nature of iLTS, with CD4 cells dominating the immune cell infiltrate; it further characterizes the cellular and spatial distribution of PD-1 and PD-L1; and it identifies novel immunologic targets in iLTS.
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http://dx.doi.org/10.1177/0194599820978271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169517PMC
June 2021

Utilization and Influence of Online Support Communities in Idiopathic Subglottic Stenosis Patients.

Laryngoscope 2021 08 29;131(8):1821-1827. Epub 2020 Sep 29.

Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University, Nashville, Tennessee, U.S.A.

Objectives: To determine the factors that shape utilization of social media-based online support communities (OSCs) and study the influence of these communities on medical decision-making in patients with Idiopathic Subglottic Stenosis (iSGS).

Study Design: Survey study.

Methods: A survey investigating OSC use was sent to the 1,056 members of the North American Airway Collaborative (NoAAC) iSGS cohort in January 2018. Responses were merged with the existing NoAAC data set containing extensive demographic data, disease-specific history, and responses to validated patient-reported outcome measures.

Results: A total of 755 individuals with iSGS and mean age of 51.8 ± 11.6 years were included (99% female, 98% white, 63% college educated) and 58% were OSC users. Younger age, female gender, and college education were each associated with OSC use (P < .05). Users spent 2.5 ± 3.3 hours per week on the platforms. Time spent on OSC was not associated with total number of prior treatments. Higher disease anxiety (FoP-Q, R = 0.26, P < .001), lower social support (MOS, R = -0.12, P = .037), and lower level of shared-decision-making with the treating physician (SDM-Q9, R = -0.16, P = .007) were weakly associated with more hours spent engaging an OSC. OSC use influenced treatment and physician choice in 35% and 26% of users, respectively. Increased time spent on OSC use was associated with increased influence on patient medical decisions regarding treatment, surgery, and physician choice (P < .05).

Conclusion: OSC engagement is common in patients with iSGS. Disease anxiety, social support, and relationship with the physician may influence OSC utilization. More OSC engagement weakly associated with greater OSC influence on patient medical decision-making.

Level Of Evidence: NA. Laryngoscope, 131:1821-1827, 2021.
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http://dx.doi.org/10.1002/lary.29110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005507PMC
August 2021

The Proximal Airway Is a Reservoir for Adaptive Immunologic Memory in Idiopathic Subglottic Stenosis.

Laryngoscope 2021 03 30;131(3):610-617. Epub 2020 Jun 30.

Department of Medicine, Division of Infectious Disease, Vanderbilt University Medical Center, Nashville, Tennessee, U.S.A.

Objectives/hypothesis: Characterization of the localized adaptive immune response in the airway scar of patients with idiopathic subglottic stenosis (iSGS).

Study Design: Basic Science.

Methods: Utilizing 36 patients with subglottic stenosis (25 idiopathic subglottic stenosis [iSGS], 10 iatrogenic post-intubation stenosis [iLTS], and one granulomatosis with polyangiitis [GPA]) we applied immunohistochemical and immunologic techniques coupled with RNA sequencing.

Results: iSGS, iLTS, and GPA demonstrate a significant immune infiltrate in the subglottic scar consisting of adaptive cell subsets (T cells along with dendritic cells). Interrogation of T cell subtypes showed significantly more CD69 CD103 CD8 tissue resident memory T cells (T ) in the iSGS airway scar than iLTS specimens (iSGS vs. iLTS; 50% vs. 28%, P = .0065). Additionally, subglottic CD8 clones possessed T-cell receptor (TCR) sequences with known antigen specificity for viral and intracellular pathogens.

Conclusions: The human subglottis is significantly enriched for CD8 tissue resident memory T cells in iSGS, which possess TCR sequences proven to recognize viral and intracellular pathogens. These results inform our understanding of iSGS, provide a direction for future discovery, and demonstrate immunologic function in the human proximal airway. Laryngoscope, 131:610-617, 2021.
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http://dx.doi.org/10.1002/lary.28840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951501PMC
March 2021

Familial Aggregation in Idiopathic Subglottic Stenosis.

Otolaryngol Head Neck Surg 2020 11 30;163(5):1011-1017. Epub 2020 Jun 30.

Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland, USA.

Objective: To evaluate inheritance patterns and define the familial clustering rate of idiopathic subglottic stenosis (iSGS).

Study Design: Retrospective observational study.

Setting: International multicenter collaborative of >30 tertiary care centers.

Methods: Patients with a clinically confirmed iSGS diagnosis within the North American Airway Collaborative's iSGS cohort consented between 2014 and 2018 were eligible for enrollment. Patient demographics and disease severity were abstracted from the collaborative's iSGS longitudinal registry. Pedigrees of affected families were created.

Results: A total of 810 patients with iSGS were identified. Positive family history for iSGS was reported in 44 patients in 20 families. The rate of familial clustering in iSGS is 2.5%. Mean age of disease onset is 42.6 years. Of the 44 patients with familial aggregation of iSGS, 42 were female and 2 were male; 13 were mother-daughter pairs and 2 were father-daughter pairs. There were 3 sister-sister pairs. There was 1 niece-aunt pair and 2 groups of 3 family members. One pedigree demonstrated 2 affected mother-daughter pairs, with the mothers being first-degree paternal cousins. Inheritance is non-Mendelian, and anticipation is present in 11 of 13 (84%) parent-offspring pairs. The mean age of onset between parents (48.4 years) and offspring (36.1 years) was significantly different ( = .016).

Conclusion: This study quantifies the rate of familial clustering of iSGS at 2.5%. Inheritance is non-Mendelian, and disease demonstrates anticipation. These data suggest that there may be a genetic contribution in iSGS.
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http://dx.doi.org/10.1177/0194599820935402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809487PMC
November 2020

Increased Expression of PD-1 and PD-L1 in Patients With Laryngotracheal Stenosis.

Laryngoscope 2021 05 17;131(5):967-974. Epub 2020 Jun 17.

Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A.

Objectives: Laryngotracheal stenosis (LTS) is a fibrotic condition of the upper airway. Recent evidence suggests dysregulated host immunity plays a role in LTS development and progression. The programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis, targeted by paradigm-shifting immunotherapies for cancer treatment, has also recently been implicated in the pathogenesis of fibrotic pulmonary disease. However, a role for the PD-1/PD-L1 axis in the proximal airway fibrosis seen in LTS patients has not been explored.

Study Design: Controlled ex vivo study.

Methods: Expression of PD-1, PD-L1, CD4, and CD8 were evaluated using immunohistochemical staining of cricotracheal resection specimens from postintubation iatrogenic laryngotracheal stenosis (iLTS), idiopathic subglottic stenosis (iSGS) patients, and normal controls derived from rapid autopsy (n = 8 per group). Fibroblasts derived from iLTS scar were also treated with transforming growth factor beta 1 (TGFβ1) and analyzed for PD-L1 expression by quantitative real-time polymerase chain reaction (n = 6).

Results: iLTS specimens exhibited increased expression of PD-1, PD-L1, and CD4 (all P < .0167) compared to controls, whereas iSGS specimens exhibited increased expression of PD-1 and CD4 (P < .0167) compared to controls. PD-1, PD-L1, and CD4 showed periepithelial patterns of expression in both disease cohorts. TGFβ1 treatment of iLTS fibroblasts increased expression of PD-L1 (the cognate ligand for PD-1).

Conclusion: Expression of both PD-1 and its ligand PD-L1 are significantly greater in patients with iLTS compared to controls, and PD-1 expression is also elevated in patients with iSGS. Given published evidence implicating the PD-1/PD-L1 axis in pulmonary fibrosis, this suggests a possible role for checkpoint inhibitors targeting the PD-1/PD-L1 axis for the treatment of LTS.

Level Of Evidence: N/A Laryngoscope, 131:967-974, 2021.
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http://dx.doi.org/10.1002/lary.28790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817064PMC
May 2021

Laryngotracheal Mucosal Surface Expression of Candidate Biomarkers in Idiopathic Subglottic Stenosis.

Laryngoscope 2021 02 5;131(2):342-349. Epub 2020 May 5.

Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.

Objectives: Idiopathic subglottic stenosis (iSGS) is an inflammatory process leading to fibrosis and narrowing of the laryngotracheal airway. There is variability in patient response to surgical intervention, but the mechanisms underlying this variability are unknown. In this pilot study, we measure expression of candidate targets at the mucosal surface of the subglottis in iSGS patients. We aim to identify putative biomarkers for iSGS that provide insights into the molecular basis of disease progression, yield a gene signature for the disease, and/or predict a response to therapy.

Study Design: In vitro comparative study of human cells.

Methods: Levels of candidate transcripts and proteins were measured in healthy and stenotic laryngotracheal tissue specimens taken from the mucosal surface in 16 iSGS patients undergoing endoscopic balloon dilation. Pre- and post-operative pulmonary function test and patient reported voice and breathing outcomes were also assessed. Unsupervised clustering was used to define patient subgroups based on expression profile.

Results: Pulmonary function and voice and breathing outcome metrics demonstrated significant post-operative improvement. Transcript levels of αSMA, CCL2, COL1A1, COL3A1, FN1, IFNG, and TGFB1 and protein levels of CCL2, IFNG, and IL-6 were significantly upregulated in stenotic as compared to healthy tissues. Marked heterogeneity was observed in the patterns of expression of candidate markers across individuals and tissue types. Patient subgroups defined by expression profile did not show a statistically significant difference in dilation interval.

Conclusion: Pro-inflammatory and pro-fibrotic pathways are significantly upregulated along the mucosal surface of stenotic laryngotracheal tissues, and CCL2 and IFNG merit further investigation as potential iSGS biomarkers.

Level Of Evidence: 4 Laryngoscope, 131:342-349, 2021.
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http://dx.doi.org/10.1002/lary.28712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641987PMC
February 2021

The authors reply.

Crit Care Med 2020 05;48(5):e431

Department of Otolaryngology, Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN Division of Allergy, Pulmonary, and Critical Care, Vanderbilt University Medical Center, Nashville, TN, and Tennessee Valley Veteran's Affairs Geriatric Research Education Clinical Center (GRECC), Nashville, TN, and Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Vanderbilt University Medical Center, Nashville, TN Department of Otolaryngology, Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, and Division of Laryngology, Vanderbilt University Medical Center, Nashville, TN.

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http://dx.doi.org/10.1097/CCM.0000000000004301DOI Listing
May 2020

Unilateral Vocal Fold Immobility-More Common Than We Think?-Reply.

JAMA Otolaryngol Head Neck Surg 2020 06;146(6):588

Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.

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http://dx.doi.org/10.1001/jamaoto.2020.0138DOI Listing
June 2020

The authors reply.

Crit Care Med 2020 04;48(4):e338-e339

Department of Otolaryngology, Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN Division of Allergy, Pulmonary, and Critical Care, Vanderbilt University Medical Center, Nashville, TN, and Tennessee Valley Veteran's Affairs Geriatric Research Education Clinical Center (GRECC), Nashville, TN, and Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Vanderbilt University Medical Center, Nashville, TN Department of Otolaryngology, Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, and Division of Laryngology, Vanderbilt University Medical Center, Nashville, TN.

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http://dx.doi.org/10.1097/CCM.0000000000004253DOI Listing
April 2020

Adult Aortotracheal Fistula as Sequela of Double Aortic Arch Repair in Infancy: A Case Report.

Ann Otol Rhinol Laryngol 2020 Jul 31;129(7):649-652. Epub 2020 Jan 31.

Department of Otolaryngology, Vanderbilt University Medical Center, Nashville, TN, USA.

Introduction: Double aortic arch is a rare congenital malformation of the aortic arch that most frequently presents in childhood. Early surgical intervention typically yields excellent outcomes.

Objectives: To describe aortotracheal fistula as a rare, yet serious complication of vascular ring and subsequent aortic aneurysm in an adult patient.

Methods: Clinical history, as well as radiographic and endoscopic imaging were obtained to describe the development, diagnosis, and clinical course of this patient's aortotracheal fistula. Additionally, follow up data was obtained to document the healing of this fistula after surgical repair.

Results: We describe a case of a 46-year-old male with DiGeorge Syndrome and a double aortic arch, repaired in childhood, which developed into an aortotracheal fistula after tracheostomy placement as an adult.

Conclusions: This case demonstrates that dangerous complications of a double aortic arch can persist into adulthood, even after surgical repair in infancy. Each patient's unique anatomy must be considered when thinking about airway management and prevention of complications of this rare congenital anomaly.
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http://dx.doi.org/10.1177/0003489420904739DOI Listing
July 2020

Unilateral Vocal Fold Immobility After Prolonged Endotracheal Intubation.

JAMA Otolaryngol Head Neck Surg 2020 02;146(2):160-167

Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.

Importance: Endotracheal intubation and mechanical ventilation are life-saving treatments for acute respiratory failure but are complicated by significant rates of dyspnea and dysphonia after extubation. Unilateral vocal fold immobility (UVFI) after extubation can alter respiration and phonation, but its incidence, risk factors, and pathophysiology remain unclear.

Objectives: To determine the incidence of UVFI after prolonged (>12 hours) mechanical ventilation in a medical intensive care unit and investigate associated clinical risk factors for UVFI after prolonged mechanical ventilation.

Design, Setting, And Participants: This subgroup analysis of a prospective cohort study was conducted in a single-center medical intensive care unit from August 17, 2017, through May 31, 2018, among 100 consecutive adult patients who were intubated for more than 12 hours. Patients were identified within 36 hours of extubation and recruited for study enrollment. Those with an established tracheostomy prior to mechanical ventilation, known laryngeal or tracheal pathologic characteristics, or a history of head and neck radiotherapy were excluded.

Exposure: Invasive mechanical ventilation via an endotracheal tube.

Main Outcomes And Measures: The incidence of UVFI as determined by flexible nasolaryngoscopy.

Results: One hundred patients (62 men [62%]; median age, 58.5 years [range, 19.0-87.0 years]) underwent endoscopic evaluation after extubation. Seven patients had UVFI, of which 6 cases (86%) were left sided. Patients with hypotension while intubated (odds ratio [OR], 10.8; 95% CI, 1.6 to ∞), patients requiring vasopressors while intubated (OR, 16.7; 95% CI, 2.4 to ∞), and patients with a preadmission diagnosis of peripheral vascular disease (OR, 6.2; 95% CI, 1.2-31.9) or coronary artery disease (OR, 5.1; 95% CI, 1.0-25.5) were more likely to develop UVFI.

Conclusions And Relevance: Unilateral vocal fold immobility occurred in 7 of 100 patients in the medical intensive care unit who were intubated for more than 12 hours. Unilateral vocal fold immobility was associated with inpatient hypotension and preadmission vascular disease, suggesting that ischemia of the recurrent laryngeal nerve may play a role in disease pathogenesis.
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http://dx.doi.org/10.1001/jamaoto.2019.3969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990766PMC
February 2020

The Incidence of Laryngotracheal Stenosis in Neonates With a History of Ventilator-Associated Pneumonia.

Laryngoscope 2020 09 4;130(9):2252-2255. Epub 2019 Dec 4.

Surgical Outcomes Center for Kids, Vanderbilt University Medical Center, Nashville, Tennessee, U.S.A.

Objectives/hypothesis: Neonatal patients requiring prolonged intubation are susceptible to both infection and laryngotracheal stenosis (LTS). This study investigated the effect of ventilator-associated pneumonia (VAP) on the development of LTS in neonates.

Study Design: Retrospective case-control study.

Methods: The incidence of LTS in neonates with VAP was compared with the incidence of LTS in matched intubated controls without VAP. Patients were treated at a tertiary-care medical center from 2004 to 2014. Eligible patient records were assessed for the development of LTS. Demographics, medical comorbidities, infection characteristics, and treatment variables were compared using unpaired t test or χ test. Statistical significance was set a priori at P < .05.

Results: When comparing the VAP patients with matched non-VAP controls, we found no significant differences in the incidence of LTS (VAP vs. non-VAP, 8.3% vs. 6.7%; P = .73). In subgroup analysis of the VAP cohort, LTS and non-LTS patients demonstrated similar VAP organisms on broncho-alveolar lavage (Klebsiella pneumoniae, Pseudomonas aeroginosa, Escherichia coli, methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, and Enterobacter). Additionally, within the VAP cohort, LTS and non-LTS patients showed similar gestational age (LTS vs. non-LTS, 31.3 days vs. 28.1 days; P = .22), birth weight (LTS vs. non-LTS, 1.6 kg vs. 1.2 kg; P = .33), and similar intubation duration (LTS vs. non-LTS, 37.8 days vs. 27.5 days; P = .52).

Conclusions: In this neonatal cohort, VAP was not associated with an increased incidence of LTS. Given severity of the burden of LTS on the healthcare system, multi-institutional longitudinal investigation into contributing risk factors for neonatal LTS is warranted.

Level Of Evidence: NA Laryngoscope, 130:2252-2255, 2020.
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http://dx.doi.org/10.1002/lary.28371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302688PMC
September 2020

Comparative Treatment Outcomes for Patients With Idiopathic Subglottic Stenosis.

JAMA Otolaryngol Head Neck Surg 2020 01;146(1):20-29

Vanderbilt Center for Quantitative Sciences, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.

Importance: Surgical treatment comparisons in rare diseases are difficult secondary to the geographic distribution of patients. Fortunately, emerging technologies offer promise to reduce these barriers for research.

Objective: To prospectively compare the outcomes of the 3 most common surgical approaches for idiopathic subglottic stenosis (iSGS), a rare airway disease.

Design, Setting, And Participants: In this international, prospective, 3-year multicenter cohort study, 810 patients with untreated, newly diagnosed, or previously treated iSGS were enrolled after undergoing a surgical procedure (endoscopic dilation [ED], endoscopic resection with adjuvant medical therapy [ERMT], or cricotracheal resection [CTR]). Patients were recruited from clinician practices in the North American Airway Collaborative and an online iSGS community on Facebook.

Main Outcomes And Measures: The primary end point was days from initial surgical procedure to recurrent surgical procedure. Secondary end points included quality of life using the Clinical COPD (chronic obstructive pulmonary disease) Questionnaire (CCQ), Voice Handicap Index-10 (VHI-10), Eating Assessment Test-10 (EAT-10), the 12-Item Short-Form Version 2 (SF-12v2), and postoperative complications.

Results: Of 810 patients in this cohort, 798 (98.5%) were female and 787 (97.2%) were white, with a median age of 50 years (interquartile range, 43-58 years). Index surgical procedures were ED (n = 603; 74.4%), ERMT (n = 121; 14.9%), and CTR (n = 86; 10.6%). Overall, 185 patients (22.8%) had a recurrent surgical procedure during the 3-year study, but recurrence differed by modality (CTR, 1 patient [1.2%]; ERMT, 15 [12.4%]; and ED, 169 [28.0%]). Weighted, propensity score-matched, Cox proportional hazards regression models showed ED was inferior to ERMT (hazard ratio [HR], 3.16; 95% CI, 1.8-5.5). Among successfully treated patients without recurrence, those treated with CTR had the best CCQ (0.75 points) and SF-12v2 (54 points) scores and worst VHI-10 score (13 points) 360 days after enrollment as well as the greatest perioperative risk.

Conclusions And Relevance: In this cohort study of 810 patients with iSGS, endoscopic dilation, the most popular surgical approach for iSGS, was associated with a higher recurrence rate compared with other procedures. Cricotracheal resection offered the most durable results but showed the greatest perioperative risk and the worst long-term voice outcomes. Endoscopic resection with medical therapy was associated with better disease control compared with ED and had minimal association with vocal function. These results may be used to inform individual patient treatment decision-making.
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http://dx.doi.org/10.1001/jamaoto.2019.3022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824232PMC
January 2020

Incidence and Outcomes of Acute Laryngeal Injury After Prolonged Mechanical Ventilation.

Crit Care Med 2019 12;47(12):1699-1706

Department of Otolaryngology, Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN.

Objectives: Upper airway injury is a recognized complication of prolonged endotracheal intubation, yet little attention has been paid to the consequences of laryngeal injury and functional impact. The purpose of our study was to prospectively define the incidence of acute laryngeal injury and investigate the impact of injury on breathing and voice outcomes.

Design: Prospective cohort study.

Setting: Tertiary referral critical care center.

Patients: Consecutive adult patients intubated greater than 12 hours in the medical ICU from August 2017 to May 2018 who underwent laryngoscopy within 36 hours of extubation.

Interventions: Laryngoscopy following endotracheal intubation.

Measurements And Main Results: One hundred consecutive patients (62% male; median age, 58.5 yr) underwent endoscopic examination after extubation. Acute laryngeal injury (i.e., mucosal ulceration or granulation tissue in the larynx) was present in 57 patients (57%). Patients with laryngeal injury had significantly worse patient-reported breathing (Clinical Chronic Obstructive Pulmonary Disease Questionnaire: median, 1.05; interquartile range, 0.48-2.10) and vocal symptoms (Voice Handicap Index-10: median, 2; interquartile range, 0-6) compared with patients without injury (Clinical Chronic Obstructive Pulmonary Disease Questionnaire: median, 0.20; interquartile range, 0-0.80; p < 0.001; and Voice Handicap Index-10: median, 0; interquartile range, 0-1; p = 0.005). Multivariable logistic regression independently associated diabetes, body habitus, and endotracheal tube size greater than 7.0 with the development of laryngeal injury.

Conclusions: Acute laryngeal injury occurs in more than half of patients who receive mechanical ventilation and is associated with significantly worse breathing and voicing 10 weeks after extubation. An endotracheal tube greater than size 7.0, diabetes, and larger body habitus may predispose to injury. Our results suggest that acute laryngeal injury impacts functional recovery from critical illness.
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http://dx.doi.org/10.1097/CCM.0000000000004015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880159PMC
December 2019

Epiglottitis.

N Engl J Med 2019 Aug;381(9):e15

Vanderbilt University Medical Center, Nashville, TN

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http://dx.doi.org/10.1056/NEJMicm1816761DOI Listing
August 2019

Open Airway Surgery in a Paraplegic: The Importance of an Adequate Cough.

Ann Otol Rhinol Laryngol 2019 Dec 31;128(12):1194-1197. Epub 2019 Jul 31.

Department of Otolaryngology - Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.

Objectives: To describe a case of open airway surgery with postoperative respiratory complications in a paraplegic woman and to review the unique respiratory physiology seen in patients with a history of cervical or thoracic spinal cord injury (SCI).

Methods: Case report and literature review.

Results: We describe the case of a 25-year-old paraplegic who developed tracheal stenosis after tracheotomy, eventually requiring tracheal resection and re-anastomosis. Her postoperative course was complicated by mucus plugging and severe atelectasis, necessitating reintubation. After extubation, the patient reported difficulty expectorating secretions ever since her SCI, requiring manual abdominal pressure from her family members to assist her when she needed to cough.

Conclusion: This first report of cricotracheal resection in a patient with paraplegia following SCI highlights the importance of an and demonstrates the unique respiratory management necessary for patients with SCI.
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http://dx.doi.org/10.1177/0003489419866471DOI Listing
December 2019

The impact of social determinants of health on laryngotracheal stenosis development and outcomes.

Laryngoscope 2020 04 29;130(4):1000-1006. Epub 2019 Jul 29.

Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.

Objectives: The social determinants of health affect a wide range of health outcomes and risks. To date, there have been no studies evaluating the impact of social determinants of health on laryngotracheal stenosis (LTS). We sought to describe the social determinants in a cohort of LTS patients and explore their association with treatment outcome.

Methods: Subjects diagnosed with LTS undergoing surgical procedures between 2013 and 2018 were identified. Matched controls were identified from intensive care unit (ICU) patients who underwent intubation for greater than 24 hours. Medical comorbidities, stenosis characteristics, and patient demographics were abstracted from the clinical record. Tracheostomy at last follow-up was recorded from the medical record and phone calls. Socioeconomic data was obtained from the American Community Survey.

Results: One hundred twenty-two cases met inclusion criteria. Cases had significantly lower education compared to Tennessee (P = .009) but similar education rates as ICU controls. Cases had significantly higher body mass index (odds ratio [OR]: 1.04, P = .035), duration of intubation (OR: 1.21, P < .001), and tobacco use (OR: 1.21, P = .006) in adjusted analysis when compared to controls. Tracheostomy dependence within the case cohort was significantly associated with public insurance (OR: 1.33, P = .016) and chronic obstructive pulmonary disease (OR: 1.34, P = .018) in adjusted analysis.

Conclusion: Intubation practices, medical comorbidities and social determinants of health may influence the development of LTS and tracheostomy dependence after treatment. Identification of at-risk populations in ICUs may allow for prevention of tracheostomy dependence through the use of early tracheostomy and specialized follow-up.

Level Of Evidence: Level 3, retrospective review comparing cases and controls Laryngoscope, 130:1000-1006, 2020.
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http://dx.doi.org/10.1002/lary.28208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808241PMC
April 2020

Early medical therapy for acute laryngeal injury (ALgI) following endotracheal intubation: a protocol for a prospective single-centre randomised controlled trial.

BMJ Open 2019 07 27;9(7):e027963. Epub 2019 Jul 27.

Department of Otolaryngology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Introduction: Respiratory failure requiring endotracheal intubation accounts for a significant proportion of intensive care unit (ICU) admissions. Little attention has been paid to the laryngeal consequences of endotracheal intubation. Acute laryngeal injury (ALgI) after intubation occurs at the mucosal interface of the endotracheal tube and posterior larynx and although not immediately manifest at extubation, can progress to mature fibrosis, restricted glottic mobility and clinically significant ventilatory impairment. A recent prospective observational study has shown that >50% of patients intubated >24 hours in an ICU develop ALgI. Strikingly, patients with AlgI manifest significantly worse subjective breathing at 12 weeks. Current ALgI treatments are largely surgical yet offer a marginal improvement in symptoms. METHODS AND ANALYSIS: A prospective, single-centre, double-blinded, randomised, control trial will be conducted at Vanderbilt Medical Center. Participants will be recruited from adult patients in ICUs. Participants will undergo a bedside flexible nasolaryngoscopy for the identification of ALgI within 72 hours postextubation. In addition, participants will be asked to complete peak expiratory flow measurements immediately postintubation. Patients found to have ALgI will be randomised to the placebo control or medical therapy group (azithromycin 250 mg and budesonide 0.5 mg for 14 days). Repeat peak expiratory flow, examination of the larynx and patient-reported Clinical COPD (chronic obstructive pulmonary disease) Questionnaire, Voice Handicap Index and 12-Item Short Form Health Survey questionnaires will be conducted at 12 weeks postextubation. Consented patients will also have patient-specific, disease-specific and procedure-specific covariates abstracted from their medical record.

Ethics And Dissemination: The Institutional Review Board (IRB) Committee of the Vanderbilt University Medical Center has approved this protocol (IRB #171066). The findings of the trial will be disseminated through peer-reviewed journals, national and international conferences.

Trial Registration Number: NCT03250975.
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http://dx.doi.org/10.1136/bmjopen-2018-027963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661707PMC
July 2019

Incidence of Laryngotracheal Stenosis after Thermal Inhalation Airway Injury.

J Burn Care Res 2019 10;40(6):961-965

Division of Trauma and Surgical Critical Care, Vanderbilt University Medical Center.

Inhalation injury is independently associated with burn mortality, yet little information is available on the incidence, risk factors, or functional outcomes of thermal injury to the airway. In patients with thermal inhalation injury, we sought to define the incidence of laryngotracheal stenosis (LTS), delineate risk factors associated with LTS development, and assess long-term tracheostomy dependence as a proxy for laryngeal function. Retrospective cohort study of adult patients treated for thermal inhalation injury at a single institution burn critical care unit from 2012 to 2017. Eligible patients' records were assessed for LTS (laryngeal, subglottic, or tracheal stenosis). Patient characteristics, burn injury characteristics, and treatment-specific covariates were assessed. Descriptive statistics, Mann-Whitney U-tests, odds ratio, and chi-square tests compared LTS versus non-LTS groups. Of 129 patients with thermal inhalation injury during the study period, 8 (6.2%) developed LTS. When compared with the non-LTS group, patients with LTS had greater mean TBSA (mean 30.3, Interquartile Range 7-57.5 vs 10.5, Interquartile Range 0-15.12, P = .01), higher grade of inhalation injury (mean 2.63 vs 1.80, P = .05), longer duration of intubation (12.63 vs 5.44; P < .001), and greater inflammatory response (mean white blood cell count on presentation 25.8 vs 14.9, P = .02, mean hyperglycemia on presentation 176.4 vs 136.9, P = .01). LTS patients had a significantly higher rate of tracheostomy dependence at last follow-up (50 vs 1.7%, P < .001). Six percent of patients with thermal inhalation injury develop LTS. LTS was associated with more severe thermal airway injury, longer duration of intubation, and more severe initial host inflammation. Patients with inhalation injury and LTS are at high risk for tracheostomy dependence. In burn patients with thermal inhalation injury, laryngeal evaluation and directed therapy should be incorporated early into multispecialty pathways of care.
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http://dx.doi.org/10.1093/jbcr/irz133DOI Listing
October 2019
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