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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.

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 (TRM ) 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.

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.

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.

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 χ2 test. Statistical significance was set a priori at P 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.

Background Patient-specific and disease-specific factors shape the course of chronic rhinosinusitis (CRS) and its response to treatment, with optimal management involving interventions tailored to these factors. Recent evidence suggests CRS inflammatory signatures depend on age. The objective of this study was to determine whether age also influences quality-of-life (QOL) and postoperative outcomes. Methods Retrospective analysis of prospectively collected QOL data from 403 adults with medically refractory CRS who underwent functional endoscopic sinus surgery (FESS) at a tertiary care medical center between 2014 and 2018 was undertaken. Total and subdomain scores from the 22-item Sino-Nasal Outcome Test (SNOT-22) and the Short Form 8 Health Survey (SF-8) measure of general health completed at preoperative and postoperative visits were reviewed. Results Patients were divided into young (18 to 39 years, n = 100), middle-aged (40 to 59 years, n = 172), and elderly (≥60 years, n = 131) groups. Baseline total SNOT-22 scores differed between groups (p = 0.01), with middle-aged patients having the highest symptom burden and elderly patients having the lowest. Similar patterns were observed for SNOT-22 subdomains. Elderly patients reported smaller improvements and were less likely to achieve a minimally important clinical difference. CRS patients had worse SF-8 scores compared to the general population, and elderly patients were the least likely to match population norms following surgery. Age was an independent predictor of QOL outcomes after FESS. Conclusion Age may play a significant role in CRS pathophysiology, symptom burden, and surgical outcomes. Elderly patients report smaller improvements in disease-specific and general health QOL after surgery. CRS management in the elderly population should incorporate age-dependent differences in symptom burden and expectations into treatment algorithms.

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.

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.