Citations

The pulmonary and renal vasculatures, in contrast to the systemic vasculature, constrict during hypoxia. The endothelium has been implicated in mediating these vascular responses to acute hypoxia via the production of endothelium-derived vasoactive factors. The present study, performed in anesthetized dogs, was designed to investigate the role of endothelium-derived relaxing factor (EDRF) to attenuate the vasoconstrictor response of the pulmonary and renal circulations during acute hypoxia. In response to hypoxia, pulmonary (2.2 +/- 0.3 to 4.5 +/- 0.6 mmHg.l-1.min) and renal (0.60 +/- 0.07 to 0.90 +/- 0.14 mmHg.ml-1.min) vascular resistances increased. Inhibition of endogenous EDRF with NG-monomethyl-L-arginine resulted in similar increases in pulmonary (3.0 +/- 0.1 to 4.8 +/- 0.4 mmHg.l-1.min) and renal (0.67 +/- 0.07 to 0.90 +/- 0.09 mmHg.ml-1.min) vascular resistances as in hypoxia. However, in the presence of both hypoxia and EDRF inhibition, an exaggerated pulmonary vascular response was observed (2.2 +/- 0.2 to 7.4 +/- 0.9 mmHg.l-1.min), in contrast to the renal vascular response to EDRF inhibition during hypoxia (0.61 +/- 0.05 to 0.95 +/- 0.10 mmHg.ml-1.min), which was not different from hypoxia or EDRF inhibition individually. The endothelium-derived contracting factor endothelin, which modestly increased during hypoxia (11.7 +/- 1.9 to 15.6 +/- 2.4 pg/ml), may also contribute to this vasoconstrictive response to hypoxia. This study suggests in the intact animal that EDRF serves to oppose the pulmonary vasoconstrictor response to hypoxia and further characterizes the role of endothelium-derived factors in the regulation of vascular function during hypoxia.

ObjectivesIdiopathic subglottic stenosis (iSGS) is rare, and its cause remains elusive. Treatment options include empiric medical therapy and endoscopic or open surgery. We present our results for open surgical technique.Study DesignCase series with chart review (1978‐2015).SettingTertiary academic center.Subjects/MethodsThirty‐three patients (32 female; median age, 51 years) met inclusion criteria and underwent cricotracheal resection with thyrotracheal anastomosis, tracheal resection with primary anastomosis, or laryngotracheoplasty with rib grafting. Continuous variables were summarized using medians and ranges while categorical features are presented using frequency counts and percentages.ResultsSixteen patients (48%) underwent a single‐stage approach with immediate extubation or temporary intubation following surgery (median, 1 day; range, 1‐3 days). Seventeen patients (52%) underwent a double‐staged approach with a median time to decannulation of 35 days (range, 13‐100 days). Twenty‐four (73%) patients underwent a previous intervention. Median stay in the intensive care unit was 1 day (range, 0‐3 days), with a median hospital stay of 4 days (range, 2‐7 days). Recurrence requiring further surgical intervention was observed in 12 patients (36%). The median time to recurrence was 8 years over an average follow‐up of 9.7 years. The most common complaint following surgery was change in voice quality (fair to poor; n = 10; 30%).ConclusionsOpen surgery should be reserved for refractory cases of iSGS; cricotracheal resection with thyrotracheal anastomosis is the preferred open technique. Recurrence may occur after open treatment, highlighting the importance of long‐term follow‐up. Patients should be counseled about the potential for worsening voice quality with the open approach.

Objectives/HypothesisIdiopathic 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.MethodsUtilizing 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.ResultsWith 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.ConclusionThese studies identify a novel pathogenic role for established large airway bacteria and provide new targets for future therapeutic intervention.Level of EvidenceNA Laryngoscope, 127:179–185, 2017

Objectives/HypothesisIdiopathic 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.MethodsUtilizing 20 human iSGS and healthy control specimens, we applied histologic, immunohistochemical, molecular, and immunologic techniques.ResultsWe 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.ConclusionOur 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 EvidenceNA Laryngoscope, 126:E356–E361, 2016

Abstract Rationale The use of tunneled indwelling pleural catheters for management of refractory pleural effusions continues to increase. Pleural space infections are among the most common and serious complication of the procedure. The risk may be higher in patients receiving immunosuppressive medications. Objectives The aim of this study was to assess the risk of infections complicating placement of a tunneled indwelling pleural catheter in patients who have received a solid organ transplant. Methods Electronic medical records were retrospectively reviewed to identify patients with prior solid organ transplant who subsequently underwent placement of a tunneled intrapleural catheter. We selected a matched sample of comparison patients without solid organ transplant who underwent the same procedure during the study period. Detailed chart abstraction was performed to compare baseline clinical information with procedure outcomes in both groups. Measurements and Main Results: Nineteen study patients underwent kidney, liver, lung, or heart transplant. Another 55 patients were included in the nontransplant comparison group. Transplant patients were taking a mean of 2.4 (range, 1–4) immunosuppressive medications. In transplant patients, the intrapleural catheter remained in place for a median of 95 days (interquartile range, 58–256 d). Two of the 19 transplant patients (16.9% 90-day Kaplan–Meier estimate) and 4 of the 55 control patients (11.0% weighted 90-day Kaplan–Meier estimate) developed a major infectious complication (not significant). There were no deaths attributed to intrapleural catheter placement in either group. Conclusions In a series of 19 patients with solid organ transplantation taking daily immunosuppressive medications who underwent placement of a tunneled intrapleural catheter, we report an 11% rate of major infectious complications over the lifetime of the catheter in the transplant group with no significant difference in 90-day estimated risk of complication between transplant and nontransplant comparison group.

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