Ian N. Jacobs

Objective: Children’s hospitals frequently care for infants with various life-threatening airway anomalies. Management of these infants can be challenging given unique airway anatomy and potential malformations. Airway emergency management must be immediate and precise, often demanding specialized equipment and/or expertise. We developed a Neonatal-Infant Airway Safety Program to improve medical responses, communication, equipment usage and outcomes for infants requiring emergent airway interventions. Patients and Methods: All patients admitted to our quaternary neonatal and infant intensive care unit (NICU) from 2008-2019 were included in this study. Our program consisted of a multidisciplinary airway response team, pager system, and emergency equipment cart. Respiratory therapists present at each emergency event recorded specialist response times, equipment utilization, and outcomes. A multidisciplinary oversite committee reviewed each incident. Results: Since 2008, there were 159 airway emergency events in our NICU (∼12 per year). Mean specialist response times decreased from 5.9±4.9 min (2008-2012, mean±SD) to 4.3±2.2 min (2016-2019, p=0.12), and the number of incidents with response times >5 min decreased from 28.8±17.8% (2008-2012) to 9.3±11.4% (2016-2019, p=0.04 by linear regression). As our program became more standardized, we noted better equipment availability and subspecialist communication. Few emergency situations (n=9, 6%) required operating room management. There were 3 patient deaths (2%). Conclusions: Our airway safety program, including readily available specialists and equipment, facilitated effective resolution of airway emergencies in our NICU and multidisciplinary involvement enabled rapid and effective changes in response to COVID-19 regulations. A similar program could be implemented in other centers.

Objectives/Hypothesis To develop an effective rabbit model of in vitro‐ and in vivo‐derived tissue‐engineered cartilage for laryngotracheal reconstruction (LTR). Study Design 1) Determination of the optimal scaffold 1% hyaluronic acid (HA), 2% HA, and polyglycolic acid (PGA) and in vitro culture time course using a pilot study of 4 by 4‐mm in vitro‐derived constructs analyzed on a static culture versus zero‐gravity bioreactor for 4, 8, and 12 weeks, with determination of compressive modulus and histology as outcome measures. 2) Three‐stage survival rabbit experiment utilizing autologous auricular chondrocytes seeded in scaffolds, either 1% HA or PGA. The constructs were cultured for the determined in vitro time period and then cultured in vivo for 12 weeks. Fifteen LTRs were performed using HA cartilage constructs, and one was performed with a PGA construct. All remaining specimens and the final reconstructed larynx underwent mechanical testing, histology, and glycosaminoglycan (GAG) content determination, and then were compared to cricoid control specimens (n = 13) and control LTR using autologous thyroid cartilage (n = 18). Methods 1) One rabbit underwent an auricular punch biopsy, and its chondrocytes were isolated and expanded and then encapsulated in eight 4 by 4‐mm discs of 1% HA, 2% HA, PGA either in rotary bioreactor or static culture for 4, 8, and 12 weeks, respectively, with determination of compressive modulus, GAG content, and histology. 2) Sixteen rabbits underwent ear punch biopsy; chondrocytes were isolated and expanded. The cells were seeded in 13 by 5 by 2.25‐mm UV photopolymerized 1% HA (w/w) or calcium alginate encapsulated synthetic PGA (13 × 5 × 2 mm); the constructs were then incubated in vitro for 12 weeks (the optimal time period determined above in paragraph 1) on a shaker. One HA and one PGA construct from each animal was tested mechanically and histologically, and the remaining eight (4 HA and 4 PGA) were implanted in the neck. After 12 weeks in vivo, the most optimal‐appearing HA construct was used as a graft for LTR in 15 rabbits and PGA in one rabbit. The seven remaining specimens underwent hematoxylin and eosin, Safranin O, GAG content determination, and flexural modulus testing. At 12 weeks postoperative, the animals were euthanized and underwent endoscopy. The larynges underwent mechanical and histological testing. All animals that died underwent postmortem examination, including gross and microhistological analysis of the reconstructed airway. Results Thirteen of the 15 rabbits that underwent LTR with HA in vitro‐ and in vivo‐derived tissue‐engineered cartilage constructs survived. The 1% HA specimens had the highest modulus and GAG after 12 weeks in vitro. The HA constructs became well integrated in the airway, supported respiration for the 12 weeks, and were histologically and mechanically similar to autologous cartilage. Conclusions The engineering of in vitro‐ and in vivo‐derived cartilage with HA is a novel approach for laryngotracheal reconstruction. The data suggests that the in vitro‐ and in vivo‐derived tissue‐engineered approaches may offer a promising alternative to current strategies used in pediatric airway reconstruction, as well as other head and neck applications. Level of Evidence NA. Laryngoscope, 126:S5–S21, 2016

Research from JAMA Otolaryngology–Head & Neck Surgery — Single- vs Double-Stage Laryngotracheal Reconstruction

Objectives To evaluate the efficacy and clinical usefulness of laryngeal electromyography (EMG) in the evaluation and management of vocal cord mobility problems in children; and to determine the ability of laryngeal EMG to differentiate vocal fold fixation versus paralysis.Study Design Case‐series review of 8 children with vocal cord immobility who underwent laryngeal EMG.Methods Eight children with bilateral vocal fold immobility underwent microlaryngoscopy and electromyography. Bipolar concentric needle electrodes were used and implanted separately into both posterior cricoarytenoid (PCA) and both thyroarytenoid (TA) muscles. EMG activity was recorded during spontaneous ventilation under a light plane of anesthesia with propofol. EMG activity was correlated with the phases of the respiratory cycle.Results Three patients had evidence of normal EMG activity with PCA activity peaking during early inspiration. Maximal TA activity occurred expiration. These patients were assumed to have vocal fold fixation. Two of these 3 patients underwent laryngotracheoplasty (LTP) with posterior glottic expansion with costal cartilage. One is being considered for LTP in the future. Five patients had abnormal EMG activity and remain tracheotomy‐dependent. Four patients exhibited synkinetic activity with peak PCA activity during expiration and peak TA activity during expiration. Two patients had both fixation and unilateral vocal cord paralysis. One was successfully decannulated after posterior graft LTP and the other is planned for the future.Conclusions Electromyography, which differentiates paralysis from fixation, is a useful diagnostic tool in the evaluation of children with vocal cord immobility.

OBJECTIVE: Polypeptide growth factors have important influences on wound‐healing and scar tissue formation. Specific growth factors or their inhibitors may potentially decrease scar tissue formation and prevent subglottic stenosis. Gene transfer using recombinant adenovirus may be an ideal method to mediate endogenous production of growth factors to inhibit fibrosis.STUDY DESIGN: The study incorporated adenovirus‐mediated transduction of normal and stenotic rat larynges and histologic analysis of the sequential expression of a β‐galactosidase marker gene over time.SETTING: The study was conducted at the animal care facility of an academic children's hospital.RESULTS: We report successful transduction in normal and injured rat larynx with peak expression of β‐galactosidase at 2 days after transduction and almost complete disappearance by 7 days. There appeared to be an early inflammatory response to the viral injection, but at 7 and 14 days after injection (transduction) the uninjured rat larynges resumed a normal histologic appearance. All distant sites stained negative for β‐galactosidase.CONCLUSION: Recombinant adenovirus‐mediated gene transfer is feasible in the rat larynx with transient duration and limited toxicity.SIGNIFICANCE: Adenovirus‐mediated gene transfer has the potential to deliver growth factors that modulate wound healing and inflammation in the larynx by inhibiting fibrosis.

Objectives Helium as a component of inspired gas decreases turbulent flow and airway resistance. Helium–oxygen mixtures have been used since the 1930s in the management of patients with upper airway obstruction. The objective of this study was to evaluate the efficacy of helium–oxygen mixtures in relieving upper airway obstruction in a pediatric population.Study Design Retrospective chart review of 42 pediatric patients who received helium–oxygen mixtures for upper airway obstruction within a 3‐year period.Methods The study protocol included 42 pediatric patients, aged 1 week to 14 years, who were admitted to the Children's Hospital of Philadelphia from June 1997 to December 2000 and who received a total of 44 treatments of helium–oxygen therapy for upper airway obstruction. Response to treatment was determined by reduction in work of breathing noted on the chart.Results Thirty‐two of 44 helium–oxygen treatments resulted in a positive response (73%). There were no significant differences in demographic characteristics between responders and nonresponders, except all of the premature infants were responders and 6 of the 9 patients with syndromes were nonresponders.Conclusions Helium–oxygen therapy is a useful adjunct therapy for upper airway obstruction. Controlled clinical trials are necessary to better define the appropriate settings for use of helium–oxygen.