High-flow nasal oxygen for children's airway surgery to reduce hypoxaemic events: a randomised controlled trial.

BACKGROUND: Tubeless upper airway surgery in children is a complex procedure in which surgeons and anaesthetists share the same operating field. These procedures are often interrupted for rescue oxygen therapy. The efficacy of nasal high-flow oxygen to decrease the frequency of rescue interruptions in children undergoing upper airway surgery is unknown. METHODS: In this multicentre randomised trial conducted in five tertiary hospitals in Australia, children aged 0-16 years who required tubeless upper airway surgery were randomised (1:1) by a web-based randomisation tool to either nasal high-flow oxygen delivery or standard oxygen therapy (oxygen flows of up to 6 L/min). Randomisation was stratified by site and age (<1 year, 1-4 years, and 5-16 years). Subsequent tubeless upper airway surgery procedures in the same child could be included if there were more than 2 weeks between the procedures, and repeat surgical procedures meeting this condition were considered to be independent events. The oxygen therapy could not be masked, but the investigators remained blinded until outcome data were locked. The primary outcome was successful anaesthesia without interruption of the surgical procedure for rescue oxygenation. A rescue oxygenation event was defined as an interruption of the surgical procedure to deliver positive pressure ventilation using either bag mask technique, insertion of an endotracheal tube, or laryngeal mask to improve oxygenation. There were ten secondary outcomes, including the proportion of procedures with a hypoxaemic event (SpO2 <90%). Analyses were done on an intention-to-treat (ITT) basis. Safety was assessed in all enrolled participants. This trial is registered in the Australian New Zealand Clinical Trials Registry, ACTRN12618000949280, and is completed. FINDINGS: From Sept 4, 2018, to April 12, 2021, 581 procedures in 487 children were randomly assigned to high-flow oxygen (297 procedures) or standard care (284 procedures); after exclusions, 528 procedures (267 assigned to high-flow oxygen and 261 assigned to standard care) in 483 children (293 male and 190 female) were included in the ITT analysis. The primary outcome of successful anaesthesia without interruption for tubeless airway surgery was achieved in 236 (88%) of 267 procedures on high-flow oxygen and in 229 (88%) of 261 procedures on standard care (adjusted risk ratio [RR] 1·02, 95% CI 0·96-1·08, p=0·82). There were 51 (19%) procedures with a hypoxaemic event in the high-flow oxygen group and 57 (22%) in the standard care group (RR 0·86, 95% CI 0·58-1·24). Of the other prespecified secondary outcomes, none showed a significant difference between groups. Adverse events of epistaxis, laryngospasm, bronchospasm, hypoxaemia, bradycardia, cardiac arrest, hypotension, or death were similar in both study groups. INTERPRETATION: Nasal high-flow oxygen during tubeless upper airway surgery did not reduce the proportion of interruptions of the procedures for rescue oxygenation compared with standard care. There were no differences in adverse events between the intervention groups. These results suggest that both approaches, nasal high-flow or standard oxygen, are suitable alternatives to maintain oxygenation in children undergoing upper airway surgery. FUNDING: Thrasher Research Fund, the Australian and New Zealand College of Anaesthetists, the Society for Paediatric Anaesthesia in New Zealand and Australia.

Jelly snakes to reduce early postoperative vomiting in children after adenotonsillectomy: The randomized controlled snakes trial.

BACKGROUND: Despite the use of dual antiemetic agents, postoperative nausea and vomiting (PONV) occurs in an unacceptably large number of patients post-tonsillectomy. There has been increased interest in alternative and non-pharmacological treatments for PONV e.g., chewing gum. We investigated if chewing a large confectionary jelly snake had prophylactic antiemetic effects postoperatively in young children. METHODS: Prospective, open-label randomised controlled trial of 240 patients, 2-16 years. Patients administered a confectionary jelly snake to chew postoperatively were compared with a control group. The primary outcome was the number of episodes of vomiting within 6 h of the operation on an intention-to-treat basis. SECONDARY OUTCOMES: incidence of nausea, vomiting at 6 and 24 h, rescue antiemetic use, acceptability, delayed discharge. RESULTS: 233 patients were randomised to receive the confectionary snake (snake group, 118) or standard care (control group, 115). The number of vomiting episodes in 6 h was similar between groups on an intention-to-treat basis, with 39 episodes across 22 (19%) patients in the control group and 31 across 19 (16%) patients in the snake group (p = 0.666). From post anaesthetic care unit until 24 h there was no difference in doses of antiemetics or delayed discharge due to PONV. A secondary as per protocol analysis did not change this result. CONCLUSIONS: Chewing of confectionery jelly snakes within one hour of waking following adenotonsillectomy with vapour-maintained anaesthesia and two prophylactic antiemetics did not further reduce the incidence of early vomiting. REGISTRATION: prospective registration at the Australia and New Zealand Clinical Trials Registry (ACTRN12618000637246).

The utility of balloon dilation for piriform aperture stenosis - A first line surgical treatment.

AIM: Describe the long-term outcomes of patients with piriform aperture stenosis managed with balloon dilation. METHODS: Review of current literature. A retrospective case series of 6 patients with piriform aperture stenosis initially managed with balloon dilation at a tertiary paediatric hospital. RESULTS: Six neonates diagnosed with piriform aperture were managed with balloon dilation under general anaesthesia after failing conservative treatment. Average age at first dilation was 28 days old (range 6-54). The piriform aperture was an average width of 5.15 mm, with a 4-6.5 mm range, as measured on axial CT scan. The average width at 25% of the nasal cavity, 50% and 75% was 7.7 mm, 9.3 mm and 9.98 mm respectively. Four neonates required only a single balloon dilation - two of these were stented post-operatively. The remaining two neonates required multiple balloon dilations with eventual drill-out through a sublabial approach. There was a trend of smaller piriform and nasal cavity diameters in those who required multiple procedures. The mean follow-up was 30 months. CONCLUSION: Balloon dilation should be considered for primary operative management in neonates with piriform aperture stenosis who fail medical interventions. Balloon dilation can treat the narrowing at and beyond the piriform aperture. Patients who require more than one dilation are more likely to have a smaller piriform aperture and may need a drill-out procedure. The impact of nasal stents on outcomes is unclear.

Management of paediatric post-tonsillectomy bleeds - does everyone need observation?

AIM: The management of patients who present with a post-tonsillectomy bleed (PTB) who are not actively haemorrhaging is contentious. In our institution, those without an active bleed are admitted for a period of observation, due to the theoretical risk of further bleeding. This paper aims to review PTB admissions to ascertain the risk of rebleeding while under observation and to identify whether there is a low-risk group who can be safely discharged without observation. METHODS: Review of current literature. Retrospective chart review of all patients who presented to Perth Children's Hospital between February 2018 and February 2022 with a PTB. Exclusion criteria included primary PTB, known blood dyscrasias and patients >16 years of age. RESULTS: A total of 826 presentations of secondary PTB (sPTB) were reviewed, with 752 admitted for a period of observation. Twenty-two (2.9%) patients rebled while under observation, with 17 managed operatively. The average age of patients who rebled was 6.2 years and they presented at an average 7.14 post-operative days. The median time to rebleed was 4.4 h. Four patients with no oropharyngeal clot at presentation subsequently re-bled (0.53%) while under observation, with 2 (0.26%) managed surgically. In patients observed with an oropharyngeal clot at presentation 18 (3.1%) rebled, with 15 (2.6%) managed operatively. CONCLUSION: Patients presenting with a sPTB have a low risk of rebleeding while under observation. Patients with a normal oropharyngeal examination at presentation have a very low risk of rebleed and should be considered for early discharge if they meet other low risk criteria. Patients who present with an oropharyngeal clot can be safely observed with a low risk of further bleeding. Patients who rebleed while under observation should have a trial of conservative management if clinically appropriate.

Congenital subglottic cyst: a rare cause for sudden airway compromise in a newborn.

A full-term infant developed stridor, respiratory distress and hypercarbia shortly after birth requiring urgent airway intervention. The patient underwent urgent intubation via rigid bronchoscopy. The diagnosis of congenital subglottic cyst was made. The cyst was decompressed and the patient was extubated the following day. On repeat laryngoscopy 1 month later, there was no residual disease and the patient remained symptom free. Congenital subglottic cysts are extremely rare and the diagnosis can be either missed or misdiagnosed with more common causes of stridor, such as laryngomalacia. Subglottic cysts may cause total airway obstruction and even death if they are large enough and not treated immediately.

Long-Term Laryngotracheal Complications After Inhalation Injury: A Scoping Review.

Long-term laryngotracheal complications (LTLC) after inhalation injury (II) are an under-recognized condition in patients with burns. The purpose of this study was to systematically review all available evidence on LTLC after II and identify gaps in knowledge to guide the direction of future research. A scoping review was performed to synthesize all available evidence on LTLC after II, as guided by the question, "What are the LTLC after II, in patients with or without a history of translaryngeal intubation and/or tracheostomy?". MEDLINE, Web of Science, Ovid Embase, Cochrane Library, and Google Scholar were searched for publications on this topic. Of the 3567 citations screened, a total of 153 full-text articles were assessed for eligibility and 49 were included in the scoping review. The overall level of evidence was low, with case reports constituting 46.7% of all included human studies. The lesions were most frequently in the trachea (36.9%), followed by the glottis (34.7%) and subglottis (19.0%). LTLC occur in 4.8 to 6.5% of patients after II and these complications are under-recognized in burns patients. The risk factors for LTLC include high-grade II, elevated initial inflammatory responses, prolonged translaryngeal intubation, and a history of tracheostomy. The goal of management is to restore airway patency, preserve voice quality, and restore normal diet and swallow function. There is limited high-level evidence on LTLC, particularly with regards to long-term functional morbidity in voice and swallow. Large, prospective studies are required to address this gap in knowledge.

Fungal Rhinosinusitis Caused by a Curvularia sp. Infection in a Female Sumatran Orangutan: A Case Report.

Mycotic nasal cavity and paranasal sinus infections in non-human primates (NHPs) are relatively uncommon diseases of the upper respiratory tract. This case study describes the clinical and pathological features as well as the diagnostic techniques and interventions applied to treat the associated disease. A 23-year-old primiparous female Sumatran orangutan residing at Perth Zoo in Western Australia developed intermittent episodes of right-sided epistaxis. An ulcerative nasal mass was identified from a diagnostic endoscopy. The mass was initially biopsied and showed the morphological characteristics of a dematiaceous fungal organism upon a histological examination. There were prominent mucosal and submucosal granulomatous infiltrates containing histocytes, giant cells, and lymphocytes admixed with fewer numbers of neutrophils and eosinophils surrounding the fungal organism. The organism was identified as Curvularia sp. by the fungal characteristics associated with the histopathology, culture growth, and PCR analysis. The mass was subsequently removed with endoscopic sinus surgery (ESS) and the orangutan was medically treated with itraconazole for several months. The recovery was uneventful and the orangutan returned to full health.

The effect of iron deficiency on quality of life outcomes after surgery for obstructive sleep apnoea.

AIM: This study aimed to assess the effect of iron deficiency on parent-reported changes in quality of life (QOL) among children receiving an adenotonsillectomy for paediatric obstructive sleep apnoea (OSA). METHODS: This was a retrospective review study that recruited children under 16 years of age undergoing an adenotonsillectomy, adenoidectomy, or tonsillectomy for clinically diagnosed paediatric OSA between June 2020 and January 2021 inclusive, in Western Australia. The main outcome measures for this study were changes in QOL by age group and iron status, defined by an absolute change of more than 3 points on OSA-18 survey domains. RESULTS: About 249 participants had iron studies performed on perioperative blood samples drawn at operation and completed both pre-operative and post-operative OSA-18 QOL questionnaires at initial consultation and 8-12 weeks post-surgery, respectively. 41.8% were iron deficient, 53.8% were borderline iron deficient and 4.4% had normal iron levels. Following surgery, a decrease was observed for all OSA-18 score domains in post-operation scores compared to pre-operation scores in both iron-deficient and borderline iron-deficient cohorts. 'Daytime Problems' in the <2 years group, within the iron-deficient cohort, was the only domain that found to be non-superior (i.e. 'not better') following surgery. CONCLUSIONS: Following adenotonsillectomy, patients with paediatric OSA reported significant improvements in QOL regardless of their iron status. Those undergoing an adenotonsillectomy for paediatric OSA had a high prevalence of iron deficiency at operation, especially those under 6 years of age.

Re-thinking congenital piriform aperture stenosis: Modern imaging demonstrates narrowing of the full nasal cavity length.

OBJECTIVE: Measure the width of the nasal cavity in cases of piriform aperture stenosis using computerised tomography scans. METHODS: Retrospective study performed at a paediatric tertiary referral centre in Australia. Comparison nasal cavity widths (measured on computerised tomography scans in the axial plane) at the piriform aperture, choana and points 25, 50 and 75% along the length of nasal cavity, between cases with piriform aperture stenosis and controls. RESULTS: In cases of piriform aperture stenosis the piriform aperture along with the nasal cavity is statistically significantly narrower than controls, measured at 25, 50 and 75% along the distance between the piriform aperture and the choana. CONCLUSION: This modern imaging review has illustrated the need for a change in the treatment paradigm for neonates with this condition, suggesting the need for further investigation of techniques that treat narrowing beyond the aperture.

Australian Aboriginal Otitis-Prone Children Produce High-Quality Serum IgG to Putative Nontypeable Haemophilus influenzae Vaccine Antigens at Lower Titres Compared to Non-Aboriginal Children.

Background: Nontypeable Haemophilus influenzae (NTHi) is the most common bacterial otopathogen associated with otitis media (OM). NTHi persists in biofilms within the middle ears of children with chronic and recurrent OM. Australian Aboriginal children suffer exceptionally high rates of chronic and recurrent OM compared to non-Aboriginal children. NTHi protein vaccines comprised of antigens associated with both adhesion and persistence in a biofilm are under development and could be beneficial for children with chronic and recurrent OM. Understanding the ontogeny of natural antibody development to these antigens provides insight into the value of vaccinating with particular antigens. Methods: An in-house multiplex fluorescent bead immunoassay was used to measure serum IgG titres and avidity for three putative vaccine antigens: recombinant soluble PilA (rsPilA), ChimV4, and outer membrane protein 26 (OMP26) in sera from Australian Aboriginal otitis-prone children (n=77), non-Aboriginal otitis-prone children (n=70) and non-otitis-prone children (n=36). Serum IgG titres were adjusted for age, and geometric mean concentrations (GMCs) were compared between groups using a univariate analysis model. Antibody avidity was calculated as a relative avidity index and compared between groups using ANOVA. Results: Australian Aboriginal otitis-prone children had lower serum IgG titres to rsPilA and ChimV4 than non-Aboriginal otitis-prone children (p<0.001), and non-otitis-prone children (p<0.020). No differences were observed between serum IgG titres from non-Aboriginal otitis-prone children and non-otitis-prone children. There were also no differences in the proportion of high avidity IgG specific for these antigens between these groups. Serum IgG titres to OMP26 were similar between all groups (p>0.670) although otitis-prone children had a higher proportion of high avidity antibodies to this antigen. Conclusions: Australian Aboriginal otitis-prone children had lower serum IgG titres to 2/3 major NTHi vaccine candidate antigens, suggesting these children are unable to develop persistent IgG responses due to repeated NTHi exposure. These reduced IgG titres may relate to earlier and more frequent exposure to diverse NTHi strains in Aboriginal children through carriage or infection. These data suggest that Aboriginal children may benefit from immunisation with vaccines containing these antigens to increase titres of protective antibodies.

Sleep Disordered Breathing and Recurrent Tonsillitis Are Associated With Polymicrobial Bacterial Biofilm Infections Suggesting a Role for Anti-Biofilm Therapies.

Background: The underlying pathogenesis of pediatric obstructive sleep disordered breathing (SDB) and recurrent tonsillitis (RT) are poorly understood but need to be elucidated to develop less invasive treatment and prevention strategies. Methods: Children aged between 1- and 16-years undergoing adenoidectomy, tonsillectomy or adenotonsillectomy for SDB (n=40), RT alone (n=18), or both SDB and RT (SDB+RT) (n=17) were recruited with age-matched healthy controls (n=33). Total bacterial load and species-specific densities of nontypeable Haemophilus influenzae (NTHi), Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae and Moraxella catarrhalis were measured by qPCR in nasopharyngeal swabs, oropharyngeal swabs, adenoid and tonsillar tissue from children with SDB, SDB+RT and RT, and in naso- and oro- pharyngeal swabs from healthy children. A subset of tonsil biopsies were examined for biofilms using 16S rRNA FISH (n=3/group). Results: The 5 bacterial species were detected in naso- and oro- pharyngeal samples from all children. These species were frequently detected in adenotonsillar tissue (except S. aureus, which was absent in adenoids) from children with SDB, SDB+RT and RT. NTHi and S. aureus were observed in tonsils from 66.7-88.2% and 33.3-58.8% of children respectively. Similar total and species-specific bacterial densities were observed in adenotonsillar tissue from children with SDB, SDB+RT or RT. Nasopharyngeal and oropharyngeal swabs were more likely to have multiple bacterial species co-detected than adenotonsillar tissue where one or two targeted species predominated. Polymicrobial biofilms and intracellular bacteria were observed in tonsils from children with adenotonsillar disease. Conclusions: Antimicrobials, particularly anti-biofilm therapies, may be a strategy for managing children with SDB.

Dysregulated Notch Signaling in the Airway Epithelium of Children with Wheeze.

The airway epithelium of children with wheeze is characterized by defective repair that contributes to disease pathobiology. Dysregulation of developmental processes controlled by Notch has been identified in chronic asthma. However, its role in airway epithelial cells of young children with wheeze, particularly during repair, is yet to be determined. We hypothesized that Notch is dysregulated in primary airway epithelial cells (pAEC) of children with wheeze contributing to defective repair. This study investigated transcriptional and protein expression and function of Notch in pAEC isolated from children with and without wheeze. Primary AEC of children with and without wheeze were found to express all known Notch receptors and ligands, although pAEC from children with wheeze expressed significantly lower NOTCH2 (10-fold, p = 0.004) and higher JAG1 (3.5-fold, p = 0.002) mRNA levels. These dysregulations were maintained in vitro and cultures from children with wheeze displayed altered kinetics of both NOTCH2 and JAG1 expression during repair. Following Notch signaling inhibition, pAEC from children without wheeze failed to repair (wound closure rate of 76.9 ± 3.2%). Overexpression of NOTCH2 in pAEC from children with wheeze failed to rescue epithelial repair following wounding. This study illustrates the involvement of the Notch pathway in airway epithelial wound repair in health and disease, where its dysregulation may contribute to asthma development.

"Cannot intubate, cannot oxygenate": A novel 2-operator technique for cannula tracheotomy in an infant animal model-a feasibility study.

BACKGROUND: Evidence regarding optimal management of the "Cannot Intubate, Cannot Oxygenate" (CICO) scenario in infants is scarce. When inserting a transtracheal cannula for front of neck access direct aspiration to confirm intratracheal location is standard practice. This postmortem "infant airway" animal model study describes a novel technique for cannula tracheotomy. AIMS: To compare a novel technique of cannula tracheotomy to an accepted technique to assess success and complication rates. METHODS: Two experienced proceduralists repeatedly performed tracheotomy using an 18-gauge BD InsyteTM cannula (BD, Franklin Lakes, NJ, USA) in 6 postmortem White New Zealand rabbits. Cannulas were attached either directly to a 5ml syringe (Direct Aspiration) or via a 25 cm length minimum volume extension tubing set (TUTA Healthcare Lidcombe, NSW, Australia) (Indirect Aspiration, 2 operator technique). Each technique was attempted a maximum of 12 times per rabbit with an ENT surgeon assessing success and complication rates endoscopically for each attempt. RESULTS: 72 tracheotomy attempts were made in total, 36 for each technique. Initial aspiration through the needle was achieved in 93% (97.2% direct versus 89% indirect). Advancement of the cannula and continued aspiration (success) into the trachea occurred in 67% for direct compared with 64% for indirect aspiration. Direct aspiration was associated with higher rates of lateral (10.3% versus 5.6%) and posterior (19.4% versus 13.9%) wall injury compared with the indirect 2-operator technique. CONCLUSION: Cannula tracheotomy in infant-sized airways is technically difficult and seems frequently associated with tracheal wall injury. The reduced incidence of injury in the indirect group warrants further investigation in preclinical and clinical trials.

Comparison of the efficacy and safety of cuffed versus uncuffed endotracheal tubes for infants in the intensive care setting: a pilot, unblinded RCT.

OBJECTIVE: To study effectiveness and safety of cuffed versus uncuffed endotracheal tubes (ETTs) in small infants in the intensive care unit (ICU). DESIGN: Pilot RCT. SETTING: Neonatal and paediatric ICUs of children's hospital in Western Australia. PARTICIPANTS: Seventy-six infants ≥35 weeks gestation and infants <3 months of age, ≥3 kg. INTERVENTIONS: Patients randomly assigned to Microcuff cuffed or Portex uncuffed ETT. MAIN OUTCOMES MEASURES: Primary outcome was achievement of optimal ETT leak in target range (10%-20%). Secondary outcomes included: reintubations, ventilatory parameters, ventilatory complications, postextubation complications and long-term follow-up. RESULTS: Success rate (achievement of mean leak in the range 10%-20%) was 13/42 (30.9%) in the cuffed ETT group and 6/34 (17.6%) in uncuffed ETT group (OR=2.09; 95% CI (0.71 to 6.08); p=0.28). Mean percentage time within target leak range in cuffed ETT group 28% (IQR: 9-42) versus 15% (IQR: 0-28) in uncuffed ETT group (p=0.01). There were less reintubations to optimise size in cuffed ETT group 0/40 versus 10/36 (p<0.001). No differences were found in gaseous exchange, ventilator parameters or postextubation complications. There were fewer episodes of atelectasis in cuffed ETT group 0/42 versus 4/34 (p=0.03). No patient had been diagnosed with subglottic stenosis at long-term follow-up. CONCLUSIONS: There was no difference in the primary outcome, though percentage time spent in optimal leak range was significantly higher in cuffed ETT group. Cuffed ETTs reduced reintubations to optimise ETT size and episodes of atelectasis. Cuffed ETTs may be a feasible alternative to uncuffed ETTs in this group of patients. TRIAL REGISTRATION NUMBER: ACTRN12615000081516.

Competency-Based Assessment Tool for Pediatric Esophagoscopy: International Modified Delphi Consensus.

OBJECTIVES/HYPOTHESIS: Create a competency-based assessment tool for pediatric esophagoscopy with foreign body removal. STUDY DESIGN: Blinded modified Delphi consensus process. SETTING: Tertiary care center. METHODS: A list of 25 potential items was sent via the Research Electronic Data Capture database to 66 expert surgeons who perform pediatric esophagoscopy. In the first round, items were rated as "keep" or "remove" and comments were incorporated. In the second round, experts rated the importance of each item on a seven-point Likert scale. Consensus was determined with a goal of 7 to 25 final items. RESULTS: The response rate was 38/64 (59.4%) in the first round and returned questionnaires were 100% complete. Experts wanted to "keep" all items and 172 comments were incorporated. Twenty-four task-specific and 7 previously-validated global rating items were distributed in the second round, and the response rate was 53/64 (82.8%) with questionnaires returned 97.5% complete. Of the task-specific items, 9 reached consensus, 7 were near consensus, and 8 did not achieve consensus. For global rating items that were previously validated, 6 reached consensus and 1 was near consensus. CONCLUSIONS: It is possible to reach consensus about the important steps involved in rigid esophagoscopy with foreign body removal using a modified Delphi consensus technique. These items can now be considered when evaluating trainees during this procedure. This tool may allow trainees to focus on important steps of the procedure and help training programs standardize how trainees are evaluated. LEVEL OF EVIDENCE: 5. Laryngoscope, 131:1168-1174, 2021.

Ivacaftor or lumacaftor/ivacaftor treatment does not alter the core CF airway epithelial gene response to rhinovirus.

BACKGROUND: Aberrant responses by the cystic fibrosis airway epithelium during viral infection may underly the clinical observations. Whether CFTR modulators affect antiviral responses by CF epithelia is presently unknown. We tested the hypothesis that treatment of CF epithelial cells with ivacaftor (Iva) or ivacaftor/lumacaftor (Iva/Lum) would improve control of rhinovirus infection. METHODS: Nineteen CF epithelial cultures (10 homozygous for p.Phe508del as CFTR Class 2, 9 p.Phe508del/p.Gly551Asp as Class 3) were infected with rhinovirus 1B at multiplicity of infection 12 for 24 h. Culture RNA and supernatants were harvested to assess gene and protein expression respectively. RESULTS: RNA-seq analysis comparing rhinovirus infected cultures to control identified 796 and 629 differentially expressed genes for Class 2 and Class 3, respectively. This gene response was highly conserved when cells were treated with CFTR modulators and were predicted to be driven by the same interferon-pathway transcriptional regulators (IFNA, IFNL1, IFNG, IRF7, STAT1). Direct comparisons between treated and untreated infected cultures did not yield any differentially expressed genes for Class 3 and only 68 genes for Class 2. Changes were predominantly related to regulators of lipid metabolism and inflammation, aspects of epithelial biology known to be dysregulated in CF. In addition, CFTR modulators did not affect viral copy number, or levels of pro-inflammatory cytokines produced post-infection. CONCLUSIONS: Though long-term clinical data is not yet available, results presented here suggest that first generation CFTR modulators do not interfere with core airway epithelial responses to rhinovirus infection. Future work should investigate the latest triple modulation therapies.

A novel approach in managing challenging tracheoesophageal fistulae.

OBJECTIVE: To analyze the outcomes of an open anterior cervical approach and tospecifically describe a novel extended tracheotomy incision ("Key-hole technique") torepair H-type and other challenging tracheoesophageal fistulae (TOF) at a singletertiary pediatric center. METHOD: A retrospective chart analysis of pediatric patients (0-18 years old) who had undergone repair of TOF's between January 2006 and March 2020 were reviewed. A case series of patients who had undergone open cervical utilizing three different techniques were included. Patient demographics, surgical management and post-operative surgical outcomes including complications were evaluated. RESULTS: During the study period, 117 pediatric patients were diagnosed and anaged with TOFs with or without oesophageal atresia. Within this group, 12 patients (10%) had anterior open cervical repair of congenital or persisting TOFs (6 males and 6 females). Eight cases (7%) had congenital Type E (known as H-type), two had type D, one type B and one type C TOF. Median gestational age was 37 weeks (range 28-41 weeks), age of presentation ranged from 1 day old to 3 years old with 67% being diagnosed within the first month of life. At the time of definitive surgery all patients had a bronchoscopy and oesophagoscopy to confirm the diagnosis, identify the level of the fistula and place a catheter through the fistula. This cases series of open anterior cervical repair of TOFs comprised of seven (58%) patients who had primary extraluminal tracheal approach, four (33%) with extended tracheotomy incision ('Key-hole' technique) and one (9%) patient with slide tracheoplasty for recurrent type C TOF in the presence of subglottic stenosis. Eleven of the twelve patients had successful open anterior cervical repair of TOF. One patient who had primary open anterior cervical repair with the 'Key-hole' technique had recurrence managed successfully with slide tracheoplasty. There were no cases of recurrent laryngeal nerve injury. CONCLUSION: This series demonstrates that open anterior cervical approach to correct TOFs is an effective and safe method in the majority of cases of congenital and acquired fistulae where there is no oesophageal atresia or the atresia is corrected (in the case of recurrent or second fistulae). We also present the outcomes of a novel surgical "Keyhole" technique to manage TOF fistulas via an extended-tracheotomy incision. We also found that slide tracheoplasty is an effective salvage operation in the case of complex recurrent fistulae.

Pediatric Airway Pathology.

Congenital or acquired disorders of the pediatric airway can affect the upper, lower, or entire airway. There are fundamental differences between the anatomy and physiology of the neonate, pediatric, and adult airways. Infants are not merely small adults in this respect and size, surface area, proportion, resistance, and compliance vary greatly between the age groups. A clear understanding of these significant differences and how they affect patients dependent on age is key to appropriate management.

Pediatric Microlaryngoscopy and Bronchoscopy in the COVID-19 Era.

Importance: As an aerosol-generating procedure, traditional pediatric microlaryngoscopy and bronchoscopy techniques must be adapted in order to reduce the risk of transmission of severe acute respiratory syndrome coronavirus 2. Objective: To describe a modified technique for pediatric microlaryngoscopy and bronchoscopy for use in the COVID-19 era and present a case series of patients for whom the technique has been used. Design, Setting, and Participants: Observational case series of pediatric patients undergoing emergency or urgent airway procedures performed at a tertiary pediatric otolaryngology department in Australia. Procedures were completed between March 23 and April 9, 2020, with a median (range) follow-up of 24.5 (11-28) days. Exposures: Modified technique for microlaryngoscopy and bronchoscopy, minimizing aerosolization of respiratory tract secretions. Main Outcomes and Measures: The main outcome was the feasibility of technique, which was measured by ability to perform microlaryngoscopy and bronchoscopy with comparable success to the usual technique (ie, adequate examination of the patient for diagnostic procedures and ability to perform interventional procedures). Results: The technique was used successfully in 8 patients (median [range] age, 160 days [27 days to 2 years 6 months]); 5 patients were male, and 3 were female. Intervention was performed on 6 patients; 2 balloon dilations for subglottic stenosis, 2 injections of hyaluronic acid for type 1 clefts, and 2 cold-steel supraglottoplasties. No adverse events occurred. Conclusions and Relevance: In this case series, feasibility of a modified technique for pediatric microlaryngoscopy and bronchoscopy was demonstrated. By reconsidering the surgical approach in light of specific COVID-19 infection risks, this technique may be associated with reduced spread of aerosolized respiratory secretions perioperatively and intraoperatively, but the technique and patient outcomes require further study.

Aberrant cell migration contributes to defective airway epithelial repair in childhood wheeze.

Abnormal wound repair has been observed in the airway epithelium of patients with chronic respiratory diseases, including asthma. Therapies focusing on repairing vulnerable airways, particularly in early life, present a potentially novel treatment strategy. We report defective lower airway epithelial cell repair to strongly associate with common pre-school-aged and school-aged wheezing phenotypes, characterized by aberrant migration patterns and reduced integrin α5ß1 expression. Next generation sequencing identified the PI3K/Akt pathway as the top upstream transcriptional regulator of integrin α5ß1, where Akt activation enhanced repair and integrin α5ß1 expression in primary cultures from children with wheeze. Conversely, inhibition of PI3K/Akt signaling in primary cultures from children without wheeze reduced α5ß1 expression and attenuated repair. Importantly, the FDA-approved drug celecoxib - and its non-COX2-inhibiting analogue, dimethyl-celecoxib - stimulated the PI3K/Akt-integrin α5ß1 axis and restored airway epithelial repair in cells from children with wheeze. When compared with published clinical data sets, the identified transcriptomic signature was also associated with viral-induced wheeze exacerbations highlighting the clinical potential of such therapy. Collectively, these results identify airway epithelial restitution via targeting the PI3K-integrin α5ß1 axis as a potentially novel therapeutic avenue for childhood wheeze and asthma. We propose that the next step in the therapeutic development process should be a proof-of-concept clinical trial, since relevant animal models to test the crucial underlying premise are unavailable.