Tobacco smoking and somatic mutations in human bronchial epithelium.

Tobacco smoking causes lung cancer1-3, a process that is driven by more than 60 carcinogens in cigarette smoke that directly damage and mutate DNA4,5. The profound effects of tobacco on the genome of lung cancer cells are well-documented6-10, but equivalent data for normal bronchial cells are lacking. Here we sequenced whole genomes of 632 colonies derived from single bronchial epithelial cells across 16 subjects. Tobacco smoking was the major influence on mutational burden, typically adding from 1,000 to 10,000 mutations per cell; massively increasing the variance both within and between subjects; and generating several distinct mutational signatures of substitutions and of insertions and deletions. A population of cells in individuals with a history of smoking had mutational burdens that were equivalent to those expected for people who had never smoked: these cells had less damage from tobacco-specific mutational processes, were fourfold more frequent in ex-smokers than current smokers and had considerably longer telomeres than their more-mutated counterparts. Driver mutations increased in frequency with age, affecting 4-14% of cells in middle-aged subjects who had never smoked. In current smokers, at least 25% of cells carried driver mutations and 0-6% of cells had two or even three drivers. Thus, tobacco smoking increases mutational burden, cell-to-cell heterogeneity and driver mutations, but quitting promotes replenishment of the bronchial epithelium from mitotically quiescent cells that have avoided tobacco mutagenesis.

Lentiviral expression of wild-type LAMA3A restores cell adhesion in airway basal cells from children with epidermolysis bullosa.

The hallmark of epidermolysis bullosa (EB) is fragile attachment of epithelia due to genetic variants in cell adhesion genes. We describe 16 EB patients treated in the ear, nose, and throat department of a tertiary pediatric hospital linked to the United Kingdom's national EB unit between 1992 and 2023. Patients suffered a high degree of morbidity and mortality from laryngotracheal stenosis. Variants in laminin subunit alpha-3 (LAMA3) were found in 10/15 patients where genotype was available. LAMA3 encodes a subunit of the laminin-332 heterotrimeric extracellular matrix protein complex and is expressed by airway epithelial basal stem cells. We investigated the benefit of restoring wild-type LAMA3 expression in primary EB patient-derived basal cell cultures. EB basal cells demonstrated weak adhesion to cell culture substrates, but could otherwise be expanded similarly to non-EB basal cells. In vitro lentiviral overexpression of LAMA3A in EB basal cells enabled them to differentiate in air-liquid interface cultures, producing cilia with normal ciliary beat frequency. Moreover, transduction restored cell adhesion to levels comparable to a non-EB donor culture. These data provide proof of concept for a combined cell and gene therapy approach to treat airway disease in LAMA3-affected EB.

Suspension laryngoscopy experiences in a tertiary airway service: A prospective study of 150 procedures.

OBJECTIVES: In most cases, suspension laryngoscopy (SL) is efficient, bloodless and with minimal post-procedure discomfort. We aimed to identify predictive patient factors for acceptable surgical views at SL as well as quantify our tertiary airway unit's complication rates. DESIGN: Prospective cohort study of 150 consecutive microlaryngoscopy procedures involving SL over an 8-month period between November 2019 and July 2020. Patients were assessed preoperatively for pre-existing oral, temporomandibular, dental, pharyngeal or laryngeal pathology, interincisor distance and qualitative gross limitations to neck extension and forward head posture. Intraoperatively, the laryngoscopic view was graded by anaesthetic and surgical teams, and complications were recorded on patient interview in recovery. SETTING: Tertiary adult airway service for predominantly benign pathology. RESULTS: Adequate surgical views were obtained in 149/150 procedures. BMI had a weak positive correlation with a more difficult view (r = .22, p = .008) but did not correlate with a statistically significant increase in any complication. There was a weak negative correlation between age and interincisor gap (r = -.20, p = .014), and wider mouth opening correlated very weakly with a lower incidence of sore throat (r = -.19, p = .023). Gross macroglossia showed a significant moderate positive correlation with tongue symptoms (r = .45, p = 1.611 × 10-8 ). CONCLUSION: In the context of an experienced airway unit with a high caseload of predominantly benign pathology, SL is very effective and safe with low associated morbidity and no mortality. The most common complication of SL is temporary sore throat and there remain recognised risks of temporary tongue and dental symptoms.

Sarcoidosis of the ear, nose and throat: A review of the literature.

OBJECTIVES: Sarcoidosis is a multisystemic inflammatory disease with extrathoracic manifestations, most commonly affecting the young and middle-aged, female and Black populations. Diagnosis usually requires evidence of non-caseating granulomata and, when treated, prognosis is usually favourable. We aim to establish the incidence, clinical features and optimal treatment of ENT manifestations of this disease. DESIGN: We performed a PubMed literature review to determine the evidence base supporting this. RESULTS: ENT manifestations are present in 5%-15% of patients with sarcoidosis, often as a presenting feature, and require vigilance for swift recognition and coordinated additional treatment specific to the organ. Laryngeal sarcoidosis presents with difficulty in breathing, dysphonia and cough, and may be treated by speech and language therapy (SLT) or intralesional injection, dilatation or tissue reduction. Nasal disease presents with crusting, rhinitis, nasal obstruction and anosmia, usually without sinus involvement. It is treated by topical nasal or intralesional treatments but may also require endoscopic sinus surgery, laser treatment or even nasal reconstruction. Otological disease is uncommon but includes audiovestibular symptoms, both sensorineural and conductive hearing loss, and skin lesions. CONCLUSIONS: The consequences of ENT manifestations of sarcoidosis can be uncomfortable, disabling and even life-threatening. Effective management strategies require good diagnostic skills and use of specific therapies combined with established treatments such as corticosteroids. Comparisons of treatment outcomes are needed to establish best practice in this area.

Bioengineered airway epithelial grafts with mucociliary function based on collagen IV- and laminin-containing extracellular matrix scaffolds.

Current methods to replace damaged upper airway epithelium with exogenous cells are limited. Existing strategies use grafts that lack mucociliary function, leading to infection and the retention of secretions and keratin debris. Strategies that regenerate airway epithelium with mucociliary function are clearly desirable and would enable new treatments for complex airway disease.Here, we investigated the influence of the extracellular matrix (ECM) on airway epithelial cell adherence, proliferation and mucociliary function in the context of bioengineered mucosal grafts. In vitro, primary human bronchial epithelial cells (HBECs) adhered most readily to collagen IV. Biological, biomimetic and synthetic scaffolds were compared in terms of their ECM protein content and airway epithelial cell adherence.Collagen IV and laminin were preserved on the surface of decellularised dermis and epithelial cell attachment to decellularised dermis was greater than to the biomimetic or synthetic alternatives tested. Blocking epithelial integrin α2 led to decreased adherence to collagen IV and to decellularised dermis scaffolds. At air-liquid interface (ALI), bronchial epithelial cells cultured on decellularised dermis scaffolds formed a differentiated respiratory epithelium with mucociliary function. Using in vivo chick chorioallantoic membrane (CAM), rabbit airway and immunocompromised mouse models, we showed short-term preservation of the cell layer following transplantation.Our results demonstrate the feasibility of generating HBEC grafts on clinically applicable decellularised dermis scaffolds and identify matrix proteins and integrins important for this process. The long-term survivability of pre-differentiated epithelia and the relative merits of this approach against transplanting basal cells should be assessed further in pre-clinical airway transplantation models.

Open and Thoracoscopic Aortopexy for Airway Malacia in Children: 15 Year Single Centre Experience.

OBJECTIVES: The objective was to report and analyse the characteristics and results of open aortopexy and thoracoscopic aortopexy for the treatment of airway malacia in a paediatric population. METHODS: We report a retrospective consecutive case series of paediatric patients undergoing aortopexy for the treatment of airway malacia at a quaternary referral centre between December 2006 and January 2021. Outcome measures included days to extubation, continued need for non-invasive ventilation, further intervention in the form of tracheostomy and death. RESULTS: 169 patients underwent aortopexy: 147 had open procedures (135 via median/limited median sternotomy and 12 thoracotomy) and 22 thoracoscopic. Mean follow up was 8.46 yrs (range 1-20 yrs). Most common site of airway malacia was the trachea (n = 106, 62.7 %), and 48 (28.4 %) had additional involvement at the bronchi with tracheobronchomalacia (TBM). 15 (8.9 %) had bronchomalacia (BM) only. Incidence of bronchial disease was lower in the thoracoscopic than open group (13.6 % vs 40.82 %; p < 0.0001). Mean time to extubation was 1.45 days, 2.59 days, 5.23 days in tracheomalacia, TBM and BM groups, respectively (p = 0.0047). Mean time to extubation was 1.35 days, 2 days, 3.67 days, and 5 days in patients with external vascular compression, TOF/OA, primary airway malacia, and laryngeal reconstruction, respectively (p = 0.0002). There were 21 deaths across the cohort, and all were in the open group. 71.4 % (n = 15) had bronchial involvement of their airway malacia. CONCLUSIONS: Open and thoracoscopic aortopexy are effective treatments for airway malacia in children. We have identified that involvement of the bronchi is a risk factor for adverse outcomes, and the optimum treatment for this patient cohort is still debatable. LEVEL OF EVIDENCE: IV. TYPE OF STUDY: Retrospective Study.

Tracheal Resection for Critical Airway Obstruction in Morquio A Syndrome.

Introduction: The primary cause of death in Morquio A syndrome (mucopolysaccharidosis (MPS) IVA) is airway obstruction, brought about by an inexorable and pathognomonic multilevel airway tortuosity, buckling, and obstruction. The relative pathophysiological contributions of an inherent cartilage processing defect versus a mismatch in longitudinal growth between the trachea and the thoracic cage are currently a subject of debate. Enzyme replacement therapy (ERT) and multidisciplinary management continue to improve life expectancy for Morquio A patients by slowing many of the multisystem pathological consequences of the disease but are not as effective at reversing established pathology. An urgent need has developed to consider alternatives to palliation of progressive tracheal obstruction to preserve and maintain these patients' hard-won good quality of life, as well as to facilitate spinal and other required surgery. Case Report. Following multidisciplinary discussion, transcervical tracheal resection with limited manubriectomy was successfully performed, without the need for cardiopulmonary bypass, in an adolescent male on ERT with the severe airway manifestations of Morquio A syndrome. His trachea was found to be under significant compressive forces at surgery. On histology, chondrocyte lacunae appeared enlarged, but intracellular lysosomal staining and extracellular glycosaminoglycan staining was comparable to control trachea. At 12 months, this has resulted in a significant improvement in respiratory and functional status, with corresponding enhancement to his quality of life. Conclusion: This addressing of tracheal/thoracic cage dimension mismatch represents a novel surgical treatment approach to an existing clinical paradigm and may be useful for other carefully selected individuals with MPS IVA. Further work is needed to better understand the role and optimal timing of tracheal resection within this patient cohort so as to individually balance considerable surgical and anaesthetic risks against the potential symptomatic and life expectancy benefits.

Lung viral infection modelling in a bioengineered whole-organ.

Lung infections are one of the leading causes of death worldwide, and this situation has been exacerbated by the emergence of COVID-19. Pre-clinical modelling of viral infections has relied on cell cultures that lack 3D structure and the context of lung extracellular matrices. Here, we propose a bioreactor-based, whole-organ lung model of viral infection. The bioreactor takes advantage of an automated system to achieve efficient decellularization of a whole rat lung, and recellularization of the scaffold using primary human bronchial cells. Automatization allowed for the dynamic culture of airway epithelial cells in a breathing-mimicking setup that led to an even distribution of lung epithelial cells throughout the distal regions. In the sealed bioreactor system, we demonstrate proof-of-concept for viral infection within the epithelialized lung by infecting primary human airway epithelial cells and subsequently injecting neutrophils. Moreover, to assess the possibility of drug screening in this model, we demonstrate the efficacy of the broad-spectrum antiviral remdesivir. This whole-organ scale lung infection model represents a step towards modelling viral infection of human cells in a 3D context, providing a powerful tool to investigate the mechanisms of the early stages of pathogenic infections and the development of effective treatment strategies for respiratory diseases.

Lessons learned from pre-clinical testing of xenogeneic decellularized esophagi in a rabbit model.

Decellularization of esophagi from several species for tissue engineering is well described, but successful implantation in animal models of esophageal replacement has been challenging. The purpose of this study was to assess feasibility and applicability of esophageal replacement using decellularized porcine esophageal scaffolds in a new pre-clinical model. Following surgical replacement in rabbits with a vascularizing muscle flap, we observed successful anastomoses of decellularized scaffolds, cues of early neovascularization, and prevention of luminal collapse by the use of biodegradable stents. However, despite the success of the surgical procedure, the long-term survival was limited by the fragility of the animal model. Our results indicate that transplantation of a decellularized porcine scaffold is possible and vascular flaps may be useful to provide a vascular supply, but long-term outcomes require further pre-clinical testing in a different large animal model.

Cell-intrinsic differences between human airway epithelial cells from children and adults.

The airway epithelium is a protective barrier that is maintained by the self-renewal and differentiation of basal stem cells. Increasing age is a principle risk factor for chronic lung diseases, but few studies have explored age-related molecular or functional changes in the airway epithelium. We retrieved epithelial biopsies from histologically normal tracheobronchial sites from pediatric and adult donors and compared their cellular composition and gene expression profile (in laser capture-microdissected whole epithelium, fluorescence-activated cell-sorted basal cells, and basal cells in cell culture). Histologically, pediatric and adult tracheobronchial epithelium was similar in composition. We observed age-associated changes in RNA sequencing studies, including higher interferon-associated gene expression in pediatric epithelium. In cell culture, pediatric cells had higher colony formation ability, sustained in vitro growth, and outcompeted adult cells in a direct competitive proliferation assay. Our results demonstrate cell-intrinsic differences between airway epithelial cells from children and adults in both homeostatic and proliferative states.

Endoscopic Multipoint Laser System for Objective Pediatric Airway Assessment.

Recent technological advances within aeronautical engineering have demonstrated the delivery of objective quantitative endoscopic measurements to within one-hundredth of a millimeter. We sought to validate this emerging laser technology in a simulation-based assessment of pediatric airway stenosis. A 4.4-mm flexible endoscope, incorporating a laser measurement system projecting 49 laser points into the endoscopic view, was used to assess a simulated model of subglottic stenosis. Multiple anteroposterior and lateral measurements were obtained for each stenosis and compared with standard airway assessment techniques. Intra- and interobserver reliability was assessed. A total of 240 multipoint laser measurements were obtained of simulated airway stenosis. The mean difference from manual measurement was 0.1886 mm. The Bland-Altman plot showed low bias (0.011) and narrow 95% limits of agreement (-0.46 to 0.48). This advanced endoscopic measurement technique shows great promise for clinical development to benefit ongoing assessment and treatment of evolving pediatric airway stenosis.

Primary Immunoglobulin G4-Related Laryngeal Disease: A Case Series and Review of Literature.

OBJECTIVE: Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognised cause of various systemic fibro-inflammatory conditions. However, laryngeal involvement as a primary feature is extremely rare. We aimed to report on a case series of such patients and examine the global literature relating to laryngeal involvement. METHODS: Having previously reported a case of IgG4-RD laryngeal pseudotumour, we describe a case series of further 4 patients with primary laryngeal IgG4-RD managed by our UK quaternary airway service and provide a brief overview of laryngeal IgG4-RD. RESULTS: Including our cases, 14 cases of primary laryngeal IgG4-RD have been reported. Vocal cord involvement is relatively uncommon. Repeat biopsies may be required to achieve histological diagnosis. Remission is achievable by commencement of immunomodulatory treatment, following which laryngeal reconstruction may be necessary. CONCLUSION: Laryngeal involvement is a rare presentation of IgG4-RD, itself a rare and difficult-to-diagnose condition. A high and prolonged index of suspicion is necessary from both surgical and pathological specialists for correct diagnosis and management.

Development data associated with effects of stiffness softening of 3D-TIPS elastomer nanohybrid scaffolds on tissue ingrowth, vascularization and inflammation in vivo.

This DiB article contains data related to the research article entitled "Cellular responses to thermoresponsive stiffness memory elastomer nanohybrid scaffolds by 3D-TIPS" (Wu et al., 2018). Thermoresponsive poly (urea-urethane) nanohybrid elastomer (PUU-POSS) scaffolds were implanted in rats for up to 3 months. The porous structure and tensile mechanical properties of the scaffolds are listed and compared before and after in vitro and in vivo tests. The details of the histological analysis of the explants with different initial stiffness and porous structures at various time points are presented. The images and data presented support the conclusion about the coupled effects of stiffness softening and the hierarchical porous structure modulating tissue ingrowth, vascularization and macrophage polarization in the article (Wu et al., 2018).

Cellular responses to thermoresponsive stiffness memory elastomer nanohybrid scaffolds by 3D-TIPS.

Increasing evidence suggests the contribution of the dynamic mechanical properties of the extracellular matrix (ECM) to regulate tissue remodeling and regeneration. Following our recent study on a family of thermoresponsive 'stiffness memory' elastomeric nanohybrid scaffolds manufactured via an indirect 3D printing guided thermally-induced phase separation process (3D-TIPS), this work reports in vitro and in vivo cellular responses towards these scaffolds with different initial stiffness and hierarchically interconnected porous structure. The viability of mouse embryonic dermal fibroblasts in vitro and the tissue responses during the stiffness softening of the scaffolds subcutaneously implanted in rats for three months were evaluated by immunohistochemistry and histology. Scaffolds with a higher initial stiffness and a hierarchical porous structure outperformed softer ones, providing initial mechanical support to cells and surrounding tissues before promoting cell and tissue growth during stiffness softening. Vascularization was guided throughout the digitally printed interconnected networks. All scaffolds exhibited polarization of the macrophage response from a macrophage phenotype type I (M1) towards a macrophage phenotype type II (M2) and down-regulation of the T-cell proliferative response with increasing implantation time; however, scaffolds with a more pronounced thermo-responsive stiffness memory mechanism exerted higher inflammo-informed effects. These results pave the way for personalized and biologically responsive soft tissue implants and implantable device with better mechanical matches, angiogenesis and tissue integration. Statement of Significance This work reports cellular responses to a family of 3D-TIPS thermoresponsive nanohybrid elastomer scaffolds with different stiffness softening both in vitro and in vivo rat models. The results, for the first time, have revealed the effects of initial stiffness and dynamic stiffness softening of the scaffolds on tissue integration, vascularization and inflammo-responses, without coupling chemical crosslinking processes. The 3D printed, hierarchically interconnected porous structures guide the growth of myofibroblasts, collagen fibers and blood vessels in real 3D scales. In vivo study on those unique smart elastomer scaffolds will help pave the way for personalized and biologically responsive soft tissue implants and implantable devices with better mechanical matches, angiogenesis and tissue integration.

Stiffness memory nanohybrid scaffolds generated by indirect 3D printing for biologically responsive soft implants.

Cell and tissue stiffness is an important biomechanical signalling parameter for dynamic biological processes; responsive polymeric materials conferring responsive functionality are therefore appealing for in vivo implants. We have developed thermoresponsive poly(urea-urethane) nanohybrid scaffolds with 'stiffness memory' through a versatile 3D printing-guided thermally induced phase separation (3D-TIPS) technique. 3D-TIPS, a combination of 3D printing with phase separation, allows uniform phase-separation and phase transition of the polymer solution at a large interface of network within the printed sacrificial preform, leading to the creation of full-scale scaffolds with bespoke anatomical complex geometry. A wide range of hyperelastic mechanical properties of the soft elastomer scaffolds with interconnected pores at multi-scale, controlled porosity and crystallinity have been manufactured, not previously achievable via direct printing techniques or phase-separation alone. Semi-crystalline polymeric reverse self-assembly to a ground-stated quasi-random nanophase structure, throughout a hierarchical structure of internal pores, contributes to gradual stiffness relaxation during in vitro cell culture with minimal changes to shape. This 'stiffness memory' provides initial mechanical support to surrounding tissues before gradually softening to a better mechanical match, raising hopes for personalized and biologically responsive soft tissue implants which promote human fibroblast cells growth as model and potential scaffold tissue integration. STATEMENT OF SIGNIFICANCE: Biological processes are dynamic in nature, however current medical implants are often stronger and stiffer than the surrounding tissue, with little adaptability in response to biological and physical stimuli. This work has contributed to the development of a range of thermoresponsive nanohybrid elastomer scaffolds, with tuneable stiffness and hierarchically interconnected porous structure, manufactured by a versatile indirect 3D printing technique. For the first time, stiffness memory of the scaffold was observed to be driven by phase transition and a reverse self-assembly from a semicrystalline phase to a quasi-random nanostructured rubber phase. Early insight into cell response during the stiffness relaxation of the scaffolds in vitro holds promise for personalized biologically responsive soft implants.

Ex utero intrapartum treatment (EXIT) for upper airway obstruction.

PURPOSE OF REVIEW: Improvements in the antenatal diagnosis of congenital malformations have led to increased detection of fetal airway obstructing lesions, and pediatric ear, nose, and throat surgeons are increasingly involved in these cases. RECENT FINDINGS: This article outlines the typical range of pathology seen, the logistics in providing support for anticipated deliveries and the multidisciplinary management of complex airway cases. SUMMARY: Traditionally, difficulty in obtaining a patent airway at delivery was a major factor in the dismal prognosis of these pregnancies. The ex utero intrapartum treatment procedure, which involves controlled partial delivery of the fetus whilst maintaining placental circulation, allows various airway maneuvers to be performed to secure the airway in a controlled fashion.

Autologous Cell Seeding in Tracheal Tissue Engineering.

PURPOSE OF REVIEW: There is no consensus on the best technology to be employed for tracheal replacement. One particularly promising approach is based upon tissue engineering and involves applying autologous cells to transplantable scaffolds. Here, we present the reported pre-clinical and clinical data exploring the various options for achieving such seeding. RECENT FINDINGS: Various cell combinations, delivery strategies, and outcome measures are described. Mesenchymal stem cells (MSCs) are the most widely employed cell type in tracheal bioengineering. Airway epithelial cell luminal seeding is also widely employed, alone or in combination with other cell types. Combinations have thus far shown the greatest promise. Chondrocytes may improve mechanical outcomes in pre-clinical models, but have not been clinically tested. Rapid or pre-vascularization of scaffolds is an important consideration. Overall, there are few published objective measures of post-seeding cell viability, survival, or overall efficacy. SUMMARY: There is no clear consensus on the optimal cell-scaffold combination and mechanisms for seeding. Systematic in vivo work is required to assess differences between tracheal grafts seeded with combinations of clinically deliverable cell types using objective outcome measures, including those for functionality and host immune response.

A comparison of tracheal scaffold strategies for pediatric transplantation in a rabbit model.

OBJECTIVES/HYPOTHESIS: Despite surgical advances, childhood tracheal stenosis is associated with high morbidity and mortality. Various tracheal scaffold strategies have been developed as the basis for bioengineered substitutes, but there is no consensus on which may be superior in vivo. We hypothesized that there would be no difference in morbidity and mortality between three competing scaffold strategies in rabbits. STUDY DESIGN: Pilot preclinical study. METHODS: Tracheal scaffolds were prepared by three methods that have been applied clinically and reported: preserved cadaveric ("Herberhold") allografts, detergent-enzymatically decellularized allografts, and synthetic scaffolds (nanocomposite polymer [polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU)]). Scaffolds were implanted into cervical trachea of New Zealand White rabbits (n = 4 per group) without cell seeding. Control animals (n = 4) received autotransplanted tracheal segments using the same technique. Animals underwent bronchoscopic monitoring of the grafts for 30 days. Macroscopic evaluation of tissue integration, graft stenosis, and collapsibility and histological examinations were performed on explants at termination. RESULTS: All surgical controls survived to termination without airway compromise. Mild to moderate anastomotic stenosis from granulation tissue was detected, but there was evidence suggestive of vascular reconnection with minimal fibrous encapsulation. In contrast, three of the four animals in the Herberhold and POSS-PCU groups, and all animals receiving decellularized allografts, required early termination due to respiratory distress. Herberhold grafts showed intense inflammatory reactions, anastomotic stenoses, and mucus plugging. Synthetic graft integration and vascularization were poor, whereas decellularized grafts demonstrated malacia and collapse but had features suggestive of vascular connection or revascularization. CONCLUSIONS: There are mirror-image benefits and drawbacks to nonrecellularized, decellularized, and synthetic grafts, such that none emerged as the preferred option. Results from prevascularized and/or cell-seeded grafts (as applied clinically) may elucidate clearer advantages of one scaffold type over another. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:E449-E457, 2017.

Congenital tracheobronchial stenosis.

Congenital tracheobronchial stenosis is a rare disease characterized by complete tracheal rings that can affect variable lengths of the tracheobronchial tree. It causes high levels of morbidity and mortality both due to the stenosis itself and to the high incidence of other associated congenital malformations. Successful management of this complex condition requires a highly individualized approach delivered by an experienced multidisciplinary team, which is best delivered within centralized units with the necessary diverse expertise. In such settings, surgical correction by slide tracheoplasty has become increasingly successful over the past 2 decades such that long-term survival now exceeds 88%, with normalization of quality of life scores for patients with non-syndrome-associated congenital tracheal stenosis. Careful assessment and planning of treatment strategies is of paramount importance for both successful management and the provision of patients and carers with accurate and realistic treatment counseling.