Result of airway reconstruction by slide tracheobronchoplasty in children with congenital heart diseases and severe airway stenosis at Hanoi Heart Hospital: A series case report

Congenital airway stenosis (tracheobronchial stenosis) in children is rare, difficult to treat and become more complex when associated with congenital heart defects. In severe airway stenosis, slide tracheobronchoplasty is the most optimal strategy to manage this condition, yet really challenging. We report case series with this combined condition of airway stenosis and congenital heart diseases, which were successfully treated by slide tracheobronchoplasty with concomitant heart repair. We also discuss about the indication, surgical technique as well as postoperative care.

Management of Laryngotracheal Stenosis in Obesity. Is This Another Co-morbidity that Can Be Improved with Weight Loss Following Bariatric Surgery?

Purpose Bariatric surgery improves several obesity-related comorbidities. Laryngotracheal stenosis is a rare condition that is usually managed with repeated endoscopic airway interventions and reconstructive airway surgery. The outcome of these definitive operations is worse in individuals with obesity. There are no studies investigating the effect of weight loss following bariatric surgery in the management of laryngotracheal stenosis. Materials and Methods In an observational study, consecutive patients with a BMI over 35 kg/m2 and laryngotracheal stenosis were prospectively recruited to a bariatric and airway stenosis database in two tertiary care centres. Patients were treated with laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy and control subjects were managed conservatively. Results A total of eleven patients with an initial body mass index of 43 kg/m2 (37–45) were enrolled to this study. Six patients underwent bariatric surgery and five subjects were treated conservatively. After 12 months, the total weight loss of patients undergoing bariatric surgery was 19.4% (14–24%) whilst 2.3% (1–3%) in the control group. The annual number of endoscopic airway interventions following bariatric surgery reduced (p = 0.002). Higher weight loss in patients led to less frequent interventions compared to control subjects (p = 0.004). Patients undergoing laryngotracheal reconstruction following bariatric surgery needed less endoscopic intervention, an annual average of 1.9 interventions before vs 0.5 intervention after. Conservatively managed control subjects required more frequent endoscopic intervention, 1.8 before vs 3.4 after airway reconstruction. Conclusion Bariatric surgery reduced the number of endoscopic airway interventions and enabled patients to undergo successful definitive airway reconstructive surgery.

Multicellular modeling of ciliopathy by combining iPS cells and microfluidic airway-on-a-chip technology

Mucociliary clearance is an essential lung function that facilitates the removal of inhaled pathogens and foreign matter unidirectionally from the airway tract and is innately achieved by coordinated ciliary beating of multiciliated cells. Should ciliary function become disturbed, mucus can accumulate in the airway causing subsequent obstruction and potentially recurrent pneumonia. However, it has been difficult to recapitulate unidirectional mucociliary flow using human-derived induced pluripotent stem cells (iPSCs) in vitro and the mechanism governing the flow has not yet been elucidated, hampering the proper humanized airway disease modeling. Here, we combine human iPSCs and airway-on-a-chip technology, to demonstrate the effectiveness of fluid shear stress (FSS) for regulating the global axis of multicellular planar cell polarity (PCP), as well as inducing ciliogenesis, thereby contributing to quantifiable unidirectional mucociliary flow. Furthermore, we applied the findings to disease modeling of primary ciliary dyskinesia (PCD), a genetic disease characterized by impaired mucociliary clearance. The application of an airway cell sheet derived from patient-derived iPSCs and their gene-edited counterparts, as well as genetic knockout iPSCs of PCD causative genes, made it possible to recapitulate the abnormal ciliary functions in organized PCP using the airway-on-a-chip. These findings suggest that the disease model of PCD developed here is a potential platform for making diagnoses and identifying therapeutic targets and that airway reconstruction therapy using mechanical stress to regulate PCP might have therapeutic value.

Pre-Clinical Application of Functional Human Induced Pluripotent Stem Cell-Derived Airway Epithelial Grafts

Airway pathologies including cancer, trauma and stenosis lack effective treatments, meanwhile airway transplantation and available tissue engineering approaches fail due to epithelial dysfunction. Autologous progenitors do not meet the clinical need for regeneration due to their insufficient expansion and differentiation, for which human induced pluripotent stem cells (hiPSCs) are promising alternatives. Airway epithelial grafts are engineered by differentiating hiPSC-derived airway progenitors into physiological proportions of ciliated (73.9+/-5.5%) and goblet (2.1 +/-1.4%) cells on a Silk Fibroin-Collagen Vitrigel Membrane (SF-CVM) composite biomaterial for transplantation in porcine tracheal defects ex vivo and in vivo. Evaluation of ex vivo tracheal repair using hiPSC-derived SF-CVM grafts demonstrate native-like tracheal epithelial metabolism and maintenance of mucociliary epithelium to day 3. In vivo studies reveal SF-CVM integration, maintenance of airway patency, showing 80.8+/-3.6% graft coverage with an hiPSC-derived pseudostratified epithelium and 70.7+/-2.3% coverage with viable cells, 3 days post-operatively. We demonstrate the utility of bioengineered, hiPSC-derived epithelial grafts for airway repair in a pre-clinical survival model, providing a significant leap for airway reconstruction approaches.

Vocal Fold Injection Augmentation for Post-Airway Reconstruction Dysphonia: A Case Series

Objectives: Post airway reconstruction dysphonia (PARD) is common and has a significant effect on the quality of life of patients. Vocal fold injection augmentation (VFIA) is one treatment that can be used to improve glottic insufficiency in some patients. The goal of this study was to characterize the use and outcomes of VFIA for PARD. Methods: Retrospective chart review from January 2007 to July 2018 at a tertiary pediatric care center. Consecutive patients with PARD who underwent VFIA, who had a preoperative voice evaluation and a follow-up evaluation within 3 months after VFIA (fat, carboxymethylcellulose gel, hyaluronic acid). Results: Thirty-four patients (20 female) underwent VFIA. The mean age at the time of the injection was 13.6 years (SD 6.1). Twenty patients (58.8%) had a history of prematurity and a mean of 1.8 open airway surgeries. After injection, 29/34 patients (85.3%) noted a subjective voice improvement. The baseline Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) overall severity score decreased by a mean of 5.7 (SD = 19.6) points, P = .12. Total pediatric Voice Handicap Index (pVHI) improved by 6.0 (SD = 19.5) points, from 57.4 (SD = 20.0) to 51.4 (SD = 17.2), P = .09. Functional pVHI subscore demonstrated a significant improvement, with a decrease of 3.4 (SD = 7.3) points, P = .02. All procedures were performed as an overnight observation and no complication occurred. Conclusion: Patients with PARD represent a complex subset of patients. VFIA is a straightforward intervention that may improve voice perception. Many patients reported subjective improvement despite minimal objective measurement. Further work is warranted to elucidate the role of injection in management of PARD

Not Just Dyspnoea: Swallowing as a Concern for Adults with Laryngotracheal Stenosis Undergoing Airway Reconstruction

Acquired laryngotracheal stenosis (LTS) is a rare condition causing dyspnea and stridor. Patients often require multiple surgical procedures with no guarantee of a definitive outcome. Difficulty swallowing is a recognised problem associated with LTS and the reconstructive surgeries required to manage the condition. The breathlessness patient’s experience impacts on swallowing, and the vulnerable structures of the larynx are implicated during complex surgeries. This leads to dysphagia post-surgery, with some patients experiencing more chronic symptoms depending on the biomechanical impact of the surgery, or a pre-existing dysphagia. Despite this there is limited observational research about the dysphagia associated with LTS, with no exploration of the patient experience. Our aim was to investigate patient experience of living with LTS focussing on dysphagia in order to guide clinical practice. A qualitative study was completed using focus groups and semi-structured interviews with 24 patients who have had reconstructive surgery for LTS. Thematic analysis was used to identify three over-arching themes: The Physical Journey, The Emotional Journey and The Medical Journey. Key sub-themes included the importance of self-management and control, presence of symptoms, benefits of therapy, living with a life-long condition, fear and anxiety, autonomy, medicalisation of normal processes and the dichotomy between staff expertise and complacency. Swallowing was connected to all themes. The results are reviewed with consideration of the wider literature of lived experience particularly in relation to other chronic conditions and those that carry a high symptom burden such as head and neck cancer. Future clinical and research recommendations have been made. Akin to other clinical groups, adults with LTS are keen that management of their swallowing is person-centred and holistic.