Colin R Butler

Colin R Butler
Great Ormond Street Hospital for Children NHS Foundation Trust | GOSH

PhD FRCS (ORL-HNS)

About

116
Publications
15,115
Reads
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2,190
Citations
Citations since 2017
66 Research Items
1667 Citations
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20172018201920202021202220230100200300400
20172018201920202021202220230100200300400
Additional affiliations
October 2011 - present
University College London
Position
  • Wellcome Research Fellow
October 2010 - November 2011
Great Ormond Street Hospital for Children NHS Foundation Trust
Position
  • Tracheal Research Fellow

Publications

Publications (116)
Preprint
Full-text available
Children infected with SARS-CoV-2 rarely progress to respiratory failure, but the risk of mortality in infected people over 85 years of age remains high, despite vaccination and improving treatment options. Here, we take a comprehensive, multidisciplinary approach to investigate differences in the cellular landscape and function of paediatric (<11y...
Article
Full-text available
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 no...
Article
Full-text available
Decellularisation of oesophagi from several species for tissue engineering is well described, but successful implantation in animal models of oesophageal replacement has been challenging. The purpose of this study was to assess feasibility and applicability of oesophageal replacement using decellularised porcine oesophageal scaffolds in a new pre-c...
Article
Full-text available
Objective: This systematic review aims to provide an overview of the current evidence-base for paediatric surgical reinnervation in unilateral and bilateral vocal fold palsies in clinical practice. We aim to assess patient demographics, surgical technique and pre- and post-operative outcome measures. Methods: A systematic literature review was p...
Article
Background Patients with MEN2 without family history often present late with advanced MTC. Surgery is not always curative but RET tyrosine kinase pathway is a potential target for molecular treatment for progressive MTC. Methods Retrospective review of clinical, genetic, biochemical and imaging data of children with MEN2 who developed recurrent an...
Article
Full-text available
It is not fully understood why COVID-19 is typically milder in children1–3. To examine differences in response to SARS-CoV-2 infection in children and adults, we analysed paediatric and adult COVID-19 patients and healthy controls (total n=93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In healthy...
Conference Paper
Full-text available
Introduction and Objectives Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic. Whilst a substantial proportion of adults infected with SARS-CoV-2 progress to develop severe disease, children rarely manifest respiratory complications. However, the underlying mecha...
Article
Full-text available
Objective Reliable airway patency diagnosis in fetal tracheolaryngeal obstruction is crucial to select and plan ex utero intrapartum treatment (EXIT) surgery. We compared the clinical utility of magnetic resonance imaging (MRI) super-resolution reconstruction (SRR) of the trachea, which can mitigate unpredictable fetal motion effects, with standard...
Article
Full-text available
Objectives: To determine the feasibility of micro-CT as a high-resolution 3D imaging tool for thyroglossal duct cysts and to evaluate its role augmenting traditional histopathological examination of resected specimens. Methods: A single centre, prospective case series of consecutive children undergoing excision of a thyroglossal duct cyst was perfo...
Article
Summary statement: Simulation resources offer an opportunity to highlight aerosol dispersion within the operating room environment. We demonstrate our methodology with a supporting video that can offer operating room teams support in their practical understanding of aerosol exposure and the importance of personal protective equipment.
Article
Subglottic haemangioma presents as progressive obstruction in the neonatal and infantile airway, with a soft lesion seen during endoscopy. Diagnosis is based on macroscopic findings, biopsy is not usually performed and propranolol is first-line treatment. In contrast, ectopic thymus is a rare differential diagnosis for subglottic mass made by histo...
Article
Full-text available
Background Development of therapeutic approaches for rare respiratory diseases is hampered by the lack of systems that allow medium-to-high-throughput screening of fully differentiated respiratory epithelium from affected patients. This is a particular problem for primary ciliary dyskinesia (PCD), a rare genetic disease caused by mutations in genes...
Preprint
Full-text available
While a substantial proportion of adults infected with SARS-CoV-2 progress to develop severe disease, children rarely manifest respiratory complications. Therefore, understanding differences in the local and systemic response to SARS-CoV-2 infection between children and adults may provide important clues about the pathogenesis of SARS-CoV-2 infecti...
Article
Background: Parathyroid failure after total thyroidectomy is the commonest adverse event amongst both children and adults. The phenomenon of late recovery of parathyroid function, especially in young patients with persistent hypoparathyroidism, is not well understood. This study investigated differences in rates of parathyroid recovery in children...
Article
A bilobed tongue base was identified in an infant with multiple other head, neck and cardiac congenital anomalies. This anatomical variation of the posterior tongue is rare, with only two other cases identified in the literature. We report a case of a 5-month-old boy with a bilobed posterior tongue incidentally identified during workup for cardiac...
Article
Background Long segment congenital tracheal stenosis (LSCTS) is a rare, complex condition which is often poorly understood by community-based health professionals (HPs). Anecdotally, such HPs often lack confidence providing care for children, resulting in children being brought to the tertiary centre more frequently than necessary. We wanted to ide...
Chapter
The larynx, trachea and bronchi have separate embryological development and as such a variety of congenitalCongenitalanomaliesCongenital anomaly are possible. In addition, improvements in neonatal intensive care have led to increased numbers of childrenChildren with secondary airwayAirwaypathologyPathology. Our preference is for conservative or end...
Chapter
Patients presenting with severe tracheal disease have very few options once all standard surgical options have been exhausted. Curative resection and or reconstruction is not possible in all cases and in some instances regular interventions to the airway are simply not enough to keep it patent. Whilst the paradigm of replacing organs de novo is cer...
Article
Objectives: Assess the clinical utility of an Endoscopic Integrated Multipoint Laser System (EMLS) to otology. This is an emerging technology from automotive engineering that may offer the ability to accurately measure anatomy and pathology using an endoscope while undertaking ear surgery. Patients: Simulated otology patients were used incorpora...
Conference Paper
Objectives Aortopexies are part of GOSH’s specialist tracheal services offered to children with severe tracheobronchomalacia, with an average of 10 cases performed per year. We wanted to identify safe and effective aspects of the anaesthetic care within this complex group of patients undergoing the procedure. Methods We looked at patient character...
Article
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...
Conference Paper
Background Lung cancer is the leading cause of cancer death, of which 80-90% are attributed to tobacco smoking. Our understanding of how tobacco exposure affects mutational burden, mutational signatures, driver mutations and clonal dynamics in normal lung tissue is limited. Also, genetic differences between normal cells and cancer cells in lung has...
Article
Full-text available
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 treatme...
Preprint
Full-text available
The airway epithelium is a key protective barrier, the integrity of which is preserved by the self-renewal and differentiation of basal stem cells. Epithelial cells are central to the pathogenesis of multiple lung diseases. In chronic lung diseases, increasing age is a principle risk factor. Few studies have explored the differences between airway...
Article
Aortopexy has been demonstrated to be an effective procedure for the treatment of tracheo(broncho)malacia in children. Several operative approaches have been proposed in the literature, including left anterior thoracotomy, right thoracotomy, full median sternotomy, or a thoracoscopic approach. In this video tutorial we present our technique for ant...
Article
Paediatric otolaryngology practice involves examining and operating in anatomical locations with high levels of aerosol generation and transmission of COVID-19 to treating clinicians, especially from the asymptomatic patient populations including children. During the COVID-19 pandemic all emergent otolaryngological conditions affecting the airway,...
Preprint
Full-text available
Development of therapeutic approaches for rare respiratory diseases is hampered by the lack of systems that allow medium-to-high-throughput screening of fully differentiated respiratory epithelium from affected patients. This is a particular problem for primary ciliary dyskinesia (PCD), a rare genetic disease caused by mutations in genes that adver...
Article
Full-text available
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...
Article
Aim: Symptomatic tracheobronchomalacia can be fatal. Successful treatment includes aortopexy. We report outcomes of the thoracoscopic approach in a single centre. Methods: All patients undergoing thoracoscopic aortopexies from 2009 to 2018 were retrospectively reviewed. Data was reported as median (interquartile range). Risk factors for subseque...
Article
Full-text available
Objectives: The objectives of this study were to measure 'health-related quality of life' (HRQoL) in children following slide tracheoplasty for long-segment tracheal stenosis (LSTS) and to explore the relationship of comorbidities and parental mental health with HRQoL outcomes. Methods: A cross-sectional study was undertaken with children who ha...
Article
Full-text available
Impact statement: Methodologies for incorporation of cells into tissue-engineered grafts, particularly at the later preclinical stages, are suboptimal and non-validated, and monitoring cell fate within scaffolds cultured in bioreactors and in vivo is challenging. In this study, we demonstrate how bioluminescence imaging (BLI) can overcome these di...
Article
Full-text available
Impact statement: This article describes a method for engrafting epithelial progenitor cells to a revascularized scaffold in a protective and supportive collagen-rich environment. This method has the potential to overcome two key limitations of existing grafting techniques as epithelial cells are protected from mechanical shear and the relatively...
Article
Full-text available
Tissue engineering is a branch of regenerative medicine that aims to manipulate cells and scaffolds to create bioartificial tissues and organs for patients. A major challenge lies in monitoring the blood supply to the new tissue following transplantation: the integration and neovascularization of scaffolds in vivo is critical to their functionality...
Conference Paper
Patients with significant airway stenosis and end-stage airway disease are faced with a dismal prognosis and often clinical solutions are not possible. Tracheal replacement has been historically challenging and is often associated with high failure rates. Methods to replace the airway are complex, and a plethora of strategies have been developed. C...
Article
Full-text available
There is considerable interest in the ex vivo propagation of primary human basal epithelial stem/progenitor cells with a view to their use in drug development, toxicity testing and regenerative medicine. These cells can be expanded in co-culture with mitotically inactivated 3T3-J2 murine embryonic feeder cells but, similar to other epithelial cell...
Data
Western blot analyses of STAT6 phosphorylation status in primary human airway basal epithelial cells treated with recombinant human HGF in the presence of anti-GAB2 siRNA. This figure is associated with Fig 4A and each group of blots (A and B) were performed on independent donor cultures. (TIFF)
Data
Receptor tyrosine kinases assayed in the R&D systems human phospho-receptor tyrosine kinase (RTK) array kit (Catalogue Number ARY001B). (TIFF)
Data
Additional western blot analyses of MET, GAB2 and STAT6 phosphorylation status in primary human airway basal epithelial cells treated with recombinant human HGF. (A) Western blot analysis of the phosphorylation status of STAT6 following treatment with a dose range of recombinant human HGF. This panel is associated with Fig 3C and was performed on a...
Data
Additional western blot analyses of HGF-induced STAT6 phosphorylation in A431 cells. (A) This panel is associated with Fig 4B and was performed on independent cell lysates. (B) This panel is associated with Fig 4C and was performed on independent A431 cell lysates but using a lower (1 mg) protein input. (C) This panel is associated with Fig 4C and...
Article
The use of operating laser poses a potential risk both to the patient and to theatre staff and so it is crucial that safety protocols and procedures are followed meticulously in every case – particularly in the setting of laser surgery in the airway. All existing guidelines and standards on laser safety highlight the importance of pre‐use checks re...
Article
Objectives: Our study describes and analyses the results from aortopexy for the treatment of airway malacia in children. Methods: Demographic data, characteristics and preoperative, operative and outcome details, including the need for reintervention, were collected for children undergoing aortopexy between 2006 and 2016. Results: One hundred...
Article
Introduction Slide tracheoplasty is now considered gold standard treatment for long segment congenital tracheal stenosis. Outcomes are typically focused upon airway patency. Dysphagia is often reported in children undergoing cardiothoracic surgery, but not specifically after slide tracheoplasty. This study was carried out to describe the nature and...
Article
Full-text available
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 morbidit...
Article
Statement of significance: Decellularization is a front-running strategy to generate scaffolds for tracheal tissue-engineering. Preservation of biomechanical properties of the trachea during this process is paramount to successful clinical transplantation. In this paper, we evaluated a novel method for biomechanical testing of decellularized trach...
Article
Full-text available
Tracheal replacement for the treatment of end-stage airway disease remains an elusive goal. The use of tissue-engineered tracheae in compassionate use cases suggests that such an approach is a viable option. Here, a stem cell-seeded, decellularized tissue-engineered tracheal graft was used on a compassionate basis for a girl with critical tracheal...
Article
Full-text available
Patients with large tracheal lesions unsuitable for conventional endoscopic or open operations may require a tracheal replacement but there is no present consensus of how this may be achieved. Tissue engineering using decellularized or synthetic tracheal scaffolds offers a new avenue for airway reconstruction. Decellularized human donor tracheal sc...
Article
Patients with large tracheal lesions unsuitable for conventional endoscopic or open operations may require a tracheal replacement but there is no present consensus of how this may be achieved. Tissue engineering using decellularized or synthetic tracheal scaffolds offers a new avenue for airway reconstruction. Decellularized human donor tracheal sc...
Article
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 s...
Conference Paper
Background Tracheal reconstruction relies on the use of a split skin graft to re-epithelialise the mucosal layer. Since split skin grafts are made up of a keratinising stratified epithelial layer, sloughing occurs within the airway with mucus retention and subsequent airway obstruction. The delivery of a graft with the same mucociliary function as...
Conference Paper
BACKGROUND: In order to treat lung cancer more effectively we must understand how pre-invasive lung cancer progresses into invasive disease. Recent data demonstrates that pre-invasive lung cancer cells migrate across normal epithelium prior to invasion. RhoA regulates cell motility in a variety of cell types through regulation of cytoskeletal dynam...
Chapter
Full-text available
Although basal cells function as human airway epithelial stem cells, analysis of these cells is limited by in vitro culture techniques that permit only minimal cell growth and differentiation. Here, we report a protocol that dramatically increases the long-term expansion of primary human airway basal cells while maintaining their genomic stability...
Article
Objective: To validate the Airway-Dyspnoea-Voice-Swallow (ADVS) instrument as a disease-specific Patient-Reported Outcome Measure in paediatric laryngotracheal stenosis. Design: Prospective observational study. Setting: A quaternary referral centre for complex airway disease. Participants: Forty-eight patients (30 males) with a mean age of 4...
Article
We would like to thank Wurtz and colleagues for their comments on our article documenting the four-year follow-up of the first tissue-engineered total tracheal replacement in a child [1]. Whilst the fate of the tracheal allograft cannot be determined with certainty, serial endoscopy and computed tomography indicate the graft embedded within the ste...
Conference Paper
Background Stem-cell-based tracheal replacement has been used to treat patients with end-stage airway disease in compassionate cases. Clinical experience suggests that restoration of an epithelial barrier is a priority to improve outcomes, but recent data suggest that a substantial number of autologous epithelial cells are required for effective en...
Conference Paper
Background Techniques to replace airway mucosa rely on split skin or buccal mucosal grafts. These grafts lead to sloughing within the airway, mucus retention, and infection because of the absence of ciliary function. To address this problem, we have tissue-engineered a respiratory epithelial sheet to replace damaged airway mucosa. This type of graf...
Article
Full-text available
RATIONALE: Stem cell-based tracheal replacement represents an emerging therapeutic option for patients with otherwise untreatable airway diseases including long-segment congenital tracheal stenosis and upper airway tumors. Clinical experience demonstrates that restoration of mucociliary clearance in the lungs following transplantation of tissue-eng...
Article
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...
Article
Full-text available
Regenerative medicine offers hope of a sustainable solution for severe airway disease by the creation of functional, immunocompatible organ replacements. When considering fetuses and newborns, there is a specific spectrum of airway pathologies that could benefit from cell therapy and tissue engineering applications. While hypoplastic lungs associat...
Article
Full-text available
Polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU) is a versatile nanocomposite biomaterial with growing applications as a bioscaffold for tissue engineering. Integration of synthetic implants with host tissue can be problematic but could be improved by topographical modifications. We describe optimization of POSS-PCU by...