SOX21 modulates SOX2-initiated differentiation of epithelial cells in the extrapulmonary airways.

SOX2 expression levels are crucial for the balance between maintenance and differentiation of airway progenitor cells during development and regeneration. Here, we describe patterning of the mouse proximal airway epithelium by SOX21, which coincides with high levels of SOX2 during development. Airway progenitor cells in this SOX2+/SOX21+ zone show differentiation to basal cells, specifying cells for the extrapulmonary airways. Loss of SOX21 showed an increased differentiation of SOX2+ progenitor cells to basal and ciliated cells during mouse lung development. We propose a mechanism where SOX21 inhibits differentiation of airway progenitors by antagonizing SOX2-induced expression of specific genes involved in airway differentiation. Additionally, in the adult tracheal epithelium, SOX21 inhibits basal to ciliated cell differentiation. This suppressing function of SOX21 on differentiation contrasts SOX2, which mainly drives differentiation of epithelial cells during development and regeneration after injury. Furthermore, using human fetal lung organoids and adult bronchial epithelial cells, we show that SOX2+/SOX21+ regionalization is conserved. Lastly, we show that the interplay between SOX2 and SOX21 is context and concentration dependent leading to regulation of differentiation of the airway epithelium.

Development of a core outcome set for congenital pulmonary airway malformations: study protocol of an international Delphi survey.

INTRODUCTION: A worldwide lack of consensus exists on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM) even though the incidence is increasing. Either a surgical resection is performed or a wait-and-see policy is employed, depending on the treating physician. Management is largely based on expert opinion and scientific evidence is scarce. Wide variations in outcome measures are seen between studies making comparison difficult thus highlighting the lack of universal consensus in outcome measures as well. We aim to define a core outcome set which will include the most important core outcome parameters for paediatric patients with an asymptomatic CPAM. METHODS AND ANALYSIS: This study will include a critical appraisal of the current literature followed by a three-stage Delphi process with two stakeholder groups. One surgical group including paediatric as well as thoracic surgeons, and a non-surgeon group including paediatric pulmonologists, intensive care and neonatal specialists. All participants will score outcome parameters according to their level of importance and the most important parameters will be determined by consensus. ETHICS AND DISSEMINATION: Electronic informed consent will be obtained from all participants. Ethical approval is not required. After the core outcome set has been defined, we intend to design an international randomised controlled trial: the COllaborative Neonatal NEtwork for the first CPAM Trial, which will be aimed at determining the optimal management of patients with asymptomatic CPAM.

Alveolar capillary dysplasia with misalignment of the pulmonary veins: clinical, histological, and genetic aspects.

Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV) is a rare and lethal disorder mainly involving the vascular development of the lungs. Since its first description, significant achievements in research have led to a better understanding of the underlying molecular mechanism of ACD/MPV and genetic studies have identified associations with genomic alterations in the locus of the transcription factor FOXF1. This in turn has increased the awareness among clinicians resulting in over 200 cases reported so far, including genotyping of patients in most recent reports. Collectively, this promoted a better stratification of the patient group, leading to new perspectives in research on the pathogenesis. Here, we provide an overview of the clinical aspects of ACD/MPV, including guidance for clinicians, and review the ongoing research into the complex molecular mechanism causing this severe lung disorder.

Iatrogenic subtotal stenosis of the right subclavian artery treated with percutaneous transluminal angioplasty.

This report describes a rare vascular complication of surgical placement of a marking clip and a possible approach to problem solving. A 55-year-old patient presented with loss of sensation in the fingers and loss of peripheral pulsations in the right arm 4 days after right upper lobectomy for a pT2N1 moderately differentiated adenocarcinoma of the lung. Duplex examination and computed tomography were performed the same day and showed a subtotal stenosis of the right subclavian artery, which was caused by the surgical placement of a metal clip to mark the surgical boundary. Selective angiography was subsequently performed. Percutaneous transluminal angioplasty (PTA) successfully dilated the stenosis and pushed the clip off. Flow in the right subclavian artery (RSA) was completely restored as were neurology and peripheral pulses. In conclusion, arterial stenosis by a surgical (marking) clip may be feasibly treated with PTA.