Lung Hypoplasia Research Articles

Management of child with unilateral lung hypoplasia for ophthalmic surgery.

Management of child with unilateral lung hypoplasia for ophthalmic surgery.

A death due to complications following late-onset congenital diaphragmatic hernia in a young child

Congenital diaphragmatic hernia (CDH) is a rare anatomical birth defect, causing the diaphragm fails to fuse completely, leaving a defect and causing herniation of the abdominal viscera towards the thoracic cavity. Though most cases of CDH are symptomatic and diagnosed in the early stages of life some asymptomatic cases may go undetected and later detect as incidental or may present with respiratory or gastrointestinal symptoms. We report a case of late-onset CDH which leads to a rapidly fatal medical emergency causing challenges in clinical diagnosis. An eight-year-old previously healthy schoolgirl was admitted to a primary care hospital following recurrent upper abdominal pain, nausea, and vomiting for a duration of 3 consecutive days. According to the parents she has taken treatment from a general practitioner. She was afebrile, hypotensive, tachycardic, and drowsy and was found unresponsive during transfer to a tertiary care hospital and was pronounced dead. On opening the thoracic cavity, it was noted that some of the abdominal contents like the entire stomach, duodenum, and proximal part of the small intestine, splenic flexure of the transverse colon were present within the left hemi thorax causing left lung hypoplasia, thoracic midline shift, intestinal compression, and elevated luminal pressure causing gastric erosions and chemical peritonitis. This case highlights the importance of higher clinical vigilance and the value of early diagnosis and timely medical attention to relatively uncommon but surgically correctable conditions like CDH.

Prenatal treprostinil reduces the pulmonary hypertension phenotype in the rat model of congenital diaphragmatic hernia.

SummaryBackgroundPersistent pulmonary hypertension (PH) causes significant mortality and morbidity in infants with congenital diaphragmatic hernia (CDH). Since pulmonary vascular abnormalities in CDH develop early during foetal development, we hypothesized that prenatal maternal administration of treprostinil, through its anti-remodelling effect, would improve the PH-phenotype in the nitrofen rat model of CDH.MethodsIn a dose-finding study in normal, healthy pregnant rats, we demonstrated target-range foetal plasma treprostinil concentrations without signs of toxicity. Next, an efficacy study was performed assessing the effects of treprostinil administration at 900 and 1500ng/kg/min from gestational day (GD) 16 until term (GD 21) in CDH and control pups. Pulmonary vascular and airway morphometry, lung mechanics, and expression patterns of genes implicated in the prostaglandin vasoactive pathway were studied.FindingsIn rats maternal administration of 1500ng/kg/min treprostinil reached target foetal concentrations, with no detrimental maternal or foetal side-effects. Prenatal exposure to 900 and 1500 ng/kg/min treprostinil reduced the medial wall thickness (%MWT) (CDH·900, 38.5± 8·4%; CDH.1500, 40·2±9·7%; CDH, 46·6±8·2%; both p < 0·0001) in rat pups with CDH, however increased the %MWT in normal foetuses (C.T.900, 36·6±11·1%; C.T.1500, 36·9±9·3%; C.P., 26·9±6·2%; both p < 0·001). Pulmonary airway development, lung hypoplasia and pulmonary function were unaffected by drug exposure.InterpretationIn pregnant rats maternally administered treprostinil crosses the placenta, attains foetal target concentrations, and is well tolerated by both mother and foetuses. This report shows a significant reduction of pulmonary arteriole muscularization with prenatal treprostinil in a nitrofen rat model, supporting the promise of this treatment approach for PH of CDH.FundingUnited Therapeutics Corporation provided treprostinil and financial support (ISS-2020-10879).

WNT/RYK signaling functions as an antiinflammatory modulator in the lung mesenchyme

A number of inflammatory lung diseases, including chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and pneumonia, are modulated by WNT/β-catenin signaling. However, the underlying molecular mechanisms remain unclear. Here, starting with a forward genetic screen in mouse, we identify the WNT coreceptor Related to receptor tyrosine kinase (RYK) acting in mesenchymal tissues as a cell survival and antiinflammatory modulator. Ryk mutant mice exhibit lung hypoplasia and inflammation as well as alveolar simplification due to defective secondary septation, and deletion of Ryk specifically in mesenchymal cells also leads to these phenotypes. By analyzing the transcriptome of wild-type and mutant lungs, we observed the up-regulation of proapoptotic and inflammatory genes whose expression can be repressed by WNT/RYK signaling invitro. Moreover, mesenchymal Ryk deletion at postnatal and adult stages can also lead to lung inflammation, thus indicating a continued role for WNT/RYK signaling in homeostasis. Our results indicate that RYK signaling through β-catenin and Nuclear Factor kappa B (NF-κB) is part of a safeguard mechanism against mesenchymal cell death, excessive inflammatory cytokine production, and inflammatory cell recruitment and accumulation. Notably, RYK expression is down-regulated in the stromal cells of pneumonitis patient lungs. Altogether, our data reveal that RYK signaling plays critical roles as an antiinflammatory modulator during lung development and homeostasis and provide an animal model to further investigate the etiology of, and therapeutic approaches to, inflammatory lung diseases.

The TALE never ends: A comprehensive overview of the role of PBX1, a TALE transcription factor, in human developmental defects.

PBX1 is a highly conserved atypical homeodomain transcription factor (TF) belonging to the TALE (three amino acid loop extension) family. Dimerized with other TALE proteins, it can interact with numerous partners and reach dozens of regulating sequences, suggesting its role as a pioneer factor. PBX1 is expressed throughout the embryonic stages (as early as the blastula stage) in vertebrates. In human, PBX1 germline variations are linked to syndromic renal anomalies (CAKUTHED). In this review, we summarized available data on PBX1 functions, PBX1-deficient animal models, and PBX1 germline variations in humans. Two types of genetic alterations were identified in PBX1 gene. PBX1 missense variations generate a severe phenotype including lung hypoplasia, cardiac malformations, and sexual development defects (DSDs). Conversely, truncating variants generate milder phenotypes (mainly cryptorchidism and deafness). We suggest that defects in PBX1 interactions with various partners, including proteins from the HOX (HOXA7, HOXA10, etc.), WNT (WNT9B, WNT3), and Polycomb (BMI1, EED) families are responsible for abnormal proliferation and differentiation of the embryonic mesenchyme. These alterations could explain most of the defects observed in humans. However, some phenotype variability (especially DSDs) remains poorly understood. Further studies are needed to explore the TALE family in greater depth.

Quantitative cardiopulmonary magnetic resonance imaging in neonatalcongenital diaphragmatic hernia.

Pulmonary arterial hypertension, impaired cardiac function and lung hypoplasia are common in infants with congenital diaphragmatic hernia (CDH) and are associated with increased morbidity and mortality. Robust noninvasive methods to quantify these abnormalities in early infancy are lacking. To determine the feasibility of MRI to quantify cardiopulmonary hemodynamics and function in infants with CDH and to investigate left-right blood flow and lung volume discrepancies. We conducted a prospective MRI study of 23 neonates (isolated left CDH: 4 pre-repair, 7 post-repair, 3 pre- and post-repair; and 9 controls) performed on a small-footprint 1.5-tesla (T) scanner. We calculated MRI-based pulmonary arterial blood flow, left ventricular eccentricity index, cardiac function and lung volume. Using the Wilcoxon rank sum test for continuous data and Fisher exact test for categorical data, we made pairwise group comparisons. The right-to-left ratios for pulmonary artery blood flow and lung volume were elevated in pre-repair and post-repair CDH versus controls (flow: P&lt;0.005; volume: P&lt;0.05 pre-/post-repair). Eccentricity index at end-systole significantly differed between pre-repair and post-repair CDH (P&lt;0.01) and between pre-repair CDH and controls (P&lt;0.001). Cardiopulmonary MRI is a viable method to serially evaluate cardiopulmonary hemodynamics and function in critically ill infants and is useful for capturing left-right asymmetries in pulmonary blood flow and lung volume.

Identification of SOX2 Interacting Proteins in the Developing Mouse Lung With Potential Implications for Congenital Diaphragmatic Hernia.

Congenital diaphragmatic hernia is a structural birth defect of the diaphragm, with lung hypoplasia and persistent pulmonary hypertension. Aside from vascular defects, the lungs show a disturbed balance of differentiated airway epithelial cells. The Sry related HMG box protein SOX2 is an important transcription factor for proper differentiation of the lung epithelium. The transcriptional activity of SOX2 depends on interaction with other proteins and the identification of SOX2-associating factors may reveal important complexes involved in the disturbed differentiation in CDH. To identify SOX2-associating proteins, we purified SOX2 complexes from embryonic mouse lungs at 18.5 days of gestation. Mass spectrometry analysis of SOX2-associated proteins identified several potential candidates, among which were the Chromodomain Helicase DNA binding protein 4 (CHD4), Cut-Like Homeobox1 (CUX1), and the Forkhead box proteins FOXP2 and FOXP4. We analyzed the expression patterns of FOXP2, FOXP4, CHD4, and CUX1 in lung during development and showed co-localization with SOX2. Co-immunoprecipitations validated the interactions of these four transcription factors with SOX2, and large-scale chromatin immunoprecipitation (ChIP) data indicated that SOX2 and CHD4 bound to unique sites in the genome, but also co-occupied identical regions, suggesting that these complexes could be involved in co-regulation of genes involved in the respiratory system.

Distinct Epithelial Cell Profiles in Normal Versus Induced-Congenital Diaphragmatic Hernia Fetal Lungs.

BackgroundRecent studies identified a great diversity of cell types in precise number and position to create the architectural features of the lung that ventilation and respiration at birth depend on. With damaged respiratory function at birth, congenital diaphragmatic hernia (CDH) is one of the more severe causes of fetal lung hypoplasia with unspecified cellular dynamics.Objectives To characterize the epithelial cell tissue in hypoplastic lungs, a careful analysis regarding pulmonary morphology and epithelial cell profile was conducted from pseudoglandular-to-saccular phases in normal versus nitrofen-induced CDH rat lungs.DesignOur analysis comprises three experimental groups, control, nitrofen (NF) and CDH, in which the relative expression levels (western blot) by group and developmental stage were analyzed in whole lung. Spatiotemporal distribution (immunohistochemistry) was revealed by pulmonary structure during normal and hypoplastic fetal lung development. Surfactant protein-C (SP-C), calcitonin gene-related peptide (CGRP), clara cell secretory protein (CCSP), and forkhead box J1 (FOXJ1) were the used molecular markers for alveolar epithelial cell type 2 (AEC2), pulmonary neuroendocrine, clara, and ciliated cell profiles, respectively.ResultsGenerally, we identified an aberrant expression of SP-C, CGRP, CCSP, and FOXJ1 in nitrofen-exposed lungs. For instance, the overexpression of FOXJ1 and CGRP in primordia of bronchiole defined the pseudoglandular stage in CDH lungs, whereas the increased expression of CGRP in bronchi; FOXJ1 and CGRP in terminal bronchiole; and SP-C in BADJ classified the canalicular and saccular stages in hypoplastic lungs. We also described higher expression levels in NF than CDH or control groups for both FOXJ1 in bronchi, terminal bronchiole and BADJ at canalicular stage, and SP-C in bronchi and terminal bronchiole at canalicular and saccular stages. Finally, we report an unexpected expression of FOXJ1 in BADJ at canalicular and saccular stages, whereas the multi cilia observed in bronchi were notably absent at embryonic day 21.5 in induced-CDH lungs.ConclusionThe recognized alterations in the epithelial cell profile contribute to a better understanding of neonatal respiratory insufficiency in induced-CDH lungs and indicate a problem in the epithelial cell differentiation in hypoplastic lungs.

Embryonic Over‐Expression Of RAGE In Mouse Lung Modulates Thyroid Transcription Factor (TTF)‐1 And Surfactant Expression

Receptors for advanced glycation end‐products (RAGE) are multi‐ligand cell surface receptors of the immunoglobin superfamily prominently expressed by lung epithelium. Previous experiments demonstrate that over‐expression of RAGE by murine alveolar epithelium throughout embryonic development causes neonatal lethality coincident with significant lung hypoplasia. In the current study, we evaluated the expression of TTF‐1, a homeodomain‐containing transcription factor critical for branching morphogeneis, in mice that differentially expressed RAGE. We also contexualized TTF‐1 expression with the abundance of FoxA2, a winged double helix DNA binding protein that influences respiratory epithelial cell differentiation, and surfactant proteins. Conditional RAGE over‐expression was induced in mice throughout gestation (embryonic day (E)0‐18.5) as well as during the critical saccular period (E15.5‐18.5) of development and analyses were conducted on E18.5 lung tissue. Histology revealed marked loss of lung tissue beginning in the canalicular stage of lung development and continuing throughout the saccular period. We discovered consistently decreased expression for both TTF‐1 and FoxA2 in lungs from TG mice compared to age‐matched controls. We also clarified diminished surfactant protein abundance in TG mice, suggesting possible hindered differentiation and/or proliferation of alveolar epithelial cells under the genetic control of these two critical transcription factors. These results demonstrate that RAGE must be specifically regulated during lung formation and that perturbation of epithelial cell differentiation culminating in respiratory distress and perinatal lethality may coincide with elevated RAGE expression in the lung parenchyma.

A Fetus with 17q23.1-q23.2 Microdeletion Presents with Primary Bilateral Lung Hypoplasia in Utero

Background:Patients with 17q23.1-q23.2 microdeletion syndrome have common features, including mild to moderate developmental delay; microcephaly; heart defects; and hand, foot, and limb abnormalities. Case Report: We describe a fetus with 2.14 Mb microdeletion involving 17q23.1-q23.2 and presenting with primary bilateral lung hypoplasia in utero. The fetal biometry measurement and estimated fetal weight had a two-week delay but they were still above the 10th percentile. There were no other structural abnormalities. Primary lung hypoplasia is infrequent and has a poor prognosis, especially when bilateral. There are no reports of fetal survival with primary bilateral lung hypoplasia. Conclusion: This is the first report of the coexistence of primary lung hypoplasia and chromosome 17q23.1-q23.2 microdeletion detected during fetal life.

A case of pulmonary artery sling, unilateral lung hypoplasia, and congenital heart disease

Vascular rings are rare congenital anomalies that primarily result from an embryological derangement of the paired aortic arches or branching pulmonary arteries. They make up &lt;1% of all cardiac defects. Double aortic arch and right-sided aortic arch with the left ligamentum arteriosum are the most common types, making up 85– 95% of cases, with pulmonary artery slings making up about 10% of cases. The prevalence is estimated as 59 per million children with very few cases reported worldwide. The clinical presentation is variable and this includes severe acute life-threatening episodes, recurrent apnea, severe respiratory distress, feeding difficulties persistent cough, wheezing, or stridor. In some cases, affected individuals may be completely asymptomatic. A high index of suspicion is needed to suspect and diagnose vascular rings as they are uncommon but surgically treatable. We present a case of a 5-day-old term neonate referred to our facility with respiratory distress associated with stridor which started 12 h post-delivery.

Management of Pulmonary Hypertension in Preterm Infants—A Review

Persistent pulmonary hypertension of newborn is being increasingly diagnosed in extremely premature infants, especially if associated with preterm prelabour rupture of membranes and lung hypoplasia. Late-onset pulmonary hypertension (PH) associated with bronchopulmonary dysplasia is because of pulmonary vascular remodeling and altered vasoreactivity. PH in both these settings is associated with around 20% increase in higher mortality and morbidity. The steps in the management of early-onset PH in these neonates, like in term infants, are supportive measures, oxygenation, lung recruitment, and ventilation. In extremely preterm infants, PH occurs because of the paucity of the pulmonary vascular bed and may not respond well to pulmonary vasodilators, such as iNO and sildenafil. Magnesium sulfate can be effective in reducing the pulmonary pressure, especially in resource-limited settings. Milrinone is considered in neonates with PH and poor cardiac function. In preterm infants with PH secondary to bronchopulmonary dysplasia, the emphasis is on oxygen therapy, nutrition, and correction of comorbidities along with some role of vasodilators.

Congenital diaphragmatic hernia. A systematic analysis

Congenital diaphragmatic hernia is a condition characterized by a defect in the diaphragm that leads to protrusion of abdominal contents into the thoracic cavity interfering with normal development of the fetal lungs. The defect may range from a small aperture in the posterior muscle rim to complete absence of the diaphragm. The pathophysiology of congenital diaphragmatic hernia is a combination of lung hypoplasia and immature birth associated with persistent pulmonary hypertension of the newborn and cardiac dysfunction. Prenatal assessment of the lung-to-head ratio and the position of the liver (presence or absence of a liver lobe in the chest) by ultrasound are used to diagnose and predict outcomes. Delivery of infants with congenital diaphragmatic hernia is recommended close to term gestation. Immediate management at birth includes bowel decompression, avoidance of mask ventilation and endotracheal tube placement if required. The primary focus of management includes gentle ventilation of the lungs, hemodynamic monitoring and treatment of pulmonary hypertension, followed by preparation for surgery only after stabilization of the newborns condition. Although the US Food and Drug Administration do not approve inhaled nitric oxide, it is commonly used to treat persistent pulmonary hypertension of the newborn induced by congenital diaphragmatic hernia. Extracorporeal membrane oxygenation is usually considered after failure of standard resuscitative interventions in neonates with congenital diaphragmatic hernia born at 34 weeks of gestational age or with body weight 2 kg and no associated gross fetal anomalies. Multiple factors such as premature birth, congenital anomalies, severity of pulmonary hypertension, type of postpartum recovery, and the need for extracorporeal membrane oxygenation affect the overall survival of infants with congenital diaphragmatic hernia. Thanks to advances in the management of patients with congenital diaphragmatic hernia, overall survival has increased, reaching 7090 %, and with the use of extracorporeal membrane oxygenation up to 50 %.

Fetal surgery for obstructive ureterocele using an ultrasound-guided needle laser ablation technique: a case series

Introduction Obstructive ureterocele is an intravesical cystic dilation of the distal end of the ureter associated with anhidramnios and dilation of both renal pelvises. Methods This is a case-series of prenatally diagnosed ureterocele. Cases were selected at a third level reference hospital in Monterrey Mexico between 2010 and 2018. Eligible patients for fetal therapy were selected when bilateral hydronephrosis and severe oligohydramnios were found before 26+0 weeks of gestation. The fetal intervention comprised an ultrasound-guided needle laser technique for ureterocele ablation. Results There were six cases of prenatal diagnosed of ureterocele, two cases showed anhidramnios at 23 weeks of gestation and were considered obstructive ureterocele. For these two cases, fetal surgery was performed using laser ablation of the ureterocele through an ultrasound-guided needle. In both, the urinary tract was decompressed, and the volume of amniotic fluid improved allowing to carry both pregnancies until term, one of them vaginally and the other by cesarean section. In the postnatal follow-up of both cases, the first neonate died due to neonatal asphyxia at 48-hours, and the second neonate required removal of the abnormal collecting system. Conclusions The use of ultrasound-guided laser ablation for the decompression of obstructive ureterocele is a safe and feasible technique in extremely premature fetuses that could allow survival of the affected fetus until term. Patients receiving an early prenatal diagnosis of obstructive ureterocele may benefit from fetal therapy to reduce the risk of lung hypoplasia and stillbirth. Established facts Prenatal mortality of bilateral obstructive ureterocele is up to 45%. Only a few techniques have been described for the management of prenatally bilateral obstructive ureterocele; among them, the puncturing of the ureterocele which may require more than one intervention during fetal, laser by fetoscopy which may increase the risk of postoperative complications, and ultrasound-guided laser fulguration which seems to be effective and safe. Novel insights The present is the first description of a case series on ureteroceles comprising two ultrasound-guided laser therapy as an effective treatment for bilateral obstructive ureterocele requiring a single intervention. The use of ultrasound-guided laser in obstructive cases avoids fatality and lung hypoplasia due to severe oligohydramnios. Still, the neonatal prognosis of the affected side at two years of age remains unchanged.

Scimitar Syndrome Outcomes in Patients with Pulmonary Hypertension: A Single Center Experience

<h3>Purpose</h3> Scimitar syndrome (SS) is a rare congenital heart disease characterized by anomalous pulmonary venous return, with associated right lung hypoplasia. This study aimed to describe the differences in characteristics and outcomes of SS patients with and without pulmonary hypertension (PH). <h3>Methods</h3> This was a retrospective cohort study that included all SS patients followed at a large pediatric institution from October 1989 through August 2021. <h3>Results</h3> A total of 84 patients diagnosed with SS were included (27% with PH). When comparing no-PH with PH patients, PH patients were diagnosed with SS at a younger age (PH: 11 days vs. no-PH: 449 days, p:0.034), frequently symptomatic by the time of diagnosis (PH: 87% vs. no-PH:79%, p:0.538), had often congenital heart disease (PH:87% vs. no-PH: 46%, p: 0.001), history of prematurity (PH: 18% vs. no-PH:11%, p: 0.716), and genetic syndromes (PH:9% vs. no-PH: 3%, p:0.301). Fifty-two percent of the SS PH patients were initiated on PH target therapy (58% phosphodiesterase inhibitors, 8% endothelin receptor antagonists and 33% dual PH target therapy). From the procedural perspective, PH patients underwent more APC occlusion procedures (PH:61% vs. no-PH:41%, p:0.218), had multiple interventional cardiology procedures (PH:83% vs. no-PH:38%, p<0.001) were younger when they underwent their first surgical scimitar vein repair (median age PH:26 months vs. no-PH:84 months, p:0.222), and had a higher incidence of restenosis after interventional cardiac procedures (PH:26% vs. no-PH:8%, 0.040). Only PH patients underwent extracorporeal mechanical circulatory support (9%), and overall had a higher rate of mortality (PH:22% vs. No-PH:5%, p:0.032). <h3>Conclusion</h3> Managing SS patients with PH is an understudied area that requires further data. This study demonstrated that such patients more frequently have a history of congenital heart disease, higher incidence of mortality, and have a greater risk of scimitar vein restenosis compared to non-PH SS patients.

Meeting abstracts from the 15th international conference on neonatal and childhood pulmonary vascular disease

Meeting abstracts from the 15th international conference on neonatal and childhood pulmonary vascular disease

Recent developments in fetal lung ultrasound

Fetal ultrasound has been employed for years to help evaluate fetal growth and development and to monitor pregnancy. Furthermore, fetal lung maturity has been assessed pre-natally by examination of the amniotic fluid, usually obtained by transabdominal amniocentesis, for lecithin, lecithin/sphingomyelin ratio, or “P” factor (fluorescent polarization measurement for lipids.) Quantitative ultrasound texture analysis of fetal lung has been proposed in previous studies as a promising noninvasive method to predict fetal lung maturity, fetal lung hypoplasia, and neonatal respiratory morbidity. This technique utilizes standard fetal lung images, which are easily obtained by sonographers during routine ultrasound examinations. Additional information then can be extracted from these images by applying quantitative processing methods that characterize the tissue. This presentation discusses how to differentiate preterm (&amp;lt;37 weeks of gestation) from term (≥37 weeks of gestation) fetal lungs by quantitative texture analysis of ultrasound images. This quantification is based on the extent of heterogeneity associated with lung maturity by employing a unique, novel noninvasive technique to determine the Heterogeneity Index (HI) in ultrasound images. The HI values are then compared in sonograms of immature lungs with mature lungs. Conceptual advances for the possibility of integrating this technology in handheld ultraportable systems for point-of-care ultrasound (POCUS) are also presented.

Prenatal Diagnosis and Outcome of Scimitar Syndrome: A Case Series of Six Patients.

Scimitar syndrome is a rare disease characterized by hypoplasia of the right lung and partial anomalous pulmonary venous drainage to the inferior vena cava. All cases with a prenatal diagnosis of scimitar syndrome with or without associated malformations in an 18-year period (2000–2018) in two large tertiary referral centers (University of Bonn and University of Cologne, Germany) were retrospectively reviewed for the intrauterine course and postnatal outcome. Six cases were diagnosed in the study period. All presented with hypoplasia of the right lung, right-sided mediastinal shift, and abnormal pulmonary venous drainage to the inferior vena cava. Systemic arterial blood supply to the right lung, albeit postnatally present in all cases, could not be detected prenatally. Major associated anomalies were present in all cases and included atrial septal defect (n = 5), coarctation (n = 3), diaphragmatic hernia (n = 2), and VACTERL association (n = 1). Half of the cohort died within 6 months after birth and all three survivors suffer from long-term pulmonary sequelae. The primary hint to the prenatal diagnosis of scimitar syndrome is the abnormal position of the heart in the chest. If searched for, abnormal venous drainage can be identified prenatally and confirms the diagnosis. The prognosis depends on the presence of associated major anomalies and the need for neonatal intervention.

Outcomes of slide tracheoplasty for congenital tracheal stenosis in 80 children: A 22-year single-center experience

PurposeThe application of slide tracheoplasty (STP) in the treatment of congenital tracheal stenosis (CTS) has improved patient outcomes over the past few decades. We reviewed our experiences with the procedure, elucidated risk factors, and discussed important aspects of perioperative management to improve outcomes. MethodPatients with CTS undergoing STP between July 1998 and December 2020 were enrolled. Patient characteristics, perioperative condition, management, operative details, and outcomes, including mortality and postoperative intervention, were collected from medical records. ResultsEighty patients underwent STP. Sixty-five patients (81.3%) had an associated cardiovascular anomaly. Thirteen patients (16.3%) had unilateral lung agenesis or hypoplasia. Preoperative mechanical ventilation was necessary in 54 (67.5%) patients, and extracorporeal membrane oxygenation (ECMO) was required in eight patients (10.0%). An endotracheal tube was placed before the stenotic entrance to avoid granulation. During STP, the trachea was dissected as little as possible to maintain the blood supply. The one-year survival rate was 88.8% (nine patients died). One patient (1.3%) required postoperative balloon dilation, and none required stenting or granulation removal. Of the survivors, 62 (92.5%) achieved successful extubation without tracheostomy. Multivariable analysis revealed complex cardiovascular anomaly (P = 0.05) and preoperative ECMO (P = 0.019) to be adverse predictors of survival. ConclusionAlthough STP can be performed successfully in CTS patients, surgeons and families should be aware of factors that may lead to a more difficult postoperative course or increase the mortality. Meticulous, perioperative positioning of the endotracheal tube and preserving the tracheal blood flow can minimize the need for postoperative intervention.

Tenascin C is dysregulated in hypoplastic lungs of miR-200b-/- mice.

We previously demonstrated that absence of miR-200b results in abnormal lung development in congenital diaphragmatic hernia due to imbalance between epithelial and mesenchymal cells. Tenascin C is a highly conserved extracellular matrix protein involved in epithelial to mesenchymal transition, tissue regeneration and lung development. Considering the involvement of Tenascin C and miR-200b and their potential interaction, we aimed to study Tenascin C during lung development in the absence of miR-200b. We collected lungs of miR-200b-/- mice (male, 8weeks). We performed Western blot (WB) analysis (N = 6) and immunofluorescence (N = 5) for Tenascin C and alpha smooth muscle actin and RT-qPCR for Tenascin C gene expression (N = 4). Using WB analysis, we observed a decreased total protein abundance of Tenascin C in miR-200b-/- lungs (miR-200b+/+: 3.8 × 107 ± 1 × 107; miR-200b-/-: 1.9 × 107 ± 5 × 106; p = 0.002). Immunofluorescence confirmed decreased total Tenascin C in miR-200b-/- lungs. Tenascin C was significantly decreased in the mesenchyme but relatively increased in the airways of mutant lungs. Total lung RNA expression of Tenascin C was higher in miR-200b-/- lungs. We report dysregulation of Tenascin C in lungs of miR-200b-/- mice. This suggests that absence of miR-200b results in abnormal Tenascin C abundance contributing to the lung hypoplasia observed in miR-200b-/- mice.