Showing papers on "Alveolar capillary dysplasia published in 2021"
TL;DR: In this paper, pulmonary endothelial progenitor cells (EPCs) were derived from pluripotent embryonic stem cells (ESC) for neonatal pulmonary disorders, and they showed promising results.
Abstract: Rationale: Although pulmonary endothelial progenitor cells (EPCs) hold promise for cell-based therapies for neonatal pulmonary disorders, whether EPCs can be derived from pluripotent embryonic stem...
20 citations
TL;DR: In this article, Pulmonary hypertension (PH) is a common complication in patients with alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a severe congenital disorder associated with pulmonary hypertension.
Abstract: Background: Pulmonary hypertension (PH) is a common complication in patients with alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a severe congenital disorder associated...
18 citations
TL;DR: In this article, the authors described the hallmarks of pediatric lung diseases such as bronchopulmonary dysplasia (BPD) and alveolar capillary dysplasticity with misalignments.
Abstract: Compromised alveolar development and pulmonary vascular remodeling are hallmarks of pediatric lung diseases such as bronchopulmonary dysplasia (BPD) and alveolar capillary dysplasia with misalignme...
11 citations
TL;DR: In this article, the authors examined lung transcriptomes in 12 histopathologically verified ACDMPV patients with or without pathogenic variants in the FOXF1 locus and analyzed gene expression profile in FENDRRdepleted fetal lung fibroblasts, IMR-90.
Abstract: Background Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal congenital lung disorder in neonates characterized by severe progressive respiratory failure and refractory pulmonary hypertension, resulting from underdevelopment of the peripheral pulmonary tree. Causative heterozygous single nucleotide variants (SNVs) or copy-number variant (CNV) deletions involving FOXF1 or its distant lung-specific enhancer on chromosome 16q24.1 have been identified in 80-90% of ACDMPV patients. FOXF1 maps closely to and regulates the oppositely oriented FENDRR, with which it also shares regulatory elements. Methods To better understand the transcriptional networks downstream of FOXF1 that are relevant for lung organogenesis, using RNA-seq, we have examined lung transcriptomes in 12 histopathologically verified ACDMPV patients with or without pathogenic variants in the FOXF1 locus and analyzed gene expression profile in FENDRR-depleted fetal lung fibroblasts, IMR-90. Results RNA-seq analyses in ACDMPV neonates revealed changes in the expression of several genes, including semaphorins (SEMAs), neuropilin 1 (NRP1), and plexins (PLXNs), essential for both epithelial branching and vascular patterning. In addition, we have found deregulation of the vascular endothelial growth factor (VEGF) signaling that also controls pulmonary vasculogenesis and a lung-specific endothelial gene TMEM100 known to be essential in vascular morphogenesis. Interestingly, we have observed a substantial difference in gene expression profiles between the ACDMPV samples with different types of FOXF1 defect. Moreover, partial overlap between transcriptome profiles of ACDMPV lungs with FOXF1 SNVs and FENDRR-depleted IMR-90 cells suggests contribution of FENDRR to ACDMPV etiology. Conclusions Our transcriptomic data imply potential crosstalk between several lung developmental pathways, including interactions between FOXF1-SHH and SEMA-NRP or VEGF/VEGFR2 signaling, and provide further insight into complexity of lung organogenesis in humans.
8 citations
TL;DR: Pediatric pulmonary hypertension (PPH) is a multifactorial disease with diverse etiologies and presenting features as mentioned in this paper, which is often a hidden component of other lung diseases, such as cystic fibrosis and bronchopulmonary dysplasia.
Abstract: Pediatric pulmonary hypertension (PPH) is a multifactorial disease with diverse etiologies and presenting features. Pulmonary hypertension (PH), defined as elevated pulmonary artery pressure, is the presenting feature for several pulmonary vascular diseases. It is often a hidden component of other lung diseases, such as cystic fibrosis and bronchopulmonary dysplasia. Alterations in lung development and genetic conditions are an important contributor to pediatric pulmonary hypertensive disease, which is a distinct entity from adult PH. Many of the causes of pediatric PH have prenatal onset with altered lung development due to maternal and fetal conditions. Since lung growth is altered in several conditions that lead to PPH, therapy for PPH includes both pulmonary vasodilators and strategies to restore lung growth. These strategies include optimal alveolar recruitment, maintaining physiologic blood gas tension, nutritional support, and addressing contributing factors, such as airway disease and gastroesophageal reflux. The outcome for infants and children with PH is highly variable and largely dependent on the underlying cause. The best outcomes are for neonates with persistent pulmonary hypertension (PPHN) and reversible lung diseases, while some genetic conditions such as alveolar capillary dysplasia are lethal. © 2021 American Physiological Society. Compr Physiol 11:2135-2190, 2021.
5 citations
23 Jan 2021
TL;DR: Pulmonary alveolar proteinosis is an example of an umbrella description, which may present at any age, and has a number of underlying causes with different specific treatments, underscoring the need to move from pattern recognition to specific diagnoses.
Abstract: Interstitial lung disease in children (chILD) is rare and encompasses more than 200 entities, with new especially genetic causes being discovered. Several classifications have been proposed, and there is considerable overlap with entities which present in adult life. Presentation may be shortly after birth with acute respiratory distress and in infancy and childhood either with a primary respiratory presentation or with systemic symptoms such as poor feeding and failure to thrive. Newborn acute presentations are usually due either to a mutation in one of the surfactant protein (Sp) genes or the alveolar capillary dysplasia (ACD)-congenital alveolar dysplasia (CAD) spectrum. The latter usually progress rapidly to extracorporeal membrane oxygenation, and early lung biopsy is advisable to prevent prolonged futile treatment being offered. Outside the newborn period, a staged protocol for investigation is proposed. This starts with a computed tomography scan, which confirms or otherwise the presence of chILD, and occasionally can lead to a specific diagnosis. In particular in settings where there is a high burden of infection, infective mimics of chILD need to be excluded. The next investigations aim to try to move from pattern recognition to specific diagnoses, both genetic and environmental. The speed of progression to lung biopsy will depend on the clinical state of the child, and the biopsy itself may suggest a hunt for a new underlying cause, such as immunodeficiency. Specific genetic causing chILD includes mutations in SpB and SpC and processing genes (thyroid transcription factor-1 [TTF-1] and adenosine triphosphate-binding cassette subfamily A) (the last three can present at any time in the life course); genes involved in Sp catabolism (granulocyte-macrophage colony factor receptor A and B genes), an increasing number implicated in the ACD-CAD spectrum, and other non-Sp related genes such as Filamin-A and integrin genes. Environmental causes are also important and vary across the world. Vaping has been implicated as causing a large number of chILDs, and a vaping history is essential in any young person with an unusual respiratory illness. Medications, both prescribed and over-the-counter such as oily laxatives, are also causes of chILD. There are important conditions of unknown cause presenting in early childhood. Neuroendocrine cell hyperplasia of infancy (NEHI) and pulmonary interstitial glycogenosis generally have a good prognosis, and are probably best considered as part of a spectrum of pulmonary dysmaturity syndromes, in some of which underlying gene mutations have been detected, for example, TTF-1 for NEHI. Pulmonary alveolar proteinosis is an example of an umbrella description, which may present at any age, and has a number of underlying causes with different specific treatments, underscoring the need to move from pattern recognition to specific diagnoses. chILDs have important implications for adult physicians; there may be late as yet poorly described sequelae of the disease or its treatment in adult life; there may be genetic implications for the wider family; and there may be late chILD relapses. Smooth transition to adult services is essential for all chILD survivors, with pediatric and adult chest physicians working closely together.
4 citations
TL;DR: Clinical presentation is not always correlated with histopathology in ACD/MPV, which should be suspected in any infants with fulminant pulmonary hypertension, and abnormal pulmonary veins and aberrant intraseptal vessels are the most important clues for diagnosis.
3 citations
TL;DR: In this paper, the authors used Sanger sequencing or next-generation sequencing to identify copy number variations (CNVs) in exons, introns, and in the upstream region of FOXF1.
3 citations
TL;DR: Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV) is a rare, lethal condition caused by irregular pulmonary vascular maturation as discussed by the authors.
Abstract: Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV) is a rare, lethal condition caused by irregular pulmonary vascular maturation. Almost all cases present in the newbor...
2 citations
TL;DR: Wang et al. as discussed by the authors reported a new case of a 3-month-old Chinese girl with alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV) that results in severe respiratory distress and pulmonary hypertension.
1 citations
TL;DR: A newborn infant patient presented with persistent pulmonary hypertension with persisting nitric oxide dependency, which led to the diagnosis of alveolar capillary dysplasia with misalignment of the pulmonary veins.
Abstract: A newborn infant patient presented with persistent pulmonary hypertension For right ventricular decompression, the ductus arteriosus was kept open by prostaglandin E 1 infusion and was stented at the age of 4 weeks during heart catheterization The child was weaned from mechanical ventilation, since pulmonary functions were adequate A small atrial septal defect was identified and closed in cardiac catheterization laboratory to decrease preductal hypoxemia Diagnostic workup led to the diagnosis of alveolar capillary dysplasia with misalignment of the pulmonary veins Suprasystemic pulmonary arterial hypertension with persisting nitric oxide dependency remained the leading symptoms The child underwent bilateral lung transplantation at the age of 28 months He is well at the age of 44 months
TL;DR: In this paper, a 14 WG fetus with an association of increased nuchal translucency (INT) and univentricular congenital heart malformation (CHM) leading to chorionic villous sampling (CVS) was reported.
Abstract: First trimester ultrasound screening is an essential fetal examination performed generally at 11-13 weeks of gestation (WG). However, it does not allow for an accurate description of all fetal organs, partly due to their development in progress. Meanwhile, increased nuchal translucency (INT) is a widely used marker known to be associated with chromosomal deleterious rearrangements. We report on a 14 WG fetus with an association of INT and univentricular congenital heart malformation (CHM) leading to chorionic villous sampling (CVS). Cytogenetic investigations performed using array-Comparative Genomic Hybridization (CGH) and fluorescence in situ hybridization (FISH) demonstrated a 1.17 Mb deletion in 16q24.1 encompassing FOXF1 arisen de novo on maternal inherited chromosome. Fetopathological study confirmed CHM with hypoplastic left heart syndrome (HLHS) associating aortic atresia, mitral stenosis, and left ventricular hypoplasia and revealed in addition specific lung lesions corresponding to alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV). This is so far the first case of first trimester prenatal diagnosis of ACDMPV due to the deletion of FOXF1 gene. An interpretation of the complex genomic data generated by ultrasound markers is facilitated considerably by the genotype-phenotype correlations on fetopathological examination.
TL;DR: In this article, a male infant with alveolar capillary dysplasia without misalignment of pulmonary veins, hyperinflammation, megalocornea and macrosomia/macrocephaly at birth was presented.
TL;DR: This review offers a conceptual framework to the general histopathologist confronted withCongenital lung disease and presents an approach to assessment in order to achieve the maximum information from the specimen.
TL;DR: In this paper, the authors describe two patients with alveolar capillary dysplasia associated with left-sided obstructive heart defects with two different genetic variants and highlight the importance of early recognition of this disease in the setting of persistent and supra-systemic pulmonary hypertension.
Abstract: Alveolar capillary dysplasia with misalignment of the pulmonary veins is an uncommon disorder that affects the lung vasculature development in the neonatal period and leads to pulmonary hypertension. We describe two patients with alveolar capillary dysplasia associated with left-sided obstructive heart defects with two different genetic variants. Our cases highlight the importance of early recognition of this disease in the setting of persistent and supra-systemic pulmonary hypertension despite surgical correction of the associated lesions. Identification of these cases will facilitate the development of a multidisciplinary approach and provide guidance to the affected families.