Predictive Value of Modified Lung Ultrasound Score for Late Respiratory Diseases in Premature Infants: A Retrospective Cohort Analysis.

The relation between chronic respiratory disease and infection with Chlamydia trachomatis in premature infants was investigated to ascertain the aetiological importance of intrauterine C trachomatis infection and chronic respiratory disease in premature infants. Serum IgM antibodies against C trachomatis were determined by enzyme linked fluorescence assay. Sections of lung tissues obtained by biopsy and at necropsy were also tested for the presence of antigens using fluorescein conjugated monoclonal antibodies to C trachomatis. Of 16 sera from premature infants with chronic respiratory diseases clinically diagnosed as bronchopulmonary dysplasia or the Wilson-Mikity syndrome, five had IgM antibodies to C trachomatis L2 strain by enzyme linked fluorescence assay (titre greater than or equal to 1/500). Of 37 sera from premature infants with extremely low birth weights, two had IgM antibodies to C trachomatis. No specific IgM antibody was detected in 31 neonates who showed raised serum IgM concentrations but who did not have respiratory tract symptoms. C trachomatis was identified from two specimens of lung tissue obtained at necropsy from premature infants with chronic respiratory disease positive for IgM antibody. These findings indicate the aetiological importance of intrauterine C trachomatis infection in chronic respiratory disease in premature infants.

Dysplasie bronchopulmonaire du nouveau-né prématuré : d’hier à aujourd’hui

Preventing Postnatal Cytomegalovirus Infection in the Preterm Infant: Should It Be Done, Can It Be Done, and at What Cost?

Bronchopulmonary dysplasia (BPD) is a prevalent respiratory disease in premature infants and is accompanied by impaired lung function, increased infection risk, and other long-term complications. This study aimed to elucidate the molecular mechanisms of BPD, especially mitophagy. Bioinformatics analyses were performed to identify differentially expressed genes (DEGs) in BPD. Weighted gene co-expression network analysis (WGCNA) was used to explore gene modules associated with mitophagy, functional enrichment analyses to identify key biological processes, and immune infiltration to assess immune cell differences. Among the 720 DEGs identified, 419 were upregulated and 301 were downregulated: these may serve as potential BPD biomarkers. WGCNA revealed that the turquoise module was strongly related to mitophagy (r = -0.6061, p < 0.05), indicating its significance in BPD pathogenesis. Enrichment analyses highlighted leukocyte migration and neutrophil extracellular trap formation, suggesting immune-mediated inflammatory response. Eight hub genes (S100P, CDC42EP3, CEACAM3, CKLF, RGL4, DOK3, B4GALT5, and MCEMP1) were identified as potential therapeutic targets. Immune infiltration analysis revealed significant differences in neutrophils and activated CD8+T cells, underscoring the immune system's role in BPD. Key molecular players and pathways involved in BPD were elucidated, providing insights for future targeted therapies addressing immunity and mitophagy in BPD. This study identifies CEACAM3 and CDC42EP3 as key genes involved in mitophagy and immune dysregulation in bronchopulmonary dysplasia (BPD). It provides novel insights into the TNF-α/NF-κB signaling pathway and its role in the pathogenesis of BPD. This study advances biomarker discovery by associating CEACAM3 with neutrophil infiltration and CDC42EP3 with CD8+ T cell activity. The selected machine learning and bioinformatics approaches enhance the diagnostic accuracy and therapeutic targeting of BPD. These findings lay the foundation for future translational research in guiding personalized interventions for high-risk neonates.

BackgroundNutrition is an essential factor in preventing and managing bronchopulmonary dysplasia (BPD), a multifactorial chronic respiratory disease in premature infants. This study examined the association between nutritional intakes during the first 2 weeks of life and BPD in extremely preterm infants.MethodsA retrospective single-center cohort study was performed in infants born <28 weeks' gestational age or with a birth weight <1,000 g. Intake of energy and ratio of enteral feeding/ total fluid intake during the first 2 weeks of life and association with outcome of BPD were examined.Results134 infants were included in our study, and 43 infants (32.1%) developed BPD. During the first 2 weeks of life, the average of total caloric intake and the ratio of enteral feeding/ total fluid intake were significantly lower in the BPD group (total caloric intake:91.90 vs. 95.72 kcal/kg/d, p < 0.05, ratio of enteral feeding/total fluid intake: 0.14 vs. 0.18, p < 0.05), while the average of total fluid intake, caloric and protein intake from parenteral nutrition did not differ between the groups. The ratio of enteral feeding/ total fluid intake during the second week were significantly lower in the BPD group (0.21 vs. 0.28, p < 0.05), while this ratio during the first week did not differ between the groups. An increase of 10% in the ratio of enteral feeding/ total fluid intake during the second week of life significantly reduced the risk of BPD (OR 0.444, 95% CI: 0.270–0.731).ConclusionsA higher ratio of enteral feeding/ total fluid intake was associated with a lower risk for BPD. Early and rapidly progressive enteral nutrition should be encouraged in extremely preterm infants in the absence of feeding intolerance.

After completing this article, readers should be able to: 1. Describe the epidemiology and pathophysiology of gastroesophageal reflux (GER) in preterm neonates. 2. Delineate the associations of GER with apnea, chronic lung disease, behavior, and growth of preterm infants. 3. Review the investigations used to evaluate GER in preterm infants. 4. Describe nonpharmacologic and pharmacologic therapies for GER. Gastroesophageal reflux (GER) is a normal physiologic event occurring across the age spectrum. It may contribute to a variety of disorders, including esophagitis, feeding problems, and airway disease in all age groups. (1) A large number of symptoms and signs have been purported to be caused by GER despite a lack of data showing a clear association between a specific symptom and GER. In preterm infants, empiric therapy often is administered using agents of unproven efficacy and safety to treat symptoms that likely are unrelated to GER. In a survey on management practices for GER in preterm infants, common treatment strategies included positioning (98%) and slopes (96%), histamine 2 (H 2) receptor antagonists (100%), feed thickeners (98%), antacids (96%), prokinetics (79%), proton pump inhibitors (PPIs) (65%), and dopamine receptor antagonists (53%). (2)(3) The safety, efficacy, and appropriate dosing recommendations for most medical therapies remain uncertain in neonates. In this review, we attempt to summarize the current literature regarding physiology, pathophysiology, and diagnostic and management strategies for GER pertinent to the neonate, with an emphasis on the preterm infant. GER describes the retrograde movement of stomach contents (air or feeding, liquid or semisolid, acid or alkaline, enzymes or bile salts) into the esophagus. GER disease (GERD) occurs when GER causes symptoms or signs such as pain, poor weight gain, esophagitis, hematemesis, and airway symptoms, including apnea, aspiration, recurrent pneumonia, chronic lung disease (CLD), or large airway inflammation. However, any of these symptoms or signs …

Bronchopulmonary dysplasia is the most common chronic respiratory disease in premature infants with growing evidence that genetic factors contribute largely to moderate and severe cases. We assessed by exome sequencing if rare genetic variants could account for extremely severe phenotypes. We selected 6 infants born very preterm with severe bronchopulmonary dysplasia and 8 very preterm born controls for exome sequencing. We filtered whole exome sequencing results to include only rare variants and selected variants and/or genes with variants that were present in at least 2 cases and absent in controls. We selected variants, all heterozygous, in 9 candidate genes, 7 with a putative role in lung development and 2 that displayed 3 variations in 3 different cases, independently of their potential role in lung development. Sequencing of 5 other severe cases for these variants did not replicate our results.Conclusion: In selected preterm born infants with severe bronchopulmonary dysplasia and controls, we failed to find any rare variant shared by several infants with an extremely severe phenotype. Our results are not consistent with the role of rare causative variants in bronchopulmonary dysplasia's development and argue for the highly polygenic nature of susceptibility of this disorder.What is Known:• Bronchopulmonary dysplasia is a multifactorial disease resulting from complex environmental and genetic interactions occurring in an immature lung.• It is not known whether rare genetic variants in coding regions could account for extreme phenotypes of the disease.What is New:• In a group of infants with an extreme phenotype of bronchopulmonary dysplasia and in comparison to controls, no common genetic variants were found, nor did variants that were select in other exome studies in this setting.• These results argue for the highly polygenic nature of susceptibility of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a very common respiratory disease in premature infants, but there is still a different understanding of the definition of BPD. Therefore, this study is intended to compare are main clinical results and health economic expenditures under different BPD definitions. This study included premature infants who came into the neonatal intensive care unit (NICU) from January 2018 to January 2020, who were not more than 32 weeks of premenstrual age. The main clinical consequences and health economic expenditures were analyzed by the National Institute of Health and Human Development definition (Workshop) and Jensen definition. Total 303 survivors were evaluated at 36 weeks. BPD was performed in 47.5% and 37.6% of infants, respectively, with Workshop's and Jensen's definitions. The percentage of unclassified BPD infants was 0.9% in Workshop's and 3.3% in Jensen's definitions. Further discussing the health economic burden and found that Jensen's definitions had a significantly correlated with NICU charges than the Workshop's definitions. Comparing the Workshop definition of BPD, the Jensens definition was better correlated to health expenditure.

Bronchopulmonary dysplasia is the most common chronic respiratory disease in premature infants. Genetic factors might contribute to bronchopulmonary dysplasia susceptibility. To identify genetic variants involved in bronchopulmonary dysplasia through a genome-wide association study. We prospectively evaluated 418 premature neonates (gestational age <28 wk), of whom 22% developed bronchopulmonary dysplasia. Two discovery series were created, using a DNA pooling strategy in neonates from white and African ancestry. Polymorphisms associated with the disease were confirmed in an independent replication population. Genes were then explored by fine mapping and associations were replicated in an external Finnish population of 213 neonates. Validated genes expression patterns were studied in rat lung, after air or hyperoxia exposure. SPOCK2 gene was identified by both discovery series. The most significant polymorphism (rs1245560; P = 1.66 × 10(-7)) was confirmed by individual genotyping, and in the replication population (P = 0.002). Fine mapping confirmed the association of rs1245560 with bronchopulmonary dysplasia in both white and African populations with adjusted odds ratios of 2.96 (95% confidence interval [CI], 1.37-6.40) and 4.87 (95% CI, 1.88-12.63), respectively. In white neonates, rs1049269 was also associated with the disease (odds ratio, 3.21; 95% CI, 1.51-6.82). These associations were replicated in the Finnish population. In newborn rat lungs, SPOCK2 mRNA levels markedly increased during the alveolar stage of lung development. After rat exposure to hyperoxia, SPOCK2 expression increased relative to air-exposed controls. We identified SPOCK2 as a new possible candidate susceptibility gene for bronchopulmonary dysplasia. Its lung expression pattern points toward a potential role in alveolarization.

BackgroundBronchopulmonary dysplasia (BPD) is a common respiratory disease in premature infants and is characterized by alveolar and pulmonary vascular dysplasia. Long-term oxygen exposure can cause BPD in preterm infants. Numerous studies have shown that long non-coding ribonucleic acid (lncRNA) is involved in the process of biological metabolism; however, its role in the development of BPD is unclear. Apoptosis-induced factor (AIF) is a key component involved in apoptosis. The Kelch-like ECH-associated protein 1/nuclear factor erythroid-2-related factor 2 (Keap1/Nrf2) signaling pathway is a body-derived antioxidant signaling pathway.MethodsIn this study, the relative expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), AIF, Keap1, and Nrf2 was detected by real-time polymerase chain reaction (PCR). Also, the apoptosis of A549 cells was detected by flow cytometry.ResultsThe results showed that, compared to the control group, the expression of MALAT1 increased significantly, and AIF decreased substantially in BPD premature infants. In the A549 hyperoxic lung injury model, compared with the air group, the expression of MALAT1 in the hyperoxia group decreased markedly, while the expression of Keap1 and Nrf2 increased considerably. Furthermore, compared with the control plasmid transfection air group (NC group), the expression of Keap1 and Nrf2 increased significantly in the small interfering RNA (siRNA) group.ConclusionsThese results indicate that MALAT1 can play a protective role in BPD via the reduction of apoptosis and anti-oxidation, offering clinicians a new way to prevent and treat BPD.

Bronchopulmonary dysplasia (BPD) is a common chronic respiratory disease in premature infants. Hyperoxia is the main pathogenic factor of BPD. Nintedanib is a small-molecule tyrosine kinase inhibitor that has been confirmed to affect several cellular processes in different diseases. The aim of this study was to explore the function of nintedanib in the treatment of BPD. Newborn Sprague-Dawley rats (postnatal day 1) were used to establish an in vivo BPD model by hyperoxia induction. Nintedanib was intraperitoneally injected into rats. Haematoxylin and eosin (H&E) staining was applied to detect lung injury in BPD rats. Cell apoptosis was determined by TUNEL (TdT-mediated dUTP nick end labelling) assay. Western blotting was applied to detect level changes of inflammatory factors IL-1β (interleukin-1 beta), CXCL-1 (C-X-C motif chemokine ligand 1), MCP-1 (monocyte chemotactic protein-1), as well as the phosphorylation of IkB (NF kappa B inhibitor) and NF-kB (nuclear factor kappa-B) in lung samples. Hyperoxia resulted in lung injury in neonatal rats, while nintedanib treatment relieved the injury. Furthermore, nintedanib alleviated hyperoxia-induced apoptosis in rat lungs. It was further observed that an inflammatory response caused by hyperoxia in lung samples was attenuated by nintedanib administration. Additionally, nintedanib inactivated the NF-κB pathway in BPD rats. Nintedanib alleviates hyperoxia-induced lung injury via targeting the NF-κB signalling pathway.

Bronchopulmonary dysplasia (BPD) is the most common chronic respiratory disease in premature infants and affects their survival rate and quality of life. There are no reliable interventions for the prevention or treatment of BPD, but the emergence of mesenchymal stem cell (MSC) therapies has brought new hope. Research has shown that paracrine may be the therapeutic mechanism of action underlying physiological improvements in the lungs of BPD patients treated with MSC therapy. The therapeutic vector in the MSC secretome comprises exosomes with low immunogenicity and stability, and that can easily cross the blood-brain barrier. In the future, exosomes may become the preferred treatment for BPD in clinical settings. Here, we review the progress of preclinical research on the use of MSC-derived exosomes as a promising treatment option for BPD. · There is a lack of effective treatment for BPD.. · MSCs' therapeutic effect is exerted through paracrine.. · MSC-derived exosomes (MSC-Exos) possess similar biological functions to MSCs.. · MSC-Exos can repair lung injury in BPD animal models..

Bronchopulmonary dysplasia (BPD) is a common respiratory disease in premature infants. With the improvement of the survival rate of extremely immature premature infants, the incidence of BPD is increasing. Pulmonary microvascular dysplasia is one of the main pathological features of new BPD. Vascular endothelial growthfactor( VEGF ) and its receptor play an important role in the development of pulmonary microvasculature, which is closely related to the occurrence of bronchial pulmonary dysplasia. This article mainly describes the influencing factors of VEGF and its receptor expression, the relationship between VEGF and BPD, the current status of VEGF applied to animal models, and the relationship between VEGF and other cytokines, so as to indicate the role of vascular endothelial factors in the development of bronchopulmonary dysplasia. Key words: Vascular endothelial growth factor; Bronchopulmonary dysplasia; Pulmonary vessels

Bronchopulmonary dysplasia (BPD) is the most common chronic respiratory disease in premature infants. However, there is a lack of effective treatment. Mesenchymal stromal cells derived extracellular vesicles (MSC-EVs), as nano- and micron-sized heterogeneous vesicles secreted by MSCs, are the main medium for information exchange between MSCs and injured tissue and organ, playing an important role in repairing tissue and organ injury. EVs include exosomes, microvesicles and so on. They are rich with various proteins, nucleic acids, and lipids. Now, EVs are considered as a new way of cell-to-cell communication. EVs mainly induce regeneration and therapeutic effects in different tissues and organs through the biomolecules they carry. The surface membrane protein or loaded protein and nucleic acid molecules carried by EVs, can activate the signal transduction of target cells and regulate the biological behavior of target cells after binding and cell internalization. MSC-EVs can promote the development of pulmonary vessels and alveoli and reduce pulmonary hypertension (PH) and inflammation and play an important role in the repair of lung injury in BPD. The regeneration potential of MSC-EVs is mainly due to the regulation of cell proliferation, survival, migration, differentiation, angiogenesis, immunoregulation, anti-inflammatory, mitochondrial activity and oxidative stress. As a new type of cell-free therapy, MSC-EVs have non-immunogenic, and are small in size and go deep into most tissues. What’s more, it has good biological stability and can be modified and loaded with drugs of interest. Obviously, MSC-EVs have a good application prospect in the treatment of lung injury and BPD. However, there are still many challenges to make MSC-EVs really enter clinical application.

Bronchopulmonary dysplasia (BPD) is a common respiratory disease in premature infants. Nesfatin-1 is considered for the treatment of BPD. This study aimed to explore the anti-inflammatory effect of nesfatin-1 in the treatment of BPD. Hyperoxia-induced newborn rats and transfected primary type II alveolar epithelial cells (AECIIs) were used to evaluate nesfatin-1's efficacy in treating BPD. Lung damage was assessed by means of wet-dry ratio measurement, Hematoxylin and Eosin staining, Masson staining, Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, and Western blotting. Interleukin 6 (Il-6), tumor necrosis factor alpha (Tnf-α), and interleukin 1β (Il-1β) levels were measured by Enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (qPCR). Neutrophils in bronchoalveolar lavage fluid were counted. High mobility group box 1 (HMGB-1), Toll-like receptor 4 (TLR4), nuclear factor kappa-light-chain-enhancer of activated B cells p65 subunit (p65), and NOD-like receptor family pyrin domain containing 3 (NLRP3) expressions were analyzed using Western blotting, while NLRP3 expression was detected through immunohistochemistry. AECIIs' viability, apoptosis, and reactive oxygen species (ROS) levels were assessed using cell counting kit-8 (CCK8), flow cytometry, and immunofluorescence, respectively. An immunofluorescence approach was used to detect surfactant protein C and ROS levels. In vivo, nesfatin-1 treatment significantly reduced the lung wet-dry ratio, increased the body weight of rats, inhibited apoptosis, alleviated lung damage, decreased inflammation, and lowered neutrophil counts (p < 0.05). In vitro, nesfatin-1 enhanced cell viability, inhibited apoptosis, decreased ROS levels (p < 0.01) and decreased mRNA levels of Il-6, Tnf-α, and Il-1β (p < 0.05) while increasing Il-10 mRNA (p < 0.01). In in vivo and in vitro scenarios, nesfatin-1 inhibited HMGB-1, TLR4, p65, and NLRP3 protein expression (p < 0.05). In hyperoxia cells, Hmgb-1 silencing showed similar results to those of nesfatin-1 treatment, while Hmgb-1 overexpression antagonized the effects of nesfatin-1 treatment. This study showed that nesfatin-1 reduces neutrophils and suppresses inflammation via the HMGB-1/TLR4/Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB)/NLRP3 pathway, suggesting its potential clinical application in the treatment of BPD.