Symptoms Of Bronchopulmonary Dysplasia Research Articles

Longer duration of initial invasive mechanical ventilation is still a crucial risk factor for moderate-to-severe bronchopulmonary dysplasia in very preterm infants: a multicentrer prospective study

ObjectivesWe aimed to evaluate the risk factors for moderate-to-severe bronchopulmonary dysplasia (BPD) and focus on discussing its relationship with the duration of initial invasive mechanical ventilation (IMV) in very preterm neonates less than 32 weeks of gestational age (GA).MethodsWe performed a prospective cohort study involving infants born at 23–31 weeks of GA who were admitted to 47 different neonatal intensive care unit (NICU) hospitals in China from January 2018 to December 2021. Patient data were obtained from the Sina-northern Neonatal Network (SNN) Database.ResultsWe identified 6538 very preterm infants, of whom 49.5% (3236/6538) received initial IMV support, and 12.6% (823/6538) were diagnosed with moderate-to-severe BPD symptoms. The median duration of initial IMV in the moderate-to-severe BPD group was 26 (17–41) days, while in the no or mild BPD group, it was 6 (3–10) days. The incidence rate of moderate-to-severe BPD and the median duration of initial IMV were quite different across different GAs. Multivariable logistic regression analysis showed that the onset of moderate-to-severe BPD was significantly associated with the duration of initial IMV [adjusted odds ratio (AOR): 1.97; 95% confidence interval (CI): 1.10–2.67], late-onset neonatal sepsis (LONS), and patent ductus arteriosus (PDA).ConclusionIn this multicenter cohort study, the duration of initial IMV was still relatively long in very premature infants, and the longer duration of initial IMV accounts for the increased risk of moderate-to-severe BPD.

LncRNA CASC2 targets CAV1 by competitively binding with microRNA-194-5p to inhibit neonatal lung injury

Long non-coding RNAs (lncRNAs) are vital regulators of different biological processes during bronchopulmonary dysplasia (BPD). This study was conducted to probe the biological roles of lncRNA CASC2 in the pathogenesis of BPD and neonatal lung injury. Firstly, a hyperoxia-induced mouse model with BPD was established. LncRNAs with differential expression in lung tissues of normal and BPD mice were analyzed by microarray. An adenovirus vector overexpressing CASC2 was constructed and its functions on BPD symptoms in model mice were analyzed. Gain- and loss-of function studies of CASC2 were performed in a bronchial epithelial cell line BEAS-2B to determine its role in cell apoptosis and proliferation under normoxic and hyperoxic conditions. The downstream mechanical molecules of lncRNA CASC2 were predicted on bioinformatics systems and confirmed by luciferase assays. The functional interactions among lncRNA CASC2, miR-194-5p, and CAV1 in BPD were determined by rescue experiments. Consequently, lncRNA CASC2 was found to be poorly expressed in BPD mice. Besides, overexpressed CASC2 was found to relieve the symptoms of BPD in neonatal mice and suppress apoptosis as well as promote proliferation in hyperoxia-induced BEAS-2B cells. Importantly, CASC2 was found to regulate CAV1 expression by competitively binding to miR-194-5p and downregulate the activity of the TGF-β1 signaling pathway, thereby suppressing lung injury. Either miR-194-5p upregulation or CAV1 downregulation blocked the roles of CASC2. To sum up, this study evidenced that CASC2 alleviates hyperoxia-induced lung injury in mouse and cell models with the involvement of a miR-194-5p-CAV1 crosstalk and the TGF-β1 inactivation.

Gastroesophageal Reflux Poses a Potential Risk for Late Complications of Bronchopulmonary Dysplasia: A Prospective Cohort Study

Bronchopulmonary dysplasia (BPD) is the most common respiratory disorder in extremely low birth weight infants. Although most symptoms of BPD improve, some late complications exist, even with regular treatment. Gastroesophageal reflux (GER), also common in extremely premature infants, may be related to many cardiorespiratory symptoms. However, the potential of GER as a risk factor for late complications associated with BPD is still unclear. The goal of this study was to determine if GER increases the risk of late complications of BPD in infants. A multicenter prospective cohort of 131 infants (79 male subjects, 52 female subjects) with BPD was enrolled. The development of late complications was assessed over an 18-month follow-up period. Twenty-four-hour pH-multichannel intraluminal impedance and gastric sodium concentrations were analyzed in all infants at 36weeks' postmenstrual age and at the last interview. Prevalence and risk factors of late complications of BPD were analyzed by using forward logistic regression. The prevalence of late complications in BPD infants was 63.79%and included respiratory symptoms (49.14%), vomiting (38.79%), retinopathy of prematurity (25.86%), hypoxic-ischemic injury (3.45%), rehospitalization (26.72%), and sudden death (0.86%). Respiratory diseases constituted the most frequent complication. The prevalence of GER in BPD was 42.24%and included acid GER (18.10%) and duodenogastroesophageal reflux (DGER; 24.14%). Risk factors for respiratory symptoms were gestational age≤ 30weeks (OR, 3.213; 95%CI, 1.221-8.460), birth weight< 1,500g (OR, 2.803; 95%CI, 1.014-7.749), invasive ventilation > 7days (OR, 4.952; 95%CI, 1.508-16.267), acid GER (OR, 4.630; 95%CI, 1.305-16.420), and DGER (OR, 5.588; 95%CI, 1.770-17.648). Infants with BPD and DGER were more prone to late complications than those with acid GER or no reflux. The prevalence of late complications is high in infants with BPD. GER (and in particular, DGER) poses a tentative risk for these late complications. ClinicalTrials.gov; No.: NCT03014453; URL: www.clinicaltrials.gov.

Effect of asiaticoside on hyperoxia-induced bronchopulmonary dysplasia in neonatal rats and related mechanism

To study the protective effect of asiaticoside against hyperoxia-induced bronchopulmonary dysplasia in neonatal rats based on the microRNA-155 (miR-155)/suppressor of cytokine signaling-1 (SOCS1) axis. Neonatal rats were randomly divided into a control group, a model group, a low-dose asiaticoside group (10 mg/kg), a middle-dose asiaticoside group (25 mg/kg), a high-dose asiaticoside group (50 mg/kg), and a budesonide group (1.5 mg/kg), with 12 rats in each group. All rats except those in the control group were exposed to a high concentration of oxygen for 14 days to establish a neonatal rat model of bronchopulmonary dysplasia. The low-, middle-, and high-dose asiaticoside groups were given asiaticoside at different doses by gavage, and those in the budesonide group were given budesonide aerosol treatment. Hematoxylin and eosin staining was used to observe lung tissue development and measure radial alveolar count (RAC) and mean linear intercept (MLI). Superoxide dismutase (SOD) and malondialdehyde (MDA) detection kits were used to measure the levels of SOD and MDA in lung tissue. ELISA was used to measure the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Quantitative real-time PCR was used to measure the mRNA expression of miR-155 and SOCS1 in lung tissue. Western blotting was used to measure the protein expression of SOCS1 in lung tissue. Compared with the control group, the model group had the symptoms of bronchopulmonary dysplasia such as a disordered structure of lung tissue, enlargement of alveolar fusion, uneven alveolar septa, enlargement of average alveolar space, and a reduction in alveolar number. The model group also had significant increases in MLI, MDA level in lung tissue, serum levels of IL-6 and TNF-α, and miR-155 level in lung tissue (P<0.05) and significant reductions in RAC, SOD level, and mRNA and protein expression of SOCS1 in lung tissue (P<0.05). Compared with the model group, the low-, middle-, and high-dose asiaticoside groups and the budesonide group had significant improvement in the above symptoms of bronchopulmonary dysplasia, significant reductions in MLI, MDA level in lung tissue, serum levels of IL-6 and TNF-α, and miR-155 level in lung tissue (P<0.05), and significant increases in RAC, SOD level, and mRNA and protein expression of SOCS1 in lung tissue (P<0.05). Asiaticoside improved the above symptoms and indices in a dose-dependent manner. There were no significant differences in the above indices between the high-dose asiaticoside and budesonide groups (P>0.05). Asiaticoside can alleviate inflammation injury induced by hyperoxia in neonatal rats and improve the symptoms of bronchopulmonary dysplasia in a dose-dependent manner, possibly by down-regulating the expression of miR-155 and up-regulating the expression of SOCS1.

Bronchopulmonary Dysplasia: An Update on Experimental Therapeutics

Bronchopulmonary dysplasia (BPD) is a chronic inflammatory lung disease that affects thousands of newborns and infants every year. Although it is accepted that BPD results from lung damage and inflammation triggered by mechanical ventilation and hyperoxia, the causes and molecular events leading to lung damage and arrested development remain unknown. While recent advances in neonatal care have improved the survival of very low-weight infants, the rates of BPD have not improved accordingly. This is mainly due to our limited understanding of the disease's pathogenesis and the effective therapeutic options available. Current therapeutics for BPD involve ventilation management, steroid treatment, and administration of various agents, such as pulmonary surfactant, caffeine, vitamin A, nitric oxide, and stem cells. However, the efficacy of these agents in preventing and ameliorating BPD symptoms varies depending on the populations studied and the disease stage. As the field moves towards personalised therapeutic approaches, this review summarises clinical and experimental studies conducted in various models, aiming to increase understanding of the cellular and molecular mechanisms by which these agents can prevent or treat BPD. Due to the increasing number of extremely premature infants, it is imperative that we continue to work towards understanding the mechanisms of BPD pathogenesis and generating more effective therapeutic options.

Особливості перебігу рахіту у дітей, які народилися передчасно та перенесли бронхолегеневу дисплазію

Objective: to establish the clinical and metabolic peculiarities of rickets of children who were born prematurely and suffered bronchopulmonary dysplasia and to evaluate the effectiveness of specific and nonspecific prevention of rickets of these children. Materials and methods. 15 infants with clinical manifestations of rickets who were born preterm (gestational age 28,87 0,56 weeks, weight 1214,0077 ,91 g) and transferred to the neonatal bronchopulmonary dysplasia (first group) investigated serum total calcium, the level of ionized calcium, inorganic phosphorus in serum, activity of alkaline phosphatase in serum. The results were compared with those of 25 premature babies of the same age and severity of rickets without bronchopulmonary dysplasia (second group) and 10 term infants of the same age and severity of rickets (group). Results. Children with rickets and osteomalacia bronchopulmonary dysplasia symptoms prevailed, particularly kraniotabes (60.00%) and availability Harissonovoyi grooves (33.33%) (p<0.05), deformity of the sternum (93.33%) and expanding the lower aperture (100.00%) (p<0.01). The data indicate that the depth of metabolic disorders in premature babies with rickets and bronchopulmonary dysplasia fairly similar as prevailing without bronchopulmonary dysplasia of premature babies and of children who were born full-term. The children of the first group all indicators biochemistry blood were significantly lower than similar indicators in children with group comparison, the level of total calcium — 1.84±0.04 mmol/l and inorganic phosphorus — 1.44±0.02 mmol/l (p<0.01), and ionized calcium — 1.06±0.03 mmol/l. The activity of alkaline phosphatase (663.53±55.10 U/L) significantly prevailing rate of term infants (p<0,05). In premature infants antenatal and postnatal prevention of rickets was broken. Conclusion. It has been established that rickets in premature infants in the background bronchopulmonary dysplasia began earlier, had mostly acute degree course and heavier compared to prematurely without bronchopulmonary dysplasia. In preterm infants with rickets, which underwent bronchopulmonary dysplasia neonatal period, the degree of hypocalcemia, hypophosphatemia was significantly lower, while the index of alkaline phosphatase significantly prevailed. It has been established that the quality of antenatal and postnatal prevention of rickets was unsatisfactory. Key words: premature babies; rickets; bronchopulmonary dysplasia.

Leukotriene Receptor Blockade as a Life-Saving Treatment in Severe Bronchopulmonary Dysplasia

Background: Bronchopulmonary dysplasia (BPD) is a major cause of mortality and morbidity in infants with an extremely low birth weight. Because there is no effective therapy, the mortality of this condition in severely affected patients is high. Therapeutic blocking of the leukotriene system seems to be a logical approach due to the known pathophysiology of BPD. Objectives: The aim of this study was to examine the therapeutic effect of montelukast in preterm children suffering from severe BPD. Methods: We performed an unblinded, prospective trial including infants born between 23 and 27 weeks of gestation suffering from severe BPD. The study drug was montelukast (1 mg/kg of body weight as a single dose daily in the 1st week of therapy, increasing to 1.5 mg/kg of body weight in the 2nd week and finally to 2 mg/kg of body weight in the 3rd week). Treatment was continued until the radiological signs and the clinical symptoms of BPD disappeared or the patient was discharged from the hospital. Each patient included in this study was matched for gestational age, birth weight, and pulmonary severity score to a control. Results: Until March 2014, a total of 22 infants were enrolled into the study. The rates of the primary outcome differed significantly between the montelukast-treated group and the control group. All but 1 of the children in the treatment group survived (91%), whereas 7 of the 11 children in the control group died (survival rate 36%; p = 0.002 using Fisher's exact test). The mean mechanical ventilation time (41.2 ± 25.3 vs. 103.7 ± 90.6 days) was significantly shorter and the mean preterm complication score (3.0 ± 1.7 vs. 5.6 ± 1.4) was significantly lower in treated patients compared to the control group. (p = 0.05 for both items; Wilcoxon's matched-pairs test). Conclusion: Based on the clinical observations, the statistical results, and the relatively low risk of the study drug montelukast, we recommend using this treatment in severe cases of BPD for infants facing a high risk of death.

Displasia broncopulmonar y prematuridad. Evolución respiratoria a corto y a largo plazo

Bronchopulmonary dysplasia (BPD) is the most frequent chronic lung disease in premature children. With the inclusion of antenatal steroid therapy, surfactant use and novel mechanical ventilation strategies, survival of premature newborns has increased, whereupon the incidence of BPD has not only decreased but has also risen in extremely premature newborns. This has led to a high respiratory morbidity in the first 2–3 years of life, with numerous admissions to hospital and respiratory exacerbations mostly due to viral infections. Although there is a trend towards improvement, during school age and adolescence, respiratory symptoms may persist, due to changes in pulmonary function often showing a lower exercise capacity. Although BPD symptoms are similar to those of asthma, as there is limitation in airflow and bronchial hyperresponsiveness (BHR), pathophysiological mechanisms could be different in both diseases. On the other hand, isolated prematurity plays an important role in the child's respiratory pathology, proving that pulmonary function alterations in preterm children are present since the first months of life. A higher respiratory morbidity has also been observed in these children when compared to full-term newborns, not only during the first years of life but also subsequently. In this study, different aspects of chronic respiratory disease associated with prematurity will be analysed, drawing special attention to clinical symptoms, respiratory function changes, BHR and exercise capacity. All these aspects will be reviewed from early childhood until adolescence and young adult age. Similarities and differences between BPD and asthma will also be discussed.