OBJECTIVES: To investigate the changes and significance of type 2 innate lymphoid cells (ILC2), interleukin-33 (IL-33), interleukin-25 (IL-25), thymic stromal lymphopoietin (TSLP), interleukin-5 (IL-5), and interleukin-13 (IL-13) in peripheral blood of preterm infants with bronchopulmonary dysplasia (BPD). METHODS: A total of 76 preterm infants with a gestational age of <32 weeks and a length of hospital stay of ≥14 days who were admitted to the Department of Pediatrics of the Affiliated Hospital of Jiangsu University from September 2020 to December 2021 were enrolled. According to the diagnostic criteria for BPD, they were divided into a BPD group with 30 infants and a non-BPD group with 46 infants. The two groups were compared in terms of the percentage of ILC2 and the levels of IL-33, IL-25, TSLP, IL-5, and IL-13 in peripheral blood on days 1, 7, and 14 after birth. RESULTS: The BPD group had significantly lower birth weight and gestational age than the non-BPD group (P<0.05). On days 7 and 14 after birth, the BPD group had significantly higher levels of ILC2, IL-33, TSLP, and IL-5 than the non-BPD group (P<0.05), and these indices had an area under the curve of >0.7 in predicting the devolpment of BPD (P<0.05). Multivariate logistic regression analysis showed that after adjusting for gestational age and birth weight, peripheral blood IL-33, TSLP and IL-5 on days 7 and 14 after birth were closely related to the devolpment of BPD (P<0.05). CONCLUSIONS Early innate immune activation and upregulated expression of related factors may be observed in preterm infants with BPD. ILC2, IL-33, TSLP, and IL-5 may be used as biological indicators for early diagnosis of BPD.
Child ; Humans ; Infant ; Infant, Newborn ; Birth Weight ; Bronchopulmonary Dysplasia/pathology* ; Cytokines ; Immunity, Innate ; Infant, Premature ; Interleukin-13 ; Interleukin-33 ; Interleukin-5 ; Lymphocytes/pathology* ; Thymic Stromal Lymphopoietin

To analyze clinical characteristics and risk factors of very low birth weight and extremely low birth weight infants with bronchopulmonary dysplasia (BPD). A retrospective epidemiological study was performed in 768 neonates (376 males) with birth weights<1 500 g and gestational age ≤ 34 weeks who survived ≥28 days. Clinical data were obtained from the multi-center clinical database of neonatal intensive care units (NICU) in 19 hospitals of Jiangsu Province between January 1, 2017 and December 31, 2017. These infants were divided into non-BPD group and BPD group according to BPD diagnositic criteria. Clinical features and potential risk factors were compared between groups with Chi-square test or nonparametric test. Risk factors for BPD were analyzed with Logistic regression analysis. Among the total of 768 eligible neonates, 577 without BPD, 191 with BPD (24.9%). Mild, moderate and severe BPD accounted for 73.3% (140/191), 23.6% (45/191) and 3.1% (6/191) of all BPD cases respectively. There were significant differences in the average gestational age (29 (28, 30) 30 (29, 31) weeks) or the average birth weight (1 170 (990, 1 300) 1 300 (1 160, 1 400) g) between BPD group and non-BPD group (-9.959,-7.202, both 0.000). The incidences of BPD in the infants with gestational age of<28 weeks, 28-31 weeks and 32-34 weeks were 51.7% (46/89), 24.8% (139/561), 5.1% (6/118) respectively. The incidences of BPD in infants with birth weigh1 000 g, 1 000- 1 249 g and 1 250-1 500 g were 62.3% (48/77), 25.9% (70/270) and 17.3% (73/421) respectively. Proportion of male (55.5% (106/191) 46.8% (270/577)), rate and length of conventional mechanical ventilation (48.7% (93/191) 14.9% (86/577), 120 (72, 259) 80 (29, 144)h), initial inhaled oxygen concentration and maximum inhaled oxygen concentration (0.35 (0.30, 0.40) 0.30(0.25, 0.40), 0.40 (0.30, 0.50) 0.30 (0.30, 0.40)) and volume of red blood cell transfusion (53(30, 90) .38(28, 55) ml) were higher in BPD group than in non-BPD group (χ(2)=4.350, 91.640, -3.557, -2.848, -3.776, -4.677, all 0.05). Rate of continuous positive airway pressure (12.6%(24/191) 19.4%(112/577)) during neonatal resuscitation in delivery room was lower in BPD group than that in non-BPD group (χ(2)=4.614, 0.032). The incidences of complications in BPD group including severe asphyxia, neonatal respiratory distress syndrome (NRDS), persistent pulmonary hypertension in newborns (PPHN), patent ductus arteriosus, anemia of prematurity, early onset sepsis, clinical sepsis and ventilator associated pneumonia were higher than that in non-BPD group (15.2%(29/191) 4.5% (26/577), 91.1% (174/191) 56.7% (327/577), 2.6% (5/191) 0.2% (1/577), 43.5% (83/191) 34.2% (197/577), 88.0% (168/191) 58.8% (339/577), 15.7% (30/191) 9.9% (57/577), 42.9% (82/191) 18.6% (107/577), 14.1% (27/191) 2.3% (13/577); χ(2)=24.605, 74.993, 9.167, 5.373, 61.866, 4.557, 43.149, 34.315, all 0.05). Multivariate logistic regression analysis showed that NRDS (4.651, 95: 1.860-11.625), clinical sepsis (1.989, 95: 1.067-3.708), ventilator associated pneumonia (3.155, 95: 1.060-9.388), conventional mechanical ventilation (2.298, 95: 1.152-4.586), and volume of red blood cell transfusion (1.013, 95: 1.002-1.024) were risk factors of BPD. BPD is more common in very low birth weight infants of male with gestational age less than 32 weeks. Using CPAP in the delivery room, active treatment of NRDS, preventing nosocomial infection, and reducing invasive ventilation and red blood cell transfusion may decrease the incidence of BPD.
Birth Weight ; Bronchopulmonary Dysplasia ; complications ; epidemiology ; pathology ; Gestational Age ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Infant, Very Low Birth Weight ; Male ; Respiratory Distress Syndrome, Newborn ; Retrospective Studies ; Risk Factors

OBJECTIVETo study the effect of rhubarb on neonatal rats with bronchopulmonary dysplasia (BPD) induced by hyperoxia.

METHODSA total of 64 rats (postnatal day 4) were randomly divided into four groups: air control, rhubarb control, hyperoxia model, and hyperoxia+rhubarb (n=16 each). The rats in the hyperoxia model and hyperoxia+rhubarb groups were exposed to hyperoxia (60% O2) to establish a BPD model. The rats in the rhubarb control and hyperoxia+rhubarb groups were given rhubarb extract suspension (600 mg/kg) by gavage daily. The pathological changes of lung tissue were evaluated by hematoxylin-eosin staining on postnatal days 14 and 21. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were measured by spectrophotometry. The mRNA and protein expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were determined by RT-PCR and Western blot respectively.

RESULTSThe hyperoxia model group showed reduced alveolar number, increased alveolar volume, and simplified alveolar structure, which worsened over the time of exposure to hyperoxia. These pathological changes were significantly reduced in the hyperoxia+rhubarb group. On postnatal days 14 and 21, compared with the air control and rhubarb control groups, the hyperoxia model group had significantly reduced radical alveolar count (RAC), significantly reduced activity of SOD in the lung tissue, and significantly increased content of MDA and mRNA and protein expression levels of TNF-α and IL-6 (P<0.05). Compared with the hyperoxia model group, the hyperoxia+rhubarb group had significantly increased RAC, significantly increased activity of SOD in the lung tissue, and significantly reduced content of MDA and mRNA and protein expression levels of TNF-α and IL-6 (P<0.05).

CONCLUSIONSRhubarb may play a protective role in rats with BPD induced by hyperoxia through inhibiting inflammatory response and oxidative stress.

Animals ; Animals, Newborn ; Bronchopulmonary Dysplasia ; metabolism ; pathology ; prevention & control ; Disease Models, Animal ; Hyperoxia ; complications ; Lung ; metabolism ; pathology ; Plant Extracts ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Rheum ; Superoxide Dismutase ; metabolism ; Tumor Necrosis Factor-alpha ; genetics

OBJECTIVETo study the expression of SUMO-modified CCAAT enhancer binding protein α (C/EBPα) in preterm rat model of bronchopulmonary dysplasisa (BPD) induced by hyperoxia exposure and its role.

METHODSEighteen preterm rats were randomly divided into an air group and a hyperoxia group (n=9 each). The model of BPD was prepared in preterm rats exposed to hyperoxia. The rats from the two groups were sacrificed on postnatal days 4, 7 and 14 respectively (3 rats at each time) and lung tissues were harvested. Periodic acid-Schiff (PAS) staining was used to observe the differentiation of rat lung tissues. Ki67 expression was detected by immunohistochemistry. Western blot was used to measure the protein expression of small ubiquitin-related modifier-1(SUMO1) and C/EBPα. A co-immunoprecipitation assay was performed to measure the protein expression of SUMO-modified C/EBPα.

RESULTSCompared with the air group, the hyperoxia group showed a decreased glycogen content in the lung tissue on postnatal day 4, and an increased content on postnatal days 7 and 14. Over the time of hyperoxia exposure, the hyperoxia group showed an increased expression of Ki67 in the lung tissue compared with the air group at all time points. Compared with the air group, the protein expression of C/EBPα increased on postnatal day 4 and decreased on postnatal days 7 and 14 in the hyperoxia group (P<0.05). The hyperoxia group had significantly upregulated expression of SUMO1 and SUMO-modified C/EBPα compared with the air group at all time points (P<0.05). In the hyperoxia group, the protein expression of SUMO-modified C/EBPα was positively correlated with the glycogen content (r=0.529, P<0.05) and the expression of Ki67 (r=0.671, P<0.05).

CONCLUSIONSHyperoxia may induce over-proliferation and differentiation disorders of alveolar epithelial cells in preterm rat model of BPD, possibly through an increased expression of SUMO-modified C/EBP&alpha.

Animals ; Animals, Newborn ; Bronchopulmonary Dysplasia ; etiology ; metabolism ; pathology ; CCAAT-Enhancer-Binding Protein-alpha ; metabolism ; Cell Proliferation ; Disease Models, Animal ; Hyperoxia ; complications ; pathology ; Ki-67 Antigen ; analysis ; Pulmonary Alveoli ; pathology ; Rats ; Rats, Sprague-Dawley ; Sumoylation

OBJECTIVETo explore the expression of CASZ1 and its relationship with the pulmonary microvascular development in lung tissue of newborn rats exposed to hyperoxia which induced bronchopulmonary dysplasia (BPD).

METHODForty-eight newborn Sprague Dawley(SD) rats (male and female unlimited) were randomly divided into two groups: experimental group and control group according to random digits table with 24 in each.The rats in experimental group were exposed to high oxygen volume fraction of 800 ml/L and the rats in control group were exposed to normal air. Eight rats were randomly selected from each group on day 3 and 7 after oxygen exposure.The sections of lung were stained with HE method in order to assess lung histological changes, the alveolar development was evaluated by the number of radial alveolar count (RAC) and septal wall thickness. CD31 was detected by immunohistochemistry (IHC) method and the capillary density was calculated. The location, distribution and expression of CASZ1 in the lung tissue were detected by the immunohistochemistry, Western blotting, and quantitative PCR (qPCR).

RESULT(1) Stained by HE, lungs of experimental group showed destroyed alveoli, alveoli fusion and increased septal wall thickness, RAC were significantly lower than those in control group(14 d: septal wall thickness (12.69 ± 0.63) μm vs. (6.53 ± 0.16) μm, RAC 5.9 ± 0.4 vs. 8.4 ± 1.0, t = 19.046, 4.760, P both = 0.000). (2) CD31 protein was expressed predominantly in cytoplasm of pulmonary microvascular endothelial cells. The experimental group CD31 average optical density (AIOD) were decreased compared with control group((16.6 ± 1.6) × 10(3) vs.(40.1 ± 2.4) × 10(3), (18.1 ± 1.4) × 10(3) vs.(83.2 ± 5.2) × 10(3), (49.2 ± 5.4) × 10(3) vs.(136.2 ± 28.1) × 10(3), t=16.185, 16.066 and 6.078, P<0.01 for all comparisons). Capillary density in experimental group was also significantly decreased compared with control group ((3.84 ± 0.15)% vs.(6.01 ± 0.22)%, (4.17 ± 0.38)% vs.(6.15 ± 0.24)%, (5.43 ± 0.44)% vs. (9.13 ± 0.25)%, t = 16.124, 8.773 and 14.076, P all < 0.01). (3)RT-qPCR and Western blotting showed that the CASZ1 mRNA significantly increased in experimental group compared with control group(0.56 ± 0.17 vs. 1.00 ± 0.26, 0.32 ± 0.29 vs. 0.58 ± 0.14, 0.14 ± 0.22 vs. 0.56 ± 0.15, t=3.890, 3.303 and 2.388, P < 0.05 for all comparisons), and the protein expression of CASZ1 also significantly increased in experimental group compared with control group (0.65 ± 0.02 vs. 0.78 ± 0.23, 0.46 ± 0.03 vs. 0.75 ± 0.05, 0.34 ± 0.22 vs. 0.75 ± 0.04, t=6.200 and 10.485 and 14.998, P < 0.05 for all comparisons). (4)The protein level of CASZ1 in experimental group was positively correlated with capillary density (r=0.519, P<0.01).

CONCLUSIONCASZ1 is involved in the whole process of newborn rats BPD and may be linked to pulmonary microvascular dysplasia.

Animals ; Animals, Newborn ; Bronchopulmonary Dysplasia ; pathology ; Female ; Hyperoxia ; pathology ; Lung ; blood supply ; pathology ; Male ; Oxygen ; adverse effects ; Pulmonary Alveoli ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Transcription Factors ; metabolism

Fetal lung development normally occurs in a hypoxic environment. Hypoxia-inducible factor (HIF)-1alpha is robustly induced under hypoxia and transactivates many genes that are essential for fetal development. Most preterm infants are prematurely exposed to hyperoxia, which can halt hypoxia-driven lung maturation. We were to investigate whether the HIF-1alpha inducer, deferoxamine (DFX) can improve alveolarization in a rat model of bronchopulmonary dysplasia (BPD). A rat model of BPD was produced by intra-amniotic lipopolysaccharide (LPS) administration and postnatal hyperoxia (85% for 7 days), and DFX (150 mg/kg/d) or vehicle was administered to rat pups intraperitoneally for 14 days. On day 14, the rat pups were sacrificed and their lungs were removed and examined. A parallel in vitro study was performed with a human small airway epithelial cell line to test whether DFX induces the expression of HIF-1alpha and its target genes. Alveolarization and pulmonary vascular development were impaired in rats with BPD. However, DFX significantly ameliorated these effects. Immunohistochemical analysis showed that HIF-1alpha was significantly upregulated in the lungs of BPD rats treated with DFX. DFX was also found to induce HIF-1alpha in human small airway epithelial cells and to promote the expression of HIF-1alpha target genes. Our data suggest that DFX induces and activates HIF-1alpha, thereby improving alveolarization and vascular distribution in the lungs of rats with BPD.
Animals ; Bronchopulmonary Dysplasia/*drug therapy/*metabolism/pathology ; Deferoxamine/*administration & dosage ; Female ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Male ; Pulmonary Alveoli/drug effects/*growth & development/metabolism/pathology ; Pulmonary Veins/drug effects/*growth & development/pathology ; Rats ; Rats, Sprague-Dawley ; Treatment Outcome ; Up-Regulation/drug effects

Conflicting results on the influences of histologic chorioamnionitis (HC) on neonatal morbidities might be partly originated from using different definition of HC. The aim of this study was to determine the relationship between HC and neonatal morbidities using definition of HC that reflects the site and extent of inflammation. This was a retrospective cohort study of 261 very low birth weight (VLBW) infants admitted at a tertiary academic center. Based on the site of inflammation, HC was categorized: any HC; amnionitis; funisitis; amnionitis+funisitis. The extent of inflammation in each site was reflected by sub-defining high grade (HG). The incidences of morbidities in infants with and without HC were compared. The bronchopulmonary dysplasia (BPD) rate was significantly higher in infants with amnionitis and the severe retinopathy of prematurity (ROP) rate was significantly higher in infants with any HC and funisitis. After adjustment for both gestational age and birth weight, the respiratory distress syndrome (RDS) rate was significantly lower in infants with all categories of HC except for HG amnionitis and HG funisitis, which are not associated with lower RDS rate. HG amnionitis was significantly associated with increased BPD rate but the association of HC with severe ROP disappeared. In conclusion, HC is significantly associated with decreased RDS and HG amnionitis with increased BPD while lacking association with other neonatal morbidities in VLBW infants. The association with HC and neonatal morbidities differs by the site and extent of chorioamnionitis.
Adult ; Birth Weight ; Bronchopulmonary Dysplasia/complications/*epidemiology ; Chorioamnionitis/classification/*epidemiology/pathology ; Cohort Studies ; Female ; Gestational Age ; Humans ; Infant, Newborn ; *Infant, Very Low Birth Weight ; Neutrophil Infiltration/immunology ; Placenta/pathology ; Pre-Eclampsia/*epidemiology/pathology ; Pregnancy ; Respiratory Distress Syndrome, Newborn/complications/*epidemiology ; Retinopathy of Prematurity/complications/*epidemiology ; Retrospective Studies ; Tertiary Care Centers

Bronchopulmonary dysplasia (BPD) is related to decreased lung function throughout life. However, the pathology and radiology pattern of BPD of adults are not documented well yet. In this case report, we present BPD case of an adult monozygotic twin showing nearly identical lesions on chest computed tomography (CT). CT images showed mixed areas of ground-glass and reticular opacities in both lungs. They had common histories of pneumonias requiring mechanical ventilations in period of infants. Pulmonary function test of one patient showed a pulmonary insufficiency with airway obstruction. Pathologic findings showed bronchiolar hyperplasia and peribronchiolar fibrosis which was similar to classic BPD patients. Our twin case report might help provide distinguishing pathology and radiology pattern of an adult pulmonary sequelaes of BPD. It might be reasonable to make close follow-up for BPD patients to evaluate the long-term outcomes of BPD survivors.
Adult* ; Airway Obstruction ; Bronchopulmonary Dysplasia* ; Fibrosis ; Humans ; Hyperplasia ; Infant ; Infant, Newborn ; Lung ; Pathology* ; Pneumonia ; Respiration, Artificial ; Respiratory Function Tests ; Survivors ; Thorax ; Twins, Monozygotic*

This study was done to evaluate respiratory syncytial virus (RSV) related readmission (RRR) and risk factors of RRR in preterm infants < 34 weeks gestational age (GA) within 1 yr following discharge from the neonatal intensive care unit (NICU). Infants (n = 1,140) who were born and admitted to the NICUs of 46 hospitals in Korea from April to September 2012, and followed up for > 1 yr after discharge from the NICU, were enrolled. The average GA and birth weight of the infants was 30(+5) +/- 2(+5) weeks and 1,502 +/- 474 g, respectively. The RRR rate of enrolled infants was 8.4% (96/1,140), and RSV accounted for 58.2% of respiratory readmissions of infants who had laboratory tests confirming etiological viruses. Living with elder siblings (odd ratio [OR], 2.68; 95% confidence interval [CI], 1.68-4.28; P < 0.001), and bronchopulmonary dysplasia (BPD) (OR, 2.95; 95% CI, 1.44-6.04; P = 0.003, BPD vs. none) increased the risk of RRR. Palivizumab prophylaxis (OR, 0.06; 95% CI, 0.03-0.13; P < 0.001) decreased the risk of RRR. The risk of RRR of infants of 32-33 weeks' gestation was lower than that of infants < 26 weeks' gestation (OR, 0.11; 95% CI, 0.02-0.53; P = 0.006). This was a nationwide study that evaluated the rate and associated risk factors of RRR in Korean preterm infants. Preterm infants with BPD or living with siblings should be supervised, and administration of palivizumab to prevent RRR should be considered.
Antiviral Agents/therapeutic use ; Birth Weight ; Bronchopulmonary Dysplasia/drug therapy/pathology ; Female ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Intensive Care Units, Neonatal ; Male ; Odds Ratio ; Palivizumab/therapeutic use ; Patient Discharge ; Patient Readmission ; Republic of Korea ; Respiratory Syncytial Virus Infections/drug therapy/*pathology/virology ; Respiratory Syncytial Viruses/*isolation & purification ; Risk Factors ; Siblings

Bronchopulmonary Dysplasia ; diagnostic imaging ; pathology ; therapy ; Female ; Glycogen Storage Disease ; diagnosis ; pathology ; therapy ; Humans ; Infant ; Infant, Newborn ; Lung ; diagnostic imaging ; growth & development ; pathology ; Lung Diseases, Interstitial ; classification ; diagnosis ; pathology ; therapy ; Male ; Neurosecretory Systems ; pathology ; Pediatrics ; Tomography, X-Ray Computed