Severe Bronchopulmonary Dysplasia Group Research Articles

Severe Bronchopulmonary Dysplasia Adversely Affects Brain Growth in Preterm Infants

Introduction: Bronchopulmonary dysplasia (BPD) is associated with neurodevelopmental outcomes of preterm infants, but its effect on brain growth in preterm infants after the neonatal period is unknown. This study aimed to evaluate the effect of severe BPD on brain growth of preterm infants from term to 18 months of corrected age (CA). Methods: Sixty-three preterm infants (42 with severe BPD and 21 without severe BPD) who underwent magnetic resonance imaging at term equivalent age (TEA) and 18 months of CA were studied by using the Infant Brain Extraction and Analysis Toolbox (iBEAT). We measured segmented brain volumes and compared brain volume and brain growth velocity between the severe BPD group and the non-severe BPD group. Results: There was no significant difference in brain volumes at TEA between the groups. However, the brain volumes of the total brain and cerebral white matter in the severe BPD group were significantly smaller than those in the non-severe BPD group at 18 months of CA. The brain growth velocities from TEA to 18 months of CA in the total brain, cerebral cortex, and cerebral white matter in the severe BPD group were lower than those in the non-severe BPD group. Conclusion: Brain growth in preterm infants with severe BPD from TEA age to 18 months of CA is less than that in preterm infants without severe BPD.

Oligohydramnios affects pulmonary functional/structural abnormalities in school-aged children with bronchopulmonary dysplasia.

The relationship between early life factors and childhood pulmonary function and structure in preterm infants remains unclear. This study investigated the impact of bronchopulmonary dysplasia (BPD) and perinatal factors on childhood pulmonary function and structure. This longitudinal cohort study included preterm participants aged ≥5 years born between 2005 and 2015. The children were grouped by BPD severity according to National Institutes of Health criteria. Pulmonary function tests (PFTs) were performed using spirometry. Chest computed tomography (CT) scans were obtained and scored for hyperaeration or parenchymal lesions. PFT results and chest CT scores were analyzed with perinatal factors. A total 150 children (66 females) aged 7.7 years (6.4-9.9 years) were categorized into non/mild BPD (n=68), moderate BPD (n=39), and severe BPD (n=43) groups. The median z score for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced midexpiratory flow (FEF25%-75%) were significantly lower in the severe versus non/mild BPD group (-1.24 vs. -0.18, -0.22 vs. 0.41, -1.80 vs. -1.12, and -1.88 vs. -1.00, respectively; all P<0.05). The median z scores of FEV1, FEV1/ FVC, and FEF25%-75% among asymptomatic patients were also significantly lower in the severe versus non/mild BPD group (-0.82 vs. 0.09, -1.68 vs. -0.87, -1.59 vs. -0.61, respectively; all P<0.05). The severe BPD group had a higher median (range) CT score than the non/mild BPD group (6 [0-12] vs. 1 [0-10], P<0.001). Prenatal oligohydramnios was strongly associated with both low pulmonary function (FEV1/FVC<lower limit of normal; odds ratio, 3.54) and high CT score (median difference, 2.54). School-aged children with severe BPD showed airflow limitations and structural abnormalities despite no subjective respiratory symptoms. These results suggest that patients with a history of prenatal oligohydramnios or prolonged mechanical ventilation require extended follow-up.

The serum thioredoxin-1 levels are not associated with bronchopulmonary dysplasia and retinopathy of prematurity

BackgroundWe hypothesized that the serum TRX-1 in extremely preterm infants (EPIs) after birth was associated with the development of severe bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP).MethodsThis single-centered retrospective study enrolled EPIs treated at our institution. Serum TRX-1 concentrations of the residual samples taken on admission, day 10–20 of life, and 36–40 weeks of postmenstrual age (PMA) were measured with an enzyme-linked immunosorbent assay.ResultsThe serum TRX-1 levels on admission were not different between the severe BPD (n = 46) and non-severe BPD groups (n = 67): [median (interquartile range) 147 (73.0–231) vs. 164 (80.5–248) ng/mL] (P = 0.57). These had no significant difference between the severe ROP (n = 47) and non-severe ROP groups (n = 66): [164 (71.3–237) vs. 150 (80.9–250) ng/mL] (P = 0.93). The TRX-1 levels at 10–20 days of life and 36–40 weeks of PMA also had no association with the development of severe BPD and ROP.ConclusionThe serum TRX-1 levels after birth are not predictive of severe BPD and ROP.ImpactSerum thioredoxin-1 levels in extremely preterm infants on the day of birth are lower than those in term or near-term infants hospitalized for transient tachypnea of the newborn.In extremely preterm infants, the serum thioredoxin-1 levels on the day of birth, at 10–20 days of life, and at postmenstrual age of 36–40 weeks were not associated with severe bronchopulmonary dysplasia and retinopathy of prematurity.The thioredoxin system is under development in extremely preterm infants; however, the serum thioredoxin-1 level is not predictive for severe bronchopulmonary dysplasia and retinopathy of prematurity.

Bronchopulmonary Dysplasia: A Five-Year Retrospective Cohort Study on Differences in Clinical Characteristics and Morbidities According to Severity Grading.

Bronchopulmonary dysplasia (BPD) is the most common complication associated with extreme prematurity. Although several criteria defining severity were developed over time, there are a few studies describing the differences in BPD phenotype and neonatal morbidities and complications between severity groups. We aimed to describe these differences in BPD patients of a neonatal intensive care unit (NICU). We conducted an observational retrospective cohort study through a medical record review over a five-year period. Participants were newborns admitted to an NICU who were diagnosed with BPD. We performed a descriptive statistical analysis of gestational complications and the use of antenatal corticosteroid therapy, birth-related data, and complications throughout the NICU stay, as well as the respiratory support used. We also compared different severity groups across these variables. The patients were divided into severe and non-severe BPD using the severity criteria of the 2001 NICHD/NHLBI/ORD consensus workshop. A total of 101 newborns with BPD participated in the study and 73 had data on BPD severity. The median gestational age was 27 weeks, ranging from 23 to 32 weeks. Of these 73 newborns, 36 had mild BPD (49.3%), 10 had moderate BPD (13.7%), and 27 had severe BPD (37.0%). When comparing severe and non-severe BPD, we found that extreme prematurity, extremely low birth weight, and small size for gestational age were more frequent in the severe BPD group (p-value=0.012, p-value<0.001, and p-value=0.012, respectively). Infants with severe BPD had a longer duration of invasive ventilation than those with mild or moderate BPD (p-value<0.001). Late sepsis, necrotizing enterocolitis, severe brain injury, and retinopathy of prematurity were more frequent in severe BPD (p-value=0.017, p-value=0.045, p-value=0.033, p-value=0.003, respectively). Previously published evidence describing causal links between BPD development and comorbidities exists but data on their impact on BPD severity are scarce. In our study, severe BPD seemed to be associated with a higher frequency of comorbidities and complications. Further studies are needed to ascertain the impact of each morbidity on the severity of BPD and if measures to prevent them could lead to potentially milder BPD disease.

Salivary cytokine - A non-invasive predictor for bronchopulmonary dysplasia in premature neonates.

To find a less invasive method of cytokine detection for premature neonates, we conducted this cohort study to investigate the salivary cytokines and to analyze their correlations with bronchopulmonary dysplasia (BPD). Premature neonates younger than 34weeks of gestational age without maternal or neonatal infection were recruited. Salivary samples were collected on their first (D1) and seventh (D7) days of life. The cytokine levels were detected by MILLPLEX® MAP Human multiplex assay. One-way analysis of variance, the Kruskal-Wallis test, Pearson's chi-square test, and logistic regression were used to analyze the data. Totally 125 neonates were enrolled and separated into four groups: control, mild, moderate, and severe BPD group. The salivary levels of D1 interleukin (IL)-6, IL-8, IL-10, IL-17, interferon (IFN)-γ, and D7 IL-6 (p=0.001, 0.001, 0.000, 0.043, 0.037 and 0.001, respectively) were significantly higher in the BPD groups than in the control group. After adjusting for the gestational age, acid-base equivalent, and absolute neutrophil count, comparing to the control group, the levels of D7 IL-17 became significantly lower in all three BPD groups (p=0.032, 0.030, and 0.030, respectively) and that of D7 IFN-α2 became significantly lower in the severe BPD group (p=0.037). Early-life salivary cytokine levels were correlated with the development of BPD in premature neonates. This study provides a novel method to predict BPD early and non-invasively.

Respiratory Severity Score and Its Association with Adverse Outcomes in Extremely Low Birth Weight Infants Undergoing Invasive Mechanical Ventilation

Background: Respiratory severity score (RSS) is a simple, non-invasive respiratory failure assessment tool that its appropriateness for lung disease severity is well-established. Objectives: This study aimed to investigate the potential value of early-life RSS values in predicting mortality or severe bronchopulmonary dysplasia (BPD) in infants with extremely low birth weight (ELBW) undergoing invasive mechanical ventilation. Methods: Following a retrospective approach, the current multi-center study intended to estimate the RSS and RSS/kg values in the first three days of life and time-weighted means of these values in ELBW babies who received invasive mechanical ventilation. Participants were categorized into two groups of survival without severe BPD and those with severe BPD or death. All RSS values and other risk factors were compared between groups. A multivariate logistic regression analysis was used to identify factors affecting severe BPD or death. The sensitivity and specificity of RSS values in predicting severe BPD or death were estimated using receiver operating characteristic (ROC) curves. Results: A total of 101 infants met the inclusion criteria. All RSS and RSS/kg values in the first three days of life were found to be significantly higher in the severe BPD or death group. The maximum area under the curve (AUC) in the ROC curves created for the respiratory severity score values was determined as RSS/kg mean with a cut-off value of 3.62 (85.3%), (P = 0.001). According to the multivariate logistic regression analysis, which included risk factors that may affect the development of severe BPD or mortality, both the mean RSS/kg score and the duration of invasive mechanical ventilation maintained statistically significant. [RSS/kg mean; OR = 2.28 (1.37 – 3.78), P = 0.001], [invasive MV duration; OR = 1.08 (95% CI, 1.03 – 1.14), P = 0.003]. Conclusions: This study demonstrated that high RSS/kg mean values in the early periods of life are valuable in predicting severe BPD or death in ELBW babies undergoing invasive mechanical ventilation. Furthermore, mean RSS had more predictive power than single RSS determinations, and incorporating body weight was associated with improved sensitivity of the score.

A comparison of newer classifications of bronchopulmonary dysplasia: findings from the Children's Hospitals Neonatal Consortium Severe BPD Group.

ObjectiveTo compare three bronchopulmonary dysplasia (BPD) definitions against hospital outcomes in a referral-based population.Study designData from the Children’s Hospitals Neonatal Consortium were classified by 2018 NICHD, 2019 NRN, and Canadian Neonatal Network (CNN) BPD definitions. Multivariable models evaluated the associations between BPD severity and death, tracheostomy, or length of stay, relative to No BPD references.ResultsMortality was highest in 2019 NRN Grade 3 infants (aOR 225), followed by 2018 NICHD Grade 3 (aOR 145). Infants with lower BPD grades rarely died (<1%), but Grade 2 infants had aOR 7–21-fold higher for death and 23–56-fold higher for tracheostomy.ConclusionsDefinitions with 3 BPD grades had better discrimination and Grade 3 2019 NRN had the strongest association with outcomes. No/Grade 1 infants rarely had severe outcomes, but Grade 2 infants were at risk. These data may be useful for counseling families and determining therapies for infants with BPD.

Oxidative and Proteolytic Inactivation of Alpha-1 Antitrypsin in Bronchopulmonary Dysplasia Pathogenesis: A Top-Down Proteomic Bronchoalveolar Lavage Fluid Analysis.

The study investigates the role of the oxidative and proteolytic inactivation of alpha-1 antitrypsin (AAT) in the pathogenesis of bronchopulmonary dysplasia (BPD) in premature infants. Bronchoalveolar lavage fluid (BALF) samples were collected on the 3rd day of life from mechanically ventilated neonates with gestational age ≤ 30 weeks and analyzed without previous treatment (top-down proteomics) by reverse-phase high-performance liquid chromatography-electrospray ionization mass spectrometry. AAT fragments were identified by high-resolution LTQ Orbitrap XL experiments and the relative abundances determined by considering the extracted ion current (XIC) peak area. Forty preterm neonates were studied: 20 (50%) did not develop BPD (no-BPD group), 17 (42.5%) developed mild or moderate new-BPD (mild + moderate BPD group), and 3 (7.5%) developed severe new-BPD (severe BPD group). Eighteen fragments of AAT and a fragment of AAT oxidized at a methionine residue were identified: significantly higher values of AAT fragments 25–57, 375–418, 397–418, 144–171, and 397–418 with oxidized methionine were found in the severe BPD group. The significantly higher levels of several AAT fragments and of the fragment 397–418, oxidized in BALF of preterm infants developing BPD, underlie the central role of an imbalance between proteases and protease inhibitors in exacerbating lung injury and inducing most severe forms of BPD. The study has some limitations, and between them, the small sample size implies the need for further confirmation by larger studies.

MicroRNA Signatures Associated with Bronchopulmonary Dysplasia Severity in Tracheal Aspirates of Preterm Infants.

Bronchopulmonary dysplasia (BPD) is a form of chronic lung disease that develops in neonates as a consequence of preterm birth, arrested fetal lung development, and inflammation. The incidence of BPD remains on the rise as a result of increasing survival of extremely preterm infants. Severe BPD contributes to significant health care costs and is associated with prolonged hospitalizations, respiratory infections, and neurodevelopmental deficits. In this study, we aimed to detect novel biomarkers of BPD severity. We collected tracheal aspirates (TAs) from preterm babies with mild/moderate (n = 8) and severe (n = 17) BPD, and we profiled the expression of 1048 miRNAs using a PCR array. Associations with biological pathways were determined with the Ingenuity Pathway Analysis (IPA) software. We found 31 miRNAs differentially expressed between the two disease groups (2-fold change, false discovery rate (FDR) < 0.05). Of these, 4 miRNAs displayed significantly higher expression levels, and 27 miRNAs had significantly lower expression levels in the severe BPD group when compared to the mild/moderate BPD group. IPA identified cell signaling and inflammation pathways associated with miRNA signatures. We conclude that TAs of extremely premature infants contain miRNA signatures associated with severe BPD. These may serve as potential biomarkers of disease severity in infants with BPD.

Clinical significance of amplitude-integrated electroencephalography in preterm infants with bronchopulmonary dysplasia

OBJECTIVE To study the changes and clinical significance of amplitude-integrated electroencephalography (aEEG) in preterm infants with bronchopulmonary dysplasia (BPD). METHODS A total of 156 preterm infants with a gestational age of ≤ 32+6 weeks who were diagnosed with BPD were enrolled as the BPD group, and 156 preterm infants without BPD who were hospitalized during the same period of time were enrolled as the control group. The aEEG scoring system for preterm infants was used to compare aEEG results between the two groups during hospitalization. A stratified analysis was conducted based on the examination time (at the corrected gestational age of ≤ 28+6 weeks, 29-30+6 weeks, 31-32+6 weeks, 33-34+6 weeks, 35-36+6 weeks, and 37-38+6 weeks). RESULTS Compared with the non-BPD group, the BPD group had a significantly lower total aEEG score at the corrected gestational age of 33-34+6 weeks (P < 0.001). The mild BPD group had a significantly lower total aEEG score than the non-BPD group at the corrected gestational age of 33-34+6 weeks (P < 0.05); the moderate BPD group had a significantly lower total aEEG score than the non-BPD group at the corrected gestational ages of 31-32+6 weeks, 33-34+6 weeks, and 35-36+6 weeks (P < 0.05); the severe BPD group had a significantly lower total aEEG score than the non-BPD group at all corrected gestational ages except ≤ 28+6 weeks and 29-30+6 weeks (P < 0.05). CONCLUSIONS Preterm infants with BPD (especially moderate to severe BPD) have a lower aEEG score than those without BPD, suggesting that their nervous system development may lag behind that of non-BPD preterm infants with the same gestational age. Therefore, early nervous system evaluation and intervention are necessary for preterm infants with BPD.

Retrospective analysis of inpatient polysomnogram characteristics and discharge outcomes in infants with bronchopulmonary dysplasia requiring home oxygen therapy.

Little is known about the polysomnogram (PSG) characteristics in infants with bronchopulmonary dysplasia (BPD), especially severe BPD, who do not need home ventilatory support but are at increased risk for chronic hypoxia and are vulnerable to its effects. This study aims to assess PSG characteristics and change in discharge outcomes in premature infants with BPD who required oxygen therapy at discharge. This is a retrospective chart review of premature infants with BPD who were admitted to a quaternary newborn and infant intensive care unit from January 1, 2012 to December 31, 2015 and who underwent polysomnography before discharge. Data from 127 patients were analyzed. The median gestational age of our patients was 26 weeks and 1 day (interquartile range [IQR]: 24.71, 28.86). The majority of the patients had moderate-to-severe BPD. The median obstructive apnea-hypopnea index was 5.3 events/h (IQR: 2.2, 10.1). The median oxygen desaturation index was 15.7 events/h (IQR: 4.7, 35). Nadir oxygen saturation measured by pulse oximeter was 81% (IQR: 76-86) and the arousal/awakening indexwas 21.9 (IQR: 13.3-30.9). No statistically significant difference was noted between severe and nonsevere BPD groups for PSG characteristics. However, average end-tidal CO2 was significantly higher in the severe BPD group (p = .0438). Infants in the severe BPD group were intubated longer than infants with nonsevere BPD (p = .0082).The corrected gestational age (CGA) at the time of discharge (CGA-PSG) and PSG (CGA-DC) was higher in severe BPD patients but not statistically different. The majority of premature infants who underwent a PSG were discharged home with oxygen, and 69% required a titration of their level of support based on results from the PSG. Our results highlight the presence of abnormal PSG characteristics in BPD patients, as early as 43 weeks CGA. These findings have not been previously described in this patient population prior to initial discharge from the hospital. A severe BPD phenotype tends to be associated with higher respiratory morbidity compared with a nonsevere BPD phenotype for the comparable CGA. PSG, when available, may be helpful for individualizing and streamlining treatment in preparation for discharge home and mitigating the effects of intermittent hypoxic episodes.

Influence of time under mechanical ventilation on bronchopulmonary dysplasia severity in extremely preterm infants: a pilot study

BackgroundThe relation between mechanical ventilation (MV) and bronchopulmonary dysplasia (BPD) - a common disease in extremely premature newborn (PTNB) - is well stabilished, but is unknown, however, how much time under MV influences the severity of the disease.AimTo define the duration under MV with greater chance to develop moderate to severe BPD in extremely PTNB and to compare clinical outcomes before and during hospitalization among patients with mild and moderate to severe BPD.MethodsFifty-three PTNB were separated into mild and moderate to severe BPD groups and their data were analyzed. Time under MV with a greater chance of developing moderate to severe BPD was estimated by the ROC curve. Perinatal and hospitalization outcomes were compared between groups. A logistic regression was performed to verify the influence of variables associated to moderate to severe BPD development, such as pulmonary hypertension (PH), gender, gestational age (GA) and weight at birth, as well the time under MV found with ROC curve. The result of ROC curve was validated using an independent sample (n = 16) by Chi-square test.ResultsTime under MV related to a greater chance of developing moderate to severe BPD was 36 days. Moderate to severe BPD group had more males (14 vs 5, p = 0,047), longer time under MV (43 vs 19 days, p < 0,001), more individuals with PH (12 vs 3, p = 0,016), worse retinopathy of prematurity (grade 3, 2 vs 11, p = 0,003), longer hospital length of stay (109 vs 81,5 days, p < 0,001), greater PMA (41 vs 38 weeks, p < 0,001) and weight (2620 vs 2031 g, p < 0,001) at discharge and the mild BPD group had more CPAP use prior to MV (12 vs 7, p = 0,043). Among all variables included in logistic regression, only PH and MV < 36 days were significant in the model, explaining 72% of variation in moderate to severe BPD development. In the validation sample, prevalence of preterm infants who needed MV for more than 36 days in the moderate to severe BPD group was 100% (n = 6) and 0% in mild BPD group (p = 0,0001).ConclusionTime under MV related to moderate to severe BPD development is 36 days, and worst outcomes are related to disease severity. PH and time under MV for more than 36 days are related to development of moderate to severe BPD.

Respiratory Morbidity and Lung Function Analysis During the First 36 Months of Life in Infants With Bronchopulmonary Dysplasia (BPD).

Purpose: To explore the lung function of bronchopulmonary dysplasia (BPD) in premature infants to guide clinical prevention, early diagnosis and treatment.Methods: Thirty infants with BPD at 4–36 months of corrected gestational age were enrolled and divided into mild BPD and moderate and severe BPD groups. Thirty full-term healthy infants, and 30 non-BPD infants at 4–36 months of corrected gestational age were included as controls. Clinical information, including respiratory infections and re-hospitalization, was compared among these groups. Furthermore, lung function analysis was performed in the infants.Results: The upper respiratory tract infection rate and re-hospitalization rate were significantly higher in the infants with BPD than in the non-BPD infants. The tidal volume/kg, proportion of time to reach peak tidal expiratory flow/total expiratory time, tidal volume exhaled at peak tidal expiratory flow/total tidal volume in BPD group were significantly lower in the BPD group than those in non-BPD group. These values gradually decreased as the severity of BPD increased. The respiratory rate (RR) in BPD group was significantly higher than that in non-BPD group. As the severity of the BPD increased, slope of the descending branch of expiration of tidal breathing flow capacity ring (TBFVL) increased.Conclusion: There is a correlation between the severity of BPD and a poor prognosis of respiratory system. TBFVL can directly reflect the characteristics of Tidal Pulmonary Function in children with different degrees of BPD.

Role of NT-proBNP in the prediction of moderate to severe Bronchopulmonary Dysplasia in preterm infants.

The objective of the study was to determine the clinical utility of brain natriuretic peptide (NT-proBNP) for prediction of moderate to severe bronchopulmonary dysplasia (BPD). We hypothesized that elevated NT-proBNP levels at 4 weeks of postnatal age may predict the severity of BPD in preterm infants. The study design was a prospective observational study. The research team enrolled and followed a cohort of 70 infants with gestational age less than or equal to 30 weeks. The plasma NT-proBNP levels were measured at the postnatal day 28th. We further followed and categorized infants into two groups. Infants with no or mild BPD (Group 1) and infants with moderate or severe BPD (Group 2). We compared plasma NT-proBNP levels at 28th day of postnatal life between Groups 1 and 2. The difference in NT-proBNP levels on day 28th between groups was used to predict the severity of BPD. Plasma NT-proBNP was significantly elevated in Group 2 compared with Group 1, median (IQR) of 845 pg/mL (553, 1632) compared with 726 pg/mL (391, 923), P = 0.02. NT-proBNP had a fair predictive accuracy (C statistics of 0.68) to determine moderate to severe BPD. NT-proBNP may be a useful biomarker in conjunction with clinical factors as a predictor of severe BPD. For future directions, the trend of NT-proBNP in infants with BPD may have clinical significance in monitoring of the disease.

A Novel Diagnostic Marker for the Severity of Bronchopulmonary Dysplasia in Very Low Birth Weight Infants: Interleukin-33

Background: Bronchopulmonary dysplasia (BPD) is an important clinical problem for premature infants. Previously, some biomarkers associated with severity of BPD have been studied. In our study, we aimed to investigate the value of interleukin-33 (IL-33) levels as a new biomarker in the follow-up of BPD severity and response to treatment. Materials and Methods: Premature infants of <32 weeks of gestational age and birth weight <1,500 g were included in the study. Infants with BPD were divided into moderate and severe BPD groups. Infants without BPD were assigned as the control group. Cord blood samples were taken from both groups immediately after birth. In addition, blood samples were obtained at the time of diagnosis of BPD and after the end of hydrocortisone (HC) treatment to measure IL-33 values in the serum. Results: During the study period, a total of 192 infants were eligible: 96 infants in the BPD group and 96 in the control group. Cord IL-33 values were similar between control (1.29 ± 0.68 pg/mL) and BPD (moderate/severe) (1.31 ± 0.84 pg/mL) groups (P = 0.813). The levels of IL-33 were higher in BPD group (3.43 ± 0.98 pg/mL) than in the control group (0.98 ± 0.51 pg/mL) (P < 0.001). IL-33 values decreased significantly after HC treatment (pretreatment: 3.43 ± 0.98 pg/mL versus post-treatment: 2.97 ± 0.28 pg/mL) (P < 0.001). In addition, IL-33 levels were significantly higher in severe BPD (3.91 ± 1.22 pg/mL) than in moderate BPD (2.82 ± 0.74) group (P < 0.001). Conclusions: Although the IL-33 level was not predictive of the development of BPD immediately after birth, it may be used as a new biomarker to diagnose, monitor, and follow the response to treatment of BPD.

Structural Pulmonary Abnormalities Still Evident in Schoolchildren with New Bronchopulmonary Dysplasia

Background: A new pattern of bronchopulmonary dysplasia (BPD) has emerged with the improved survival of preterm children. Objectives: Our aim was to characterize structural abnormalities associated with new BPD and to evaluate whether the severity of high-resolution computed tomography (HRCT) changes is associated with lung function. Methods: HRCT scans were performed on 21 schoolchildren with a history of new BPD (mild, n = 9; moderate, n = 4; and severe, n = 8) with a mean age of 12.7 years (range: 8.7-16.7). Scans were interpreted by 2 radiologists using a structured scoring system. Spirometry (forced expiratory volume in 1 s [FEV₁] and maximum mid-expiratory flow [MMEF]) and the diffusion capacity of the lung for carbon monoxide (DLCO) were measured. Results: At least 1 HRCT abnormality was evident in 17 children (81%), including linear-to-triangular subpleural opacities (71%), air trapping (29%), mosaic perfusion (24%), peribronchial thickening (14%), and emphysema (14%). The HRCT score was higher in the severe BPD group (11.50; 95% CI 2.86-20.14) than in the mild or moderate BPD group (1.39; 95% CI 0.24-2.54, and 2.75; 95% CI 0.28-5.22, respectively). HRCT scores were inversely related to FEV₁ (β -4.23; 95% CI -6.97 to -1.49, p = 0.004) and MMEF (β -3.45; 95% CI -6.10 to -0.80, p = 0.013) but not to DLCO. The duration of the initial mechanical ventilation was associated with HRCT scores (p = 0.014). Conclusions: Structural lung abnormalities are common among schoolchildren with a history of new BPD, resembling abnormalities described in the presurfactant era. HRCT abnormalities are associated with the duration of early mechanical ventilation and the severity of BPD and they are correlated with spirometry.

Clinical Utility of Echocardiography for the Diagnosis and Prognosis in Children with Bronchopulmonary Dsyplasia.

BackgroundBronchopulmonary dysplasia (BPD) may result in chronic pulmonary artery hypertension and right ventricular (RV) dysfunction. Various echocardiographic assessments of RV dysfunction have been used to determine whether echocardiographic measurements of premature infants with BPD could provide sensitive measures of RV function that correlates with BPD severity.MethodsTwenty-eight control subjects without BPD (non BPD group), 28 patients with mild BPD, 11 patients with moderate BPD, and six patients with severe BPD underwent echocardiograms with standard measurement such as ejection fraction by M-mode, tricuspid regurgitation pressure gradient, myocardial performance index (MPI) derived from pulse Doppler, and tissue Doppler imaging (TDI) measurements. BPD severity was classified by the NICHD/NHLBI/ORD workshop rating scale. Twenty-eight control subjects without BPD (non BPD group), 28 patients with mild BPD, 11 patients with moderate BPD, and six patients with severe BPD underwent echocardiograms with standard measurement such as ejection fraction by M-mode, tricuspid regurgitation pressure gradient, myocardial performance index (MPI) derived from pulse Doppler, and TDI measurements. BPD severity was classified by the NICHD/NHLBI/ORD workshop rating scale.ResultsNone of the standard echocardiographic findings was significantly different between the control group and BPD groups. However, mean septal TDI-MPI of the severe BPD group (0.68 ± 0.06) was significantly (p < 0.01) higher than that of the non-BPD (0.58 ± 0.10) or the mild BPD group (0.59 ± 0.12). In addition, mean RV TDI-MPI of the severe BPD group (0.71 ± 0.13) was significantly (p < 0.05) higher than that of the non-BPD group (0.56 ± 0.08) or the mild BPD group (0.60 ± 0.125). Linear regression showed a good correlation between the severity of BPD and RV TDI-MPI (p = 0.01, R = 0.30) or septal TDI-MPI (p = 0.04, R = 0.24).ConclusionEchocardiographic evaluation of RV function based on an assessment of RV TDI-MPI can provide RV dysfunction parameter in premature infants with BPD.

New BPD predicts lung function at school age: Follow-up study and meta-analysis.

New treatment practices have improved survival of preterm infants and decreased airway pathology in bronchopulmonary dysplasia (BPD). Our aim was to investigate whether preterm birth, BPD, and the severity of BPD predict lung function in school children that are born in surfactant era. We studied pulmonary function of 88 school-aged children born very preterm (gestational age <32 weeks) and paired them with 88 age- and sex-matched controls born at term. Spirometry and diffusion capacity were recorded. We also performed a meta-analysis covering the era of antenatal corticosteroid and surfactant treatment. BPD was defined as oxygen dependence for ≥ 28 days and it was severity-graded by oxygen requirement at 36 weeks postmenstrual age (mild, none; moderate, FiO2 = 0.22-0.29; severe, FiO2 ≥ 0.30). Preterm children had lower forced expiratory volume in 1 sec (FEV1 ) 86.4 ± 11.8 versus 94.9 ± 10.1 (mean % predicted ± SD; P < 0.001), and lower diffusion capacity (DLCO) 87.6 ± 13.9 versus 93.7 ± 12.0 (P = 0.005) compared with term controls. BPD group differed in both FEV1 (P = 0.037) and DLCO (P = 0.018) from those without BPD. For meta-analysis, search identified 210 articles. Together with present results, six articles met the inclusion criteria. FEV1 of no BPD, all BPD, and moderate to severe BPD groups differed from that in term controls by -7.4, -10.5, and -17.8%, respectively. According to meta-analysis and follow-up study, the adverse effects of prematurity on pulmonary function are still detectable in school-age. BPD was associated with reductions in both diffusion capacity and spirometry. New interventions are required to document a further decrease in the life-long consequences of prematurity.

Characteristics of lung function in preterm infants with varying degrees of bronchopulmonary dysplasia

To explore the characteristics of lung function in preterm infants with varying degrees of bronchopulmonary dysplasia(BPD). There were 407 infants (278 males and 129 females) were recruited from Shenzhen Children' Hospital between January 2011 and October 2012.Among them 188 term infants (term group)and 113 preterm infants (non-BPD preterm group) were selected as controls. A total of 106 BPD infants from the observation group were divided into mild(n = 48), moderate (n = 42) and severe(n = 16) sub-groups according to the definition of BPD. Infants with diseases interfering with lung function, such as congenital heart disease, congenital diaphragmatic hernia, or thoracic wall deformities, were excluded. Lung function was tested at a postmenstrual age (PMA) of 44 weeks.q test, Dunnett C test and Spearman analysis were used for statistical analysis. The age range was 17-116 d, test weight range 1.83-7.00 kg and test height range 40.0-64.0 cm.In non-BPD preterm group, the respiratory rate (RR) was higher than that in term group ((50 ± 13) vs (44 ± 10) times/min,P < 0.01) ,while the tidal volume(TV), ratio of time to peak tidal expiratory time and expiratory time (Tpef/Te) and peak expiratory flow(TPEF) were all less than those in term group ((25 ± 9) vs (29 ± 7)ml,29% ± 9% vs 33% ± 8%, (59 ± 23) vs (65 ± 25)ml/s,all P < 0.05) .Neither functional residual capacity(FRC) nor lung clearance index (LCI) had significant statistical difference between two groups ((20 ± 5) vs (19 ± 5)ml/kg, 8.4 ± 2.8 vs 8.7 ± 3.4, all P > 0.05)) . In moderate and severe BPD groups, RR ((57 ± 9), (58 ± 10) times/min) were both higher than that in non-BPD group(both P < 0.05) while RR in mild group ((53 ± 13)times/min)had no statistical significant difference with non-BPD group (P > 0.05). The values of TV and LCI in mild, moderate and severe BPD groups have no statistical significance with non-BPD group (all P > 0.05). Except for mild BPD group(24% ± 13%, (18 ± 5)ml/kg), Tpef/Te and FRC in both moderate and severe groups (20% ± 9% and 18% ± 5%, (15 ± 3)and (15 ± 4)ml/kg)were less than those in non-BPD group(all P < 0.05). Only in severe BPD group ((85 ± 11)ml/s), TPEF was higher than that in non-BPD group(P < 0.05). Correlation analysis showed that, except for LCI, all of these parameters were significantly associated with the degree of BPD(all P < 0.05). For BPD and non-BPD preterm infants, there are various changes in respiratory rhythm, lung volume, ventilation inhomogeneity, ventilatory efficiency and small airway resistance. The increases of pulmonary elastic recoil and degree of major airway constriction are obvious in moderate and severe BPD infants.

Elastase Inhibitory Activity of Airway α1-Antitrypsin Is Protected by Treatment With a Catalytic Antioxidant in a Baboon Model of Severe Bronchopulmonary Dysplasia

Recent studies in animal models of bronchopulmonary dysplasia (BPD) suggest that antioxidant treatments may be beneficial for the disease. However, the mechanisms by which these drugs improve the course of BPD are not completely known. Alpha1-antitrypsin (α1-AT) is one of the major serine protease inhibitors in human plasma that has antielastase and antiapoptotic activities. Both activities of α1-AT are dependent on its reactive site loop (RSL), which is highly susceptible to oxidative inactivation. In this study, we investigated the elastase inhibitory activity of α1-AT in two different baboon models of BPD, the "new BPD" and the "severe BPD" models, and determined the effect of treatment with a catalytic antioxidant, Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP), on the elastase inhibitory activity of α1-AT in the severe BPD model. Our results demonstrate the presence of sufficient elastase inhibitory activity of the airway α1-AT in the new but not in the severe BPD model. Treatment of severe BPD group baboons with the catalytic antioxidant MnTE-2-PyP resulted in augmentation of the elastase inhibitory activity of α1-AT. These findings suggest that prevention of the oxidative inactivation of α1-AT may be one of the mechanisms by which antioxidant therapy improves the pulmonary outcomes in animal models of severe BPD.