Definition Of Bronchopulmonary Dysplasia Research Articles

Predicting Long-Term Respiratory Outcomes in Premature Infants: Is It Time to Move beyond Bronchopulmonary Dysplasia?

Premature birth has been shown to be associated with adverse respiratory health in children and adults; children diagnosed with bronchopulmonary dysplasia (BPD) in infancy are at particularly high risk. Since its first description by Northway et al. about half a century ago, the definition of BPD has gone through several iterations reflecting the changes in the patient population, advancements in knowledge of lung development and injury, and improvements in perinatal care practices. One of the key benchmarks for optimally defining BPD has been the ability to predict long-term respiratory and health outcomes. This definition is needed by multiple stakeholders for hosts of reasons including: providing parents with some expectations for the future, to guide clinicians for developing longer term follow-up practices, to assist policy makers to allocate resources, and to support researchers involved in developing preventive or therapeutic strategies and designing studies with meaningful outcome measures. Long-term respiratory outcomes in preterm infants with BPD have shown variable results reflecting not only limitations of the current definition of BPD, but also potentially the impact of other prenatal, postnatal and childhood factors on the respiratory health. In this manuscript, we present an overview of the long-term respiratory outcomes in infants with BPD and discuss the role of other modifiable or non-modifiable factors affecting respiratory health in preterm infants. We will also discuss the limitations of using BPD as a predictor of respiratory morbidities and some of the recent advances in delineating the causes and severity of respiratory insufficiency in infants diagnosed with BPD.

Newer bronchopulmonary dysplasia definitions and prediction of health economics impacts in very preterm infants.

To compare the abilities of bronchopulmonary dysplasia (BPD) definitions to predict hospital charges as a surrogate of disease complexity. Retrospective study of infants admitted to the neonatal intensive care unit (NICU) less than 32 weeks gestational age. Subjects were classified according to the Canadian Neonatal Network (CNN), the National Institute of Child Health and Human Development (NICHD) (2018), and Jensen BPD definitions as none, mild (1), moderate (2), or severe (3) BPD. Spearman's correlation was performed to evaluate the association of BPD definitions with health economics outcomes. One hundred and sixty-eight infants were included with mean birth weight of 1197 g and mean gestational age of 28.4 weeks. More infants were classified as no BPD according to CNN definition (79%) in comparison to NICHD 2018 (64.3%) and Jensen (59.5%) definitions. There were fewer infants as the grade of severity increased for all definitions, this was most linear for Jensen definition with Grade 1 present in 25%, Grade 2 in 12.5%, and Grade 3 in 3%. A stronger correlation with NICU length of stay, NICU hospital charges, NICU charges per day, and first year of life hospital charges was detected for Jensen definition (correlation coefficient of 0.58, 0.66, 0.64, 0.67, respectively) in comparison to CNN and NICHD 2018 definitions (p < .0001). Jensen BPD definition had the strongest correlation with first year health economics outcomes in our study. Validating recent BPD definitions using population-based data is imperative to improve family counseling and enhance the designs of quality improvement initiatives and therapeutic research studies targeting patient-centric outcomes.

Bronchopulmonary Dysplasia: Then, Now, and Next

Bronchopulmonary dysplasia (BPD) has evolved considerably since its first description over 50 years ago. This review aims to provide a historical framework for conceptualizing BPD and a current understanding of the changing definition, epidemiology, pathophysiology, treatment, and outcomes of BPD. The transdisciplinary approach that led to the initial phenotypic description of BPD continues to hold promise today. Investigators are refining the definition of BPD in light of changes in clinical care and increasing survival rates of very preterm infants. Despite improvements in perinatal care the incidence of BPD continues to increase. There is growing recognition that antenatal risk factors play a key role in the development of BPD. Strategies designed to prevent or limit neonatal lung injury continue to evolve. Defining the phenotype of infants with BPD can meaningfully direct treatment. Infants with BPD benefit from an interdisciplinary approach to longitudinal care with a focus on growth and neurocognitive development. While the ultimate impact of BPD on long-term pulmonary morbidity remains an active area of investigation, current data indicate that most children and adolescents with a history of BPD have a quality of life comparable to that of other preterm infants.

Refining the Definition of BPD: Characterization of Intercurrent Episodes

Background: The main definitions of bronchopulmonary dysplasia (BPD), proposed by Jobe-Bancalari, Shennan et al., and Walsh et al., focus on oxygen (O2)-need and ventilatory support for the first weeks of life and at 36 weeks of post-menstrual age (PMA). Oxygen need at 36 weeks of PMA is sometimes due to intercurrent episodes (IEs) other than BPD. The aim of this retrospective study was to characterize IEs and determine their impact on BPD in preterm infants born at 28 days and at 36 weeks of PMA (±10 days) was analyzed. We classified each infant according to the three BPD definitions. Patients requiring O2 or ventilator support at 36 weeks of PMA, with no need for O2 in the first 28 days of life, were qualified for having IEs if their O2/ventilator dependence (at 36 weeks) had a limited duration and/or could be ascribed to a known condition. Then, the contribution of IEs to the BPD rate was evaluated.Results: Out of 1,210 patients, the BPD infants were 431 (35.6%), 169 (14.0%), and 186 (15.4%) according to Jobe-Bancalari, Shennan et al., and Walsh et al., respectively. Twenty-eight patients had IEs (16.6% of those on O2 at 36 weeks of PMA) indicating a mild BPD overestimation (P=0.065).Conclusion: We proposed a definition of IEs and found that IEs could lead to a potential BPD overestimation. Further research is needed to find out if patients with IE, similarly to infants with BPD, are prone to childhood complications and need preventive measures.

Bronchopulmonary dysplasia predicted at birth by artificial intelligence.

AimTo develop a fast bedside test for prediction and early targeted intervention of bronchopulmonary dysplasia (BPD) to improve the outcome.MethodsIn a multicentre study of preterm infants with gestational age 24‐31 weeks, clinical data present at birth were combined with spectral data of gastric aspirate samples taken at birth and analysed using artificial intelligence. The study was designed to develop an algorithm to predict development of BPD. The BPD definition used was the consensus definition of the US National Institutes of Health: Requirement of supplemental oxygen for at least 28 days with subsequent assessment at 36 weeks postmenstrual age.ResultsTwenty‐six (43%) of the 61 included infants developed BPD. Spectral data analysis of the gastric aspirates identified the most important wave numbers for classification and surfactant treatment, and birth weight and gestational age were the most important predictive clinical data. By combining these data, the resulting algorithm for early diagnosis of BPD had a sensitivity of 88% and a specificity of 91%.ConclusionA point‐of‐care test to predict subsequent development of BPD at birth has been developed using a new software algorithm allowing early targeted intervention of BPD which could improve the outcome.

Incidence of bronchopulmonary dysplasia and mortality of very low birth weight infants in Vojvodina

Introduction/Objective. The incidence of bronchopulmonary dysplasia (BPD) varies depending on the prematurity rate, definition, and therapy that are applied at a certain center. The average incidence of BPD for very low birth weight infants (VLBW) in developed countries ranges 4?53%. The mortality of VLBW infants is high and represents 50% of the total neonatal and infant mortality. In recent years, the survival limits are shifted towards lower gestations. The aim of our study was to determine the incidence and severity of BPD in VLBW infants in Vojvodina and the overall mortality. Methods. This retrospective study was conducted from January 2006 to December 2011 and included 504 infants with birth weight &lt; 1,500 g. Results. In the total premature infants? population, 82.3% survived by the gestational age of 36 weeks. According to the original definition of BPD, as supplemental oxygen use at 28 days of life, BPD had 45.4% of infants. According to the severity based definition 19.4% had mild BPD, 19.8% moderate BPD and 6.5% severe BPD. If BPD is observed as supplemental oxygen use at 36 weeks postmenstrual age, BPD had 26% of infants. Conclusion. The overall mortality and incidence of BPD in our study are comparable to those in some developed countries and lower compared to underdeveloped countries.

Bronchopulmonary dysplasia: how can we improve its outcomes?

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of preterm infants with multiple factors affected from prenatal to postnatal periods. Despite significant advances in neonatal care over almost 50 years, BPD rates have not decreased; in fact, they may have even increased. Since more preterm infants, even at periviable gestational age, survive today, different stages of lung development affect the pathogenesis of BPD. Hence, the definition of BPD has changed from “old” to “new.” In this review, we discuss the various definitions of BPD, risk factors from the prenatal to postnatal periods, management strategies by phase, and future directions for research.

The level of extracellular superoxide dismutase in the first week of life in very and extremely low birth weight infants and the risk of developing bronchopulmonary dysplasia.

Background Antioxidant enzymes may play a significant role in the development of bronchopulmonary dysplasia (BPD). The aim of the study was to assess the relationship between the level of extracellular superoxide dismutase (SOD3) in the serum at days 1 and 7 of life and the risk of developing BPD. Methods The study comprised 103 neonates born before 32 weeks' gestation with a birth weight of ≤1500 g. Results In the investigated group, the median serum SOD3 level at day 1 of life was 4.01 ng/mL [interquartile range (IQR) 2.59-5.09 ng/mL] and at day 7 of life 3.13 ng/mL (IQR 2.49-4.34 ng/mL). A statistically significant decrease in the serum SOD3 level was found in the first week of life, P < 0.0001. No correlation was found between the serum SOD3 level at day 1 of life and gestational age R = 0.07, P = 0.4543 and birth weight R = 0.10, P = 0.3083. No statistically significant correlation was found between the dynamics of change in the SOD3 level in serum at days 1 and 7 of life and the risk of BPD development for the definition of BPD at day 28 of life, P = 0.8764 nor at 36 weeks' postmenstrual age, P = 0.6598. Conclusion The study revealed a statistically significant decrease in the serum SOD3 level in the first week of life in very and extremely low birth weight infants born before 32 weeks of gestation. In the clinical setting, no relationship was observed between the level of SOD3 in serum and the risk of developing BPD.

Impact of chest radiography-based definition of bronchopulmonary dysplasia.

Bubbly/cystic appearance on chest radiograph is an important factor in severe-type bronchopulmonary dysplasia (BPD) in Japan. The aim of this study was to determine the perinatal characteristics and neonatal complications of the bubbly/cystic(+) group in extremely preterm infants with BPD, that is, oxygen dependency at day 28 after birth (BPD28). This was a multicenter retrospective cohort study of population data from infants (birthweight, <1,500 g) enrolled in the Neonatal Research Network of Japan. Of the 15 480 infants born at <28 weeks' gestational age (GA) between 2003 and 2012, 8,979 met the BPD28 criteria. The BPD28 infants were classified according to bubbly/cystic appearance on radiograph (±) at >28 postnatal days. The bubbly/cystic(+) group had lower GA and birthweight and required longer mechanical ventilation and oxygen dependency than the bubbly/cystic(-) group. After adjustment for confounding factors, bubbly/cystic appearance was an independent risk factor for home oxygen therapy at discharge. Bubbly/cystic appearance on chest radiograph was a predictor of short-term respiratory outcomes in infants with BPD28, which is diagnosed much earlier (≥28 postnatal days), and has a potentially different etiology to BPD36 (oxygen and/or positive pressure respiratory support dependency at 36 weeks' postmenstrual age).

Sharing Data to Accelerate Medicine Development and Improve Neonatal Care: Data Standards and Harmonized Definitions

Sharing Data to Accelerate Medicine Development and Improve Neonatal Care: Data Standards and Harmonized Definitions

The definition of bronchopulmonary dysplasia: an evolving dilemma.

The definition of bronchopulmonary dysplasia (BPD) continues to be a challenging one. The evolution of the disease as well as its definition are discussed. Limitations of the current as well as newer suggested definitions of BPD are summarized. Recognition of the variability of the pulmonary phenotype is a critical aspect of the disease that needs to identified, utilizing biomarkers that will potentially better inform the next iteration of the definition of BPD.

Bronchopulmonary dysplasia appropriateness as a surrogate marker for long-term pulmonary outcomes: A Systematic review.

Bronchopulmonary dysplasia (BPD) is used to clinically describe the severity of lung disease and to serve as a common surrogate endpoint for long-term pulmonary morbidity in clinical trials, but its performance as a surrogate end-point warrants evaluation. Our objective was to assess real-world performance of BPD as a surrogate marker for long-term pulmonary outcomes. We performed a systematic review of large, multi-centered, blinded, randomized control trials to evaluate the use of BPD as a surrogate marker for long-term pulmonary outcomes. Long-term pulmonary outcomes occurred within two years and included measures of hospital utilization, respiratory illness, respiratory medication, and mortality. Direction and magnitude of effect were evaluated using number needed to treat analysis. Five studies were included in our review. Studies varied in definition of BPD and in long-term outcomes measured. Only one study found a significant, consistent risk reduction in both BPD and any long-term pulmonary outcome. Two studies found significant reductions in long-term pulmonary outcomes with a non-significant reduction in BPD. BPD is an imperfect surrogate marker for long-term pulmonary outcomes. It did not consistently predict the magnitude or direction of the effect of an intervention on longer-term pulmonary outcomes. Furthermore, there was significant variation in the definitions of BPD and in the long-term pulmonary outcomes used. There is a need for future work to identify more predictive surrogate markers and a need for better standardization of assessments of long-term pulmonary outcomes.

Novel therapeutics for bronchopulmonary dysplasia.

This review provides a concise summary of recent literature pertaining to emerging therapies for bronchopulmonary dysplasia (BPD). To provide context for the presented therapies, a brief overview of recently proposed changes to the definition of BPD and the concept of expanded respiratory outcomes is included. New or redefined respiratory outcomes are required to improve accuracy in evaluating new therapies and correlating results with long-term clinical outcomes of importance. Dexamethasone is no longer the only steroid-based therapy showing promise for impacting BPD. Early trials indicate hydrocortisone, inhaled budesonide, and a budesonide-surfactant combination may be of benefit to preterm infants. Additionally, simple approaches like increasing utilization of mother's own milk may deserve more emphasis. Of significant interest is the traction stem cell therapies are acquiring as one of the more anticipated treatments for BPD. A new preclinical meta-analysis demonstrates the benefits of mesenchymal stromal cell therapy in animal models while the results of early clinical trials remain eagerly awaited. BPD continues to be the most frequently occurring significant morbidity for extremely preterm infants, yet highly effective therapies remain elusive. Promising new treatments are on the horizon, but only continued efforts to complete well-designed clinical trials will determine the true impact of these emerging therapies.

Bronchopulmonary Dysplasia: Can We Agree on a Definition?

The advances in obstetric and neonatal care over the last half century have resulted in changes in pathophysiology and clinical presentation of bronchopulmonary dysplasia (BPD). In contrast to the original description of BPD by Northway et al as a severe lung injury in relatively mature preterm infants, the most common form of BPD currently is characterized by chronic respiratory insufficiency in extremely preterm infants. This evolution in the presentation of BPD, along with changes in respiratory support strategies such as increased use of nasal cannula oxygen, has presented a unique challenge to find a definition that describes the severity of lung damage and predict the long-term respiratory outcomes with some accuracy.The limitations of current definitions of BPD include inconsistent correlation with long-term respiratory outcomes, inability to classify infants dying from severe respiratory failure prior to 36 weeks' postmenstrual age, and potential inappropriate categorization of infants on nasal cannula oxygen or with extrapulmonary causes of respiratory failure. In the long term, the aim for a new definition of BPD is to develop a classification based on the pathophysiology and objective lung function evaluation providing a more accurate assessment for individual patients. Until then, a consensus definition that encompasses current clinical practices, provides reasonable prediction of later respiratory outcomes, and is relatively simple to use should be achieved.

Are we ready to modify our definition of bronchopulmonary dysplasia (BPD) to improve prognostication?

Are we ready to modify our definition of bronchopulmonary dysplasia (BPD) to improve prognostication?

Review shows that using surfactant a number of times or as a vehicle for budesonide may reduce the risk of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) remains the most common respiratory morbidity in immature infants. This review describes the diagnosis of BPD has evolved and summarises the therapeutic approaches that have made it possible to limit the incidence of BPD. We reviewed the literature from the first definition of BPD by Northway in 1967 to the surfactant treatment policies that are currently in use, drawing on more than 50 papers up to 2017. Our review showed that improvements in neonatal survival have been associated with an increased risk of severe BPD, significant levels of long-term morbidity and the increased use of healthcare resources. These issues have encouraged researchers to explore potential new treatments that limit the incidence of BPD. Repeated surfactant instillation and the use of surfactant as a vehicle for budesonide are promising strategies for alleviating the burden of chronic lung disease. Ongoing research on surfactant or stem cell therapy may further improve the respiratory prognosis for prematurely born children. Considerable research has been carried out into the increase in BPD, which has resulted from improvements in neonatal survival. Key areas of research include repeated surfactant administration, using surfactant as a vehicle for budesonide and stem cell therapy.

Chorioamnionitis: Is a major player in the development of bronchopulmonary dysplasia?

Chorioamnionitis is an inflammation in the fetal membranes or placenta. When chorioamnionitis develops, fetal lungs are exposed to inflammatory cytokines and mediators via amniotic fluid. Because inflammation plays a pivotal role in the development of bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurity, fetal lung inflammation induced by chorioamnionitis has been considered to be one of the major pathogenetic factors for BPD. Although there have been a number of studies that demonstrated the relationship between chorioamnionitis and BPD, there are still controversies on this issue. The controversies on the relationship between chorioamnionitis and BPD arise from not-unified definitions of chorioamnionitis and BPD, different study populations, and the proportion of contribution between inflammation and infectious microorganisms. The publication bias also contributes to the controversies. Clinical trials targeting chorioamnionitis or microorganisms that cause chorioamnionitis will answer on the actual relationship between chorioamnionitis and BPD and provide a novel prophylactic strategy against BPD based on that relationship.

Scoping review shows wide variation in the definitions of bronchopulmonary dysplasia in preterm infants and calls for a consensus.

A comprehensive and evidence-based definition for BPD needs to be developed for benchmarking and prognostic use.

BRONCHOPULMONARY DYSPLASIA: TREATMENT AND PREVENTION

Since 1967, when it was first defined and described the nature and definition of bronchopulmonary dysplasia (BPD) has evolved. Based on clinical and radiographic evidence of pulmonary disease in moderately to late premature infants with a history of respiratory distress syndrome, BPD was familiarly defined as a chronic form of lung disease in neonates treated with oxygen and positive pressure ventilation for a primary lung disorder, the nature of BPD has evolved into a “new” form of BPD typically seen in neonates surviving at the threshold of viability and characterized primarily by arrest of alveolar and vascular development. Infants develop BPD in about 1.5% of all newborn births. The incidence of BPD appears to be growing in conjunction with the increased survival of very-low-birth-weight infants who are treated for and recover from respiratory distress syndrome (RDS). This review has been an up-date of literature data, including animal studies, human pilot studies, randomized controlled trials (RCTs), meta-analyses and systematic reviews published on the PubMed data base.

Mechanisms of Lung Injury and Bronchopulmonary Dysplasia.

Although bronchopulmonary dysplasia (BPD) is the most frequent adverse outcome for infants born at < 30 weeks gestational age, there remain major gaps in understanding the pathophysiology, and thus there are few effective targeted therapies to prevent and treat BPD. This review will focus on the substantial problems and knowledge gaps for the clinician and investigator when considering lung injury and BPD. The epidemiology of BPD is clear: BPD is a lung injury syndrome predominantly in extremely low-birth-weight infants with an incidence that increases as gestation/birth weight decrease, with growth restriction, in males and with fetal exposures and with injury from postdelivery respiratory care. However, we do not have a good definition of BPD that identifies the infants that die of respiratory disease before 36 weeks or that predicts long-term outcomes as well. The injury resulting in BPD likely begins as altered lung development before delivery in many infants (small for gestational age, chorioamnionitis, tobacco exposure), can be initiated by resuscitating at birth, and then amplified by postnatal exposures (oxygen, mechanical ventilation, infection). Conceptually the events leading to BPD are the continued interplay of lung development that is altered progressively by injury and repair to result in poorly defined phenotypes of BPD. The injury pathways prominently cause inflammation, and as a proof of principle, corticosteroids can decrease the incidence and severity of BPD, as demonstrated by three recent trials of the early use of steroids. There are likely "adaptation" and "tolerance" responses that modulate the injury and repair to increase or decrease the damage, interactions that are not understood. BPD is a more complex disease.