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Therapeutic Advances in Respiratory... 2019Emerging evidence suggests that adverse early life events can affect long-term health trajectories throughout life. Preterm birth, in particular, is a significant early... (Review)
Review
Emerging evidence suggests that adverse early life events can affect long-term health trajectories throughout life. Preterm birth, in particular, is a significant early life event that affects approximately 10% of live births. Worldwide, prematurity is the number one cause of death in children less than 5 years of age and has been shown to disrupt normal lung development with lasting effects into adult life. Along with impaired lung development, interventions used to support gas exchange and other sequelae of prematurity can lead to the development of bronchopulmonary dysplasia (BPD). BPD is a chronic respiratory disease of infancy characterized by alveolar simplification, small airways disease, and pulmonary vascular changes. Although many survivors of BPD improve with age, survivors of BPD often have chronic lung disease characterized by airflow obstruction and intermittent pulmonary exacerbations. Long-term lung function trajectories as measured by FEV1 can be lower in children and adults with a history BPD. In this review, we discuss the epidemiology and manifestations of BPD and its long-term consequences throughout childhood and into adulthood. Available evidence suggests that disrupted lung development, genetic susceptibility and subsequent environment and infectious events that occur in prenatal and postnatal life likely increase the predisposition of children with BPD to develop early onset chronic obstructive pulmonary disease (COPD).
Topics: Adult; Bronchopulmonary Dysplasia; Child; Forced Expiratory Volume; Humans; Infant, Newborn; Infant, Premature; Lung; Pulmonary Disease, Chronic Obstructive
PubMed: 31818194
DOI: 10.1177/1753466619892492 -
Seminars in Perinatology Nov 2018Over 50 years after its first description, Bronchopulmonary Dysplasia (BPD) remains a devastating pulmonary complication in preterm infants with respiratory failure and... (Review)
Review
Over 50 years after its first description, Bronchopulmonary Dysplasia (BPD) remains a devastating pulmonary complication in preterm infants with respiratory failure and develops in 30-50% of infants less than 1000-gram birth weight. It is thought to involve ventilator- and oxygen-induced damage to an immature lung that results in an inflammatory response and ends in aberrant lung development with dysregulated angiogenesis and alveolarization. Significant morbidity and mortality are associated with this most common chronic lung disease of childhood. Thus, any therapies that decrease the incidence or severity of this condition would have significant impact on morbidity, mortality, human costs, and healthcare expenditure. It is clear that an inflammatory response and the elaboration of growth factors and cytokines are associated with the development of BPD. Numerous approaches to control the inflammatory process leading to the development of BPD have been attempted. This review will examine the anti-inflammatory approaches that are established or hold promise for the prevention or treatment of BPD.
Topics: Animals; Anti-Inflammatory Agents; Bronchopulmonary Dysplasia; Disease Models, Animal; Humans; Infant, Extremely Premature; Infant, Newborn; Infant, Very Low Birth Weight; Inflammation; Inflammation Mediators; Mice; Signal Transduction
PubMed: 30446300
DOI: 10.1053/j.semperi.2018.09.009 -
Chest May 2023Patients with bronchopulmonary dysplasia (BPD) have poor respiratory trajectories and are at increased risk of lung function decline with age. Lung transplant (LTx) is a...
BACKGROUND
Patients with bronchopulmonary dysplasia (BPD) have poor respiratory trajectories and are at increased risk of lung function decline with age. Lung transplant (LTx) is a possible treatment option for this growing patient population, but little has been published on LTx in this patient group.
RESEARCH QUESTION
What are the characteristics of patients with BPD who are listed for LTx? How do waitlist and post-LTx outcomes for BPD compare with LTx for other diagnoses?
STUDY DESIGN AND METHODS
The United Network for Organ Sharing (UNOS) registry was queried for patients of all ages listed for or who underwent LTx (2000-2020). Descriptive analysis, waitlist outcomes, and post-LTx survival at 1, 5, and 10 years were assessed comparing patients with BPD vs LTx patients with other diagnoses. Post-LTx survival for patients with BPD born in the pre-surfactant era (pre-SE, before 1990) and those born in the post-surfactant era (post-SE) was compared. Propensity score matching was performed to control for the risk factors and match patients with BPD with other LTx patients on a 1:1 ratio.
RESULTS
BPD was reported in 65 patients, of whom 32 (49.2%) underwent LTx. Patients with BPD at listing were younger than those with other diagnoses (median age, 21 [interquartile range, 5-31] years vs 57 [45-63] years; P < .001), and more were likely to receive mechanical ventilation at listing (23% vs 3.7%; P < .001). Patients with BPD had an FEV of 17% compared with 34% predicted in other patients (P = .002). Patients with BPD had an overall similar post-LTx survival compared with patients with other diagnoses (P = .106), even following propensity score matching (P = .41).
INTERPRETATION
LTx for BPD has increased over the last 20 years. Patients with BPD have similar post-LTx outcomes compared with those of other patient populations in the modern era. Thus, LTx could be considered for patients with BPD experiencing progressive respiratory deterioration.
Topics: Infant, Newborn; Humans; Young Adult; Adult; Bronchopulmonary Dysplasia; Lung Transplantation; Pulmonary Surfactants; Respiratory Function Tests; Surface-Active Agents
PubMed: 36610665
DOI: 10.1016/j.chest.2022.12.032 -
American Journal of Respiratory Cell... Feb 2022Bronchopulmonary dysplasia (BPD) is a debilitating disease in premature infants resulting from lung injury that disrupts alveolar and pulmonary vascular development.... (Review)
Review
Bronchopulmonary dysplasia (BPD) is a debilitating disease in premature infants resulting from lung injury that disrupts alveolar and pulmonary vascular development. Despite the use of lung-protective ventilation and targeted oxygen therapy, BPD rates have not significantly changed over the last decade. Recent evidence suggests that sepsis and conditions initiating the systemic inflammatory response syndrome in preterm infants are key risk factors for BPD. However, the mechanisms by which sepsis-associated systemic inflammation and microbial dissemination program aberrant lung development are not fully understood. Progress has been made within the last 5 years with the inception of animal models allowing mechanistic investigations into neonatal acute lung injury and alveolar remodeling attributable to endotoxemia and necrotizing enterocolitis. These recent studies begin to unravel the pathophysiology of early endothelial immune activation via pattern recognition receptors such as Toll-like receptor 4 and disruption of critical lung developmental processes such as angiogenesis, extracellular matrix deposition, and ultimately alveologenesis. Here we review scientific evidence from preclinical models of neonatal sepsis-induced lung injury to new data emerging from clinical literature.
Topics: Bronchopulmonary Dysplasia; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Infant, Premature, Diseases; Sepsis; Systemic Inflammatory Response Syndrome
PubMed: 34644520
DOI: 10.1165/rcmb.2021-0353PS -
Pediatric Pulmonology Sep 2022Infants and children diagnosed with bronchopulmonary dysplasia (BPD) have a higher likelihood of recurrent hospitalizations and asthma-like symptoms....
INTRODUCTION
Infants and children diagnosed with bronchopulmonary dysplasia (BPD) have a higher likelihood of recurrent hospitalizations and asthma-like symptoms. Socio-environmental factors that influence the frequency and severity of pulmonary symptoms in these children during the preschool age are poorly understood. In this study, we used the Area Deprivation Index (ADI) to evaluate the relationship between the socio-environmental exposures in children with BPD and respiratory outcomes during the first few years of life.
METHODS
A registry of subjects recruited from outpatient BPD clinics at Johns Hopkins University (n = 909) and the Children's Hospital of Philadelphia (n = 125) between January 2008 and October 2021 was used. Subjects were separated into tertiles by ADI scores aggregated to ZIP codes. Caregiver questionnaires were used to assess the frequency of respiratory morbidities and acute care usage for respiratory symptoms.
RESULTS
The mean gestational age of subjects was 26.8 ± 2.6 weeks with a mean birthweight of 909 ± 404 g. The highest tertile (most deprived) of ADI was significantly associated with emergency department visits (aOR 1.72; p = 0.009), hospital readmissions (aOR 1.66; p = 0.030), and activity limitations (aOR 1.55; p = 0.048) compared to the lowest tertile. No association was seen with steroid, antibiotic or rescue medication use, trouble breathing, or nighttime symptoms.
CONCLUSION
In this study, children with BPD who lived in areas of higher deprivation were more likely to be rehospitalized and have ED visits for respiratory reasons. Identifying socio-environmental factors that contribute to adverse pulmonary outcomes in children with BPD may provide opportunities for earlier interventions to improve long-term pulmonary outcomes.
Topics: Bronchopulmonary Dysplasia; Child; Child, Preschool; Disease Progression; Gestational Age; Hospitalization; Humans; Infant; Infant, Newborn; Morbidity; Surveys and Questionnaires
PubMed: 35559602
DOI: 10.1002/ppul.25969 -
Pediatric Pulmonology Nov 2021While there is a very large focus on the abnormalities of parenchymal lung development and extensive efforts to minimize alveolar damage with "gentle ventilation" and...
While there is a very large focus on the abnormalities of parenchymal lung development and extensive efforts to minimize alveolar damage with "gentle ventilation" and noninvasive respiratory support for neonates with bronchopulmonary dysplasia (BPD), there is relatively little consideration for the implications of central airway disease in this patient population. There are significant changes in the structure and conformation of the central airway during the last half of gestation, and premature birth disrupts this natural developmental process. The arrest of maturation results in a smaller airway that is more compliant, easier to deform, and more susceptible to damage. Consequently, neonates with BPD are prone to developing central airway pathology, particularly for patients who require intubation and positive pressure ventilation. Central airway disease can be divided into dynamic and fixed airway obstruction and results in increased respiratory morbidity in neonates with chronic lung disease of prematurity.
Topics: Airway Obstruction; Bronchopulmonary Dysplasia; Humans; Infant, Newborn; Intermittent Positive-Pressure Ventilation; Positive-Pressure Respiration; Premature Birth
PubMed: 33835725
DOI: 10.1002/ppul.25417 -
Current Opinion in Pediatrics Apr 2011Bronchopulmonary dysplasia (BPD) remains the most common severe complication of preterm birth. A number of recent animal models and clinical studies provide new... (Review)
Review
PURPOSE OF REVIEW
Bronchopulmonary dysplasia (BPD) remains the most common severe complication of preterm birth. A number of recent animal models and clinical studies provide new information about pathophysiology and treatment.
RECENT FINDINGS
The epidemiology of BPD continues to demonstrate that birth weight and gestational age are most predictive of BPD. Correlations of BPD with chorioamnionitis are clouded by the complexity of the fetal exposures to inflammation. Excessive oxygen use in preterm infants can increase the risk of BPD but low saturation targets may increase death. Numerous recent trials demonstrate that many preterm infants can be initially stabilized after delivery with continuous positive airway response (CPAP) and then be selectively treated with surfactant for respiratory distress syndrome. The growth of the lungs of the infant with BPD through childhood remains poorly characterized.
SUMMARY
Recent experiences in neonatology suggest that combining less invasive care strategies that avoid excessive oxygen and ventilation, decrease postnatal infections, and optimize nutrition may decrease the incidence and severity of BPD.
Topics: Bronchopulmonary Dysplasia; Chorioamnionitis; Female; Humans; Infant, Newborn; Infant, Premature; Multipotent Stem Cells; Nitric Oxide; Oxygen Inhalation Therapy; Pregnancy; Respiration, Artificial
PubMed: 21169836
DOI: 10.1097/MOP.0b013e3283423e6b -
Nutrients Aug 2022Bronchopulmonary dysplasia (BPD) represents a severe sequela in neonates born very prematurely. The provision of adequate nutritional support in this high-risk... (Review)
Review
Bronchopulmonary dysplasia (BPD) represents a severe sequela in neonates born very prematurely. The provision of adequate nutritional support in this high-risk population is challenging. The development of the lungs and physical growth are closely linked together in infants with BPD. Growth deficiency has been associated with pulmonary dysfunction, whereas improvement in respiratory status results in growth acceleration. Currently, there is not enough data regarding optimal nutritional strategies in this population. Nutrition in these infants should provide sufficient calories and nutrients to establish growth, avoid growth retardation and assist alveolarization of the lungs. Meticulous follow-up is mandatory during and after discharge from the Neonatal Intensive care Unit (NICU) to minimize growth retardation and improve lung function. Despite the significant literature supporting the contribution of growth and nutrition in the avoidance of BPD, there is limited research regarding interventions and management of infants with established BPD. Our aim was to review clinical strategies applied in everyday clinical practice and identify debates on the nutritional approach of newborns with BPD. Well-organized interventions and clinical trials regarding the somatic development and nutrition of infants with BPD are warranted.
Topics: Bronchopulmonary Dysplasia; Growth Disorders; Humans; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Nutritional Status; Patient Discharge
PubMed: 36014815
DOI: 10.3390/nu14163311 -
Respiratory Research May 2021Surfactant protein D (SP-D) is a collectin protein synthesized by alveolar type II cells in the lungs. SP-D participates in the innate immune defense of the lungs by... (Review)
Review
Surfactant protein D (SP-D) is a collectin protein synthesized by alveolar type II cells in the lungs. SP-D participates in the innate immune defense of the lungs by helping to clear infectious pathogens and modulating the immune response. SP-D has shown an anti-inflammatory role by down-regulating the release of pro-inflammatory mediators in different signaling pathways such as the TLR4, decreasing the recruitment of inflammatory cells to the lung, and modulating the oxidative metabolism in the lungs. Recombinant human SP-D (rhSP-D) has been successfully produced mimicking the structure and functions of native SP-D. Several in vitro and in vivo experiments using different animal models have shown that treatment with rhSP-D reduces the lung inflammation originated by different insults, and that rhSP-D could be a potential treatment for bronchopulmonary dysplasia (BPD), a rare disease for which there is no effective therapy up to date. BPD is a complex disease in preterm infants whose incidence increases with decreasing gestational age at birth. Lung inflammation, which is caused by different prenatal and postnatal factors like infections, lung hyperoxia and mechanical ventilation, among others, is the key player in BPD. Exacerbated inflammation causes lung tissue injury that results in a deficient gas exchange in the lungs of preterm infants and frequently leads to long-term chronic lung dysfunction during childhood and adulthood. In addition, low SP-D levels and activity in the first days of life in preterm infants have been correlated with a worse pulmonary outcome in BPD. Thus, SP-D mediated functions in the innate immune response could be critical aspects of the pathogenesis in BPD and SP-D could inhibit lung tissue injury in this preterm population. Therefore, administration of rhSP-D has been proposed as promising therapy that could prevent BPD.
Topics: Alveolar Epithelial Cells; Animals; Bronchopulmonary Dysplasia; Humans; Inflammation Mediators; Lung; Pulmonary Surfactant-Associated Protein D; Recombinant Proteins; Respiratory System Agents; Signal Transduction
PubMed: 33964929
DOI: 10.1186/s12931-021-01738-4 -
Seminars in Perinatology Nov 2018Bronchopulmonary Dysplasia (BPD) is a disorder with a multifactorial etiology and highly variable clinical phenotype. Several traditional biomarkers have been... (Review)
Review
Bronchopulmonary Dysplasia (BPD) is a disorder with a multifactorial etiology and highly variable clinical phenotype. Several traditional biomarkers have been identified, but due to the complex disease phenotype, these biomarkers have low predictive accuracy for BPD. In recent years, newer technologies have facilitated the in-depth and unbiased analysis of 'big data' in delineating the diagnosis, pathogenesis, and mechanisms of diseases. Novel systems-biology based 'omic' approaches, including but not limited to genomics, microbiomics, proteomics, and metabolomics may help define the multiple cellular and humoral interactions that regulate normal as well as abnormal lung development and response to injury that are the hallmarks of BPD.
Topics: Biomarkers; Bronchopulmonary Dysplasia; Female; Genomics; Humans; Infant, Newborn; Intercellular Signaling Peptides and Proteins; Lung; Metabolomics; Neonatology; Predictive Value of Tests; Pregnancy; Proteomics; Respiratory Mucosa
PubMed: 30487069
DOI: 10.1053/j.semperi.2018.09.004