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Lung Apr 2018Bronchopulmonary dysplasia (BPD) is potentially one of the most devastating conditions in premature infants with longstanding consequences involving multiple organ... (Review)
Review
Bronchopulmonary dysplasia (BPD) is potentially one of the most devastating conditions in premature infants with longstanding consequences involving multiple organ systems including adverse effects on pulmonary function and neurodevelopmental outcome. Here we review recent studies in the field to summarize the progress made in understanding in the pathophysiology, prognosis, prevention, and treatment of BPD in the last decade. The work reviewed includes the progress in understanding its pathobiology, genomic studies, ventilatory strategies, outcomes, and therapeutic interventions. We expect that this review will help guide clinicians to treat premature infants at risk for BPD better and lead researchers to initiate further studies in the field.
Topics: Animals; Bronchopulmonary Dysplasia; Genetic Predisposition to Disease; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Lung; Phenotype; Premature Birth; Prognosis; Respiration, Artificial; Risk Factors; Treatment Outcome
PubMed: 29374791
DOI: 10.1007/s00408-018-0084-z -
Nature Reviews. Disease Primers Nov 2019In the absence of effective interventions to prevent preterm births, improved survival of infants who are born at the biological limits of viability has relied on... (Review)
Review
In the absence of effective interventions to prevent preterm births, improved survival of infants who are born at the biological limits of viability has relied on advances in perinatal care over the past 50 years. Except for extremely preterm infants with suboptimal perinatal care or major antenatal events that cause severe respiratory failure at birth, most extremely preterm infants now survive, but they often develop chronic lung dysfunction termed bronchopulmonary dysplasia (BPD; also known as chronic lung disease). Despite major efforts to minimize injurious but often life-saving postnatal interventions (such as oxygen, mechanical ventilation and corticosteroids), BPD remains the most frequent complication of extreme preterm birth. BPD is now recognized as the result of an aberrant reparative response to both antenatal injury and repetitive postnatal injury to the developing lungs. Consequently, lung development is markedly impaired, which leads to persistent airway and pulmonary vascular disease that can affect adult lung function. Greater insights into the pathobiology of BPD will provide a better understanding of disease mechanisms and lung repair and regeneration, which will enable the discovery of novel therapeutic targets. In parallel, clinical and translational studies that improve the classification of disease phenotypes and enable early identification of at-risk preterm infants should improve trial design and individualized care to enhance outcomes in preterm infants.
Topics: Adrenal Cortex Hormones; Bronchopulmonary Dysplasia; Humans; Infant, Newborn; Infant, Premature; Lung
PubMed: 31727986
DOI: 10.1038/s41572-019-0127-7 -
Birth Defects Research. Part A,... Mar 2014Bronchopulmonary dysplasia (BPD) is among the most common and serious sequelae of preterm birth. BPD affects at least one-quarter of infants born with birth weights less... (Review)
Review
Bronchopulmonary dysplasia (BPD) is among the most common and serious sequelae of preterm birth. BPD affects at least one-quarter of infants born with birth weights less than 1500 g. The incidence of BPD increases with decreasing gestational age and birth weight. Additional important risk factors include intrauterine growth restriction, sepsis, and prolonged exposure to mechanical ventilation and supplemental oxygen. The diagnosis of BPD predicts multiple adverse outcomes including chronic respiratory impairment and neurodevelopmental delay. This review summarizes the diagnostic criteria, incidence, risk factors, and long-term outcomes of BPD.
Topics: Bronchopulmonary Dysplasia; Female; Humans; Incidence; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Male; Risk Factors
PubMed: 24639412
DOI: 10.1002/bdra.23235 -
Journal of Translational Medicine Feb 2018Bronchopulmonary dysplasia (BPD) is the result of a complex process in which several prenatal and/or postnatal factors interfere with lower respiratory tract... (Review)
Review
BACKGROUND
Bronchopulmonary dysplasia (BPD) is the result of a complex process in which several prenatal and/or postnatal factors interfere with lower respiratory tract development, leading to a severe, lifelong disease. In this review, what is presently known regarding BPD pathogenesis, its impact on long-term pulmonary morbidity and mortality and the available preventive and therapeutic strategies are discussed.
MAIN BODY
Bronchopulmonary dysplasia is associated with persistent lung impairment later in life, significantly impacting health services because subjects with BPD have, in most cases, frequent respiratory diseases and reductions in quality of life and life expectancy. Prematurity per se is associated with an increased risk of long-term lung problems. However, in children with BPD, impairment of pulmonary structures and function is even greater, although the characterization of long-term outcomes of BPD is difficult because the adults presently available to study have received outdated treatment. Prenatal and postnatal preventive measures are extremely important to reduce the risk of BPD.
CONCLUSION
Bronchopulmonary dysplasia is a respiratory condition that presently occurs in preterm neonates and can lead to chronic respiratory problems. Although knowledge about BPD pathogenesis has significantly increased in recent years, not all of the mechanisms that lead to lung damage are completely understood, which explains why therapeutic approaches that are theoretically effective have been only partly satisfactory or useless and, in some cases, potentially negative. However, prevention of prematurity, systematic use of nonaggressive ventilator measures, avoiding supraphysiologic oxygen exposure and administration of surfactant, caffeine and vitamin A can significantly reduce the risk of BPD development. Cell therapy is the most fascinating new measure to address the lung damage due to BPD. It is desirable that ongoing studies yield positive results to definitively solve a major clinical, social and economic problem.
Topics: Bronchopulmonary Dysplasia; Humans; Lung; Prevalence; Treatment Outcome
PubMed: 29463286
DOI: 10.1186/s12967-018-1417-7 -
International Journal of Molecular... Aug 2020Bronchopulmonary dysplasia (BPD) is the most common chronic morbidity in preterm infants. In the absence of effective interventions, BPD is currently a major therapeutic... (Review)
Review
Bronchopulmonary dysplasia (BPD) is the most common chronic morbidity in preterm infants. In the absence of effective interventions, BPD is currently a major therapeutic challenge. Several risk factors are known for this multifactorial disease that results in disrupted lung development. Inflammation plays an important role and leads to persistent airway and pulmonary vascular disease. Since corticosteroids are potent anti-inflammatory agents, postnatal corticosteroids have been used widely for BPD prevention and treatment. However, the clinical responses vary to a great degree across individuals, and steroid-related complications remain major concerns. Emerging studies on the molecular mechanism of lung alveolarization during inflammatory stress will elucidate the complicated pathway and help discover novel therapeutic targets. Moreover, with the advances in metabolomics, there are new opportunities to identify biomarkers for early diagnosis and prognosis prediction of BPD. Pharmacometabolomics is another novel field aiming to identify the metabolomic changes before and after a specific drug treatment. Through this "metabolic signature," a more precise treatment may be developed, thereby avoiding unnecessary drug exposure in non-responders. In the future, more clinical, genetic, and translational studies would be required to improve the classification of BPD phenotypes and achieve individualized care to enhance the respiratory outcomes in preterm infants.
Topics: Adrenal Cortex Hormones; Biomarkers; Bronchopulmonary Dysplasia; Early Diagnosis; Humans; Metabolomics; Phenotype; Precision Medicine; Translational Research, Biomedical
PubMed: 32854293
DOI: 10.3390/ijms21176112 -
American Journal of Respiratory and... Sep 2019Current diagnostic criteria for bronchopulmonary dysplasia rely heavily on the level and duration of oxygen therapy, do not reflect contemporary neonatal care, and do...
Current diagnostic criteria for bronchopulmonary dysplasia rely heavily on the level and duration of oxygen therapy, do not reflect contemporary neonatal care, and do not adequately predict childhood morbidity. To determine which of 18 prespecified, revised definitions of bronchopulmonary dysplasia that variably define disease severity according to the level of respiratory support and supplemental oxygen administered at 36 weeks' postmenstrual age best predicts death or serious respiratory morbidity through 18-26 months' corrected age. We assessed infants born at less than 32 weeks of gestation between 2011 and 2015 at 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Of 2,677 infants, 683 (26%) died or developed serious respiratory morbidity. The diagnostic criteria that best predicted this outcome defined bronchopulmonary dysplasia according to treatment with the following support at 36 weeks' postmenstrual age, regardless of prior or current oxygen therapy: no bronchopulmonary dysplasia, no support ( = 773); grade 1, nasal cannula ≤2 L/min ( = 1,038); grade 2, nasal cannula >2 L/min or noninvasive positive airway pressure ( = 617); and grade 3, invasive mechanical ventilation ( = 249). These criteria correctly predicted death or serious respiratory morbidity in 81% of study infants. Rates of this outcome increased stepwise from 10% among infants without bronchopulmonary dysplasia to 77% among those with grade 3 disease. A similar gradient (33-79%) was observed for death or neurodevelopmental impairment. The definition of bronchopulmonary dysplasia that best predicted early childhood morbidity categorized disease severity according to the mode of respiratory support administered at 36 weeks' postmenstrual age, regardless of supplemental oxygen use.
Topics: Bronchopulmonary Dysplasia; Evidence-Based Medicine; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Male; Pediatrics; United States
PubMed: 30995069
DOI: 10.1164/rccm.201812-2348OC -
Cells Apr 2022Premature newborns are at a higher risk for the development of respiratory distress syndrome (RDS), acute lung injury (ALI) associated with lung inflammation, disruption... (Review)
Review
Premature newborns are at a higher risk for the development of respiratory distress syndrome (RDS), acute lung injury (ALI) associated with lung inflammation, disruption of alveolar structure, impaired alveolar growth, lung fibrosis, impaired lung angiogenesis, and development of bronchopulmonary dysplasia (BPD) with severe long-term developmental adverse effects. The current therapy for BPD is limited to supportive care including high-oxygen therapy and pharmacotherapy. Recognizing more feasible treatment options to improve lung health and reduce complications associated with BPD is essential for improving the overall quality of life of premature infants. There is a reduction in the resident stem cells in lungs of premature infants with BPD, which strongly suggests a critical role of stem cells in BPD pathogenesis; this warrants the exploration of the potential therapeutic use of stem-cell therapy. Stem-cell-based therapies have shown promise for the treatment of many pathological conditions including acute lung injury and BPD. Mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (EVs) including exosomes are promising and effective therapeutic modalities for the treatment of BPD. Treatment with MSCs and EVs may help to reduce lung inflammation, improve pulmonary architecture, attenuate pulmonary fibrosis, and increase the survival rate.
Topics: Acute Lung Injury; Animals; Bronchopulmonary Dysplasia; Disease Models, Animal; Humans; Infant; Infant, Newborn; Mesenchymal Stem Cell Transplantation; Pulmonary Fibrosis; Quality of Life
PubMed: 35455954
DOI: 10.3390/cells11081275 -
Pediatric Research Feb 2021Bronchopulmonary dysplasia (BPD) is a major complication in prematurely born infants. Pulmonary hypertension (PH) associated with BPD (BPD-PH) is characterized by... (Review)
Review
Bronchopulmonary dysplasia (BPD) is a major complication in prematurely born infants. Pulmonary hypertension (PH) associated with BPD (BPD-PH) is characterized by alveolar diffusion impairment, abnormal vascular remodeling, and rarefication of pulmonary vessels (vascular growth arrest), which lead to increased pulmonary vascular resistance and right heart failure. About 25% of infants with moderate to severe BPD develop BPD-PH that is associated with high morbidity and mortality. The recent evolution of broader PH-targeted pharmacotherapy in adults has opened up new treatment options for infants with BPD-PH. Sildenafil became the mainstay of contemporary BPD-PH therapy. Additional medications, such as endothelin receptor antagonists and prostacyclin analogs/mimetics, are increasingly being investigated in infants with PH. However, pediatric data from prospective or randomized controlled trials are still sparse. We discuss comprehensive diagnostic and therapeutic strategies for BPD-PH and briefly review the relevant differential diagnoses of parenchymal and interstitial developmental lung diseases. In addition, we provide a practical framework for the management of children with BPD-PH, incorporating the modified definition and classification of pediatric PH from the 2018 World Symposium on Pulmonary Hypertension, and the 2019 EPPVDN consensus recommendations on established and newly developed therapeutic strategies. Finally, current gaps of knowledge and future research directions are discussed. IMPACT: PH in BPD substantially increases mortality. Treatment of BPD-PH should be conducted by an interdisciplinary team and follow our new treatment algorithm while still kept tailored to the individual patient. We discuss recent developments in BPD-PH, make recommendations on diagnosis, monitoring and treatment of PH in BPD, and address current gaps of knowledge and potential research directions. We provide a practical framework, including a new treatment algorithm, for the management of children with BPD-PH, incorporating the modified definition and classification of pediatric PH (2018 WSPH) and the 2019 EPPVDN consensus recommendations on established and newly developed therapeutic strategies for BPD-PH.
Topics: Biomarkers; Bronchopulmonary Dysplasia; Cardiac Catheterization; Cardiac Surgical Procedures; Echocardiography; Endothelin Receptor Antagonists; Heart Failure; Humans; Hypertension, Pulmonary; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Magnetic Resonance Imaging; Nitric Oxide; Oxygen Inhalation Therapy; Prostaglandins I; Sildenafil Citrate; Tomography, X-Ray Computed; Tricuspid Valve Insufficiency; Vascular Resistance; Vasodilator Agents
PubMed: 32521539
DOI: 10.1038/s41390-020-0993-4 -
Neonatology 2021Bronchopulmonary dysplasia (BPD) remains a major morbidity for infants born preterm. Postnatal corticosteroids might reduce the risk of developing BPD, or reduce its... (Review)
Review
Bronchopulmonary dysplasia (BPD) remains a major morbidity for infants born preterm. Postnatal corticosteroids might reduce the risk of developing BPD, or reduce its severity when it occurs, because of their powerful anti-inflammatory effects. However, corticosteroids have adverse effects, including on the developing brain. There have been numerous randomized clinical trials of corticosteroids given via various routes, of varying types, and started at different postnatal ages. There is some evidence that inhaled corticosteroids started earlier in the postnatal period may reduce BPD, but increase mortality. Inhaled corticosteroids started after the first week of age have little effect, but data are sparse. Systemic corticosteroids started in the first week after birth reduce BPD but increase cerebral palsy. Systemic corticosteroids started after the first week of age reduce both BPD and mortality, without evidence of long-term neurological harm. However, no studies have been powered to look for important adverse long-term neurological effects. Of the 2 systemic corticosteroids assessed, most effects relate to dexamethasone and not to hydrocortisone, but hydrocortisone in the first week after birth may reduce mortality, and is worthy of further study. There are limited data directly comparing inhaled versus systemic corticosteroids, with no evidence of superiority of one mode over the other. Corticosteroids instilled into the trachea using surfactant as a vehicle to distribute the drug through the lungs offer promise in preventing BPD. For current clinical practice, systemic corticosteroids should be avoided in the first week of life, and thereafter used only in infants at high risk of BPD.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Bronchopulmonary Dysplasia; Dexamethasone; Glucocorticoids; Humans; Infant; Infant, Newborn; Infant, Premature; Pharmaceutical Preparations
PubMed: 33975319
DOI: 10.1159/000515950 -
Journal of Perinatology : Official... Aug 2021Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly affecting extremely preterm infants. Although mechanical ventilation and oxygen requirements in... (Review)
Review
Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly affecting extremely preterm infants. Although mechanical ventilation and oxygen requirements in premature infants are identified as inciting mechanisms for inflammation and the development of BPD over time, data now support an array of perinatal events that may stimulate the inflammatory cascade prior to delivery. Corticosteroids, such as dexamethasone and hydrocortisone, have proven beneficial for the prevention and management of BPD postnatally due to their anti-inflammatory characteristics. This review aims to examine the pharmacologic properties of several corticosteroids, appraise the existing evidence for postnatal corticosteroid use in preterm infants, and assess steroid management strategies to ameliorate BPD. Finally, we aim to provide guidance based on clinical experience for managing adrenal suppression resulting from prolonged steroid exposure since this is an area less well-studied.
Topics: Anti-Inflammatory Agents; Bronchopulmonary Dysplasia; Humans; Hydrocortisone; Infant; Infant, Newborn; Infant, Premature; Steroids
PubMed: 34012057
DOI: 10.1038/s41372-021-01083-w