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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 -
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 -
Paediatric Respiratory Reviews Sep 2022Survival of preterm infants has increased steadily over recent decades, primarily due to improved outcomes for those born before 28 weeks of gestation. However, this... (Review)
Review
Survival of preterm infants has increased steadily over recent decades, primarily due to improved outcomes for those born before 28 weeks of gestation. However, this has not been matched by similar improvements in longer-term morbidity. One of the key long-term sequelae of preterm birth remains bronchopulmonary dysplasia (also called chronic lung disease of prematurity), contributed primarily by the effect of early pulmonary inflammation superimposed on immature lungs. Non-invasive modes of respiratory support have been rapidly introduced providing modest success in reducing the incidence of bronchopulmonary dysplasia when compared with invasive mechanical ventilation, and improved clinical practice has been reported from population-based studies. We present a comprehensive review of the key modes of non-invasive respiratory support currently used in preterm infants, including their mechanisms of action and evidence of benefit from clinical trials.
Topics: Infant; Female; Infant, Newborn; Humans; Infant, Premature; Intermittent Positive-Pressure Ventilation; Bronchopulmonary Dysplasia; Premature Birth; Infant, Premature, Diseases; Respiratory Distress Syndrome, Newborn; Continuous Positive Airway Pressure
PubMed: 35562288
DOI: 10.1016/j.prrv.2022.04.002 -
Pediatric Pulmonology Nov 2021Bronchopulmonary dysplasia (BPD) still carries a heavy burden of morbidity and mortality in survivors of extreme prematurity. The disease is characterized by... (Review)
Review
Bronchopulmonary dysplasia (BPD) still carries a heavy burden of morbidity and mortality in survivors of extreme prematurity. The disease is characterized by simplification of the alveolar structure, involving a smaller number of enlarged alveoli due to decreased septation and a dysmorphic pulmonary microvessel growth. These changes lead to persistent abnormalities mainly affecting the smaller airways, lung parenchyma, and pulmonary vasculature, which can be assessed with lung function tests and imaging techniques. Several longitudinal lung function studies have demonstrated that most preterm-born subjects with BPD embark on a low lung function trajectory, never achieving their full airway growth potential. They are consequently at higher risk of developing a chronic obstructive pulmonary disease-like phenotype later in life. Studies based on computer tomography and magnetic resonance imaging, have also shown that in these patients there is a persistence of lung abnormalities like emphysematous areas, bronchial wall thickening, interstitial opacities, and mosaic lung attenuation also in adult age. This review aims to outline the current knowledge of pulmonary and vascular growth in survivors of BPD and the evidence of their lung function and imaging up to adulthood.
Topics: Adult; Bronchopulmonary Dysplasia; Humans; Infant, Newborn; Lung; Pulmonary Alveoli; Pulmonary Disease, Chronic Obstructive; Respiratory Physiological Phenomena
PubMed: 33729686
DOI: 10.1002/ppul.25380 -
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 -
Respiratory Care Oct 2021Bronchopulmonary dysplasia (BPD) is a chronic lung disease most commonly seen in preterm infants of low birthweight who required postnatal respiratory support. Although... (Review)
Review
Bronchopulmonary dysplasia (BPD) is a chronic lung disease most commonly seen in preterm infants of low birthweight who required postnatal respiratory support. Although overall incidence rates have not changed, recent advancements in medical care have resulted in lower mortality rates, and those affected are beginning to live longer. As a result, the long-term repercussions of BPD are becoming more apparent. Whereas BPD has been thought of as a disease of just the lungs, resulting in abnormalities such as increased susceptibility to pulmonary infections, impaired exercise tolerance, and pulmonary hypertension, the enduring complications of BPD have been found to extend much further. This includes an increased risk for cerebral palsy and developmental delays, lower intelligence quotient (IQ) scores, impaired executive functioning, behavioral challenges, delays in expressive and receptive language development, and an increased risk of growth failure. In addition, the deficits of BPD have been found to influence much more than just physical health; BPD survivors have been noted to have higher rates of health care use, starting with the initial hospitalization and continuing with therapy and specialist follow-up, as well as impairments in quality of life, both physical and psychological, that continue into adulthood. The long-term consequences of BPD may best be addressed through future research, including better understanding of the pathophysiologic mechanisms leading to BPD, further comparisons between newborns with BPD and those without, and long-term assessment and management of BPD patients as adults.
Topics: Adult; Bronchopulmonary Dysplasia; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Lung; Quality of Life
PubMed: 34552015
DOI: 10.4187/respcare.08401 -
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 -
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 -
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