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Biomarkers for Bronchopulmonary Dysplasia in the Preterm Infant.

Rivera L, Siddaiah R, Oji-Mmuo C, Silveyra GR, Silveyra P - Front Pediatr (2016)

Bottom Line: Over the past few decades, the incidence of BPD has significantly raised as a result of improved survival of VLBW infants requiring mechanical ventilation.Due to the current lack of effective treatment available for BPD and PH, research is currently focused on primary prevention strategies, and identification of biomarkers for early diagnosis, that could also represent potential therapeutic targets.We also present a brief summary of the information available on current strategies and guidelines to prevent and diagnose BPD and PH, as well as their pathophysiology, risk factors, and experimental therapies currently available.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, The Pennsylvania State University College of Medicine , Hershey, PA , USA.

ABSTRACT
Bronchopulmonary dysplasia (BPD) is a chronic inflammatory lung disease of very-low-birth-weight (VLBW) preterm infants, associated with arrested lung development and a need for supplemental oxygen. Over the past few decades, the incidence of BPD has significantly raised as a result of improved survival of VLBW infants requiring mechanical ventilation. While early disease detection is critical to prevent chronic lung remodeling and complications later in life, BPD is often difficult to diagnose and prevent due to the lack of good biomarkers for identification of infants at risk, and overlapping symptoms with other diseases, such as pulmonary hypertension (PH). Due to the current lack of effective treatment available for BPD and PH, research is currently focused on primary prevention strategies, and identification of biomarkers for early diagnosis, that could also represent potential therapeutic targets. In addition, novel histopathological, biochemical, and molecular factors have been identified in the lung tissue and in biological fluids of BPD and PH patients that could associate with the disease phenotype. In this review, we provide an overview of biomarkers for pediatric BPD and PH that have been identified in clinical studies using various biological fluids. We also present a brief summary of the information available on current strategies and guidelines to prevent and diagnose BPD and PH, as well as their pathophysiology, risk factors, and experimental therapies currently available.

No MeSH data available.


Related in: MedlinePlus

Embryonic and fetal lung development and bronchopulmonary dysplasia (BPD): five stages are identified in human fetal lung development that can be affected by both antenatal and postnatal factors, resulting in increased susceptibility to develop BPD. Preterm infants born at the canalicular or saccular stages have incomplete lung development and high risk for BPD. However, not all preterm infants develop BPD, indicating that other factors can contribute to the disease development, and the disease could be preventable. A summary of risk factors and potential prevention and management strategies is presented in the diagram.
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Figure 1: Embryonic and fetal lung development and bronchopulmonary dysplasia (BPD): five stages are identified in human fetal lung development that can be affected by both antenatal and postnatal factors, resulting in increased susceptibility to develop BPD. Preterm infants born at the canalicular or saccular stages have incomplete lung development and high risk for BPD. However, not all preterm infants develop BPD, indicating that other factors can contribute to the disease development, and the disease could be preventable. A summary of risk factors and potential prevention and management strategies is presented in the diagram.

Mentions: To have a clear understanding of the pathophysiology of BPD, it is necessary to understand the normal lung development and the molecular pathways associated with the disease. Five stages have been identified in lung development: embryonic, pseudoglandular, canalicular, saccular, and alveolar (Figure 1). The first stage, named embryonic stage (4–7 weeks gestation), begins with the formation of a lung bud that emerges from the ventral foregut and posterior division to form two buds that lie on either side of the future esophagus. Successive branching within the expanding mesenchyme continues to form lobar and segmental airways in each lung. At the end of the embryonic stage, a network of nerves and ganglia are developed along with the smooth muscle to form the airways. These nerves and ganglia increased in size at 16 to 18 weeks gestation (8). Both the smooth muscle and mesenchymal cells secrete neurotrophic factors involved in both nerve growth and extension into the airways (9, 10). Next, during the pseudoglandular stage (7–17 weeks gestation), further division of the airway buds occurs, and there is a continuous differentiation of epithelial cells to form adult structures of cartilage, vascular networks, submucosal glands, and bronchial smooth muscle. At the following stage, the canalicular stage (17–27 weeks gestation), branching continues and respiratory airways form. In order to form the blood gas barrier, the epithelium starts thinning and becomes surrounded by a network of capillaries. Differentiation of the epithelial cells into type I and II pneumocytes occurs, and type II cells begin to produce surfactant. In this stage, sex differences begin to appear, with the female lung developing faster than the male lung, resulting in increased risk for BPD in prematurely born males than females (11, 12). In the saccular stage (24–36 weeks gestation) surfactant maturation continues, and the connective tissue forms thin septa within the airspaces containing a double pulmonary capillary layer (13, 14). Finally, in the alveolar stage, new tissue ridges lift off the existing primary septa and extend into the airspaces, where they subdivide the sacs into smaller alveoli (secondary septation) (15). This final stage begins at 36 weeks gestation and remains throughout infancy and adolescence.


Biomarkers for Bronchopulmonary Dysplasia in the Preterm Infant.

Rivera L, Siddaiah R, Oji-Mmuo C, Silveyra GR, Silveyra P - Front Pediatr (2016)

Embryonic and fetal lung development and bronchopulmonary dysplasia (BPD): five stages are identified in human fetal lung development that can be affected by both antenatal and postnatal factors, resulting in increased susceptibility to develop BPD. Preterm infants born at the canalicular or saccular stages have incomplete lung development and high risk for BPD. However, not all preterm infants develop BPD, indicating that other factors can contribute to the disease development, and the disease could be preventable. A summary of risk factors and potential prevention and management strategies is presented in the diagram.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4814627&req=5

Figure 1: Embryonic and fetal lung development and bronchopulmonary dysplasia (BPD): five stages are identified in human fetal lung development that can be affected by both antenatal and postnatal factors, resulting in increased susceptibility to develop BPD. Preterm infants born at the canalicular or saccular stages have incomplete lung development and high risk for BPD. However, not all preterm infants develop BPD, indicating that other factors can contribute to the disease development, and the disease could be preventable. A summary of risk factors and potential prevention and management strategies is presented in the diagram.
Mentions: To have a clear understanding of the pathophysiology of BPD, it is necessary to understand the normal lung development and the molecular pathways associated with the disease. Five stages have been identified in lung development: embryonic, pseudoglandular, canalicular, saccular, and alveolar (Figure 1). The first stage, named embryonic stage (4–7 weeks gestation), begins with the formation of a lung bud that emerges from the ventral foregut and posterior division to form two buds that lie on either side of the future esophagus. Successive branching within the expanding mesenchyme continues to form lobar and segmental airways in each lung. At the end of the embryonic stage, a network of nerves and ganglia are developed along with the smooth muscle to form the airways. These nerves and ganglia increased in size at 16 to 18 weeks gestation (8). Both the smooth muscle and mesenchymal cells secrete neurotrophic factors involved in both nerve growth and extension into the airways (9, 10). Next, during the pseudoglandular stage (7–17 weeks gestation), further division of the airway buds occurs, and there is a continuous differentiation of epithelial cells to form adult structures of cartilage, vascular networks, submucosal glands, and bronchial smooth muscle. At the following stage, the canalicular stage (17–27 weeks gestation), branching continues and respiratory airways form. In order to form the blood gas barrier, the epithelium starts thinning and becomes surrounded by a network of capillaries. Differentiation of the epithelial cells into type I and II pneumocytes occurs, and type II cells begin to produce surfactant. In this stage, sex differences begin to appear, with the female lung developing faster than the male lung, resulting in increased risk for BPD in prematurely born males than females (11, 12). In the saccular stage (24–36 weeks gestation) surfactant maturation continues, and the connective tissue forms thin septa within the airspaces containing a double pulmonary capillary layer (13, 14). Finally, in the alveolar stage, new tissue ridges lift off the existing primary septa and extend into the airspaces, where they subdivide the sacs into smaller alveoli (secondary septation) (15). This final stage begins at 36 weeks gestation and remains throughout infancy and adolescence.

Bottom Line: Over the past few decades, the incidence of BPD has significantly raised as a result of improved survival of VLBW infants requiring mechanical ventilation.Due to the current lack of effective treatment available for BPD and PH, research is currently focused on primary prevention strategies, and identification of biomarkers for early diagnosis, that could also represent potential therapeutic targets.We also present a brief summary of the information available on current strategies and guidelines to prevent and diagnose BPD and PH, as well as their pathophysiology, risk factors, and experimental therapies currently available.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, The Pennsylvania State University College of Medicine , Hershey, PA , USA.

ABSTRACT
Bronchopulmonary dysplasia (BPD) is a chronic inflammatory lung disease of very-low-birth-weight (VLBW) preterm infants, associated with arrested lung development and a need for supplemental oxygen. Over the past few decades, the incidence of BPD has significantly raised as a result of improved survival of VLBW infants requiring mechanical ventilation. While early disease detection is critical to prevent chronic lung remodeling and complications later in life, BPD is often difficult to diagnose and prevent due to the lack of good biomarkers for identification of infants at risk, and overlapping symptoms with other diseases, such as pulmonary hypertension (PH). Due to the current lack of effective treatment available for BPD and PH, research is currently focused on primary prevention strategies, and identification of biomarkers for early diagnosis, that could also represent potential therapeutic targets. In addition, novel histopathological, biochemical, and molecular factors have been identified in the lung tissue and in biological fluids of BPD and PH patients that could associate with the disease phenotype. In this review, we provide an overview of biomarkers for pediatric BPD and PH that have been identified in clinical studies using various biological fluids. We also present a brief summary of the information available on current strategies and guidelines to prevent and diagnose BPD and PH, as well as their pathophysiology, risk factors, and experimental therapies currently available.

No MeSH data available.


Related in: MedlinePlus