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Bronchopulmonary dysplasia early changes leading to long-term consequences.

Hilgendorff A, O'Reilly MA - Front Med (Lausanne) (2015)

Bottom Line: Remodeling of the extracellular matrix, apoptosis as well as altered growth factor signaling characterize the disease.The immediate consequences of these early insults have been studied in different animal models supported by results from in vitro approaches leading to the successful application of some findings to the clinical setting in the past.Interesting results point towards a tremendous impact of these early injuries on the pulmonary repair capacity as well as aging related processes in the adult lung.

View Article: PubMed Central - PubMed

Affiliation: Comprehensive Pneumology Center, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL) , Munich , Germany ; Neonatology, Perinatal Center Grosshadern, Dr. von Hauner Children's Hospital, Ludwig-Maximilians University , Munich , Germany.

ABSTRACT
Neonatal chronic lung disease, i.e., bronchopulmonary dysplasia, is characterized by impaired pulmonary development resulting from the impact of different risk factors including infections, hyperoxia, and mechanical ventilation on the immature lung. Remodeling of the extracellular matrix, apoptosis as well as altered growth factor signaling characterize the disease. The immediate consequences of these early insults have been studied in different animal models supported by results from in vitro approaches leading to the successful application of some findings to the clinical setting in the past. Nonetheless, existing information about long-term consequences of the identified early and most likely sustained changes to the developing lung is limited. Interesting results point towards a tremendous impact of these early injuries on the pulmonary repair capacity as well as aging related processes in the adult lung.

No MeSH data available.


Related in: MedlinePlus

Neonatal hyperoxia disrupts postnatal alveolar development in the lung. Representative tissue slides (H&E stains) of newborn mouse lung exposed to room air or 100% oxygen from birth to PN10. Thickened alveolar septae (thick arrow), inflammatory cells (thin arrow), and simplified alveoli (asterisks).
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Figure 1: Neonatal hyperoxia disrupts postnatal alveolar development in the lung. Representative tissue slides (H&E stains) of newborn mouse lung exposed to room air or 100% oxygen from birth to PN10. Thickened alveolar septae (thick arrow), inflammatory cells (thin arrow), and simplified alveoli (asterisks).

Mentions: To understand how oxygen affects lung development, non-human primates, preterm sheep, newborn guinea pigs, and newborn rodents have been exposed to excessive levels of oxygen [for review in Ref. (91)]. Early-life oxygen exposure leads to many characteristic pathologic features of the so called “new” BPD, including inhibition of microvascular development, alveolar simplification, inflammation, and mild interstitial thickening [Figure 1 and Ref. (92, 93)]. It also recapitulates many diseases in children who were born preterm, including altered host response to respiratory viral infections, mild cognitive changes, and cardiovascular disease. Despite the widespread use of hyperoxia as a tool to study BPD, a codified model of oxygen exposure has yet to be established, making the extrapolation of outcomes between different investigators using different doses and durations of hyperoxia on different developmental windows possible (91). Today, preterm infants are often exposed to excess oxygen during the saccular stage of lung development, and discharged breathing room air when entering the first phase of completion in alveolarization. In order to mimic these clinically relevant conditions, the influence of oxygen on saccular stages in lung development, i.e., mouse E17.5 to PN should be separated from its impact on the phase of alveolarization, i.e., mouse PN5–PN14 (94). Models using oxygen exposure during alveolar development may therefore better resume the characteristic picture of the so called “old BPD,” the scarring lung disease seen in infants born in late gestation in the pre-surfactant era. The process of organ maturation clearly is a modifier of the pulmonary response to oxygen exposure, as hyperoxia has been shown to reduce bone marrow, circulating and lung endothelial progenitor cells in the developing but not in the adult mouse lung (95). Additionally, different oxygen concentrations affected lung development and the host response to influenza A virus in neonatal mice (96). Hence, a better understanding of how dose and duration of the respective harmful agent interfere with a certain developmental window is important to make progress in the development of treatment strategies that could improve pulmonary health in preterm infants.


Bronchopulmonary dysplasia early changes leading to long-term consequences.

Hilgendorff A, O'Reilly MA - Front Med (Lausanne) (2015)

Neonatal hyperoxia disrupts postnatal alveolar development in the lung. Representative tissue slides (H&E stains) of newborn mouse lung exposed to room air or 100% oxygen from birth to PN10. Thickened alveolar septae (thick arrow), inflammatory cells (thin arrow), and simplified alveoli (asterisks).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4325927&req=5

Figure 1: Neonatal hyperoxia disrupts postnatal alveolar development in the lung. Representative tissue slides (H&E stains) of newborn mouse lung exposed to room air or 100% oxygen from birth to PN10. Thickened alveolar septae (thick arrow), inflammatory cells (thin arrow), and simplified alveoli (asterisks).
Mentions: To understand how oxygen affects lung development, non-human primates, preterm sheep, newborn guinea pigs, and newborn rodents have been exposed to excessive levels of oxygen [for review in Ref. (91)]. Early-life oxygen exposure leads to many characteristic pathologic features of the so called “new” BPD, including inhibition of microvascular development, alveolar simplification, inflammation, and mild interstitial thickening [Figure 1 and Ref. (92, 93)]. It also recapitulates many diseases in children who were born preterm, including altered host response to respiratory viral infections, mild cognitive changes, and cardiovascular disease. Despite the widespread use of hyperoxia as a tool to study BPD, a codified model of oxygen exposure has yet to be established, making the extrapolation of outcomes between different investigators using different doses and durations of hyperoxia on different developmental windows possible (91). Today, preterm infants are often exposed to excess oxygen during the saccular stage of lung development, and discharged breathing room air when entering the first phase of completion in alveolarization. In order to mimic these clinically relevant conditions, the influence of oxygen on saccular stages in lung development, i.e., mouse E17.5 to PN should be separated from its impact on the phase of alveolarization, i.e., mouse PN5–PN14 (94). Models using oxygen exposure during alveolar development may therefore better resume the characteristic picture of the so called “old BPD,” the scarring lung disease seen in infants born in late gestation in the pre-surfactant era. The process of organ maturation clearly is a modifier of the pulmonary response to oxygen exposure, as hyperoxia has been shown to reduce bone marrow, circulating and lung endothelial progenitor cells in the developing but not in the adult mouse lung (95). Additionally, different oxygen concentrations affected lung development and the host response to influenza A virus in neonatal mice (96). Hence, a better understanding of how dose and duration of the respective harmful agent interfere with a certain developmental window is important to make progress in the development of treatment strategies that could improve pulmonary health in preterm infants.

Bottom Line: Remodeling of the extracellular matrix, apoptosis as well as altered growth factor signaling characterize the disease.The immediate consequences of these early insults have been studied in different animal models supported by results from in vitro approaches leading to the successful application of some findings to the clinical setting in the past.Interesting results point towards a tremendous impact of these early injuries on the pulmonary repair capacity as well as aging related processes in the adult lung.

View Article: PubMed Central - PubMed

Affiliation: Comprehensive Pneumology Center, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL) , Munich , Germany ; Neonatology, Perinatal Center Grosshadern, Dr. von Hauner Children's Hospital, Ludwig-Maximilians University , Munich , Germany.

ABSTRACT
Neonatal chronic lung disease, i.e., bronchopulmonary dysplasia, is characterized by impaired pulmonary development resulting from the impact of different risk factors including infections, hyperoxia, and mechanical ventilation on the immature lung. Remodeling of the extracellular matrix, apoptosis as well as altered growth factor signaling characterize the disease. The immediate consequences of these early insults have been studied in different animal models supported by results from in vitro approaches leading to the successful application of some findings to the clinical setting in the past. Nonetheless, existing information about long-term consequences of the identified early and most likely sustained changes to the developing lung is limited. Interesting results point towards a tremendous impact of these early injuries on the pulmonary repair capacity as well as aging related processes in the adult lung.

No MeSH data available.


Related in: MedlinePlus