Bronchopulmonary dysplasia: clinical aspects and preventive and therapeutic strategies

Abstract 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of long-term outcomes of BPD is difficult because the adults presently available to study have received outdated treatment.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

Magnetic resonance imaging of pulmonary damage in the term and premature rat neonate exposed to hyperoxia

Immaturity and oxygen toxicity have been implicated in the pathogenesis of the neonatal disease bronchopulmonary dysplasia. The present study aimed to investigate the use of magnetic resonance imaging (MRI) to assess hyperoxia-mediated lung injury in the term and premature neonate. Term (gestation, 22 d) and premature (21 d) rat pups were exposed to hyperoxia (>95%) or air for a 6-d period (n = 7) and assessed for lung damage by MRI. Pulmonary signal intensities of T₁-weighted images were significantly increased in both hyperoxia-exposed term and premature neonates, relative to air-breathing controls (p < 0.01). T₂-weighted MRI signal intensities were also greater in premature and term rat pups exposed to hyperoxia, but failed to reach significance (p > 0.05). Elevated MRI pulmonary signal intensities may have represented an increase in magnetic resonance–detectable free water, possibly indicating an increase in edema. Corresponding histologic evidence of lung injury was detected in both term and premature rat pups exposed to hyperoxia. Histologic samples indicated focal regions of alveolar hemorrhage, immune cell infiltration, edema, and collapse in both term and premature rat neonates exposed to hyperoxia. Alveolar air space was assessed (n = 5) by light microscopy within a 0.5 mm² region of the superior left and inferior right pulmonary lobes of each treatment group. Alveolar area of the superior left lung lobe of the premature hyperoxia treatment group was significantly smaller than other treatment groups (p < 0.05). Reduced area for respiratory exchange was probably a result of observed focal areas of edema and collapse. MRI-detectable increases in lung signal intensity may have represented an increase in hyperoxia-induced pulmonary edema in the 6-d-old rat neonate. Increases in signal intensity correlated with the appearance of edema in pulmonary histologic samples. Premature delivery had a less defined effect on lung injury but possibly exacerbated hyperoxia-mediated pulmonary damage

Comparison between intratracheal and intravenous administration of liposome-DNA complexes for cystic fibrosis lung gene therapy

Intratracheal (i.t.) and intravenous (i.v.) delivery of DNA-vector formulations are two strategies to obtain gene transfer to the lung. It is still uncertain, however, which of these two modes of delivery will be more effective in the treatment of cystic fibrosis and other lung diseases. In this study, we attempted to optimize formulations of the cationic liposome DODAC:DOPE (dioleoyldimethylammoniumchloride:dioleoylphosphatidylethanolamine) complexed to plasmids encoding chloramphenicol acetyltransferase for i.t. and i.v. injection into CD-1 mice and compared the two methods. Our results showed that both methods conferred reporter gene expression in the lung that was significantly higher relative to injection of plasmid DNA alone. Expression using either mode of administration was maximal 24 h after injection and declined to around 10% of day 1 levels 2 weeks after injection. For i.v. delivery of DODAC:DOPE-DNA complexes multilamellar vesicles were more effective than large unilamellar vesicles in all organs investigated. Recombinant DNA could be detected in the distal lung region following either route of administration. However, i.t. administration predominantly led to DNA deposition in epithelial cells lining the bronchioles, eg in clara cells, whereas i.v. administration resulted in DNA deposition in the alveolar region of the lung including type II alveolar epithelial cells.link_to_OA_fulltex

Nanocarriers for Vascular Delivery of Anti-Inflammatory Agents

There is a need for improved treatment of acute vascular inflammation in conditions such as ischemia-reperfusion injury, acute lung injury, sepsis, and stroke. The vascular endothelium represents an important therapeutic target in these conditions. Furthermore, some anti-inflammatory agents (AIAs) (e.g., biotherapeutics) require precise delivery into subcellular compartments. In theory, optimized delivery to the desired site of action may improve the effects and enable new mechanisms of action of these AIAs. Diverse nanocarriers (NCs) and strategies for targeting them to endothelial cells have been designed and explored for this purpose. Studies in animal models suggest that delivery of AIAs using NCs may provide potent and specific molecular interventions in inflammatory pathways. However, the industrial development and clinical translation of complex NC-AIA formulations are challenging. Rigorous analysis of therapeutic/side effect and benefit/cost ratios is necessary to identify and optimize the approaches that may find clinical utility in the management of acute inflammation