Strategies for preventing bronchopulmonary dysplasia

PURPOSE OF REVIEW: Neonatologists and pulmonary biologists have long sought preventive treatments for bronchopulmonary dysplasia (BPD). The purpose of this review is to highlight recent reports of a number of potential treatments intended to prevent BPD and to discuss the controversies surrounding preventive strategies. RECENT FINDINGS: The evolution of BPD from a disorder of pulmonary injury affecting moderately preterm infants, to one characterized by a developmental pulmonary arrest among survivors of extreme prematurity has important implications for BPD prevention. Recent recognition that the pathogenesis of BPD might have prenatal origins raises new challenges and opportunities for studies of BPD prevention; however, most current preventive strategies for BPD focus on respiratory management. Neither past nor current clinical trials have shown a conclusive benefit of a single preventive treatment strategy. Promising but still largely unproven preventive respiratory treatments include: high frequency oscillatory ventilation, permissive hypercapnea, and inhaled nitric oxide. Observational and recent laboratory data support the need for randomized clinical trials of continuous positive airway pressure versus mechanical ventilation. Additionally, clinical trials are needed to address the deficit in our knowledge of the potential benefits and risks of postnatal low dose corticosteroid treatment. Further study of superoxide dismutase, inositol, and alpha-1 proteinase inhibitor also are warranted on the basis of recent clinical trials or meta-analyses. SUMMARY: Only Vitamin A has proven a safe and effective preventive treatment for BPD. Additional studies of respiratory technologies, management strategies, and protective molecules are needed. Directed cytokine and genetic therapies are on the horizon.     

支气管肺发育不良的研究进展

支气管肺发育不良(BPD)是威胁早产儿健康问题的主要原因.随着新生儿治疗新技术的不断应用,"新"BPD已经替代了"老"BPD.BPD的发生涉及多种因素的相互作用,很多预防和治疗策略已用于BPD.

Abstract：

Bronchopulmonary dysplasia(BPD) is one of the main causes which threatend the health of preterm infants. As neonatal intensive care improved, the "new" BPD have replaced the" old" BPD. The development of BPD involved many factors, and several preventative and therapeutic strategies have been used in BPD.     

支气管肺发育不良研究的新进展

支气管肺发育不良(bmnchopulmonary dysplasia,BPD)是常发生于早产儿长期应用高浓度氧气和辅助机械通气后的一种慢性肺疾病。随着新生儿重症监护技术的迅速发展,越来越多的早产儿和极低体重儿得以存活,但BPD的发病率并未随之显著降低甚或有增高趋势,是新生儿重症监护的重要并发症和婴幼儿时期最常见的慢性呼吸系统疾病。     

Prevention of bronchopulmonary dysplasia

The clinical syndrome of bronchopulmonary dysplasia (BPD) in preterm infants results primarily from an arrest of lung vascular and alveolar development. The most likely mediators are proinflammatory cytokines that are induced by antenatal exposure to infection, postnatal ventilation, and oxygen exposure. New epidemiologic data suggest that attempts to avoid intubation and ventilation are the best ways to avoid severe BPD. The claim that one ventilation technique is better than another remains unconvincing, and any strategy that maintains the lung open and minimizes tidal volumes probably will be helpful. More adverse effects of postnatal steroids are being recognized. New insights into the pathophysiology of BPD and a new emphasis on minimizing ventilation and ventilator-mediated injury should improve outcomes for very preterm infants.     

Ureaplasma and bronchopulmonary dysplasia

Advances in neonatal intensive care have greatly improved survival rates for children born in a very early stage of lung development (i.e. less than 26 weeks of gestation). In these premature babies, even low levels of oxygen and methods of minimally invasive ventilation may disrupt the growth of the distal airways, a condition described as “new” bronchopulmonary dysplasia (BPD).Ureaplasma infection can occur in utero or in the perinatal period in premature infants, in some of which the infection with these organisms triggers an important lung pro-inflammatory and pro-fibrotic response, and may increase the risk of developing BPD. The inflammation may be worsened by exposure to oxygen and mechanical ventilation. At present, clinical studies have not clarified the role of Ureaplasma in the pathogenesis of BPD and there is insufficient evidence to determine whether antibiotic treatment of Ureaplasma has influence on the development of BPD and its comorbidities.Future research in the context of well-designed and controlled clinical trials of adequate statistical power should focus on how to determine whether the treatment of Ureaplasma decreases lung inflammation, reduces rates of BPD, and improves long-term neurodevelopment.     

Management of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is a common and important complication of prematurity and is associated with significant mortality, morbidity and healthcare resource utilization. Despite advances in both perinatal and neonatal care the incidence of the condition continues to rise. The management of BPD and its related problems remains a major challenge to neonatologists and paediatricians. There is unlikely to be a single intervention which will dramatically alter the management of BPD and thus multiple interventions have been proposed to prevent and treat the disease. Many of these interventions are still not evidence based and some of those that are have been shown to have unacceptable long-term effects. It is useful to conceptualize BPD in three stages, namely (i) prevention, (ii) treatment of evolving BPD and (iii) treatment of established BPD. In this review current and potential future management approaches to BPD and the relevant evidence for these are discussed within the framework of these three stages.     

Management of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD), also known as chronic lung disease of prematurity, and typically defined as the need for supplemental oxygen at 36 weeks' postmenstrual age, affects approximately 10% and 40% of very low birth weight and extremely low birth weight infants, respectively. Contributing factors include infection, oxygen exposure and ventilator induced lung injury, which can lead to impaired lung function. Several preventative and therapeutic strategies have been used in BPD, including lung protective ventilator strategies, and pharmacologic interventions. While many infants with BPD are treated with a wide variety of medications, little evidence for the efficacy of these treatments exist. This article will review current practice in the prevention and management of this complication of prematurity.     

Mesenchymal stem cells for the prevention of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is a chronic lung disease in preterm infants who have been treated with supplemental oxygen and mechanical ventilation. Despite major advances in perinatal and neonatal medicine, limited progress has been made in reducing BPD rates. The use of mesenchymal stem cells (MSC) is a promising and innovative therapy for several diseases because they are easy to extract and they have low immunogenicity, anti‐inflammatory properties, and regenerative ability. According to several pre‐clinical studies that have used BPD animal models, one mechanism of action for MSC in BPD is mainly due to the paracrine effects of MSC‐derived humoral factors, such as interleukin (IL)‐6, IL‐8, vascular endothelial growth factor, collagen, and elastin, rather than the multilineage and regenerative capacities of MSC. Cell‐free preparations derived from MSC, including conditioned media and exosomes, remain a pre‐clinical technology despite their great clinical potential. A first‐in‐human clinical trial of MSC treatment for BPD was performed as a phase I dose‐escalation trial using umbilical cord blood‐derived MSC. That trial demonstrated the short‐ and long‐term safety and feasibility of MSC, given that significantly reduced inflammatory marker expression was observed in tracheal aspirates. As of recently, several clinical trials of MSC use for BPD are ongoing or are planned in some countries to investigate the efficacy of MSC in the prevention or treatment of BPD in premature infants. Many clinicians are currently awaiting the results from these trials so that MSC can be used clinically for human BPD.