Lung Growth in Infants and Toddlers Residing at High Altitude

描述(由申请人提供)：首席研究员的长期目标是了解肺生长和发育的决定因素，以便最大限度地提高肺功能，最大限度地减少与早期肺部疾病相关的发病率和死亡率。这项拟议的研究将在阿根廷图卡曼大学与康拉多·拉普尔博士合作完成，作为NIH赠款R01 HL054062的延伸。从出生起就居住在高海拔地区的幼儿和成人比居住在海平面地区的受试者肺部更大。这些发现表明，居住在高海拔地区的慢性低氧刺激了相对于躯体生长的肺生长，这是对慢性需要增加氧合的一种补偿机制。然而，目前尚不清楚这种对肺生长的刺激是否会增加婴儿或蹒跚学步的婴儿的肺体积，或者需要显著增加能量消耗，这可能要到较大的年龄才会发生。目前还没有对高海拔地区婴儿和蹒跚学步儿童的肺容量进行测量。此外，还没有关于生命早期肺部生长和能量消耗之间关系的数据。刺激肺生长的年龄是由此产生的肺结构和功能的重要决定因素。肺切除后，婴儿会增加实质肺组织，以达到成年时正常的肺体积和肺泡表面积；相反，成人肺切除后，肺代偿性生长是通过扩大肺而不使肺泡表面积正常化来实现的。我们建议使用居住在高海拔地区的自然条件来评估慢性低氧对生命早期肺生长的刺激作用。这项建议将评估婴幼儿的肺容量、氧气消耗和血清生长因子，这是一个重要且难以评估的年龄组。我们假设，居住在高海拔地区的慢性低氧刺激了生命早期的肺生长和能量消耗，这与较高的血清血管内皮生长因子水平有关。了解慢性缺氧是如何刺激人类，特别是生命早期的肺生长的，将对设计先天性青紫型心脏病婴儿、肺发育不良婴儿和早产婴儿的治疗策略具有重要的临床意义。从出生起就居住在高海拔的幼儿和成人长期暴露在低氧环境中，他们的肺部比居住在海平面的受试者更大。目前尚不清楚这种对肺生长的刺激是否会增加婴儿或幼儿的肺体积，因为在这个年龄段还没有测量结果。了解慢性缺氧是否会在生命早期产生更大的肺，可能会为刺激患有慢性肺病的婴儿的肺生长提供治疗策略。

DESCRIPTION (provided by applicant): The principal investigator's long term goals are to understand the determinants of lung growth and development so as to maximize lung function and minimize the morbidity and mortality associated with lung disease early in life. This proposed research will be done in Argentina at University of Tucaman in collaboration with Dr. Conrado Llapur, as an extension of NIH grant R01 HL054062. Young children and adults residing at high altitude since birth have larger lungs than subjects residing at sea-level. These findings indicate that chronic hypoxia from residing at high altitude stimulates lung growth relative to somatic growth as a compensatory mechanism for the chronic need to increase oxygenation. However, it is not known whether this stimulus to lung growth produces an increased lung volume in infants or toddlers or requires a marked increase in energy expenditure, which may not occur until an older age. There have been no measurements of lung volumes in infants and toddlers at high altitude. In addition, there is no data on the relationship between lung growth and energy expenditure early in life. The age at which lung growth is stimulated is an important determinant of the resultant lung structure and function. Following lung resection, infants will increase parenchymal lung tissue to achieve normal lung volume and alveolar surface area in adulthood; in contrast, following lung resection in adulthood, compensatory lung growth occurs by expansion of the lung without normalization of alveolar surface area. We propose to use the naturally occurring condition of residing at high altitude to evaluate the effects of chronic hypoxia as a stimulus to lung growth early in life. This proposal will assess lung volumes, oxygen consumption, and serum growth factors in infants and toddlers, an important and difficult age group to evaluate. We hypothesize that chronic hypoxia from residing at high altitude stimulates lung growth and energy expenditure early in life, which is associated with higher serum levels of vascular endothelial growth factor. Understanding how chronic hypoxia stimulates lung growth in humans, particularly early in life, will have important clinical implications for designing therapeutic strategies for infants with congenital cyanotic heart disease, infants with hypoplastic lungs, and infants born prematurely. Young children and adults residing at high altitude since birth are exposed to chronically low levels of oxygen and they have larger lungs than subjects residing at sea-level. It is not known whether this stimulus to lung growth produces increased lung volume in infants or toddlers, as there have been no measurements in this age group. Understanding whether chronic hypoxia produces larger lungs early in life may offer therapeutic strategies to stimulate lung growth in infants with chronic lung disease.