Lung Growth in Infants and Toddlers Residing at High Altitude

描述（由申请人提供）：主要研究者的长期目标是了解肺生长和发育的决定因素，从而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Tucaman大学与Dr. Conrado Llapur合作完成，作为NIH拨款R01 HL054062的延伸。自出生以来居住在高海拔地区的幼儿和成人的肺比居住在海平面的人的肺大。这些发现表明，居住在高海拔地区的慢性缺氧刺激了肺的生长，而不是身体的生长，这是一种慢性需要增加氧合的补偿机制。然而，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容量，或者需要显著增加能量消耗，这可能要到老年才会发生。目前还没有对婴幼儿在高海拔地区的肺容量进行测量。此外，还没有关于肺生长和生命早期能量消耗之间关系的数据。肺生长受到刺激的年龄是最终肺结构和功能的重要决定因素。肺切除术后，婴儿将增加实质肺组织，以达到成年后正常的肺体积和肺泡表面积；相反，在成年期肺切除术后，代偿性肺生长通过肺扩张发生，而肺泡表面积没有正常化。我们建议使用自然发生的高海拔居住条件来评估慢性缺氧对生命早期肺生长的刺激作用。该提案将评估婴幼儿的肺容量、耗氧量和血清生长因子，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缺氧刺激了生命早期的肺部生长和能量消耗，这与较高的血清血管内皮生长因子水平有关。了解慢性缺氧如何刺激人类肺部生长，特别是在生命早期，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。自出生以来居住在高海拔地区的幼儿和成人长期暴露在低氧环境中，他们的肺比居住在海平面的人大。目前尚不清楚这种刺激肺生长是否会增加婴儿或幼儿的肺容量，因为没有对该年龄组进行测量。了解慢性缺氧是否会在生命早期产生更大的肺，可能为刺激患有慢性肺病的婴儿肺部生长提供治疗策略。

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.