Lung Growth in Infants and Toddlers Residing at High Altitude

描述（由申请方提供）：主要研究者的长期目标是了解肺生长和发育的决定因素，以最大限度地提高肺功能，并最大限度地降低生命早期与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Conrado Llapur博士合作完成，作为NIH资助R 01 HL 054062的扩展。出生后居住在高海拔地区的幼儿和成人比居住在海平面的受试者具有更大的肺。这些研究结果表明，居住在高海拔地区的慢性缺氧刺激肺生长相对于躯体生长作为一种补偿机制的慢性需要增加氧合。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幼儿的肺容量，或者需要显著增加能量消耗，这可能直到年龄较大时才会发生。在高海拔地区，还没有对婴儿和幼儿的肺容量进行测量。此外，没有关于生命早期肺部生长和能量消耗之间关系的数据。肺生长受到刺激的年龄是肺结构和功能的重要决定因素。肺切除术后，婴儿将增加肺实质组织，以达到正常的肺体积和肺泡表面积在成年期;相反，在成年期肺切除术后，代偿性肺生长发生肺扩张，而肺泡表面积没有正常化。我们建议使用居住在高海拔地区的自然发生的条件，以评估慢性缺氧的影响，作为一个刺激肺生长在生命早期。这项提案将评估婴儿和幼儿的肺容量、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。我们推测，长期居住在高海拔地区的慢性缺氧刺激肺生长和能量消耗的生命早期，这是与较高的血清血管内皮生长因子水平。了解慢性缺氧如何刺激人类肺生长，特别是在生命早期，将有重要的临床意义，为设计治疗策略，先天性紫绀型心脏病，肺发育不良的婴儿，早产儿的婴儿。居住在高海拔地区的幼儿和成人从出生起就暴露在长期低水平的氧气中，他们的肺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容量，因为在这个年龄组中没有测量。了解慢性缺氧是否会在生命早期产生更大的肺，可能会提供治疗策略，以刺激患有慢性肺病的婴儿的肺生长。

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.