Lung Growth in Infants and Toddlers Residing at High Altitude

高海拔地区婴幼儿的肺部生长

• 批准号: 7544967
• 负责人: Robert S. Tepper
• 金额: $ 5.08万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7544967
• 关键词: Acute; Adolescent; Adult; Age; Altitude; Alveolar; Area; Argentina; Birth; Cardiac Output; Child; Chronic; Chronic lung disease; Clinical; Collaborations; Complement; Data; Diffuse; Early treatment; Effectiveness; Energy Metabolism; Environment; Environmental air flow; Excision; Funding; Goals; Grant; Growth; Growth Factor; Growth and Development function; Heart Diseases; Human; Hypoxia; Individual; Infant; Life; Living Wills; Lung; Lung Volume Measurements; Lung diseases; Measurement; Morbidity - disease rate; Oxygen; Oxygen Consumption; PGF gene; Physiological; Premature Birth; Principal Investigator; Pulmonary Diffusing Capacity; Relative (related person); Research; Respiratory physiology; Sea; Serum; Stimulus; Structure; Structure of parenchyma of lung; Surface; Therapeutic; Tissues; Toddler; United States National Institutes of Health; Universities; Vascular Endothelial Growth Factors; age group; design; lung volume; mortality; parent grant; response; treatment strategy

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.

描述（由申请人提供）：主要研究者的长期目标是了解肺部生长和发育的决定因素，以最大程度地提高肺功能并最大程度地减少与肺​​部早期相关的发病率和死亡率。这项拟议的研究将在阿根廷的图卡曼大学与Conrado Llapur博士合作，作为NIH Grant R01 HL054062的扩展。自出生以来，居住在高海拔地区的幼儿和成人的肺部比居住在海平面的受试者更大。这些发现表明，居住在高海拔高度的慢性缺氧相对于躯体生长刺激肺的生长，这是增加氧合作用的慢性需求的补偿机制。但是，尚不清楚这种肺部生长的刺激是否会导致婴儿或幼儿的肺部量增加，或者需要明显增加能量消耗的增加，直到年龄较大才可能发生。在高海拔的婴儿和幼儿中没有测量肺体积的测量。此外，没有关于肺部生长与生命早期能量消耗之间关系的数据。刺激肺部生长的年龄是所得肺结构和功能的重要决定因素。肺切除后，婴儿将增加实质性肺组织，以达到成年期正常的肺部体积和肺泡表面积。相反，成年后的肺切除后，通过肺部扩张而没有牙槽表面积的归一化来实现补偿性肺的生长。我们建议利用居住在高海拔的天然发生的条件，以评估慢性缺氧作为生命早期肺部生长的刺激的影响。该建议将评估婴儿和幼儿的肺量，消耗氧和血清生长因子，这是一个重要且困难的年龄组。我们假设居住在高海拔高度的慢性缺氧会刺激肺部生长和生命早期的能量消耗，这与血清血管内皮生长因子的较高水平有关。了解慢性缺氧如何刺激人类的肺部生长，尤其是生命的早期，将对先天性氰基疾病，患有肺部肺动脉症和婴儿过早出生的婴儿设计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暴露于慢性氧气水平，并且比居住在海平面的受试者的肺部更大。尚不清楚这种对肺部生长的刺激是否会导致婴儿或幼儿的肺部量增加，因为该年龄段没有测量。了解慢性缺氧是否会在生命早期产生较大的肺部可能会提供治疗策略，以刺激慢性肺部疾病的婴儿的肺部生长。