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.
|Llapur, Conrado J; Martínez, Myriam R; Caram, María Marta et al. (2013) Increased lung volume in infants and toddlers at high compared to low altitude. Pediatr Pulmonol 48:1224-30|