It is widely held that infancy is a critical time for rapid growth of the airways and lung parenchyma and that events affecting lung function early in life may have lifelong consequences. In contrast to our extensive knowledge of respiratory mechanics in older children and adults, our understanding of lung growth the first 2 years of life is very limited. Partial forced expiratory maneuvers have been adapted for use in infants, however, the technique is being questioned because there is no certainty that FL is reached, forced expiratory flows can be produced only over the tidal breathing range, and the variability of flow is high. We have developed a new method which allows the measurement of full forced vital capacity maneuvers, fractional lung volumes, and static pressure volume curves in infants and young children.
The Specific Aims of this project are to apply these new techniques: 1A) To determine in a large group of infants and very young children the lung volume range over which flow limitation is achieved. Flow limitation will be determined by constructing isovolume pressure flow (IVPF) curves using an esophageal catheter to measure transpulmonary pressure. 1B) To develop and validate a non-invasive technique that can replace IVPF curves in assessing the presence of FL in this age group. The non-invasive techniques tested will include: l) the external orifice technique, 2) superimposing an oscillating pressure at the body surface, and 3) lung sound analysis for forced expiratory wheeze. 2A) To determine during the first 24 months of life the relative growth of the airways and the lung parenchyma as assessed by maximal flows, lung volumes, static recoil pressures, and density dependence. 2B) To establish reference data between O and 24 months of life. 3A,B) To evaluate the development of airway responsiveness during the first 24 months of life using changes in maximal expiratory flows and fractional lung volumes following an aerosolized bronchodilator. The results of this project will greatly increase our knowledge of the normal mechanical development of the respiratory system over the first 2 years of life. Such information will provide the scientific basis for understanding the effects of the important respiratory disorders of early childhood (asthma, cystic fibrosis, bronchopulmonary dysplasia) on lung growth and maturation. These data will in addition allow us to better detect respiratory dysfunction and more efficiently assess the effects of therapeutic interventions in infants and young children. The comparability of these new methods for assessing lung function in infants to standard measures of pulmonary function in adults and older children will allow investigators and clinicians to more precisely quantify the effects of respiratory disease processes on the lungs and the airways longitudinally from infancy through adulthood.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL054062-03
Application #
2668736
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1996-03-01
Project End
2000-02-29
Budget Start
1998-03-01
Budget End
1999-02-28
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Pediatrics
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Chang, Daniel V; Assaf, Santiago J; Tiller, Christina J et al. (2016) Membrane and Capillary Components of Lung Diffusion in Infants with Bronchopulmonary Dysplasia. Am J Respir Crit Care Med 193:767-71
Assaf, Santiago J; Chang, Daniel V; Tiller, Christina J et al. (2015) Lung parenchymal development in premature infants without bronchopulmonary dysplasia. Pediatr Pulmonol 50:1313-9
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
Henry, F S; Llapur, C J; Tsuda, A et al. (2012) Numerical modelling and analysis of peripheral airway asymmetry and ventilation in the human adult lung. J Biomech Eng 134:061001
Chakr, Valentina C; Llapur, Conrado J; Sarria, Edgar E et al. (2012) Ventilation homogeneity improves with growth early in life. Pediatr Pulmonol 47:373-80
Sarria, E E; Mattiello, R; Rao, L et al. (2011) Computed tomography score and pulmonary function in infants with chronic lung disease of infancy. Eur Respir J 38:918-23
Rao, Laxmi; Tiller, Christina; Coates, Cathy et al. (2010) Lung growth in infants and toddlers assessed by multi-slice computed tomography. Acad Radiol 17:1128-35
Balinotti, Juan E; Chakr, Valentina C; Tiller, Christina et al. (2010) Growth of lung parenchyma in infants and toddlers with chronic lung disease of infancy. Am J Respir Crit Care Med 181:1093-7
Llapur, C J; Martínez, T M; Coates, C et al. (2009) Lung structure and function of infants with recurrent wheeze when asymptomatic. Eur Respir J 33:107-12
Balinotti, Juan E; Tiller, Christina J; Llapur, Conrado J et al. (2009) Growth of the lung parenchyma early in life. Am J Respir Crit Care Med 179:134-7

Showing the most recent 10 out of 26 publications