GROWTH OF AIRWAYS AND LUNG PARENCHYMA IN NORMAL INFANTS

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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.