Growth of Airways and Lung Parenchyma in Normal Infants

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This proposal will apply state-of-the-arttechniques to assess normal growth and development of the lung parenchyma in infants and toddlers, an important and difficult age group to evaluate. Understanding lung growth early in life is critical for designing therapeutic strategies to promote lung growth in infants with lung disease. We will also evaluate the chronic pulmonary sequelae related to premature birth, as well as compare the effects upon lung structure and function of two different strategies for ventilatory support of very premature infants. Our laboratory developed the methodology to assess forced expiratory maneuvers in infants, and we have adapted this technique to measure single-breath diffusing capacity in infants, as an in- vivo assessment of surface area for gas exchange. In addition, a technique to obtain high resolution CT images in infants at elevated lung volumes without artifactsfrom respiratory motion, we will obtain in-vivo quantitative measurements of the lung parenchyma! tissue density, as well as airway size and wall thickness. Ventilation inhomogeneity within the lung will also be assessed from washout studies of inert gases with differing diffusivity. Lastly, we will extend our computational model of the conducting airways to include the acinar structure, which will assist in interpreting the physiologic data and mechanisms contributing to pulmonary dysfunction in infants born prematurely. SPECIFIC AIM # 1: Determine the relationship between parenchymal tissue and alveolar volume with normal lung growth early in life. We hypothesize that during the first two years of life that parenchymal surface area and alveolar volume increase with somatic growth; however, the ratio of surface area to volume remains constant, while ventilation within the lung becomes more homogenous. SPECIFIC AIM # 2: Determine the pulmonary sequelae of premature birth and assessthe effectivenessof early treatment strategies upon the pulmonary sequelae. We hypothesize that premature birth impedes growth and development of the lung parenchyma and the airways at a corrected-age of 1-year. In addition, initiating continuous positive airway pressure (CPAP) and a permissive ventilatory strategy in very premature infants at birth will improve lung growth and lung function compared to treatment with early surfactant and conventional ventilation.