Growth of Airways and Lung Parenchyma in Normal Infants

该提案将应用最先进的技术来评估肺的正常生长和发育 婴儿和幼儿的软组织，这是一个重要且难以评估的年龄组。了解肺 生命早期的生长对于设计治疗策略以促进肺发育的婴儿至关重要。 疾病我们还将评估与早产相关的慢性肺部后遗症，以及 比较两种不同的呼吸支持策略对肺结构和功能的影响， 早产儿我们的实验室开发了评估用力呼气动作的方法， 婴儿，我们已经采用了这种技术来测量婴儿的单次呼吸弥散能力，作为一种 用于气体交换的表面积的体内评估。此外，获得高分辨率CT的技术 在没有来自呼吸运动的伪影的情况下， 肺实质的定量测量!组织密度以及气道大小和壁厚。 肺内的通气不均匀性也将通过惰性气体的洗脱研究进行评估， 不同的扩散率。最后，我们将扩展我们的传导气道的计算模型，以包括 腺泡结构，这将有助于解释生理数据和机制， 早产儿肺功能障碍。 具体目标#1：确定实质组织与肺泡体积之间的关系， 肺的正常生长 我们假设，在生命的头两年，肺实质表面积和肺泡体积 随着体细胞的生长而增加;然而，表面积与体积的比率保持不变，而 肺内的通气变得更加均匀。 具体目标#2：确定早产的肺部后遗症并评估 肺部后遗症的早期治疗策略。 我们假设早产会阻碍肺实质的生长和发育， 矫正年龄为1岁时的气道。此外，启动持续气道正压通气（CPAP）和 极早产儿出生时的允许性呼吸策略将改善肺生长和肺功能 与早期表面活性剂和常规通气治疗相比。

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.