Growth of Airways and Lung Parenchyma in Normal Infants

描述（由申请人提供）：本提案将采用最先进的技术来评估婴幼儿肺实质的正常生长和发育，这是一个重要且难以评估的年龄组。了解生命早期的肺生长对于设计治疗策略以促进患有肺部疾病的婴儿的肺生长至关重要。我们还将评估与早产相关的慢性肺部后遗症，并比较两种不同策略对极早产儿呼吸支持的肺结构和功能的影响。我们的实验室开发了评估婴儿用力呼气动作的方法，我们已经采用这种技术来测量婴儿的单次呼吸弥散量，作为气体交换表面积的体内评估。此外，一种技术，以获得高分辨率的CT图像，在婴儿在肺体积升高，没有伪影的呼吸运动，我们将获得在体内定量测量的肺实质组织密度，以及气道大小和壁厚。肺内通气不均匀性也将通过不同扩散率惰性气体的洗脱研究进行评估。最后，我们将扩展我们的计算模型的传导气道，包括腺泡结构，这将有助于解释的生理数据和机制，导致肺功能障碍的早产儿。具体目标#1：确定生命早期正常肺生长时实质组织和肺泡体积之间的关系。我们假设，在生命的前两年，实质表面积和肺泡体积随着躯体生长而增加;然而，表面积与体积的比率保持恒定，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，并评估早期治疗策略对肺部后遗症的有效性。我们假设早产在1岁的校正年龄时会阻碍肺实质和气道的生长和发育。此外，与早期表面活性剂和常规通气治疗相比，在极早产儿出生时启动持续气道正压通气（CPAP）和允许性通气策略将改善肺生长和肺功能。

DESCRIPTION (provided by applicant): This proposal will apply state-of-the-art techniques 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 artifacts from respiratory motion, we will obtain in vivo quantitative measurements of the lung parenchymal 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 assess the effectiveness of 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.