Growth of Airways and Lung Parenchyma in Normal Infants

描述(由申请人提供)：这项建议将应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段。在生命早期了解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，以及比较两种不同的早产儿机械支持策略对肺结构和功能的影响。我们实验室开发了评估婴儿用力呼气动作的方法，并将这项技术应用于测量婴儿的单次呼吸扩散能力，作为体内气体交换表面积的评估。此外，为了在没有呼吸运动伪影的情况下在婴儿肺容量增加时获得高分辨率CT图像，我们将在体内获得肺实质组织密度以及气道大小和壁厚的定量测量。通过对具有不同扩散系数的惰性气体的冲刷研究，也将评估肺内通风的不均一性。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，这将有助于解释导致早产儿肺功能障碍的生理数据和机制。具体目标1：在生命早期确定肺实质组织和肺泡体积与正常肺生长的关系。我们假设，在生命的头两年，实质表面积和肺泡体积随着躯体的生长而增加；然而，表面积与体积的比率保持不变，而肺内的通风变得更加均匀。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，在校正后的1岁时，早产会阻碍肺实质和呼吸道的生长和发育。此外，与早期使用表面活性物质和常规机械通气相比，在极早产儿出生时启动持续气道正压(CPAP)和允许的呼吸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.