Growth of Airways and Lung Parenchyma in Normal Infants

描述（由申请人提供）：本提案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组。了解生命早期的肺生长对于设计促进肺部疾病婴儿肺生长的治疗策略至关重要。我们还将评估与早产相关的慢性肺后遗症，并比较两种不同的通气支持策略对极早产儿肺结构和功能的影响。我们的实验室开发了评估婴儿强制呼气动作的方法，我们已经采用这种技术来测量婴儿的单次呼吸扩散能力，作为气体交换表面积的体内评估。此外，一项在婴儿肺容量升高时获得高分辨率CT图像的技术，没有呼吸运动的伪影，我们将获得肺实质组织密度的体内定量测量，以及气道大小和壁厚。肺内的通气不均匀性也将通过不同扩散率的惰性气体的冲洗研究来评估。最后，我们将扩展我们的传导气道的计算模型，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：确定实质组织和肺泡体积与生命早期正常肺生长之间的关系。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，表面积与体积的比例保持不变，而肺内的通气变得更加均匀。特定目的2：确定早产的肺后遗症，并评估早期治疗策略对肺后遗症的有效性。我们假设早产阻碍了1岁矫正年龄时肺实质和气道的生长发育。此外，与早期表面活性剂和常规通气治疗相比，在出生时开始持续气道正压通气（CPAP）和允许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.