Department of Mathematics and Applied Mathematics, Virginia Commonwealth University, Richmond, Virginia, United States.
Department of Bioengineering, University of Colorado Denver | Anschutz Medical Campus, Aurora, Colorado, United States.
Am J Physiol Lung Cell Mol Physiol. 2023 Aug 1;325(2):L190-L205. doi: 10.1152/ajplung.00123.2022. Epub 2023 Jun 20.
Thoracoabdominal asynchrony (TAA), the asynchronous volume changes between the rib cage and abdomen during breathing, is associated with respiratory distress, progressive lung volume loss, and chronic lung disease in the newborn infant. Preterm infants are prone to TAA risk factors such as weak intercostal muscles, surfactant deficiency, and a flaccid chest wall. The causes of TAA in this fragile population are not fully understood and, to date, the assessment of TAA has not included a mechanistic modeling framework to explore the role these risk factors play in breathing dynamics and how TAA can be resolved. We present a dynamic compartmental model of pulmonary mechanics that simulates TAA in the preterm infant under various adverse clinical conditions, including high chest wall compliance, applied inspiratory resistive loads, bronchopulmonary dysplasia, anesthesia-induced intercostal muscle deactivation, weakened costal diaphragm, impaired lung compliance, and upper airway obstruction. Sensitivity analyses performed to screen and rank model parameter influence on model TAA and respiratory volume outputs show that risk factors are additive so that maximal TAA occurs in a virtual preterm infant with multiple adverse conditions, and addressing risk factors individually causes incremental changes in TAA. An abruptly obstructed upper airway caused immediate nearly paradoxical breathing and tidal volume reduction despite greater effort. In most simulations, increased TAA occurred together with decreased tidal volume. Simulated indices of TAA are consistent with published experimental studies and clinically observed pathophysiology, motivating further investigation into the use of computational modeling for assessing and managing TAA. A novel model of thoracoabdominal asynchrony incorporates literature-derived mechanics and simulates the impact of risk factors on a virtual preterm infant. Sensitivity analyses were performed to determine the influence of model parameters on TAA and respiratory volume. Predicted phase angles are consistent with prior experimental and clinical results, and influential parameters are associated with clinical scenarios that significantly alter phase angle, motivating further investigation into the use of computational modeling for assessing and managing thoracoabdominal asynchrony.
胸腹不同步（TAA）是指呼吸过程中胸廓和腹部之间的容量变化不同步，与新生儿呼吸窘迫、肺容积进行性丧失和慢性肺部疾病有关。早产儿容易出现 TAA 风险因素，如肋间肌无力、表面活性物质缺乏和柔软的胸壁。TAA 在这个脆弱人群中的原因尚未完全阐明，迄今为止，TAA 的评估并未包括一个机械建模框架，以探索这些风险因素在呼吸动力学中的作用以及如何解决 TAA。我们提出了一个肺部力学的动态房室模型，该模型可以模拟早产儿在各种不利临床情况下的 TAA，包括高胸壁顺应性、应用吸气阻力负荷、支气管肺发育不良、麻醉诱导的肋间肌失活、削弱的肋膈肌无力、肺顺应性降低和上呼吸道阻塞。为筛选和对模型 TAA 和呼吸容量输出的模型参数影响进行排名而进行的敏感性分析表明，风险因素具有累加性，因此，患有多种不利条件的虚拟早产儿会出现最大 TAA，而单独解决风险因素会导致 TAA 的增量变化。上呼吸道突然阻塞会导致立即出现几乎反常的呼吸和潮气量减少，尽管呼吸努力更大。在大多数模拟中，TAA 的增加伴随着潮气量的减少。模拟的 TAA 指标与已发表的实验研究和临床观察到的病理生理学一致，这促使进一步研究使用计算模型来评估和管理 TAA。一个新的胸腹不同步模型结合了文献中得出的力学，并模拟了风险因素对虚拟早产儿的影响。进行了敏感性分析，以确定模型参数对 TAA 和呼吸容量的影响。预测的相位角与先前的实验和临床结果一致，并且有影响力的参数与显著改变相位角的临床情况相关，这促使进一步研究使用计算模型来评估和管理胸腹不同步。
