AIRWAY AND TISSUE MECHANICS AT BREATHING FREQUENCIES

呼吸频率下的气道和组织力学

• 批准号: 2226738
• 负责人: KENNETH R LUTCHEN
• 金额: $ 15.66万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-01-05 至 1997-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2226738
• 关键词: asthma; biomechanics; bronchoconstrictors; bronchodilators; dogs; human subject; hyperpnea; lung; mathematical model; model design /development; plethysmography; pulmonary respiration; respiratory airflow disorder; respiratory airway pressure; respiratory airway volume; respiratory pharmacology

How important is the separate contribution of airway (Raw) and lung tissue (RT) resistance to energy dissipation during physiological breathing? Recent animal studies invoking the alveolar capsule technique have indicated that RT amount to about 80% of the total lung resistance (RL) when ventilated around 0.3 HZ. With a constrictive agonist, there is often a greater percent increase in RT than in Raw. These findings appear in striking contrast to the earlier views regarding parenchymal mechanics, i.e., they imply that rather than bronchoconstriction the correct term is"pulmonary constriction". It seems intuitive, then, that during breathing, tissue resistance should be important in man as well. If so, specific treatment modalities (eg., systemic versus topical (airway) steroid treatment for the asthmatic inflammatory condition) should be re- evaluated. Previous measurements in human asthmatics have been possible primarily at 1.0-1.5 HZ and have reported that RT was 6+35% of RL. However, between the spontaneous breathing frequency (-0.15 HZ) and 2 HZ the RT decreases while Raw remains fairly constant. Consequently, it is highly likely that in asthmatic RT is much higher during normal breathing. This proposal will test the following hypothesis: The tissue is a more dominant constricted lungs. In man one cannot use alveolar capsules. We have developed a new approach called an optimal ventilator waveform (OVW) for measuring RL and lung elastance (EL). The OVW contains energy at several frequencies and by novel design maintains ventilation while eliminating nonlinear distortion on the RL and EL from 0.1-5 HZ. Our preliminary data show that with the OVW in healthy or severely constricted lungs we can partition the airway and tissue properties associated with physiological tidal breathing in-situ, i.e., without requiring alveolar capsules. We will first apply the OVW in dogs to separate airway and tissue properties in-situ and in open chest conditions then in-situ during administration of a constrictive agonist. Also the separation will be performed at two PEEP levels. Then airway and tissue properties will be measured in healthy and asthmatic humans before and after a bronchodilator and also at increased lung volumes. These data will allow us to distinguish changes in airway and tissue properties associated with hyperinflation from those associated with agonist induced constriction (in dogs) or human asthma. By use of resident gases with different viscosities and densities we will identify if airway inhomogeneities or turbulence bias the airway-tissue separations and, if so, we propose techniques to remove this bias. The conclusions from this proposal may significantly modify the current view of asthma as exclusively an airways disease. Eventually, our approach can lead to the identification of the primary site of inflammation associated with the so-called late-phase asthmatics who do not respond well to topically administered steroids.

气道（原始）和肺组织的单独贡献有多重要 (RT)生理呼吸过程中能量耗散的阻力？ 最近的动物研究援引肺泡囊技术， 表明RT约占总肺阻力（RL）的80%， 在0.3HZ左右通风时。 使用收缩激动剂， RT的增加百分比大于Raw。 这些发现出现在 与关于实质力学的早期观点形成鲜明对比， 也就是说，这意味着正确的术语不是支气管收缩， 是“肺收缩” 这似乎是直观的，然后，在 呼吸、组织阻力对人体也很重要。 如果是这样的话， 特定的治疗方式（例如，全身与局部（气道） 类固醇治疗的哮喘炎症条件），应重新 评估。 以前在人类哮喘患者中的测量是可能的 主要在1.0-1.5 HZ下，并且已经报道RT是RL的6 ± 35%。 然而，在自主呼吸频率（-0.15HZ）和2 HZ之间， RT降低而Raw保持相当恒定。 根据该结果 在哮喘患者中，RT很可能在正常呼吸期间高得多。 该提议将检验以下假设： 优势收缩肺。 人不能使用肺泡囊。 我们 开发了一种新方法，称为最佳呼吸机波形（OVW） 用于测量RL和肺弹性（EL）。 OVW包含的能量为 几个频率和新颖的设计保持通风， 消除了0.1-5 HZ范围内RL和EL上的非线性失真。 我们 初步数据显示，在健康或严重收缩的OVW中， 我们可以将呼吸道和组织特性 原位生理性潮式呼吸，即，不需要肺泡 胶囊 我们将首先在狗中应用OVW以分离气道， 原位和开胸条件下的组织性质，然后在 收缩激动剂的施用。 分离也将是 在两个PEEP水平下进行。 然后气道和组织特性将被 在使用支气管扩张剂前后， 以及肺容量的增加。 这些数据将使我们能够 区分与以下疾病相关的气道和组织性质的变化 与激动剂诱导的收缩相关的过度膨胀（在 狗）或人哮喘。 通过使用具有不同粘度的驻留气体 我们将确定气道不均匀性或湍流偏差 气道组织分离，如果是这样，我们提出的技术， 这种偏见。 这项建议的结论可能会大大改变 目前认为哮喘只是一种呼吸道疾病。 最终，我们的 这种方法可以识别炎症的原发部位 与所谓的晚期哮喘患者有关， 局部使用类固醇