AIRWAY AND TISSUE MECHANICS AT BREATHING FREQUENCIES

呼吸道(RAW)和肺组织的单独贡献有多重要 (RT)在生理呼吸过程中对能量消耗的抵抗力？ 最近的动物研究引用了肺泡囊技术， RT约占总肺阻力(RL)的80% 当通风在0.3 HZ左右时。对于缩窄性激动剂，通常会有 RT比Raw增加更多的百分比。这些发现发表在 与早期关于实体力学的观点形成鲜明对比的是， 即，它们暗示正确的术语不是支气管收缩，而是 是“肺收缩”。因此，这似乎是直觉的，在此期间 呼吸、组织阻力对人类也应该很重要。如果是的话， 具体的治疗方式(如全身或局部治疗(呼吸道)) 对于哮喘炎症状况的类固醇治疗)应重新考虑 已评估。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，并已报道RT为RL的6+35%。 然而，在自发呼吸频率(-0.15赫兹)和2赫兹之间 RT减小，而Raw保持相当恒定。因此，它是 哮喘患者正常呼吸时RT很可能要高得多。 这一提议将检验以下假设：组织是一种更 显性的肺收缩。人不能使用肺泡囊。我们 已经开发出一种名为最佳呼吸机波形(OVW)的新方法 用于测量RL和肺弹性(EL)。卵子含有能量在 多个频率，并通过新颖的设计保持通风，同时 消除0.1-5 HZ范围内RL和EL上的非线性失真。我们的 初步数据显示，如果卵子处于健康或严重收缩状态 肺，我们可以划分与之相关的呼吸道和组织属性 原地生理性潮气呼吸，即不需要肺泡 胶囊。我们将首先在狗身上应用卵子来分离呼吸道和 组织特性在原位和开胸条件下，然后在原位 给药收缩的激动剂。另外，分离将是 在两个PEEP级别下执行。那么呼吸道和组织的属性就会 健康人和哮喘患者使用支气管扩张剂前后的测量 肺容量的增加也是如此。这些数据将使我们能够 区分与以下疾病相关的呼吸道和组织特性的变化 与激动剂引起的收缩相关的恶性充气(在 狗)或人类哮喘。通过使用不同粘度的居留气体 以及密度，我们将确定是否存在呼吸道不均匀或湍流偏向 呼吸道组织分离，如果是这样的话，我们提出了移除 这种偏见。这项提案的结论可能会显著修改 目前认为哮喘完全是一种呼吸道疾病。最终，我们的 入路可以确定炎症的主要部位 与反应不佳的所谓晚期哮喘患者有关 到局部使用类固醇。

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.