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（RAW）和肺组织的单独贡献有多重要 （RT）在生理呼吸期间对能量耗散的抵抗力？ 最新的动物研究调用牙槽胶囊技术具有 指出RT约为总肺阻力（RL）的80％ 当通风左右在0.3 Hz左右。 有了狭窄的激动剂，经常有 RT比RAW的百分比高。 这些发现出现在 与早期有关实质力学的观点形成鲜明对比的是 即，他们暗示而不是支气管收缩正确的术语 是“肺部收缩”。 因此，似乎很直观 呼吸，耐组织性也应在人类中也很重要。 如果是这样， 特定的治疗方式（例如，全身与局部（气道） 类固醇治疗哮喘性炎症状况）应重新 评估。 以前的人类哮喘患者已经进行了测量 主要在1.0-1.5 Hz时，报告RT为RL的6+35％。 但是，在自发呼吸频率（-0.15 Hz）和2 Hz之间 RT减小，而RAW保持相当恒定。 因此，是 在正常呼吸期间，在哮喘的RT中极有可能要高得多。 该建议将检验以下假设：组织更多 肺部主导地位。 在人中，一个人不能使用牙槽胶囊。 我们 已经开发了一种称为最佳呼吸机波形（OVW）的新方法 用于测量RL和肺弹性（EL）。 OVW包含能量 几个频率和新颖的设计可保持通风 从0.1-5 Hz消除RL和EL上的非线性失真。 我们的 初步数据表明，在健康或严重限制的OVW中 肺我们可以将气道和组织特性划分 生理潮汐呼吸原位，即无需肺泡 胶囊。 我们将首先将OVW在狗中应用于呼吸道和 组织特性在原位和开放的胸部条件下，然后在原位 限制性激动剂的给药。 分离将是 在两个窥视水平上进行。 然后气道和组织特性是 在支气管扩张剂之前和之后，以健康和哮喘的人进行测量 并在肺部量增加时。 这些数据将使我们能够 区分气道和组织特性的变化 与激动剂诱导的收缩相关的过度充气（在 狗）或人类哮喘。 通过使用具有不同粘度的居民气体 和密度我们将确定气道是否不均匀或湍流偏见 气道组织分离，如果是的话，我们提出了去除的技术 这个偏见。 该提案的结论可能会大大改变 当前的哮喘视为仅是气道疾病。 最终，我们的 方法可以导致炎症的主要部位识别 与所谓的后期哮喘患者相关 局部施用类固醇。