沙丁胺醇对哮喘病人大小气道解痉的对比研究
摘要
哮喘是以复发性支气管收缩和气道炎症为特征的慢性肺疾病。如果在这过程中，气道痉挛占主导地位，痉挛一旦恢复，症状即可消失。虽然随着研究的深入，人们认识到哮喘不只包括气道痉挛，它还表现出大量粘液分泌，气道上皮破坏等病理变化，慢性病变的患者，还表现出反复气道痉挛、气道炎症的后果——气道重建，但这些改变反过来促进气道高反应性，气道因而更加敏感易痉挛。由此可见，无论哮喘急性发作还是慢性过程，无论何种因素是诱发哮喘的始动因子，只要能够导致气道平滑肌收缩产生气道痉挛，就可以产生哮喘的呼吸困难，胸闷，咳嗽，咳痰等症状。
我们常常通过检测气道阻力来了解哮喘病人大小气道痉挛的程度，气道阻力往往通过各种非介入的检查来获得一系列指标来衡量，最经典的是用力呼气测量法，临床上常常采取支气管扩张试验作为诊断哮喘的重要指标。支气管扩张试验是指使用一定剂量的支气管扩张药物使狭窄的支气管扩张，以测定其扩张程度的肺功能试验。
支气管扩张试验系使用一定剂量的扩张支气管药物，使狭窄的支气管扩张，以测定其扩张程度，进而反映气道反应性大小的肺功能试验。临床上常用来判断支气管狭窄的可逆程度，作为支气管哮喘诊断的辅助方法。目前判断支气管扩张试验阳性的肺功能标准为：一秒钟
用力呼气容量（forced expiratory flow in one second, FEV1.0）、呼气流量峰值（peak expiratory flow, PEF）。根据现行的判断支气管扩张试验阳性标准哮喘的诊断率≤70％。为提高哮喘诊断的阳性率，人们对其它指标：最大呼气中段流量（maximal midexpiriraory flow, MMEF）、50%肺活量最大呼气流量（expiration of 50% FVC, V50）、25%肺活量最大呼气流量（expiration of 25% FVC, V25）用力肺活量（forced vital capacity FVC）及气道阻力（airway resistance, Raw）、比气道传导率（specific airway conductance, sGaw）、弹性阻力等在支气管扩张试验中的应用进行了研究。
我们在对哮喘患者进行常规的支气管扩张试验基础上，分别于雾化吸入沙丁胺醇后15分钟、30分钟、1小时、2小时时测量 FVC、FEV1.0、PEF、MMEF、V50、V25。结果发现反应大气道功能的指标FVC、FEV1、PEF的拟合直线方程斜率远远大于反映小气道的功能指标MMEF、V50、V25所所拟合的直线方程斜率。也就是说,吸入沙丁胺醇气雾剂后,经过相同一段时间后,大气道扩张程度要大于小气道的扩张程度.
产生大小气道扩张能力不同的可能原因如下：
由于小气道的平滑肌相对较多，因此吸入沙丁胺醇后，作用对象相对的增多，这一扩增的程度则要相应的比大气道低。
人体吸入气体，从面积仅为5cm2的气管，扩散到80 cm2的广阔区域中去，其气流速度在运行中逐级减慢。沙丁胺醇气雾剂所形成的气
溶胶直径约为4-5μm，人体吸入后，由于惯性嵌顿和重力沉降作用而易在大气道沉积。惯性嵌顿即按照Newton定律，粒子的惯性与其质量成正比，咽喉、气管及其分支处，气道突然改变，气流速度快、内压低，粒子易与黏膜撞击而被扑获。重力沉降作用即气体在大气道呈湍流状态，易加速粒子的沉积。因此，进一步支持了大气道扩张程度较高的结论。
小气道平滑肌随着气道炎症的过程增生重建，收缩能力增加，却没有足够的抵御能力，即使给予药物，恢复能力也受到影响，这可能是大小气道反应差不同的一个原因。
小气道比大气道阻塞程度更严重，这种病理解剖上的不同，可能造成了大小气道反应程度不同。
总之，本研究在首次发现了哮喘病人吸入支气管扩张及后，大、小气道的舒张能力不同。本研究中所发现的结论对进一步了解支气管痉挛、解痉挛线性规律，对临床医生科学地指导哮喘病人用药，对更加科学的管理哮喘病人等均可提供有益的研究依据。
Asthma is a chronic bronchial disease with reiteratively bronchial constriction and airway inflammation.in the during of asthma, if the bronchial constriction is the most important reason, constriction disappeare, symptom will be alleviative.The constriction of airway sooth muscle will lead outbreak of asthma whether in acute spasm or chronic course of disease.
Bronhodilation test is a sort of pulmonary function test (PFT) which use bronchodilator drug to dilate the narrow airways. With the degree of airways dilatation, we can judge the state of airway reactivity. Therefore, bronchodilation test is often used as an assist method to diagnose asthma. Now the indexes of judge bronchodilation test are forced expiratory flow (PEF). However, according to the current standard of bronchodilation test positive, the diagnosis rate of asthma is only ≦70％.In order to raise the positive rate of diagnosing asthma, people investigate other indexes, such as maximal midexpiratory flow (MMEF), forced vital capacity (FVC), expiration of 50% FVC (V50), expiration of 25% FVC (V25), airway
resistance (Raw), specific airway conductance (sGaw), etc.
After performing regular bronchodilation test., asthma patients were examined PFT when 15 minutes, 30 minutes, 1 hour, 2 hour, respectively. The indexes include FVC, FEV1, PEF, MMEF, and V50and V25. We found that straight line of slope indexes which reflecting the function of large airways including FVC, FEV1, and PEF is higher than indexes which reflecting the function of small airway including MMEF,V50, and V25. It means large airways can resume better after inhale the bronchpdilator drug in the same time.
Below are the possible reasons:
First, there are more airway sooth muscles in the small airway on the same area, then concentration of drug will decent.
Second, the air inspired to human body diffuses from bronchus which area is only 5 cm2 into broad regions of about 80cm2. The speed of airflow gets slower while running from one grade to next one. The collosol diameter of salbutamol aerosol is about 4-5 μm It is easy to deposit in large airways because of inertia halt and gravity sedimentation. The inertia halt is that the inertia of particle is proportional to its mass and
speed of running according to Newton Law. In the throat, bronchus and and it’s branches, the airway directions suddenly change and the speed of airflow is fast and internal pressure is low. So particles are apt to struck airflow is at the state of turbulent in large airways, which accelerate the particles to deposit. This supports the viewpoint that large airways dilate first.
Last, there are more serious in the small airway, then the mending will be affected.
In conclusion, our results may be helpful to raise the positive rate of bronchodilation test and guide to therapy of asthma.
我们常常通过检测气道阻力来了解哮喘病人大小气道痉挛的程度，气道阻力往往通过各种非介入的检查来获得一系列指标来衡量，最经典的是用力呼气测量法，临床上常常采取支气管扩张试验作为诊断哮喘的重要指标。支气管扩张试验是指使用一定剂量的支气管扩张药物使狭窄的支气管扩张，以测定其扩张程度的肺功能试验。
支气管扩张试验系使用一定剂量的扩张支气管药物，使狭窄的支气管扩张，以测定其扩张程度，进而反映气道反应性大小的肺功能试验。临床上常用来判断支气管狭窄的可逆程度，作为支气管哮喘诊断的辅助方法。目前判断支气管扩张试验阳性的肺功能标准为：一秒钟
用力呼气容量（forced expiratory flow in one second, FEV1.0）、呼气流量峰值（peak expiratory flow, PEF）。根据现行的判断支气管扩张试验阳性标准哮喘的诊断率≤70％。为提高哮喘诊断的阳性率，人们对其它指标：最大呼气中段流量（maximal midexpiriraory flow, MMEF）、50%肺活量最大呼气流量（expiration of 50% FVC, V50）、25%肺活量最大呼气流量（expiration of 25% FVC, V25）用力肺活量（forced vital capacity FVC）及气道阻力（airway resistance, Raw）、比气道传导率（specific airway conductance, sGaw）、弹性阻力等在支气管扩张试验中的应用进行了研究。
我们在对哮喘患者进行常规的支气管扩张试验基础上，分别于雾化吸入沙丁胺醇后15分钟、30分钟、1小时、2小时时测量 FVC、FEV1.0、PEF、MMEF、V50、V25。结果发现反应大气道功能的指标FVC、FEV1、PEF的拟合直线方程斜率远远大于反映小气道的功能指标MMEF、V50、V25所所拟合的直线方程斜率。也就是说,吸入沙丁胺醇气雾剂后,经过相同一段时间后,大气道扩张程度要大于小气道的扩张程度.
产生大小气道扩张能力不同的可能原因如下：
由于小气道的平滑肌相对较多，因此吸入沙丁胺醇后，作用对象相对的增多，这一扩增的程度则要相应的比大气道低。
人体吸入气体，从面积仅为5cm2的气管，扩散到80 cm2的广阔区域中去，其气流速度在运行中逐级减慢。沙丁胺醇气雾剂所形成的气
溶胶直径约为4-5μm，人体吸入后，由于惯性嵌顿和重力沉降作用而易在大气道沉积。惯性嵌顿即按照Newton定律，粒子的惯性与其质量成正比，咽喉、气管及其分支处，气道突然改变，气流速度快、内压低，粒子易与黏膜撞击而被扑获。重力沉降作用即气体在大气道呈湍流状态，易加速粒子的沉积。因此，进一步支持了大气道扩张程度较高的结论。
小气道平滑肌随着气道炎症的过程增生重建，收缩能力增加，却没有足够的抵御能力，即使给予药物，恢复能力也受到影响，这可能是大小气道反应差不同的一个原因。
小气道比大气道阻塞程度更严重，这种病理解剖上的不同，可能造成了大小气道反应程度不同。
总之，本研究在首次发现了哮喘病人吸入支气管扩张及后，大、小气道的舒张能力不同。本研究中所发现的结论对进一步了解支气管痉挛、解痉挛线性规律，对临床医生科学地指导哮喘病人用药，对更加科学的管理哮喘病人等均可提供有益的研究依据。
Asthma is a chronic bronchial disease with reiteratively bronchial constriction and airway inflammation.in the during of asthma, if the bronchial constriction is the most important reason, constriction disappeare, symptom will be alleviative.The constriction of airway sooth muscle will lead outbreak of asthma whether in acute spasm or chronic course of disease.
Bronhodilation test is a sort of pulmonary function test (PFT) which use bronchodilator drug to dilate the narrow airways. With the degree of airways dilatation, we can judge the state of airway reactivity. Therefore, bronchodilation test is often used as an assist method to diagnose asthma. Now the indexes of judge bronchodilation test are forced expiratory flow (PEF). However, according to the current standard of bronchodilation test positive, the diagnosis rate of asthma is only ≦70％.In order to raise the positive rate of diagnosing asthma, people investigate other indexes, such as maximal midexpiratory flow (MMEF), forced vital capacity (FVC), expiration of 50% FVC (V50), expiration of 25% FVC (V25), airway
resistance (Raw), specific airway conductance (sGaw), etc.
After performing regular bronchodilation test., asthma patients were examined PFT when 15 minutes, 30 minutes, 1 hour, 2 hour, respectively. The indexes include FVC, FEV1, PEF, MMEF, and V50and V25. We found that straight line of slope indexes which reflecting the function of large airways including FVC, FEV1, and PEF is higher than indexes which reflecting the function of small airway including MMEF,V50, and V25. It means large airways can resume better after inhale the bronchpdilator drug in the same time.
Below are the possible reasons:
First, there are more airway sooth muscles in the small airway on the same area, then concentration of drug will decent.
Second, the air inspired to human body diffuses from bronchus which area is only 5 cm2 into broad regions of about 80cm2. The speed of airflow gets slower while running from one grade to next one. The collosol diameter of salbutamol aerosol is about 4-5 μm It is easy to deposit in large airways because of inertia halt and gravity sedimentation. The inertia halt is that the inertia of particle is proportional to its mass and
speed of running according to Newton Law. In the throat, bronchus and and it’s branches, the airway directions suddenly change and the speed of airflow is fast and internal pressure is low. So particles are apt to struck airflow is at the state of turbulent in large airways, which accelerate the particles to deposit. This supports the viewpoint that large airways dilate first.
Last, there are more serious in the small airway, then the mending will be affected.
In conclusion, our results may be helpful to raise the positive rate of bronchodilation test and guide to therapy of asthma.
引文
1. King D, Asthma diagnosis by spiromery. Sensitive or specific?[J]. Aust Fam Physician, 1998, 27(3): 183-186.
2．汪敏刚主编。支气管哮喘 。第二版。人民卫生出版社，1986，41页。
3. Boushey HA ,et al . Bronchial hyperreactivity. Am Rev Respire Dis 1980:121:384-413.
4．吕坤聚，等。白血病介素－8与豚鼠气道高反应性关系探讨。中华结核和呼吸杂志 1997: 20:280-282.
5.Masaki Fujimura ,et al . Involvement of Thromboxane A2 in Bronchial Hyperresponsiveness of Asthma. Pulmonary Pharmacology 1995: 8: 251-257.
6.Shiba K , et al .Structural changes of airway wall impair respiratory function, even in mild asthma. Chest 2002: 122(5): 1622-6.
7．王忠慧，等。哮喘豚鼠模型支气管平滑肌钙通道特性的变化。中华结核和呼吸杂志 2001：24（9）：539-541.
8．李明华，段凯生，朱栓立主编。哮喘病学。第一版。人民卫生出版社，1998，104页。
9．向旭东，等。长期咀嚼槟榔者气道高反应性的变化。中华结核和呼吸杂志 2001：24（3）：179
10.D.E.Davies, et al. Asthma: the importance of epithelial mesenchymal communication in pathogenesis Inflammation and the airway epithelium in asthma. The International Journal of Biochemistry & Cell Biology 2002: 34:1520-1526.
11．王忠慧，等。哮喘豚鼠模型支气管平滑肌钙通道特性的变化。中华结核和呼吸杂志 2001：24（9）：539-541。
12. Robert F, et al. Inlammatory events in asthma: An expanding equation. J Allergy Clin Immunol 2000:june: s633-636.
13. Johnson PR, et al. Airway smooth muscle cell proliferation is increase in asthma. Am J Respir Crit Care Med 2001 : 164 (3) : 474-7 。
2．汪敏刚主编。支气管哮喘 。第二版。人民卫生出版社，1986，41页。
3. Boushey HA ,et al . Bronchial hyperreactivity. Am Rev Respire Dis 1980:121:384-413.
4．吕坤聚，等。白血病介素－8与豚鼠气道高反应性关系探讨。中华结核和呼吸杂志 1997: 20:280-282.
5.Masaki Fujimura ,et al . Involvement of Thromboxane A2 in Bronchial Hyperresponsiveness of Asthma. Pulmonary Pharmacology 1995: 8: 251-257.
6.Shiba K , et al .Structural changes of airway wall impair respiratory function, even in mild asthma. Chest 2002: 122(5): 1622-6.
7．王忠慧，等。哮喘豚鼠模型支气管平滑肌钙通道特性的变化。中华结核和呼吸杂志 2001：24（9）：539-541.
8．李明华，段凯生，朱栓立主编。哮喘病学。第一版。人民卫生出版社，1998，104页。
9．向旭东，等。长期咀嚼槟榔者气道高反应性的变化。中华结核和呼吸杂志 2001：24（3）：179
10.D.E.Davies, et al. Asthma: the importance of epithelial mesenchymal communication in pathogenesis Inflammation and the airway epithelium in asthma. The International Journal of Biochemistry & Cell Biology 2002: 34:1520-1526.
11．王忠慧，等。哮喘豚鼠模型支气管平滑肌钙通道特性的变化。中华结核和呼吸杂志 2001：24（9）：539-541。
12. Robert F, et al. Inlammatory events in asthma: An expanding equation. J Allergy Clin Immunol 2000:june: s633-636.
13. Johnson PR, et al. Airway smooth muscle cell proliferation is increase in asthma. Am J Respir Crit Care Med 2001 : 164 (3) : 474-7 。
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