Sharafkhaneh Amir, Babb Tony G, Officer Todd M, Hanania Nicholas A, Sharafkhaneh Hossein, Boriek Aladin M
Baylor College of Medicine, MED VAMC, Bldg 100 (111i), Houston, TX 77030, USA.
Am J Respir Crit Care Med. 2007 Feb 15;175(4):330-5. doi: 10.1164/rccm.200602-255OC. Epub 2006 Nov 16.
Improvement in FEV(1) is a main endpoint in clinical trials assessing the efficacy of bronchodilators. However, the effect of bronchodilators on maximal expiratory flow may be confounded by thoracic gas compression (TGC).
To determine whether TGC confounds effect of albuterol on FEV(1).
We evaluated the response to albuterol inhalation in 10 healthy subjects, 9 subjects with asthma, and 15 subjects with chronic obstructive pulmonary disease (COPD) with mean (SD) age in years of 38 (SD, 11), 45 (SD, 11), and 64 (SD, 8), respectively. Lung mechanics were measured at baseline and 20 minutes after inhalation of 180 micro g of albuterol. We then applied a novel method to calculate FEV(1) corrected for the effect of TGC (NFEV(1)).
Prior to albuterol administration, NFEV(1) was significantly higher than FEV(1). However, post-albuterol inhalation, FEV(1) increased more than NFEV(1) because of reduced TGC. In multiple regression analysis, the changes in TGC, inspiratory lung resistance, and ratio of residual volume to total lung capacity postalbuterol predicted more than 75% of FEV(1) improvement in patients with COPD.
Improvements in FEV(1) after albuterol in patients with COPD are due to reduction of lung resistance, hyperinflation, and TGC. The latter is negligible during tidal breathing. Thus, although reduction of lung resistance and hyperinflation may result in improved dyspnea with a bronchodilator, the contribution of TGC reduction to improvement of FEV(1) may not exert any meaningful clinical effect during tidal breathing. This fact has to be taken into consideration when assessing the efficacy of new bronchodilators.
第一秒用力呼气容积（FEV₁）的改善是评估支气管扩张剂疗效的临床试验中的主要终点。然而，支气管扩张剂对最大呼气流量的影响可能会受到胸内气体压缩（TGC）的干扰。
确定TGC是否会混淆沙丁胺醇对FEV₁的影响。
我们评估了10名健康受试者、9名哮喘患者和15名慢性阻塞性肺疾病（COPD）患者对沙丁胺醇吸入的反应，他们的平均（标准差）年龄分别为38岁（标准差11）、45岁（标准差11）和64岁（标准差8）。在基线以及吸入180微克沙丁胺醇20分钟后测量肺力学。然后我们应用一种新方法来计算校正了TGC影响的FEV₁（NFEV₁）。
在给予沙丁胺醇之前，NFEV₁显著高于FEV₁。然而，吸入沙丁胺醇后，由于TGC降低，FEV₁的增加幅度大于NFEV₁。在多元回归分析中，COPD患者吸入沙丁胺醇后TGC、吸气肺阻力和残气量与肺总量之比的变化预测了FEV₁改善的75%以上。
COPD患者吸入沙丁胺醇后FEV₁的改善是由于肺阻力降低、肺过度充气和TGC降低。后者在潮气呼吸期间可忽略不计。因此，尽管肺阻力降低和肺过度充气可能会导致使用支气管扩张剂后呼吸困难改善，但TGC降低对FEV₁改善的贡献在潮气呼吸期间可能不会产生任何有意义的临床效果。在评估新型支气管扩张剂的疗效时必须考虑这一事实。
