Fahy J V, Kim K W, Liu J, Boushey H A
Department of Medicine, University of California, San Francisco 94143, USA.
J Allergy Clin Immunol. 1995 Apr;95(4):843-52. doi: 10.1016/s0091-6749(95)70128-1.
To infer possible mechanisms of acute airway inflammation and mucus hypersecretion in acute severe asthma, we performed cellular and biochemical analysis on sputum from 18 adults with acute severe asthma and compared the results with results of analysis of sputum from 12 adults with cystic fibrosis (CF). We found that in subjects with asthma neutrophils made up more than 75% of sputum cells in 10 samples whereas eosinophils made up more than 75% of cells in only three samples. Fifty percent of the subjects with asthma reported that their asthma exacerbation was precipitated by a respiratory tract infection, and these subjects had a significantly higher percentage of neutrophils in their sputum (85% +/- 6% vs 57% +/- 12%, p = 0.05). In the CF samples neutrophils made up more than 95% and eosinophils less than 1% of cells in all samples analyzed. Analysis of fluid phase chemicals in asthmatic and CF sputum samples showed that despite overall lower mean values of neutrophil elastase (27 +/- 11 micrograms/ml vs 466 +/- 121 micrograms/ml, p = 0.0001) and interleukin-8 (IL-8) (55 +/- 15 ng/ml vs 186 +/- 24 ng/ml, p = 0.0001), some of the asthmatic samples had values for these variables that overlapped those in the CF samples. In addition, the asthmatic samples were distinguished by the presence of higher tryptase (10 +/- 7 U/L vs 0.9 +/- 0.9 U/L, p = 0.0001) and interleukin-6 (1166 +/- 447 ng/ml vs 186 +/- 24 ng/ml; p = 0.0001) levels and by a higher ratio of albumin to mucin-like glycoprotein (0.8 +/- 0.5 vs 0.1 +/- 0.002, p = 0.02). DNA levels were lower in the asthmatic samples (0.5 +/- 0.3 mg/ml vs 3.5 +/- 1.2 mg/ml, p = 0.05). We conclude that neutrophils predominate more frequently than eosinophils as the major inflammatory cell in sputum from patients with asthma in acute exacerbation. We speculate that this may be because respiratory tract infections are a frequent precipitant of acute asthma. In addition, the high IL-8 levels and free neutrophil elastase activity observed in asthmatic sputum suggests that IL-8 may mediate airway neutrophilia in acute asthma and that neutrophil elastase may mediate mucin glycoprotein hypersecretion in acute asthma, as has been proposed for the mucin hypersecretion in CF.
为了推断急性重症哮喘中急性气道炎症和黏液分泌过多的可能机制，我们对18例急性重症哮喘成年患者的痰液进行了细胞和生化分析，并将结果与12例囊性纤维化（CF）成年患者的痰液分析结果进行了比较。我们发现，在哮喘患者中，10份样本中的中性粒细胞占痰液细胞的75%以上，而嗜酸性粒细胞仅在3份样本中占细胞的75%以上。50%的哮喘患者报告其哮喘发作是由呼吸道感染诱发的，这些患者痰液中的中性粒细胞百分比显著更高（85%±6%对57%±12%，p = 0.05）。在CF样本中，所有分析样本中的中性粒细胞占比超过95%，嗜酸性粒细胞占比不到1%。对哮喘和CF痰液样本中的液相化学物质分析表明，尽管中性粒细胞弹性蛋白酶（27±11微克/毫升对466±121微克/毫升，p = 0.0001）和白细胞介素-8（IL-8）（55±15纳克/毫升对186±24纳克/毫升，p = 0.0001）的总体平均值较低，但一些哮喘样本中这些变量的值与CF样本中的值重叠。此外，哮喘样本的特征是存在较高的类胰蛋白酶（10±7 U/L对0.9±0.9 U/L，p = 0.0001）和白细胞介素-6（1166±447纳克/毫升对186±24纳克/毫升；p = 0.0001）水平，以及白蛋白与黏蛋白样糖蛋白的比例较高（0.8±0.5对0.1±0.002，p = 0.02）。哮喘样本中的DNA水平较低（0.5±0.3毫克/毫升对3.5±1.2毫克/毫升，p = 0.05）。我们得出结论，在急性加重期哮喘患者的痰液中，中性粒细胞作为主要炎症细胞比嗜酸性粒细胞更频繁地占主导地位。我们推测这可能是因为呼吸道感染是急性哮喘的常见诱发因素。此外，哮喘痰液中观察到的高IL-8水平和游离中性粒细胞弹性蛋白酶活性表明，IL-8可能介导急性哮喘中的气道中性粒细胞增多，并且中性粒细胞弹性蛋白酶可能介导急性哮喘中的黏蛋白糖蛋白分泌过多，正如针对CF中的黏蛋白分泌过多所提出的那样。
