Pan Yang, Huang Ke-Wu, Ye Qing, Liu Xue-Song, Wu Bao-Mei, Zhang Jun, Chang Xiao-Hong, Lu Yong, Wang Chen
Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing 100020, China.
Zhonghua Jie He He Hu Xi Za Zhi. 2009 Sep;32(9):679-84.
To observe the airway inflammation and peripheral airway function in asthmatic patients with different control levels, and to investigate whether the airway inflammation profile detected by induced sputum reflects the peripheral airway dysfunction.
The recruited asthmatic subjects (n = 66) were divided into 3 groups: asthma controlled (8 male and 13 female), asthma partly controlled (12 male and 16 female), asthma uncontrolled (6 male and 11 female). Twenty healthy subjects served as the control group (9 male and 11 female). On the 1(st) day, all the subjects were required to take asthma control test (ACT), and to receive measurement of lung function by oscillometry and spirometry as well as inflammatory cell profile of induced sputum and the concentration of eosinophil cationic protein (ECP). Exhaled nitric oxide (FE(NO)) was measured on the 2(nd) day, and oscillometry methacholine provocation was conducted for patients whose baseline FEV(1) was > or = 70% predicted. The provocation process was terminated when airway resistance was increased by twice of the basic value, or when the methacholine reached the highest concentration. Then airway resistance and lung function were examined after 3 minutes. Finally, airway resistance and lung function were measured again after the subjects had 5 consecutive deep inspirations (DI). Correlation analysis was conducted between ACT scores and inflammatory cells count, ECP concentrations of induced sputum and FE(NO) among different groups. The correlations were also made between the change of peripheral airway resistance triggered by provocation or DI and ACT scores, total eosinophil, ECP level of induced sputum, FE(NO) respectively.
The total eosinophil count and ECP level in induced sputum and FE(NO) in asthmatic patients increased with the decline of control level. Negative correlations between ACT scores and total eosinophil count as well as the ECP level were observed (r = -0.43, -0.56, P < 0.01). In the healthy control group, the percentage of increase in peripheral airway resistance (R(5)-R(20)) and central airway resistance (R(20)) did not show significant difference (F = 3.472, P > 0.05) with methacholine provocation, while the percentage of increase in R(5)-R(20) was greater than in R(20) in both controlled and partly controlled asthmatic patients with provocation (F = 18.09 and 14.14, P < 0.01), though the change of R(5)-R(20) showed no correlations with ACT scores, eosinophil count of induced sputum, ECP level and FE(NO). After DI, R(5)-R(20) decreased from (0.13 +/- 0.14) kPa x L(-1) x s(-1) to (0.08 +/- 0.09) kPa x L(-1) x s(-1) (t = 2.84, P < 0.05) in the healthy control group, while R(5)-R(20) increased from (0.24 +/- 0.15) kPa x L(-1) x s(-1) to (0.30 +/- 0.16) kPa x L(-1) x s(-1) in the controlled asthma group, from (0.31 +/- 0.18) kPa x L(-1) x s(-1) to (0.39 +/- 0.17) kPa x L(-1) x s(-1) in the partly controlled asthma group (t = 3.90 and 4.68, P < 0.01, respectively). No correlations were observed between the change of R(5)-R(20) after DI and ACT scores, total eosinophil counts, ECP level as well as FE(NO) (r = -0.07, 0.28, -0.14, 0.14, P > 0.05).
Even in asthma patients with controlled disease, eosinophilic inflammation in the airway was still present, and the eosinophilic inflammation became more severe with the decline of control level. Bronchodilatory effect caused by DI disappeared in asthmatic patients. The inflammation profile detected by induced sputum did not reflect the dysfunction of peripheral airways.
观察不同控制水平哮喘患者的气道炎症及外周气道功能，探讨诱导痰检测的气道炎症特征是否反映外周气道功能障碍。
将纳入的哮喘患者（n = 66）分为3组：哮喘控制组（男8例，女13例）、哮喘部分控制组（男12例，女16例）、哮喘未控制组（男6例，女11例）。20名健康受试者作为对照组（男9例，女11例）。第1天，所有受试者均需进行哮喘控制测试（ACT），并接受振荡法和肺量计测定肺功能，以及诱导痰炎症细胞特征和嗜酸性粒细胞阳离子蛋白（ECP）浓度检测。第2天测定呼出一氧化氮（FE(NO)），对基线FEV(1)≥预计值70%的患者进行振荡法乙酰甲胆碱激发试验。当气道阻力增加至基础值的两倍或乙酰甲胆碱达到最高浓度时终止激发过程。然后在3分钟后检查气道阻力和肺功能。最后，受试者连续5次深吸气（DI）后再次测量气道阻力和肺功能。对不同组间ACT评分与诱导痰炎症细胞计数、ECP浓度及FE(NO)进行相关性分析。同时对激发试验或DI引发的外周气道阻力变化与ACT评分、诱导痰总嗜酸性粒细胞、ECP水平、FE(NO)分别进行相关性分析。
哮喘患者诱导痰中总嗜酸性粒细胞计数、ECP水平及FE(NO)随控制水平下降而升高。ACT评分与总嗜酸性粒细胞计数及ECP水平呈负相关（r = -0.43，-0.56，P < 0.01）。健康对照组中，乙酰甲胆碱激发试验后外周气道阻力（R(5)-R(20)）和中心气道阻力（R(20)）增加百分比差异无统计学意义（F = 3.472，P > 0.05），而在控制组和部分控制组哮喘患者激发试验中R(5)-R(20)增加百分比大于R(20)（F = 18.09和14.14，P < 0.01），尽管R(5)-R(20)变化与ACT评分、诱导痰嗜酸性粒细胞计数、ECP水平及FE(NO)无相关性。DI后，健康对照组R(5)-R(20)从(0.13±0.14)kPa·L⁻¹·s⁻¹降至(0.08±0.09)kPa·L⁻¹·s⁻¹（t = 2.84，P < 0.05），而控制组哮喘患者R(5)-R(20)从(0.24±0.15)kPa·L⁻¹·s⁻¹升至(0.30±0.16)kPa·L⁻¹·s⁻¹，部分控制组哮喘患者从(0.31±0.18)kPa·L⁻¹·s⁻¹升至(0.39±0.17)kPa·L⁻¹·s⁻¹（t分别为3.90和4.68，P < 0.01）。DI后R(5)-R(20)变化与ACT评分、总嗜酸性粒细胞计数、ECP水平及FE(NO)无相关性（r = -0.07，0.28，-0.14，0.14，P > 0.05）。
即使在病情控制的哮喘患者中，气道嗜酸性粒细胞炎症仍然存在，且嗜酸性粒细胞炎症随控制水平下降而加重。哮喘患者中DI引起的支气管舒张作用消失。诱导痰检测的炎症特征不能反映外周气道功能障碍。
