稳定期寡粒细胞型哮喘患者的临床、功能和炎症特征：与痰液不同表型比较
2018/05/03
摘要
背景：根据诱导痰细胞计数，划分四种不同的哮喘表型(嗜酸粒细胞型、中性粒细胞型、混合型和寡粒细胞型)。本研究旨在检测寡粒细胞型哮喘患者的功能和炎性特征。
方法：240例哮喘患者根据诱导痰细胞计数分为4种表型。。所有患者都进行肺功能测试，并测量呼出气一氧化氮(FeNO)。检测痰上清液中IL-8、IL-13、嗜酸性阳离子蛋白(ECP)水平。记录治疗状态、哮喘控制和重症难治性哮喘(SRA)情况。
结果：患者分为四种表型:嗜酸粒细胞型(40%)、混合型(6.7%)、中性粒细胞型(5.4%)和寡粒细胞型(47.9%)。虽然哮喘控制水平在不同组间没有差异(P=0.288)，但寡粒细胞型哮喘患者肺功能较好(FEV1 % pred)，嗜酸粒细胞型、混合型、中性粒细胞型和寡粒细胞型中位数 (IQR) 分别为: 71.5 (59.0-88.75) vs 69.0 (59.0-77.6) vs 68.0 (60.0-85.5) vs 80.5 (69.7-95.0)， P=0.009。重症难治性哮喘更常见于嗜酸粒细胞型哮喘和混合型哮喘（分别为41.6% 和43.7% ），较少见于中性粒细胞型哮喘和寡粒细胞型哮喘（分别为25% 和21.7% ）， P=0.01。FeNO和ECP在嗜酸性粒细胞型哮喘和混合型哮喘中更高，IL-8在中性粒细胞型哮喘和混合型哮喘中更高，寡粒细胞型哮喘中FeNO、ECP、IL-8水平均较低（所有比较P＜0.001）。有趣的是，有14.8%的寡粒细胞型哮喘患者哮喘控制水平较差。
结论：寡粒细胞型哮喘很可能代表一种“良性”哮喘表型，与良好的治疗反应有关，而非哮喘的“真实”表型。然而，对于尽管得到了最优治疗但仍未获得良好控制的寡粒细胞型哮喘患者，代表了需要进一步研究以进行潜在新型靶向干预的哮喘人群。
Clinical, functional and inflammatory characteristics in patients with paucigranulocytic stable asthma: Comparison with different sputum phenotypes
Ntontsi P; Loukides S; Bakakos P; Kostikas K; Papatheodorou G; Papathanassiou E; Hillas G; Koulouris N; Papiris S; Papaioannou AI.
Allergy；2017; 72(11):1761-1767.
Abstract
BACKGROUND: According to induced sputum cell count, four different asthma phenotypes have been recognized (eosinophilic, neutrophilic, mixed and paucigranulocytic). The aim of this study was to detect functional and inflammatory characteristics of patients with paucigranulocytic asthma.
METHODS: A total of 240 asthmatic patients were categorized into the four phenotypes according to cell counts in induced sputum. All patients underwent pulmonary function tests, and measurement of fraction of exhaled nitric oxide (FeNO). The levels of IL-8, IL-13 and eosinophilic cationic protein (ECP) were also measured in sputum supernatant. Treatment, asthma control and the presence of severe refractory asthma (SRA) were also recorded.
RESULTS: Patients were categorized into the four phenotypes as follows: eosinophilic (40%), mixed (6.7%), neutrophilic (5.4%) and paucigranulocytic (47.9%). Although asthma control test did not differ between groups (P=.288), patients with paucigranulocytic asthma had better lung function (FEV1 % pred) [median (IQR): 71.5 (59.0-88.75) vs 69.0 (59.0-77.6) vs 68.0 (60.0-85.5) vs 80.5 (69.7-95.0), P=.009] for eosinophilic, mixed, neutrophilic and paucigranulocytic asthma, respectively, P=.009). SRA occurred more frequently in the eosinophilic and mixed phenotype (41.6% and 43.7%, respectively) and less frequently in the neutrophilic and paucigranulocytic phenotype (25% and 21.7%, respectively, P=.01). FeNO, ECP and IL-8 were all low in the paucigranulocytic, whereas as expected FeNO and ECP were higher in eosinophilic and mixed asthma, while IL-8 was higher in patients with neutrophilic and mixed asthma (P<.001 for all comparisons). Interestingly, 14.8% of patients with paucigranulocytic asthma had poor asthma control.
CONCLUSIONS: Paucigranulocytic asthma most likely represents a "benign" asthma phenotype, related to a good response to treatment, rather than a "true" phenotype of asthma. However, paucigranulocytic patients that remain not well controlled despite optimal treatment represent an asthmatic population that requires further study for potential novel targeted interventions.
背景：根据诱导痰细胞计数，划分四种不同的哮喘表型(嗜酸粒细胞型、中性粒细胞型、混合型和寡粒细胞型)。本研究旨在检测寡粒细胞型哮喘患者的功能和炎性特征。
方法：240例哮喘患者根据诱导痰细胞计数分为4种表型。。所有患者都进行肺功能测试，并测量呼出气一氧化氮(FeNO)。检测痰上清液中IL-8、IL-13、嗜酸性阳离子蛋白(ECP)水平。记录治疗状态、哮喘控制和重症难治性哮喘(SRA)情况。
结果：患者分为四种表型:嗜酸粒细胞型(40%)、混合型(6.7%)、中性粒细胞型(5.4%)和寡粒细胞型(47.9%)。虽然哮喘控制水平在不同组间没有差异(P=0.288)，但寡粒细胞型哮喘患者肺功能较好(FEV1 % pred)，嗜酸粒细胞型、混合型、中性粒细胞型和寡粒细胞型中位数 (IQR) 分别为: 71.5 (59.0-88.75) vs 69.0 (59.0-77.6) vs 68.0 (60.0-85.5) vs 80.5 (69.7-95.0)， P=0.009。重症难治性哮喘更常见于嗜酸粒细胞型哮喘和混合型哮喘（分别为41.6% 和43.7% ），较少见于中性粒细胞型哮喘和寡粒细胞型哮喘（分别为25% 和21.7% ）， P=0.01。FeNO和ECP在嗜酸性粒细胞型哮喘和混合型哮喘中更高，IL-8在中性粒细胞型哮喘和混合型哮喘中更高，寡粒细胞型哮喘中FeNO、ECP、IL-8水平均较低（所有比较P＜0.001）。有趣的是，有14.8%的寡粒细胞型哮喘患者哮喘控制水平较差。
结论：寡粒细胞型哮喘很可能代表一种“良性”哮喘表型，与良好的治疗反应有关，而非哮喘的“真实”表型。然而，对于尽管得到了最优治疗但仍未获得良好控制的寡粒细胞型哮喘患者，代表了需要进一步研究以进行潜在新型靶向干预的哮喘人群。
（邓稞 张红萍 王刚 四川大学华西医院中西医结合科呼吸病组）
（Allergy；2017; 72(11):1761-1767.）
（Allergy；2017; 72(11):1761-1767.）
Clinical, functional and inflammatory characteristics in patients with paucigranulocytic stable asthma: Comparison with different sputum phenotypes
Ntontsi P; Loukides S; Bakakos P; Kostikas K; Papatheodorou G; Papathanassiou E; Hillas G; Koulouris N; Papiris S; Papaioannou AI.
Allergy；2017; 72(11):1761-1767.
Abstract
BACKGROUND: According to induced sputum cell count, four different asthma phenotypes have been recognized (eosinophilic, neutrophilic, mixed and paucigranulocytic). The aim of this study was to detect functional and inflammatory characteristics of patients with paucigranulocytic asthma.
METHODS: A total of 240 asthmatic patients were categorized into the four phenotypes according to cell counts in induced sputum. All patients underwent pulmonary function tests, and measurement of fraction of exhaled nitric oxide (FeNO). The levels of IL-8, IL-13 and eosinophilic cationic protein (ECP) were also measured in sputum supernatant. Treatment, asthma control and the presence of severe refractory asthma (SRA) were also recorded.
RESULTS: Patients were categorized into the four phenotypes as follows: eosinophilic (40%), mixed (6.7%), neutrophilic (5.4%) and paucigranulocytic (47.9%). Although asthma control test did not differ between groups (P=.288), patients with paucigranulocytic asthma had better lung function (FEV1 % pred) [median (IQR): 71.5 (59.0-88.75) vs 69.0 (59.0-77.6) vs 68.0 (60.0-85.5) vs 80.5 (69.7-95.0), P=.009] for eosinophilic, mixed, neutrophilic and paucigranulocytic asthma, respectively, P=.009). SRA occurred more frequently in the eosinophilic and mixed phenotype (41.6% and 43.7%, respectively) and less frequently in the neutrophilic and paucigranulocytic phenotype (25% and 21.7%, respectively, P=.01). FeNO, ECP and IL-8 were all low in the paucigranulocytic, whereas as expected FeNO and ECP were higher in eosinophilic and mixed asthma, while IL-8 was higher in patients with neutrophilic and mixed asthma (P<.001 for all comparisons). Interestingly, 14.8% of patients with paucigranulocytic asthma had poor asthma control.
CONCLUSIONS: Paucigranulocytic asthma most likely represents a "benign" asthma phenotype, related to a good response to treatment, rather than a "true" phenotype of asthma. However, paucigranulocytic patients that remain not well controlled despite optimal treatment represent an asthmatic population that requires further study for potential novel targeted interventions.
