重症哮喘研究中混合痰粒细胞对肺功能的纵向影响
2021/03/25
摘要
背景：报告指出痰细胞计数存在纵向变异性，而另一些报告则描述了其存在稳定性。与持续升高的嗜酸性粒细胞百分数相比，痰中嗜酸性粒细胞百分数变异大与肺功能丧失相关，但嗜中性粒细胞升高与更严重的哮喘有关。
目的：纵向探索痰中粒细胞的稳定性或变异性，及其与重要临床特征的关系。
方法：重症哮喘研究计划（SARP 3）队列在基线和三年内每年进行全面的表型特征分析。成功获取痰液的成人研究对象被分为3个纵向痰液组：嗜酸性粒细胞持续<2%，嗜酸性粒细胞持续>2%，或嗜酸性粒细胞持续高度可变>2SD组。受试者同样被分配到3个纵向中性粒细胞组中的1个（50%为界值）。
测量与主要结果：与其它嗜酸性粒细胞组相比，在痰嗜酸性粒细胞持续<2％组在基线和整个三年中肺功能最高（支气管扩张剂前FEV1％，p <0.01，FEV1 / FVC，p <0.001）。尽管高度可变嗜酸性粒细胞组在第3年报告更多的哮喘急性发作，但医疗保健的利用没有差异。纵向中性粒细胞组几乎没有差异。然而，与持续嗜酸性粒细胞<2％+ <50％嗜中性粒细胞组相比，持续嗜酸性粒细胞> 2％+> 50％中性粒细胞组合支气管扩张剂前FEV1％预测值更低（p = 0.049）。
结论：痰中嗜酸性粒细胞持续> 2％且中性粒细胞持续> 50％的受试者表现出更多的肺功能丧失，而痰嗜酸性粒细胞高度可变研究对象的医疗保健利用率更高。
关键词：嗜酸性粒细胞，中性粒细胞，纵向炎症，急性发作，卫生保健利用
Mixed Sputum Granulocyte Longitudinal Impact on Lung Function in the Severe Asthma Research Program
Am J Respir Crit Care Med. 2021 Feb 5. doi: 10.1164/rccm.202009-3713OC.Online ahead of print
Annette T. Hastie PhD, David T. Mauger PhD, Loren C. Denlinger MD PhD, Andrea Coverstone MD, Mario Castro MD, Serpil Erzurum MD, Nizar Jarjour MD, Bruce D. Levy MD6, Deborah A. Meyers PhD, Wendy C. Moore MD, Brenda R. Phillips , Sally E. Wenzel MD, John V. Fahy MD, Elliot Israel M, Eugene R. Bleecker MDnand the NHLBI Severe Asthma Research Program (SARP) 3 Investigators
Abstract
Rationale: Reports indicate longitudinal variability in sputum differential cell counts while others describe stability. Highly variable sputum eosinophil percents are associated with greater lung function loss than persistently elevated eosinophil percents, but elevated neutrophils are linked to more severe asthma.
Objectives: To examine sputum granulocyte stability or variability longitudinally and associations with important clinical characteristics.
Methods: The Severe Asthma Research Program (SARP 3) cohort underwent comprehensive phenotype characterization at baseline and annually over three years. Adult subjects with acceptable sputum were assigned to one of 3 longitudinal sputum groups: Eosinophils predominantly <2%, predominantly >2%, or highly variable (>2SD determined from independent, repeated baseline eosinophil %). Subjects were similarly assigned to 1 of 3 longitudinal neutrophil groups with a 50% cut-point.
Measurements and Main Results: The group with predominantly <2% sputum eosinophils had highest lung function (pre bronchodilator FEV1%predicted, p<0.01 and FEV1/FVC ratio, p<0.001) at baseline and throughout three years compared to other eosinophil groups. Healthcare utilization did not differ although the highly variable eosinophil group reported more asthma exacerbations at year 3. Longitudinal neutrophil groups showed few differences. However, combination of predominantly >2% eosinophil and >50% neutrophil groups resulted in the lowest prebronchodilator FEV1%predicted (p=0.049) compared to predominantly <2% eosinophils +<50% neutrophils.
Conclusions: Subjects with predominantly >2% sputum eosinophils in combination with predominantly >50% neutrophils showed greater loss of lung function, whereas those with highly variable sputum eosinophils had greater healthcare utilization.
Key Words: eosinophils, neutrophils, longitudinal inflammation, exacerbations, healthcare utilization
背景：报告指出痰细胞计数存在纵向变异性，而另一些报告则描述了其存在稳定性。与持续升高的嗜酸性粒细胞百分数相比，痰中嗜酸性粒细胞百分数变异大与肺功能丧失相关，但嗜中性粒细胞升高与更严重的哮喘有关。
目的：纵向探索痰中粒细胞的稳定性或变异性，及其与重要临床特征的关系。
方法：重症哮喘研究计划（SARP 3）队列在基线和三年内每年进行全面的表型特征分析。成功获取痰液的成人研究对象被分为3个纵向痰液组：嗜酸性粒细胞持续<2%，嗜酸性粒细胞持续>2%，或嗜酸性粒细胞持续高度可变>2SD组。受试者同样被分配到3个纵向中性粒细胞组中的1个（50%为界值）。
测量与主要结果：与其它嗜酸性粒细胞组相比，在痰嗜酸性粒细胞持续<2％组在基线和整个三年中肺功能最高（支气管扩张剂前FEV1％，p <0.01，FEV1 / FVC，p <0.001）。尽管高度可变嗜酸性粒细胞组在第3年报告更多的哮喘急性发作，但医疗保健的利用没有差异。纵向中性粒细胞组几乎没有差异。然而，与持续嗜酸性粒细胞<2％+ <50％嗜中性粒细胞组相比，持续嗜酸性粒细胞> 2％+> 50％中性粒细胞组合支气管扩张剂前FEV1％预测值更低（p = 0.049）。
结论：痰中嗜酸性粒细胞持续> 2％且中性粒细胞持续> 50％的受试者表现出更多的肺功能丧失，而痰嗜酸性粒细胞高度可变研究对象的医疗保健利用率更高。
关键词：嗜酸性粒细胞，中性粒细胞，纵向炎症，急性发作，卫生保健利用
(张欣1 张红萍1 王刚2 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（Am J Respir Crit Care Med.2021 Feb 5. doi: 10.1164/rccm.202009-3713OC.Online ahead of print）
（Am J Respir Crit Care Med.2021 Feb 5. doi: 10.1164/rccm.202009-3713OC.Online ahead of print）
Mixed Sputum Granulocyte Longitudinal Impact on Lung Function in the Severe Asthma Research Program
Am J Respir Crit Care Med. 2021 Feb 5. doi: 10.1164/rccm.202009-3713OC.Online ahead of print
Annette T. Hastie PhD, David T. Mauger PhD, Loren C. Denlinger MD PhD, Andrea Coverstone MD, Mario Castro MD, Serpil Erzurum MD, Nizar Jarjour MD, Bruce D. Levy MD6, Deborah A. Meyers PhD, Wendy C. Moore MD, Brenda R. Phillips , Sally E. Wenzel MD, John V. Fahy MD, Elliot Israel M, Eugene R. Bleecker MDnand the NHLBI Severe Asthma Research Program (SARP) 3 Investigators
Abstract
Rationale: Reports indicate longitudinal variability in sputum differential cell counts while others describe stability. Highly variable sputum eosinophil percents are associated with greater lung function loss than persistently elevated eosinophil percents, but elevated neutrophils are linked to more severe asthma.
Objectives: To examine sputum granulocyte stability or variability longitudinally and associations with important clinical characteristics.
Methods: The Severe Asthma Research Program (SARP 3) cohort underwent comprehensive phenotype characterization at baseline and annually over three years. Adult subjects with acceptable sputum were assigned to one of 3 longitudinal sputum groups: Eosinophils predominantly <2%, predominantly >2%, or highly variable (>2SD determined from independent, repeated baseline eosinophil %). Subjects were similarly assigned to 1 of 3 longitudinal neutrophil groups with a 50% cut-point.
Measurements and Main Results: The group with predominantly <2% sputum eosinophils had highest lung function (pre bronchodilator FEV1%predicted, p<0.01 and FEV1/FVC ratio, p<0.001) at baseline and throughout three years compared to other eosinophil groups. Healthcare utilization did not differ although the highly variable eosinophil group reported more asthma exacerbations at year 3. Longitudinal neutrophil groups showed few differences. However, combination of predominantly >2% eosinophil and >50% neutrophil groups resulted in the lowest prebronchodilator FEV1%predicted (p=0.049) compared to predominantly <2% eosinophils +<50% neutrophils.
Conclusions: Subjects with predominantly >2% sputum eosinophils in combination with predominantly >50% neutrophils showed greater loss of lung function, whereas those with highly variable sputum eosinophils had greater healthcare utilization.
Key Words: eosinophils, neutrophils, longitudinal inflammation, exacerbations, healthcare utilization
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肺泡巨噬细胞清除凋亡细胞可防止屋尘螨诱导的哮喘性肺炎症的发生
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成人中-重度哮喘对肠外糖皮质激素的应答及肺功能纵向变化曲线
