痰炎症表型对哮喘小气道功能障碍和疾病转归的纵向影响
2022/03/17
摘要
背景：关于气道炎症表型与一些重要哮喘特征（如小气道功能障碍（SAD））之间的关系知之甚少。
目的：描述气道炎症表型对SAD和哮喘预后的纵向影响。
方法：我们在基线和一年后测量诱导痰中的嗜酸性粒细胞和中性粒细胞计数，将197例成人哮喘患者分为四种炎症表型。我们使用肺活量测定法、体容量描记法、脉冲振荡法、惰性气体单次和多次呼气冲洗法对肺功能进行了全面评估。我们比较了两种表型之间的肺功能、哮喘严重程度、恶化频率和症状控制。我们研究了持续性痰液炎症表型的纵向影响以及痰液细胞计数的变化对肺功能的影响。
结果：患者分为嗜酸性粒细胞型（23%，n=45）、中性粒细胞型（33%，n=62）、混合细胞型（22%，n=43）和寡细胞型（24%，n=47）表型。嗜酸性粒细胞型和混合细胞型哮喘患者的气流阻塞率和严重恶化率高于寡细胞型哮喘患者，且症状控制较差。嗜酸性粒细胞型和混合细胞型哮喘患者的所有SAD指标均较寡细胞型哮喘患者差（所有p值均<0.05）。与中性粒细胞型哮喘相比，嗜酸性哮喘还表现出更严重的远端气流阻塞、增加的通气不均匀性（所有p值均<0.05），以及更高的严重恶化趋势（p=0.07）。纵向而言，与持续性中性粒细胞型、持续性寡细胞型或非持续性哮喘表型相比，持续性混合细胞型哮喘与最差的SAD随访指标相关。在FEV1稳定的患者中，持续性混合细胞型患者的小气道阻力（R5-20）平均增加率（+103%）高于持续性中性粒细胞型患者（+26%），p=0.040，或持续性寡细胞型哮喘患者（-41%），p=0.028。经吸入或口服皮质类固醇或抗嗜酸性生物制剂治疗等混杂因素校正后的多变量模型表明，痰嗜酸性粒细胞而非中性粒细胞计数的变化是FEV1、FEF25-75、SREF、RV和LCI纵向变化的独立预测因子。
结论：在哮喘中，气道嗜酸性炎症是肺功能损害和不良疾病转归的主要驱动因素，气道嗜中性粒细胞的共存也可能加剧这种情况，从而导致严重的混合型哮喘。即使在FEV1稳定的患者中，持续气道嗜酸性粒细胞增多也可能与动态SAD相关。
Longitudinal Impact of Sputum Inflammatory Phenotypes on Small Airway Dysfunction and Disease Outcomes in Asthma
Mustafa Abdo, Frauke Pedersen, Anne-Marie Kirsten, Vera Veith, Heike Biller, Frederik Trinkmann, Erika von Mutius, Matthias Kopp, Gesine Hansen, Klaus F Rabe, Thomas Bahmer, Henrik Watz, ALLIANCE study group
Abstract
Background: Little is known about the relationship between airway inflammatory phenotypes and some important asthma features such as small airway dysfunction (SAD).
Objective: To describe the longitudinal impact of airway inflammatory phenotypes on SAD and asthma outcomes
METHODS: We measured eosinophil and neutrophil counts in induced sputum at baseline and one year later to stratify 197 adult asthma patients into four inflammatory phenotypes. We conducted a comprehensive assessment of lung function using spirometry, body plethysmography, impulse oscillometry, inert gas single and multiple breath washouts. We compared lung function, asthma severity, exacerbation frequency and symptom control between the phenotypes. We studied the longitudinal impact of persistent sputum inflammatory phenotypes and the change of sputum cell counts on lung function.
Results: Patients were stratified into eosinophilic (23%, n=45), neutrophilic (33%, n=62), mixed granulocytic (22%, n=43), and paucigranulocytic (24%, n=47) phenotypes. Eosinophilic and mixed granulocytic asthma patients had higher rates of airflow obstruction and severe exacerbation as well as poorer symptom control than paucigranulocytic asthma patients. All SAD measures were worse in eosinophilic and mixed than in paucigranulocytic asthma patients (all p-values <0.05). Eosinophilic asthma also indicated worse distal airflow obstruction, increased ventilation inhomogeneity (all p-values <0.05), and higher tendency for severe exacerbation (p= 0.07) than neutrophilic asthma. Longitudinally, persistent mixed granulocytic asthma was associated with the worst follow-up measures of SAD compared to persistent neutrophilic, persistent paucigranulocytic or non-persistent asthma phenotypes. In patients with stable FEV1, the mean increase in small airway resistance (R5-20) was greater in persistent mixed granulocytic patients (+103%) than in patients with persistent neutrophilic (+26%), p=0.040, or persistent paucigranulocytic asthma (-41%), p=0.028. Multivariate models adjusted for confounders and treatment with inhaled or oral corticosteroids or anti-eosinophilic biologics indicated that the change of sputum eosinophil rather than neutrophil counts is an independent predictor for the longitudinal change in FEV1, FEF25-75, sReff, RV and LCI.
Conclusion: In asthma, airway eosinophilic inflammation is the main driver of lung function impairment and poor disease outcomes, which might also be aggravated by the coexistence of airway neutrophilia to confer a severe mixed asthma phenotype. Persistent airway eosinophilia might be associated with dynamic SAD even in patients with stable FEV1.
背景：关于气道炎症表型与一些重要哮喘特征（如小气道功能障碍（SAD））之间的关系知之甚少。
目的：描述气道炎症表型对SAD和哮喘预后的纵向影响。
方法：我们在基线和一年后测量诱导痰中的嗜酸性粒细胞和中性粒细胞计数，将197例成人哮喘患者分为四种炎症表型。我们使用肺活量测定法、体容量描记法、脉冲振荡法、惰性气体单次和多次呼气冲洗法对肺功能进行了全面评估。我们比较了两种表型之间的肺功能、哮喘严重程度、恶化频率和症状控制。我们研究了持续性痰液炎症表型的纵向影响以及痰液细胞计数的变化对肺功能的影响。
结果：患者分为嗜酸性粒细胞型（23%，n=45）、中性粒细胞型（33%，n=62）、混合细胞型（22%，n=43）和寡细胞型（24%，n=47）表型。嗜酸性粒细胞型和混合细胞型哮喘患者的气流阻塞率和严重恶化率高于寡细胞型哮喘患者，且症状控制较差。嗜酸性粒细胞型和混合细胞型哮喘患者的所有SAD指标均较寡细胞型哮喘患者差（所有p值均<0.05）。与中性粒细胞型哮喘相比，嗜酸性哮喘还表现出更严重的远端气流阻塞、增加的通气不均匀性（所有p值均<0.05），以及更高的严重恶化趋势（p=0.07）。纵向而言，与持续性中性粒细胞型、持续性寡细胞型或非持续性哮喘表型相比，持续性混合细胞型哮喘与最差的SAD随访指标相关。在FEV1稳定的患者中，持续性混合细胞型患者的小气道阻力（R5-20）平均增加率（+103%）高于持续性中性粒细胞型患者（+26%），p=0.040，或持续性寡细胞型哮喘患者（-41%），p=0.028。经吸入或口服皮质类固醇或抗嗜酸性生物制剂治疗等混杂因素校正后的多变量模型表明，痰嗜酸性粒细胞而非中性粒细胞计数的变化是FEV1、FEF25-75、SREF、RV和LCI纵向变化的独立预测因子。
结论：在哮喘中，气道嗜酸性炎症是肺功能损害和不良疾病转归的主要驱动因素，气道嗜中性粒细胞的共存也可能加剧这种情况，从而导致严重的混合型哮喘。即使在FEV1稳定的患者中，持续气道嗜酸性粒细胞增多也可能与动态SAD相关。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(J Allergy Clin Immunol Pract. 2022 Mar 4;S2213-2198(22)00221-5. doi: 10.1016/j.jaip.2022.02.020.)
(J Allergy Clin Immunol Pract. 2022 Mar 4;S2213-2198(22)00221-5. doi: 10.1016/j.jaip.2022.02.020.)
Longitudinal Impact of Sputum Inflammatory Phenotypes on Small Airway Dysfunction and Disease Outcomes in Asthma
Mustafa Abdo, Frauke Pedersen, Anne-Marie Kirsten, Vera Veith, Heike Biller, Frederik Trinkmann, Erika von Mutius, Matthias Kopp, Gesine Hansen, Klaus F Rabe, Thomas Bahmer, Henrik Watz, ALLIANCE study group
Abstract
Background: Little is known about the relationship between airway inflammatory phenotypes and some important asthma features such as small airway dysfunction (SAD).
Objective: To describe the longitudinal impact of airway inflammatory phenotypes on SAD and asthma outcomes
METHODS: We measured eosinophil and neutrophil counts in induced sputum at baseline and one year later to stratify 197 adult asthma patients into four inflammatory phenotypes. We conducted a comprehensive assessment of lung function using spirometry, body plethysmography, impulse oscillometry, inert gas single and multiple breath washouts. We compared lung function, asthma severity, exacerbation frequency and symptom control between the phenotypes. We studied the longitudinal impact of persistent sputum inflammatory phenotypes and the change of sputum cell counts on lung function.
Results: Patients were stratified into eosinophilic (23%, n=45), neutrophilic (33%, n=62), mixed granulocytic (22%, n=43), and paucigranulocytic (24%, n=47) phenotypes. Eosinophilic and mixed granulocytic asthma patients had higher rates of airflow obstruction and severe exacerbation as well as poorer symptom control than paucigranulocytic asthma patients. All SAD measures were worse in eosinophilic and mixed than in paucigranulocytic asthma patients (all p-values <0.05). Eosinophilic asthma also indicated worse distal airflow obstruction, increased ventilation inhomogeneity (all p-values <0.05), and higher tendency for severe exacerbation (p= 0.07) than neutrophilic asthma. Longitudinally, persistent mixed granulocytic asthma was associated with the worst follow-up measures of SAD compared to persistent neutrophilic, persistent paucigranulocytic or non-persistent asthma phenotypes. In patients with stable FEV1, the mean increase in small airway resistance (R5-20) was greater in persistent mixed granulocytic patients (+103%) than in patients with persistent neutrophilic (+26%), p=0.040, or persistent paucigranulocytic asthma (-41%), p=0.028. Multivariate models adjusted for confounders and treatment with inhaled or oral corticosteroids or anti-eosinophilic biologics indicated that the change of sputum eosinophil rather than neutrophil counts is an independent predictor for the longitudinal change in FEV1, FEF25-75, sReff, RV and LCI.
Conclusion: In asthma, airway eosinophilic inflammation is the main driver of lung function impairment and poor disease outcomes, which might also be aggravated by the coexistence of airway neutrophilia to confer a severe mixed asthma phenotype. Persistent airway eosinophilia might be associated with dynamic SAD even in patients with stable FEV1.
上一篇：
小气道功能障碍在哮喘控制和恶化中的作用：一项使用亚特兰蒂斯研究数据的纵向观察分析
下一篇：
刺激诱发性职业性哮喘的临床特点
