成年重症哮喘患者气道表面活性蛋白D缺乏
2016/08/08
摘要
背景：表面活性蛋白D（SP-D）是气道中固有免疫防御抵御病原体必不可少的成分。SP-D也可调节过敏性炎症和促进凋亡细胞的移除。SP-D失调异常可见于多种肺部疾病。本研究旨在探索是否难治性重症哮喘患者气道和血清SP-D水平有所改变。
方法：从10例健康对照和50例哮喘患者（22例轻症哮喘，28例重症哮喘）中收集了匹配的血清和肺泡灌洗液标本并测定SP-D浓度。应用蛋白印迹技术分析这些样本的SP-D量的变化。
结果:重症哮喘患者肺泡灌洗液标本中SP-D的水平显著低于对照组和轻症哮喘患者SP-D (P < .001)，并且重症哮喘患者肺泡灌洗液中SP-D水平与肺泡灌洗液中嗜酸性粒细胞阳离子蛋白浓度呈负相关关系。与健康对照及轻症哮喘相比，重症哮喘患者血清SP-D明显升高(P < .001)，且肺泡灌洗液/血清比值显著降低。重症哮喘患者肺泡灌洗液SP-D水平降低，伴随血清SP-D水平增加，与血清中 SP-D降解片段、中性粒细胞计数和脂多糖增加有关。
结论：这些结果提示重症哮喘患者气道内固有免疫缺陷，这个缺陷表现为的肺泡灌洗液SP-D浓度降低及伴随气道中性粒细胞增多的改变的细菌表现。此外，重症哮喘患者肺泡灌洗液中SP-D漏入血清可能提供了一个外周血生物标志物，这个生物标志物反应上皮损伤加重和/或周围气道中上皮的通透性增强。
Airway Surfactant Protein D Deficiency in Adults With Severe Asthma
Rose-Marie A. Mackay, PhD; Christopher L. Grainge, MD, PhD; Laurie C. Lau, PhD; Clair Barber, BSc;
Howard W. Clark, MD, DPhil; and Peter H. Howarth, MD, DM
Chest. 2016 May;149(5):1165-72.
Abstract
BACKGROUND: Surfactant protein D (SP-D) is an essential component of the innate immune defense against pathogens within the airways. SP-D also regulates allergic inflammation and promotes the removal of apoptotic cells. SP-D dysregulation is evident in several pulmonary diseases. Our aim was to investigate whether airway and serum levels of SP-D are altered in treatment-resistant severe asthma.
METHODS: SP-D concentrations were measured in matched serum and BAL samples collected from 10 healthy control subjects (HC) and 50 patients with asthma (22 with mild asthma [MA] and 28 with severe asthma [SA]). These samples were also evaluated by using Western blot analysis to investigate variations in SP-D size.
RESULTS: SP-D levels in BAL samples were significantly lower in SA compared with HC and MA (P < .001) and inversely correlated with BAL eosinophil cationic protein concentrations in SA (P < .01). Serum SP-D was significantly increased in SA compared with HC and MA (P < .001), and BAL/serum ratios were significantly lower in SA compared with HC and MA (P < .001). Reduced SP-D levels in BAL samples, with concomitant increases in serum in SA, were associated with degraded fragments of SP-D in the serum and increased BAL neutrophil counts and lipopolysaccharide levels.
CONCLUSIONS: These findings suggest defective innate immunity within the airways in SA, as reflected by low BAL SP-D concentrations and altered bacterial presence with airway neutrophilia. Furthermore, BAL SP-D leakage into the serum in patients with SA may provide a peripheral blood biomarker, reflecting increased epithelial damage and/or epithelial permeability within the peripheral airways.
背景：表面活性蛋白D（SP-D）是气道中固有免疫防御抵御病原体必不可少的成分。SP-D也可调节过敏性炎症和促进凋亡细胞的移除。SP-D失调异常可见于多种肺部疾病。本研究旨在探索是否难治性重症哮喘患者气道和血清SP-D水平有所改变。
方法：从10例健康对照和50例哮喘患者（22例轻症哮喘，28例重症哮喘）中收集了匹配的血清和肺泡灌洗液标本并测定SP-D浓度。应用蛋白印迹技术分析这些样本的SP-D量的变化。
结果:重症哮喘患者肺泡灌洗液标本中SP-D的水平显著低于对照组和轻症哮喘患者SP-D (P < .001)，并且重症哮喘患者肺泡灌洗液中SP-D水平与肺泡灌洗液中嗜酸性粒细胞阳离子蛋白浓度呈负相关关系。与健康对照及轻症哮喘相比，重症哮喘患者血清SP-D明显升高(P < .001)，且肺泡灌洗液/血清比值显著降低。重症哮喘患者肺泡灌洗液SP-D水平降低，伴随血清SP-D水平增加，与血清中 SP-D降解片段、中性粒细胞计数和脂多糖增加有关。
结论：这些结果提示重症哮喘患者气道内固有免疫缺陷，这个缺陷表现为的肺泡灌洗液SP-D浓度降低及伴随气道中性粒细胞增多的改变的细菌表现。此外，重症哮喘患者肺泡灌洗液中SP-D漏入血清可能提供了一个外周血生物标志物，这个生物标志物反应上皮损伤加重和/或周围气道中上皮的通透性增强。
(王程仕1 张丽1 张欣1 王刚1 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（Chest. 2016 May;149(5):1165-72.）
（Chest. 2016 May;149(5):1165-72.）
Airway Surfactant Protein D Deficiency in Adults With Severe Asthma
Rose-Marie A. Mackay, PhD; Christopher L. Grainge, MD, PhD; Laurie C. Lau, PhD; Clair Barber, BSc;
Howard W. Clark, MD, DPhil; and Peter H. Howarth, MD, DM
Chest. 2016 May;149(5):1165-72.
Abstract
BACKGROUND: Surfactant protein D (SP-D) is an essential component of the innate immune defense against pathogens within the airways. SP-D also regulates allergic inflammation and promotes the removal of apoptotic cells. SP-D dysregulation is evident in several pulmonary diseases. Our aim was to investigate whether airway and serum levels of SP-D are altered in treatment-resistant severe asthma.
METHODS: SP-D concentrations were measured in matched serum and BAL samples collected from 10 healthy control subjects (HC) and 50 patients with asthma (22 with mild asthma [MA] and 28 with severe asthma [SA]). These samples were also evaluated by using Western blot analysis to investigate variations in SP-D size.
RESULTS: SP-D levels in BAL samples were significantly lower in SA compared with HC and MA (P < .001) and inversely correlated with BAL eosinophil cationic protein concentrations in SA (P < .01). Serum SP-D was significantly increased in SA compared with HC and MA (P < .001), and BAL/serum ratios were significantly lower in SA compared with HC and MA (P < .001). Reduced SP-D levels in BAL samples, with concomitant increases in serum in SA, were associated with degraded fragments of SP-D in the serum and increased BAL neutrophil counts and lipopolysaccharide levels.
CONCLUSIONS: These findings suggest defective innate immunity within the airways in SA, as reflected by low BAL SP-D concentrations and altered bacterial presence with airway neutrophilia. Furthermore, BAL SP-D leakage into the serum in patients with SA may provide a peripheral blood biomarker, reflecting increased epithelial damage and/or epithelial permeability within the peripheral airways.
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慢性阻塞性肺疾病患者、哮喘-慢性阻塞性肺疾病重叠综合征患者和气流受限的哮喘患者之间肺功能的比较
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呼吸道过敏的孩子对抗空气播散的真菌的IgE抗体血清浓度
