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Volume 47 Issue 4
May  2022
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Article Navigation >  Journal of Bengbu Medical College  > 2022,  47 > 4: (504-507)  

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Analysis of the diagnostic efficacy of eosinophil percentage and interferon-γ in bronchiectasis with asthma

  • Department of Respiratory Medicine, Xingtai Third Hospital, Xingtai Hebei 054000, China

  • Corresponding author: LI Ai-jun, 972187874@qq.com
  • Received Date: 2020-06-13
    Accepted Date: 2020-11-04
  • ObjectiveTo investigate the diagnostic value of eosinophil percentage(EOS%) and interferon-γ(IFN-γ) in bronchiectasis with asthma.MethodsA total of 165 patients with asthma or bronchiectasis were selected, including 48 patients with bronchiectasis combined with asthma in group A, 60 patients with asthma alone in group B, and 57 patients with bronchiectasis alone in group C.The clinical data of patients were collected, WBC, CRP, PCT, PO2, pCO2, EOS% and IFN-γ levels were measured and analyzed.Logistic regression was used to fit the IFN-γ and EOS% joint diagnosis model and draw the ROC curve to evaluate the diagnostic value.The area under the ROC curve was compared by Hanley-McNeil method.ResultsEOS% in group A and group B was significantly higher than that in group C(P < 0.01), and there was no significant difference in EOS% between group A and group B(P>0.05).IFN-γ in group A was significantly lower than that in group B and group C(P < 0.01).The sensitivity of EOS% in the diagnosis of bronchiectasis with asthma was 0.684, the specificity was 0.621;the sensitivity of IFN-γ in the diagnosis of bronchiectasis with asthma was 0.614, the specificity was 0.661.The sensitivity and specificity of IFN-γ combined with EOS% in the diagnosis of bronchiectasis with asthma were 0.754 and 0.601, respectively.ConclusionsThe sensitivity and specificity of EOS% combined with IFN-γ in the diagnosis of bronchiectasis combined with asthma are high, which has high diagnosis value.
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  • [1] TIOTIU A, MARTINET Y, JANKOWSKI R, et al. Gamma globulin replacement therapy in uncontrolled, severe asthma associated with humoral immunodeficiency: a series of five case reports[J]. J Asthma, 2019, 56(1): 79. doi: 10.1080/02770903.2018.1426768
    [2] PAINE NJ, JOSEPH MF, BACON SL, et al. Association between depression, lung function, and inflammatory markers in patients with asthma and occupational asthma[J]. J Occup Environ Med, 2019, 61(6): 453. doi: 10.1097/JOM.0000000000001562
    [3] NEOPHYTOU AM, OH SS, WHITE MJ, et al. Secondhand smoke exposure and asthma outcomes among African-American and Latino children with asthma[J]. Thorax, 2018, 73(11): 1041. doi: 10.1136/thoraxjnl-2017-211383
    [4] GAI XY, ZHANG LJ, CHANG C, et al. Metabolomic analysis of serum glycerophospholipid levels in eosinophilic and neutrophilic asthma[J]. Biomed Environ Sci, 2019, 32(2): 96.
    [5] MAGLIONE M, AKSAMIT T, SANTAMARIA F. Paediatric and adult bronchiectasis: Specific management with coexisting asthma, COPD, rheumatological disease and inflammatory bowel disease[J]. Respirology, 2019, 24(11): 143.
    [6] KIM DH, SOHN JH, PARK HJ, et al. CpG Oligodeoxynucleotide inhibits cockroach-induced asthma via induction of IFN-γ+ Th1 Cells or Foxp3 Regulatory T Cells in the lung[J]. Allergy Asthma Immunol Res, 2016, 8(3): 264. doi: 10.4168/aair.2016.8.3.264
    [7] 赵转华, 聂秀红. 支气管哮喘、慢性阻塞性肺疾病及哮喘-慢性阻塞性肺疾病重叠患者的气道阻力比较[J]. 国际呼吸杂志, 2018, 38(5): 321. doi: 10.3760/cma.j.issn.1673-436X.2018.05.001
    [8] 王丹, 杨丹, 王小虎, 等. 支气管哮喘发病中的固有免疫机制[J]. 中华结核和呼吸杂志, 2018, 41(3): 228. doi: 10.3760/cma.j.issn.1001-0939.2018.03.016
    [9] DUPIN C, MARCHAND-ADAM S, FAVELLE O, et al. Asthma and hypogammaglobulinemia: an asthma phenotype with low type 2 inflammation[J]. J Clin Immunol, 2016, 36(8): 1.
    [10] MUÑOZ G, DE GRACIA J, BUXÓ M, et al. Long-term benefits of airway clearance in bronchiectasis: a randomised placebo-controlled trial[J]. Eur Respir J, 2018, 51(1): 1701926. doi: 10.1183/13993003.01926-2017
    [11] 雒志明, 高赏, 任魁, 等. 支气管哮喘控制测试评分与外周血嗜酸性粒细胞计数的相关性研究[J]. 中国病案, 2018, 19(1): 91. doi: 10.3969/j.issn.1672-2566.2018.01.032
    [12] BORTNICK A, CHERNOVA I, SPENCER SP, et al. No strict requirement for eosinophils for bone marrow plasma cell survival[J]. Eur J Immunol, 2018, 48(5): 815. doi: 10.1002/eji.201747229
    [13] HU B, FENG X, WANG L, et al. 5-BDBD ameliorates an OVA-induced allergic asthma by the reduction of Th2 cytokines production[J]. Iran J Basic Med Sci, 2018, 21(4): 364.
    [14] 张海宁, 张晴, 张辉, 等. 支气管扩张症合并哮喘患者中IL-4和IFN-γ的表达水平及临床意义[J]. 临床肺科杂志, 2017, 22(3)573. doi: 10.3969/j.issn.1009-6663.2017.03.053
    [15] 豆雪芹, 刘冬, 许西琳, 等. FeNO和外周血EOS%对支气管扩张合并哮喘的诊断价值[J]. 现代临床医学, 2018, 44(3): 183.
    [16] 涂智毅, 苏国秋, 郭晓珍, 等. 单纯支气哮喘和支气管哮喘合并支气管扩张症患者呼出气一氧化氮水平的差异比较[J]. 中国医药科学, 2019, 9(11): 26. doi: 10.3969/j.issn.2095-0616.2019.11.008
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Analysis of the diagnostic efficacy of eosinophil percentage and interferon-γ in bronchiectasis with asthma

    Corresponding author: LI Ai-jun, 972187874@qq.com
  • Department of Respiratory Medicine, Xingtai Third Hospital, Xingtai Hebei 054000, China
  • Received Date: 2020-06-13
  • Accepted Date: 2020-11-04
  • Available Online: 2022-04-15

Abstract: ObjectiveTo investigate the diagnostic value of eosinophil percentage(EOS%) and interferon-γ(IFN-γ) in bronchiectasis with asthma.MethodsA total of 165 patients with asthma or bronchiectasis were selected, including 48 patients with bronchiectasis combined with asthma in group A, 60 patients with asthma alone in group B, and 57 patients with bronchiectasis alone in group C.The clinical data of patients were collected, WBC, CRP, PCT, PO2, pCO2, EOS% and IFN-γ levels were measured and analyzed.Logistic regression was used to fit the IFN-γ and EOS% joint diagnosis model and draw the ROC curve to evaluate the diagnostic value.The area under the ROC curve was compared by Hanley-McNeil method.ResultsEOS% in group A and group B was significantly higher than that in group C(P < 0.01), and there was no significant difference in EOS% between group A and group B(P>0.05).IFN-γ in group A was significantly lower than that in group B and group C(P < 0.01).The sensitivity of EOS% in the diagnosis of bronchiectasis with asthma was 0.684, the specificity was 0.621;the sensitivity of IFN-γ in the diagnosis of bronchiectasis with asthma was 0.614, the specificity was 0.661.The sensitivity and specificity of IFN-γ combined with EOS% in the diagnosis of bronchiectasis with asthma were 0.754 and 0.601, respectively.ConclusionsThe sensitivity and specificity of EOS% combined with IFN-γ in the diagnosis of bronchiectasis combined with asthma are high, which has high diagnosis value.

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  • 支气管扩张合并支气管哮喘是呼吸系统疾病中一种比较特殊的慢性气道炎症，不仅仅可以表现为支气管扩张的慢性咳嗽、咳痰、咯血的临床表现，还可以表现为哮喘的症状，容易出现漏诊，可能是因为病人炎症反应较重时咳嗽、咳痰症状较明显而哮喘症状不典型，易出现哮喘的漏诊，当病人出现哮喘急性发作时若同时伴有咳嗽、咳痰，往往被认为合并感染，易出现支气管扩张的漏诊[1-2]。气管扩张并哮喘发病机制目前尚未完全明确，两种疾病临床表现复杂，症状较单纯的支气管扩张或支气管哮喘重，治疗难度大，住院时间长，而早期诊断尤为重要[3]。嗜酸性粒细胞(EOS)被认为是引起支气管哮喘黏膜损伤的重要炎症细胞，在哮喘病人疾病进展中起着重要作用，哮喘与EOS浸润气道上皮及气道的高反应性所致的气道重塑有关[4-5]。干扰素-γ(IFN-γ)是主要由T细胞分泌的细胞因子，具有抑制炎症因子释放、减轻气道过敏性炎症的作用[6]。本研究旨在探讨外周血EOS百分比(EOS%)、IFN-γ对支气管扩张合并支气管哮喘的诊断价值。现作报道。

1.   资料与方法

    1.1.   一般资料

  • 收集2017年3月至2019年10月于我院就诊的支气管哮喘或者支气管扩张病人共165例，其中支气管扩张合并哮喘为A组48例，单纯哮喘为B组60例，单纯支气管扩张为C组57例。本研究经我院伦理委员会批准，病人同意签署知情同意书。

    • 1.2.   纳入与排除标准

  • 纳入标准：符合支气管哮喘或者支气管扩张的诊断。根据《成人支气管扩张专家共识(2012年)》，胸部高分辨率CT符合以下之一者为支气管扩张，(1)邻近肺段的支气管直径与扩张的支气管直径之比 < 1；(2)胸膜下1 cm范围内有支气管影；(3)某段的支气管远端大于支气管近端；(4)伴行动脉管径与支气管扩张直径之比>1。哮喘的诊断参照《哮喘防治指南(2016年版)》，符合以下症状和体征，同时符合气流受限客观检查的一种: (1)反复发作的喘息、气急，伴或不伴胸闷、咳嗽，常与接触变应原、冷空气、刺激性物质有关；(2)发作时双肺闻及散在哮鸣音，呼气音延长；(3)上诉症状和体征可自行缓解；(4)气流受限客观检查有支气管舒张试验阳性、支气管激发试验阳性、呼气流量峰值平均每日变异率>10%或者周平均变异率>20%。支气管哮喘合并支气管扩张需同时满足支气管扩张和哮喘的诊断。能配合肺功能检测，并签署知情同意书。

    排除标准：(1)1周内有饮酒、剧烈活动或使用支气管扩张剂；(2)有呼吸道感染病史或合并其他部位感染；(3)近期使用全身或吸入糖皮质激素；(4)合并其他心肺疾病，如慢性阻塞性肺病、慢性肺源性心脏病、重叠综合征、冠心病、心肌病等；(5)伴严重心、血液、肿瘤、免疫系统疾病及寄生虫等疾病。

    • 1.3.   研究方法与观察指标

  • 抽取病人外周静脉血5 mL，用iChem-540型全自动生化分析仪(库贝尔医疗器械有限公司)检测病人血清嗜酸性粒细胞百分比(EOS%)水平、白细胞(WBC)水平。采用酶联免疫吸附试验检测IFN-γ、C反应蛋白(CRP)、降钙素原(PCT)表达水平，试剂盒由上海丰寿公司提供。采用自动血气分析仪检测血液氧分压(PO2)、二氧化碳分压(PCO2)水平，仪器由上海涵飞医疗器械公司提供。

    • 1.4.   统计学方法

  • 采用方差分析、χ2检验和logistic回归分析，并绘制ROC曲线评估诊断价值。

2.   结果

    2.1.   3组病人临床资料比较

  • 3组病人性别、年龄、体质量指数(BMI)、WBC差异均无统计学意义(P>0.05)，A组、B组病人EOS%明显高于C组，A组病人IFN-γ明显低于B组、C组(P < 0.01)(见表 1)。

    分组 n 男 女 年龄/岁 病程/月 BMI/(kg/m2) PO2/mmHg PCO2/mmHg WBC/(×109) CRP/(mg/L) PCT/(ng/mL) EOS% IFN-γ/(ng/L)
    A组 48 21 27 64.25±4.15 24.29±2.79 20.88±3.31 58.33±0.97 51.68±0.94 14.78±2.16 48.45±4.47 10.67±1.05 5.36±0.78 19.82±5.14
    B组 60 26 34 63.07±5.42 21.03±2.77 21.03±2.77 59.05±0.68 52.13±0.79 13.90±2.89 49.16±5.78 9.77±1.57 5.27±0.54 24.82±4.79**
    C组 57 27 30 64.18±5.32 23.97±2.50 20.95±2.25 58.90±0.69 51.80±0.58 14.68±1.98 50.78±4.14 10.56±2.21 1.17±0.52**## 29.57±3.15**##
    F — 0.23△ 0.98 25.39 0.04 12.30 5.03 2.29 3.21 4.69 850.22 63.76
    P — >0.05 >0.05 < 0.01 >0.05 < 0.01 < 0.01 >0.05 < 0.05 < 0.05 < 0.01 < 0.01
    MS组内 — — 25.470 7.213 7.723 0.606 0.600 5.751 23.889 2.906 0.376 19.451
    t检验：与A组比较**P < 0.01;与B组比较##P < 0.01。△示χ2值

    • 2.2.   EOS%、IFN-γ诊断支气管扩张合并哮喘的ROC曲线

  • 以支气管合并哮喘为自变量(是赋值为1，否赋值为0)，IFN-γ、EOS%为因变量进行logistic回归分析，得到回归方程为Logit(P) =1.782+0.223 EOS% + 0.456 IFN-γ，模型中概率值变量pre-1 = 1/[1+exp(-Logit(P)]。并根据logistic回归模型中的概率值pre-1拟合联合ROC曲线绘制ROC曲线，结果显示EOS%诊断支气管扩张合并哮喘ROC曲线下面积(AUC)为0.633，95%CI：0.566~0.700，截断值为4.35%，敏感性为0.684，特异性为0.621；IFN-γ诊断支气管扩张合并哮喘截断值为33.56 ng/L，AUC为0.603，95%CI：0.533~0.672，敏感性为0.614，特异性为0.661；联合诊断AUC: 0.744, 敏感性为0.754，95%CI：0.681~0.807，特异性为0.601(见表 2)。

    检验变量 敏感性 特异性 阳性预测值 阴性预测值 约登指数 AUC 95%CI
    IFN-γ 0.614(30/48) 0.661(78/117) 0.435(30/69) 0.813(78/96) 0.275 0.603 0.533~0.672
    EOS% 0.684(33/48) 0.621(73/117) 0.429(33/77) 0.830(73/88) 0.305 0.633 0.566~0.700
    联合诊断 0.754(37/48) 0.601(70/117) 0.440(37/84) 0.864(70/81) 0.355 0.744 0.681~0.807
3.   讨论

  • 哮喘是由肥大细胞、EOS、上皮细胞等多种炎症细胞和炎症因子共同参与的气道表态反应性疾病，支气管扩张是气道器质性病变而导致的气道慢性炎症反应[7-8]。支气管扩张和哮喘在临床上症状相似，尤其是合并感染时难以互相鉴别，支气管扩张合并支气管哮喘的可能原因为扩张的支气管结构破坏，易滋生细菌和病毒并导致反复感染，久而久之会导致气道稳定性降低，气道分泌物无法排除等，从而导致咳嗽、咳痰、喘息等症状，从而导致哮喘[9-10]。目前指南主张以激素抗炎和抗生素抗感染治疗为主，辅以排痰、吸氧、化痰等治疗，但治疗效果较差，而早期诊断能明显提高治疗效果，因此，探索支气管扩张合并支气管哮喘的诊断方式对于预后有重要意义。

    EOS是WBC中的一种，主要反映过敏反应及免疫反应，在过敏、寄生虫感染、皮肤感染等病人体内明显增高，EOS在支气管哮喘疾病的发生和进展中发挥重要作用，研究发现，哮喘病人支气管内有大量EOS浸润，EOS可分泌IL-3、IL-5多种细胞因子，而IL-3、IL-5等细胞因子也可诱导EOS分化，进一步加重气道炎症，目前临床指南推荐将EOS作为抗炎治疗的靶点[11-12]。进一步深入研究发现，CD4细胞同时参与支气管扩张和哮喘疾病的发生和发展，因此推测两者之间有一定的联系。哮喘发病机制之一为Th1、Th2细胞的失调，而IFN-γ是促进Th0向Th1细胞转化的关键因子，可反映Th1细胞数量和功能状态，可通过检测IFN-γ的表达量反映哮喘的严重程度[13]。张海宁等[14]研究发现支气管扩张合并哮喘病人体内IFN-γ表达量明显低于单纯哮喘和支气管扩张病人，对于支气管扩张合并哮喘的辅助检查有重要价值。本研究结果显示3组病人性别、年龄、BMI、WBC差异无统计学意义(P>0.05)，A组、B组病人EOS%明显大于C组，A组病人IFN-γ明显小于B组、C组(P < 0.01)。表明支气管扩张合并哮喘和哮喘病人EOS%明显高于单纯支气管扩张病人，支气管扩张合并哮喘病人IFN-γ明显低于单纯支气管扩张和哮喘。豆雪芹等[15]研究发现支气管扩张合并哮喘病人EOS%明显增高，更易表现为个人过敏史，对支气管扩张合并哮喘的辅助诊断有重要参考价值。涂智毅等[16]研究发现支气管扩张合并哮喘病人IFN-γ高于单纯哮喘病人，但相关性分析未发现明显差异，尚需进一步临床探讨。

    logistic回归分析结果显示IFN-γ、EOS%是支气管扩张合并哮喘的危险因素。EOS%、IFN-γ诊断支气管扩张合并哮喘的敏感性分别为0.684、0.614，特异性为0.621、0.661；联合诊断AUC: 0.744, 敏感性为0.754，特异性为0.601。表明EOS%、IFN-γ是支气管扩张合并哮喘的危险因素，并且ROC曲线显示EOS%、IFN-γ单独诊断支气管扩张合并哮喘的特异性较低，易造成临床误诊，而敏感性低则会导致临床漏诊率高，诊断价值较低。而EOS%、IFN-γ联合诊断支气管扩张合并哮喘的敏感性明显提高，可以减少单纯支气管扩张合并哮喘的临床漏诊，提高诊断价值，相比于传统的高分辨率CT和肺功能等检查方法，具有便捷、快速和价格低廉的优点，尤其适用于卧床不宜行相关检查的重症病人，且AUC较高，预测准确性较高，具有更高的临床价值。

    综上，支气管扩张合并哮喘和哮喘病人EOS%明显高于单纯支气管扩张，支气管扩张合并哮喘病人IFN-γ明显低于单纯支气管扩张和哮喘，且EOS%、IFN-γ联合诊断支气管扩张合并哮喘的敏感性和特异性均较高。

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