诱导痰嗜酸粒细胞与慢性持续期支气管哮喘病情严重程度的关系

目的 观察初诊不同病情严重程度慢性持续期支气管哮喘(简称哮喘)患者的诱导痰嗜酸粒细胞(eosinophil,EOS)比例变化,探讨二者之间的关系,并分析诱导痰EOS比例与肺功能的相关性.方法 收集专科门诊就诊的63例初诊慢性持续期哮喘患者,根据症状分为轻度持续、中度持续、重度持续3组,分别予诱导痰和肺功能检查.观察不同病情严重程度的患者气道炎症状况.对所得数据用SPSS 15.0软件分析,各组间总体分析采用Kruskal-Wallis法,两组间分析采用Mann-Whitney U test法.结果 ①慢性持续期患者诱导痰EOS比例随病情严重程度增加呈增高趋势,重度持续患者诱导痰EOS比例显著高于轻度持续患者(41.8%vs 17.8%,P=0.033),但轻度持续与中度持续、中度持续与重度持续患者之间比较诱导痰EOS比例差异无统计学意义(P>0.05);②诱导痰EOS比例与第1秒用力呼气容积差异无统计学意义(r=-0.111,P>0.05),与第1秒用力呼气容积/用力肺活量(%)差异无统计学意义(r=-0.154,P>0.05).结论 慢性持续期哮喘患者病情严重程度与诱导痰EOS比例有关,但症状不能完全反映气道炎症程度.评价哮喘患者的严重程度时应结合临床症状和气道炎症程度综合考虑.     

诱导痰嗜酸粒细胞与慢性持续期支气管哮喘病情严重程度的关系

目的观察初诊不同病情严重程度慢性持续期支气管哮喘（简称哮喘）患者的诱导痰嗜酸粒细胞（eosinophil,EOS）比例变化,探讨二者之间的关系,并分析诱导痰EOS比例与肺功能的相关性。方法收集专科门诊就诊的63例初诊慢性持续期哮喘患者,根据症状分为轻度持续、中度持续、重度持续3组,分别予诱导痰和肺功能检查。观察不同病情严重程度的患者气道炎症状况。对所得数据用SPSS 15．0软件分析,各组间总体分析采用Kruskal—wallis法,两组间分析采用Mann-Whitney U test法。结果①慢性持续期患者诱导痰EOS比例随病情严重程度增加呈增高趋势,重度持续患者诱导痰EOS比例显著高于轻度持续患者（41．8％vs17．8％,P=0．033）,但轻度持续与中度持续、中度持续与重度持续患者之间比较诱导痰EOS比例差异无统计学意义（P〉0．05）;②诱导痰EOS比例与第1秒用力呼气容积差异无统计学意义（r=-0．111,P〉0．05）,与第1秒用力呼气容积／用力肺活量（％）差异无统计学意义（r=-0．154,P〉0．05）。结论慢性持续期哮喘患者病情严重程度与诱导痰EOS比例有关,但症状不能完全反映气道炎症程度。评价哮喘患者的严重程度时应结合临床症状和气道炎症程度综合考虑。     

诱导痰炎性标志物检测在判定哮喘严重程度和鉴别诊断中的应用

目的探讨哮喘患者诱导痰中嗜酸性粒细胞(Eos)和嗜酸细胞阳离子蛋白(ECP)与其哮喘严重程度的关系及鉴别诊断价值。方法选择武汉大学人民医院2002-07~2004-06的门诊哮喘患者59例,检测其肺功能并分别采用瑞氏染色及荧光免疫法检测高渗盐水诱导痰中Eos数量和ECP质量浓度。选择同期20例慢性阻塞性肺疾病患者和10名健康人作为对照。结果哮喘患者诱导痰中Eos数量与患者第1秒用力呼气容积/用力肺活量(FEV1%)呈显著负相关(r=-0·65,P<0·01);ECP质量浓度与患者FEV1%呈显著负相关(r=-0·59,P<0·01)。随病情加重哮喘患者诱导痰中Eos数量和ECP质量浓度逐渐升高,且轻度、中度和重度患者之间比较差异有统计学意义(P<0·05)。哮喘患者诱导痰中Eos数量和ECP质量浓度显著高于慢性阻塞性肺疾病组和健康组(P<0·01)。结论诱导痰中Eos和ECP质量浓度可了解哮喘的严重程度,并有助于与慢性阻塞性肺疾病的鉴别。     

诱导痰气道炎症指标与支气管哮喘病情关系的探讨

目的 探讨气道炎症指标对支气管哮喘(简称哮喘)患者病情监测及治疗的意义.方法 收集2004年1月至2006年1月在北京大学第三医院呼吸科门诊就诊的近半年来未使用口服或吸入激素治疗的哮喘患者87例.进行哮喘症状评分、肺功能检查、诱导痰上清液检测白介素-8(IL-8)浓度及嗜酸粒细胞阳离子蛋白(ECP)浓度,对所有患者病情分级状况和气道炎症指标进行分析,探讨病情严重程度与气道炎症之间的关系;分析急性发作与气道炎症之间的关系.结果 (1)重度哮喘患者中性粒细胞、IL-8水平较轻中度患者明显增高;(2)急性发作期患者嗜酸性粒细胞(EOS)、ECP较缓解期明显增高;(3)中性粒细胞与第1秒用力呼气量(FEV1)呈负相关(r=-0.522,P＜0.05);中性粒细胞与IL-8呈正相关(r=0.832,P＜0.05);(4)ECP、EOS与FEV1、症状评分均无相关性(r=-0.209,r=-0.189,P均＞0.05;r=-0.289,r=-0.229,P均＞0.05);ECP与EOS呈正相关(r=0.852,P＜0.01);(5)中性粒细胞对重度哮喘的阳性预测值为91%,EOS对哮喘急性发作的阳性预测值为92.5%,ECP对哮喘急性发作的阳性预测值98.5%.结论 (1)中性粒细胞、IL-8与病情严重程度有关,重度哮喘患者中性粒细胞、IL-8明显增高;(2)ECP、EOS与哮喘的急性发作有关,急性发作期哮喘患者ECP、EOS明显增高;(3)气道炎症指标可用于监测哮喘病情和调整哮喘治疗.     

哮喘患者诱导痰中TARC、MDC水平变化及糖皮质激素对其影响

目的探讨胸腺活化调节趋化因子(TARC)及巨噬细胞衍生趋化因子(MDC)在哮喘中的作用及评价哮喘发作严重程度方面的临床价值。方法选择35例慢性持续期哮喘患者(轻中度组20例、重度组15例)及20例健康体检者(对照组),ELISA法检测诱导痰内TARC、MDC水平,痰涂片计数嗜酸性粒细胞百分比(EOS%);测定肺功能,记录1秒钟用力呼气量占预计值的百分比(FEV1%pred),分析TARC、MDC、EOS%、FEV1%pred之间的相关性。结果治疗前轻中度、重度哮喘组诱导痰TARC、MDC水平均高于对照组(P<0.01),重度组TARC水平高于轻中度组(P<0.05);诱导痰TARC水平与MDC、EOS%呈正相关;MDC与EOS%呈正相关,与FEV1%pred呈负相关;轻中度、重度哮喘组治疗后TARC水平较治疗前降低(P<0.05)。结论 TARC的水平可作为哮喘患者临床病情判定和疗效观察的良好指标,吸入糖皮质激素至少部分是通过降低TARC水平减轻气道炎症反应;MDC可能与哮喘气道炎症的慢性持续过程有关。     

支气管哮喘气道炎症可能机制的探讨

目的 探讨支气管哮喘(简称哮喘)患者气道炎症特征及其可能机制,并进一步观察吸入糖皮质激素治疗对气道炎性细胞分类计数、炎症介质等的影响.方法 分别选择轻度(轻度组)、中度(中度组)和重度(重度组)持续哮喘患者15例、14例和19例,正常对照组15名,分别行哮喘症状控制评分、肺功能测定、诱导痰炎性细胞分类计数、调节激活正常T细胞表达和分泌细胞因子(RANTES)、嗜酸粒细胞阳离子蛋白(ECP)、白介素8(IL-8)及髓过氧化物酶(MPO)浓度检测,然后规范吸人糖皮质激素治疗4周,随访复查上述指标.结果 诱导痰NEU%、IL-8及MPO重度组明显升高,分别为(62.40±22.05)%、594.53±85.11、39.25±10.67与轻度组[(47.23±15.12)%、183.63±120.98、12.47±4.15]、中度组[(46.13±19.23)%、352.76±71.72、22.93±7.35]、正常对照组[(31.44±13.31)%、103.26±36.33、10.22±4.13]比较差异均有统计学意义(P＜0.01);RANTES、嗜酸粒细胞百分比(EOS%)和ECP浓度在各哮喘组间比较差异无统计学意义(P＞0.05).EOS%与RANTES、ECP水平呈正相关(r=0.557,P＜0.05;r=0.852,P＜0.01);NEU%与IL-8、MPO水平呈正相关(r=0.732,P＜0.05;r=0.806,P＜0.05);经糖皮质激素治疗后,对轻、中、重度哮喘患者合并进行分析表明,治疗后症状评分由(9.8±5.4)分下降至(4.0±3.5)分和肺功能指标第一秒用力呼气容积占预计值百分比由(62.2±23.3)%升高至(75.9±17.5)%显著改善,差异有统计学意义(P＜0.01).在接受糖皮质激素治疗后,RANTES、EOS%和ECP水平均显著降低.另外MPO水平也显著降低(P＜0.01);但治疗后在重度组仍显著高于轻、中度组(P＜0.01).但IL-8、NEU%治疗后无明显降低(P＞0.05),而且治疗后IL-8、NEU%在重度组仍显著高于轻、中度组(P＜0.01).结论 中性粒细胞增多是重度哮喘的气道炎症特征之一,EOS与病情严重程度无关.EOS哮喘的发生可能与RANTES的趋化、EOS的活化、ECP的释放有关,激素可以抑制EOS气道炎症.而中性粒细胞哮喘的发生可能与IL-8的趋化、NEU的活化、MPO的释放有关.     

慢性阻塞性肺疾病患者诱导痰中α-防御素1—3含量与病情程度的相关性研究

目的探讨慢性阻塞性肺疾病急性加重期（AECOPD）患者治疗前后诱导痰中α-防御素1-3（HNP1—3）含量、中性粒细胞比例（N％）与肺功能及血气分析结果的相关性,以探讨HNP1—3在COPD发病机制中的可能作用。方法收集AECOPD患者42例（根据肺功能检测结果分为轻度组11例、中度组13例、重度组18例）治疗前后及20例急性支气管炎痊愈者（对照组）的诱导痰,分别进行痰中性粒细胞计数并计算其百分比,用ELISA方法检测诱导痰中HNP1—3的含量;测定各观察对象治疗前后的血气分析及肺功能,分析HNP1—3含量与N％、肺功能和血气分析的相关性。结果COPD患者诱导痰中HNP1-3水平、N％、PaCO2随病情严重程度的增加而增高（P〈0．01）,并明显高于对照组（P〈0．01）,FEV,％pred、FEV,／FVC、PaO2随病情严重程度的增加而降低（P〈0．01）,明显低于对照组（P〈0．01）。三组患者诱导痰中HNP1—3含量分别与N％呈显著正相关（r=0．887～0．973,P值均〈0．01）,与FEV,Yoopred、FEV,／FVC、Pa02分别呈显著负相关（r=0．721～0．973,P值均〈0．01）。经治疗一周后,轻度、中度、重度患者FEV,Voopred、FEV1／FVC、PaO2明显增高,诱导痰中HNP1—3含量、N％明显降低。结论HNPl—3参与了COPD炎症的过程,此过程与中性粒细胞有关。痰中HNPl3含量可作为COPD患者病情严重程度的指标,并有助于判断预后。     

晚发型重度难治性哮喘气道炎症表型与激素疗效的临床研究

目的探讨成人晚发型重度难治性哮喘患者的气道炎症类型及对激素治疗的反应,以期阐明该型哮喘的发病机制和治疗策略。方法连续收集正常对照者(A组)、确诊的成人晚发型轻中度(B组)、重度哮喘患者(C组),分别采集哮喘患者治疗前以及激素治疗后的诱导痰液,进行炎性细胞分类计数,采用酶联免疫吸附测定法检测痰中IL-17、IL-8、IL-6、IL-5浓度及中性粒细胞弹性蛋白酶水平,并记录患者治疗前后的肺功能、哮喘控制评分等基线情况。比较三组患者间的不同以及治疗前后的差别,并采用相关分析及多元直线回归方程筛选与气道炎症和哮喘控制评分相关的指标。结果在全部146例哮喘患者中,重度哮喘所占比例将近1/3。与轻中度哮喘相比,重度哮喘患者有着较低的特应质比例、FEV1值和哮喘控制评分,但年龄及体质指数均较高。诱导痰细胞检查显示,治疗前的重度哮喘诱导痰嗜酸细胞比例低于轻中度哮喘(4.59%vs.7.74%,P0.01),而中性粒细胞比例则明显增加(63.22%vs.22.8%,P0.01)。轻中度哮喘的气道炎症类型以嗜酸性粒细胞型为主,重度哮喘则以中性粒细胞型为最多(P0.01)。与正常对照和轻中度哮喘相比,重度哮喘患者诱导痰中的炎症介质IL-17、IL-8、IL-6及中性粒细胞弹性蛋白酶浓度亦显著升高(P0.01)。相关分析显示,哮喘患者痰中性粒细胞比例与IL-17浓度正相关(r=0.545,P0.01)。而直线回归分析提示,哮喘控制评分与IL-17和体质指数呈负回归关系(P0.01)。激素治疗可明显降低轻中度哮喘诱导痰内嗜酸性粒细胞和中性粒细胞比例及炎症介质浓度,提高哮喘控制评分和FEV1(P0.01),而重度哮喘仅有诱导痰嗜酸细胞计数及IL-5浓度的降低,余炎性介质浓度、中性粒细胞比例及哮喘控制评分无改善(P0.05)。结论成人晚发型重度哮喘是不同于轻中度哮喘的一种特殊亚型,其气道炎症成分复杂,以中性粒细胞为主,激素治疗仅可改善以嗜酸性粒细胞为主的炎症成分,但对中性粒细胞性炎症则无作用。对该型哮喘应探索新的治疗途径。     

哮喘慢性持续期患者肺功能与生存质量的相关性

目的探讨哮喘慢性持续期患者肺功能与生存质量的相关性。方法统计分析2012年5月至2014年5月贺州市人民医院呼吸内科收治的100例支气管哮喘患者的临床资料。结果和治疗前相比,治疗后两组患者的FEV1、FEV1%、PEF、PEF%、AQLQ、日间和夜间症状评分均明显升高(P0.05);和乙组患者相比,甲组患者治疗前后的FEV1、FEV1%、PEF、PEF%、AQLQ、日间和夜间症状评分均明显升高(P0.05);两组患者治疗前后的AQLQ与FEV1%、PEF%均呈显著的正相关关系(P0.05)。结论哮喘慢性持续期患者肺功能与生存质量呈显著的正相关关系,患者病情严重程度能够在两者的联系中得到全面的反映。     

哮喘诱导痰中弹性蛋白酶和α_1-抗胰蛋白酶水平与气道炎症气流受限的关系

目的:探讨中重度支气管哮喘(哮喘)患者诱导痰中弹性蛋白酶和α1-抗胰蛋白酶水平及其与气道炎症和气流受限的关系。方法:测定12例慢性持续期中重度哮喘患者(哮喘组),12例稳定期中度慢性阻塞性肺疾病(COPD)患者和10例健康对照者的(健康对照组)肺功能。并对其诱导痰进行炎性细胞分类计数,测定诱导痰上清液中IL-8、弹性蛋白酶浓度和α1-抗胰蛋白酶的活性。结果:哮喘和COPD患者诱导痰中弹性蛋白酶浓度和α1-抗胰蛋白酶活性与健康对照组比较差异有统计学意义,且与中性粒细胞数、IL-8浓度呈正相关,但与FEV1/FVC百分比值呈负相关。哮喘和COPD患者诱导痰中弹性蛋白酶浓度/α1-抗胰蛋白酶活性比值与健康对照组比较差异有统计学意义,且与FEV1/FVC百分比值呈正相关。结论:中重度哮喘患者诱导痰中存在弹性蛋白酶与α1-抗胰蛋白酶间失平衡,增高的弹性蛋白酶与其气道炎症和气流受限有关(与COPD患者相类似),这在其气道重塑的发病机制中可能发挥重要作用。IL-8参与了中重度哮喘患者气道炎症和气道重塑的过程。     

诱导痰炎性标志物对支气管哮喘和慢性阻塞性肺疾病稳定期的鉴别诊断价值

目的 探讨诱导痰中嗜酸细胞（Eos）和嗜酸细胞阳离子蛋白（ECP）水平对支气管哮喘与慢性阻塞性肺疾病（COPD）稳定期的鉴别诊断价值.方法 选择支气管哮喘患者62例,检测肺功能并分别采用瑞氏染色及荧光免疫法检测高渗盐水诱导痰中Eos数量和ECP水平.选择51例慢性阻塞性肺疾病稳定期患者和30名健康人作为对照.结果 支气管哮喘患者诱导痰中Eos数量[（14.4±6.3）%]和ECP水平[（413±199）μg/L]显著高于COPD稳定期组[（3.2±1.5）%、（54±35）μg/L,P〈0.01]和对照组[（1.1±0.6）%、（46±23）μg/L,P〈0.01].以诱导痰中Eos≥7%和ECP≥100μg/L作为与稳定期COPD鉴别的标准,诊断哮喘的敏感性分别为79.3%和81.2%,特异性分别为81.0%和83.0%.联合检测两者的敏感性和特异性分别为85.2%和86.0%.结论 检测诱导痰Eos和ECP水平有助于支气管哮喘与COPD稳定期的鉴别.     

Classifying asthma severity in children: mismatch between symptoms, medication use, and lung function

Current guidelines for asthma care categorize asthma severity based on the frequency of asthma symptoms, medication use, and lung function measures. The objective of this study was to determine whether lung function measures are consistent with levels of asthma severity as defined by the National Asthma Education and Prevention Program/Expert Panel Report 2 Guidelines. Parents of children aged 5-18 years with asthma seen in two outpatient subspecialty clinics completed questionnaires regarding asthma medication use and symptom frequency over the preceding 1 and 4 weeks, respectively. All children performed spirometry. When asthma severity was based on the higher severity of asthma symptom frequency or medication use, asthma was mild intermittent in 6.9% of participants, mild persistent in 27.9%, moderate persistent in 22.4%, and severe persistent in 42.9%. FEV(1) % predicted did not differ by level of asthma severity. FEV(1)/FVC decreased as asthma severity increased (p < 0.0001) and was abnormal in 33% of the participants, and a greater percentage of participants had an abnormal FEV(1)/FVC as asthma severity increased (p = 0.0001). In children, asthma severity classified by symptom frequency and medication usage does not correlate with FEV(1) categories defined by National Asthma Education and Prevention Program Guidelines. FEV(1) is generally normal, even in severe persistent childhood asthma, whereas FEV(1)/FVC declines as asthma severity increases.     

哮喘豚鼠肺组织中嗜酸细胞凋亡与白细胞介素5mRNA表达？…

目的 探讨哮喘时嗜酸细胞（ＥＯＳ）凋亡与肺组织白细胞介素５（ＩＬ－５）ｍＲＮＡ表达的关系。方法 将豚鼠随机分为对照组（正常组７只）、哮喘组（８只）、地塞米松组（８只），应用脱氧核糖核酸末端转移酶介导的缺口末端标记（ＴＵＮＥＬ）技术和原位杂交方法，检测支气管肺泡灌洗液（ＢＡＬＦ）中不同密度ＥＯＳ凋亡百分比和肺组织ＩＬ－５ｍＲＮＡ的表达。结果 （１）正常对照组ＢＡＬＦ中低密度ＥＯＳ、正常密度ＥＯＳ凋是     

Atopy,but not obesity is associated with asthma severity among children with persistent asthma

Background and Objective: Obesity is associated with an increased risk of asthma in children. Atopic sensitization is a major risk factor for asthma including severe asthma in children. It is unclear if obesity is associated with worse asthma control or severity in children and how its effects compare to atopy. We sought to examine relationships of weight status and atopy to asthma control and severity among a population of predominantly low income, minority children and adolescents with persistent asthma. Methods: A cross-sectional analysis of 832 children and adolescents, age range 5–17 years, with persistent asthma was performed. Clinical assessments included asthma questionnaires of symptoms, asthma severity score, health care utilization and medication treatment step, lung function testing, and skin prick testing as well as measures of adiposity. Data were collected between December 2010 and August 2014 from Johns Hopkins Hospital in Baltimore, MD and Children's Hospital of Boston, MA. Results: Obesity was not associated with worse asthma control or severity in this group of predominantly low income, minority children and adolescents with persistent asthma. However, a greater degree of atopy was associated with lower lung function, higher asthma severity score, and higher medication treatment step. Conclusion: Atopy may be a more important risk factor for asthma severity than obesity among low-income minority children and adolescents with persistent asthma living in Northeastern cities in the United States.     

Clinical assessment of asthma severity partially corresponds to sputum eosinophilic airway inflammation

In the aim to evaluate the relationship between sputum eosinophil percentages and eosinophil cationic protein (ECP) concentrations, as markers of airway inflammation, and different Levels of asthma severity, we examined 223 patients consecutively observed in our asthma clinic. Diagnosis of asthma was made according to internationally accepted criteria. Asthma severity was evaluated according to frequency of symptoms, FEV1, peak expiratory flow variability and level of asthma treatment needed to control asthma. Spontaneous or induced sputum was collected. Adequate sputum samples were obtained in 68 untreated subjects and in 117 subjects regularly treated with ICS. A control group of 14 normal subjects was also examined. In untreated subjects, mild intermittent asthmatics showed a lower sputum eosinophil percentage in comparison with other groups of asthma severity, while no difference in ECP levels was detected. In treated subjects, severe asthmatics showed higher levels of sputum eosinophils and ECP in comparison with other groups of asthma severity. Mild persistent and moderate persistent patients did not differ for sputum eosinophils or ECP in both untreated and treated subjects. Controls were significantly different from all groups of untreated and treated asthmatics. In conclusion, the assessment of asthma severity according to clinical and functional findings only partially corresponds to the severity of eosinophilic airway inflammation as assessed by induced sputum analysis.     

Effect of FP inhalation and airway inflammation assessed by ECP in asthma]

We studied the effects of fluticasone propionate (FP) inhalation and the airway inflammation in beclomethasone dipropionate (BDP)-resistant bronchial asthma. Twenty-five patients who had used BDP and whose mean PEF was less then 80% were enrolled in this study. After 2 weeks of BDP inhalation. FP inhalation was administered. The total eosinophil count in the peripheral blood (/microliter), their percentage of the total WBC count (% Eos), the count in induced sputum, the serum ECP content and the induced sputum ECP content were measured before and after 6 weeks of FP treatment. There was a significant increase of morning and evening PEF, from 63.1% to 76.1% and from 63.6% to 76.2%, respectively. There was a significant positive correlation between the peripheral blood % Eos and the % increase of PEF (p < 0.01). There was also a significant positive correlation between the induced sputum % Eos and the % increase of PEF (p < 0.05). The induced sputum ECP content was still as high as 180 micrograms/l after FP treatment. The mean % PEF did not reach 80% after FP treatment. This study suggests that airway inflammation persists in some severe asthma patients despite inhalation of FP 800 micrograms.     

Categorizing asthma severity

The National Asthma Education and Prevention Program (NAEPP) Expert Panel II recommended a stepped care pharmacotherapy approach to asthma treatment based on an objective assessment of asthma severity using daytime symptoms, nocturnal symptoms, and physiologic lung function. The worst grade of the individual variables determines overall asthma severity. With this approach, patterns of asthma severity categorization might vary among individual variables; one variable might have a predominant effect on overall categorization. During the run-in, pretreatment phase of five controlled clinical trials, data from 744 inhaled steroid nonusers and 685 inhaled steroid users on asthma control were collected and asthma severity categorized. In inhaled steroid nonusers nocturnal symptoms classified the majority of patients as severe, persistent, but wheeze classified 27.3% of patients as mild, intermittent and 25.7% as mild, persistent. If the worst grade from the four asthma symptoms was used for severity grading, most patients were categorized as severe, persistent. beta-Agonist use and FEV(1) classified most as moderate, persistent. There was poor correlation between variables in severity categorization. Severity grading for European patients was similar to that for U.S. patients. Applying the Expert Panel II recommended method for asthma severity categorization to a large data set illustrates that a single variable, nocturnal symptoms, determined to a large extent overall categorization. Development of a validated method for asthma severity categorization is essential for using a stepped care approach to asthma pharmacotherapy.