双盲对照吸入倍氯米松一年对气道高反应性与哮喘的防治作用

目的探讨长期吸入糖皮质激素对哮喘患者的治疗作用和对无症状的气道高反应性（ＢＨＲ）者发生哮喘的预防作用。方法以随机、双盲对照法比较５９例ＢＨＲ学生，年龄１２～１８岁，吸入倍氯米松干粉剂（ＢＤＰ，６００μｇ／ｄ）或安慰剂１年对气道反应性及哮喘症状的作用。结果试验１年后哮喘ＢＤＰ组气道高反应性（使ＦＥＶ１较基础值下降２０％的累积吸入组胺量的对数ｌｇＰＤ２０－ＦＥＶ１）显著下降（分别为０．３８５±０．４２４、１．１８７±０．６０３μｍｏｌ组胺，Ｐ＜０．０２），只有３０％哮喘者仍有喘息，而对照组则有８６％仍有喘息（Ｐ＝０．０７６）；无症状ＢＨＲ学生的ｌｇＰＤ２０－ＦＥＶ１在ＢＤＰ组及对照组间差异无显著性，但ＢＤＰ组不出现喘息症状，而对照组则有３例出现喘息（１５％）；ＢＨＲ者吸入ＢＤＰ组的累积症状计分显著低于对照组（分别为１．５０±２．５４分、５．５８±６．２２分，Ｐ＜０．０１）。结论ＢＤＰ能降低哮喘患者的ＢＨＲ及减轻其症状，且可能有预防无症状ＢＨＲ者发生哮喘的作用     

糖皮质激素对哮喘患者白细胞介素-5mRNA表达与嗜酸性粒细胞激活作用的影响

为了观察糖皮质激素对哮喘患者白细胞介素（ＩＬ）－５ｍＲＮＡ表达与嗜酸性粒细胞激活作用的影响，本研究用逆转录（ＲＴ）－聚合酶链反应（ＰＣＲ）法半定量分析了哮喘患者用糖皮质激素治疗前后外周血单个核细胞（ＰＢＭＣ）中ＩＬ－５ｍＲＮＡ表达水平的变化，检测了血清嗜酸细胞阳离子蛋白（ＥＣＰ）浓度、一秒钟用力呼气容积（ＦＥＶ１）下降２０％时的乙酰甲胆碱（ＭＣＨ）激发浓度（ＭＣＨ－ＰＣ２０值）和基础ＦＥＶ１占用力肺活量比值（ＦＥＶ１％）等指标。结果发现，糖皮质激素不仅能改善哮喘患者的气道高反应性和通气功能，而且还可抑制ＰＢＭＣ中ＩＬ－５ｍＲＮＡ的表达和降低血清ＥＣＰ浓度（Ｐ＜０．０５）；血清ＥＣＰ浓度下降幅度或ＭＣＨ－ＰＣ２０值改善幅度与ＩＬ－５ｍＲＮＡ表达水平下降幅度之间均呈显著正相关（ｒ分别为０．５４２６和０．４８５７，Ｐ值＜０．０５）。提示糖皮质激素可能是通过抑制ＩＬ－５基因的转录，从而抑制后者对嗜酸性粒细胞的活化，而发挥其抗气道炎症反应和降低气道高反应性的作用。     

慢性干咳伴有气道高反应性即是咳嗽变异性哮喘吗？

目的评价气道反应性测定在咳嗽变异性哮喘（ＣＶＡ）诊断中的价值。方法１２４例慢性干咳患者经气道反应性测定后，分为咳嗽气道高反应阳性组（ＣＢＨ－Ｐ组）３５例，咳嗽气道高反应阴性组（ＣＢＨ－Ｎ组）３３例。观察常规肺功能、抗原皮肤点刺试验阳性率、血嗜酸性粒细胞计数、血ＩｇＥ水平、泼尼松试验阳性率并随访２年后发展成典型哮喘例数。结果３５例ＣＢＨ－Ｐ组一秒钟用力呼气容积占用力肺活量比值（ＦＥＶ１％）为７４±１０（Ｐ＜０．０１），３３例ＣＢＨ－Ｎ组为８３±１０（Ｐ＜０．０５）。抗原皮肤点刺试验阳性率ＣＢＨ－Ｐ组为５１％，ＣＢＨ－Ｎ组为１２％；血嗜酸性粒细胞计数ＣＢＨ－Ｐ组为０．５±０．１×１０９／Ｌ，ＣＢＨ－Ｎ组为０．３±０．１×１０９／Ｌ；泼尼松试验阳性率ＣＢＨ－Ｐ组为８３％，ＣＢＨ－Ｎ组为１５％。随访２年后发展成典型哮喘例数中ＣＢＨ－Ｐ组有１６例发展成典型哮喘。在ＣＢＨ－Ｐ组中发展成典型哮喘与未发展成典型哮喘患者在皮肤抗原点刺试验阳性率、常规肺功能、反应阈值（Ｄｍｉｎ）及致喘阈值（Ｄｃｗ／Ｄｍｉｎ）等方面差异均无显著性。结论气道反应性测定是诊断ＣＶＡ的重要依据，但不是唯一的诊断标准，还应结合其它临床资料综合判断     

吸入皮质激素对哮喘患者血清嗜酸粒细胞和T－淋巴细胞功能的影响

为研究吸入皮质激素倍氯米松对哮喘患合体内嗜酸粒细胞、Ｔ－淋巴细胞功能状态的影响，对治疗前后哮喘患者血清嗜酸性阳离子蛋白（ＥＣＰ）、可溶性白细胞介素－２（ｓＩＬ－２Ｒ）浓度及患者乙酰甲胆碱气道反应性进行检测。结果表明。吸入皮质激素６周后，血清ＥＣＰ、ｓＩＬ－２Ｒ浓度降低，肺功能改善、乙酰甲胆碱－ＰＣ＿（２０）（ＦＥＶ＿１下降２０％时的乙酰甲胆碱激发浓度）值增高。提示：糖皮质激索能抑制嗜酸性粒细胞、Ｔ－淋巴细胞激活。具有抗炎和降低气道高反应性的作用。     

二丙酸倍氯米松干粉剂治疗晚发老年哮喘的临床观察

目的 观察吸入类固醇二丙酸倍氯米松（ＤＢＰ）干粉剂对晚发老年哮喘（ＬＯＡ）的疗效。方法 将２２例ＬＯＡ患者与２３例非老年２哮喘患者进行对比研究,观察吸入β２受体激动剂沙丁胺醇干粉剂后１秒钟用力呼气容积（ＦＥＶ１）的变化以及吸入ＤＢＰ干粉剂后ＦＥＶ１及其占预计值百分比（ＦＥＶ１％）、早晚最大呼气流速（ＰＥＦＲ）及其日内变异率等变化。结果 两组患者在吸入沙丁胺醇干粉剂后ＦＥＶ１均明显增高（Ｐ〈０．０１     

白细胞介素—8与豚鼠气道高反应性关系探讨

目的探讨白介素－８（ＩＬ－８）与哮喘气道高反应性（ＡＨＲ）产生的关系。方法经鼻腔给予豚鼠ＩＬ－８（０．５μｇ／ｋｇ或５μｇ／ｋｇ）３周，每周２次，在最后一次给予后２４小时，测定动物气道对吸入不同浓度组织胺（２５、５０、１００或２００μｇ／ｍｌ）的反应性；对支气管肺泡灌洗液（ＢＡＬＦ）中各种细胞成分计数；光镜下观察气道及肺组织的病理改变。结果豚鼠经ＩＬ－８处理后，其气道内压随吸入组织胺浓度的升高而增加，与对照组比较差异有显著性（Ｐ＜０．０５或０．０１）；ＢＡＬＦ中中性粒细胞数较对照组明显增多（Ｐ＜０．０１），而嗜酸性细胞减少（Ｐ＜０．０５）；气管、支气管粘膜及管壁周围有大量中性粒细胞浸润，对照组无此改变。结论ＩＬ－８能引起气道中性粒细胞炎症，同时伴有ＡＨＲ的产生，推测ＩＬ－８在哮喘ＡＨＲ的产生中起着重要作用。     

哮喘患者气道阻力变化对中枢驱动的影响

目的：了解哮喘患者气道阻力的变化对中枢驱动的影响。方法对１３例正常人和２１例哮喘患者作气道反应性测定,于激发试验前后分别测定吸气初０．１ｓ时口腔阻断压（０．０１）,其中１０例哮喘患者激发试验后吸入喘乐宁,测定ＦＥＶ１及Ｐ０．１结果：正常人９名（９／１３）、哮喘患者１９例（１９／２１例）组胺激发试验后Ｐ０．１较激发前显著升高,两组Ｐ０．１升高人数的百分比比较差异无显著性,哮喘患者激发后ＦＥＶ１％与Ｐ     

CD86对抗原引起气道嗜酸细胞浸润和气道高反应性作用的研究

目的　探讨ＣＤ８６ 分子对抗原引起气道炎症和气道高反应性的影响,加深认识ＣＤ８６ 在支气管哮喘发病机制中的作用。方法　应用鸡卵清蛋白致敏和刺激ＢＡＬＢ／ｃ 小鼠（ 每组８ 只） 以诱导嗜酸细胞（ＥＯＳ）聚集到气道,收集支气管肺泡灌洗液（ＢＡＬＦ） 细胞并以流式细胞仪检测ＣＤ８６ 分子的表达水平;观察静脉注射抗ＣＤ８６ 单克隆抗体后ＢＡＬＦ中ＥＯＳ数和气道反应性的变化。结果　小鼠经抗原致敏和刺激后ＢＡＬＦ中可以见到大量的ＥＯＳ,气道反应性亦明显升高,ＢＡＬＦ细胞所表达的ＣＤ８６ 水平也随之增高。经抗ＣＤ８６ 单克隆抗体处理后,ＢＡＬＦ中ＥＯＳ数降低了６７％ （ Ｐ＜０－０１）;同时,气道反应性也下降６９％ （ Ｐ＜ ０－０１）。此外,抗ＣＤ８６ 单克隆抗体还可以抑制肺组织局部白细胞介素４ 和白细胞介素５ 的产生。结论　抗ＣＤ８６ 单克隆抗体能够抑制气道ＥＯＳ浸润和降低气道反应性,其作用机制可能是通过抑制局部白细胞介素４ 和白细胞介素５ 产生而实现。提示抑制气道抗原呈递细胞的活性应有益于哮喘的治疗。     

吸入皮质激素对哮喘患者血清嗜酸粒细胞和T—淋巴细胞功能的…

为研究吸入皮质激素倍氯米松对哮喘患者体内嗜酸粒细胞、Ｔ－淋巴细胞功能状态的影响，对治疗前后哮喘患者血清嗜酸性阳离子蛋白（ＥＣＰ）、可溶性白细胞介素－２（ｓＩＬ－２Ｒ）浓度及患者乙酰甲胆碱气道反应性进行检测。结果表明，吸入皮质激素６周后，血清ＥＣＰ、ｓＩＬ－２Ｒ浓度降低，肺功能改善，乙酰甲胆碱－ＰＣ２０（ＦＥＶ１下降２０％时的乙酰甲胆碱激发浓度）值增高。提示：糖皮质激素能抑制嗜酸性粒细胞、Ｔ－淋巴细     

吸入糖皮质激素治疗非哮喘性慢性阻塞性疾病的研究

目的 研究中等剂量二丙酸氯地米松（ＢＤＰ）短疗程吸入治疗非哮喘慢性阻塞性肺疾病（ＣＯＰＤ）是否有疗效，方法 按照随机，对照，单盲的设计，６１例非哮喘性ＣＯＰＤ患分两组，分别予ＢＤＰ（１０００μｇ．ｄ＾－１）与安慰剂吸入治疗６周，治疗前后测定肺功能一秒钟用力呼气容积（ＦＥＶ１）用力肺活量（ＦＶＣ），最大呼气中段流速（ＭＭＥＦ）值和血浆内纱（ＥＴ－１）的浓度，并记录临床症状记分，生活质量记分，结果     

Is asymptomatic bronchial hyperresponsiveness an indication of potential asthma? A two-year follow-up of young students with bronchial hyperresponsiveness.

To determine the possibility that asymptomatic bronchial hyperresponsiveness (BHR) develops into symptomatic asthma, a two-year follow-up study was conducted in 81 students (48 male, 33 female; 11 to 17 years) who were found to have BHR in a 3,067 population survey (BHR group). Eighty-eight age-matched students (48 male, 40 female) with normal bronchial responsiveness served as control subjects. Daily symptom cards were recorded. Peak expiratory flow rate was measured for 24 h when symptoms occurred. Histamine inhalation tests were performed at the beginning of the study and at the end of the first and the second year. In the BHR group, 58 students remained bronchial hyperresponsive at the end of follow-up. Nine of 31 students with initially diagnosed bronchial asthma had their symptoms relieved entirely, but ten asymptomatic students developed asthma. The incidence of newly diagnosed asthma (12.5 percent in the BHR group or 20 percent in the asymptomatic BHR group) and the total percentage of diagnosed asthma (39.5 percent) in the BHR group were significantly higher than those (2.27 percent, 2.27 percent) in the control group. FVC and FEV1 showed no significant difference between two groups. PD20 FEV1 values in newly diagnosed asthmatics were significantly lower than those in asymptomatic students both at the beginning (3.05 +/- 1.56 mumol vs 6.14 +/- 1.60 mumol, p < 0.05) or the end (3.47 +/- 1.73 mumol vs 6.55 +/- 1.51 mumol, p < 0.05). The percentage of early respiratory illness was significantly higher in those with newly diagnosed asthma (80 percent) than in asymptomatic students (22.3 percent), but atopic index and the percentage of parental asthma showed no difference between two groups. In nine asthmatics whose symptoms were relieved entirely in the two-year follow-up, PD20 FEV1 was undetectable within the cumulative dose of 7.8 mumol of histamine in three students and rose from 4.58 +/- 1.85 mumol to 7.62 +/- 1.02 mumol in the remaining six. The higher the BHR, the more likely the students developed asthma. About 45 percent of asymptomatic students with PD20 < or = 3.2 mumol developed asthma in the following two years and 80 percent of them had a history of early respiratory illness, suggesting that they may have subclinical or potential asthma.     

哮喘儿童持续吸入低剂量糖皮质激素的全身性副作用

目的 探讨我国哮喘儿童吸入糖皮质激素的全身性副作用.方法 将30例14岁以下轻度哮喘儿童随机分为安慰剂组(A组)、二丙酸倍氯松(BDP)200 μg组(B组)、BDP 400 μg组(C组),每组10例,分别持续吸入安慰剂及BDP 200、400 μg/d 1年,观察患儿气道高反应性(BHR)、身高增长、骨密度(BMD)、钙磷代谢及下丘脑-垂体-肾上腺轴(HPAA)功能的影响.结果 B组及C组患儿吸入BDP后PD20-FEV1即一秒钟用力呼气容积下降20% 时累积吸入的组胺剂量[Log(PD20- FEV1)]分别为(2.70±0.13) μg及(3.15±0.18) μg,与治疗前[B组(2.04±0.47) μg,C组(1.94±0.46) μg]比较,差异有显著性(P均<0.01),而B组与C组间比较,差异有显著性(P<0.01).A、B及C组患儿吸入BDP后血骨钙素分别为(29±12) μg/L、(22±6) μg/L、(31±11) μg/L,血钙为(2.49±0.11) mmol/L、(2.39±0.28) mmol/L、(2.20±0.35) mmol/L, 血磷为(1.8±0.6) mmol/L、(1.7±0.7) mmol/L、(1.5±0.4) mmol/L,血碱性磷酸酶为(410±113) U/L、(337±99) U/L、(351±122) U/L(P>0.05),桡骨BMD为(0.40±0.10) g/cm2、(0.42±0.05 ) g/cm2、(0.44±0.02) g/cm2,尺骨BMD为(0.32±0.07) g/cm2、(0.36±0.08) g/cm2、(0.35±0.04) g/cm2,腰椎4～5BMD为(0.62±0.09) g/cm2、(0.59±0.08) g/cm2、(0.64±0.06) g/cm2,血皮质醇基础值为(350±86)nmol/L、(407±199) nmol/L、(365±71)nmol/L, 三组间比较差异无显著性(P均>0.05).但C组治疗后血皮质醇对促肾上腺皮质激素(ACTH)刺激的反应值为(482±97) nmol/L, 与治疗前(621±199 )nmol/L比较,差异有显著性(P<0.01),而A组和B组治疗后分别为 (566±203) nmol/L,(452±97)nmol/L,与治疗前[A组(534±204)nmol/L,B组(481±82)nmol/L]比较,差异无显著性(P均>0.05).A组患儿吸入BDP后身高标准差计分(SDS)为(1.2±0.9)分,B组为(1.3±0.9)分,C组为(1.0±0.7)分,三组比较差异均无显著性(P均>0.05).结论 14岁以下轻度儿童哮喘吸入200 μg/d的BDP即能有效降低BHR,且无明显全身性副作用.而当剂量达400 μg/d时,血皮质醇对ACTH刺激的反应性明显降低,有必要作进一步的研究.     

Comparison of percentage fall in FVC at the provocative concentration of methacholine causing a 20% fall in FEV(1) between patients with asymptomatic bronchial hyperresponsiveness and mild asthma

BACKGROUND: A significant proportion of individuals who have no symptoms of asthma or other respiratory diseases show bronchial hyperresponsiveness (BHR). BHR is usually assessed by measuring the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)). The percentage fall in FVC at the PC(20) (DeltaFVC) has been suggested to reflect maximal airway response and to be a more useful index of disease severity in asthma than PC(20). The aim of this study was to investigate whether asymptomatic BHR would differ from symptomatic BHR with regard to DeltaFVC. METHODS: Methacholine bronchial challenge tests were conducted in children with no past or current symptoms of asthma, allergic rhinitis, or other respiratory diseases, who were identified among siblings of children with asthma. Forty-three children with asymptomatic BHR (PC(20) < 16 mg/mL) were recruited, and 43 children with mild asthma who were matched for age, sex, and PC(20) were selected (mild asthma group). The DeltaFVC on methacholine concentration-response curves was retrospectively analyzed in the two groups. RESULTS: There were no differences in the frequency of atopy, blood eosinophil counts, serum IgE levels, and spirometric values between the asymptomatic BHR and mild asthma groups. Mean (+/- SD) DeltaFVC was significantly (p = 0.005) lower in the asymptomatic BHR group (14.5 +/- 3.6%) than in the mild asthma group (16.9 +/- 4.3%). CONCLUSIONS: Our results suggest that children with asymptomatic BHR have a lower level of maximal airway response than mild asthmatics with a similar degree of BHR. This may be a possible explanation for the lack of symptoms in subjects with asymptomatic BHR.     

小剂量布地奈德粉吸入剂治疗轻度支气管哮喘患者的远期疗效

目的　探讨小剂量布地奈德粉吸入剂(商品名:普米克都保)长期吸入治疗轻度支气管哮喘(简称哮喘)的远期疗效和不良反应。方法　将52例轻度哮喘患者分为3组。吸入糖皮质激素组(A组)22例:每晚吸入布地奈德粉吸入剂200μg。口服糖皮质激素组(B组)15例:在哮喘发作期给予泼尼松5mg每天1次口服,茶碱控释片(商品名:舒弗美)02g每天2次口服;沙丁胺醇(商品名:喘乐宁)气雾剂2揿(每揿100μg)每天3次吸入。非糖皮质激素组(C组)15例:发作期只给茶碱控释片02g每天2次口服,沙丁胺醇气雾剂2揿每天3次吸入。全部病例连续治疗3年,停药后随访1年。在此4年间,检测各组患者治疗前、后一秒钟用力呼气容积(FEV1)、气道阻力(Raw)、气道传导率(Gaw)、气道高反应性(BHR)、临床疗效、血浆皮质醇浓度以及促肾上腺皮质激素(ACTH)刺激后的反应等。结果　(1)治疗前A、B、C3组绝大多数病例的BHR均在3~4级,分别为91%(20/22)、100%(15/15)、93%(14/15)。治疗后A组18例(82%)转为1~2级;B组13例(87%)仍为3~4级;C组15例(100%)病例为3~5级。A、B、C3组间比较差异有统计学意义(P均<001)。(2)A、B、C3组Raw治疗前分别为(623±103)%、(605±90)%、(638±108)%,治疗后分别为(158±24)%、(340±61)%、(420±81)%,3组间比较差异有统计学意义(P均<001)。(3     

Immunohistochemical analysis of bronchial mucosa in severe asthmatics treated with long-term, high-dose inhaled BDP]

To analyze specific mucosal changes in asthmatic patients receiving long-term, high-dose beclomethazone dipropionate (BDP) inhalation therapy, we performed bronchial mucosal biopsies and immunohistochemical analysis of patients who had been treated with or without BDP-inhalation. Our study enrolled 6 chronic severe asthmatics who were treated with 1,800 micrograms/day or more of BDP with regular use for more than 3 years (HD-BDP group), 6 mild asthmatics who were not treated with BDP (non-BDP group), and 6 control subjects. Specimens of bronchial mucosa were stained with anti-EG 2 (eosinophils), anti-UCHLA-1 (T lymphocytes) and anti-tryptase (mast cells). Although limited eosinophil infiltration was observed in the HD-BDP and control groups, a significant increase was noted in the non-BDP group. The infiltration of both T lymphocytes and mast cells exhibited a statistically significant increase in the non-BDP group compared to the HD-BDP and control groups. In chronic severe asthmatics, airway mucosal cell infiltration was reduced by high-dose and long-term inhaled BDP therapy, and BDP also relieved their asthmatic symptoms. However, in mild asthmatics, bronchial mucosal cell infiltration remained high. For such patients, we concluded that initiating BDP therapy from an early stage may bring clinical improvement and help prevent cell infiltration.     

Bronchial Sensitivity to Histamine in Former Asthmatics: Redevelopment of Symptoms During a Year of Followup

The aim of this protocol was to study bronchial responsiveness in 23 former asthmatics who were free of symptoms for at least 5 years. Bronchial hyperreactivity (BHR) was evaluated with histamine challenge test and the results were compared with those of 20 normal subjects and 20 current asthmatic patients. Among the former asthmatics 65% fulfilled the criteria of BHR. During 1 year of followup, two former asthmatics redeveloped asthma symptoms. Interestingly, one patient had no BHR when initially tested. These findings suggest that the absence of BHR does not guarantee the nonrecurrence of asthma symptoms in former asthmatics.     

Changes in bronchial reactivity in asthmatic children after treatment with beclomethasone alone or in association with salbutamol

Airway inflammation is consistently present in patients with severe asthma. The combination of inhaled steroids and bronchodilators may be useful both for treating symptoms and improving the underlying inflammatory condition. We have compared the effect of beclomethasone dipropionate (BDP) combined with salbutamol (S), BDP alone, and placebo, on the severity of bronchial responsiveness in 30 children with allergic asthma during the period of specific allergen exposure. In children treated with BDP alone, PC20-FEV1 methacholine was 0.66 +/- 0.54 at the beginning and 1.91 +/- 2.11 at the end of the study period (p greater than 0.05). In children treated with BDP + S PC20, methacholine was 1.21 +/- 1.43 at the beginning and 4.22 +/- 3.88 at the end of the study (p less than 0.05). The group of children treated with placebo had a PC20-FEV1 methacholine of 0.79 +/- 0.61 at the beginning of the study and 0.80 +/- 0.46 at the end of the study. The results of the present study show that maintenance treatment with inhaled beclomethasone combined with salbutamol may lead to greater improvement in bronchial hyperreactivity than treatment with inhaled beclomethasone dipropionate alone.     

Beclomethasone dipropionate attenuates airways hyperresponsiveness to neurokinin A and histamine in asthma

BACKGROUND: Inhaled corticosteroids (ICS) are the most effective anti-inflammatory agents available for the treatment of asthma but they produce only modest effects on airway inflammation and non-specific bronchial hyperresponsiveness (BHR). However, little is known about the possibility that treatment with ICS might cause additional protection on BHR to inhaled tachykinins such as neurokinin A (NKA). OBJECTIVE: Therefore, we compared the effects of beclomethasone dipropionate (BDP) on the degree of BHR to inhaled histamine and NKA in a double-blind, controlled, cross-over study of asthmatic patients. METHODS: Patients attended the laboratory before and after each 6 weeks treatment period to undertake concentration-response studies with histamine and NKA. Bronchial responsiveness to both funs was expressed as the provocative concentration producing a 20% decrease in FEV(1) from baseline (PC(20)). RESULTS: BDP therapy attenuated the constrictor response to both agonists to a similar degree, their geometric mean (range) PC(20) values increasing from 0.47 (0.21-1.41) mg/ml to 2.43 (0.51-4.50) mg/ml (P<0.01, post-salb vs. post-BDP treatment) and from 101.7 (27.3-356.1) microg/ml to 666.7 (151.5-1,000) microg/ml (P<0.01, post-salb vs. post-BDP treatment) for histamine and NKA, respectively. CONCLUSION: Airway responsiveness to histamine and NKA is reduced by BDP to the same extent. As a result of these findings, provocation with NKA is unlikely to provide additional useful information in the assessment of airway inflammation in asthma.     

Bronchial hyperresponsiveness in adolescents with long-term asthma remission: importance of a Family history of bronchial hyperresponsiveness

BACKGROUND: The mechanisms responsible for bronchial hyperresponsiveness (BHR) in symptomatic asthma include genetic predisposition and airway inflammation, but the causes of BHR in adolescents with asthma remission are poorly understood. It has been shown that BHR in adolescents with asthma remission was not reduced by prolonged treatment with inhaled corticosteroids, in contrast to the BHR of symptomatic asthma. OBJECTIVE: The aim of this study was to investigate whether family history of BHR may contribute to the persistence of BHR in asthma remission during adolescence. METHODS: One hundred twenty-six adolescents with long-term asthma remission (neither symptoms nor any medication used during the previous 2 years) and their parents underwent a methacholine inhalation test. The provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)) and the bronchial responsiveness (BR) index were calculated for each individual. RESULTS: Sixty-nine adolescents (54.8%) were found to have persisting BHR (PC(20) < 18 mg/mL). The frequency of BHR and the BR index were significantly higher in parents (n = 138) of the BHR-persisting group (28.3% and 1.150 +/- 0.103, respectively [mean +/- 1 SD]) than in parents (n = 114) of BHR-nonpersisting group (16.7% [p = 0.030] and 1.124 +/- 0.088 [p = 0.029], respectively). Furthermore, adolescents (n = 56) with at least one BHR-positive parent were found to have a higher frequency of BHR (66.1% vs 45.7%, p = 0.023) and a higher BR index (1.244 +/- 0.090 vs 1.204 +/- 0.082, p = 0.011) than adolescents (n = 70) with non-BHR parents. CONCLUSION: Our results suggest that adolescents in asthma remission are more likely to have BHR when there is a family history of BHR. Further studies are needed to examine the possible involvement of genetic factors in the BHR of adolescents in asthma remission.     

Induced sputum analysis in asymptomatic young adults with bronchial hyperresponsiveness to methacholine

BACKGROUND AND OBJECTIVES: BHR is a clinical feature of asthma and factors crucial to the development of BHR remain to be elucidated. Asymptomatic BHR also occurs in the general population. This study examined the prevalence of asymptomatic BHR in a population of young Japanese atopic individuals to identify whether airway inflammation is present in asthmatic patients but not in asymptomatic subjects with BHR. METHODS: Fifty atopic volunteers (aged 18-23 years) without lower respiratory symptoms were recruited and their bronchial responsiveness to methacholine was measured in order to categorize them into two groups, those with BHR (PC(20) below 8 mg/mL) and those without BHR. We evaluated the inflammatory cell profiles and measured IL-5 and IL-13 levels in sputum from subjects of each group by ELISA. Results were compared with those for young adult asthmatic patients. RESULTS: In the young atopic group, 17 subjects (34.0%) exhibited BHR. Compared with asthmatic patients sputum from asymptomatic subjects with BHR contained significantly lower numbers of eosinophils (P < 0.001) and had significantly lower levels of IL-5 (P = 0.088) and IL-13 (P = 0.032). There were no significant differences in each inflammatory parameter between the two asymptomatic groups. CONCLUSIONS: In young adult atopic subjects with asymptomatic BHR, airway inflammation does not necessarily play a determining role in the development of BHR to methacholine itself, though it might be an important factor in the onset of asthma.