哮喘时糖皮质激素的应用

自从认识到哮喘是以嗜酸细胞和肥大细胞浸润为主的气道变应性炎症、气道高反应性（ＢＨＲ）为特征的疾病，气道炎症是ＢＨＲ的基础，应用肾上腺皮质激素（ＧＣｓ）治疗哮喘便成为最主要的手段。ＧＣｓ以扩散方式透过细胞膜与肾上腺皮质激素受体（ＧＣＲ）结合而发挥作用。ＧＣＲ为一细胞内可溶性蛋白、与ＧＣｓ呈高度亲合力和与一性，它一个类固醇结合并单位和二个Ｈｓｐ９０（热休克蛋白）亚单位组成。类固醇亚单位从羧基端到氨基端分别有类固醇结合区、ＤＮＡ结合区和免疫结合区，ＨＳＰ９０覆盖着ＤＮＡ结合区、使ＧＣＲ处于无活性状态，…     

过敏性哮喘：速发反应,迟发反应与持续气道高反应性及其机制

哮喘是气道慢性炎症性疾病，气道高反应性为其病理生理特征。过敏性哮喘患者吸入致敏原后半数以上出现双相气道反应，即速发生反应（ＥＡＲ）与迟发反应（ＬＡＲ），部分只出现速发反应。此外，致敏原的吸入可导致非特异性气道反应性升高（ＡＲ）。三者共同构成持续气道高反应性。本篇综述过敏性哮喘气道反应各时相的病理基础，阐明其细胞、分子生物学机制，对哮喘的治疗和发病机制的进一步研究具重要的参考价值。     

过敏性哮喘患者细胞因子对IgE生成机制的探讨

对３０例过敏性哮喘患者发作期和缓解期及３０例健康成年人的外周血，采用ＥＬＩＳＡ双抗体夹心法，测定血清ＩｇＥ，可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）和白细胞介素－４（ＩＬ－４）水平，生物学方法测定血清ＩＬ－２水平和３Ｈ－ＴｄＲ掺入法定量测定血清ＩＬ－６。结果：过敏性哮喘患者发作期血清ＩｇＥ、ｓＩＬ－２Ｒ、ＩＬ－４和ＩＬ－６水平明显升高，与缓解期和对照组有明显差异（Ｐ＜０．０１），而发作期血清ＩＬ－２水平明显下降，与缓解期和对照组有明显差异（Ｐ＜０．０１），且血清ＩｇＥ分别与ｓＩＬ－２Ｒ和ＩＬ－４水平有明显正相关（Ｐ均＜０．０１），与ＩＬ－２水平有明显负相关（Ｐ＜０．０１）。说明ＩｇＥ合成增加是过敏性哮喘的关键，细胞因子有促进Ｂ细胞合成ＩｇＥ的作用，并且直接参与过敏性哮喘气道炎症的形成。     

白介素4受体与支气管哮喘

支气管哮喘（哮喘）是由多种细胞特别是Ｔ细胞、肥大细胞和嗜酸粒细胞介导的慢性气道炎症，以气道高反应性和可逆性气道阻塞为特征。白介素４受体（ＩＬ－４Ｒ）的α亚基作为ＩＬ－４和ＩＬ－１３的受体，参与了哮喘的病理生理过程。本就ＩＬ－４Ｒ的生物学功能及其与哮喘关系的研究进展作一综述。     

血栓素A2及相关前列腺素与哮喘关系的新认识

支气管哮喘（哮喘）的基本特征是气道炎症，微血管渗漏，粘液分别增加，平滑肌收缩所致的可逆性气道阻塞及支气管高反应性（ＢＨＲ），在哮喘患，其血栓素Ａ２（ＴＸＡ２）及相关前列腺素（ＰＧｓ）如前列朱素Ｄ２，前列腺素Ｆ２α（ＰＧＦ２α）的生成量均高于正常人，这些物质能够诱发上述哮喘的基本特征，在哮喘的发病机制中起重要作用，有些拮抗ＴＸＡ２受体（ＴＰ受体）或抑制ＴＸＡ２合成酶系的平喘药物已经进入临床试验。     

哮喘患者血清白介素-2受体水平的初步研究

采用双抗体夹心法测定了４０例发作期哮喘患者血清可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）水平及应用β２－受体激动剂治疗后的变化。结果：哮喘患者血清ｓＩＬ－２Ｒ水平（６５５．５０±３２０．２５ＫＵ／Ｌ），明显高于健康对照组（２７３．８８±９７．４６）ＫＵ／Ｌ（Ｐ＜０．０１）。提示哮喘时血清中增高的ｓＩＬ－２Ｒ是导致机体免疫功能低下的重要因素之一。用β２－受体激动剂治疗后对血清ｓＩＬ－２Ｒ水平影响不大。     

白介素-12治疗支气管哮喘的研究进展

支气管哮喘（哮喘）是一种气道慢性炎症性疾病，具有较高的发病率和病死率。作为Thl型细胞因子，IL-12能促进Th0向Thl分化，抑制Th2型炎症反应。大量的动物实验已经证实，IL-12无论单独应用还是作为免疫佐剂，均可逆转哮喘动物体内Th2／Th1失衡和抑制气道变态反应性炎症。同时，IL-12基因治疗在动物实验中也显示了哮喘治疗作用。虽然临床研究显示外源性IL-12治疗哮喘会伴有严重细胞因子毒性作用，但随着用药方式的更新，IL-12可能会成为新一代的抗哮喘药物。     

老年人哮喘发病机制及临床特点的探讨

目的探讨老年人哮喘发病机制、临床特点及其与慢性支气管炎的区别。方法对２０例６０岁以后发生哮喘的患者（晚发老年哮喘）和１５例６０岁以前发生哮喘的患者（早发老年哮喘）与１６例６０岁以上的慢性支气管炎患者进行了对比研究。全部患者进行肺功能和支气管舒张试验，测定血及痰中嗜酸性粒细胞百分比计数、血浆皮质醇水平。结果晚发老年哮喘临床特征如下：（１）肺功能下降严重，吸入喘乐宁气雾剂后一秒钟用力呼气容积（ＦＥＶ１０）改善率明显高于慢性支气管炎组（Ｐ＜００５）；（２）痰嗜酸性粒细胞百分比计数显著高于慢性支气管炎组（Ｐ＜００５）；（３）血浆糖皮质激素水平明显低于慢性支气管炎组（Ｐ＜００５）。结论（１）晚发老年哮喘患者肺功能损伤严重，吸入β２受体激动剂后ＦＥＶ１０可获较大改善；（２）晚发老年哮喘患者气道内嗜酸性粒细胞增加在气道炎症及发病中起重要作用，痰嗜酸性粒细胞的检测可用于老年人哮喘的辅助诊断     

气道组胺H2受体与哮喘发病机理关系的动物实验研究

报告（１）１０＾－６ｍｏｌ／Ｌ甲双咪胍能舒张预先用组胺诱发收缩的豚鼠气管螺旋条，用１０＾－６ｍｏｌ／Ｌ甲双咪胍预处理可使各浓度组胺诱发螺旋条最大收缩力降低、组胺累积剂量反应曲线右移。（２）地麻普利（３ｍｇ／ｋｇ）静脉注射对抗原激发引起的豚鼠肺功能降低有保护作用。提示组胺Ｈ２受体（Ｈ２Ｒ）参与气道平滑肌舒张，并通过抑制变态反应中炎性介质的释放而改善肺功能，从而在哮喘发病中起一定保护作用。     

抗反流治疗对伴有胃食管反流病的支气管哮喘患者气道反应性的影响

支气管哮喘（简称哮喘）患者易并发胃食管反流病（ｇａｓｔｒｏｅｓｏｐｈａｇｅａｌｒｅｆｌｕｘｄｉｓｅａｓｅ，ＧＥＲＤ），有研究认为ＧＥＲＤ有诱发和加剧哮喘的作用［１，２］。气道高反应性是支气管哮喘的重要特征之一。本研究探讨抗反流治疗对伴有ＧＥＲＤ的支...     

Effect of age,height, and prechallenge respiratory resistance on bronchial hyperresponsiveness in childhood asthma using the forced oscillation technique

To evaluate the effects of age, height and prechallenge respiratory system resistance (Rrs) on bronchial responsiveness to methacholine inhalation (BRm) as measured by the oscillation technique in children with mild asthma, we studied BRm in 92 atopic children aged from 8 to 13 years (mean ± SD, 10.5 ± 1.7 years). Inhalation challenge was performed by administering progressively doubling doses of methacholine, until a twofold increase in Rrs from baseline had been reached. The minimum cumulative dose of methacholine (Dmin) at which Rrs deviated from baseline was identified by the point of deflection of the continuously recorded Rrs tracing. The Dmin represented the amount of methacholine which elicited BRm. By using single-regression analysis, height was negatively correlated with Rrs (p < 0.001). Height was positively and Rrs was negatively correlated with age (p < 0.001 and p < 0.001, respectively). Furthermore, height and age were correlated with Dmin (p < 0.001 and p < 0.001, respectively), but prechallenge Rrs was not correlated with Dmin (p > 0.1). To minimize the effect of height and prechallenge Rrs on BRm, the relationships between Dmin and age was studied in a subgroup with a narrow range of heights (135–155 cm, n = 32), and a narrow range of prechallenge Rrs (5.0–6.9 cmH₂ O/L/s, n = 42); there remained a statistically significant correlation between Dmin and age in the groups with comparable heights (p = 0.026) and Rrs (p = 0.003). These data suggest that the BHR in childhood asthma may be affected by height and age when measured by the oscillation technique. Considering the many advantages of the oscillation method, this technique may be very suitable for measuring BHR in childhood asthma. Pediatr Pulmonol. 1996;22:1–6. © 1996 Wiley-Liss, Inc.     

Evaluation of bronchial hyperresponsiveness by monitoring of transcutaneous oxygen tension and arterial oxygen saturation during methacholine challenge in asthmatic children.

BACKGROUND: Bronchial hyperresponsiveness (BHR) is a key feature of asthma, but the measurement of BHR is hampered by the fact that most tests of airway caliber are difficult to conduct at a young age. Methacholine-induced bronchoconstriction is associated with significant hypoxemia, which can be assessed noninvasively by transcutaneous oxygen pressure (tcPO2) and pulse oximetry. Evaluating BHR by monitoring tcPO2 instead of respiratory resistance (Rrs) has been used over a wide age range in childhood. OBJECTIVE: To investigate whether there is a consistent relationship between changes in arterial oxygen saturation (SaO2) and respiratory resistance (Rrs) similar to the relationship between tcPO2 and Rrs during methacholine challenge in young children and to assess the usefulness of SaO2 as a parameter for the indirect measurement of BHR. METHOD: We performed methacholine inhalation challenge by monitoring SaO2, tcPO2 and Rrs in 37 asthmatic children 5 to 7 years of age. Consecutive doses of methacholine were doubled until a 10% decrease in tcPO2 from the baseline was reached. We recorded the cumulative dose of methacholine (Dmin) at the inflection point of tcPO2 (Dmin-tcPO2), SaO2 (Dmin-SaO2), and Rrs(Dmin-Rrs). RESULTS: The mean value of Dmin-Rrs was 4.27 +/- 2.02 units, the mean value of Dmin-tcPO2 was 4.48 +/- 2.01 units, and the mean value of Dmin-SaO2 was 4.57 +/- 0.20 units. Inhalation of increasing doses of methacholine raised Rrs curvilinearly and depressed tcPO2 and SaO2. There were no significant differences between any of the parameters. There were significant relationships between Dmin-tcPO2 and Dmin-Rrs (r = 0.914, p < 0.001) and between Dmin-SaO2 and Dmin-Rrs (r = 0.905, p < 0.001) and a relationship between Dmin-tcPO2 and Dmin-SaO2 (r = 0.949, p < 0.001). CONCLUSION: We concluded that measurement of SaO2 and/or tcPO2 during methacholine inhalation challenge may be used to assess bronchial hyperresponsiveness. This study showed that both SaO2 and tcPO2 monitoring are safe, useful, and tolerable for use in children who are too young to cooperate with lung function tests.     

Astograph法支气管激发试验对哮喘诊断价值的研究

目的 评价Astograph法支气管激发试验在哮喘诊断中的价值.方法 测定80例哮喘患者和125例非哮喘患者的肺功能和气道反应性、敏感性,应用统计学方法分析两组指标间的差异,寻找能够诊断哮喘的指标及其临界值.结果 肺功能各项指标哮喘组均低于非哮喘组(FVC除外).激发试验指标Dmin和PD35哮喘组低于非哮喘组(P<0.01),但Rrs、Grs、SGrs、SGrs/Grs间的差异无统计学意义(P>0.05).哮喘组中SGrs与Dmin、PD35正相关(P<0.01;r=0.5029,0.2937).非哮喘组SGrs与PD35相关(P<0.01,r=-0.4264).以Dmin诊断哮喘,ROC曲线下面积为0.956,临界值5.9165,敏感性0.966,特异性0.925.以PD35诊断哮喘,ROC曲线下面积为0.949,临界值13.277,敏感性0.977,特异性0.895.结论 Astograph法气道激发试验有助于支气管哮喘的诊断,其中以Dmin≤5.9165 Unit或PD35≤13.277 Unit为阳性标准有较好的特异性及敏感性.     

内皮素和一氧化氮平衡在哮喘犬发病机制中的作用

目的 探讨内皮素（ＥＴ）和一氧化氮（ＮＯ）平衡失调在支气管哮喘（简称哮喘）发病机制中的作用。方法 吸入猪蛔虫抗原复制过敏性哮喘犬模型，随机将实验动物分为五组，即对照组（Ａ组，６只），哮喘组（Ｂ组，６只）生理盐水＋哮喘组（Ｃ组，６只）Ｎ＾Ｇ－单甲基左旋精氨酸（Ｌ－ＮＭＭＡ）＋哮喘组（Ｄ组，６只）和左旋精氨本－ａｒｇ）＋哮喘组（Ｅ组，６只），观察了ＥＴ－１和ＮＯ对犬气道平滑肌的影响。结果 ＥＴ－１使呼     

Bronchial sensitivity and bronchial reactivity in children with cough variant asthma

BACKGROUND: Cough variant asthma (CVA) is diagnosed in some children with chronic cough who do not have wheezing. However, the precise mechanism of CVA in children is unclear. OBJECTIVE: To evaluate the physiologic differences in the airways of children with classic asthma and CVA, the methacholine dose-response curves of respiratory resistance (Rrs) were studied. PATIENTS AND METHODS: CVA was diagnosed in 31 children with chronic cough (age range, 5 to 14 years; 19 boys and 12 girls; mean age, 8.5 years) on the basis of methacholine inhalation challenge using an oscillation method. For comparison, the study included 86 age-matched children with classic asthma (age range, 5 to 15 years; 42 boys and 44 girls; mean age, 9.5 years), 25 age-matched children with cough (age range, 5 to 15 years; 17 boys and 8 girls; mean age, 8.8 years), and 23 age-matched control subjects (8 boys and 15 girls; mean age, 9.2 years). Consecutive doses of methacholine were doubled until a 200% increase in Rrs from baseline was reached. The cumulative dose of methacholine at the inflection point of Rrs was considered to represent the bronchial sensitivity to inhaled methacholine (minimum dose of methacholine [Dmin]). The slope of the methacholine dose-response curve (SRrs), which was considered to represent bronchial reactivity, was measured from the increasing Rrs curve. RESULTS: The values of Dmin in classic asthma patients and in CVA patients were significantly lower than those for cough patients and control subjects. There was no significant difference in the values of Dmin between the classic asthma and CVA patients. The value of SRrs in CVA patients was significantly lower than that in classic asthma patients, cough patients, and control subjects (p < 0.05, p < 0.01, and p < 0.01, respectively). There was no significant difference in the value of SRrs between classic asthma patients, cough patients, and control subjects. CONCLUSIONS: These data show that bronchial reactivity in the children with CVA was significantly lower than that in the children with classic asthma, and this specificity has an effect on prolonged cough without wheezing in children with CVA.     

Relationship between bronchial hyperresponsiveness and development of asthma in wheezy infants

STUDY OBJECTIVES: To evaluate the relationship between bronchial hyperresponsiveness (BHR) in infants with wheezing and the subsequent development of asthma. INTERVENTION: Bronchial reactivity to inhaled methacholine (BRm) during the infantile period was studied using the transcutaneous partial pressure of oxygen (tcPO(2)) method. Children were followed long-term for the development of asthma. PATIENTS: Fourteen children with bronchiolitis (mean age, 0.7 years) and 48 with wheezy bronchitis (mean age, 2.3 years) were enrolled. For comparison, 40 children with asthma (mean age, 4.6 years) and 27 healthy control subjects without chronic respiratory disease (mean age, 2.7 years) were studied. MEASUREMENTS: Consecutive doses of methacholine were doubled until a 10% decrease in tcPO(2) from baseline was reached. The cumulative dose of methacholine (Dmin) at the inflection point of tcPO(2) (Dmin-PO(2)) was recorded. RESULTS: During > 10 years of follow-up, seven patients with bronchiolitis developed asthma and all patients in the higher BRm set developed asthma, compared with none in the lower BRm set. In the wheezy bronchitis group, Dmin-PO(2) values in the 32 patients who developed asthma were lower than those in patients who had not developed asthma (p < 0.001). CONCLUSIONS: We concluded that there is a tendency for infants with a clinical diagnosis of bronchiolitis or wheezy bronchitis and who show BHR in the infantile period to develop asthma. The presence of increased BHR after infantile respiratory diseases associated with wheezing may be a prelude to the development of childhood asthma.     

Evaluation of Bronchial Hyperresponsiveness by Monitoring of Transcutaneous Oxygen Tension and Arterial Oxygen Saturation during Methacholine Challenge in Asthmatic Children

Background. Bronchial hyperresponsiveness (BHR) is a key feature of asthma, but the measurement of BHR is hampered by the fact that most tests of airway caliber are difficult to conduct at a young age. Methacholine-induced bronchoconstriction is associated with significant hypoxemia, which can be assessed noninvasively by transcutaneous oxygen pressure (tcPO₂) and pulse oximetry. Evaluating BHR by monitoring tcPO₂ instead of respiratory resistance (Rrs) has been used over a wide age range in childhood.

Objective. To investigate whether there is a consistent relationship between changes in arterial oxygen saturation (SaO₂) and respiratory resistance (Rrs) similar to the relationship between tcPO₂ and Rrs during methacholine challenge in young children and to assess the usefulness of SaO₂ as a parameter for the indirect measurement of BHR.

Method. We performed methacholine inhalation challenge by monitoring SaO₂, tcPO₂ and Rrs in 37 asthmatic children 5 to 7 years of age. Consecutive doses of methacholine were doubled until a 10% decrease in tcPO₂ from the baseline was reached. We recorded the cumulative dose of methacholine (Dmin) at the inflection point of tcPO₂ (Dmin-tcPO₂), SaO₂ (Dmin-SaO₂), and Rrs(Dmin-Rrs).

Results. The mean value of Dmin-Rrs was 4.27 ± 2.02 units, the mean value of Dmin-tcPO₂ was 4.48 ± 2.01 units, and the mean value of Dmin-SaO₂ was 4.57 ± 0.20 units. Inhalation of increasing doses of methacholine raised Rrs curvilinearly and depressed tcPO₂ and SaO₂. There were no significant differences between any of the parameters. There were significant relationships between Dmin-tcPO₂ and Dmin-Rrs (r = 0.914, p < 0.001) and between Dmin-SaO₂ and Dmin-Rrs (r = 0.905, p < 0.001) and a relationship between Dmin-tcPO₂ and Dmin-SaO₂ (r = 0.949, p < 0.001).

Conclusion. We concluded that measurement of SaO₂ and/or tcPO₂ during methacholine inhalation challenge may be used to assess bronchial hyperresponsiveness. This study showed that both SaO₂ and tcPO₂ monitoring are safe, useful, and tolerable for use in children who are too young to cooperate with lung function tests.     

Bronchial hyperresponsiveness in children with atopic and nonatopic asthma

We have studied the bronchial hyperresponsiveness of children with atopic and nonatopic asthma by methacholine inhalation challenge, using a new device, the "Astograph." Three parameters, initial respiratory resistance (Rrs cont), bronchial sensitivity (Dmin), and bronchial reactivity (St), were studied. The Rrs cont values of atopic asthma were higher than those of the disease controls (p less than 0.05), while there was no difference between nonatopic asthma and disease controls. The Dmin values of atopic and nonatopic asthma were lower than those of disease controls (p less than 0.001; p less than 0.01). The St values of atopic and nonatopic asthma were higher than those of disease controls (p less than 0.001; p less than 0.01). There was no difference of Rrs cont and Dmin between the children with atopic and nonatopic asthma. However, St of the children with nonatopic asthma was remarkably higher than that of the children with atopic asthma (p less than 0.001). These data suggested that there was a remarkable difference of bronchial response to methacholine between the children with atopic asthma and those with nonatopic asthma.     

Effect of aging on the relationship between asthma severity and bronchial hyperresponsiveness in children with asthma.

An association between asthma and bronchial hyperresponsiveness (BHR) has been demonstrated. It is possible that the relationship between asthma severity and BHR in children with asthma is different in infants and in adolescents. The aim of this study is therefore to evaluate the effect of aging on the relationship between the severity of asthma and BHR in children with asthma. We measured BHR in 386 subjects ranging from 2 to 20 years of age. The subjects consisted of 323 children with asthma (boys:girls = 193:130, mean age 9.7 years) and 63 age-matched controls (boys:girls = 25:38, mean age 8.2 years). BHR was measured using the methacholine inhalation challenge by measuring the transcutaneous oxygen pressure (tcPO2) in children less than 6 years of age (Dmin-PO2) and by measuring the respiratory resistance (Rrs) in children 6 years of age and older (Dmin-Rrs). Throughout the whole age range, both the Dmin-PO2 and Dmin-Rrs in each asthma severity group were higher than those in the controls. In the asthmatics aged 2-5 years, the Dmin-PO2 levels in the mild asthma group were higher than those in the moderate and severe asthma groups (p < 0.001, p < 0.001, respectively), and the Dmin-PO2 levels in the moderate asthma group were also higher than those in the severe asthma group. This tendency was also found in the age ranges of 6-9 years and 10-13 years. In the asthmatics aged 14-20 years, the Dmin-Rrs levels were not significantly different among the three groups. Taken together, these data show that aging has an effect on the relationship between the severity of asthma and BHR during childhood and that BHR may not be the sole determinant for the severity of asthma in adolescence.     

Household Smoking and Bronchial Hyperresponsiveness in Children with Asthma

This study investigated whether household environmental tobacco smoke (ETS) exposure is associated with increased bronchial hyperresponsiveness (BHR) in children with asthma. Two hundred forty-nine children, ages 7-11 years, sampled from a larger group with reported asthma or multiple asthma symptoms identified in a community survey in Cape Town, underwent histamine challenge testing and had urinary cotinine measured. Parents were interviewed for information on smoking habits and a variety of covariates. Children with asthma whose mothers smoked had a lower frequency of BHR than asthmatic children of nonsmoking mothers, particularly if the mother smoked ≥15 cigarettes daily. BHR was also less common among children sharing a house with four or more smokers vs. fewer or none. BHR was unrelated to paternal smoking. In contrast, FEV₁ was lower among children whose mothers currently smoked. The findings do not support a mechanism whereby ETS exposure aggravates existing childhood asthma by increasing BHR. This association may be masked, however, by the degree to which mothers of asthmatic children adjust their smoking. The results are consistent with an adverse effect of maternal smoking on lung function in asthmatic children.