湖北地区汉族变应性哮喘患儿Tim-3启动子区基因多态性研究

目的 探讨湖北地区汉族儿童T细胞免疫球蛋白黏蛋白域蛋白．3（Tim-3）启动子区1541位C〉T和574位G〉T单核苷酸变异及其与变应性哮喘易感性之间的关系。方法 分别采用聚合酶链反应．限制性片段长度多态性（PCR-RFLP）和引物特异PCR-核酸序列测定技术检测湖北143例哮喘患儿和72名健康儿童Tim-3启动子区1541位C〉T和574位G〉T单核苷酸变异，讣算基因型和等位基因频率。结果 湖北地区健康儿童Tim-3启动子区1541位C／C、C／T和T／T基因型频率分别是0．961、0．039和0，而哮喘患儿频率分别为0．935、0．065、0，其基因型频率与对照组差异无统计学意义（r=0．3825，P=0．5362）；湖北健康儿童中Tim-3启动子区574位G／G、G／T和T／T基因型频率分别为0．992、0．008和0，而哮喘患儿频率分别为0．941、0．059、0，两组基因型频率差异有统计学意义（χ^2=4．134，P=0．042）。结论 湖北汉族儿童Tim-3启动子区存在多态性变异，其中574位G〉T多态性可能与湖北汉族儿童变应性哮喘易感性有关。     

National Study of Emergency Department Visits for Acute Exacerbation of Chronic Obstructive Pulmonary Disease, 1993–2005

Objectives: Little is known about recent trends in U.S. emergency department (ED) visits for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) or about ED management of AECOPD. This study aimed to describe the epidemiology of ED visits for AECOPD and to evaluate concordance with guideline‐recommended care. Methods: Data were obtained from National Hospital Ambulatory Medical Care Survey (NHAMCS). ED visits for AECOPD, during 1993 to 2005, were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM) codes. Concordance with guideline recommendations was evaluated using process measures. Results: Over the 13‐year study period, there was an average annual 0.6 million ED visits for AECOPD, and the visit rates for AECOPD were consistently high (3.2 per 1,000 U.S. population; P_trend = 0.13). The trends in the use of chest radiograph, pulse oximetry, or bronchodilator remained stable (all P_trend > 0.5). By contrast, the use of systemic corticosteroids increased from 29% in 1993–1994 to 60% in 2005, antibiotics increased from 14% to 42%, and methylxanthines decreased from 15% to <1% (all P_trend < 0.001). Multivariable analysis showed patients in the South (vs. the Northeast) were less likely to receive systemic corticosteroids (odds ratio [OR] = 0.6; 95% confidence interval [CI] = 0.4 to 0.9). Conclusions: The high burden of ED visits for AECOPD persisted. Overall concordance with guideline‐recommended care for AECOPD was moderate, and some emergency treatments had improved over time.     

Th2细胞因子调节哮喘炎症细胞转运机制的研究

目的 探讨Th2细胞因子IL-5、IL-13调节哮喘炎症过程中肺和骨髓之间的细胞转运机制。方法 建立哮喘动物模型,获取肺泡灌洗液,检测IL-5、IFN-γ,浓度并进行病理分析;应用原位杂交技术检测肺组织IL-5、IL-13 mRNA表达和骨髓IL-5mRNA表达;免疫组化法观察肺、骨髓IL-5免疫反应细胞;流式细胞仪检测骨髓CD34、CD3阳性细胞。结果 哮喘组肺泡灌洗液IL-5浓度明显高于对照组(P<0.001);哮喘组肺组织病理改变显示小气道痉挛,管壁周围炎性细胞浸润,以嗜酸粒细胞、淋巴细胞为主;哮喘组肺组织IL-5、IL-13 mRNA表达较对照组显著增加(P<0.01);哮喘组骨髓IL-5 mRNA阳性细胞明显增加(P<0.001),与肺组织IL-5 mRNA表达的增高密切相关(P<0.05);此外,哮喘组肺组织和骨髓IL-5免疫反应细胞显著增加(P<0.01),骨髓CD34、CD3细胞均显著增高(P<0.01),并且CD34增高与骨髓细胞表达IL-5 mRNA密切相关(P<0.05)。结论IL-5可能在转录和转录后水平均参与调节骨髓嗜酸粒细胞的功能和炎症细胞在肺和骨髓之间的转运。     

备劳特联合爱喘乐雾化吸入治疗儿童哮喘急性发作的疗效观察

目的 :观察氧雾化吸入备劳特和爱喘乐治疗儿童哮喘急性发作的疗效。方法 :选择 15 8例哮喘急性发作患儿作为研究对象 ,分为观察组和对照组。观察组采用氧驱动雾化吸入备劳特和爱喘乐 ;对照组静脉滴注氨茶碱和地塞米松。结果 :观察组显效率 87.3% (96 /110 ) ,总有效率 99.1% (10 9/110 ) ,临床治愈率 94 .5 % (10 4 /110 ) ;对照组显效率 2 2 .9% (11/48) ,总有效率 6 0 .4 % (2 9/48) ,临床治愈率 5 4 .2 % (2 6 /48)。观察组显效率、总有效率及临床治愈率皆显著高于对照组 ,差异有高度统计意义 (P <0 .0 1)。观察组治疗后心率较治疗前明显下降 ,差异有统计意义(P <0 .0 5 )。结论 :采用氧驱动雾化吸入备劳特和爱喘乐能快速、有效地控制哮喘发作。     

血小板激活因子拮抗剂YM-264对抗原引起气道嗜酸性粒细胞浸润的影响

应用鸡卵清蛋白致敏和刺激小鼠复制过敏性气道炎症反应模型研究血小板激活因子选择性拮抗剂ＹＭ－２６４对抗原引起气道嗜酸性粒细胞（ＥＯＳ）浸润的影响。结果发现，正常小鼠支气管肺泡灌洗液（ＢＡＬＦ）中未见到ＥＯＳ；致敏小鼠给予抗原多次反复吸入刺激后，ＢＡＬＦ中ＥＯＳ急剧增多。在ＹＭ－２６４治疗各组中，ＹＭ－２６４的不同剂量分别导致ＥＯＳ数下降２７．０％、４８．２％及６７．９％。还发现ＹＭ－２６４抑制ＥＯＳ对气道的浸润伴随着白细胞介素（ＩＬ）－５水平的明显下降。提示ＹＭ－２６４通过抑制ＩＬ－５的产生从而抑制了ＥＯＳ在气道的聚集。     

Sensitization to Zygophyllum fabago pollen. A clinical and immunologic study

Zygophyllum fahago is a herbaceous plant found widely in the Mediterranean area. There are no previous reports of its allergenicity. An aerobiologic and clinical survey was conducted in Murcia, southern Spain, to determine the quantity of airborne pollen and establish the possible role of this pollen as a cause of allergic symptoms. With a Hirst volumetric trap, we determined the atmospheric concentrations of this pollen in 1993, 1994,1995, and 1996. Of 1180 patients tested, 181 (15,34%) had a positive skin test. To determine its allergenicity, we divided 47 patients into three groups: in group 1, all the patients had symptoms of rhinoconjunctivitis plus asthma; in groups 2 and 3, rhinoconjunctivitis. In group 1, we performed a bronchial provocation test (BPT): in groups 2 and 3, we performed nasal provocation (NPT) and conjunctival provocation (CPT) tests, respectively, SDS-PAGE was used to characterize the antigenic fractions and RAST inhibition to determine cross-reactivity with other pollens. The pollen dispersion period is from May to September (445 grains/m³), BPT was positive in 13 of 15 patients, NPT in 14 of 16 patients, and CPT in 13 of 16 patients. RAST inhibition revealed cross-reactivity with Mercurialis, Ricinus, Olea. and Betula. SDS-PAGE identified 25 IgE antibody-binding components, five of which (60, 65, 41, 38, and 15.5/14,7 kDa) were recognized by 40% of the sera. By SDS-PAGE immunoblotting with sunflower antiprofilin rabbit serum and affinity chromatography we established that the Z. fahago extract has profilin. This study shows that this pollen becomes airborne and elicits an IgE response which triggers respiratory symptoms in allergic subjects.     

Overexpression of suppressor of cytokine signalling-5 augments eosinophilic airway inflammation in mice

BACKGROUND: Enhanced expression of the suppressor of cytokine signalling (SOCS)-5 might be of therapeutic benefit for T-helper type 2 (Th2) dominant diseases, as its expression is reported to result in a reduction of Th2 differentiation in vitro due to the inhibition of IL-4 signalling. OBJECTIVE: To investigate the regulatory role of SOCS-5 in vivo, we explored the phenotype of an experimental asthma model developed in SOCS-5 transgenic (Tg) mice. METHODS: The SOCS-5 Tg mice or wild-type (WT) mice were sensitized and repeatedly challenged with ovalbumin (OVA). We examined bronchoalveolar lavage fluid (BALF), lung specimens, and airway hyperresponsiveness (AHR) to methacholine. RESULTS: The production of IFN-gamma by CD4(+) T cells from unprimed SOCS-5 Tg mice was significantly increased in comparison with unprimed wild-type mice, indicating that SOCS-5 Tg mice have a Th1-polarizing condition under natural conditions. However, in an asthma model, significantly more eosinophils in the airways and higher levels of IL-5 and IL-13 in BALF were observed in the SOCS-5 Tg than the wild-type mice. AHR in the asthma model of SOCS-5 Tg was also more enhanced than that of wild-type mice. OVA-stimulated CD4(+) T cells from the primed SOCS-5 Tg mice produced significantly more IL-5 and IL-13 than CD4(+) T cells from wild-type mice. CONCLUSION: Our results demonstrate that the overexpression of SOCS-5 does not inhibit Th2 response, but rather augments the phenotype of the asthma model in vivo. This finding throws into question the therapeutic utility of using enhancement of SOCS-5 expression for Th2-dominant disease.     

Comparison of the efficacy and safety of ciclesonide 160 μg once daily vs. budesonide 400 μg once daily in children with asthma

Ciclesonide is an onsite-activated inhaled corticosteroid (ICS) for the treatment of asthma. This study compared the efficacy, safety and effect on quality of life (QOL) of ciclesonide 160 microg (ex-actuator; nominal dose 200 microg) vs. budesonide 400 microg (nominal dose) in children with asthma. Six hundred and twenty-one children (aged 6-11 yr) with asthma were randomized to receive ciclesonide 160 microg (ex-actuator) once daily (via hydrofluoroalkane metered-dose inhaler and AeroChamber Plus spacer) or budesonide 400 microg once daily (via Turbohaler) both given in the evening for 12 wk. The primary efficacy end-point was change in forced expiratory volume in 1 s (FEV1). Additional measurements included change in daily peak expiratory flow (PEF), change in asthma symptom score sum, change in use of rescue medication, paediatric and caregiver asthma QOL questionnaire [PAQLQ(S) and PACQLQ, respectively] scores, change in body height assessed by stadiometry, change in 24-h urinary cortisol adjusted for creatinine and adverse events. Both ciclesonide and budesonide increased FEV1, morning PEF and PAQLQ(S) and PACQLQ scores, and improved asthma symptom score sums and the need for rescue medication after 12 wk vs. baseline. The non-inferiority of ciclesonide vs. budesonide was demonstrated for the change in FEV1 (95% confidence interval: -75, 10 ml, p = 0.0009, one-sided non-inferiority, per-protocol). In addition, ciclesonide and budesonide showed similar efficacy in improving asthma symptoms, morning PEF, use of rescue medication and QOL. Ciclesonide was superior to budesonide with regard to increases in body height (p = 0.003, two-sided). The effect on the hypothalamic-pituitary-adrenal axis was significantly different in favor of ciclesonide treatment (p < 0.001, one-sided). Both ciclesonide and budesonide were well tolerated. Ciclesonide 160 microg once daily and budesonide 400 microg once daily were effective in children with asthma. In addition, in children treated with ciclesonide there was significantly less reduction in body height and suppression of 24-h urinary cortisol excretion compared with children treated with budesonide after 12 wk.     

How Frequent Are Asthma Exacerbations in a Pediatric Primary Care Setting and Do Written Asthma Action Plans Help in Their Management?

Purpose. In the National Heart, Lung, and Blood Institute Guidelines for the Diagnosis and Management of Asthma, the expert panel recommends that a written asthma action plan be provided for all patients with asthma. Studies evaluating the usefulness of the asthma action plan in children are limited. We aim to determine exacerbation frequency and usefulness of the asthma action plan in managing exacerbations that occur in a pediatric primary care setting. Methods. Caretakers of asthmatic children attending the general pediatric clinic in an inner-city hospital completed a one-page questionnaire covering topics such as asthma severity, frequency of exacerbations, and possession/usefulness of an asthma action plan. Although controversy exists over the definition of yellow and red zone exacerbations, we defined the yellow zone as symptoms that require albuterol more than three times a day or more than two nights in succession. The red zone was defined as symptoms requiring systemic corticosteroids and/or an urgent physician visit. Results. Seventy of 75 subjects completed the survey. Almost 80% of respondents carried the diagnosis of persistent asthma, whereas the remainder had intermittent asthma. Exacerbation frequency over a 3-month period was determined. Approximately 80% of children experienced at least one yellow zone episode: 42% had one or two yellow zone episodes, and 39.6% had between three and five episodes. Sixty-three percent of patients did not experience a single red zone exacerbation. Almost 75% (44 of 59) of subjects possessed an asthma action plan. Ninety percent (37 of 41) of respondents with action plans found the plan to be useful in managing exacerbations. Conclusion. Approximately four of every five asthmatic children seen in this primary care setting experienced a yellow zone exacerbation at least once during a 3-month period. One third experienced at least one red zone episode. Nine of every 10 caretakers with an action plan reported the asthma action plan to be of value in managing exacerbations.     

Pycnogenol® as an Adjunct in the Management of Childhood Asthma

A randomized, placebo-controlled, double-blind study involving 60 subjects, aged 6-18 years old, was conducted over a period of 3 months to determine the effect of Pycnogenol® (a proprietary mixture of water-soluble bioflavonoids extracted from French maritime pine) on mild-to-moderate asthma. After baseline evaluation, subjects were randomized into two groups to receive either Pycnogenol® or placebo. Subjects were instructed to record their peak expiratory flow with an Assess® Peak Flow Meter each evening. At the same time, symptoms, daily use of rescue inhalers (albuterol), and any changes in oral medications were also recorded. Urine samples were obtained from the subjects at the end of the run-in period, and at 1-, 2-, and 3-month visits. Urinary leukotriene C₄/D₄/E₄ was measured by an enzyme immunoassay. Compared with subjects taking placebo, the group who took Pycnogenol® had significantly more improvement in pulmonary functions and asthma symptoms. The Pycnogenol® group was able to reduce or discontinue their use of rescue inhalers more often than the placebo group. There was also a significant reduction of urinary leukotrienes in the Pycnogenol® group. The results of this study demonstrate the efficacy of Pycnogenol® as an adjunct in the management of mild-to-moderate childhood asthma.