Inhibition of high-mobility group box 1 in lung reduced airway inflammation and remodeling in a mouse model of chronic asthma

The role of high-mobility group box 1 (HMGB1) in chronic allergic asthma is currently unclear. Both airway neutrophilia and eosinophilia and increase in HMGB1 expression in the lungs in our murine model of chronic asthma. Inhibition of HMGB1 expression in lung in ovalbumin (OVA)-immunized mice decreased induced airway inflammation, mucus formation, and collagen deposition in lung tissues. Analysis of the numbers of CD4⁺ T helper (Th) cells in the mediastinal lymph nodes and lungs revealed that Th17 showed greater increases than Th2 cells and Th1 cells in OVA-immunized mice; further, the numbers of Th1, Th2, and Th17 cells decreased in anti-HMGB1 antibody (Ab)-treated mice. In OVA-immunized mice, TLR-2 and TLR-4 expression, but not RAGE expression, was activated in the lungs and attenuated after anti-HMGB1 Ab treatment. The results showed that increase in HMGB1 release and expression in the lungs could be an important pathological mechanism underlying chronic allergic asthma and HMGB1 might a potential therapeutic target for chronic allergic asthma.     

Airway fibrosis in a mouse model of airway inflammation

BALB/c mice were sensitized to ovalbumin by systemic injection and then exposed for up to 8 weeks to ovalbumin aerosols in whole body chambers. A pattern of airway inflammation, mucous cell hypertrophy and hyperplasia, and airway remodeling with submucosal fibrosis was observed as lesions evolved over time. Larger conducting airways were removed from the lungs by microdissection. Airway fibrosis was quantified by direct assay for collagen content, which was significantly increased after 4 and 8 weeks of exposure to ovalbumin aerosol. Based upon PCR analysis of mRNA levels in the airways, most of the newly synthesized collagen was Type I. Relaxin, administered by continuous infusion over the second half of a 4-week exposure to ovalbumin, was able to inhibit the accumulation of collagen in the airways of exposed mice. Thus, stimulation of collagen degradation by an activator of collagen breakdown by matrix metalloproteinases appears to be an effective therapeutic strategy in prevention of airway fibrosis in this animal model. Whole body plethysmography of unrestrained mice indicated functional changes in airway reactivity in the lungs of exposed animals occurring in conjunction with the reported structural changes. This result indicates that the ovalbumin-exposed mouse may be a suitable model for examining structure-function relationships in the lungs of animals with a predictable time course of airway inflammation, remodeling, and fibrosis and for testing potential new drugs for treatment of asthma or chronic bronchitis at a mechanistic level.     

Susceptibility to ovalbumin-induced airway inflammation and fibrosis in inducible nitric oxide synthetase-deficient mice: mechanisms and consequences

In a previous study, we showed that BALB/c mice demonstrate significant increases in accumulation of airway collagen after 4 weeks of exposure to ovalbumin aerosol. In the current study we examined the response to ovalbumin aerosol of a different strain of mice, C57BL/6, and compared this response to an otherwise isogenic C57BL strain (iNOS(-/-)) in which the gene for inducible nitric oxide synthetase (iNOS) had been knocked out. We hypothesized that C57BL mice, a Th-1-responsive strain, would be relatively resistant to ovalbumin exposure compared with our previous observations in the BALB/c strain, a Th-2 responder. Our results are consistent with this hypothesis, especially with respect to the accumulation of collagen in the airways of the mice exposed to ovalbumin and increased airway reactivity to challenge with methacholine, as measured by the Penh response. Since NO participates in multiple signal transduction pathways, there was no a priori reason to predict whether iNOS(-/-) mice would be more or less susceptible to allergen-induced airway inflammation than their parental wild-type strain. Responses to ovalbumin exposure of the Th-1-responsive C57BL animals were significantly less (or slower) than those we observed with the iNOS(-/-) mice. Significant increases in airway collagen content were seen only after 6 weeks of exposure of the C57BL mice, as contrasted with 4 weeks in the iNOS(-/-) animals. At each time point examined, Penh values for the iNOS(-/-) mice were significantly increased, while no increases were observed with the C57BL strain. Thus, the iNOS(-/-) mice are more susceptible to ovalbumin-induced airway inflammation and fibrosis than the C57BL strain, giving results intermediate between the previous observations in BALB/c mice and our current findings in C57BL animals with the various assays performed. We also asked whether the effects of knocking out the iNOS gene were exerted before or after the release of TGF-beta(1) by eosinophils and other effector cells in the lung. We measured the response of C57BL and iNOS(-/-) mice to direct intratracheal challenge with TGF-beta(1). There was no apparent response of C57BL mice to TGF-beta(1) at 4 or 11 days after TGF-beta(1) challenge, as evaluated by bronchoprovocation testing. On the other hand, the observed Penh values were significantly greater in iNOS(-/-) mice that had also received TGF-beta(1) 4 days previously. These results strongly support the hypothesis that the increased sensitivity of iNOS(-/-) mice to ovalbumin is at least partially dependent on pathways that come into play subsequent to the release of TGF-beta(1) by effector cells in the lungs of mice exposed to ovalbumin aerosol.     

A geranyl acetophenone targeting cysteinyl leukotriene synthesis prevents allergic airway inflammation in ovalbumin-sensitized mice

Asthma is associated with increased pulmonary inflammation and airway hyperresponsiveness. The current use of corticosteroids in the management of asthma has recently raised issues regarding safety and lack of responsiveness in 5-10% of asthmatic individuals. The aim of the present study was to investigate the therapeutic effect of a non-steroidal small molecule that has cysteinyl leukotriene (cysLT) inhibitory activity, upon attenuation of allergic lung inflammation in an acute murine model. Mice were sensitized with ovalbumin (OVA) and treated with several intraperitoneal doses (100, 20, 2 and 0.2 mg/kg) of 2,4,6,-trihydroxy-3-geranylacetophenone (tHGA). Bronchoalveolar lavage was performed, blood and lung samples were obtained and respiratory function was measured. OVA sensitization increased pulmonary inflammation and pulmonary allergic inflammation was significantly reduced at doses of 100, 20 and 2 mg/kg with no effect at the lowest dose of 0.2 mg/kg. The beneficial effects in the lung were associated with reduced eosinophilic infiltration and reduced secretion of Th2 cytokines and cysLTs. Peripheral blood reduction of total IgE was also a prominent feature. Treatment with tHGA significantly attenuated altered airway hyperresponsiveness as measured by the enhanced pause (Penh) response to incremental doses of methacholine. These data demonstrate that tHGA, a synthetic non-steroidal small molecule, can prevent acute allergic inflammation. This proof of concept opens further avenues of research and development of tHGA as an additional option to the current armamentarium of anti-asthma therapeutics.     

盐酸氨溴索对毛细支气管炎小鼠IL-17/STAT3通路及气道高反应的影响

目的 探究盐酸氨溴索对毛细支气管炎小鼠气道高反应性及白细胞介素17(IL-17)/信号传导转录激活因子3(STAT3)通路的影响.方法 采用随机数字表法将72只Balb/c小鼠随机分为对照组、模型组、布地奈德组(20 mg/kg)、盐酸氨溴索高、中、低剂量(60、30、15 mg/kg)组,每组12只.除对照组外,其余...     

火把花根片对哮喘豚鼠气道炎症的作用

目的探讨火把花根片对哮喘豚鼠气道慢性炎症的作用。方法建立哮喘豚鼠动物模型 :将豚鼠 2 6只随机分为 3组 ,A组为火把花根组 (9只 ) ,B组为地塞米松组 (9只 ) ,C组为哮喘对照组 (8只 ) ,观测豚鼠支气管肺泡灌洗液 (BALF)细胞总数、嗜酸性粒细胞、淋巴细胞、中性粒细胞数量以及蛋白浓度和肺组织病理学的变化。结果A组BALF细胞总数、以嗜酸性粒细胞为主的炎性细胞数量及蛋白浓度均低于C组 (P <0 0 1) ,其肺组织气道慢性炎症表现亦较C组减轻。结论火把花根片可显著抑制哮喘豚鼠的气道慢性炎症     

沙美特罗/氟替卡松对慢性阻塞性肺疾病患者急性加重期气道炎症的影响

Objective To investigate the influence of salmeterol with fluticasone on airway inflammation of patients with acute exacerbation chronic obstructive pulmonary disease (COPD).Methods 40 COPD patients in the stage of acute exacerbation were randomly divided into salmeterol with fluticasone group( A group) and controll group (B group).Bronchial alveolar lavage( BAL) was performed as usual.The concentrations of IL-8 and TNF-α in bronchial alveolar lavage fluid(BALF) were measured by ELISA.The results were compared with that of 18 healthy volunteers.Results The levels of IL-8 and TNF-a in BALF of patients in A group(10.60 ± 1.42) μg/L, (14.80 ± 2.05) μg/Land B group( 10.77 ± 1.98) μg/L, (14.70 ± 2.03) μg/L were significantly higher than that of C group (3.40 ±0.65)μg/L, (4.67 ± 1.01) μg/L( all P <0.01) ;Before treatment,the levels of IL-8 and INF-α in BALF of A group( 10.60 ± 1.42)μg/L,(14.80 ±2.05) μg/L and B group( 10.77 ± 1.98) μg/L,(14.70 ±2.03) μg/L had no significant differences (all P > 0.05) ,and the concentrations of IL-8 and TNF-a in BALF in group A (4.39 ± 0.92)μg/L,(5.84 ±1.26) μg/L were significantly lower than that in group B(9.69 ± 1.43) μg/L, (12.88 ± 2.51) μg/L after two weeks treatment ( all P < 0.01).Conclusion Salmeterol with fluticasone could inhibit airway inflammation of COPD patients in the stage of acute exacerbation.     

氨茶碱辅助糖皮质激素对支气管哮喘患者气道炎症的改善作用研究

目的 探讨氨茶碱辅助糖皮质激素对支气管哮喘患者气道炎症的改善作用.方法 选取2014年2月至2015年3月我院呼吸内科收治的60例支气管哮喘患者为研究对象,采用抽签随机法均分为观察组和对照组,对照组给予糖皮质激素治疗,观察组在对照组基础上联合氨茶碱辅助治疗.观察治疗后两组临床疗效及气道炎症指标[白细胞介素-5(IL-5)、白细胞介素-10(IL-10)、肿瘤坏死因子(TNF-α)].结果 治疗后观察组总有效率较对照组显著高(86.67％ vs.63.33％;P＜0.05).两组治疗后IL-5、IL-10、TNF-α分别均较治疗前显著降低,且观察组IL-5[(9.82±3.82) pg/ml]、IL-10[(9.60±3.98) pg/ml]、TNF-α[(9.85±3.01) pg/ml]分别均较对照组显著降低,差异均有统计学意义(P＜0.05).结论 氨茶碱辅助糖皮质激素对支气管哮喘患者临床疗效显著,对患者气道炎症的改善作用显著,值得临床推广应用.     

支气管哮喘患者诱导痰中白细胞介素-9水平及其与气道炎症的关系

目的探讨支气管哮喘患者诱导痰中白细胞介素-9（IL-9）的水平及其与炎症细胞和肺功能的关系。方法分别选择28例支气管哮喘急性发作患者（哮喘急性发作组）和28例健康对照（健康对照组）,分别检测哮喘急性发作期和治疗后缓解期及健康对照组的肺功能;并用酶联免疫吸附实验（ELISA）测定诱导痰上清液中IL-9的水平。结果哮喘发作组患者诱导痰中IL-9水平明显高于哮喘缓解期,比较差异有统计学意义（P〈0.05）,哮喘发作组和缓解期组痰中IL-9水平高于健康对照组,比较差异有统计学意义（P〈0.05）。哮喘发作组患者诱导痰中IL-9水平与中性粒细胞数及嗜酸性粒细胞数均呈正相关（r值分别为0.68、0.81,P〈0.05）,与第一秒用力呼气容积占预计值的百分比（FEV%）呈负相关（r=-0.65,P〈0.05）。结论支气管哮喘患者诱导痰中增高的IL-9水平与其气道炎症和气流受限有关。     

咪喹莫特抑制哮喘大鼠气道炎症转录水平的研究

目的：探讨咪喹莫特拮抗支气管哮喘气道炎症的分子机制。方法：卵清蛋白腹腔注射与雾化吸入建立大鼠哮喘模型，采用逆转录－聚合酶链反应（RT－PCR）测定了不同剂量咪喹莫特对哮喘大鼠肺组织白介素（IL）－4mRNA、IL－5mRNA、IL－12mRNA和干扰素（IFN）－γ mRNA表达的影响。结果：咪喹莫特各治疗组及地塞米松组能显抑制哮喘大鼠肺组织中IL－4、IL－5mRNA的表达（与哮喘相比，均为P＜0．001；与空白对照组比，均为P＞0．05），各咪喹莫特组同时能显增加IL－12、IFN－γ mRNA表达（与哮喘组比，均为P＜0．001；与空白对照组比，均为P＞0．05），而地塞米松组不能增加IL－12、IFN－γ mRNA的表达（与哮喘组比，均为P＞0．05；与空白对照组比，均为P＜0．001）。咪喹莫特各治疗组间无显性差异。结论：咪喹莫特能降低哮喘大鼠肺组织中IL－4和IL－5基因转录，增加IL－12和IFN－γ基因转录，进而 抑制嗜酸性粒细胞的聚集、活化，发挥其抗气道炎症的作用。     

Effects of inhaled aminophylline on airway constriction and inflammation in ovalbumin-sensitized guinea pigs

Abstract

Background: The systemic administration of theophylline is useful for asthma treatment. However its narrow therapeutic range makes it difficult to use. Little is known about its potential in inhalation therapy, particularly repeated inhalation.

Objective: The purpose of this study is to investigate the therapeutic usefulness of inhaled aminophylline in an asthma model.

Methods: The effects of pretreatment with inhaled aminophylline (25?mg/mL for 30?min/dose) on airway response and inflammation after an ovalbumin (OVA) challenge and airway hypersensitivity to acetylcholine (Ach) were evaluated using guinea pigs sensitized with OVA.

Results: Aminophylline relaxed the ACh-induced contraction of tracheal smooth muscle in vitro in a concentration-dependent manner. Pretreatment with single-dose aminophylline inhalation suppressed OVA-induced airway constriction to the same extent as the intraperitoneal pretreatment with high-dose aminophylline (10–20?mg/kg). However, pretreatment with single-dose aminophylline inhalation did not suppress eosinophil infiltration into airways (neither bronchoalveolar lavage [BAL] fluid nor lung tissue) and did not suppress airway hyperreactivity to ACh, 24?h after OVA challenge. Repeated inhalation of aminophylline (twice daily for 7 days) suppressed the infiltration of eosinophils and suppressed airway hypersensitivity to ACh. In addition, high concentrations of aminophylline inhibited production of oxygen radicals by BAL cells.

Conclusion: Single-dose inhalation treatment with aminophylline has transient but relatively strong bronchodilating effects due to delivery of high doses into local airways. Repeated inhalation treatment suppressed airway inflammation and hypersensitivity induced by allergens. Therefore, inhaled aminophylline may be useful for asthma treatment.     

Glutathione-conjugated toluene diisocyanate causes airway inflammation in sensitised mice

Toluene diisocyanate (TDI) is a highly volatile compound that reacts readily with nucleophilic compounds, sulfhydryl groups in particular. Since the epithelial lining fluid of the airways contains high levels of the sulfhydryl, glutathione (GSH), inhalation of TDI is likely to result in the formation of GS-TDI conjugates. We therefore investigated whether GS-TDI is capable of provoking irritant and/or allergic reactions. Irritant effects of GS-TDI were studied after intratracheal administration of a range of doses of GS-TDI in saline to naive BALB/c mice. GS-TDI caused a dose-dependent increase in neutrophils in the lungs 24 h after instillation. A dose equivalent to 150 g of TDI or lower had no effect. For provocation of allergic reactions, mice were sensitised by application of 1% TDI onto the skin on days 0 and 1, and challenged intratracheally with a sub-irritant dose of GS-TDI on day 8. GS-TDI did not induce non-specific tracheal hyperreactivity to carbachol 24 and 48 h after challenge in TDI-sensitised mice. However, it increased the numbers of neutrophils in the lungs as compared with the control mice. These findings suggest that GSH conjugation does not diminish the capacity of TDI to elicit irritant-induced inflammation in the lungs of mice at doses above 150 g of TDI in the conjugate. Moreover, the capacity to induce allergic-specific inflammation was retained at concentrations of GS-TDI being devoid of irritant activity. However, the GS-TDI conjugate failed to induce non-specific tracheal hyperreactivity. This may be the consequence of the deposition of excess of GSH upon local dissociation of the conjugate.     

Negligible respiratory irritation and inflammation potency of pigmentary TiO2 in mice

Abstract

Titanium dioxide (TiO₂) is manufactured in millions of tons yearly, and it is used widely as pigment in various applications. Until recently, TiO₂ was considered toxicologically harmless and without adverse health effects. In this study, respiratory irritation and inflammation potencies of commercially available pigmentary TiO₂ particles (<5?µm, rutile) were studied. Single head-only exposures (30?min) of male Crl:OF1 mice at mass concentrations 6, 11, 21, and 37?mg/m³, and repeated exposures (altogether 16?h, 1?h/day, 4 days/week for 4 weeks) of female BALB/c/Sca mice at mass concentration of 16?mg/m³ to pigmentary TiO₂ were conducted. Minor sensory irritation was observed during acute and repeated exposures seen as elongation of the break after the inhalation, which is typical in sensory irritation, and caused by closure of the glottis inhibiting airflow from the lungs after inspiration. No pulmonary irritation, airflow limitation, nasal or pulmonary inflammation was observed. In conclusion, the respiratory irritation and inflammation potencies of the studied pigmentary TiO₂ particles seemed to be low and thus can serve as an ideal control exposure agent in short-term studies in mice.     

Microvascular remodelling in chronic airway inflammation in mice

1. Chronic inflammation is associated with blood vessel remodelling, including vessel proliferation and enlargement, and changes in vessel phenotype. We sought to characterize these changes in chronic airway inflammation and to determine whether corticosteroids that inhibit inflammation, such as dexamethasone, can also reduce microvascular remodelling. 2. Chronic airway inflammation was induced in C3H mice by infection with Mycoplasmapulmonis and the tracheal vessels treatment also decreased the immunoreactivity for P-selectin and the number of adherent leucocytes (595 +/- 203 vs 2,024 +/- 393 cells/ mm2 in treated and non-treated infected mice, respectively). 6. We conclude that microvascular enlargement and changes in vessel phenotype are features of some types of chronic inflammation and, furthermore, that dexamethasone reverses the microvascular enlargement, changes in vessel phenotype and leucocyte influx associated with chronic inflammatory airway disease.     

IL-17A 及IL-17RA 在不同恶性程度胶质瘤中表达的研究

摘要： 目的 研究白细胞介素 （IL） -17A 及其受体 （IL-17RA） 在不同恶性程度胶质瘤中表达的差异。方法 收集胶质瘤患者 50 例, 按照世界卫生组织的分类系统分为Ⅰ级 12 例, Ⅱ级 18 例, Ⅲ级 13 例, Ⅳ级 7 例。取患者外周血以及胶质瘤组织, 荧光实时定量 PCR 检测 IL-17A 及 IL-17RA 的 mRNA 水平, 采用免疫组化和 Western blot 检测 IL-17A 及 IL-17RA 的蛋白表达水平。结果 免疫组化染色结果显示, 随着胶质瘤恶性程度增加, IL-17A 及其受体 IL-17RA 表达增加。外周血中, IL-17A 及其受体 IL-17RA 的 mRNA 水平随着胶质瘤恶性程度增加而上升 （F 分别为 8.96、 10.34, 均 P＜0.05）。胶质瘤组织中 IL-17A 及其受体 IL-17RA 的 mRNA 水平随着胶质瘤恶性程度增加而上升 （F 分别为 11.21、 14.11, 均 P＜0.05）。在外周血和胶质瘤组织中, IL-17A 及其受体 IL-17RA 的蛋白水平随着胶质瘤恶性程度增加也上升 （外周血 F 分别为 9.90、 11.80, 均 P＜0.05; 胶质瘤组织 F 分别为 8.15、 14.46,均 P＜ 0.05）。结论 IL-17A 及其受体 IL-17RA 的表达与胶质瘤恶性程度呈正相关性。     

Inhibitory effect of Platycodi Radix on ovalbumin-induced airway inflammation in a murine model of asthma

Asthma is a chronic inflammatory disease of the airways characterized by an associated increase in airway responsiveness. In this study, we investigated the inhibitory effect of an aqueous extract from the root of Platycodi Radix (Changkil: CK) on airway inflammation in a murine model of asthma. Mice were sensitized and challenged by ovalbumin (OVA) inhalation to induce chronic airway inflammation and airway remodeling. CK markedly decreased the number of infiltrated inflammatory cells and the levels of Th1 and Th2 cytokines and chemokines compared with those in the OVA-induced group. In addition, CK reduced OVA-specific IgE levels in bronchoalveolar lavage (BAL) fluid. Based on lung histopathological studies, inflammatory cell infiltration and mucus hypersecretion were inhibited by CK administration compared to that in the OVA-induced group. Lung weight was reduced after CK administration. Also, increased generation of ROS in BAL fluid, as well as NF-κB nuclear translocation, by inhalation of OVA was diminished by CK. Moreover, CK reduced the OVA-induced upregulation of matrix metalloproteases activity. These findings indicate that oxidative stress may play a crucial role in the pathogenesis of bronchial asthma induced by OVA and that CK may be useful as an adjuvant therapy for the treatment of bronchial asthma.     

Narirutin inhibits airway inflammation in an allergic mouse model

1. Flavonoids are naturally occurring compounds that possess anti-allergic, anti-inflammatory, antiproliferative and anti-oxidant properties. In the present study, we investigated whether the flavonoid narirutin could reduce airway inflammation in ovalbumin (OVA)-sensitized/challenged NC/Nga mice, a model of allergic eosinophilic airway inflammation. 2. Mice were initially immunized intraperitoneally with OVA on Days 0 and 7 and then challenged with inhaled OVA on Days 14, 15 and 16. In addition, some mice received narirutin orally at doses of 0.1, 1 or 10 mg/kg bodyweight daily on Days 7-16. 3. At 10 mg/kg, but not 0.1 or 1 mg/kg, narirutin significantly diminished OVA-induced airway inflammation caused by infiltration of lung tissue with inflammatory and mucus-producing cells, as well as reduced eosinophil counts in the peripheral blood and bronchoalveolar lavage fluid (BALF), interleukin (IL)-4 levels in BALF and IgE levels in serum. 4. The mechanism of the anti-inflammatory effect of narirutin are likely to be associated with a reduction in the OVA-induced increases of IL-4 and IgE in a murine model of allergic eosinophilic airway inflammation. These findings suggest that narirutin may be an effective new tool in the treatment of bronchial asthma.     

Effect of long-term exposure to low-level toluene on airway inflammatory response in mice

Volatile organic compounds are the main substances causing multiple chemical sensitivity reactions in human. Our laboratory has previously showed that the exposure of low-level formaldehyde causes immunogenic and neurogenic inflammatory responses in mice. The aim of the present study was to investigate the effect of long-term, low-level toluene exposure on airway inflammatory responses in mice lung. We exposed female C3H mice to filtered air (0ppm) or 50ppm of toluene for 6h/day on 5days/week for 6 or 12 weeks in the whole body exposure chamber. One day following the last toluene exposure, we collected bronchoalveolar lavage fluid from each mouse and examined cellular infiltration and production of cytokines, chemokines, neurotrophins and substance P by using ELISA method. We found that the number of total cells and macrophages increased significantly in both 6 and 12-week-exposed mice. In addition, the production of interferon-gamma and substance P were decreased significantly and nerve growth factor was not affected in both 6 and 12-week-exposed mice. In contrast, neurotrophin-3 production in bronchoalveolar lavage fluid was significantly increased only in 12-week-exposed mice. Our findings suggest that long-term (12-week) exposure of mice to low-level toluene modulates airway inflammatory response via neurological signaling.     

吸入激素联合口服孟鲁司特钠防止小儿气道变应性炎症向纵深发展前瞻性研究

目的 探讨应用储雾罐经口鼻吸入糖皮质激素联合口服孟鲁司特钠阻断气道变态反应性炎症向纵深发展,防止变应性鼻炎（AR）向咳嗽变异型哮喘（CVA）、支气管哮喘（BA）转化的效果.方法 232例AR患儿被随机分为对照组114例,观察组118例.对照组予口服氯雷他定片,体重＜30 kg,每次5 mg,每日1次,体重≥30 kg,每次10 mg,每日1次.观察组在对照组治疗基础上,吸入丙酸氟替卡松定量气雾剂,每次1揿（125μg）,每日2次,症状控制后减为每日1次,采用带有活瓣的储雾罐辅助吸入,若患儿能够配合,嘱闭口呼吸1分钟.同时口服孟鲁司特钠,1～5岁用4 mg,6～ 14岁用5 mg,每天1次.两组疗程均为3个月.疗程结束后,每月至少随访1次,随访时间3年.若症状未愈或复发,继续以上治疗3个月.治疗后半年、1年、2年、3年比较两组AR未愈或复发以及CVA和BA发生率.若患儿诊断为BA则按有关治疗常规进行治疗.若符合CVA诊断标准,再将患儿随机分成两组,观察组按上述治疗方案继续半年治疗,对照组仅予祛痰、止咳、抗感染等治疗.症状未控制时每1～2周随访1次,症状控制后每月随访1次,随访时间3年.治疗后半年、1年、2年、3年比较两组CVA未愈或复发以及BA发生率.结果 治疗后半年、1年、2年、3年AR未愈或复发率在对照组和观察组分别为52％、60％、71％、80％和14.15％、16.38％、18.87％、25.47％,CVA发生率在对照组和观察组分别为40％、48％、57％、71％和15.09％、16.98％、20.75％、23.73％,BA发生率在对照组和观察组分别为30％、39％、47％、53％和11.32％、13.21％、16.04％、18.87％,对照组均明显高于观察组（P≤0.001）;CVA未愈或复发率在对照组和观察组分别为45％、55％、62.5％、75％和17.5％、25％、30％、37.5％,转化为BA在对照组和观察组分别是35％、45％、60％、70％和10％、12.5％、15％、17.5％,对照组均明显高于观察组（P＜0.01）.且随着随访时间延长,上述各项发生率对照组比观察组增加更为明显.结论通过应用储雾罐经口鼻吸入糖皮质激素联合口服孟鲁司特钠,可防止AR及CVA反复,且可防止AR向CVA和BA转化,阻断气道变态反应性炎症向纵深发展.