孟鲁司特联合布地奈德在小儿咳嗽变异性哮喘中的疗效分析

目的:观察孟鲁司特联合布地奈德治疗儿童咳嗽变异性哮喘的临床疗效。方法:选择四川省成都市第六人民医院儿科门诊及住院诊治的咳嗽变异性哮喘儿童48例,随机分为布地奈德气雾剂组(对照组,n=24)和布地奈德加孟鲁司特组(实验组,n=24)。对照组常规吸入布地奈德气雾剂,实验组在常规吸入布地奈德气雾剂基础上加服孟鲁司特,每晚顿服,共20周,并随访20周。结果:两组显效及有效例数比较,差异无统计学意义(P>0.05);但两组总有效例数比较差异有统计学意义(P<0.05),实验组疗效优于对照组。实验组每月哮喘日间及夜间发作次数以及每月使用短效支气管扩张剂的天数较对照组明显减少(P<0.05)。两组第1秒钟用力呼气容积、呼气峰流速比较,差异有统计学意义(P<0.05),实验组改善较明显。结论:孟鲁司特钠与吸入布地奈德联合治疗儿童咳嗽变异性哮喘,疗效优于单纯应用布地奈德皮质激素。     

Childhood cough variant asthma and its relationship to classic asthma.

BACKGROUND: In pediatrics, some patients with chronic cough who have no evidence of a causative disease are diagnosed as having cough variant asthma (CVA). The precise prognosis of infants and children with CVA, however, is still unclear. OBJECTIVE: To evaluate the relationship between CVA and classic asthma in childhood. METHODS: To diagnose CVA, we performed a methacholine inhalation challenge with use of a transcutaneous oxygen pressure (tcPO2) monitoring system in 100 children with chronic cough, and 75 children (45 boys and 30 girls; mean age, 5.7 years) were diagnosed as having CVA. These patients underwent follow-up monitoring for more than 3 years to ascertain whether classic asthma developed. For comparison, 53 age-matched children with classic asthma (30 boys and 23 girls; mean age, 5.6 years) and 30 age-matched control subjects (12 boys and 18 girls; mean age, 5.5 years) also participated in this study. Consecutive doses of methacholine were doubled until a 10% decrease in tcPO2 from the baseline was reached. The cumulative dose of methacholine at the inflection point of tcPO2 (Dmin-PO2) was considered to represent the sensitivity of tcPO2 to inhaled methacholine. RESULTS: After 3 years or more of follow-up assessments, 52 of the 75 patients answered our questionnaire. Of the responding patients, 28 had been diagnosed as having classic asthma. A significant difference was noted in the age at onset of CVA between the children in whom classic asthma developed (the asthma-developed group) and those in whom classic asthma did not develop (the asthma-free group). No statistically significant differences in Dmin-PO2 between the asthma-developed group and the asthma-free group or between the girls and the boys, however, were foun CONCLUSIONS: This study showed that 75% of children with chronic cough had CVA, that classic asthma developed in 54% of the children with CVA, and that it is not the severity of bronchial hyperresponsiveness in CVA but the age at onset of CVA that is a risk factor for the development of classic asthma in childhood CVA.     

孟鲁司特钠治疗感染后咳嗽的疗效观察

目的探讨孟鲁司特钠治疗感染后咳嗽的疗效。方法收集2012年1月至2013年12月本院呼吸科门诊就诊的感染后咳嗽患者150例,按随机数字表分为观察组（n=75）和对照组（n=75）。对照组给予复方甲氧那明治疗,酌情应用阿奇霉素;观察组在对照组的基础上加用孟鲁司特钠睡前口服,疗程均为2周。比较治疗前后两组患者的日间、夜间及全天咳嗽症状积分,记录与治疗相关的不良反应。结果治疗前观察组和对照组的日间、夜间及全天咳嗽症状积分组间比较,差异均无统计学意义（均P〉0．05）。与治疗前比较,治疗后两组患者日间咳嗽症状积分均显著降低（观察组：0．41±0．25比1．97±0．63,对照组：0．52±0.31比1．82±0．71,均P〈0．05）。治疗后观察组夜间咳嗽症状积分较治疗前明显降低（0．32±0．18比2．01±0．58,P〈O．05）,而对照组治疗前后夜间咳嗽症状积分差异无统计学意义（P〉0．05）。与治疗前比较,治疗后两组患者全天咳嗽症状积分均显著降低（观察组：0．73±0．62比3．98±1．25,对照组：1．72±0．98比3．74±1．41,均P〈0．05）。观察组与对照组的不良反应发生率分别为9．3％（7／75）、10．7％（8n5）,差异无统计学意义（x2=0．074,P〉O．05）。结论孟鲁司特钠可有效控制感染后咳嗽,尤其是感染后夜间咳嗽。     

Longitudinal decline in pulmonary function in atopic cough and cough variant asthma

OBJECTIVE: Cough variant asthma and atopic cough are different clinical manifestations of eosinophilic airway inflammation presenting with isolated chronic non-productive cough. The aim of this study was to examine the longitudinal change in pulmonary function in cough variant asthma and atopic cough. METHODS: Longitudinal change in FEV1 was prospectively examined in 20 patients with cough variant asthma, 14 patients with atopic cough and 271 asymptomatic healthy subjects. All were lifetime non-smokers. Of the 20 cough variant asthma patients, 13 were taking long-term inhaled corticosteroid therapy (ICS) (beclomethasone dipropionate 615 +/- 58 micro g/day) and the other seven were not. Spirometry was taken at first visit, after cough was almost completely relieved on therapy, and at least once every year for 5 or more years afterwards. RESULTS: The slope of longitudinal change in FEV1 was not significantly different among cough variant asthma patients (- 0.029 +/- 0.007/year), atopic cough patients (- 0.021 +/- 0.022/year) and asymptomatic subjects (- 0.028 +/- 0.002 L/year). In patients with cough variant asthma, the slope in patients not taking inhaled corticosteroids (ICS) was 0.032 +/- 0.007 L/year, which was not significantly different from that in patients taking ICS (- 0.027 +/- 0.010 L/year). CONCLUSION: Pulmonary function decline is not greater in cough variant asthma than atopic cough and the normal population, and long-term ICS has no effect on the decline in cough variant asthma.     

Atopic features of cough variant asthma and classic asthma with wheezing

Background Cough variant asthma is a phenotype of asthma solely presenting with coughing. It involves airway inflammation and remodelling as does classic asthma with wheezing, and a subset of patients may progress to classic asthma. The atopic features of cough variant asthma remain unclear. Objective To compare atopic features between patients with cough variant asthma and those with classic asthma, and to examine the possible correlation of these features with the future development of wheezing in the former group. Methods Total and specific IgE levels of seven common aeroallergens [house dust mite (HDM), Gramineae/Japanese cedar/weed pollens, moulds, cat/dog dander] were examined in 74 cough variant asthma patients and in 115 classic asthma patients of varying severity. Forty of the former patients were prospectively observed for 2 years to determine whether cough variant asthma progressed to classic asthma despite inhaled corticosteroid treatment. Results Patients with classic asthma had higher total IgE (P<0.0001), larger numbers of sensitized allergens (P=0.03), and higher rates of sensitization to dog dander (24% vs. 3%, P<0.0001), HDM (46% vs. 28%, P=0.02), and moulds (17% vs. 7%, P=0.047) than did patients with cough variant asthma. Wheezing developed in six (15%) patients with cough variant asthma, who were sensitized to larger numbers of allergens (P=0.02) and had higher rates of sensitization to HDM (P=0.01) and dog dander (P=0.02) than the 34 patients in whom wheezing did not develop. Among the patients with classic asthma, total and specific IgE variables were similar in the subgroup with mild disease (n=60) and the subgroup with moderate‐to‐severe disease (n=55), as reported previously. Conclusions Atopy may be related to the development of wheezing in patients with cough variant asthma. To prevent the progression of cough variant asthma to classic asthma, avoidance of relevant allergens may be essential.     

Oral montelukast treatment of preschool-aged children with acute asthma.

BACKGROUND: Increased amounts of cysteinyl leukotrienes have been demonstrated in urine samples from asthmatic patients, particularly during exacerbations of asthma. Although the use of leukotriene receptor antagonists has been recommended in the treatment of chronic asthma, no guidelines are available regarding their use in the treatment of acute asthma. OBJECTIVE: To investigate the safety and effectiveness of a 4-mg tablet of oral montelukast in addition to short-acting beta2-agonist bronchodilator as the initial treatment in mild to moderate asthma exacerbations in children between 2 and 5 years old. METHODS: Fifty-one patients who were experiencing mild to moderate asthma exacerbation were included in a randomized, double-blind, placebo-controlled, parallel-group study. Each patient received either a 4-mg tablet of montelukast or placebo in addition to inhaled salbutamol and were followed up for 4 hours. The pulmonary index score, respiratory rate, and pulse were determined at baseline and throughout 4 hours after administration. RESULTS: Compared with placebo, the pulmonary index scores and respiratory rates were significantly lower in the montelukast group starting at 90 minutes (P = .01). This difference persisted at 120, 180, and 240 minutes of the study (P = .008, P = .02, and P = .048, respectively). At the end of the first hour of treatment, oral steroid need was 20.8% and 38.5% in patients randomized to the montelukast and placebo groups, respectively (P = .22). Hospitalization rates were not different between the 2 treatment groups. CONCLUSION: A single 4-mg tablet of montelukast had the potential to provide additive clinical benefit in mild to moderate acute asthma in preschool-aged children when administered concomitantly with short-acting beta2-agonist bronchodilators as the initial treatment.     

The efficacy of montelukast in the treatment of cat allergen-induced asthma in children

BACKGROUND: Montelukast is a leukotriene antagonist approved for the treatment of childhood asthma in children age 2 years and older. There are limited studies on its effects on allergic asthma in children. OBJECTIVE: We sought to evaluate montelukast's effects on upper and lower airway responses to intense cat allergen exposure. METHODS: In a double-blind, placebo-controlled, cross-over trial 18 subjects aged 6 to 14 years with cat-induced asthma were randomly assigned to receive 1 week each of either montelukast or placebo, followed by a 1-hour cat challenge in an environmental exposure unit. Upper and lower respiratory tract symptoms were rated, and spirometry and acoustic rhinometry were performed. Challenges were stopped early if the subject became too uncomfortable or had a greater than 50% decrease in FEV1. RESULTS: Overall changes in FEV1 were significantly different with montelukast treatment and remained significant after adjusting for allergen level (P =.02; adjusted P =.01). Lower respiratory tract symptom scores were significantly reduced with montelukast versus placebo (P =.007) but lost significance after adjusting for allergen level (P =.16). Challenge length was significantly longer with montelukast versus placebo (P <.001) and remained significant after adjusting for allergen level (P =.019). Montelukast did not significantly affect upper respiratory responses, as measured by means of symptom scores (P =.43) and changes in acoustic rhinometry (P =.078). CONCLUSIONS: Montelukast was significantly more effective than placebo in attenuating lower respiratory responses and extending challenge length when cat-sensitive children with mild persistent asthma were exposed to high levels of cat allergen.     

Fluticasone propionate/salmeterol combination compared with montelukast for the treatment of persistent asthma.

BACKGROUND: Asthma is a chronic disease characterized by inflammation and bronchoconstriction. Medications that are able to effectively treat both components are advantageous. OBJECTIVE: To compare the efficacy of an inhaled corticosteroid and a long-acting beta2-agonist combination product with a leukotriene antagonist for initial maintenance therapy in patients who were symptomatic while receiving short-acting beta2-agonists alone. METHODS: A 12-week, randomized, double-blind, double-dummy, multicenter study was conducted in 432 patients 15 years of age and older with persistent asthma who were symptomatic on short-acting beta2-agonists alone. Fluticasone propionate 100 microg and salmeterol 50 microg combination product (FSC) twice daily or montelukast 10 mg once daily was administered. RESULTS: At endpoint, compared with montelukast, FSC significantly increased morning predose forced expiratory volume in 1 second (0.61 +/- 0.03 L vs 0.32 +/- 0.03 L), morning peak expiratory flow rate (peak expiratory flow rate; 81.4 +/- 5.9 L/minute vs 41.9 +/- 4.8 L/minute), evening peak expiratory flow rate (64.6 +/- 5.3 L/minute vs 38.8 +/- 4.7 L/minute), the percentage of symptom-free days (40.3 +/- 2.9% vs 27.0 +/- 2.7%), the percentage of rescue-free days (53.4 +/- 2.8% vs 26.7 +/- 2.5%), and the percentage of nights with no awakenings (29.8 +/- 2.5% vs 19.6 +/- 2.1%) (P < or = 0.011, all comparisons). At endpoint, FSC significantly reduced asthma symptom scores (-1.0 +/- 0.1 vs -0.7 +/- 0.1) and rescue albuterol use (-3.6 +/- 0.2 puffs/day vs -2.2 +/- 0.2 puffs/day) compared with montelukast (P < 0.001). At endpoint, patients treated with FSC also had a significantly greater improvement in quality of life scores and were more satisfied with their treatment compared with montelukast-treated patients (P < or = 0.001). Both treatments were well tolerated. CONCLUSIONS: Initial maintenance therapy with FSC provides greater improvement in asthma control and patient satisfaction than montelukast.     

中枢BDNF对咳嗽变异性哮喘豚鼠模型的调控作用

目的:研究脑源性神经营养因子(BDNF)在豚鼠咳嗽变异性哮喘(CVA)发生发展中的调控机制和对生长相关蛋白43(GAP-43)表达的影响。方法:选择Hartley雄性豚鼠为研究对象,制备并鉴定CVA豚鼠模型,确定CVA发作时脑内BDNF含量和(GAP-43)表达的变化。人为改变CVA豚鼠中枢BDNF含量,观察外周气道炎症和中枢GAP-43表达的相应改变。结果:制备的CVA豚鼠模型通过鉴定符合要求。(1)模型组豚鼠中枢BDNF和GAP-43表达量明显高于生理盐水对照组(P0.05)。(2)与中枢注射人工脑脊液的CVA豚鼠相比,注射外源性BDNF可以增加肺组织气道周围的物质P免疫阳性反应物并加剧外周气道炎症,同时中枢GAP-43免疫阳性反应物分布增多(154.3±25.7 vs 78.2±22.8,P0.01)。结论:中枢BDNF在豚鼠CVA发生发展中具有调控作用,这种作用可能通过调节GAP-43表达产生。     

舒利迭联合孟鲁司特治疗咳嗽变异性哮喘患者气道炎症的影响分析

目的 探讨舒利迭联合孟鲁司特治疗咳嗽变异性哮喘患者气道炎症的影响.方法 选择2015年3月至2016年3月我院诊治的咳嗽变异性哮喘患者70例作为研究对象.按随机数表法分为观察组和对照组各35例.对照组采用舒利迭进行治疗,观察组在对照组的基础上联合孟鲁司特进行治疗.比较两组患者的症状改善用时情况、肺通气功能、促炎症细胞因子水平、嗜酸性粒细胞(Eosinophil,Eos)及呼出气一氧化氮(Fractional exhaled nitric oxide,FeNO)水平.结果 治疗后,观察组症状缓解和消失用时均短于对照组[(6.05±1.44)d比(7.21±1.52)d,(7.63±1.75)d比(8.74±1.58)d](P<0.05);观察组患者肺通气功能中第1秒用力呼气容积(FEV 1)、第1秒用力呼气容积占预计值百分比(FEV 1/pred)、第1秒用力呼气容积占用力肺活量比值(FEV 1/FVC)及呼气峰流速占预计值百分比(PEF/pred)均高于对照组(P<0.05);观察组的白细胞介素(interleukin,IL)-12高于对照组[(84.26±10.97)ng/L比(68.13±9.82)ng/L](P<0.05),肿瘤坏死因子 α(tumour necrosis factor-α,TNF-α)及IL-6均低于对照组[(0.65±0.13)ng/L比(0.94±0.16)ng/L,(14.11±3.78)ng/L比(20.43±4.14)ng/L](P<0.05);观察组患者的Eos及FeNO均低于对照组[(2.61±1.75)%比(5.34±2.03)%,(45.68±11.43)ppb比(78.46±18.42)ppb](P<0.05).结论 舒利迭联合孟鲁司特治疗咳嗽变异性哮喘能有效改善患者肺通气功能,缩短治疗时间,缓解患者气道炎症并改善患者的炎症反应状态,效果显著,值得推广.     

Analysis of vascular endothelial growth factor levels in induced sputum samples from patients with cough variant asthma.

BACKGROUND: We previously found that vascular endothelial growth factor (VEGF) levels in induced sputum samples are increased in patients with classic asthma and are associated with the degree of airflow obstruction and airway microvascular permeability. OBJECTIVE: To examine VEGF levels and the degree of airway microvascular permeability in patients with cough variant asthma (CVA). METHODS: Levels of VEGF in induced sputum samples and airway microvascular permeability were examined in 12 controls, 16 patients with CVA, and 16 patients with classic asthma. We also evaluated the relationship between VEGF level and the clinical features of these 2 disorders. RESULTS: Mean (SD) VEGF levels and airway vascular permeability index values were significantly higher in patients with CVA (VEGF: 2,520 [1,050] pg/mL; P < .001; vascular permeability index: 0.017 [0.006]; P = .003) and classic asthma (4,750 [1,260] pg/mL; P < .001; 0.028 [0.009]; P < .001) than in controls (1,420 [1,230] pg/mL; 0.009 [0.003]). Furthermore, these values were significantly higher in patients with classic asthma vs CVA. We also found significant correlations between VEGF level and airway vascular permeability index in patients with CVA (r = 0.60; P = .02) vs classic asthma (r = 0.83; P = .001). Furthermore, VEGF levels were inversely correlated with the degree of airflow obstruction and airway hyperresponsiveness to methacholine in patients with CVA and classic asthma. CONCLUSIONS: Airway microvascular hyperpermeability induced by elevated VEGF levels contributes to abnormal airway function in CVA and classic asthma, and differences in the clinical features of these 2 disorders may depend on airway VEGF levels.     

Methacholine vs adenosine on intra and extrathoracic airway hyperresponsiveness in patients with cough variant asthma

Background: Airway hyperresponsiveness (AHR) can be studied by bronchoprovocation test (BPT) using direct (methacholine – MCh) or indirect (adenosine 5′‐monophosphate – AMP) stimuli. These two substances have not been compared in cough variant asthma (CVA). Objective: We designed a randomized, single‐blind, cross‐over study to compare AMP and MCh in the detection of CVA. Additionally, we examined whether assessment of extrathoracic airway hyperresponsiveness (EAHR) during MCh and AMP helped in the evaluation of CVA. Methods: Patients with CVA with previous positive MCh BPT performed challenges with AMP and MCh. The variables were: (i) a provocative dose producing a 20% fall in forced expiratory volume in 1 s (FEV₁) value (PD₂₀MCh); (ii) a provocative dose producing a 25% fall in the maximal mid‐inspiratory flow (FIF₅₀) from baseline (PD₂₅MCh) for MCh; (iii) a provocative concentration producing a 20% fall in FEV₁ value (PC₂₀AMP) and (iv) a provocative concentration producing a 25% fall in the FIF₅₀ from baseline (PC₂₅AMP) for AMP. Results: All 113 patients with CVA responded to PD₂₀MCh and 96% and 69% responded to PC₂₀AMP, if we used PC₂₀ ≤ 200 mg/ml or PC₂₀ ≤ 100 mg/ml, respectively, with an excellent correlation between these two tests (r = 0.87 and 0.76, respectively). Extrathoracic AHR associated with AHR was found in 10% in MCh challenge and in 11% with AMP challenge and no patients had EAHR alone. Conclusion: Adenosine challenges correlate well with MCh in patients with CVA. A minority (c. 10%) of CVA patients have EAHR as measured by these tests, while most had AHR as assessed with each of the challenge agents.     

普米克令舒治疗儿童咳嗽变异型哮喘的临床观察

目的观察观察普米克令舒治疗儿童咳嗽变异型哮喘的临床效果。方法采用随机分组,自2002年1月~2004年12月门诊及病房诊治的123例咳嗽变异型哮喘患儿分为3组。治疗组35例,予普米克令舒雾化吸入,对照1组42例,予必可酮雾化吸入,对照2组46例,予酮替芬及舒喘灵。治疗组及对照1组在对照2组基础上进行。观察治疗后咳嗽改善快慢情况,作统计学分析。结果治疗组与对照1组症状改善快慢方面没有显著性差异,两组差异没有统计学意义(P>0.05),与对照2组有显著性差异,两组有统计学意义(P<0.01)。结论普米克令舒联合抗过敏药及支气管扩张剂能有效治疗儿童咳嗽变异型哮喘,应用更方便。     

Effect of montelukast on peripheral airflow obstruction in children with asthma.

BACKGROUND: Montelukast is a widely used controller agent in childhood asthma. It is modestly effective in reducing symptoms, decreasing the need for rescue albuterol, and improving forced expiratory volume in 1 second (FEV1). OBJECTIVE: To determine whether montelukast therapy improves peripheral airway obstruction as measured by lung volumes, air trapping, airway resistance (Raw), and specific conductance (Sgaw). METHODS: Twenty-one children aged 9 to 18 years with mild-to-moderate asthma were randomized into a double-blind, placebo-controlled study to receive montelukast (5 or 10 mg) or matching placebo daily for 8 weeks. Symptoms and albuterol use were recorded twice daily, and exhaled nitric oxide measurement, forced oscillometry, spirometry, and body box plethysmography (before and after beta-agonist use) were performed at randomization and at 2, 4, 6, and 8 weeks. Circulating eosinophil counts and serum eosinophil cationic protein (ECP) levels were obtained at randomization and at 8 weeks. RESULTS: Montelukast-treated patients had lower residual volume (P = .05), residual volume-total lung capacity ratio (P = .04), Raw (P = .02), Sgaw (P = .03), and serum ECP levels (P = .02) at 8 weeks compared with those treated with placebo. There was a trend toward reduced daytime and nighttime albuterol use, although the difference did not reach statistical significance. There were no significant differences in FEV1, FEV1-forced vital capacity ratio, exhaled nitric oxide levels, or daytime and nighttime symptom scores between the 2 groups. CONCLUSIONS: Montelukast therapy was associated with less air trapping, hyperinflation, and Raw and better Sgaw compared with placebo. Lower serum ECP levels, a surrogate measure of airway inflammation, were associated with improvements in lung function.     

Effects of 24-week add-on treatment with ciclesonide and montelukast on small airways inflammation in asthma

BackgroundEosinophilic inflammation of the small airways is a key process in asthma that often smolders in treated patients. The long-term effects of add-on therapy on the persistent inflammation in the small airways remain unknown.ObjectiveTo examine the effects of add-on therapy with either ciclesonide, an inhaled corticosteroid with extrafine particles, or montelukast on small airway inflammation.MethodsSixty patients with stable asthma receiving inhaled corticosteroid treatment were enrolled in a randomized, open-label, parallel comparison study of 24-week add-on treatment with ciclesonide or montelukast. Patients were randomly assigned to 3 groups: ciclesonide (n = 19), montelukast (n = 22), or no add-on as controls (n = 19). At baseline and at weeks 4, 12, and 24, extended nitric oxide analysis; pulmonary function tests, including impulse oscillometry; blood eosinophil counts; and asthma control tests (ACTs) were performed.ResultsA total of 18 patients in the ciclesonide group, 19 in the montelukast group, and 15 in the control group completed the study and were analyzed. With repeated-measures analysis of variance, ciclesonide produced a significant decrease in alveolar nitric oxide and a significant improvement in ACT scores over time. Montelukast produced significant decreases in alveolar nitric oxide concentrations and blood eosinophil counts over time and slightly improved ACT scores, whereas no such changes were observed in the control group. Alveolar nitric oxide concentrations with ciclesonide and reactance area at low frequencies with montelukast produced greater improvements over time compared with control.ConclusionCiclesonide add-on therapy and montelukast add-on therapy may act differently, but both separately can improve small airway abnormalities and provide better asthma control.Trial Registrationumin.ac.jp/ctr Identifier: UMIN000001083