青春型双歧杆菌对哮喘儿童树突状细胞功能的影响

目的研究青春型双歧杆菌对过敏性哮喘儿童外周血单个核细胞来源的树突状细胞（dendritic calls,DC）表面共刺激分子表达及其细胞因子分泌的影响。方法从15例过敏性哮喘儿童和15例非哮喘儿童的外周血单个核细胞诱导生成未成熟DC．与青春型双歧杆菌共培养48小时后．用流式细胞仪检测DC表面CD86和HLA-DR分子的表达,用ELISA方法检测培养上清中自细胞介素（IL）-10、IL-12和IFN-γ的水平。结果经双歧杆菌刺激后,哮喘儿童DC表面CD86表达明显增高（P〈0．05）,DC分泌IL-12和IFN-γ水平明显增高;而双歧杆菌刺激对非哮喘儿童的CD86和HLA-DR表达无明显影响,但可使其DC分泌IL-12及IL-10水平明显增高。结论青春型双歧杆菌既可以通过上调CD86的表达,促进DC成熟;又可刺激DC分泌IL-12和IFN-γ,改变Th2优势分化,纠正Th1/Th2失衡,这可能是益生菌防治变态反应性疾病的机制之一。     

A Population-based Clinical Study of Allergic and Non-allergic Asthma

Background. The aim of this study was to describe differences between allergic and non-allergic asthma in a large community-based sample of Danish adolescents and adults. Methods. A total of 1,186 subjects, 14 to 44 years of age, who in a screening questionnaire had reported a history of airway symptoms suggestive of asthma and/or allergy, or who were taking any medication for these conditions were clinically examined. All participants were interviewed about respiratory symptoms, and furthermore skin test reactivity, lung function, and airway responsiveness were measured. Results. A total of 489 individuals had clinical asthma of whom 61% had allergic asthma, whereas 39% had non-allergic asthma. Subjects with non-allergic asthma were more likely to be females, OR = 2.24 (1.32–3.72), p = 0.003, and to have cough as the predominant symptom, OR = 1.96, (1.19–3.23), p = 0.008, but were less likely to have AHR, OR = 0.40, (0.24–0.66), p < 0.001, food allergy, OR = 0.28, (0.11–0.73), p = 0.009, and symptoms of rhinitis, OR = 0.08 (0.05–0.14) compared with subjects with allergic asthma. Subjects with non-allergic asthma had had persistent symptoms within the last 4 weeks more often than subjects with allergic asthma (68% vs. 53%), p = 0.001. Conclusions. Non-allergic asthma accounts for two in every five cases of asthma in adults and constitutes symptomatically, and in terms of lung function, a more severe form of disease than allergic asthma.     

microRNA在过敏性哮喘中的作用

microRNA(miRNA)是一种短单链小分子RNA,与蛋白质一起形成RNA诱导沉默复合体,引起靶mRNA的降解或抑制其翻译,所以miRNA的变化可影响机体大部分基因的表达。自从在哺乳动物细胞中被发现后,miRNA在过敏性疾病中的重要作用近些年来正逐步得到研究者重视。该文综述了miRNA在过敏性哮喘中的功能,主要包括miRNA的生成、调节辅助T细胞极化、在炎性反应和组织反应中的变化,胞外miRNA作为过敏性哮喘诊断的生物指标;并对miRNAs在未来的研究和应用进行展望。     

淋巴免疫治疗过敏性哮喘的临床疗效

目的评价标准化屋尘螨过敏原淋巴免疫治疗过敏性哮喘的临床疗效及安全性。方法 72例屋尘螨致敏性哮喘患者,随机分为治疗组和对照组,每组各36例,对照组给予布地奈德气雾剂和沙丁胺醇气雾剂治疗;治疗组在上述药物治疗同时,行超声引导下分别于0、4、8、12、16和20周行腹股沟淋巴结内注射屋尘螨过敏原制剂,除0周用药剂量为100 SQ-U外,其余5次应用剂量均为1000 SQ-U。治疗前后两组患者分别进行血清屋尘螨特异性IgE(sIgE)检测、哮喘控制测试(asthma control test,ACT),药物用量评分、肺功能[第1秒用力呼气容积占预计值的百分比(percentage of forced expiratory volume in first second to predicted value,FEV1%)、第1秒用力呼气容积与用力肺活量比值(ratio of forced expiratory volume in first second to forced vital capacity,FEV1/FVC)和峰流速占预计值的百分比(percentage of peak expiratory flow to predicted value,PEF%)]检测并记录患者疗程中的不良反应。结果治疗组32例患者完成了淋巴免疫治疗,2例因怀孕退出,2例失访;对照组32例按要求完成了对照观察,4例失访。治疗组患者治疗后4、8、12、16和20周ACT评分分别为(15.72±2.00)、(16.44±2.06)、(18.88±1.29)、(20.16±1.43)、(23.97±1.03),高于治疗前(0)周(15.34±2.15),差异有统计学意义(P<0.01);12、16和20周ACT评分均高于对照组同时间ACT评分[(16.63±2.12)、(16.81±2.10)、(16.87±2.30)],差异有统计学意义(P<0.01)。治疗后肺功能检测(FEV1%、FEV1/FVC和PEF%)分别为(74.81±5.91)、(77.31±5.43)、(74.09±4.71),均明显高于治疗前各项[(57.06±7.49)、(60.31±7.04)、(50.81±6.57)]及治疗后对照组水平[(54.91±7.79)、(59.44±8.77)、(50.38±8.13)],差异有统计学意义(P<0.01)。治疗组治疗后药物用量评分(0.66±0.43)和血清屋尘螨sIgE浓度(1.69±0.92)kU/L明显低于治疗前[(2.19±0.78)、(2.73±1.09)kU/L],且明显低于对照组[(1.92±0.77)、(3.09±1.29)kU/L],差异均有统计学差异(P<0.01)。32例淋巴免疫治疗患者进行了192次浅表淋巴结注射,未发生局部不良反应和全身不良反应。结论过敏原淋巴免疫治疗不仅临床疗效显著,而且大大缩短了疗程,减少了变应原剂量、注射次数和不良反应的发生,为安全、有效的病因治疗方法。     

The Impact of Comorbid Atopic Disease on Asthma: Clinical Expression and Treatment

Clinically, asthma and allergic rhinitis involve separate regions of the respiratory tract while representing a common underlying inflammatory syndrome. Much evidence supports an epidemiologic association between the diseases, paranasal sinus involvement in both conditions, and parallel relationship in severity and treatment outcomes. Pathophysiologic mechanisms, including immunoglobulin E (IgE)- mediated inflammation, are also shared. Blocking IgE with the recombinant humanized monoclonal antibody omalizumab demonstrated clinical efficacy in patients with upper and lower airway diseases. IgE blockade, leukotriene modulation, and B-cell depletion therapy have all exhibited success in chronic inflammation, reinforcing and expanding the beneficial role of immunomodulation of global mediators.     

A 26-Week,Randomized, Double-Blind,Placebo-Controlled,Multicenter Study to Evaluate the Effect of Omalizumab on Asthma Control in Patients with Persistent Allergic Asthma

Objective. The 2007 National Heart, Lung, and Blood Institute (NHLBI) asthma guidelines shifted the focus of care from asthma severity to ongoing assessment of asthma control using the components of impairment and risk. We evaluated the effect of omalizumab on asthma control in patients with persistent allergic asthma inadequately controlled with NHLBI Step 4 or above asthma therapy. Methods. In this double-blind, placebo-controlled study, patients ≥12 years (n = 271) received omalizumab (n = 136) or placebo (n = 135) every 2 or 4 weeks for 24 weeks. The primary efficacy variable, change from baseline in Asthma Control Test (ACT) total score, and Investigator’s Global Evaluation of Treatment Effectiveness (IGETE, secondary efficacy variable) were evaluated at week 24. Results. ACT score improved more with omalizumab compared with placebo (least squares means [LSMs]: 5.01, 4.36); however, the difference was not significant (p = .1779). Similarly, IGETE was not significantly different (p = .1177), but more patients treated with omalizumab (26/127, 20%) compared with placebo (19/131, 15%) had IGETE rated as “Excellent.” Significant benefits were observed for omalizumab compared with placebo for change in ACT score (LSMs: 6.66, 5.27; p = .0334) and IGETE (p = .0321) at week 24 in a subgroup of patients with very poorly controlled asthma (ACT ≤ 15) at baseline. There were no significant differences for the subgroup of patients with forced expiratory volume in 1 second ≤ 80% predicted at baseline. Adverse events (AEs) were similar between groups with no drug-related serious AEs or deaths. Conclusions. For allergic asthma patients with NHLBI Step 4 or above asthma therapy, omalizumab consistently improved asthma control; however, compared with placebo, differences were not significant. Placebo-treated patients had substantial improvement in their ACT score, which may have limited the ability to detect differences between treatment groups. Subgroup analyses showed significant improvements with omalizumab versus placebo in patients with very poorly controlled asthma.     

Gender Differences in IgE-Mediated Allergic Asthma in the Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) Study

Background. The TENOR study consists of a large cohort of subjects with severe or difficult-to-treat asthma. The objective of this analysis was to evaluate demographic and clinical characteristics of subjects 12 years of age or older with immunoglobulin E (IgE)-mediated allergic asthma (skin test positive with an IgE level ≥ 30 to ≤700 IU/mL), and specifically, to assess gender differences in this cohort. Methods. A total of 4,756 subjects were enrolled by 283 US study sites between January and October 2001. Of those subjects 12 years or older at baseline with an IgE measure and who were skin tested (n = 2,843), 1,783 (63%) were skin test positive and had an IgE level between ≥ 30 to ≤ 700 IU/mL. Results. Compared to males, females reported significantly greater healthcare utilization (steroid bursts in previous 3 months: 50% vs 42%, p < 0.001; unscheduled office visits in previous 3 months: 50% vs 36%, p < 0.0001; missed 1+ days of work/school in previous 2 weeks: 14% vs 10%, p < 0.01). Females also reported significantly more asthma control problems and lower asthma-related quality of life (4.6 ± 1.3 vs 5.2 ± 1.2; p < 0.0001); the difference was clinically meaningful. Asthma triggers and allergic comorbidities, such as allergic rhinitis and atopic dermatitis, were more common in female subjects. Despite their overall worse health outcomes, female subjects demonstrated better lung function, had similar treatment patterns, and showed no differences in physician-assessed asthma severity when compared with males. Conclusions. The reasons for these gender differences in subjects with IgE-mediated allergic asthma are complex, but results from this analysis suggest that detailed evaluations of asthma patients, including symptom-related questions and asthma-related healthcare utilization, are needed to accurately assess asthma severity and control.     

Clinical Manifestations of Allergic Bronchopulmonary Aspergillosis without Major Features of Asthma Diagnosed by the New Criteria in Japan

Allergic bronchopulmonary aspergillosis (ABPA) is a severe form of asthma in which structural airway destruction occurs due to a hypersensitivity reaction to fungi. A 25-year-old man without any major features of asthma had lung infiltration with dilatation of the central bronchus, high-attenuation mucus with histological eosinophilic invasion, fungi detected on cultures, and positive Aspergillus-specific immunoglobulin E (IgE) and precipitating antibody of Aspergillus, with a significant elevation of blood eosinophils and slightly increased total IgE. He recovered rapidly with systemic corticosteroid therapy without recurrence over 1-year follow-up and an increased forced expiratory volume in one second, which supported the possibility of ABPA without any major features of asthma.     

Prevalence of Asthma and Allergic Rhinitis Among School Children of Karachi,Pakistan, 2007

In recent times, the incidence of allergic diseases, particularly bronchial asthma, has been increasing worldwide. However, there appears to be no published data on the prevalence of allergic diseases among school children (3 to 16 years of age) in Karachi, Pakistan, with only limited data available among few age groups under one ISAAC study. The objective of this project was to investigate the prevalence of allergic diseases among school children (3 to 16 years of age) in the city of Karachi. The questionnaire that was used for data collection had previously been used for a similar study in neighboring Saudi Arabia and the U.A.E. In 2007, a total of 3,000 surveys were distributed in various schools of Karachi, of which 2,325 completed surveys were obtained. SPSS was used to perform statistical analysis on the collected data. Survey results showed that the frequency of diagnosed (previously seen by physicians) cases of asthma stood at 15.8%, while the frequency of allergic rhinitis was found to be 28.50% among these children. Other parameters that were analyzed included dry cough (20.1%), wheezing (11.7%), breathlessness (15.40%), and eczema (21.8%). Furthermore, smoking by family members was found to be associated with asthma (p value less than 0.05), allergic rhinitis (p value less than 0.05), breathlessness (p value less than 0.05), dry cough (p value 0.002), and wheezing (p value less than 0.05). This study reveals that there is a significant number of school children in the metropolitan city of Karachi who have various allergic symptoms. It also sheds light on the fact that exposure to indoor environmental factors as well as family atopy can play a key role in increasing the chances of an individual to experience asthma and other allergy symptoms.     

Association of Hepatitis A Exposure and TIM-1 with Childhood Allergic Asthma

Background. Hepatitis A virus (HAV) receptor (TIM-1) polymorphism plays an important role in asthma and autoimmune diseases. Objective. To analyze the association of TIM-1 polymorphism and HAV infection with childhood allergic asthma in Southwest China. Methods. TIM-1 exon 4 (157insMTTTVP) and two polymorphism loci, ?416G>C and ?1454G>A, in the HAV receptor promoter region were studied. Polymerase chain reaction (PCR) was used to test the genotypes of three polymorphism loci among 579 cases of asthma and 524 controls. The HAV infection status was determined in a case–control study with stratified analysis. Results. HAV exposure associated with childhood allergic asthma in the study population was compared with controls (odds ratio (OR) = 0.181, 95% confidence interval (CI) 0.126–0.260, p < .001). The ?416G>C polymorphism was associated with asthma (OR = 1.384, 95% CI 1.148–1.669, p < .001), but the insertion variant 157delMTTTVP of exon 4 and the ?1454G>A polymorphism were not. Conclusion. Our results indicated that the ?416G>C polymorphism of the TIM-1 gene is associated with childhood allergic asthma, providing a better understanding of the pathogenesis of the allergic asthma among children aged below 15 years in Southwest China.     

地塞米松、沙丁胺醇气雾剂联合红景天治疗100例急性高原反应的临床观察

目的:观察地塞米松、沙丁胺醇气雾剂联合红景天治疗急性高原反应的临床疗效。方法:选择急性高原反应患者100例作为观察对象,按照随机数字表法分为观察组和对照组,每组50例。观察组采用地塞米松、沙丁胺醇气雾剂联合红景天口服液进行治疗。对照组采用红景天口服液进行治疗。在用药15 d后测定患者呼吸频率、脉搏、血压、红细胞计数及血红蛋白水平等指标,比较2组疗效。结果:观察组总有效率高于对照组(84.0%vs 62.0%,P0.05)。用药后2组高原反应基础生理指标中呼吸频率、收缩压及观察组脉搏、舒张压、红细胞计数及血红蛋白水平均显著降低(P0.05或P0.01),且观察组上述指标均显著低于对照组(均P0.05或P0.01);观察组患者的急性高原反应评分明显低于对照组,血氧饱和度明显高于对照组(均P0.01)。结论:地塞米松、沙丁胺醇气雾剂联合红景天能够有效控制患者的急性高原反应症状,改善患者的高原反应基础生理指标,降低患者的急性高原反应评分,缩短病程。     

Effect of Omalizumab as Add-On Therapy on Asthma-Related Quality of Life in Severe Allergic Asthma: A Brazilian Study (QUALITX)

Objective. To assess the impact of omalizumab as an add-on therapy to standard treatment with inhaled corticosteroids (ICS) and long-acting beta-2 agonists (LABA) on asthma-related quality of life (QoL) in patients with severe allergic asthma. Methods. This was a 20-week, randomized, open-label, study involving Brazilian patients (>12 years) with severe persistent allergic asthma inadequately controlled despite regular treatment with, at least, ICS (≥500 μg/day fluticasone or equivalent) + LABA. The primary objective was to assess the mean change from baseline in overall Asthma-related Quality of Life Questionnaire (AQLQ) score in omalizumab-treated patients compared with the control group. Secondary outcome measures included rescue medication use, incidence of asthma exacerbations, perception of treatment efficacy among patients, mean change from baseline in AQLQ score, and >1.5-point increase in overall AQLQ score. Results. In the omalizumab group, overall AQLQ score was 3.2 (0.9) (mean [SD]) at baseline and 4.4 (1.3) at week 20 versus 3.0 (1.0) at baseline and 3.0 (1.1) at week 20 in the control group. Mean change from baseline on overall AQLQ score at week 20 in the omalizumab group was 1.2 (0.2) versus 0 (0.1) in the control group, showing a significant increase in scores from baseline in the omalizumab group (p < .001). There was also a statistically significant difference (p < .001) in the number of patients who showed a >1.5-point increase from baseline in overall AQLQ score after 20 weeks, thus indicating a better QoL in the omalizumab group. There was no significant difference with respect to the use of rescue medication, incidence of asthma exacerbation, and adverse events between treatment groups. The global evaluation of treatment effectiveness was significantly better for omalizumab (p < .001). Conclusion. Omalizumab was well tolerated and significantly improved the overall AQLQ score. Hence, it is a potential add-on therapy for severe persistent allergic asthma not controlled by standard prescribed treatment in Brazilian patients.     

The Serbian Version of the Pediatric Asthma Quality of Life Questionnaire in Daily Practice

Asthma is the most common chronic disease in children and adolescents and a serious global health problem, thus severely affecting the health related quality of life (HRQL). This study was aimed at exploring the potential role of the Serbian, self administered version of the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) in the routine clinical evaluation of children suffering from bronchial asthma. One hundred Serbian children and adolescents (62 males and 38 females), aged 7 to 17 years, affected by allergic asthma, were enrolled. Each patient was evaluated once, and asthma control and severity were assessed, spirometry was performed, FeNO measurements were performed and the patients completed the self-administered version of the PAQLQ. PAQLQ differed according to asthma severity, NO variation and Asthma Control Test (ACT) score. No correlations were found between the questionnaire's score and FEV₁ percent of predicted. The Serbian version of the PAQLQ is a feasible aid to clinical measurements and used in routine practice gives a good insight into asthma control and severity.     

Comparative features of Asthma with frequent or infrequent exacerbations: A longitudinal study of retrospective and prospective events

Background: A “frequent exacerbator phenotype” has been described, mostly in the population of patients with severe asthma. Further data are needed on such exacerbation-prone patients in milder asthma. Aim: To compare the characteristics of frequent and nonfrequent exacerbators in asthma of different severities and to assess the stability of the exacerbator status. Methods: This was an observational study comparing baseline data from frequent (≥2 exacerbations in the past year) and nonfrequent (<2 exacerbations in the past year) exacerbators. Patients were also followed up for one year. Information regarding clinical, physiologic, and inflammatory characteristics was collected at baseline and one-year follow-up. Results: Forty-seven frequent and 53 nonfrequent exacerbators were recruited. No specific clinical, physiologic, or inflammatory characteristic was observed in the frequent as compared to the nonfrequent exacerbators at baseline. Fifty-eight percent of patients reporting frequent exacerbations at baseline remained in this group after one year of follow-up. Forty-two and 62% of patients with, respectively, mild-to-moderate asthma and severe asthma had frequent exacerbations. In a post hoc analysis according to asthma severity, frequent exacerbators with severe asthma had a higher body mass index and poorer asthma control, although they reported higher adherence to medication, in comparison to frequent exacerbators with mild-to-moderate asthma. No specific characteristics could discriminate between frequent and nonfrequent exacerbators of the same asthma severity. Conclusions: Frequent exacerbators with severe asthma present some specific characteristics not observed in frequent exacerbators with mild-to-moderate disease. However, the latter group should be identified to reassess treatment needs and potential contributing factors.     

Effects of Obstructive Sleep Apnea and Gastroesophageal Reflux Disease on Asthma Control in Obesity

Background. Obesity is a risk factor for asthma. Obese asthmatics often have poor asthma control and respond poorly to therapy. It has been suggested that co-morbidities associated with obesity, such as reflux and obstructive sleep apnea, could be important factors contributing to poor asthma control in obese patients. Objectives. The purpose of this study was to determine if (1) reflux and/or (2) symptoms of sleep apnea contribute to poor asthma control in obesity. Methods. We studied asthmatic subjects participating in a trial of reflux treatment. Participants underwent baseline evaluation of asthma symptoms and lung function. Overall 304 participants underwent esophageal pH probe testing; 246 participants were evaluated for obstructive sleep apnea symptoms. Results. Of 402 participants in this trial, 51% were obese. Role of reflux in asthma control. Those with higher body mass index (BMI) reported a higher prevalence of reflux symptoms, but the prevalence of pH probe acid reflux was similar in all groups. Reflux was not associated with measures of asthma control in obese patients. Role of obstructive sleep apnea in asthma control. Symptoms and self-report of obstructive sleep apnea were more common with increasing BMI and associated with worse asthma control as measured by the Juniper Asthma Control questionnaire and Asthma Symptom Utility Index. Conclusions. Our data suggest that obstructive sleep apnea, but not gastroesophageal reflux disease, may contribute significantly to poor asthma control in obese patients.     

The Impact of Spirometry on Pediatric Asthma Diagnosis and Treatment

Research has shown that spirometry is underutilized in the clinical setting. This study profiles the use of spirometry in an asthma management program at an inner-city community health clinic. Eligible subjects included 56 children who presented with an acute asthma exacerbation. Physicians recorded patient diagnosis before and after viewing spirometry. Bivariate and multivariate analysis was used to determine associations between symptoms and forced expiratory volume in 1 second (FEV₁). Physicians changed 30.4% of patients' treatment plans after viewing spirometry results. Wheezing was significantly associated with FEV₁ in bivariate analysis; however, multivariate modeling failed to identify significant relationships. The use of spirometry influenced patient diagnosis and treatment.