High prevalence of asthma symptoms in Warao Amerindian children in Venezuela is significantly associated with open-fire cooking: a cross-sectional observational study

Background

The International Study on Asthma and Allergies in Childhood (ISAAC) reported a prevalence of asthma symptoms in 17 centers in nine Latin American countries that was similar to prevalence rates reported in non-tropical countries. It has been proposed that the continuous exposure to infectious diseases in rural populations residing in tropical areas leads to a relatively low prevalence of asthma symptoms. As almost a quarter of Latin American people live in rural tropical areas, the encountered high prevalence of asthma symptoms is remarkable. Wood smoke exposure and environmental tobacco smoke have been identified as possible risk factors for having asthma symptoms.

Methods

We performed a cross-sectional observational study from June 1, 2012 to September 30, 2012 in which we interviewed parents and guardians of Warao Amerindian children from Venezuela. Asthma symptoms were defined according to the ISAAC definition as self-reported wheezing in the last 12 months. The associations between wood smoke exposure and environmental tobacco smoke and the prevalence of asthma symptoms were calculated by means of univariate and multivariable logistic regression analyses.

Results

We included 630 children between two and ten years of age. Asthma symptoms were recorded in 164 of these children (26%). The prevalence of asthma symptoms was associated with the cooking method. Children exposed to the smoke produced by cooking on open wood fires were at higher risk of having asthma symptoms compared to children exposed to cooking with gas (AOR 2.12, 95% CI 1.18 - 3.84). Four percent of the children lived in a household where more than ten cigarettes were smoked per day and they had a higher risk of having asthma symptoms compared to children who were not exposed to cigarette smoke (AOR 2.69, 95% CI 1.11 - 6.48).

Conclusion

Our findings suggest that children living in rural settings in a household where wood is used for cooking or where more than ten cigarettes are smoked daily have a higher risk of having asthma symptoms.     

Discovery and optimization of CRTH2 and DP dual antagonists

A series of phenylacetic acid derivatives was discovered as CRTH2 antagonists. Modification of the series led to compounds that are also antagonists of DP. Since activation of CRTH2 and DP are believed to play key roles in mediating responses of asthma and other immune diseases, this series was optimized to increase the dual antagonistic activities and improve pharmacokinetic properties. These efforts led to selection of AMG 009 as a clinical candidate.     

Interleukin-10 does not mediate inhalational tolerance in a chronic model of ovalbumin-induced allergic airway disease

OBJECTIVE: IL-10 is a potent anti-inflammatory cytokine, and IL-10-producing regulatory T cells are effective inhibitors of murine asthmatic responses. This study determined whether IL-10-dependent mechanisms mediated the local inhalational tolerance seen with chronic inhalational exposure to antigen. METHODS: Wildtype and IL-10(-/-) mice were sensitized with ovalbumin (OVA) and then challenged with daily OVA inhalations for 10 days or 6 weeks. RESULTS: The 10-day animals developed allergic airway disease, characterized by BAL eosinophilia, histologic airway inflammation and mucus secretion, methacholine hyperresponsiveness, and OVA-specific IgE production. These changes were more pronounced in IL-10(-/-) mice. The 6-week IL-10(-/-) and wildtype animals both developed inhalational tolerance, with resolution of airway inflammation but persistence of OVA-specific IgE production. CONCLUSION: IL-10 may have anti-inflammatory effects in the acute stage of murine allergic airways disease, but the cytokine does not mediate the development of local inhalational tolerance with chronic antigen exposure.     

Epigenetics of hyper-responsiveness to allergen challenge following intrauterine growth retardation rat

Background

Epidemiological studies have revealed that intrauterine growth retardation (IUGR) or low birth weight is linked to the later development of asthma. Epigenetic regulatory mechanisms play an important role in the fetal origins of adult disease. However, little is known regarding the correlation between epigenetic regulation and the development of asthma following IUGR.

Methods

An IUGR and ovalbumin (OVA)-sensitization/challenge rat model was used to study whether epigenetic mechanisms play a role in the development of asthma following IUGR.

Results

Maternal nutrient restriction increased histone acetylation levels of the endothelin-1 (ET-1) gene promoter in lung tissue of offspring, but did not cause significant alterations of DNA methylation. The effect was maintained until 10 weeks after birth. Furthermore, these epigenetic changes may have induced IUGR individuals to be highly sensitive to OVA challenge later in life, resulting in more significant changes related to asthma.

Conclusions

These findings suggest that epigenetic mechanisms might be closely associated with the development of asthma following IUGR, providing further insight for improved prevention of asthma induced by environmental factors.     

双歧杆菌对过敏性哮喘儿童树突状细胞分泌IL-10、IL-12等细胞因子的影响

目的探讨双歧杆菌对过敏性哮喘儿童外周血单核细胞（PBMC）来源的树突状细胞（DC）分泌IL-1β、IL-6、IL-10、IL-12、IL-23和IFN-γ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,加入双歧杆菌后继续培养DC2d,用ELISA方法检测培养上清中IL-1β、IL-6、IL-10、IL-12、IL-23和IFN-γ的水平。结果双歧杆菌能明显刺激哮喘儿童DC分泌IL-12、IFN-γ,IL-1β及IL-6和非哮喘儿童DC分泌IL-12、IL-10、IL-1β及IL-23水平增高。结论双歧杆菌能够刺激过敏性哮喘儿童DC分泌IL-12和IFN-γ,可能改变Th2优势分化,纠正Th1／Th2失衡。同时双歧杆菌还能刺激哮喘儿童DC分泌IL-1p及IL-6增高,达到促进,Th17细胞分化的作用。     

支气管哮喘急性发作期超敏C- 反应蛋白、白细胞、中性粒细胞比例检测的意义及比较

目的:探讨超敏C-反应蛋白(hs-CRP)、血白细胞总数(WBC)、中性粒细胞比例(N%)在支气管哮喘(简称哮喘)急性发作期诊治中的临床意义。方法:分析60例患者治疗前及自觉症状缓解时hs-CRP、WBC、N%动态变化情况,观察上述指标在急性发作期的阳性率以及自觉症状缓解时的阴性率。结果:①hs-CRP、N%、WBC在自觉症状缓解时均明显低于哮喘急性发作期(P<0.05);②哮喘患者急性发作期hs-CRP、N%阳性率均高于WBC阳性率,且与后者比较均具有统计学差异(P<0.05);③哮喘患者经治疗自觉症状缓解时hs-CRP、WBC阴性率均高于N%阴性率,且与后者比较均具有统计学差异(P<0.05)。结论:血清hs-CRP既可作为哮喘患者急性发作期感染的敏感指标,又是反映急性发作期治疗效果的早期评判指标,比WBC、N%更迅速、敏感。     

高渗盐水雾化吸入治疗儿童支原体肺炎继发哮喘发作及对其T淋巴细胞亚群及Th1、Th2型细胞因子的影响

目的:探讨高渗盐水雾化吸入治疗儿童支原体肺炎继发哮喘发作的临床疗效及对其T淋巴细胞亚群及Th1、Th2型细胞因子的影响。方法:选取我院2015年6月到2017年6月间收治的支原体肺炎继发哮喘发作患儿100例为研究对象。随机分为对照组和观察组,各50例。两组均给予吸氧、抗生素、维持酸碱度、电解质平衡及相应症状等对症治疗,对照组给予生理盐水结合沙丁胺醇进行雾化治疗,观察组采用3%高渗盐水结合沙丁胺醇进行雾化治疗,比较两组患儿发热、咳嗽、肺内啰音、咽部肿痒等症状消失时间及临床疗效;比较两组治疗前后CD3~+、CD4~+、CD8~+、CD4~+/CD8~+、IFN-γ及IL-4水平情况。结果:观察组患儿发热、咳嗽、肺内啰音、咽部肿痒等临床症状消失时间显著早于对照组,差异有统计学意义(P0.05);观察组总有效率96.00%明显高于对照组80.00%,差异有统计学意义(P0.05);两组患儿治疗前CD3~+、CD4~+、CD8~+、CD4~+/CD8~+、IFN-γ及IL-4水平比较差异无统计学意义(P0.05);治疗后CD3~+、CD4~+、CD4~+/CD8~+及IFN-γ水平均明显升高,CD8~+及IL-4水平明显降低,差异均有统计学意义(均P0.05);且观察组治疗后CD3~+、CD4~+、CD4~+/CD8~+及IFN-γ水平均明显高于对照组,CD8~+及IL-4水平明显低于对照组,差异均有统计学意义(均P0.05)。结论:高渗盐水雾化吸入能够显著改善支原体肺炎继发哮喘发作患儿临床症状,提高CD3~+、CD4~+、CD4~+/CD8~+及Th1水平,抑制CD8~+及Th2水平,临床疗效确切,值得临床推广应用。     

孟鲁司特钠联合布地奈德混悬液对哮喘急性发作患儿血清EOS、ECP水平和肺功能的影响

目的:探索孟鲁司特钠联合布地奈德混悬液对哮喘急性发作患儿血清嗜酸性粒细胞(EOS)、嗜酸性粒细胞阳离子蛋白(ECP)水平和肺功能的影响。方法:选择自2015年10月至2016年10月我院收治的200例支气管哮喘急性发作患儿,按照随机数表法分成观察组和对照组各100例。对照组患儿口服孟鲁司特钠,观察组患儿在对照组基础上给予布地奈德气雾剂进行雾化治疗,两组均治疗1周。统计分析两组患儿的临床有效率,肺功能指标,包括第1秒用力呼气容积(FEV1)、用力肺活量(FVC)及FEV1/FVC,对比治疗前后两组患儿血清中EOS、ECP水平的变化。结果:治疗后,观察组的总有效率为97.00%,显著高于对照组的81.00%(P0.05);经治疗后两组患儿肺功能指标均较治疗前明显改善,且观察组患儿优于对照组(P0.05);两组患儿治疗后EOS、ECP水平均低于治疗前,而观察组患儿低于对照组,差异均有统计学意义(P0.05)。结论:孟鲁司特钠联合布地奈德对于小儿哮喘的急性发作具有良好的临床疗效,能显著改善患儿肺功能和血清中炎症因子的水平,减轻患儿体内的炎症反应,值得在临床上推广应用。     

Add-on therapy options in asthma not adequately controlled by inhaled corticosteroids: a comprehensive review

Many patients with persistent asthma can be controlled with inhaled corticosteroids (ICS). However, a considerable proportion of patients remain symptomatic, despite the use of ICS. We present systematically evidence that supports the different treatment options. A literature search was made of Medline/PubMed to identify randomised and blinded trials. To demonstrate the benefit that can be obtained by increasing the dose of ICS, dose-response studies with at least three different ICS doses were identified. To demonstrate whether more benefit can be obtained by adding long-acting β₂-agonist (LABA), leukotriene antagonist (LTRA) or theophylline than by increasing the dose of ICS, studies comparing these options were identified. Thirdly, studies comparing the different "add-on" options were identified. The addition of a LABA is more effective than increasing the dose of ICS in improving asthma control. By increasing the dose of ICS, clinical improvement is likely to be of small magnitude. Addition of a LTRA or theophylline to the treatment regimen appears to be equivalent to doubling the dose of ICS. Addition of a LABA seems to be superior to an LTRA in improving lung function. However, addition of LABA and LTRA may be equal with respect to asthma exacerbations. However, more and longer studies are needed to better clarify the role of LTRAs and theophylline as add-on therapies.