Effect of influenza vaccinations on immune response and serum eotaxin level in patients with allergic bronchial asthma

BACKGROUND: One of the most promising markers of allergic inflammation is eotaxin, which has a selective influence on the migration of eosinophils. Its serum content significantly correlates with the intensity of allergic symptoms, so it might be interesting to know whether vaccination has any influence on serum expression of this chemokine. AIMS: Comparison of the humoral response to influenza vaccine and post-vaccination changes in the serum eotaxin level in patients with allergic bronchial asthma and healthy controls. METHODS: Forty-two asthmatics and 45 healthy individuals were vaccinated with a single dose of influenza subunit vaccine (Influvac). The serum eotaxin level and the antibody response to haemagglutinin (HI) and neuraminidase (NI) glycoproteins were measured before and after vaccination. RESULTS: A significant increase of geometric mean titres of HI and NI was observed in both groups. There were no significant differences between the groups in meanfold increase of HI and NI titres, response rate and protective level of HI. After vaccination, a significant decrease of the mean serum eotaxin value was observed in patients with asthma (149.4 +/- 71.0 versus 125.1 +/- 67.0, p= 0.0017), while no similar effect was present in healthy individuals (153.4 +/- 56.9 versus 159.3 +/- 54.4, p= 0.5). CONCLUSIONS: The results indicate that in patients with allergic bronchial asthma influenza vaccinations assure efficient protective antibody level and modulate the serum level of eotaxin.     

喘息的"度"与支气管哮喘阶梯治疗

目的:探讨掌握喘息"度"与支气管哮喘阶梯治疗的关系。方法:充分掌握支气管哮喘分级治疗方案和支气管哮喘病情,将喘息"度"细致化,与分级治疗用药"度"密切结合起来,对于完全理想的控制哮喘将会起到极大的指导作用,对于升阶梯和降阶梯治疗都会起到重要而细致的指导作用。必须将平喘治疗措施置于患者全身病情变化及总体治疗之下,会取得更加理想的哮喘控制效果。而强化支气管哮喘患者教育在支气管哮喘理想治疗中占据极为重要的地位,甚至直接关系到哮喘控制的持久性和稳定性。应得到高度重视。结果:喘息"度"与支气管哮喘的发作程度密切相关,准确把握并分级十分重要。结论:准确把握喘息"度"并与支气管哮喘分级治疗方法结合,将对稳定平息支气管哮喘起到意想不到的效果。     

Genome-wide association study of bronchial asthma in the Volga-Ural region of Russia

Bronchial asthma is a chronic inflammatory respiratory disease that is caused by the complex interaction of environmental influences and genetic susceptibility. The first genome-wide association study of bronchial asthma discovered a significant association between SNPs within 17q12-21 genomic region and childhood bronchial asthma in individuals of European descent. Association with this genomic region was then replicated in a number of independent samples of European and Asian descent. Here we report results of the first genome-wide association study of bronchial asthma in the Volga-Ural region of Russia. The present study includes 358 unrelated patients with physician-diagnosed bronchial asthma and 369 disease-free control subjects of different ethnic origin (Russians, Tatars and Bashkirs). Genotyping of DNA samples was carried out using the Illumina Human610 quad array as a part of GABRIEL project (contract from the EC No LSHB-CT-2006-018996). After QC filtering procedures, a final set of 550915 SNPs genotyped in 330 cases and 348 controls was tested for association with bronchial asthma. Five markers on chromosome 17q12-21 showed statistically significant association with bronchial asthma (p < or = 4.79 x 10(-7)). SNP rs7216389 with the strongest evidence for association (p = 1.01 x 10(-7)) is located within the first intron of the GSDMB gene. Evidence for association was stronger with childhood-onset asthma (p = 1.97 x 10(-6) for SNP rs7216389) compared to late-onset asthma (p = 1.8 x 10(-4) for SNP rs7216389). Our replication study using three SNPs within GSDMB gene confirmed association with only childhood-onset asthma. In summary, these results suggest an important role for genetic variants within 17q12-q21 region in the development of bronchial asthma in the Volga-Ural region of Russia.     

miR-1165-3p、miR-145水平在支气管哮喘患者中的表达及其临床意义

摘要 目的：探讨微小RNA（MicroRNA,miR）-1165-3p、miR-145水平在支气管哮喘患者中的表达及其临床意义。方法：收集2021年1月-2022年3月中国人民解放军总医院第六医学中心62例支气管哮喘患者作为研究组,其中轻度急性发作27例,中度急性发作22例,重度急性发作13例。另收集同时期、同年龄段30例健康体检者作为对照组。采用实时荧光定量PCR（RT-PCR）检测各组血清miR-1165-3p、miR-145表达水平。采用Spearman相关分析不同程度支气管哮喘患者与血清miR-1165-3p、miR-145之间的相关性。通过受试者工作特征（ROC）分析血清miR-1165-3p、miR-145表达水平对不同程度支气管哮喘的诊断效能。结果：与对照组相比,研究组中白细胞介素-6（IL-6）、嗜酸性粒细胞、总免疫球蛋白E（IgE）水平显著升高,第1秒用力呼气容积（FEV₁）占预测值百分比（FEV₁%）则显著降低,差异均有统计学意义（P＜0.05）。不同严重程度支气管哮喘患者（轻度、中度、重度）血清miR-1165-3p、miR-145表达水平均高于健康对照组,支气管哮喘越严重,其表达水平越高,且组间、组内比较差异均有统计学意义（P＜0.05）。Spearman相关分析显示,miR-1165-3p、miR-145、IL-6表达水平与哮喘严重程度呈正相关（P＜0.05）,FEV₁%与哮喘严重程度呈负相关（P＜0.05）,嗜酸性粒细胞、总IgE与哮喘严重程度无相关性（P＞0.05）。对轻度、中度、重度急性支气管哮喘发作的诊断效能显示：血清miR-1165-3p的曲线下面积（AUC）（0.95CI）分别为3.085（0.326～29.221）、0.712（0.611～0.829）、0.755（0.602～0.948）。血清miR-145的AUC（0.95CI）分别为0.833（0.708～0.979）、0.754（0.590～0.964）、0.816（0.671～0.993）。结论：血清miR-1165-3p、miR-145表达水平具有较高的诊断效能,支气管哮喘越严重,诊断的特异性越高,可作为支气管哮喘严重程度的无创诊断指标。     

支气管哮喘患者疾病认知状况调查及控制水平的影响因素分析

目的:调查支气管哮喘患者疾病认知状况,并分析控制水平的影响因素。方法:选取2018年7月~2020年7月期间贵州医科大学附属医院诊治的支气管哮喘患者100例,采用面对面问卷调查的方式调查所有患者疾病认知状况。采用哮喘控制测试(ACT)对患者哮喘控制水平进行评估。根据ACT结果将患者分为哮喘未控制组(n=57)和哮喘控制组(n=43)。分析哮喘控制水平的影响因素。结果:支气管哮喘患者对疾病认知相关问题的回答正确率均在60%以上,但仅有12%的患者使用过峰流速仪。本研究中100例患者均完成ACT,其中完全控制17例,控制良好26例,未控制57例,分别占比17.00%、26.00%、57.00%,哮喘控制率为43.00%。由单因素分析显示,支气管哮喘患者的哮喘控制水平与性别、家庭月收入、文化程度、家族史、吸烟史、居住处是否空气污染、病程、哮喘用药依从性、使用吸入性糖皮质激素治疗、抑郁情况、焦虑情况有关(P<0.05)。多因素Logistic回归分析显示:焦虑情况、抑郁情况、居住处空气污染、吸烟史是支气管哮喘患者哮喘控制水平的危险因素,而哮喘用药依从性、使用吸入性糖皮质激素治疗是支气管哮喘患者哮喘控制水平的保护因素(P<0.05)。结论:支气管哮喘患者对疾病有一定的正确认知,但仍未达到理想状态。哮喘控制水平受多种因素影响,可根据相关影响因素做出针对性的干预措施,以改善支气管哮喘控制水平。     

The role of functional single nucleotide polymorphisms of the human glucocorticoid receptor gene NR3C1 in Polish patients with bronchial asthma

N363S and ER22/23EK polymorphisms observed within glucocorticoid receptor gene (NR3C1) may play an important role in the development of bronchial asthma. NR3C1 gene is associated with an altered sensitivity to GCs. The aim of the research project was to study the correlation between this NR3C1 gene polymorphisms and occurrence of asthma in the population of Polish asthmatics. Peripheral blood was obtained from 207 healthy volunteers and 221 asthma patients. Genotyping was carried out with PCR-RFLP method. In the groups of patients with uncontrolled moderate asthma and uncontrolled severe disease, the genotype distribution for the investigated polymorphisms was as follows: N363S-AA, AG, GG occurring with 0.881/0.073/0.046 frequency and ER22/23EK-GG, GA, AA occurring with 0.963/0.037/0.000 frequency. Chi-square analysis revealed a significantly different (P < 0.05) distribution between cases and controls for the N363S polymorphisms. The N363S polymorphism of NR3C1 gene is significantly associated with bronchial asthma, susceptibility to the development of moderate to severe form of uncontrolled bronchial asthma.     

Serum levels of soluble IL-2R, CD4 and CD8 in bronChial asthma

The aim of the present study was to compare serum levels of soluble forms of interleukin-2 receptor, CD4 and CD8, released by lymphocytes during activation of the immune system, in patients with allergic bronchial asthma, with those in healthy subjects. Significantly higher levels of soluble IL-2R and soluble CD4 were found in patients with asthma compared with the control group. In contrast, lower levels of soluble CD8 values were found in patients with asthma compared to the control group. Significant correlations were found for both sIL-2R and sCD4 and these two molecules, with lung function measured as bronchial responsiveness to inhaled methacholine. These results strengthen previous suggestions that in allergic bronchial asthma, activation of T cells plays a significant role in the disease pathogenesis.     

Genome-wide association study of bronchial asthma in the Volga-Urals region of Russia

Bronchial asthma is a chronic inflammatory respiratory disease caused by a complex interaction of environmental influences and genetic susceptibility. The first genome-wide association study of bronchial asthma discovered a significant association between single nucleotide polymorphisms (SNPs) located within the genomic region 17q12-q21 and childhood bronchial asthma in individuals of European descent. This result was later replicated in a number of independent population samples of European and Asian origin. Here we report the results of the first genome-wide association study of bronchial asthma in the Volga-Urals region of Russia. The study involved 358 unrelated patients with physician-diagnosed bronchial asthma and 369 disease-free control subjects of different ethnicity (Russians, Tatars, and Bashkirs). DNA specimens were genotyped using an Illumina Human610 quad array as a part of the GABRIEL project (EC contract no. LSHB-CT-2006-018996). After QC filtering procedures, a final set of 550 915 SNPs genotyped in 330 patients and 348 controls was tested for association with bronchial asthma. Five markers on chromosome 17q12-21 showed significant association with bronchial asthma (p ≤ 4.79 × 10⁻⁷). The rs7216389 SNP located in GSDMB intron 1 showed the strongest evidence for association (p = 1.01 × 10⁻⁷). Association with childhood asthma (p = 1.97 × 10⁻⁶ for rs7216389) was stronger than with late-onset asthma (p = 1.8 × 10⁻⁴ for rs7216389). A replication study of three SNPs located within GSDMB confirmed association only with childhood asthma. In sum, these results suggest that genetic variants of 17q12–q21 play an important role in susceptibility to bronchial asthma in the Volga-Urals region of Russia.     

The influence of the bronchodilatation test on the duration of forced expiratory tracheal noises in young men

The diagnostic efficiency of estimating the duration of forced expiratory noises under the conditions of bronchial obstruction has been shown. The objective of this study was to analyze the response of the forced expiratory noise duration to the bronchodilatation test with the β₂-agonist in the age- and genderhomogenous group of healthy volunteers and bronchial asthma patients selected as a model of variable bronchial obstruction. Two hundred and sixty young men (16–25 years old) were examined. It was shown that the prevailing type of response in bronchial asthma patients with spirometry confirmed bronchial obstruction was shortened forced expiratory noises. Furthermore, the degree of the shortening considerably depended on the severity of the background bronchial obstruction. The absence of a statistically significant response of the forced expiratory noise duration dominated among healthy volunteers (nonsmokers as well as smokers) and bronchial asthma patients without a spirometry confirmed bronchial obstruction. However, the shortened response occurred much more frequently in bronchial asthma patients than in healthy volunteers. The high specificity (86%) of the response as shortened forced expiratory noises to the β₂-agonist may be useful for diagnostics.     

CARD15 and TLR4 genes polymorphisms in atopic bronchial asthma

In order to investigate whether single nucleotide polymorphisms G(+2722)C and 3020insC in CARD15 gene and Asp299Gly in TLR4 gene contribute to atopic bronchial asthma we performed a comparative analysis of alleles and genotypes frequencies of these polymorphisms in Russian patients from Moscow. DNA samples from 283 patients with atopic bronchial asthma and 227 healthy donors were genotyped. There were associations neither of G(+2722)C and 3020insC in CARD15 gene and Asp299Gly in TLR4 gene with asthma nor of markers of CARD15 gene with asthma severity. Haplotype frequency analysis of CARD15 gene polymorphisms did not reveal significant difference between groups. However, a strong association was found between Asp299Gly and asthma severity. Allele Asp of this marker showed association with mild atopic bronchial asthma and allele Gl--with moderate/severe asthma = 0.47, 95% CI [0.24-0.93] i OR = 2.12, 95% CI [1.08-4.18] respectively).     

Influence of influenza viral infection on airway smooth muscle activity

The contractility of airway smooth muscle (ASM) plays an important role in pathophysiology of several bronchial disorders. Increased contraction of ASM during asthma and respiratory viral infection has been attributed to the release of mediators acting through different receptors. In the present study, influence of influenza type A virus (H1N1) infection has been examined on ASM responsiveness to various bronchoactive agents e.g. adenosine, histamine, 5-hydroxytryptamine (5-HT) and isoproterenol in an organ bath set up for isolated tissue preparation. The contractile effect of adenosine, histamine and 5-HT was enhanced, however, relaxant response of isoproterenol was attenuated with the duration following viral exposure. The most prominent response was observed 48 to 72 hr after infection and tissues from multiple exposure to virus infected animals showed the maximum contractile response. Results demonstrated the deleterious effect of viral infection on ASM function and the findings will be helpful in understanding the mechanism of influenza virus induced bronchoconstriction.     

重症支气管哮喘患者肺泡灌洗液病原菌分布及血清CRP和TNFα水平

目的 研究重症支气管哮喘患者肺泡灌洗液中病原菌分布及血清C反应蛋白(CRP)、肿瘤坏死因子(TNFα)水平,为该病的治疗提供参考。 方法 选取2017年5月至2019年5月我院收治的支气管哮喘患者为研究对象,按照病情严重程度分为重度组(n=85)和轻度组(n=80)。收集两组患者肺泡灌洗液并进行细菌培养,同时抽取两组患者静脉血检测血清CRP、TNFα水平。采用Spearman相关系数分析法分析血清CRP、TNFα水平与哮喘程度的关系。 结果 重度组患者肺泡灌洗液中检出革兰阳性菌23株,占36.51%;革兰阴性菌38株,占60.32%;真菌2株,占3.17%。革兰阳性菌中肺炎链球菌占47.83%,金黄色葡萄球菌占30.43%;革兰阴性菌中大肠埃希菌占23.68%,流感嗜血杆菌占26.32%。重度组患者肺泡灌洗液中革兰阴性菌比例及血清CRP与TNFα水平均显著高于轻度组(均P结论 重度支气管哮喘患者肺泡灌洗液中革兰阴性菌占比较高,同时其血清CRP、TNFα水平也较高。CRP、TNFα水平与哮喘严重程度成正比。     

Site of airway obstruction in pulmonary disease: direct measurement of intrabronchial pressure.

To partition the central and peripheral airway resistance in awake humans, a catheter-tipped micromanometer sensing lateral pressure of the airway was wedged into the right lower lobe of a 3-mm-ID bronchus in 5 normal subjects, 7 patients with chronic bronchitis, 8 patients with emphysema, and 20 patients with bronchial asthma. We simultaneously measured mouth flow, transpulmonary pressure, and intra-airway lateral pressure during quiet tidal breathing. Total pulmonary resistance (RL) was calculated from transpulmonary pressure and mouth flow and central airway resistance (Rc) from intra-airway lateral pressure and mouth flow. Peripheral airway resistance (Rp) was obtained by the subtraction of Rc from RL. The technique permitted identification of the site of airway resistance changes. In normal subjects, RL was 3.2 +/- 0.2 (SE) cmH2O.l-1.s and the ratio of Rp to RL was 0.24 during inspiration. Patients with bronchial asthma without airflow obstruction showed values of Rc and Rp similar to those of normal subjects. Although Rc showed a tendency to increase, only Rp significantly increased in those patients with bronchial asthma with airflow obstruction and patients with chronic bronchitis and emphysema. The ratio of Rp to RL significantly increased in three groups of patients with airflow obstruction (P less than 0.01). These observations suggest that peripheral airways are the predominant site of airflow obstruction, irrespective of the different pathogenesis of chronic airflow obstruction.     

Genetic blood markers in arthritic diseases]

In the course of studying patients affected with arthritic diseases (bronchial asthma, sugar diabetes) a relationship between those diseases and the blood groups of the Hp and MN systems was established. Patients with bronchial asthma more frequently than in the controls belonged to the Hp 2-2 type and to blood groups MN and O (I), whereas the patients affected with sugar diabetes are usually of the Hp 2-1 type and belong to the belong to the blood groups MN and A(II). The investigation of patients affected with other diseases having a pathogenesis similar to that of bronchial asthma or of diabetes and the observation of healthy persons after prophylactic inoculations as well as the study of sugar metabolism in healthy persons all confirm the relationship of Hp, MN and ABO antigens with arthritic diseases.     

支气管哮喘遗传因子研究

研究谷胱甘肽-S-转移酶 （glutathione S-transferase, GST）M1和T1基因多态性与支气管哮喘（asthma bronchial）的关系。采取聚合酶链反应对60名支气管哮喘患者和60名正常对照进行了GSTM1和GSTT1基因非缺失（+）和缺失（0）等位基因分布频率研究。结果表明,与对照组相比,支气管哮喘患者GSTM1基因缺失的纯合子（0/0）频率（81.2%）显著升高（χ2=32.46,P<0.001;wχ2=28.75,P<0.001）。对于GSTT1也得到类似资料。而支气管哮喘患者GSTT1基因缺失等位基因（0/0）频率（71.7%）比对照组（11.7%）显著升高（χ2=26.72,P<0.001;wχ2=35.75,P<0.001）。表明GSTM1、GSTT1缺失等位基因纯合性在哮喘患者中最有特征性的。GSTM1 0/0、GSTT1 0/0结合的频率患者组为61.7%,对照组仅为1.7%（χ2=27.3,P<0.001）。提示GSTM1和GSTT1基因多态性与哮喘有显著性关联,两个基因的突变可以被视为发生支气管哮喘遗传风险因子。     

Inflammatory and mechanical factors of allergen-induced bronchoconstriction in mild asthma and rhinitis.

We studied whether different bronchial responses to allergen in asthma and rhinitis are associated with different bronchial inflammation and remodeling or airway mechanics. Nine subjects with mild asthma and eight with rhinitis alone underwent methacholine and allergen inhalation challenges. The latter was preceded and followed by bronchoalveolar lavage and bronchial biopsy. The response to methacholine was positive in all asthmatic but in only two rhinitic subjects. The response to allergen was positive in all asthmatic and most, i.e., five, rhinitic subjects. No significant differences between groups were found in airway inflammatory cells or basement membrane thickness either at baseline or after allergen. The ability of deep inhalation to dilate methacholine-constricted airways was greater in rhinitis than in asthma, but it was progressively reduced in rhinitis during allergen challenge. We conclude that 1) rhinitic subjects may develop similar airway inflammation and remodeling as the asthmatic subjects do and 2) the difference in bronchial response to allergen between asthma and rhinitis is associated with different airway mechanics.     

2007～2011年鄂州市气传致敏真菌调查及其与支气管哮喘的相关性

目的 探讨2007年5月～ 2011年4月鄂州市气传致敏真菌和支气管哮喘关系,以了解该地区支气管哮喘情况.方法 运用暴片调查法和暴皿调查法统计和记录鄂州市气传致敏真菌的种类及数量.选择该时期内鄂州市100例支气管哮喘患者采用真菌变应原浸液作过敏原皮试发现有35例患者皮内试验阳性,将35例发作期患者和40例稳定期支气管哮喘患者行曲霉特异性IgE测定.结果 100例支气管哮喘患者皮内实验组阳性35例,阳性率为35％,而在35例患者中IgE阳性有31例,检测符合率为88.58％,稳定期患者中阳性反应例数2例,阳性率为5％,两组阳性率比较差异具有显著性（P＜0.05）.结论 鄂州市气传致敏真菌和支气管哮喘密切相关,主要致病菌为曲霉,是支气管哮喘的致敏原之一,需要注意环境卫生以减少气传致敏真菌的数量.     

家族性支气管哮喘的遗传方式分析

为研究家族性支气管哮喘的遗传方式, 进一步确定在群体中的传递规律,用群体研究法调查邯郸地区有家族史的支气管哮喘家系。采用家系分析法和Smith无偏差校正法, 进行理论值与观察值符合程度的卡方检验分析。72个家族性支气管哮喘的家系, 包括109个核心家系, 其亲属的患病率为0.46。分析结果表明, 有单基因遗传的倾向。用家系法分析, 符合常染色体显性遗传。对D-× dd婚配家系用Smith法分析, χ² = 3.181, P > 0.05, 所得结果支持常染色体显性遗传(Autosomal domiant inheritance, AD), 并提示不同的婚 配类型, 遗传方式可能不同, 存在着遗传异质性, 研究结果可为家族性支气管哮喘的预防、诊断和治疗提供参考依据。     

Circadian Variation in Allergen and Nonspecific Bronchial Responsiveness in Asthma

In a majority of patients, exacerbations of asthma occur more frequently during the night than day. Many hypotheses have been proposed to explain such variation in asthma. The airways of asthmatic persons are characterized by an abnormal degree of inflammation and bronchial hyperre-sponsiveness to both nonspecific and specific challenges. Studies of both children and adults with asthma document marked circadian rhythmicity in the response of airways to bronchial challenges with histamine, methacho-line, acetylcholine, saline, and house dust mite. Taken together, the findings of these investigations indicate that the hyperreactivity of airways to these agents is more profound and prolonged following evening and overnight tests compared to tests conducted in the midday and afternoon. The temporal pattern in bronchial response to the hyperventilation of cold dry air is different. The hyperresponsiveness of airways to this challenge is greatest in the afternoon. The amplitude of the circadian rhythm in airway hyperreactivity seems to be correlated to the amplitude of the circadian rhythm of pulmonary function; the greater the day-night difference in bronchial reactivity is, the greater is the day-night difference in flow rates.     

Lovastatin inhibits bronchial hyperresponsiveness by reducing RhoA signaling in rat allergic asthma

Recent studies revealed an importance of a monomeric GTP-binding protein, RhoA, in contraction of bronchial smooth muscle (BSM). RhoA and its downstream have been proposed as a new target for the treatment of airway hyperresponsiveness in asthma. Statins are known to inhibit the functional activation of RhoA via the depletion of geranylgeranylpyrophosphate. To determine the beneficial effects of statins on the airway hyperresponsiveness in allergic bronchial asthma, we investigated the effects of systemic treatment with lovastatin on the augmented BSM contraction and activation of RhoA in rats with allergic bronchial asthma. Rats were sensitized and repeatedly challenged with 2,4-dinitrophenylated Ascaris suum antigen. Animals were also treated with lovastatin (4 mg kg(-1) day(-1) ip) once a day before and during the antigen inhalation period. Repeated antigen inhalation caused a marked BSM hyperresponsiveness to ACh with the increased expression and translocation of RhoA. Lovastatin treatments significantly attenuated both the augmented contraction and RhoA translocation to the plasma membrane. Lovastatin also reduced the increased cell number in bronchoalveolar lavage fluids and histological changes induced by antigen exposure, whereas the levels of immunoglobulin E in sera and interleukins-4, -6, and -13 in bronchoalveolar lavage fluids were not significantly changed. These findings suggest that lovastatin ameliorates antigen-induced BSM hyperresponsiveness, an important factor of airway hyperresponsiveness in allergic asthmatics, probably by reducing the RhoA-mediated signaling.