Cytological and biochemical indices of induced sputum in patients with bronchial asthma and chronic obstructive bronchitis

The aim of our research was to study the apoptotic index and the representativeness of CD95-receptor in the effector cells, in addition to estimation of the content of tumor necrosis factor-alpha in the induced sputum supernatant observed in patients with bronchial asthma and chronic obstructive bronchitis. These indices were evaluated in the disease dynamics and involves various treatment programs. The object of our research was induced sputum. The analysis has proven that apoptotic index of effector cell nuclei, representativeness of CD95-receptor and the content of tumor necrosis factor-alpha in the induced sputum differed, respectively, in patients with bronchial asthma and chronical obstructive bronchitis, and depended on the period of disease and employed treatment. The induced sputum analysis results can be used for the airway inflammation activity monitoring, with regard to these diseases and to treatment efficiency monitoring.     

支气管扩张合并支气管哮喘患者的病原菌检测及危险因素分析

目的分析支气管扩张合并支气管哮喘患者的病原菌及危险因素。方法选取湖州市中心医院115例支气管扩张合并支气管哮喘患者作为观察组,另选取同期110例健康体检者作为对照组。分析患者病原菌的组成、耐药性及发病危险因素。结果观察组患者送检痰样本经痰培养,阳性检出者68例,阳性率为59.13%(68/115)。全部样本共分离出104株病原菌,其中革兰阴性菌92株(以铜绿假单胞菌最多,占54.81%),革兰阳性菌8株,真菌4株。药敏试验结果表明革兰阴性菌对复方新诺明、头孢曲松、左旋左氧氟沙星和阿莫西林/克拉维酸等药物的耐药性均较高,对妥布霉素、亚胺培南、头孢哌酮/舒巴坦和哌拉西林的耐药性较低。Logistic回归分析显示,吸烟史、药物过敏史、食物过敏史、过敏性鼻炎、哮喘、过敏性肺炎、慢性支气管炎及慢性阻塞性肺疾病均是支气管扩张伴支气管哮喘发生的危险因素。结论支气管扩张合并支气管哮喘患者其病原菌以革兰阴性菌为主,吸烟史、药物过敏史、食物过敏史、过敏性鼻炎等是支气管扩张伴支气管哮喘发生的危险因素。     

基层医院哮喘的规范化治疗初探

目的：了解临床工作实践中支气管哮喘防治指南（GINA方案）在基层医院的实施情况及遇到的问题并提出今后解决办法。方法：对门诊及病房住院的患者进行调查研究,采用统一设计的表格、问卷及必要的检查,对结果进行统计和分析。结果：正规治疗与非正规治疗的患者的花费情况具有明显差别,差异具有统计学意义。当地91．2％支气管哮喘曾经误诊为慢性支气管炎。治疗不规范,曾吸入激素治疗的占全部患者的18．1％,曾经和正在口服私人配制的平喘药物（粉剂或胶囊）的占65．8％;病情复发时给予输液、利用抗生素治疗的占73．6％;给予大剂量激素、不规范治疗（包括长期用激素治疗、不逐渐减量）治疗的78．7％;结论：当地哮喘治疗还存在很多问题,形式非常严峻,有待于进一步加大GINA治疗方案的推广。     

Effect of inhalation therapy with beclomethasone dipropionate on unspecific bronchial hyperreactivity in patients with asthma]

An effect of beclomethasone dipropionate (Beclocort-Polfa) was investigated in the group of 24 patients with atopic and non-atopic bronchial asthma who have shown unspecific bronchial hyperreactivity to histamine during the periods of remission. The drug was administered in the form of aerosol in a daily dose of 1.0 mg for 4 weeks. Provocative histamine dose was established with Bronchoscreen device (Jaeger) thrice:prior to the treatment, after 1 week of placebo therapy, and after 1 month of beclomethasone administration. Statistically significant increase in histamine dose for provocation of bronchospasm (p < 0.01) being nearly twice higher than the baseline value has been noted in patients treated with beclomethasone dipropionate aerosol. It advocates such a treatment in unspecific bronchial hyperreactivity independently of the type of the bronchial asthma.     

Clinical evaluation of broncho-vaxom efficiency]

Broncho-vaxom was administered to 40 patients with recurrent respiratory infections, allergic-infectious bronchial asthma and chronic bronchitis. Broncho-vaxom was administered in the dose of one capsule for the first month, and 1 capsule for 10 days in the third, fourth, and fifth month. A favourable clinical effect has been achieved in over 50% of the treated patients manifested by the decrease in the number and severity of respiratory infections and reductions in antibiotics use. These results confirm clinical efficiency of this vaccine.     

III. Serum and sputum immunoglobulin E levels in respiratory diseases in adults

Using a solid-phase radioimmunoassay, serum IgE level was determined in 46 normal subjects, 53 patients with bronchial asthma, 44 patients with chronic bronchitis and / or emphysema, and 19 patients with restrictive lung disease. Sputum IgE was measured simultaneously in 51 of the subjects. The range of serum IgE concentration in the normal subjects was wide. It varied between 15 and 750 ng/ml with a mean of 135 ng. Asthmatic patients had significantly higher levels of serum IgE with a mean of 579 ng/ml, but only 30% fell outside the normal 95% confidence limits. Patients with chronic bronchitis, emphysema and restrictive lung diseases had normal IgE levels. There was a significant correlation between serum and sputum IgE levels.     

Effect of cimetidine and ranitidine on bronchial reactivity in patients with asthma

The results of studies on the effect of cimetidine and ranitidine on the bronchial reactivity in a group of 10 patients with atopic bronchial asthma are discussed. The patients received 800 mg of cimetidine daily for 6 days and, after a three-day interval, 300 mg of ranitidine daily for a further 6 days. Bronchial reactivity was determined with the histamine test, according to Spector and Farr, before the administration of each drug and on the third and sixth days of each course of the treatment. A comparison of the effect of cimetidine and ranitidine on the bronchial reactivity in the same patients revealed that a 3-day exposure to each of the two drugs, cimetidine enhanced bronchial reactivity to a greater extent than ranitidine; the difference between the action of the two drugs being statistically significant (p less than 0.05). Bronchial reactivity was found to increase significantly after a 6-day treatment with each of the drugs but no statistically significant differences were noted comparing the effect of these drugs.     

Bronchodilator treatment in moderate asthma or chronic bronchitis: continuous or on demand? A randomised controlled study.

OBJECTIVE--To examine the effect of bronchodilator treatment given continuously versus on demand on the progression of asthma and chronic bronchitis and to compare the long term effects of a beta 2 adrenergic drug (salbutamol) and an anticholinergic drug (ipratropium bromide). DESIGN--Two year randomised controlled prospective ''crossover'' study in which patients were assigned to one of two parallel treatment groups receiving continuous treatment or treatment on demand. SETTING--29 general practices in the catchment area of the University of Nijmegen. PATIENTS--223 patients aged greater than or equal to 30 with moderate airway obstruction due to asthma or chronic bronchitis, selected by their general practitioners. INTERVENTIONS--1600 micrograms salbutamol or 160 micrograms ipratropium bromide daily (113 patients) or salbutamol or ipratropium bromide only during exacerbations or periods of dyspnoea (110). No other pulmonary treatment was permitted. MAIN OUTCOME MEASURES--Decline in ventilatory function and change in bronchial responsiveness, respiratory symptoms, number of exacerbations, and quality of life. RESULTS--Among 144 patients completing the study, after correction for possible confounding factors the decline in forced expiratory volume in one second was -0.072 l/year in continuously treated patients and -0.020 l/year in those treated on demand (p less than 0.05), irrespective of the drug. The difference in the decline in patients with asthma was comparable with that in patients with chronic bronchitis (asthma: 0.092 v -0.025 l/year; chronic bronchitis: -0.082 v -0.031 l/year). Bronchial responsiveness increased slightly (0.4 doubling dose) with continuous treatment in chronic bronchitis, but exacerbations, symptoms, and quality of life were unchanged. Salbutamol and ipratropium bromide had comparable effects on all variables investigated. CONCLUSIONS--Continuous bronchodilator treatment without anti-inflammatory treatment accelerates decline in ventilatory function. Bronchodilators should be used only on demand, with additional corticosteroid treatment, if necessary.     

Use of induced sputum in the investigation of occupational asthma

The diagnosis of occupational asthma relies mainly on the demonstration of changes in airway calibre and airway responsiveness after exposure to occupational agents in the laboratory or at the workplace. However, spirometry or peak expiratory flow measurements may be open to misinterpretation when they are not performed optimally. As in non-occupational asthma, airway inflammation is one of the main characteristics of occupational asthma. Induced sputum, a non invasive method to assess airway inflammation, has been successfully used in the management of asthma. This article reviews the studies that have investigated and characterized the changes in sputum cell counts occurring in subjects with occupational asthma after exposure to occupational agents in the laboratory or at the workplace in order to assess the place of induced sputum in the investigation of occupational asthma. It also reviews the use of induced sputum during the follow-up of workers with occupational asthma after removal from exposure. This article also describes a new condition identified thanks to the use of induced sputum : occupational eosinophilic bronchitis. In conclusion, induced sputum is a useful tool in the investigation of occupational asthma. Its use on a regular basis in the investigation of occupational asthma also allows for the possibility of diagnosis of overlooked conditions such as occupational eosinophilic bronchitis. Its role in the surveillance of workers at risk to develop occupational asthma remains to be determined.     

The characteristics of the humoral antibacterial immunity of young children with respiratory organ diseases]

The state of antibacterial humoral immunity in young children with acute bronchitis, acute obstructive bronchitis and bronchial asthma at the period of exacerbation has been shown with the use of the enzyme immunoassay. The concentration of antibodies to endotoxin positively correlates with the severity of clinical manifestations of the endogenic intoxication of the body. As the inflammatory process in the bronchial tree increases, the spectrum bacterial agents to which elevated concentrations of specific antibodies can be detected becomes wider, and this finds its maximum reflection in bronchial asthma.     

IgE-containing immune complexes in bronchial asthma]

Level of circulating immunological complexes and their immunoglobulin content have been determined in 36 asthmatic patients, including 15 patients with atopic asthma and 21 patients with infectious asthma. A technique of staphylococcal protein A binding has shown, that the level of the circulating immunological complexes is increased in patients with infectious bronchial asthma. An amount of IgE in these complexes has been increased in both atopic and infectious bronchial asthma. However, a level of IgE-containing immunological complexes has been higher in the atopic asthma, then that in infectious form of the disease. An increased IgA content in the immunological complexes has been noted in the infectious asthma.     

Results of utilization of intermittent normobaric hypoxia in patients with bronchial asthma and chronic obstructive bronchitis]

The results of intermittent normobaric hypoxytherapy in 42 patients with bronchial asthma (BA) and 14 patients with chronic obstructive bronchitis (COB) are analyzed. The positive effect is obtained in 76% of patients with BA and 92.8% of patients with COB. In the group of patients with BA the best effect was achieved for atopic form of BA--in 90% of patients, the effect was less pronounced for infection-allergic form--in 73.9% and for mixed form of BA--in 66.7%. In the process of treatment the attacks of asphyxia disappeared or became more occasional in 60.7% of patients; in 32.1% the attacks were more easily arrested or stopped independently; 33.8% of patients decreased doses of constantly taken drugs; in 33% cough ceased or decreased, sputum became to expectorate better; in 41% of patients dyspnea disappeared and considerably decreased. Improvement of the state in 54% of patients was retained for one year and more, in 29%--for 6 months, in 16.6%--for 3-4 months. The course of treatment consisted of 20-25 sessions. The patients breathed in hypoxic gas mixture containing 10% of oxygen (HGM-10) under intermittent conditions alternating with respiration of free air.     

Effects of bronchial secretions of patients with bronchial asthma and chronic bronchitis on the motility of ciliated cells of the ciliated epithelium

It has been shown that bronchial mucus from patients with bronchial asthma and chronic bronchitis can produce a ciliostatic effect when incubated with strips of frog palate mucosa. This effect can more often be found during clinical exacerbation and is supposed to be reversible. The ciliostatically active samples of bronchial mucus taken from asthmatic patients markedly inhibit reactivation glycerol models of frog's ciliated epithelium. It can therefore be suggested that the found activity acts directly on tubulin-dynein complex of the cilia. In contrast to these findings, the ciliostatically active samples of bronchial of glycerol models and therefore possibly act through some other mechanism.     

Clinico-immunologic aspects of using mildronate in patients with bronchopulmonary diseases

The immunity status of 35 patients with chronic bronchitis and infectious and allergic bronchial asthma was studied. Defects in the humoral immunity were revealed. To correct the immunity status, all the patients were treated with mildronate. The immunomodulatory effect of mildronate was found in all the groups of the patients. Mildronate was shown to increase the activity of a secondary immune response and the bronchial potency in the persons with infectious and allergic asthma.     

Evaluation of the forced expiration technique as an adjunct to postural drainage in treatment of cystic fibrosis.

Sixteen patients with cystic fibrosis were treated with conventional physiotherapy aided by an assistant. The results were compared with those produced by physiotherapy using the forced expiration technique cleared more sputum in less time than conventional physiotherapy. A sputum in less time than conventional physiotherapy. A second study showed that an assistant did not further improve the results obtained by the patient performing the forced expiration technique himself. These findings mean that patients with cystic fibrosis who have had to rely on the help of others for their home treatment may now perform more effective treatment without help. The forced expiration technique might also be helpful for patients with chronic bronchitis, asthma, or bronchiectasis.     

The high lipid content of respiratory mucins in cystic fibrosis is related to infection

Seven human bronchial mucins secreted by patients suffering from chronic bronchitis or from cystic fibrosis were prepared by exclusion from a Sepharose CL-2B column in 6 M guanidinium chloride. Their behaviour in CsBr density gradient centrifugation was compared. The mucin fractions were associated with peptides and lipids, the abundance of which decreases with the buoyant density. The lipid content of the mucin fractions appears to be related to the infectious character of the bronchial secretion and seems to be independent of cystic fibrosis. The content of fatty acids remaining after delipidation of mucin fractions from patients with chronic bronchitis or with cystic fibrosis also appears to be related more to the purulent character of the sputum than to cystic fibrosis or chronic bronchitis.     

The Prevalence of Chronic Respiratory Disease in the Male Physicians of London,Ontario

a survey of respiratory disease among male physicians of London, Ontario, resulted in a 96.3% response.The age-standardized rates of chronic bronchitis were not very different from others reported in the recent medical literature, taking into account smoking habits, but the overall prevalence of bronchial asthma was high (7.4%), with a low prevalence in the category “obstructive lung disease”. The possibility of overlap or interchange in these diagnoses is raised, although the diagnosis of bronchial asthma in this particular group is believed to be well established in every case.A history of seasonal hay fever was given by 19.4%.One of 88 (1%) non-smokers had bronchitis, whereas six of them (7%) had asthma.Rhonchi heard in the chest, on a single examination, appeared to be most closely related to current smoking habits, ventilatory function tests and also to a clinical diagnosis of chronic bronchitis or obstructive lung disease, but not to bronchial asthma.     

基于网络药理学和分子对接探讨藏麻黄挥发性成分对支气管炎的作用机制

麻黄(Ephedrae Herba)具有发汗散寒、宣肺平喘、利水消肿的功效。现代研究表明麻黄对治疗支气管、哮喘有疗效。藏麻黄(Ephedra saxatilis)为西藏特有的麻黄属植物,其根、茎具有特殊香气,且目前其挥发性成分未有报道。为评价挥发性成分对支气管炎作用,用气质联用仪测定分析藏麻黄根、茎挥发性成分,并结合网络药理学和分子对接方法分析挥发性成分治疗支气管炎的关键靶点。分析检测到67个挥发性化合物,茎中含有挥发性主要成分为2,3,5,6-四甲基吡嗪(10.92%)、Z-9-十五烯醇(9.15%)、二羟基苯乙酮(7.92%);根含有的挥发性主要成分为亚油酸(7.81%)、红没药醇(7.1%)、Z-9-十五烯醇(5.98%)。有34个挥发性成分能够作用32个支气管炎疾病靶点。蛋白互作网络分析预测IL6、TNF、PTGS2、CXCL8为藏麻黄挥发性成分治疗支气管可能的潜在靶点。这些靶点与挥发性成分丁子香酚、月桂酸、反式法尼醇、α-萜品醇、榄香醇和棕榈酸6种化合物靶点相互结合程度高,且分子对接效果好。本研究推测藏麻黄挥发性成分对支气管炎的治疗作用机制可能是通过抑菌作用参与炎症反应,并通过抑制TNF、IL-17、Toll样受体等炎症与免疫信号通路中IL6、TNF、PTGS2、CXCL8的表达,从而起到治疗支气管炎的作用。研究结果为挖掘藏麻黄挥发性成分中治疗支气管炎靶标分子及其产品开发提供重要参考依据。     

百令胶囊联合罗氟司特治疗老年支气管哮喘的效果及对免疫功能的影响

目的:研究百令胶囊联合罗氟司特治疗老年支气管哮喘的效果及对免疫功能的影响。方法:选择2018年3月~2019年3月我院第六派驻门诊部收治的110例老年支气管哮喘患者,随机分为两组,每组各55例。对照组患者口服罗氟司特片,每次500 mg,每天1次。观察组患者联合服用百令胶囊,每次5粒,每天3次。比较两组的临床控制率,治疗前后两组诱导痰中炎症因子、中性粒细胞、呼出气一氧化氮(fractional exhaled nitric oxide,FeNO)水平和免疫功能的变化。结果:治疗后,观察组的临床控制率为70.91%(39/55),明显高于对照组[40.00%(22/55)](P<0.05);两组的CD4+、CD4+/CD8+和CD3+均较治疗前明显升高,且观察组的CD4+、CD4+/CD8+和CD3+明显高于对照组(P<0.05);两组患者诱导痰中中性粒细胞绝对值、中性粒细胞百分比、白细胞介素-4(interleukin-4,IL-4)、FeNO、白细胞介素-17(interleukin-17,IL-17)均较治疗前明显降低(P<0.05),诱导痰中的干扰素-γ(Interferon gamma,IFN-γ)均较治疗前明显升高(P<0.05),且观察组诱导痰中的组中性粒细胞绝对值、中性粒细胞百分比、IL-4、FeNO、IL-17明显低于对照组(P<0.05),诱导痰中的IFN-γ均明显高于对照组(P<0.05)。结论:百令胶囊联合罗氟司特对老年支气管哮喘患者具有显著的疗效,其机制可能与抑制中性粒细胞的激活、调节T淋巴细胞亚群的平衡和抑制相关炎症因子的释放相关。     

Obstructive Sleep Apnoea Modulates Airway Inflammation and Remodelling in Severe Asthma

Background

Obstructive sleep apnoea (OSA) is frequently observed in severe asthma but the causal link between the 2 diseases remains hypothetical. The role of OSA-related systemic and airway neutrophilic inflammation in asthma bronchial inflammation or remodelling has been rarely investigated. The aim of this study was to compare hallmarks of inflammation in induced sputum and features of airway remodelling in bronchial biopsies from adult patients with severe asthma with and without OSA.

Materials and Methods

An overnight polygraphy was performed in 55 patients referred for difficult-to-treat asthma, who complained of nocturnal respiratory symptoms, poor sleep quality or fatigue. We compared sputum analysis, reticular basement membrane (RBM) thickness, smooth muscle area, vascular density and inflammatory cell infiltration in bronchial biopsies.

Results

In total, 27/55 patients (49%) had OSA diagnosed by overnight polygraphy. Despite a moderate increase in apnoea-hypopnoea index (AHI; 14.2±1.6 event/h [5–35]), the proportion of sputum neutrophils was higher and that of macrophages lower in OSA than non-OSA patients, with higher levels of interleukin 8 and matrix metalloproteinase 9. The RBM was significantly thinner in OSA than non-OSA patients (5.8±0.4 vs. 7.8±0.4 μm, p<0.05). RBM thickness and OSA severity assessed by the AHI were negatively correlated (rho = -0.65, p<0.05). OSA and non-OSA patients did not differ in age, sex, BMI, lung function, asthma control findings or treatment.

Conclusion

Mild OSA in patients with severe asthma is associated with increased proportion of neutrophils in sputum and changes in airway remodelling.