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。     

Response of Leucocyte Adenyl Cyclase to Isoprenaline and Effect of Alpha-blocking Drugs in Extrinsic Bronchial Asthma

The finding by several workers that biochemical responses to catecholamines are diminished in asthmatic patients during periods of active asthma as compared to normal subjects has led to the recognition of the beta-adrenergic blockade phenomenon, a common accompaniment of extrinsic bronchial asthma. Using an intact cell method to measure leucocyte adenyl cyclase activity, we have been able to show that there is a noticeably reduced responsiveness of this enzyme system (which is now identified with beta-receptor function) to isoprenaline in the leucocytes of patients suffering from acute bronchial asthma, but that asthmatic patients in remission could not be distinguished from normal persons in this respect. Evidently the defective beta-receptor function may be associated with overactivity of the alpha-receptors in acute bronchial asthma, since the responsiveness to isoprenaline stimulation could be restored towards normal by concomitant treatment of the leucocytes of these patients with alpha-receptor blocking drugs such as phentolamine or thymoxamine. Ouabain, though somewhat less potent, also enhanced responsiveness to isoprenaline stimulation. The relation of these results to the clinical observation of adrenaline resistance in active asthma suggests that alpha-receptor blocking drugs may be of value in restoring the sensitivity of beta-receptors to sympathomimetic amines.     

Disodium Cromoglycate in the Prevention of Induced Asthma

In 13 patients with allergic asthma disodium cromoglycate protected fully only two from an allergen-induced asthmatic attack.Inhalation of disodium cromoglycate did not improve lung function in five patients with long-standing chronic asthma.Previous clinical trials do not show convincing evidence that this drug improves bronchial asthma in a high percentage of cases, but it seems to help a small minority of patients.     

TLR3, TLR4 and TLRs7–9 Induced Interferons Are Not Impaired in Airway and Blood Cells in Well Controlled Asthma

Defective Rhinovirus induced interferon-β and interferon-λ production has been reported in bronchial epithelial cells from asthmatics but the mechanisms of defective interferon induction in asthma are unknown. Virus infection can induce interferon through Toll like Receptors (TLR)3, TLR7 and TLR8. The role of these TLRs in interferon induction in asthma is unclear. This objective of this study was to measure the type I and III interferon response to TLR in bronchial epithelial cells and peripheral blood cells from atopic asthmatics and non-atopic non-asthmatics. Bronchial epithelial cells and peripheral blood mononuclear cells from atopic asthmatic and non-atopic non-asthmatic subjects were stimulated with agonists to TLR3, TLR4 & TLRs7–9 and type I and III interferon and pro-inflammatory cytokine, interleukin(IL)-6 and IL-8, responses assessed. mRNA expression was analysed by qPCR. Interferon proteins were analysed by ELISA. Pro-inflammatory cytokines were induced by each TLR ligand in both cell types. Ligands to TLR3 and TLR7/8, but not other TLRs, induced interferon-β and interferon-λ in bronchial epithelial cells. The ligand to TLR7/8, but not those to other TLRs, induced only type I interferons in peripheral blood mononuclear cells. No difference was observed in TLR induced interferon or pro-inflammatory cytokine production between asthmatic and non-asthmatic subjects from either cell type. TLR3 and TLR7/8,, stimulation induced interferon in bronchial epithelial cells and peripheral blood mononuclear cells. Interferon induction to TLR agonists was not observed to be different in asthmatics and non-asthmatics.     

Undifferentiated Bronchial Fibroblasts Derived from Asthmatic Patients Display Higher Elastic Modulus than Their Non-Asthmatic Counterparts

During asthma development, differentiation of epithelial cells and fibroblasts towards the contractile phenotype is associated with bronchial wall remodeling and airway constriction. Pathological fibroblast-to-myofibroblast transition (FMT) can be triggered by local inflammation of bronchial walls. Recently, we have demonstrated that human bronchial fibroblasts (HBFs) derived from asthmatic patients display some inherent features which facilitate their FMT in vitro. In spite of intensive research efforts, these properties remain unknown. Importantly, the role of undifferentiated HBFs in the asthmatic process was systematically omitted. Specifically, biomechanical properties of undifferentiated HBFs have not been considered in either FMT or airway remodeling in vivo. Here, we combine atomic force spectroscopy with fluorescence microscopy to compare mechanical properties and actin cytoskeleton architecture of HBFs derived from asthmatic patients and non-asthmatic donors. Our results demonstrate that asthmatic HBFs form thick and aligned ‘ventral’ stress fibers accompanied by enlarged focal adhesions. The differences in cytoskeleton architecture between asthmatic and non-asthmatic cells correlate with higher elastic modulus of asthmatic HBFs and their increased predilection to TGF-β-induced FMT. Due to the obvious links between cytoskeleton architecture and mechanical equilibrium, our observations indicate that HBFs derived from asthmatic bronchi can develop considerably higher static tension than non-asthmatic HBFs. This previously unexplored property of asthmatic HBFs may be potentially important for their myofibroblastic differentiation and bronchial wall remodeling during asthma development.     

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.     

Co-Culture of Human Bronchial Fibroblasts and CD4+ T Cells Increases Th17 Cytokine Signature

Background

Airway inflammation is an important characteristic of asthma and has been associated with airway remodelling and bronchial hyperreactivity. The mucosal microenvironment composed of structural cells and highly specialised extracellular matrix is able to amplify and promote inflammation. This microenvironment leads to the development and maintenance of a specific adaptive response characterized by Th2 and Th17. Bronchial fibroblasts produce multiple mediators that may play a role in maintaining and amplifying this response in asthma.

Objective

To investigate the role of bronchial fibroblasts obtained from asthmatic subjects and healthy controls in regulating Th17 response by creating a local micro-environment that promotes this response in the airways.

Methods

Human bronchial fibroblasts and CD4⁺T cells were isolated from atopic asthmatics and non-atopic healthy controls. CD4⁺T were co-cultured with bronchial fibroblasts of asthmatic subjects and healthy controls. RORc gene expression was detected by qPCR. Phosphorylated STAT-3 and RORγt were evaluated by western blots. Th17 phenotype was measured by flow cytometry. IL-22, IL17, IL-6 TGF-β and IL1-β were assessed by qPCR and ELISA.

Results

Co-culture of CD4⁺T cells with bronchial fibroblasts significantly stimulated RORc expression and induced a significant increase in Th17 cells as characterized by the percentage of IL-17⁺/CCR6⁺ staining in asthmatic conditions. IL-17 and IL-22 were increased in both normal and asthmatic conditions with a significantly higher amount in asthmatics compared to controls. IL-6, IL-1β, TGF-β and IL-23 were significantly elevated in fibroblasts from asthmatic subjects upon co-culture with CD4⁺T cells. IL-23 stimulates IL-6 and IL-1β expression by bronchial fibroblasts.

Conclusion

Interaction between bronchial fibroblasts and T cells seems to promote specifically Th17 cells profile in asthma. These results suggest that cellular interaction particularly between T cells and fibroblasts may play a pivotal role in the regulation of the inflammatory response in asthma.     

Relationship between Breathlessness and Anxiety in Asthma and Bronchitis: A Comparative Study

Two personality testing forms, the Eysenck Personality Inventory Form A and the Cattell Self Analysis Form, were completed on 471 hospital patients who fell within the general diagnostic range of asthma, bronchitis, or both. Respiratory diagnoses were based on the standard M.R.C. questionary. All categories of patients showed a tendency towards neuroticism, anxiety, and introversion, and the scores were slightly higher for bronchitics than for asthmatics. Neuroticism and anxiety increased with increasing respiratory disability. Variations in these scores with age of onset of symptoms and length of history were small.     

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.     

支气管哮喘患者心理特征研究进展

支气管哮喘是全球范围内影响巨大的慢性气道炎症性呼吸道疾病,近年来随着空气污染的加剧和吸烟人数的增多,其发病率呈逐年上升的趋势,引起医学界越来越多的关注。支气管哮喘是由遗传因素、生物因素、心理因素等多种发病因素综合影响所致,随着研究的深入,有关心理因素对支气管哮喘的作用取得了重大的进展,其中支气管哮喘患者存在明显的人格特征和情绪障碍,并且患者特有的人格特征以及情绪障碍会对患者的病情和生活质量产生一定的影响。鉴于此,本文就支气管哮喘患者的性格特征、情绪特征以及其对疾病的影响进行简要阐述,以供临床参考。     

Serum levels of total IgE and soluble CD23 in bronchial asthma

The aim of the present study was to compare, during the pollen season, serum levels of total IgE and soluble CD23 (sCD23) from patients with allergic bronchial asthma, with those from healthy subjects. Significantly higher levels of total IgE and sCD23 were found in patients with asthma compared to the control group. Both in normal controls and in asthmatic patients, a significant correlation was shown between the levels of these two molecules. In asthmatic patients, significant correlations were found for both total IgE and sCD23, with lung function measured as bronchial responsiveness to inhaled methacholine. These results suggest that in asthmatic patients, in addition to the study of total serum IgE levels, the assessment of sCD23 serum levels may be helpful in the evaluation of disease activity.     

Establishment and evaluation of a mouse model of bronchial asthma with Yin deficiency syndrome

Objective: To establish and evaluate a mouse model of bronchial asthma with Yin deficiency syndrome. Methods: The mouse model of bronchial asthma with Yin deficiency syndrome was established by the treatment with injecting ovalbumin(OVA) two times to sensitize, inhaling OVA 14 times to stimulate, and using thyroxin through lavage during late stimulation. This model was evaluated through body weight, asthmatic behaviors, respiratory function, autonomous activity, lung pathology, and pulmonary fluid clearance. Results: OVA combined with thyroxin was an appropriate method to induce the mouse model with increased food and water intake, autonomous activity, asthmatic behaviors score, and respiratory rate, decreased body weight, tidal volume, and wet/dry ratio of lung, and changed with pathology of lung tissue. The changes of the above mentioned parameters indicated that the model was the bronchial asthma with Yin deficiency syndrome. Conclusion: The OVA combined with thyroxin is a good pattern to establish a mouse model of bronchial asthma with Yin deficiency syndrome successfully, which can highly simulate the clinical symptoms of this disease.     

The effects of diethylcarbamazine on the ultrastructure of lung cells in vivo

The pulmonary surfactant synthesis is disturbed in experimentally induced asthma, as are the intracellular storage capacity and its physical activity. These alterations may also be present in chronic asthmatic patients, and therefore the dysfunction of the pulmonary surfactant system may play an important role in the pathophysiology of asthma. Some clinical reports have described favorable results with the use of diethylcarbamazine (DEC) in patients with bronchial asthma showing that DEC is effective in terminating acute attacks of bronchial asthma. The present study aimed to analyze the ultrastructural alterations of lung cells after treatment in vivo with diethylcarbamazine. After 12 days of treatment with DEC, when compared with control samples, type II pneumocytes showed active nuclei with abundant euchromatin and evident nucleoli, and a substantially greater number of mature secretion vesicle. On the other hand, type I pneumocytes showed no morphological alterations. After DEC treatment, lung macrophages also presented several characteristics of cellular activation such as nuclei with a prominence of euchromatin and central nucleoli as well as an abundance of early and late endossomes distributed throughout the cytoplasm. These results confirm that DEC exerts a role in the activation of important pulmonary cellular pathways, which are probably related to the clinical improvement of asthma symptoms after DEC treatment.     

Identification of Relationships Between Interleukin 15 mRNA and Brain-Derived Neurotrophic Factor II mRNA Levels With Formal Components of Temperament in Asthmatic Patients

Asthma is a chronic inflammatory and heterogeneous disease developing mostly through allergic inflammation, which modifies the expression of various cytokines and neurotrophins. Previous studies suggest the involvement of interleukin (IL)-15 in the regulation of immune response in asthma. Brain-derived neurotrophic factor (BDNF) II plays an important role as a regulator of development and survival of neurons as well as maintenance of their physiological activity. Chronic stress associated with asthma and elevated IL-15 mRNA and BDNFII mRNA levels may affect the mood and a subjective sensation of dyspnoea-inducing anxiety. Psychopathological variables and numerous cytokine/neurotrophin interactions influence the formation of temperament and strategies of coping with stress. The aim of the study was to identify the role of IL-15 mRNA and BDNFII mRNA expressions and their effect on components of temperament and strategies of coping with stress in asthmatics. A total of 352 subjects (176 healthy volunteers and 176 asthmatic patients) participated in the study. The Formal Characteristic of Behaviour-Temperament Inventory (FCB-TI), Coping Inventory for Stressful Situations (CISS), Beck Depression Inventory, State-Trait Anxiety Inventory, and Borg Rating of Perceived Exertion (RPE) Scale were applied in all the subjects. The expression of IL-15 and BDNFII gene was measured using quantitative real-time polymerase chain reaction (qRT-PCR). Different levels of IL-15 and BDNFII expressions between healthy volunteers and patients were revealed in the study. IL-15 enhanced the BDNFII mRNA expression among patients with bronchial asthma. The depression level negatively correlated with the BDNFII mRNA expression. This neurotrophin modified the temperament variable. BDNFII significantly affected (proportional relationship) the level of briskness in asthmatic patients. BDNFII might influence the level and style of coping with stress (emotion-oriented style). This hypothesis requires further studies on protein functional models. The obtained data confirms the role of IL-15 and BDNFII in the pathomechanisms of depression and formation of selected traits defining the temperament in asthmatics.     

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.     

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.     

Psychosocial characteristics of patients with bronchial asthma and coronary disease: similarities and differences

The authors compare two groups of subjects: patients with bronchial asthma and those with coronary disease, with regard to some social characteristics, abilities and perception of factors which they conceive are important in the etiology of their disease. Data were obtained by means of a questionnaire based on a known calibrated scale. A group of 100 patients with bronchial asthma and a group of 102 patients with coronary disease were examined. The significance of the difference was tested by chi 2, t-test, Wilcoxon's test and multivariate discriminative analysis. The results showed statistically significant differences between the patients with bronchial asthma and those with coronary disease in some social and psychological characteristics and also with regard to perception of potential etiological factors of their disease. However, no difference was found in life style and habits between the coronary and asthmatic patients.     

Analysis of novel disease-related genes in bronchial asthma

Bronchial asthma is a complex disease characterized by airway inflammation involving interleukin (IL)-4 and IL-13. We have applied microarray analyses to human bronchial epithelial cultures to probe for genes regulated by these cytokines and have identified a subset of disease-relevant genes by comparison with cDNA libraries derived from normal and asthmatic bronchial biopsies. Squamous cell carcinoma antigen-1 (SCCA1) and SCCA2, the cysteine and serine protease inhibitors, respectively, showed the highest expression by IL-4 and IL-13, and particularly, SCCA1 was significantly increased in the asthmatic cDNA library. STAT6 was shown to be involved in expression of SCCA1 and SCCA2 in vitro. Furthermore, serum levels of SCCA were also elevated in asthmatic patients. Taken together, it was supposed that SCCA may play some role in the pathogenesis of bronchia asthma, and measuring its serum level may be relevant for diagnosing or monitoring the status of bronchial asthma. In a complex disorder such as asthma, this combination of in vitro and in vivo genomic approaches is a powerful discriminatory method enabling identification of novel disease-related genes and their mechanisms of regulation.     

T cells of atopic asthmatics preferentially infiltrate into human bronchial xenografts in SCID mice

T cells play an important role in the pathogenesis of bronchial asthma. However, it is not completely known how circulating lymphocytes infiltrate into the airways of asthmatic patients. Because SCID mice are unable to reject xenogenic transplants, many xenotransplant models using various human tissues have been developed. Therefore, to examine the interaction between bronchi and T lymphocytes of asthma, it may be possible to use the human bronchial xenograft and PBMC xenograft in SCID mice. We transplanted human bronchi into the subcutaneum of SCID mice and i.p. injected PBMCs that were obtained from patients with atopic asthma, atopic dermatitis and rheumatoid arthritis, and normal subjects (asthmatic, dermatitis, rheumatic, and normal huPBMC-SCID mice). There was no difference in the percentage of CD3-, CD4-, CD8-, CD25-, CD45RO-, CD103-, and cutaneous lymphocyte Ag-positive cells in PBMCs among the patients with asthma, dermatitis, rheumatoid arthritis, and normal subjects, and CD3-positive cells in peripheral blood of asthmatic, dermatitis, rheumatic, and normal huPBMC-SCID mice. The number of CD3-, CD4-, and CD8-positive cells in the xenografts of asthmatic huPBMC-SCID mice was higher than those of dermatitis, rheumatic, and normal huPBMC-SCID mice. IL-4 mRNA and IL-5 mRNA were significantly higher in the xenografts of asthmatic huPBMC-SCID mice than those in the xenografts of normal huPBMC-SCID mice, but there were no significant differences in the expressions of IL-2 mRNA or IFN-gamma mRNA between them. These findings suggest that T cells, especially Th2-type T cells, of asthmatics preferentially infiltrate into the human bronchi.