Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149514 (bronchitis)
 6,902 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunologic and histologic changes associated with lung allograft rejection are believed to result from the presentation of donor lung alloantigens to recipient lymphocytes resulting in up-regulated Th1 lymphocyte activity. The ability of allogeneic lung immune cells to induce the pathologic and immunologic changes associated with acute lung allograft rejection are unknown. The current study determined whether allogeneic (C57BL/6, I-a(b)) bronchoalveolar lavage (BAL) cells (> or = 97% macrophages), when instilled into the lungs of recipient BALB/c mice (I-a(d)), induced the histology and immunology associated with acute lung allograft rejection. BALB/c mice received BAL cells from either C57BL/6 mice (allogeneic instillate) or BALB/c mice (autologous instillate) or PBS (control) by nasal insufflation weekly for 4 wk. Allogeneic BAL cells resulted in a lymphocytic bronchitis and vasculitis analogous to grade 1 to 2 lung allograft rejection. The mice given allogeneic instillates had a greater percentage of lymphocytes in the BAL fluid than those given autologous instillates. After instillation of allogeneic BAL cells, the Th1 cytokines, IL-2 and IFN-gamma (IFN-gamma), were produced locally in greater quantities and more frequently than Th2 cytokine IL-10. IL-4, another Th2 cytokine, was not detected. The local production of IgG1 and IgG2a, which are dependent on IL-4 and IFN-gamma, respectively, were increased. However, only IgG2a was deposited in the perivascular and peribronchiolar tissues. These data show that installation of allogeneic BAL cells into the airways of recipient mice induced up-regulated Th1 lymphocyte activity and caused the histologic changes associated with lung allograft rejection.
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PMID:Allogeneic bronchoalveolar lavage cells induce the histology of acute lung allograft rejection, and deposition of IgG2a in recipient murine lungs. 765 Apr 3

The T cell hypothesis of asthma, particularly chronic asthma, is based around the concept that the disease is driven and maintained by the persistence of a specialized subset of chronically activated T memory cells sensitized against an array of allergenic, occupational or viral antigens which home to the lung after appropriate antigen exposure or viral infection. Allergens induce a CD4+ T helper (Th) cell response, whereas viruses recognize CD8+ T cytotoxic (Tc) cells. In the asthmatic airway there appears to be both CD4+ and CD8+ cells with a type 2 cytokine phenotype (i.e. Th2 and Tc2 type). These cells produce: interleukin (IL)-5, IL-3 and granulocyte macrophage colony-stimulating factor, which recruit, mobilize and activate eosinophils for subsequent mucosal tissue damage; and IL-4, an essential co-factor for local or generalized IgE production. This in turn leads to eosinophilic desquamative bronchitis, with epithelial shedding, mucus hypersecretion and bronchial smooth muscle contraction. Thus, although the eosinophil is largely responsible for airway symptoms, its function appears to be under T cell control. Support for this hypothesis includes: the observations that activated T cells and their products can be identified in biopsies from the major variants of the disease (atopic, nonatopic [intrinsic] and occupational asthma); the co-localization of mRNA for type 2 cytokines to CD4+ and CD8+ cells in atopic and non-atopic asthma; the presence of chronically activated cytokine-producing T cells in corticosteroid-resistant asthma; the association of disease severity with type 2 cytokines, especially IL-5; and the efficacy of cyclosporin A in chronic steroid-dependent disease. Inhibitors and/or antagonists directed against more precise T cell-associated molecular targets hold promise for the future treatment of chronic asthma.
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PMID:T cells as orchestrators of the asthmatic response. 925 5

Chemical exposure may result in respiratory conditions such as chronic bronchitis, bronchial hyperresponsiveness, and chronic airway obstruction. Clinical studies have shown that during the course of disease, cytokine networks are changed. In order to study the relationship between blood cytokines and respiratory symptoms in an occupational setting, we investigated 106 chemical workers during a routine yearly medical examination in 1995. Lung function was measured with flow volume curves and impedance using the forced oscillation technique (FOT). Smoking-status and respiratory symptoms were determined by questionnaires. Cytokines were selected on biological plausibility and measured both in a whole blood assay (TNF-alpha, IL-8) and in serum (IL-4, IL-5, IL-6, IFN-gamma). The hypothesis is that blood levels of TNF-alpha and IL-8 are increased in bronchitis, while serum levels of IL4, IL-5 are increased and IFN-gamma is decreased in asthmatic workers. Spontaneous IL-8 release was significantly higher in workers with bronchitis (P < 0.05) or chronic bronchitis (P < 0.01) compared to workers without those respiratory symptoms, also after correction for age, pack-years, and blood lymphocyte numbers or compared to a matched control group. No correlation was present between specific cytokines and asthmatic symptoms. These data suggest that blood IL-8 may be considered as a useful marker for bronchitis.
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PMID:Blood interleukin-8 production is increased in chemical workers with bronchitic symptoms. 935 25

Asthma and chronic obstructive pulmonary disease (COPD) are complex conditions with imprecise definitions, which make definitive morphological comparisons difficult. The airways in asthma are occluded by tenacious plugs of exudate and mucus, and there is fragility of airway surface epithelium, thickening of the reticular layer beneath the epithelial basal lamina (the last two not usually features of COPD), and bronchial vessel congestion and oedema. There is an increased inflammatory infiltrate comprising 'activated' lymphocytes and eosinophils with release of granular content in the latter, and enlargement of bronchial smooth muscle, particularly in medium-sized bronchi. CD4+ve lymphocytes predominate over CD8+ve cells and neutrophils are sparse. In contrast, three conditions contribute to COPD. In chronic bronchitis there is cough and mucous hypersecretion with enlargement of tracheobronchial submucosal glands and a disproportionate increase of mucous acini. CD8+ve lymphocytes predominate over CD4+ve cells and there are increased numbers of subepithelial macrophages and intra-epithelial neutrophils. Exacerbations of bronchitis are associated with a tissue eosinophilia, apparent absence of IL-5 protein but gene expression for IL-4 and IL-5 is present. In small or peripheral airways disease, there is inflammation of bronchioli and mucous metaplasia and hyperplasia, with increased intraluminal mucus, increased wall muscle, fibrosis, and airway stenoses (also referred to as chronic obstructive bronchiolitis). Respiratory bronchiolitis involving increased numbers of pigmented macrophages is a critically important early lesion. Increasingly severe peribronchiolitis includes infiltration of T lymphocytes in which the CD8+ subset again predominates. These inflammatory changes may predispose to the development of centrilobular emphysema and reduced FEV1 via the destruction of alveolar attachments. In emphysema there is abnormal, permanent enlargement of airspaces distal to the terminal bronchiolus (i.e. within the acinus) accompanied by destruction of alveolar walls and without obvious fibrosis. The severity of emphysema, rather than type, appears to be the most important determinant of chronic deterioration of airflow, and in this there may be significant loss of elastic recoil and microscopic emphysema prior to the observed macroscopic destruction of the acinus.
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PMID:Differences and similarities between chronic obstructive pulmonary disease and asthma. 1042 18

Chronic obstructive pulmonary disease (COPD) is a cytotoxic T lymphocyte (CD8)- and macrophage (CD68)-predominant chronic inflammatory disorder of the conducting airways and alveoli. This is often associated with a neutrophilia, inflammation of small airways and destruction of tissue beyond the terminal bronchiolus, i.e. emphysema. In contrast, asthma is a helper T cell (CD4; type 2)-predominant chronic inflammatory disorder of the conducting airways in which there is T lymphocyte-derived gene expression for interleukin (IL)-4 and IL-5 but not interferon gamma. There is fragility of airway surface epithelium, thickening of the reticular basement membrane, bronchial vessel congestion and (when severe) an increase in the mass of bronchial smooth muscle. This is usually (but not always) associated with tissue and peripheral blood eosinophilia rather than a neutrophilia and there is exudative plugging of the airways. These differences of inflammatory profile, remodelling and lung function are seen when smokers with COPD are compared with non-smoking mild asthmatics. However there may be important similarities and overlap, particularly in more severe asthma when neutrophils predominate and in the older and or smoking asthmatic when reversibility of airflow is less obvious. We have recently demonstrated gene expression for IL-4 and IL-5 in and around the mucus-secreting glands of airways resected from smokers without a history of asthma. Also exacerbations of bronchitis may be associated with a tissue eosinophilia. On examination of bronchial biopsies from these patients we show surprisingly strong gene expression for IL-4, IL-5 and even human eotaxin and RANTES (regulated on activation normal T cell expressed and secreted). Whilst CD4 T lymphocytes of the Th2 phenotype might be expressing these cytokines in bronchitis, CD8 T lymphocytes are also capable of secreting IL-4 and IL-5. Viruses may modulate these changes in distinct lymphocyte functional phenotypes. The relevance and importance of CD4/CD8 T lymphocyte ratio to the development of COPD is discussed.
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PMID:Lymphocytes, chronic bronchitis and chronic obstructive pulmonary disease. 1119 94

Since the first decades of the twentieth century, some authors have believed bacterial respiratory infection to be an important triggering factor in bronchial asthma, drawing attention to an asthmatic response to infection. In this context, already in 1995, we presented a study on nasal secretion cultures and the relationship between IgE and sensitization to allergens. There was a statistically significant association between patients with sensitization to Dermatophagoides, elevated IgE levels and Staphylococcus Aureus positive cultures. Following the studies by Norn, we performed a study in 40 children, aged 2-14 years, and observed that these children with sensitization to mites and positive culture released higher histamine levels than did children with negative cultures and controls. The differences were statistically significant. In agreement with other authors, we also found that the presence of both S. aureus and D. pteronyssinus favored antigen specific histamine release. In the last few years, when the increase in the prevalence of bronchial asthma began to be studied, the role of infection, among other factors, in favoring this increase began to be examined. Using the methodology of the ISAAC project, we distributed a parallel questionnaire containing questions on triggering and contributing factors among which was respiratory infection. We found that there was an association between having three of more episodes of bronchitis in the previous year, accompanied by fever and with a duration of more than 7 days and having asthma at some time (OR: 29.09). This association was even higher in patients with wheezing in the previous 12 months (OR: 43.26) and was also associated with the need to present to the emergency department (OR: 30.65). From these results we conclude that respiratory infection is an aggravating factor in asthma, as we already know. For several years, several authors have studied how non-nosocomial respiratory infections can directly modulate Th1/Th2 response. In order to obtain our own results, we studied serum interleukin 4 (IL4) and interferon-gamma (IFN-gamma) in 42 children aged 3-17 years. The most frequent IL-4 values expressed in ng/ml were between 0.25-0.40, with little variation in the sample, which did not permit correlation among variables. Concerning IFN-gamma, we found values between < 5 and 605 pg/ml. In children undergoing antigen-specific immunotherapy, we observed mean IFN-gamma values of 115.86 pg/ml, while children not undergoing immunotherapy and those who had been administered this treatment for less than 1 year, had a mean of 66.06 pg/ml. These differences were statistically significant (p = 0.035), thus revealing a Th1 response to immunotherapy. These differences were not statistically significant when children who had been administered immunotherapy for less than 1 year were included. When we studied children with bacterial immunotherapy and grouped them in the same way, we found that the mean IFN-gamma of the children undergoing immunotherapy for more than 1 year was 56.4 pg/ml compared with 101.75 pg/ml in those without immunotherapy. This difference was statistically significant (p = 0.034). We are able to conclude that bacterial immunotherapy modifies Th1 response, inhibiting it in children with higher susceptibility to infection. In view of these preliminary results, it would be interesting to continue to study interleukins in order to determine the modification of these substances by immunotherapy in a prospective study and with a sample selected in relation to immunotherapy and not other parameters, since those we have studied have shown no relationship.
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PMID:[The role of infection in asthma]. 1143 90

Eosinophilia has been reported during exacerbations of bronchitis, but the mechanisms of tissue recruitment of eosinophils are unclear. We quantified eosinophils and the concurrent expression of cytokines and chemokines probably responsible for the tissue eosinophilia in bronchial biopsies obtained from three groups of nonatopic subjects: (1) healthy nonsmokers (n = 7; FEV1 % predicted = 108 +/- 4 [mean +/- SEM]); (2) nonasthmatic smokers with chronic bronchitis (CB) in a stable phase of their disease (n = 11; FEV1 % predicted: 75 +/- 5); and (3) nonasthmatic subjects with CB who sought medical advice for an exacerbation of their condition (n = 9; FEV(1) % predicted: 61 +/- 8). We applied anti-EG2 antibody and immunostaining to detect and count eosinophils. We performed in situ hybridization to visualize and enumerate cells expressing the genes for interleukin (IL)-4 and IL-5 and the eosinophil chemokines eotaxin, monocyte chemoattractant protein (MCP)-4, or regulated on activation, normal T-cell expressed and secreted (RANTES). We confirmed an increase in EG2-positive eosinophils in patients with CB in exacerbation. We found messenger RNA (mRNA) positivity for IL-4 and IL-5 in CB, but the between-group differences were not statistically significant. However, the numbers of lymphomononuclear cells expressing eotaxin mRNA were significantly greater in the smokers with CB than in the healthy nonsmokers without CB (p < 0.01). Following an exacerbation, RANTES expression was upregulated and this chemokine was strongly expressed in both the surface epithelium and in subepithelial lymphomononuclear cells: only RANTES showed a significant positive correlation with the increasing number of EG2-positive cells (r = 0.51; p < 0.03). In conclusion, an allergic profile of inflammation can also occur in CB: the marked upregulation of RANTES in the epithelium and subepithelium most likely accounts for the increased eosinophilia associated with an exacerbation of bronchitis.
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PMID:Exacerbations of Bronchitis: bronchial eosinophilia and gene expression for interleukin-4, interleukin-5, and eosinophil chemoattractants. 1143 30

We wished to determine if the inflammatory cells surrounding the airway mucus-secreting glands in chronic bronchitis (CB) were associated with interleukin (IL)-4 and IL-5 mRNA expression and whether the CD8 T cell population expressed these cytokines. Digoxigenin-labeled IL-4 and IL-5 antisense RNA probes were used to detect gene expression in 11 asymptomic smokers (AS), 11 smokers with CB alone with normal lung function, and 10 smokers with chronic bronchitis and coexisting chronic obstructive pulmonary disease (CB+COPD; FEV(1)% of predicted of 43-77% and FEV(1)/ FVC of 51-68%). There were approximately three times as many IL-4 than IL-5 mRNA(+) cells. The highest number of IL-4 mRNA(+) cells were in the submucosal glands of the CB group with normal lung function (216/mm(2)), significantly higher than the values in either the AS (63/mm(2)) or the CB+COPD (87/mm(2)) groups, respectively (p < 0.01). There were similar group differences when the total numbers of inflammatory cells were compared. Accordingly, there was a positive correlation between the number of IL-4 mRNA(+) cells and the total number of inflammatory cells in both the subepithelium and glandular compartments (r = 0.60; p = 0.01 and r = 0.70; p = 0.02, respectively). There were no significant associations between the numbers of CD8(+) and IL-4 or IL-5 mRNA(+) cells. Of 1328 IL-4(+) and 1404 CD8(+) cells counted none was double labeled. Of 727 IL-5(+) and 1569 CD8(+) cells, none was double labeled. In contrast, as a positive control, 34% of tumor necrosis factor (TNF)-alpha(+) cells were also CD8(+) and 15% of CD8(+) cells were TNF-alpha positive. Thus, cells other than the CD8(+) phenotype produce IL-4 and IL-5 in CB. We conclude that there is increased inflammation and IL-4 gene expression in the mucus-secreting glands and the airway mucosa of smokers with bronchitis: both are lower in those with CB and coexisting COPD suggesting that airway inflammation in CB is reduced when airway obstruction develops.
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PMID:Interleukin-4 and interleukin-5 gene expression and inflammation in the mucus-secreting glands and subepithelial tissue of smokers with chronic bronchitis. Lack of relationship with CD8(+) cells. 1175 Nov 91

The recent understanding of the key role of adhesion molecules in the pathogenesis of chest allergy in parasitic infections may provide a pharmacological target for the associated asthmatic symptoms. Circulating levels of the endothelial cell adhesion molecules (CAMs): sICAM-1, sVCAM-1 and sE-selectin in sera of 18 allergic asthmatic patients. 16 fascioliasis cases (acute & chronic), 24 fascioliasis cases with allergic chest manifestations and 10 apparently healthy control subjects were estimated by ELISA method. Also, IL-4 serum level was evaluated in all groups. Chest allergy in association with fascioliasis included mainly bronchial asthma, beside eosinophilic bronchitis, persistent wheezing and chronic cough. The study provided evidence that adhesion molecules expression is up regulated in acute and chronic fascioliasis cases with allergic chest manifestations. sVCAM-1 seemed to be an early indicator of asthma development in human fascioliasis. IL-4 cytokine was suggested to be responsible for the increased expression especially in the chronic phase of the disease, yet the role of other cytokines cannot be excluded.
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PMID:Role of endothelial cell adhesion molecules in the development of allergy in human fascioliasis. 1273 9

There is compelling evidence that human mast cells contribute to the pathophysiology of asthma. Mast cells, but not T cells or eosinophils, localize within the bronchial smooth muscle bundles in patients with asthma but not in normal subjects or those with eosinophilic bronchitis, a factor likely to be important in determining the asthmatic phenotype. The mechanism of mast cell recruitment by asthmatic airway smooth muscle involves the CXCL10/CXCR3 axis, and several mast cell mediators have profound effects on airway smooth muscle function. The autacoids are established as potent bronchoconstrictors, whereas the proteases tryptase and chymase are being demonstrated to have a range of actions consistent with key roles in inflammation, tissue remodeling, and bronchial hyperresponsiveness. IL-4 and IL-13, known mast cell products, also induce bronchial hyperresponsiveness in the mouse independent of the inflammatory response and enhance the magnitude of agonist-induced intracellular Ca2+ responses in cultured human airway smooth muscle. There are therefore many pathways by which the close approximation of mast cells with airway smooth muscle cells might lead to disordered airway smooth muscle function. Mast cells also infiltrate the airway mucous glands in subjects with asthma, showing features of degranulation, and a positive correlation with the degree of mucus obstructing the airway lumen, suggesting that mast cells play an important role in regulating mucous gland secretion. The development of potent and specific inhibitors of mast cell secretion, which remain active when administered long-term to asthmatic airways, should offer a novel approach to the treatment of asthma.
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PMID:The role of the mast cell in the pathophysiology of asthma. 1675 Sep 87


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