UMLS:C0149514 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0149514 (bronchitis)
6,902 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methods to examine sputum for indices of airway inflammation are evolving. We have examined the repeatability and the validity of an improved method to measure sputum cells and fluid-phase eosinophil cationic protein (ECP), major basic protein (MBP), eosinophil-derived neurotoxin (EDN), albumin, fibrinogen, tryptase, and interleukin-5 (IL-5). Sputum was induced with hypertonic saline twice within 6 d in 10 healthy subjects, 19 stable asthmatics, and 10 smokers with nonobstructive bronchitis. The method included the processing of freshly expectorated sputum separated from saliva, treatment with a fixed proportion of dithiothreitol 0.1% followed by Dulbecco's phosphate-buffered saline, making cytospins, and collecting the supernatant. The reproducibility of measurements, calculated by the intraclass correlation coefficient, was high for all indices measured with the exception of total cell counts and proportion of lymphocytes. Asthmatics, in comparison with healthy subjects and smokers with bronchitis, had a higher proportion of sputum eosinophils (median percent 5.2 versus 0.5 and 0.3), metachromatic cells (0.3 versus 0.07 and 0.08), ECP (1,040 micrograms/L versus 288 and 352), MBP (1,176 micrograms/L versus 304 and 160), and EDN (1,512 micrograms/L versus 448 and 272). Asthmatics differed from healthy subjects, but not from smokers with bronchitis, in the proportion of neutrophils (46.9% versus 24.1%), albumin (704 versus 288 micrograms/mL), and fibrinogen (2,080 versus 440 ng/mL). Smokers with bronchitis showed a trend for a higher neutrophil count and levels of albumin and fibrinogen than healthy subjects. The proportion of sputum eosinophils correlated positively with ECP, MBP, EDN, albumin and fibrinogen levels, and metachromatic cell counts correlated with tryptase. In asthmatics, IL-5 correlated with eosinophil counts. There was a significant negative correlation between sputum indices and expiratory flows and methacholine PC20. Thus, the methods of measuring cell and fluid phase markers in induced sputum used in this study are reproducible and valid. They can therefore be used to reliably measure these indices of airway inflammation.
...
PMID:Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. 2597 85

Interleukin-4 (IL-4) and IL-5 are cytokines with important roles in IgE production and eosinophilia. Interleukin-4 is essential for IgE production, and IL-5 is the major factor involved in the production and activation of eosinophils. These two phenomena commonly occur together in parasitic infestation and allergic disease. Both cytokines are produced by T helper 2 (Th2) and Th0 cells but not by Th1 cells, and in a number of experimental systems IL-4 is required for the production of IL-5. This article presents evidence that IL-4 and IL-5 are not always co-ordinately produced. There is evidence for selective production of either IL-4 or IL-5 in response to immune stimulation by different adjuvants. Dissociation of production of these two cytokines has also been reported in several pathological situations. An example is intrinsic or non-atopic asthma, with eosinophilic bronchitis but without elevated IgE production, where there is evidence for excessive production of IL-5 but not IL-4. Different microenvironmental factors may favour production of either IL-4 or IL-5. For example, IL-2 stimulates the production of IL-5 but not IL-4. Therefore the Th2 model does not account for all immune responses involving IL-4 or IL-5. Responses characterized by IL-4 without IL-5, and IL-5 without IL-4, can also occur.
...
PMID:Dissociation of production of interleukin-4 and interleukin-5. 879 28

A paradigm shift, championed largely by cellular immunologists, has redefined asthma as an immune mediated phenomenon characterised by an interleukin 5 (IL-5) driven eosinophilic bronchitis. This change in emphasis has provoked intense interest in the possibility that inhibitors of IL-5 production, or antagonists of its activity, will provide a new generation of anti-asthma drugs.
...
PMID:Anti-interleukin 5 strategies as a potential treatment for asthma. 917 43

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.
...
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.
...
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.
...
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.
...
PMID:Lymphocytes, chronic bronchitis and chronic obstructive pulmonary disease. 1119 94

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.
...
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.
...
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

Airway inflammation with eosinophils is now reported to occur not only in asthma but in other airway diseases such as cough variant asthma, chronic cough, atopic cough, episodic symptoms without asthma, allergic rhinitis, and COPD. Although the prevalence of eosinophilic bronchitis (EB) is less than in asthma, the causes, mechanisms and treatment of EB in these conditions appears to be similar to asthma where allergen induced IL-5 secretion and symptoms are readily responsive to inhaled corticosteroids. The prognosis of EB without asthma is not known but it may be a precursor for asthma and, if so, recognition of this syndrome may permit effective treatment and reduction in the rising prevalence of asthma. Induced sputum analysis allows recognition of EB in clinical practice. The place of the asthma treatment paradigm with early and sustained corticosteroid treatment needs to be defined in EB without asthma. Airway wall remodelling can occur in rhinitis, COPD, and cough variant asthma with EB. The mechanisms and long term implications of this complication in EB without asthma need to be clarified.
...
PMID:Eosinophilic bronchitis: clinical manifestations and implications for treatment. 1182 51

1 2 3 Next >>