Eosinophil infiltration of the mucosa is a feature of asthmatic airways. Their adhesion to bronchial epithelial cells has been proposed to lead to the generation of inflammation mediators which may contribute to asthma pathology. Bronchial epithelial cells (BEAS-2B cell line) and peripheral blood eosinophils were cultured alone or in combination and the production of an inflammatory cytokine, IL-6, was measured. IL-6 was produced principally by epithelial cells and the production was enhanced more than 10-fold in the presence of eosinophils. Significant augmentation of epithelial IL-6 production persisted even when eosinophils were fixed with paraformaldehyde. The eosinophil-induced IL-6 production was extensively inhibited by inhibitors of p38 mitogen-activated protein (MAP) kinase or nuclear factor ??B (NF??B). (more…)
Exacerbations of asthma are frequently associated with rhinoviral infection. Rhinoviruses infect respiratory epithelial cells, ...
Toll-like receptors (TLRs) act as receptors for numerous stimuli of immune cells, including bacterial cell wall constituents (l ...
Airway hyper-responsiveness in asthma may involve smooth muscle growth, a manifestation of airway remodelling. The involvement ...
Contact of pathogens with the innate immune system will most frequently occur at epithelia, and the biology of the airway epitheliu ...
Vascular Endothelial Growth Factor (VEGF), originally described as a vascular permeability factor generating tissue oedema, has be ...
Two long-acting ß 2 -adrenergic agonists (LABAs), salmeterol and formoterol, have been demonstrated to be safe and effective agents in children, both in terms of bronchodilation and prevention of exercise-induced bronchospasm. Their onsets of action differ, with formoterol having an onset similar to albuterol (3 minutes), while salmeterol has a slower onset of action (10–20 minutes). Following a single-dose administration, both agents demonstrate durations of action up to 12 hours. Following regular twice-daily administration, bronchodilation remains effective; however, a level of tolerance (or tachyphylaxis) (more…)
For most patients, asthma is not controlled as defined by guidelines; whether this is achievable has not been prospectively stu ...
This study evaluated budesonide formoterol efficacy and safety of a novel asthma management strategy for both maintenance and s ...
Asthma control is improved by combining inhaled corticosteroids with long acting beta-agonists but patients still require relie ...
Regular use of ß-agonists has been known to lead to tolerance to their bronchodilator effects. It is not known how quickly toleranc ...
Current internationally recognized guidelines indicate that symptomatic asthmatics using a low to medium inhaled corticosteroid ...
Airway remodelling is considered to be of major importance in the pathology of asthma, with subepithelial basement membrane thickening in particular being indicative of early development of the disease and characteristic of its progression. Airway fibroblasts are central cells in the processes of remodelling: increased deposition of fibroblast-derived connective tissue proteins and differentiation of fibroblasts into contractile myofibroblasts are consistent observations in morphological studies of moderate to severe asthmatic airways. The secretory function of fibroblasts is under the control of locally produced growth factors such as vascular endothelial cell growth factor (VEGF, see below) and platelet-derived growth factor (PDGF). (more…)
Vascular Endothelial Growth Factor (VEGF), originally described as a vascular permeability factor generating tissue oedema, has be ...
Local micro environmental factors are crucial in determining both susceptibility to vascular remodeling and the extent of angio ...
Tumour Necrosis Factor is a pro-inflammatory cytokine implicated in the pathogenesis of asthmatic airway inflammation, hyper-react ...
Asthma is a continuing problem for healthcare, particularly in the industrialized world. Some 150 million people are estimated ...
Airway hyper-responsiveness in asthma may involve smooth muscle growth, a manifestation of airway remodelling. The involvement ...
Current internationally recognized guidelines indicate that symptomatic asthmatics using a low to medium inhaled corticosteroid dose (400–800 µg/day of beclomethasone or equivalent) alone should preferentially be commenced on a long-acting agonist ß2 prior to an leukotriene receptor antagonists LTRA (British guideline on the management of asthma 2003; GINA Workshop Report 2004). However, two recent large trials have performed head to-head comparisons of add-on long-acting ß2 agonist versus LTRA as therapeutic adjuncts to inhaled corticosteroids, using exacerbation frequency (rather than lung function and symptoms) as the primary end point. (more…)
Leukotrienes can be found in the airway and urine following both spontaneous exacerbations of asthma and acute exposure to bron ...
Despite optimum drug delivery and good compliance with inhaled corticosteroids, many patients experience symptoms and exacerbat ...
Two long-acting ß 2 -adrenergic agonists (LABAs), salmeterol and formoterol, have been demonstrated to be safe and effective ag ...
Treating allergic rhinitis may have a downstream effect on concomitant asthma and this may be due to attenuation of the underlying ...
Regular use of ß-agonists has been known to lead to tolerance to their bronchodilator effects. It is not known how quickly toleranc ...
Despite optimum drug delivery and good compliance with inhaled corticosteroids, many patients experience symptoms and exacerbations. Dose–response studies using inhaled corticosteroids have generally been unable to demonstrate any significant difference between individual doses of inhaled corticosteroids. For example, a metaanalysis evaluated eight studies (2324 asthmatics) where the effects of at least two doses of inhaled fluticasone were measured. (more…)
Current internationally recognized guidelines indicate that symptomatic asthmatics using a low to medium inhaled corticosteroid ...
Leukotrienes can be found in the airway and urine following both spontaneous exacerbations of asthma and acute exposure to bron ...
Treating allergic rhinitis may have a downstream effect on concomitant asthma and this may be due to attenuation of the underlying ...
The guidelines for asthma management recommend the use of regular inhaled corticosteroid in patients with mild persistent asthma, b ...
This study was similar to the study of Harrison and colleagues, which looked at doubling the dose of inhaled corticosteroid dur ...
The immunologic mechanisms of sublingual immunotherapy are less established. In Cochrane analysis, the authors concluded that there was an increase in IgG4 but no stable effect on IgE levels in adults. In addition, the induction of allergen-specific IgA has been reported. There are conflicting data concerning lympho-proliferative responses. So far the evidence on changes in Th1/Th2/Treg activity induced by sublingual immunotherapy need to be confirmed. The effects on T-cell reactivity and cytokine secretion show strong variation in a number of studies. (more…)
Allergen-specific immunotherapy aims to correct the underlying immune imbalance associated with specific immunotherapy allergic rhi ...
The precise mechanisms underlying the effects of Specific Immunotherapy are not well understood but several studies have shown ...
The increasing prevalence of allergic disease in the Western world has led to the concept of the ‘allergic march’ to describe t ...
Allergen-specific immunotherapy is highly effective in the treatment of IgE-mediated allergy diseases such as rhinitis, conjunc ...
Histamine is a low-molecular-weight monoamine that binds to four different G-protein-coupled receptors, and has recently been d ...
Treg cells or regulatory T cells constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dysregulated immune response appears to be an important pathogenetic factor. Cardinal events during allergic inflammation can be classified as activation, organ-selective homing, survival and reactivation, and effector functions of immune system cells. T cells are activated by aeroallergens, food antigens, autoantigens, and bacterial exotoxins superantigens in allergic inflammation. They are under the influence of the skin, lung, or nose-related chemokine network and show organ-selective homing. (more…)
Allergen-specific immunotherapy is highly effective in the treatment of IgE-mediated allergy diseases such as rhinitis, conjunc ...
The induction of immune tolerance and specific immune suppression are essential processes in the control of immune responses. R ...
The intracellular forkhead winged transcription factor Foxp3 (forkhead box P3) appears to be specifically expressed by naturall ...
An emerging concept is that pro-inflammatory signals lead to loss of Regulatory T Cells (Treg) function. Pasare and Medzhitov ( ...
Regulatory T cells Treg (picture above) is the existence of suppressor cells, which limit ongoing immune responses and prevent ...
Allergen-specific immunotherapy is highly effective in the treatment of IgE-mediated allergy diseases such as rhinitis, conjunctivitis, asthma, and venom allergy hypersensitivity. It is the only treatment that leads to lifelong tolerance against previously disease-causing allergens due to restoration of the normal immunity. (more…)
Allergen-specific immunotherapy aims to correct the underlying immune imbalance associated with specific immunotherapy allergic rhi ...
Histamine is a low-molecular-weight monoamine that binds to four different G-protein-coupled receptors, and has recently been d ...
The precise mechanisms underlying the effects of Specific Immunotherapy are not well understood but several studies have shown ...
Treg cells or regulatory T cells constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dys ...
The immunologic mechanisms of sublingual immunotherapy are less established. In Cochrane analysis, the authors concluded that t ...
The intracellular forkhead winged transcription factor Foxp3 (forkhead box P3) appears to be specifically expressed by naturally occurring Treg cells, particularly in mice, although in humans there is evidence of upregulation of Foxp3 in all T cells on activation. Foxp3 is required for the development and function of naturally occurring regulatory t cells (treg) and expression is sufficient to convert non-regulatory CD4+CD25T cells into cells with regulatory activity. Conversion of peripheral CD4+CD25 naive T cells to Foxp3+CD4+CD25 foxp3+ Treg cells can be induced by TGF-ß. In a murine asthma model, these TGF-ß-induced Treg prevented house-dust mite-induced allergic pathogenesis or infection pathogenesis in lungs. A single independent report has suggested that IL-4 and IL-13 also induce Foxp3+CD25+ Treg from CD4+CD25precursors. (more…)
Regulatory T cells Treg (picture above) is the existence of suppressor cells, which limit ongoing immune responses and prevent ...
An emerging concept is that pro-inflammatory signals lead to loss of Regulatory T Cells (Treg) function. Pasare and Medzhitov ( ...
Treg cells or regulatory T cells constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dys ...
The induction of immune tolerance and specific immune suppression are essential processes in the control of immune responses. R ...
Allergen-specific immunotherapy is highly effective in the treatment of IgE-mediated allergy diseases such as rhinitis, conjunc ...
A variety of proinflammatory cells, mediators, and cytokines orchestrate the development of airway hyperresponsiveness, which results in the episodic airflow obstruction characteristic of asthma. As a consequence, modulation of the underlying disease process with antii-nflammatory agents is firmly established as being the cornerstone of successful management. Inhaled corticosteroids are the most potent antiinflammatory agents available and satisfactorily suppress underlying airway inflammation in most individuals. (more…)
The cysteinyl leukotrienes (LTC 4 , LTD 4 and LTE 4 ) are lipid mediators produced from an arachidonic acid precursor following ...
Antihistamines have been shown to be effective in seasonal allergic rhinitis and chronic idiopathic urticaria. They improve qua ...
In the UK, Europe and the USA, montelukast is licensed for once-daily oral administration in adults and is also available as a ...
Leukotrienes can be found in the airway and urine following both spontaneous exacerbations of asthma and acute exposure to bron ...
Despite optimum drug delivery and good compliance with inhaled corticosteroids, many patients experience symptoms and exacerbat ...