Toll-like receptors (TLRs) act as receptors for numerous stimuli of immune cells, including bacterial cell wall constituents (lipopolysaccharide [LPS] from Gram-negative bacteria and lipopeptides from Gram-positive species), plasma proteins and extracellular matrix breakdown products. TLR2 and TLR4 bind lipopeptide and LPS respectively, mediating responses of alveolar macrophages and other immune cells to bacterial infection in the lungs. Exposure of lungs to LPS leads to pro-inflammatory responses of a number of cell types, including airway smooth muscle, which secretes a number of cytokines involved in leucocyte recruitment and the Th2 polarization of immune responses. Human airway smooth muscle cells were cultured with LPS in the absence and presence of peripheral blood mononuclear cells to determine direct and leucocyte-dependent TLR-mediated responses. (more…)
One especially favored target for immune recognition is bacterial lipopolysaccharide (LPS). This macromolecule is found only in ...
Airway hyper-responsiveness in asthma may involve smooth muscle growth, a manifestation of airway remodelling. The involvement ...
Innate immunity depends on both resident and recruited leukocytes. The macrophage without doubt plays an import- ant role in the de ...
Acetylcholine is a neurotransmitter of the nerve vagus, the functional effects mediated by binding to muscarinic receptors. Results ...
Eosinophil infiltration of the mucosa is a feature of asthmatic airways. Their adhesion to bronchial epithelial cells has been ...
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 ...
Negative family characteristics such as family conflict and family dysfunction discriminated children who died of asthma from children with equally severe asthma who did not die. Parenting difficulties have been associated with a higher risk for the development of asthma early in life. In addition, children with the highest risk of developing early-onset asthma were those in families with both parenting problems and high stress. Evidence for a asthma and stress link has been demonstrated through temporal studies, as experiencing an acute negative life event increased children’s risk for an asthma attack 4 to 6 weeks after the occurrence of the event. (more…)
Learning to relax is important not only to release tension or stress but can ease your sinus and help you to copy with it. True rel ...
The two strongest risk factors for asthma in childhood are a family history and immediate hypersensitivity to common allergens. ...
Asthma is a frightening condition. I have lived with asthma symptoms for 17 years and the thought of an allergy induced asthma atta ...
Acupuncture for acne, psoriasis, allergies and related conditions is the current interest of several study groups, to investigate a ...
The genetic basis of asthma heritability has been extensively studied and the studies are yielding some understanding. There is ...
The cysteinyl leukotrienes (LTC 4 , LTD 4 and LTE 4 ) are lipid mediators produced from an arachidonic acid precursor following a series of enzymatic steps. Arachidonic acid is firstly released from the phospholipid bilayer by phospholipase A 2 and may be metabolized by either the cyclooxygenase (COX) or 5-lipoxygenase pathway. Once the unstable precursor LTA 4 has been produced, it may be converted in neutrophils or monocytes to the noncysteinyl LTB 4 by LTA 4 hydrolase. In mast cells, eosinophils, macrophages, and basophils, LTA 4 may alternatively be converted into LTC 4 by LTC 4 synthase and subsequently into LTD 4 and LTE 4. (more…)
The prevalence of aspirin-sensitive asthma is uncertain although it may exist in up to 20% of all asthmatics patients. The char ...
Some features seem to be common to severe asthma and Chronic Obstructive Pulmonary Disease with reversibility of airflow limita ...
A variety of proinflammatory cells, mediators, and cytokines orchestrate the development of airway hyperresponsiveness, which r ...
Leukotrienes are present in increased amounts in exhaled breath condensate (EBC) in patients with asthma. So far, no data have ...
Two main strategies have been developed to block the effects of cysteinyl leukotrienes in the airway. One method is to use drug ...
The response to injury usually begins with dilatation of small blood vessels in and around the injured site (figure bellow). This response (called vasodilatation) results from relaxation of smooth muscle in the vascular walls. It can begin within seconds after an acute injury or develop over hours or days of low-grade irritation or infection. Vasodilatation initially results in increased blood flow through arterioles, capillaries, and venules of the affected region, leading to redness (erythema) and warmth. As the vessels dilate, endothelial cells lining some of the vessels actively retract away from one another to create temporary, microscopic gaps in the endothelial lining. Endothelial retraction occurs only in the smallest venules (often called postcapillary venules), which are thin-walled vessels with lumenal diameters of 20 - 60 µm. (more…)
Some of the immediate sequelae of injury are uncomfortably familiar: Soon after an injury occurs, the affected site and its sur ...
Acute inflammatory response constitute the first line of defense against infection pathogenesis and how immune system works as ...
Once it is tethered onto the venule wall, the neutrophil or other leukocyte comes into contact with a wide variety of inflammatory ...
Neutrophils make up an army of more-or-less identical circulating phagocytes that are poised to respond quickly and in vast numbers ...
The airway circulation has many potential roles in asthma. The vasculature has a major influence on upper airway patency in nasal i ...
Some of the immediate sequelae of injury are uncomfortably familiar: Soon after an injury occurs, the affected site and its surrounding tissues become reddened, warm, swollen, and painful. These four signs which are probably the most useful and ubiquitous diagnostic clues in all of clinical medicine are hallmarks of acute inflammation, the body’s initial physiologic reaction to tissue distress. In its simplest form, inflammation is a response carried out by blood vessels and by the endothelial cells that line them. (more…)
The response to injury usually begins with dilatation of small blood vessels in and around the injured site (figure bellow). Th ...
Once it is tethered onto the venule wall, the neutrophil or other leukocyte comes into contact with a wide variety of inflammatory ...
Acute inflammatory response constitute the first line of defense against infection pathogenesis and how immune system works as ...
Nearly all tissues, organs, and serosal cavities harbor a population of resident phagocytes. Most contain only a diffuse scattering ...
Innate immune responses are seen in a very broad range of tissues. Indeed, the Toll-like receptors (TLRs, one of the most important ...
Some features seem to be common to severe asthma and Chronic Obstructive Pulmonary Disease with reversibility of airflow limitation. The neutrophil chemoattractant leukotriene B 4 (LTB 4) may play a role in Chronic Obstructive Pulmonary Disease and in some forms of asthma. In this study, 55 smokers with no disease, Chronic Obstructive Pulmonary Disease (with or without bronchodilator reversibility of airflow limitation) or asthma underwent measurement of LTB 4 in sputum supernatants and exhaled breath condensate asthma (EBC). Both Chronic Obstructive Pulmonary Disease and asthma patients had higher levels of LTB 4 than control subjects; patients with asthma or reversible Chronic Obstructive Pulmonary Disease exhibited significantly higher levels of LTB 4 than those with irreversible Chronic Obstructive Pulmonary Disease. (more…)
Leukotrienes are present in increased amounts in exhaled breath condensate (EBC) in patients with asthma. So far, no data have ...
The cysteinyl leukotrienes (LTC 4 , LTD 4 and LTE 4 ) are lipid mediators produced from an arachidonic acid precursor following ...
A role for Leukotriene B4 in the induction of airway hyper-responsiveness was explored through the use of transgenic mice defic ...
Adjusting the inhaled glucocorticoid dose based on indices of airway inflammation has been proposed as a means of achieving more ef ...
With the help of well-trained and experienced pulmonary function technicians, children as young as 4 to 5 years of age should b ...
Roflumilast is an oral, once-daily inhibitor of phosphodiesterase type 4 (PDE4) that prevents the breakdown of cyclic adenosine monophosphate (cAMP) levels, leading to inhibition of pro-inflammatory signalling. This study investigated the effects of repeated doses of 250 or 500 µg of roflumilast on airway asthma responses to allergen. (more…)
Roflumilast is an oral, once-daily PDE4 inhibitor with antiinflammatory activity in development for the treatment of asthma. Ro ...
Marimastat is a synthetic broad-spectrum matrix metalloproteinase (MMP) inhibitor. This study assessed the anti-inflammatory effect ...
Treating allergic rhinitis may have a downstream effect on concomitant asthma and this may be due to attenuation of the underlying ...
Tumour Necrosis Factor is a pro-inflammatory cytokine implicated in the pathogenesis of asthmatic airway inflammation, hyper-react ...
Despite optimum drug delivery and good compliance with inhaled corticosteroids, many patients experience symptoms and exacerbat ...