			Home About us Contact

Leukotriene Receptor Antagonists (leukotriene + receptor_antagonist)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Leukotriene pathway genetics and pharmacogenetics in allergy

ALLERGY, Issue 6 2009
N. P. Duroudier
Leukotrienes (LT) are biologically active lipid mediators known to be involved in allergic inflammation. Leukotrienes have been shown to mediate diverse features of allergic conditions including inflammatory cell chemotaxis/activation and smooth muscle contraction. Cysteinyl leukotrienes (LTC4, LTD4 and, LTE4) and the dihydroxy leukotriene LTB4 are generated by a series of enzymes/proteins constituting the LT synthetic pathway or 5-lipoxygenase (5-LO) pathway. Their function is mediated by interacting with multiple receptors. Leukotriene receptor antagonists (LTRA) and LT synthesis inhibitors (LTSI) have shown clinical efficacy in asthma and more recently in allergic rhinitis. Despite growing knowledge of leukotriene biology, the molecular regulation of these inflammatory mediators remains to be fully understood. Genes encoding enzymes of the 5-LO pathway (i.e. ALOX5, LTC4S and LTA4H) and encoding for LT receptors (CYSLTR1/2 and LTB4R1/2) provide excellent candidates for disease susceptibility and severity; however, their role remains unclear. Preliminary data also suggest that 5-LO pathway/receptor gene polymorphism can predict patient responses to LTSI and LTRA; however, the exact mechanisms require elucidation. The aim of this review was to summarize the recent advances in the knowledge of these important mediators, focusing on genetic and pharmacogenetic aspects in the context of allergic phenotypes. [source]

Inflammation and remodeling in the adult and child with asthma

PEDIATRIC PULMONOLOGY, Issue S21 2001
Peter Jeffery MSc
Abstract Inflammation and remodeling are characteristic features of the conducting airways in asthma, but the relationships between inflammation, inappropriate remodeling, bronchial hyperresponsiveness, and reduced pulmonary function are still unclear. In both adults and children with asthma, there are structural changes of the conducting airways that include injury and loss of the surface epithelium, thickening of the reticular basement membrane, increases of underlying collagen, blood vessels, and airway smooth muscle, and plugging of the airways by exudate. Bronchial biopsies obtained from persons with mild stable asthma already demonstrate the presence of inflammation. Many of the inflammatory and structural changes begin early in childhood. Whereas corticosteroids markedly reduce many aspects of inflammation, it is not known whether and how they affect the changes associated with airway wall remodeling. Leukotriene receptor antagonists appear to be antiinflammatory and able to reduce the proliferation of bronchial smooth muscle. Pediatr Pulmonol. 2001; Supplement 21:3,16. © 2001 Wiley-Liss, Inc. [source]

Comparison of glucocorticoid and cysteinyl leukotriene receptor antagonist treatments in an experimental model of chronic airway inflammation in guinea-pigs

CLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2004
E. A. Leick-maldonado
Abstract Background Leukotriene receptor antagonists have been demonstrated in several studies to possess bronchodilating and anti-inflammatory properties in asthma. However, there are few experimental studies performed to compare the effects of anti-leukotrienes and glucocorticoids, most used anti-inflammatory agents in asthma. In the present study, we evaluated the effects of treatment with dexamethasone or montelukast on eosinophil and mononuclear cell recruitment in an experimental model of allergen-induced chronic airway inflammation in guinea-pigs (GP). Methods GP were submitted to increasing concentrations of aerosols of ovalbumin (OVA) twice a week for 4 weeks. After 2 weeks, animals were treated daily with dexamethasone, montelukast or saline solution. After this period, GP were anaesthetized, tracheostomized, mechanically ventilated and challenged with OVA aerosol. Results Maximal changes of respiratory system resistance and elastance induced by OVA challenge were attenuated by dexamethasone (P<0.001), but not by montelukast treatment. Neither dexamethasone nor montelukast significantly influenced bronchial oedema formation. Dexamethasone but not montelukast induced a decrease in mononuclear cells in airways (P<0.001). Eosinophil infiltration in the bronchial wall was reduced by both dexamethasone and montelukast (P<0.005). Only dexamethasone treatment reduced the levels of exhaled nitric oxide (P<0.025). Conclusion Although leukotriene receptor antagonist treatment reduces eosinophil accumulation induced by multiple antigen challenges, glucocorticoid treatment attenuates both eosinophil and mononuclear cell infiltration. [source]

Leukotriene receptor antagonists for the treatment of allergic rhinitis

CLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2002
C. Sander
No abstract is available for this article. [source]

Exploring the role of leukotriene receptor antagonists in the management of allergic rhinitis and comorbid asthma

CLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 2 2003
R. Pawankar
Summary The links between asthma and rhinitis are well documented and are based upon epidemiological, immunological and clinical observations. Leukotriene receptor antagonists (e.g. montelukast) are an established, effective and well tolerated treatment option for asthma, and more recent evidence now demonstrates their clinical utility in the treatment of allergic rhinitis. In seasonal allergic rhinitis, montelukast monotherapy has been shown to provide relief from daytime nasal symptoms (including congestion, runny nose, nasal itching and sneezing), as well as nighttime and eye symptoms. These clinical benefits were associated with reduced eosinophil counts in the blood, suggesting an effect on the underlying mechanisms of allergic inflammation. In addition, studies that have evaluated the combination of an antileukotriene with an antihistamine have typically shown a numerical and sometimes statistical benefit of combination therapy. Given the frequent coexistence and shared pathophysiologies of asthma and allergic rhinitis, a common therapeutic approach would seem warranted. Leukotriene receptor antagonists, such as montelukast, are emerging as a rational approach to ,one airway' disease management. [source]

Leukotriene receptor antagonists and rhinitis: uncharted territory

CLINICAL OTOLARYNGOLOGY, Issue 1 2007
I. Srouji
No abstract is available for this article. [source]

TBXA2R gene polymorphism and responsiveness to leukotriene receptor antagonist in children with asthma

CLINICAL & EXPERIMENTAL ALLERGY, Issue 2 2008
J-H. Kim
No abstract is available for this article. [source]

Effect of montelukast pretreatment on inducible nitric oxide synthase mRNA expression in the lungs of antigen-challenged allergic mice

CLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2003
K. Sade
Summary Background Growing evidence suggests that inducible nitric oxide synthase (iNOS) is the main source of the high output of exhaled nitric oxide (NO) in asthma. Treatment of asthmatic patients with glucocorticoids reduces high levels of exhaled NO mainly by inhibiting the transcription of iNOS. A similar reduction in exhaled NO was recently observed in patients treated with the leukotriene receptor antagonists, but the exact interaction between these drugs and iNOS remains obscure. Objective The purpose of this study was to evaluate the effect of a leukotriene receptor antagonist, montelukast, on the expression and activity of iNOS in a murine model of allergic asthma. Methods Twenty-four BALB/c mice were sensitized to OVA and were equally divided into 3 groups (Groups 1,3). Eight additional mice were sham sensitized and served as a negative control group (Group 4). Group 1 received montelukast 1 mg/kg/day in their drinking water, Group 2 received dexamethasone 1 mg/kg/day in their drinking water and Groups 3 and 4 received plain tap water. After 1 week, the animals were challenged by inhalation of OVA and, 3 h later, they were killed and their lung cells were isolated by enzymatic tissue digestion. NO generation was measured by a Griess assay, and iNOS mRNA was studied by RT-PCR. Results A significant increase in iNOS mRNA expression and in NO generation was evident after allergen challenge compared with the controls. Pretreatment with montelukast mildly decreased NO production without producing a concomitant significant decrease in iNOS mRNA expression. Conclusion: Unlike pretreatment with glucocorticoids, we failed to find compelling evidence for a major role for montelukast treatment in the modulation of iNOS mRNA in a murine model of acute asthma. [source]

Caring for patients with allergic rhinitis

JOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 6 2007
AE-C Nurse Practitioner, APRN-C, Certified Asthma Educator, Clinical Assistant Professor2), Mary Lou Hayden MS
Abstract Purpose: Allergic rhinitis (AR) affects up to 40 million Americans, with an estimated cost of $2.7 billion per annum. This review discusses several therapeutic options that reduce the symptoms of AR, including allergen avoidance, antihistamines, intranasal corticosteroids (INS), leukotriene receptor antagonists, and immunotherapy. Data sources: The articles included in this review were retrieved by a search of Medline literature on the subjects of AR, antihistamines, INS, leukotriene antagonists, and immunotherapy, as well as current published guidelines for the treatment of AR. Conclusions: Allergen avoidance is recommended for all patients prior to pharmacologic therapy. Oral and nasal H1 -antihistamines are recommended to alleviate the mild and intermittent symptoms of AR, and INS are recommended as the first-line treatment choice for mild persistent and more moderate-to-severe persistent AR. Implications for practice: There are a number of different types of therapy for the management of AR; with so many options available, successful tailoring of treatment to suit individual requirements is realistically achievable. [source]

Recent developments of ocular allergy in children

ACTA OPHTHALMOLOGICA, Issue 2009
F CHIAMBARETTA
First we summarize the clinical presentations associated with the classification of ocular allergy, and present the last agreement for treatment. Vernal keratoconjunctivitis is the more severe form affecting children and iatrogenic complications must be avoided. In vernal keratoconjunctivitis, a new grading system is introduced based on clinical signs and symptoms of ocular surface inflammation. Based on this new grading of vernal keratoconjunctivitis, different treatment options are proposed, essentially steroid sparing. Based on new information about the pathogenesis of vernal keratoconjunctivitis, recent and more selective drugs like anti-chemokine receptor antibodies and leukotriene receptor antagonists and cyclosporine are evaluated. [source]

Vernal keratoconjunctivitis: a major review

ACTA OPHTHALMOLOGICA, Issue 2 2009
Sunil Kumar
Abstract. Vernal keratoconjunctivitis (VKC) is a chronic, bilateral, at times asymmetrical, seasonally exacerbated, allergic inflammation of the ocular surface, involving tarsal and/or bulbar conjunctiva. Though the allergic nature of this entity has been accepted for a long time, the accumulation of a large amount of immunological data has proved that the pathogenesis of VKC is much more complex than a mere type 1 hypersensitivity reaction. In the past several years, many clinical and experimental studies about the cells and mediators involved in initiating and perpetuating the ocular allergic inflammation have shown that T helper type 2 cells and their cytokines, corneal fibroblasts and epithelium along with various growth factors play an important role in the pathogenesis of VKC. Based on this information about the pathogenesis of VKC newer, more selective drugs like anti-chemokine receptor antibodies and leukotriene receptor antagonists are under evaluation. Cyclosporine has been shown to be effective in the treatment of VKC but further randomized control trials are required to establish the minimum effective concentration. [source]

Anti-inflammatory treatment of asthma: differentiation and trial-and-error

ACTA PAEDIATRICA, Issue 8 2009
Ole D Wolthers
Abstract The relative lack of evidence for anti-inflammatory treatment of some phenotypes of asthma in children has been highlighted in recent guidelines and consensus reports specifically aiming at the paediatric population. Consequently, we are left with a need for defining treatment strategies in the clinical setting. The decision to initiate antiinflammatory treatment should be based on assessments of the individual child's age, the type of asthma, severity, heredity and atopic condition, adherence factors and sensitivity to systemic adverse effects of treatment options. Inhaled corticosteroids are potent anti-inflammatory agents that are effective in the whole spectrum of asthma in school age children. In toddlers with viral wheeze and in children with mild asthma oral leukotriene receptor antagonists or inhaled corticosteroids may be given on a trial-and-error basis. Conclusion:, To treat all children with asthma equally effectively from infancy through adolescence does not mean that they should be treated identically and in some types of asthma a trial-and-error approach may be warranted. [source]

Effects of various anti-asthmatic agents on mite allergen-pulsed murine bone marrow-derived dendritic cells

CLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2005
I. Machida
Summary Background Dendritic cells (DCs) play an important role in the immune response and are critically involved in asthma. ,2 -agonists could potentially exacerbate type 2 T helper (Th2) cell-mediated immune response. Objectives To determine the effects of various anti-asthmatic agents on DCs function both in vitro and in vivo. Methods Murine bone marrow-derived DCs were pulsed with mite allergen in the presence of pranlukast, salbutamol, salmeterol or fluticasone. These DCs were then inoculated intranasally into naïve mice to induce allergic airway inflammation in vivo. Results Pranlukast reduced IL-10 and increased IL-12, while fluticasone reduced both IL-10 and IL-12 production by mite allergen-pulsed DCs. Allergic airway inflammation in pranlukast- and fluticasone-treated and mite allergen pulsed DCs-harbouring mice was attenuated and such response was associated with inhibition of Th2 response in the airway. Salbutamol did not alter cytokine production, while salmeterol reduced IL-12 production by mite allergen-pulsed DCs. Lung pathology in ,2 -agonist-harbouring mice was comparable with those of mite allergen-pulsed DCs-harbouring mice. Conclusions Our results indicate that leukotriene receptor antagonists and corticosteroids inhibit DCs-induced Th2 skewed immune response, and that short- and long-acting ,2 -agonists do not modify DCs-induced allergic airway inflammation. [source]

Effect of montelukast pretreatment on inducible nitric oxide synthase mRNA expression in the lungs of antigen-challenged allergic mice

Cysteinyl leukotrienes as common mediators of asthma and allergic disease

CLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 2 2003
S-E. Dahlén
Summary The cysteinyl leukotrienes (CysLTs) induce a number of pro-inflammatory effects including smooth muscle contraction, an increase in blood flow, plasma exudation, mucous secretion, and activation of inflammatory cells. They play a key role in asthma and allergy, and can be recovered from different body fluids (e.g. bronchoaleveolar or nasal lavage and urine) during allergen-induced hypersensitivity reactions. The advent of antileukotriene agents (i.e. leukotriene receptor antagonists or leukotriene synthesis inhibitors) has helped clarify how the different mechanisms contribute to inflammation, as well as offer new treatment options for both asthma and allergy. It is now clear that the release of leukotrienes is the final common path for the many different factors causing airway obstruction and inflammation. In asthma, clinical studies have shown that treatment with antileukotrienes can improve pulmonary function, alleviate symptoms, reduce asthma exacerbations, and decrease the need for bronchodilator therapy. Similarly, in patients with allergic rhinitis, improvements have been seen in nasal symptoms, eye symptoms and quality of life. Antileukotrienes provide a new opportunity for simultaneous management of allergic diseases of the upper and lower respiratory tract, and are a rational treatment approach to the concept of ,one airway' disease. In future, their utility may also extend to inflammatory disorders of other organ systems (e.g. skin). [source]

Exploring the role of leukotriene receptor antagonists in the management of allergic rhinitis and comorbid asthma

Is there a role for antileukotrienes in urticaria?

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 3 2006
G. Di Lorenzo
Summary In vitro and in vivo clinical and experimental data have suggested that leukotrienes play a key role in inflammatory reactions of the skin. Antileukotriene drugs, i.e. leukotriene receptor antagonists and synthesis inhibitors, are a new class of anti-inflammatory drugs that have shown clinical efficacy in the management of asthma. We searched the MedLine database and carried out a manual search on journals specializing in allergy and dermatology for the use of antileukotriene drugs in urticaria. Montelukast might be effective in chronic urticaria associated with aspirin or food additive hypersensitivity or with autoreactivity to intradermal serum injection when taken with an antihistamine but not in moderate chronic idiopathic urticaria. Evidence for the effectiveness of zafirlukast and the 5-lipoxygenase inhibitor, zileuton, in chronic urticaria is mainly anecdotal. In addition, there is anecdotal evidence of effectiveness of antileukotrienes in primary cold urticaria, delayed pressure urticaria and dermographism. No evidence exists for other physical urticarias, including cholinergic, solar and aquagenic urticarias, vibratory angio-oedema, and exercise-induced anaphylaxis. [source]