montelukast and Bronchial-Spasm

To examine the role of leukotriene-receptor antagonists (LTRAs) in management of asthma.. Most data were derived from randomized, double-blind, controlled trials.. Leukotrienes appear to have an important role in the pathophysiology of asthma, including airway inflammation. Leukotriene-receptor antagonists are effective in improving asthma control end points, such as allergen, ASA, and exercise challenge, in clinical models of asthma. In chronic asthma, LTRA administration reduces asthma symptoms and rescue beta 2-agonist use, changes that are paralleled by improvements in lung function. Both zafirlukast and montelukast decrease circulating levels of eosinophils and could have other useful anti-inflammatory properties. Administration of LTRAs allows doses of inhaled corticosteroids to be reduced. Currently available LTRAs are free of serious side effects and are available as oral formulations.. Leukotriene-receptor antagonists belong to a new class of asthma medication. While inhaled corticosteroids remain first-line therapy for managing chronic asthma, LTRAs should be considered for patients with ASA-sensitive asthma; as adjunct therapy when low to moderate doses of inhaled steroid alone provide incomplete control; or as adjunct therapy to allow reduction in doses of inhaled corticosteroids.

Topics: Acetates; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Bronchial Spasm; Chronic Disease; Cyclopropanes; Double-Blind Method; Humans; Indoles; Leukotriene Antagonists; Phenylcarbamates; Quinolines; Randomized Controlled Trials as Topic; Respiratory Therapy; Sulfides; Sulfonamides; Time Factors; Tosyl Compounds

Topics: Acetates; Anti-Asthmatic Agents; Asthma; Bradykinin; Bronchial Provocation Tests; Bronchial Spasm; Cyclopropanes; Forced Expiratory Volume; Humans; Quinolines; Sulfides

The angiotensinogen (AGT) gene enhances the effect of several bronchoconstrictors and produces a peptide that is accumulated in the airways of asthma patients; events that may underpin the pathogenesis of aspirin-intolerant asthma (AIA). To carry out a case-control analysis between AGT and aspirin-induced bronchospasm following treatment with an anti-asthma drug, montelukast (MLK), 38 single nucleotide polymorphisms (SNPs) in AGT were genotyped in 56 AIA cohort. Genotyping was performed with TaqMan assay and haplotypes were inferred using PHASE algorithm ver. 2.0. Statistical analyses of each SNPs and haplotypes were performed using SAS version 9.1. Among 13 variants displaying significant signals, two SNPs (+2401C>G and +2476C>T) in the intronic region of AGT were significantly associated with modification of drug response even after correction for multiple testing (P=0.0009-0.002; P(corr)=0.02-0.03). Furthermore, the two variants also exhibited associations with MLK response rate (P=0.0003-0.0006; P(corr)=0.006-0.01). Although our results are preliminary and further replication in a larger-scale group of subjects should be warranted, these observations provide evidence that AGT variants might be one of genetic factors involved in the response of anti-asthma drugs in AIA patients.

Topics: Acetates; Adolescent; Adult; Aged; Algorithms; Angiotensinogen; Anti-Asthmatic Agents; Asian People; Aspirin; Asthma, Aspirin-Induced; Bronchial Spasm; Case-Control Studies; Cyclopropanes; Drug Hypersensitivity; Female; Genetic Predisposition to Disease; Genetic Variation; Genotype; Haplotypes; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Quinolines; Republic of Korea; Sulfides; Young Adult

1. To determine which mediators are involved in antigen-induced bronchospasm and microvascular leakage in the airways of ovalbumin sensitised Brown Norway rats we investigated the effect of a histamine H(1) receptor antagonist, mepyramine, a 5-HT receptor antagonist, methysergide, and a cys-leukotriene-1 receptor antagonist, montelukast. 2. Ovalbumin at 1 mg kg(-1) i.v. caused a significant increase in microvascular leakage in the airways and at 3 mg kg(-1) i.v. caused a significant increase in airways resistance. 3. Histamine (1 mg kg(-1) i.v.), 5-HT (0.1 mg kg(-1) i.v.) and leukotriene D(4) (LTD(4), 50 microg kg(-1) i.v.) caused a significant increase in microvascular leakage in the airways. 4. Mepyramine (1 mg kg(-1) i.v.), methysergide (0.1 mg kg(-1) i.v.), or montelukast (30 mg kg(-1) i.v.) inhibited histamine, 5-HT or LTD(4) -induced microvascular leakage respectively. 5. Methysergide (0.1 mg kg(-1) i.v.) reduced ovalbumin-induced microvascular leakage in the trachea and at 0.3 mg kg(-1) i.v. inhibited bronchospasm (38 and 58%, respectively). Montelukast (30 mg kg(-1) p.o.) reduced ovalbumin-induced microvascular leakage in airway tissue to basal levels (78%) and inhibited ovalbumin-induced bronchospasm (50%). Mepyramine (3 mg kg(-1) i.v.) had no effect on ovalbumin-induced leakage or bronchospasm. 6. A combination of all three compounds (mepyramine, methysergide and montelukast) reduced ovalbumin-induced microvascular leakage in airway tissue to basal levels (70 - 78%) and almost completely inhibited bronchospasm (92%). 7. Antigen-induced bronchospasm appears to equally involve the activation of 5-HT and cys-leukotriene-1 receptors whereas ovalbumin-induced microvascular leakage appears to be predominantly mediated by cys-leukotriene-1 receptors.

Topics: Acetates; Animals; Anti-Asthmatic Agents; Bronchi; Bronchial Spasm; Capillary Permeability; Cyclopropanes; Histamine; Histamine H1 Antagonists; Leukotriene D4; Male; Methysergide; Ovalbumin; Pyrilamine; Quinolines; Rats; Rats, Inbred BN; Respiratory Hypersensitivity; Serotonin; Serotonin Antagonists; Sulfides; Trachea

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adult; Albuterol; Asthma; Bronchial Spasm; Child; Cromolyn Sodium; Cyclopropanes; Exercise; Female; Growth Disorders; Humans; Hydroxyurea; Indoles; Ipratropium; Lactation; Leukotriene Antagonists; Nebulizers and Vaporizers; Nedocromil; Phenylcarbamates; Pregnancy; Pregnancy Complications; Quinolines; Salmeterol Xinafoate; Sulfides; Sulfonamides; Theophylline; Tosyl Compounds

Leukotrienes have been implicated as major mediators of ASA-induced respiratory reactions. In several prior studies, pretreatment of ASA-sensitive respiratory disease (ASRD) patients with leukotriene modifiers have sometimes allowed subjects to tolerate previously established provoking doses of oral ASA or inhalation ASA-lysine, without respiratory reactions.. The purpose of this study was to examine whether ASA-provoked respiratory reactions would be blocked or attenuated by pretreatment with a cystLT1 receptor antagonist, montelukast, particularly if ASA doses were increased above their threshold doses.. Baseline ASA oral challenges were performed. Eight to 12 days later, following pretreatment with montelukast 10 mg daily, threshold and then escalating doses of ASA were used during repeat oral ASA challenges. The differences in responses between baseline and montelukast protected ASA oral challenges were then compared.. Nine of 10 patients, despite pretreatment with montelukast, experienced at least naso-ocular reactions during their second oral ASA challenges. In four of nine patients, asthmatic reactions also occurred. In comparing baseline and montelukast protected ASA challenges, there were no statistically significant differences in their responses.. Pretreatment with montelukast allowed only one patient to proceed through all challenge doses of ASA without any reactions. The remaining nine patients enjoyed only partial protection from respiratory reactions. Montelukast pretreatment was generally not effective in altering upper airway reactions and only partly effective in altering lower airway reactions.

Topics: Acetates; Adult; Aged; Aspirin; Asthma; Bronchial Spasm; Cyclopropanes; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Quinolines; Sulfides

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Asthma; Bone Density; Bronchial Spasm; Bronchodilator Agents; Child; Child, Preschool; Choice Behavior; Cromolyn Sodium; Cyclopropanes; Exercise; Female; Growth; Humans; Hydroxyurea; Indoles; Infant, Newborn; Ipratropium; Lactation; Leukotriene Antagonists; Phenylcarbamates; Pregnancy; Pregnancy Complications; Quinolines; Salmeterol Xinafoate; Sulfides; Sulfonamides; Tachycardia; Theophylline; Tosyl Compounds