OBJECTIVE: : To investigate the effects of cysteinyl leukotrienes receptor (CysLTR) antagonists on global cerebral ischemia/reperfusion (CI/R) injury in gerbils, and to explore its mechanism. METHODS: : Totally 40 gerbils weighting 45-65 g were randomized into sham, saline, Pranlukast and HAMI 3379 groups with 10 animals in each. The CI/R model was established in gerbils by bilateral common carotid occlusion for 10 min followed by reperfusion. After ischemia, the CysLTR antagonists Pranlukast (0.1 mg/kg) and HAMI 3379 (0.1 mg/kg) were injected intraperitoneally for 5 consecutive days in the last two groups,while the former two groups were injected with saline only (10 mL/kg). After 24 h or 14 d reperfusion, neurological deficit score was evaluated and the behavioral dysfunction was assessed, respectively. And 14 d after reperfusion, the neuron morphology of cerebral cortex was observed in brain sections stained with Cresyl violet. In addition, the Iba-1 (microgila) and GFAP (astrocyte) positive cells in cerebral cortex were observed by using immunohistochemitry method. RESULTS: : CI/R models were successfully established in 21 out of 30 gerbils with 7 in saline group, 6 in Pranlukast group, and 8 in HAMI 3379 group. Compared with saline group, Pranlukast and HAMI 3379 significantly attenuated neurological deficits, improved the behavioral function 24 h after reperfusion(all <0.01); Pranlukast and HAMI 3379 also significantly improved the behavioral function 14 days after reperfusion(<0.05 or <0.01). Compared with saline group, the neurological symptom scores in Pranlukast and HAMI 3379 groups presented a trend of amelioration 14 d after reperfusion, but it was not significant(>0.05). In addition, Pranlukast and HAMI 3379 also inhibited the neuron loss and injury, suppressed microgila and astrocyte activation 14 d after reperfusion(all <0.01). CONCLUSIONS : CysLTR antagonists Pranlukast and HAMI 3379 have long-term neuroprotective effect on chronic brain injury induced by global cerebral ischemia/reperfusion in gerbils.
Animals ; Behavior, Animal ; drug effects ; Brain Injury, Chronic ; drug therapy ; Brain Ischemia ; Gerbillinae ; Leukotriene Antagonists ; pharmacology ; therapeutic use ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Random Allocation ; Receptors, Leukotriene ; metabolism ; Reperfusion Injury ; drug therapy

Noncardiac chest pain (NCCP) is one of the most common esophageal symptoms and lacks a clearly defined mechanism. The most common cause of NCCP is gastroesophageal reflux disease (GERD). One of the accepted mechanisms of NCCP in a patient without GERD has been altered visceral sensitivity. Mast cells may play a role in visceral hypersensitivity in irritable bowel syndrome. In this case, a patient with NCCP and dysphagia who was unresponsive to proton pump inhibitor treatment had an increased esophageal mast cell infiltration and responded to 14 days of antihistamine and antileukotriene treatment. We suggest that there may be a relationship between esophageal symptoms such as NCCP and esophageal mast cell infiltration.
Adult ; Chest Pain/*etiology ; Esophageal Diseases/*complications/drug therapy ; Esophagus/cytology/pathology ; Female ; Histamine Antagonists/therapeutic use ; Humans ; Leukotriene Antagonists/therapeutic use ; Mast Cells/metabolism ; Mastocytosis/*complications/drug therapy

OBJECTIVE: To systematically evaluate the efficacy and safety of leukotriene receptor antagonist (LTRA) combined intranasal corticosteroids in the treatment of allergic rhinitis (AR). METHOD: The randomized controlled trials (RCT) about the combined therapy of LTRA and nasal corticosteroids from January 1985 to May 2014 were searched in OVID, PubMed, EMBASE, CNKI, WanFang Data, and Cochrane Library. Two reviewers independently screened the literatures, extracted the data, and evaluated the methodological quality. Then meta-ana- lyses were conducted by using RevMan 5.1 software. RESULT: A total of 5 RCTs were included upon literature search. The results of meta-analyses showed that the efficacy of nasal corticosteroids plus LTRA was superior to nasal corticosteroids alone in total nasal symptom scores and individual nasal symptom scores (rhinorrhea, sneezing) [WMD = -4.49, 95% CI (-4.95(-)-4.03)-, P < 0.01; WMD = -0.43, 95% CI (-0.78(-)-0.07), P < 0.05; WMD = -0.10, 95% CI (-0.6(-)-0. 04), P < 0.01], with significant differences. However, compa- ring the subgroup treated with nasal corticosteroids combined LTRA against the subgroup treated with nasal corti- costeroids alone, we found no significant differences for RQLQ score and for individual nasal symptom scores (nasal blockage, nasal itching) [WMD = -15.19, 95% CI (-55.37(-)-25. 00), P > 0.05; WMD = 0.01, 95% CI(-) 0.06-0.08), P > 0. 05; WMD = -0.15,95% CI (-0.43(-)-0.13), P > 0.05]. CONCLUSION Based on limited evidence, we preliminary concluded the combined therapy of nasal corticosteroids and LTRA was more effective than nasal corticosteroids alone in the management of AR. Further large-scale, well-designed RCTs were still required to validate the add-on efficacy of LTRA for AR patients.
Administration, Intranasal ; Adrenal Cortex Hormones ; therapeutic use ; Drug Therapy, Combination ; Humans ; Leukotriene Antagonists ; therapeutic use ; Nose ; Randomized Controlled Trials as Topic ; Rhinitis, Allergic ; drug therapy

Allergic rhinitis (AR) clinically expressed by sneezing, rhinorrhea, nasal itching and congestion is an allergen-driven mucosal inflammatory disease which is modulated by immunoglobulin E. Epidemiological studies have indicated that prevalence of AR continues to increase, and it has been a worldwide health problem that places a significant healthcare burden on individuals and society. Given the evolving understanding of the process by which an allergen is recognized and the roles of mediators which account for AR progress, the pathogenesis of AR has become clearer. Current studies have demonstrated local allergic rhinitis (LAR) that patients with both sug- gestive symptoms of AR and a negative diagnostic test for atopy may have local allergic inflammation is a prevalent entity in patients evaluated with rhinitis, but further research remains needed. Management of AR includes aller- gen avoidance, pharmacological treatment and allergen-specific immunotherapy. Recently montelukast has exhibited previously undocumented anti-inflammatory properties, leukotriene receptor antagonists therefore may serve a more important role in the treatment of AR. Not only has immunotherapy proved its efficacy, but also been able to alter disease course and thereby mitigate progression to asthma. Thus immunotherapy can be initiated while receiving pharmacotherapy, especially in children with AR. As clinical guidelines, the ARIA (Allergic Rhinitis and its Impact on Asthma) provides basic principles of effective treatment of AR. Besides, choosing an appropriate treatment strategy should be based on the severity and chronicity of patient's symptom. The aim of this review was to provide an update mainly on the pathophysiology, epidemiology, and management of AR.
Acetates ; therapeutic use ; Allergens ; Anti-Inflammatory Agents ; therapeutic use ; Asthma ; prevention & control ; Child ; Humans ; Hypersensitivity, Immediate ; diagnosis ; physiopathology ; Immunoglobulin E ; immunology ; Immunotherapy ; Inflammation ; physiopathology ; Leukotriene Antagonists ; therapeutic use ; Prevalence ; Quinolines ; therapeutic use ; Rhinitis, Allergic ; diagnosis ; immunology ; physiopathology

OBJECTIVETo study the application value of asthma predictive index (API)-based group therapy in wheezing children under 5 years of age.

METHODSA total of 239 wheezing children under 5 years of age were divided into API-positive (n=126) and API-negative groups (n=113). Each group was randomly assigned to inhaled corticosteroids (ICS) subgroup and montelukast sodium (leukotriene receptor antagonist, LTRA) subgroup. The ICS and LTRA subgroups received the same drug therapy at the same dosage within the first four weeks of treatment. In the stable period of disease, the ICS subgroup only received aerosol inhalation of budesonide suspension, while the LTRA group was orally given montelukast sodium only. Asthma symptom scores were assessed and recorded at different time points.

RESULTSIn the first four weeks of treatment, ICS and LTRA were effective both in the API-positive and API-negative groups; the two groups showed significant improvements in asthma symptom scores, and the asthma symptom score showed no significant difference between the ICS and LTRA subgroups of each group. After 24 weeks of treatment, the two therapies were still effective; in the API-positive group, the LTRA subgroup had a better treatment outcome than the ICS subgroup, but there was no significant difference in treatment outcome between the LTRA and ICS subgroups of the API-negative group.

CONCLUSIONSFor wheezing children under 5 years of age, therapeutic strategies can be chosen based on API in the stable period of disease, so as to better control wheezing.

Administration, Inhalation ; Adrenal Cortex Hormones ; administration & dosage ; Asthma ; diagnosis ; drug therapy ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Leukotriene Antagonists ; therapeutic use ; Male ; Psychotherapy, Group ; Respiratory Sounds ; diagnosis ; drug effects

OBJECTIVE: To investigate the leukotriene D4 synthase gene A (LTD4S A)-444 C polymorphism in persistent allergic rhinitis (AR) of Chinese Han nationality and to evaluate its relevance to clinical responsiveness of leukotriene receptor antagonist. METHOD: There were 150 patients [87 males, 63 females, average age (38 +/- 14)] diagnosed with persistent AR in Allergy clinic in our hospital from March 2010 to March 2012; 146 healthy controls (78 males, 68 females, mean age (39 +/- 12)). We detected LT D4SA-444C polymorphism and allele frequencies with Polymerase Chain Reaction (PCR) and-Restriction Fragment Length polymorphism (RELP). The treatment group received monotherapy leukotriene receptor antagonist (montelukast) for 4 weeks. Urinary leukotriene D4 (LTD4) levels were detected by enzyme-linked immunosorbent assay (ELISA) before and after treatment, respectively. We evaluated anti-leukotriene treatment response according to the changement of symptoms, signs PTS and urinary LTD4. We tested correlation between LT D4S gene-444C allele frequency and the treatment response by multivariate analysis of variance. RESULT: (1) LTD4S gene-444 genotype AA/CC, AC/CC frequency is 70.7% (106/150) and 29.3% (44/150), allele A, C frequencies is 67.3% (101/150) and 32.7% (49/150) in AR group, and LTD4S gene-444 genotype AA/CC, AC/CC frequency is 76.7% (112/146) and 23.3% (34/ 146), allele A, C frequencies is 74.0% (108/146) and 26.0% (38/146) in healthy control group, there is not statistically significant difference between two groups. (2) Among 150 AR patients, compared to patients with AA/CC genotype, the genotype AC/CC patients are younger [average age (35 +/- 9), and (50 +/- 18) respectively, F = 5.891, P < 0.05], with earlier age of onset [(31 +/- 4), and (46 +/- 6) respectively, F = 6.985, P < 0.05], longer course of disease [(8.7 +/- 2.1), and (3.1 +/- 2.0) respectively, F = 11.43, P < 0.05], higher symptom scores (8.2 +/- 0.2; 4.8 +/- 0.3), higher signs score (7.3 +/- 3.3; 3.4 +/- 5.1), and the difference was statistically significant. (3) After 4 weeks of montelukast treatment in AR patients, treatment response of anti-leukotriene in genotype AC/ CC patients is better than those in AA/CC genotype patients (F = 11.01, P < 0.05), the differences of treatment response between two groups were correlated with LTD4 levels in vivo, clinical symptoms and signs of patients. CONCLUSION In a Chinese Han population the LTD4SA-444B polymorphism might be one of the factors in the clinical response to leukotriene receptor antagonists in persistent AR patients.
Adult ; Arachidonate 5-Lipoxygenase ; genetics ; Case-Control Studies ; Female ; Gene Frequency ; Humans ; Leukotriene Antagonists ; therapeutic use ; Male ; Middle Aged ; Polymorphism, Genetic ; Rhinitis, Allergic ; drug therapy ; genetics ; Young Adult

BACKGROUNDEvidence has demonstrated that the distal lung, which includes airways of < 2 mm in diameter and lung parenchyma, constitutes an important component of asthma pathology. Cysteinyl leukotrienes (CysLTs) are potent proinflammatory mediators and bronchoconstrictors involved in the asthmatic process. Guidelines recommend the leukotriene-modifying agents for asthma treatment. We hypothesized that a leukotriene receptor antagonist with an inhaled corticosteroid (ICS) and long-acting β2 agonist (LABA) combination would improve small airways function in moderate-to- severe asthmatics evaluated by physiological tests and high-resolution computed tomography (HRCT) analysis. This study was performed at a tertiary university hospital in Beijing.

METHODSThis was a randomized, double-blind, parallel study performed in 38 patients with moderate-to-severe asthma treated with salmeterol/futicasone (SFC) plus montelukast (SFC+M) or SFC plus placebo over 24 weeks. Small airway function was assessed by physiological studies and HRCT image analysis.

RESULTSMontelukast significantly improved air trapping as expressed by the residual volume (RV)/total lung capacity (TLC). Over 24 weeks of treatment, RV/TLC was improved by (15.41 ± 6.67)% in patients receiving SFC+M while RV/TLC was decreased by (8.57 ± 10.26)% in patients receiving SFC alone, the difference between the two groups was significant (P = 0.02). There was a trend towards a significant difference in forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) in the SFC+M group compared to that in the SFC group ((17.87 ± 8.17)% vs. (12.28 ± 9.20)%, P = 0.056). There was no significant change in percentage wall area (WA%) after 24 weeks of add-on treatment with montelukast. Patients receiving SFC+M showed significant improvement in the ratio of CT-determined values at full expiration to those at full inspiration (E/I ratio) (0.894 ± 0.005 vs. 0.871 ± 0.003, P = 0.002).

CONCLUSIONWe have shown, using lung function tests and HRCT image technique, that add-on therapy with montelukast improves distal lung function reflected by air trapping, but not airway wall thickness in moderate-to-severe asthma.

Acetates ; therapeutic use ; Adult ; Airway Remodeling ; drug effects ; Anti-Asthmatic Agents ; therapeutic use ; Asthma ; drug therapy ; physiopathology ; Double-Blind Method ; Female ; Forced Expiratory Volume ; drug effects ; Humans ; Leukotriene Antagonists ; therapeutic use ; Male ; Middle Aged ; Pilot Projects ; Quinolines ; therapeutic use ; Total Lung Capacity ; drug effects

Acetates ; administration & dosage ; therapeutic use ; Asthma ; drug therapy ; etiology ; metabolism ; Bronchiolitis, Viral ; drug therapy ; Cysteine ; metabolism ; Humans ; Infant ; Infant, Newborn ; Leukotriene Antagonists ; administration & dosage ; therapeutic use ; Leukotrienes ; biosynthesis ; Nasopharynx ; secretion ; Quinolines ; administration & dosage ; therapeutic use ; Respiratory Syncytial Virus Infections ; drug therapy ; metabolism ; virology ; Risk Factors

Adrenergic beta-2 Receptor Agonists ; administration & dosage ; pharmacokinetics ; therapeutic use ; Asthma ; drug therapy ; Bronchitis ; drug therapy ; Bronchodilator Agents ; administration & dosage ; therapeutic use ; Child ; Child, Preschool ; Delayed-Action Preparations ; Drug Synergism ; Drug Therapy, Combination ; Glucocorticoids ; administration & dosage ; therapeutic use ; Humans ; Infant ; Leukotriene Antagonists ; administration & dosage ; therapeutic use ; Respiratory Sounds ; drug effects ; Terbutaline ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; therapeutic use ; Transdermal Patch

OBJECTIVE: Study the practicability of non-surgical treatment for adenoidal hypertrophy. METHOD: Fifty-seven children were recruited in a randomized,placebo-controlled trial. Group T1 underwent intranasal corticosteroids treatment, group T2 underwent leukotriene receptor antagonists treatment, group C underwent placebo treatment:the records of 3 groups were analyzed. RESULT: After a 12-week treatment with intranasal corticosteroids or leukotriene receptor antagonists, group T1 and T2 patients demonstrated significant improvements in clinical symptoms and a more-pronounced reduction in adenoid size compared with control group patients, the difference was statistically significant. No statistically significant difference in group T1 and T2 patients. CONCLUSION Intranasal corticosteroids and leukotriene receptor antagonists may be considered useful in decreasing adenoid pad size and the severity of symptoms related to adenoidal hypertrophy. Children with adenoidal hypertrophy should be considered for non-surgical treatment before surgery is planned.
Adenoids ; pathology ; Administration, Intranasal ; Adrenal Cortex Hormones ; administration & dosage ; therapeutic use ; Child ; Child, Preschool ; Female ; Humans ; Hypertrophy ; drug therapy ; Leukotriene Antagonists ; administration & dosage ; therapeutic use ; Male