montelukast and Hypertrophy

Background/aim: The incidence of adenoid hypertrophy is 2%-3% in children. Adenoidectomy is a commonly performed procedure in children that may cause complications such as early or late bleeding (4%-5%), recurrence of adenoid tissue (10%-20%), and postoperative respiratory problems (27%). Therefore, medical therapy alternatives to adenoidectomy are important and must be tried before surgery. In this study, we investigated the efficacy of mometasone furoate, montelukast, and a combination of these drugs in pediatric patients with adenoid hypertrophy who were scheduled for reduction with medical therapy after not being recommended for surgery.Materials and methods: The study included 120 children with adenoid hypertrophy aged between 4 and 10 years. The patients were randomized into 4 separate groups, with 30 in each group. Group 1 received 100 μg of mometasone furoate per day, group 2 received 4/5 mg (for age) montelukast per day, and group 3 received mometasone furoate + montelukast. Medical therapy continued for 3 months in the treatment groups. Group 4, which comprised patients with mild symptoms, received no treatment and was the control group. The pre- and posttreatment adenoid tissue ratios in lateral neck radiographs were recorded in the four groups. Results: When radiologic measurements of adenoid-to-air passage were calculated, an improvement of 21.76% was observed in group 1 after treatment. The rate of improvement was 22.51% in group 2. There was a 21.79% reduction in adenoid size in group 3 after 3 months? treatment and 12.46% in the control group. There were statistically significant differences between pre- and posttreatment values in every single group administered corticosteroids, montelukast, and combined therapy (P < 0.05).Conclusion: According to our results, both montelukast and mometasone furoate therapies were similarly successful in treating adenoid hypertrophy. Combined therapy has no superiority over single-therapy treatment.

Topics: Acetates; Adenoids; Administration, Intranasal; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Child; Child, Preschool; Cyclopropanes; Drug Therapy, Combination; Female; Humans; Hypertrophy; Male; Mometasone Furoate; Nasal Obstruction; Prospective Studies; Quinolines; Recurrence; Sulfides; Treatment Outcome

Inflammatory mediators and drugs which affect inflammation can influence the healing of injured tissues. Leukotrienes are potent inflammatory mediators, and similar to prostaglandins, are metabolites of arachidonic acid which can have positive or negative effects on bone and cartilage tissues. Here we tested the hypothesis that blocking the negative regulation of leukotrienes, would lead to enhanced endochondral bone formation during fracture repair. A closed femoral fracture was created in mice. Animals were divided into three groups for treatment with either montelukast sodium, a cysteinyl leukotriene type 1 receptor antagonist (trade name Singulair), zileuton, a 5-lipoxygenase enzyme inhibitor (trade name Zyflo), or carrier alone. The fractures were analyzed using radiographs, quantitative gene expression, histology and histomorphometry, and immunohistochemistry. Both the montelukast sodium group and the zileuton group exhibited enhanced fracture repair when compared with controls. Both treatment groups exhibited increased callous size and earlier bone formation when compared to controls as early as day 7. Gene expression analysis of treatment groups showed increased markers of chondrocyte proliferation and differentiation, and increased early bone formation markers when compared with controls. Treatment with montelukast sodium directly targeted the cysteinyl leukotriene type 1 receptor, leading to increased chondrocyte proliferation at early time points. These novel findings suggests a potential mechanism by which the cysteinyl leukotriene type 1 receptor acts as a negative regulator of chondrocyte proliferation, with important and previously unrecognized implications for both fracture repair, and in a broader context, systemic chondrocyte growth and differentiation.

Topics: Acetates; Animals; Arachidonate 5-Lipoxygenase; Cell Proliferation; Chondrocytes; Cyclopropanes; Fracture Healing; Fractures, Bone; Gene Expression Regulation; Hydroxyurea; Hypertrophy; Leukotriene Antagonists; Leukotriene B4; Mice; Models, Biological; Osteogenesis; Quinolines; Radiography; Receptors, Leukotriene; Sulfides

Airway structural changes that occur in patients with asthma in response to persistent inflammation are termed airway remodeling. The cysteinyl leukotrienes (LTC(4), D(4) and E(4)) are known to play important roles in the pathobiology of asthma. To evaluate the effect of low dose montelukast (MK) on the development of airway remodeling using a chronic murine model of allergic airway inflammation with subepithelial fibrosis, BALB/c mice, after intraperitoneal ovalbumin (OVA) sensitization on days 0 and 14, received intranasal OVA periodically on days 14-75. MK treated mice received montelukast sodium intraperitoneally on days 26-75. The OVA sensitized/challenged mice developed an extensive eosinophil cell inflammatory response, goblet cell hyperplasia, mucus occlusion, and smooth muscle hypertrophy of the airways. In addition, in OVA sensitized/challenged mice, dense collagen deposition/fibrosis was seen throughout the lung interstitium surrounding the airways, blood vessels, and alveolar septae. The cysteinyl leukotriene 1 (CysLT1) receptor antagonist, MK significantly reduced the airway eosinophil infiltration, goblet cell hyperplasia, mucus occlusion, and lung fibrosis except airway smooth muscle hypertrophy in the OVA sensitized/challenged mice. The OVA sensitized/challenged mice had significantly increased epithelial desquamation compared with control mice. MK markedly reduced epithelial desquamation of airways in OVA/MK treated animals compared with OVA sensitized/challenged mice. MK treatment did not affect the levels of CysLT in lung tissue. Our results show that the important role of cysteinyl leukotrienes in the pathogenesis of asthma. Lower dose of CysLT1 receptor antagonism has a significant anti-inflammatory effect on allergen-induced lung inflammation and fibrosis but not airway smooth muscle hypertrophy in an animal model of asthma.

Topics: Acetates; Airway Obstruction; Animals; Anti-Asthmatic Agents; Asthma; Collagen; Cyclopropanes; Cysteine; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Goblet Cells; Hyperplasia; Hypertrophy; Leukotriene Antagonists; Leukotrienes; Lung; Mice; Mice, Inbred BALB C; Mucus; Muscle, Smooth; Pulmonary Fibrosis; Quinolines; Receptors, Leukotriene; Respiratory Mucosa; Sulfides