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1.
Airway mechanics after withdrawal of a leukotriene receptor antagonist in children with mild persistent asthma: Double-blind, randomized, cross-over study.
Kim, JH, Lee, S, Shin, YH, Ha, EK, Lee, SW, Kim, MA, Yoon, JW, Baek, HS, Choi, SH, Han, MY
Pediatric pulmonology. 2020;(12):3279-3286
Abstract
BACKGROUND To determine the response of airway mechanics and the changes in asthma symptoms to stepping down of leukotriene receptor antagonist (LTRA) therapy. METHODS Thirty children (mean age: 7.1 years) with mild, well-controlled, and persistent asthma who took LTRA as maintenance treatment were randomized into a double-blind, placebo-controlled, cross-over study. Each group received an LTRA (montelukast) or placebo daily for 2 weeks, followed by a 1-week washout period, and then the alternate treatment for 2 weeks. Spirometry and impulse oscillation system (IOS) measurements before and after four puffs of salbutamol inhalation, fractional exhaled nitric oxide (FeNO), and the childhood asthma control test (C-ACT) were evaluated at baseline, the end of placebo treatment, and the end of LTRA treatment. RESULTS Changes of FEV1 /FVC (p = .113) and FEV1 (p = .109) from baseline to posttreatment did not differ significantly between the placebo and montelukast groups. In the placebo group, prebronchodilator (pre-) FEV1 /FVC was decreased (83% vs. 86%) and bronchodilator response (BDR) in FEV1 was diminished (10.7% vs. 6.4%) at posttreatment compared with baseline. However, the montelukast group had no significant changes in pre-FEV1 /FVC (p = .865) and BDR in FEV1 (p = .461). In addition, compared with the montelukast group, the placebo group showed no significant changes in Rrs5 (total airway resistance), Rrs5-20 (peripheral airway resistance), FeNO, and symptoms by the C-ACT. CONCLUSION In children with well-controlled mild persistent asthma, changes in spirometry, IOS, FeNO, and C-ACT results did not differ between the placebo and montelukast groups within 2 weeks.
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2.
Effects of Medical Therapy on Mild Obstructive Sleep Apnea in Adult Patients.
Smith, DF, Sarber, KM, Spiceland, CP, Ishman, SL, Augelli, DM, Romaker, AM
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2019;(7):979-983
Abstract
STUDY OBJECTIVES Patients with obstructive sleep apnea (OSA) have been shown to have high levels of inflammatory markers. Anti-inflammatory treatment with montelukast and intranasal steroids have demonstrated efficacy for mild OSA in children; this has not been fully evaluated in adults. This study investigated the response of mild OSA in adults to anti-inflammatory medical therapy. METHODS Adults aged ≥ 21 years with an apnea-hypopnea index (AHI) ≤ 15 events/h on polysomnography (PSG) were recruited to a prospective double-blind, randomized control trial. Patients were treated for 12 weeks with montelukast and fluticasone or placebo. All underwent a pretreatment and posttreatment PSG. Epworth Sleepiness Scale (ESS) score was obtained pretreatment and at 6 and 12 weeks posttreatment. RESULTS A total of 26 patients completed the study with 13 in each group. Mean age in the treatment and placebo groups were 58.3 ± 10.3 and 54.8 ± 14 years, respectively. There was no significant difference between groups reporting nasal congestion (P = .186), rhinitis (P = .666), or snoring (P = .177). There was no difference in the pretreatment ESS score (P = .077), body mass index (P = .173), or AHI (P = .535). The posttreatment PSG in the treatment group demonstrated a significant increase in total sleep time (P = .02) and percent of stage R sleep (P = .05). Neither group showed significant change in AHI. In patients in the treatment group, the 6- and 12-week follow-up ESS scores were not significantly different from pretreatment scores (P = .37-.46). CONCLUSIONS Intranasal steroids and montelukast did not decrease AHI; however, total sleep time and percent of stage R sleep significantly increased. Self-reported improvement could be explained by observed changes in sleep parameters. Larger prospective studies could help elucidate the effects of medical therapy on adult patients with OSA. CLINICAL TRIAL REGISTRATION Registry: ClinicalTrials.gov; Title: Montelukast and Nasa ICS for Treatment of Mild Obstructive Sleep Apnea in Adults; Identifier: NCT01089647; URL: https://clinicaltrials.gov/ct2/show/record/NCT01089647.
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3.
Effect of montelukast combined with methylprednisolone for the treatment of mycoplasma pneumonia.
Wu, H, Ding, X, Zhao, D, Liang, Y, Ji, W
The Journal of international medical research. 2019;(6):2555-2561
Abstract
OBJECTIVE To study the effect of the leukotriene receptor agonist montelukast combined with methylprednisolone on inflammatory response and peripheral blood lymphocyte subset content in children with mycoplasma pneumonia. METHODS Seventy-four children were enrolled and randomly divided into a standard treatment group and a montelukast plus methylprednisolone group. Serum levels of inflammatory cytokines and corresponding cytokines of T lymphocyte subsets were measured, and peripheral blood was collected to determine the T cell subset content. RESULTS At 3 days and 7 days after treatment, serum MCP-1, PCT, ICAM-1, CXCL8, CRP, IFN-γ, and IL-17 levels and peripheral blood Th1 and Th17 content were significantly decreased in both groups, while serum IL-4 and TGF-β levels and peripheral blood Treg and Th2 content were significantly increased. However, serum MCP-1, PCT, ICAM-1, CXCL8, CRP, IFN-γ, and IL-17 levels and peripheral blood Th1 and Th17 content were significantly lower while serum IL-4 and TGF-β levels and peripheral blood Treg and Th2 content were significantly higher in the montelukast plus methylprednisolone group compared with the control group. CONCLUSION Montelukast combined with methylprednisolone for the treatment of mycoplasma pneumonia can inhibit inflammatory responses and regulate levels of Th1/Th2 and Th17/Treg cells.
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4.
Phenotyping patients with chronic cough: Evaluating the ability to predict the response to anti-inflammatory therapy.
Sadeghi, MH, Wright, CE, Hart, S, Crooks, M, Morice, A
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2018;(3):285-291
Abstract
BACKGROUND Whether the fraction of exhaled nitric oxide (FeNO) measurement can predict the response to anti-inflammatory treatment in chronic cough is unknown. OBJECTIVE To explore whether the effectiveness of treatment with 10 mg of montelukast or 20 mg of prednisolone in patients with chronic cough is predicted by FeNO level. METHODS In this randomized, open-label, controlled pilot study conducted in the Clinical Trial Unit in Castle Hospital in the United Kingdom, 50 nonsmoking patients with a cough that lasted more than 8 weeks were sequentially enrolled in the study. Thirty patients with high FeNO levels (≥30 ppb) were randomized in a 1:1 ratio to receive 10 mg of montelukast or 20 mg of prednisolone for 2 weeks followed by 10 mg of montelukast for 2 weeks. Twenty patients with a low FeNO level (≤20 ppb) received 10 mg of montelukast. The primary objective was to determine the effectiveness of treatment on 24-hour cough counts. RESULTS The 24-hour cough counts decreased in both groups by approximately 50% (P < .005), indicating that FeNO did not predict treatment response. However, it was a good marker for eosinophilic inflammation with a high degree of correlation with blood and sputum eosinophilia (P < .001). CONCLUSION These results suggest that prior investigation may not predict response to anti-inflammatory treatment, which may be consequent on localized leukotriene-mediated inflammation. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02479074.
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5.
Lack of long-term add-on effect by montelukast in postoperative chronic rhinosinusitis patients with nasal polyps.
Van Gerven, L, Langdon, C, Cordero, A, Cardelús, S, Mullol, J, Alobid, I
The Laryngoscope. 2018;(8):1743-1751
Abstract
OBJECTIVES/HYPOTHESIS Eosinophils and mast cells are among the key cells in inflammatory diseases like chronic rhinosinusitis (CRS) and asthma. Leukotriene antagonists have proven to be effective in the treatment of asthma, but data about their efficacy in CRS are scarce, whereas data on montelukast as an add-on treatment to intranasal corticosteroids (INCS) in a postoperative setting are completely lacking. STUDY DESIGN Prospective, randomized, open-label trial. METHODS In this trial with long-term follow-up, we evaluated the efficacy of montelukast as an add-on treatment to INCS in postoperative CRS with nasal polyp (CRSwNP) patients. CRSwNP patients (N = 72) undergoing endoscopic sinus surgery were randomized in two arms for the postoperative treatment. One group (N = 36) received INCS in monotherapy, whereas the other group (N = 36) received INCS in association with montelukast for 1 year. The efficacy of montelukast with INCS was evaluated by assessing both subjective (total five-symptom score [T5SS]) and objective (nasal polyp score [NPS], Lund-Mackay [LMK] score, and subjective olfactometry [Barcelona Smell Test 24]) outcome parameters and compared with the gold standard of INCS in monotherapy. RESULTS After 1 year of surgery, T5SS, NPS, and LMK score were significantly reduced in patients treated with either INCS or INCS plus montelukast, without significant differences between the two treatment arms. Improvement of smell loss by olfactometry was also observed with no differences between arms. Similar findings were observed at 3 and 6 months. CONCLUSIONS These results suggest that the addition of montelukast to INCS should not be recommended in the treatment of postoperative CRSwNP patients. LEVEL OF EVIDENCE 1b Laryngoscope, 1743-1751, 2018.
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6.
Comparison of the efficacy and mechanisms of intranasal budesonide, montelukast, and their combination in treatment of patients with seasonal allergic rhinitis.
Chen, H, Lou, H, Wang, Y, Cao, F, Zhang, L, Wang, C
International forum of allergy & rhinology. 2018;(11):1242-1252
Abstract
BACKGROUND Although intranasal steroids and anti-cysteinyl-leukotriene-receptor antagonists are efficacious in the treatment of seasonal allergic rhinitis (SAR), combinations of these agents have not unequivocally been demonstrated to be superior to the individual drugs. We aimed to compare the efficacy and potential mechanisms of budesonide nasal spray (BD), oral montelukast (MNT), and combination therapy comprising a half-dose of budesonide plus montelukast (hBD+MNT) in SAR patients. METHODS We performed a single-center, randomized, open-label study in SAR subjects (n = 100). Participants were randomized to receive BD (256 μg), MNT (10 mg), or hBD (128 μg)+MNT for 14 days. Symptom severity scores, nasal cavity volume (NCV), fraction of exhaled nitric oxide (FeNO), eosinophil cationic protein (ECP), histamine and cysteinyl-leukotrienes (CysLTs), and T-cell subsets were assessed before and after treatment. RESULTS All treatments significantly improved symptoms from baseline; however, hBD+MNT produced significantly greater improvements in nasal congestion compared with BD or MNT alone. The BD and hBD+MNT groups had fewer patients with uncontrolled symptoms and improved NCV to a greater level than the MNT group. FeNO was decreased to a significantly greater extent from baseline after hBD+MNT treatment than after BD and MNT treatments. ECP, histamine, and CysLTs showed significantly greater decreases after BD and hBD+MNT treatments than after MNT treatment. BD decreased T-helper 1 (Th1) and Th2 cells and increased T-regulatory (Treg) cells in nasal mucosa and MNT decreased Th1 cells and increased Treg cells in peripheral blood, and this trend was reflected with hBD+MNT. CONCLUSION The hBD+MNT combination may have an overall better efficacy profile than BD and MNT monotherapy for treatment of SAR.
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7.
An Open-Label, Multi-Institutional, Randomized Study to Evaluate the Additive Effect of a Leukotriene Receptor Antagonist on Cough Score in Patients with Cough-Variant Asthma Being Treated with Inhaled Corticosteroids.
Miwa, N, Nagano, T, Ohnishi, H, Nishiuma, T, Takenaka, K, Shirotani, T, Nakajima, T, Dokuni, R, Kawa, Y, Kobayashi, K, et al
The Kobe journal of medical sciences. 2018;(4):E134-E139
Abstract
Cough-variant asthma is one of the most common reasons for chronic cough. It is important to treat appropriately cough-variant asthma because 30% to 40% of cough-variant asthma becomes a typical asthma. However, little is known about the treatment of cough-variant asthma except for inhaled corticosteroid (ICS). The aim of this study was to validate the additive efficacy of a leukotriene receptor antagonist (LTRA) on cough score and respiratory function in patients with cough-variant asthma being treated with ICS. A total 28 patients were randomly assigned to either an ICS + LTRA group or an ICS group. There were statistically significant improvements in cough scores in the ICS + LTRA group from 0 weeks (6.7 ± 4.4) to 2 weeks (2.9 ± 3.2) (P < 0.05), 4 weeks (0.7 ± 1.1) (P < 0.001), and 8 weeks (0.8 ± 1.2) (P < 0.001). However similar improvements were not evident in the ICS group from 0 weeks (6.7 ± 4.4) to 2 weeks (5.6 ± 10.0) (P = 0.59), 4 weeks (4.6 ± 7.6) (P = 0.32), and 8 weeks (2.9 ± 5.2) (P = 0.08). On the other hand, no significant changes were evident in the forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC). In conclusion, the LTRA was useful in improving cough in patients with cough-variant asthma, even though it appeared to be ineffective in improving respiratory function.
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8.
Montelukast for bronchiolitis obliterans syndrome after lung transplantation: A randomized controlled trial.
Ruttens, D, Verleden, SE, Demeyer, H, Van Raemdonck, DE, Yserbyt, J, Dupont, LJ, Vanaudenaerde, BM, Vos, R, Verleden, GM
PloS one. 2018;(4):e0193564
Abstract
Bronchiolitis obliterans syndrome (BOS) remains the major problem which precludes long-term survival after lung transplantation. Previously, an open label pilot study from our group demonstrated a possible beneficial effect of montelukast in progressive BOS patients with low airway neutrophilia (<15%), and already on azithromycin treatment, in whom the further decline in pulmonary function was attenuated. This was, however, a non-randomized and non-placebo controlled trial. The study design is a single center, prospective, interventional, randomized, double blind, placebo-controlled trial, with a two arm parallel group design and an allocation ratio of 1:1. Randomization to additional montelukast (10 mg/day, n = 15) or placebo (n = 15) was performed from 2010 to 2014 at the University Hospitals Leuven (Leuven, Belgium) in all consecutive patients with late-onset (>2years posttransplant) BOS ≥1. Primary end-point was freedom from graft loss 1 year after randomization; secondary end-points were acute rejection, lymphocytic bronchiolitis, respiratory infection rate; and change in FEV1, airway and systemic inflammation during the study period. Graft loss at 1 y and 2y was similar in both groups (respectively p = 0. 981 and p = 0.230). Montelukast had no effect on lung function decline in the overall cohort. However, in a post-hoc subanalysis of BOS stage 1 patients, montelukast attenuated further decline of FEV1 during the study period, both in absolute (L) (p = 0.008) and % predicted value (p = 0.0180). A linear mixed model confirmed this association. Acute rejection, lymphocytic bronchiolitis, respiratory infections, systemic and airway inflammation were comparable between groups over the study period. This randomized controlled trial showed no additional survival benefit with montelukast compared to placebo, although the study was underpowered. The administration of montelukast was associated with an attenuation of the rate of FEV1 decline, however, only in recipients with late-onset BOS stage 1.
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9.
Evaluation of switching low-dose inhaled corticosteroid to pranlukast for step-down therapy in well-controlled patients with mild persistent asthma.
Harada, S, Harada, N, Itoigawa, Y, Katsura, Y, Kasuga, F, Ishimori, A, Makino, F, Ito, J, Atsuta, R, Takahashi, K
The Journal of asthma : official journal of the Association for the Care of Asthma. 2016;(2):207-12
Abstract
OBJECTIVE Treatment guidelines for asthma recommend step-down therapy for well-controlled asthma patients. However, the precise strategy for step-down therapy has not been well defined. We investigated whether well-controlled patients with mild persistent asthma can tolerate a step-down therapy of either a reduced dose of inhaled corticosteroid (ICS) or a switch to a leukotriene receptor antagonist (LTRA), pranlukast hydrate. METHODS We recruited 40 adult patients with mild persistent asthma who were well-controlled for at least 3 months with a low-dose ICS therapy. The patients were randomly assigned to either an ICS dose reduction or a switch to pranlukast for 6 months. RESULTS FeNO levels in the pranlukast group were significantly increased over that in the ICS group. There were no significant differences between the two groups for lung function, FOT, at the endpoint. The percentage of patients with controlled asthma was 72.2% in the pranlukast group and 90% in the ICS group. No statistically significant difference between the two groups in the percentages of patients with treatment failure was observed. CONCLUSIONS Patients with mild persistent asthma that is well-controlled by a low dose of ICS can be switched to pranlukast safely for at least 6 months. However, 27.8% of the pranlukast group failed to maintain well-control, and FeNO levels increased with the switch to pranlukast at 6 months. This study was been limited by the small sample size and should therefore be considered preliminary. Further studies are needed to investigate the therapeutic efficacy of LTRA monotherapy as a step-down therapy.
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10.
Montelukast as an add-on treatment in steroid dependant nephrotic syndrome, randomised-controlled trial.
Zedan, MM, El-Refaey, A, Zaghloul, H, Abdelrahim, ME, Osman, A, Zedan, MM, Eltantawy, N
Journal of nephrology. 2016;(4):585-92
Abstract
BACKGROUND The underlying mechanisms of nephrotic syndrome (NS) are still under debate and the need for more effective and less toxic treatment is challenging. We aimed to evaluate the efficacy of montelukast, a leukotriene receptor antagonist as an add-on therapy, and to explore the leukotriene (LT) biology in steroid-dependent nephrotic syndrome (SDNS). METHODS A randomized controlled trial was conducted including 32 patients with SDNS who were randomly assigned to receive standard steroid treatment only [low-dose steroid (LDS) group] or standard steroid therapy plus montelukast (Montelukast group). Urine protein/creatinine ratio, serum albumin, creatinine, cholesterol, and plasma LTs (LTB4/C4/D4/E4) were evaluated in all patients before and after treatment. RESULTS After treatment, both groups showed a significant decrease of LTB4 and LTC4/D4/E4. Further, the Montelukast group showed a significant decrease in serum creatinine and a significant increase in diastolic blood pressure and protein/creatinine ratio. It also showed a marked decrease in plasma LTC4/D4/E4 compared to the LDS group, although not statistically significant. CONCLUSIONS Our findings highlight the effect of montelukast on renal function, but suggest that the clinical and laboratory efficacy of the addition of montelukast to steroids in maintenance treatment of SDNS is debatable.