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The leukotriene receptor antagonist montelukast in the treatment of non-alcoholic steatohepatitis: A proof-of-concept, randomized, double-blind, placebo-controlled trial.
Abdallah, MS, Eldeen, AH, Tantawy, SS, Mostafa, TM
European journal of pharmacology. 2021;:174295
Abstract
Non-alcoholic fatty liver disease (NAFLD) is associated with fat accumulation in the liver which can progress into non-alcoholic steatohepatitis (NASH). There is no specific treatment strategy for NASH. In this context, this study aimed at evaluating the efficacy and safety of montelukast in the treatment of patients with NASH. In this randomized double-blind placebo-controlled study, 52 overweight/obese patients with NASH were randomized into group 1 (n = 26) which received montelukast 10 mg tablets once daily and group 2 (n = 26) which received placebo tablets once daily for 12 weeks. The fibro-scan was used to assess liver stiffness as a primary outcome at baseline and 12 weeks post-treatment. Furthermore, patients were assessed for biochemical analysis of liver aminotransferases, metabolic parameters, TNF-α, 8-hydroxy-2'-deoxyguanosine (8-OHdG), liver fibrosis biomarkers including hyaluronic acid (HA) and transforming growth factor beta-1 (TGF-β1). Beck depression inventory questionnaire was used to report depressive symptoms. Data were statistically analyzed by paired and unpaired student's t-test, and Chi-square test. A total number of 44 patients completed the study. The two groups were statistically similar at baseline. After treatment and as compared to baseline data and placebo, montelukast showed a statistically significant improvement in liver stiffness, liver enzymes, metabolic parameters (except LDL-C), TNF-α, 8-OHdG, and liver fibrosis biomarkers (HA and TGF-β1). Furthermore, montelukast was well tolerated and didn't provoke depression. In this proof-of-concept study, treatment with montelukast may represent a promising therapeutic strategy for patients with non-alcoholic steatohepatitis secondary to its efficacy and safety. Clinicaltrial.gov ID: NCT04080947.
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Prospective randomised multicentre study to demonstrate the benefits of haemodialysis without acetate (with citrate): ABC-treat Study. Acute effect of citrate.
de Sequera Ortiz, P, Pérez García, R, Molina Nuñez, M, Muñoz González, RI, Álvarez Fernández, G, Mérida Herrero, E, Camba Caride, MJ, Blázquez Collado, LA, Alcaide Lara, MP, Echarri Carrillo, R, et al
Nefrologia. 2019;(4):424-433
Abstract
INTRODUCTION Dialysis fluid (DF), an essential element in hemodialysis (HD), is manufactured in situ by mixing three components: treated water, bicarbonate concentrate and acid concentrate. To avoid the precipitation of calcium and magnesium carbonate that is produced in DF by the addition of bicarbonate, it is necessary to add an acid. There are 2 acid concentrates that contain acetate (ADF) or citrate (CDF) as a stabilizer. OBJECTIVE To compare the acute effect of HD with CDF vs. ADF on the metabolism of calcium, phosphorus and magnesium, acid base balance, coagulation, inflammation and hemodynamic stability. METHODS Prospective, multicenter, randomized and crossed study, of 32 weeks duration, in patients in three-week HD, AK-200-Ultra-S or Artis monitor, 16 weeks with ADF SoftPac®, prepared with 3mmol/L of acetate, and 16 weeks with CDF SelectBag Citrate®, with 1mmol/L of citrate. Patients older than 18 years were included in HD for a minimum of 3 months by arteriovenous fistula. Epidemiological, dialysis, pre and postdialysis biochemistry, episodes of arterial hypotension, and coagulation scores were collected monthly during the 8 months of the study. Pre and post-dialysis analysis were extracted: venous blood gas, calcium (Ca), ionic calcium (Cai), phosphorus (P), magnesium (Mg) and parathyroid hormone (PTH) among others. ClinicalTrials.gov NCT03319680. RESULTS We included 56 patients, 47 (84%) men and 9 (16%) women, mean age: 65.3 (16.4) years, technique HD/HDF: 20 (35.7%)/36 (64.3%). We found differences (p<0.05) when using the DF with citrate (C) versus acetate (A) in the postdialysis values of bicarbonate [C: 26.9 (1.9) vs. A: 28.5 (3) mmol/L], Cai [C: 1.1 (0.05) vs. A: 1.2 (0.08) mmol/L], Mg [C: 1.8 (0.1) vs A: 1, 9 (0.2) mg/dL] and PTH [C: 255 (172) vs. 148 (149) pg/mL]. We did not find any differences in any of the parameters measured before dialysis. Of the 4,416 sessions performed, 2,208 in each group, 311 sessions (14.1%) with ADF and 238 (10.8%) with CDF (p<0.01), were complicated by arterial hypotension. The decrease in maximum blood volume measured by Hemoscan® biosensor was also lower [-3.4 (7.7) vs -5.1 (8.2)] although without statistical significance. CONCLUSION Dialysis with citrate acutely produces less postdialysis alkalemia and significantly modifies Ca, Mg and PTH. CDF has a positive impact on hemodynamic tolerance.
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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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Fluctuation Analysis of Peak Expiratory Flow and Its Association with Treatment Failure in Asthma.
Kaminsky, DA, Wang, LL, Bates, JH, Thamrin, C, Shade, DM, Dixon, AE, Wise, RA, Peters, S, Irvin, CG
American journal of respiratory and critical care medicine. 2017;(8):993-999
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Abstract
RATIONALE Temporal fluctuations have been demonstrated in lung function and asthma control, but the effect of controller therapy on these fluctuations is unknown. OBJECTIVES To determine if fluctuations in peak expiratory flow (PEF) are predictive of subsequent treatment failure and may be modified by controller therapy. METHODS We applied detrended fluctuation analysis to once-daily PEF data from 493 participants in the LOCCS (Leukotriene Modifier Corticosteroid or Corticosteroid-Salmeterol) trial of the American Lung Association Airways Clinical Research Centers. We evaluated the coefficient of variation of PEF (CVpef) and the scaling exponent α, reflecting self-similarity of PEF, in relation to treatment failure from the run-in period of open-label inhaled fluticasone, and the treatment periods for subjects randomized to (1) continued twice daily fluticasone (F), (2) once daily fluticasone plus salmeterol (F + S), or (3) once daily oral montelukast (M). MEASUREMENTS AND MAIN RESULTS The CVpef was higher in those with treatment failure in the F and F + S groups in the run-in phase, and all three groups in the treatment phase. α was similar between those with and without treatment failure in all three groups during the run-in phase but was higher among those with treatment failure in the F and F + S groups during the treatment phase. Participants in all three groups showed variable patterns of change in α leading up to treatment failure. CONCLUSIONS We conclude that increased temporal self-similarity (α) of more variable lung function (CVpef) is associated with treatment failure, but the pattern of change in self-similarity leading up to treatment failure is variable across individuals.
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Fluticasone, Azithromycin, and Montelukast Treatment for New-Onset Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation.
Williams, KM, Cheng, GS, Pusic, I, Jagasia, M, Burns, L, Ho, VT, Pidala, J, Palmer, J, Johnston, L, Mayer, S, et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2016;(4):710-716
Abstract
Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT) is associated with high mortality. We hypothesized that inhaled fluticasone, azithromycin, and montelukast (FAM) with a brief steroid pulse could avert progression of new-onset BOS. We tested this in a phase II, single-arm, open-label, multicenter study (NCT01307462). Thirty-six patients were enrolled within 6 months of BOS diagnosis. The primary endpoint was treatment failure, defined as 10% or greater forced expiratory volume in 1 second decline at 3 months. At 3 months, 6% (2 of 36, 95% confidence interval, 1% to 19%) had treatment failure (versus 40% in historical controls, P < .001). FAM was well tolerated. Steroid dose was reduced by 50% or more at 3 months in 48% of patients who could be evaluated (n = 27). Patient-reported outcomes at 3 months were statistically significantly improved for Short-Form 36 social functioning score and mental component score, Functional Assessment of Cancer Therapies emotional well-being, and Lee symptom scores in lung, skin, mouth, and the overall summary score compared to enrollment (n = 24). At 6 months, 36% had treatment failure (95% confidence interval, 21% to 54%, n = 13 of 36, with 6 documented failures, 7 missing pulmonary function tests). Overall survival was 97% (95% confidence interval, 84% to 100%) at 6 months. These data suggest that FAM was well tolerated and that treatment with FAM and steroid pulse may halt pulmonary decline in new-onset BOS in the majority of patients and permit reductions in systemic steroid exposure, which collectively may improve quality of life. However, additional treatments are needed for progressive BOS despite FAM.
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Montelukast for postinfectious cough in adults: a double-blind randomised placebo-controlled trial.
Wang, K, Birring, SS, Taylor, K, Fry, NK, Hay, AD, Moore, M, Jin, J, Perera, R, Farmer, A, Little, P, et al
The Lancet. Respiratory medicine. 2014;(1):35-43
Abstract
BACKGROUND Postinfectious cough is common in primary care, but has no proven effective treatments. Cysteinyl leukotrienes are involved in the pathogenesis of postinfectious cough and whooping cough (pertussis). We investigated the effectiveness of montelukast, a cysteinyl leukotriene receptor antagonist, in the treatment of postinfectious cough. METHODS In this randomised, placebo-controlled trial, non-smoking adults aged 16-49 years with postinfectious cough of 2-8 weeks' duration were recruited from 25 general practices in England. Patients were tested for pertussis (oral fluid anti-pertussis toxin IgG) and randomly assigned (1:1) to montelukast 10 mg daily or image-matched placebo for 2 weeks. Patients chose whether to continue study drug for another 2 weeks. The randomisation sequence was computer-generated and stratified by general practice. Patients, health-care professionals, and researchers were masked to treatment allocation. Effectiveness was assessed with the Leicester Cough Questionnaire to measure changes in cough-specific quality of life; the primary outcomes were changes in total score between baseline and two follow-up stages (2 weeks and 4 weeks). The primary analysis was by intention to treat with imputation by last observation carried forward. Recruitment closed on Sept 21, 2012, and follow-up has been completed. This trial is registered with EudraCT (2010-019647-19), UKCRN Portfolio (ID 8360), and ClinicalTrials.gov (NCT01279668). FINDINGS From April 13, 2011, to Sept 21, 2012, we randomly assigned 276 patients to montelukast (n=137) or placebo (n=139). 70 (25%) patients had laboratory-confirmed pertussis. Improvements in cough-specific quality of life occurred in both groups after 2 weeks (montelukast: mean 2·7, 95% CI 2·2-3·3; placebo: 3·6, 2·9-4·3), but the difference between groups did not meet the minimum clinically important difference of 1·3 (mean difference -0·9, -1·7 to -0·04, p=0·04). This difference was not statistically significant in any sensitivity analyses. After 2 weeks, 192 of 259 participants from whom data were available elected to continue study drug (99 [77%] of 129 participants on montelukast; 93 [72%] of 130 on placebo). After 4 weeks, there were no significant between-group differences in cough-specific quality of life improvement (montelukast: 5·2, 4·5-5·9; placebo: 5·9, 5·1-6·7; mean difference -0·5, -1·5 to 0·6, p=0·38) or adverse event rates (21 (15%) of 137 patients on montelukast reported one or more adverse events; 31 (22%) of 139 on placebo; p=0·14). The most common adverse events reported were increased mucus production (montelukast, n=6; placebo, n=2), gastrointestinal disturbance (montelukast, n=3; placebo, n=5), and headache (montelukast, n=2; placebo, n=6). One serious adverse event was reported (placebo, n=1), which was unrelated to study drug (shortness of breath and throat tightness after severe coughing bouts). INTERPRETATION Montelukast is not an effective treatment for postinfectious cough. However, the burden of postinfectious cough in primary care is high, making it an ideal setting for future antitussive treatment trials. FUNDING National Institute for Health Research School for Primary Care Research, UK.
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[Clinical and laboratory evaluation of the efficiency of chronic hemodialysis treatment using acidosuccinate in patients with terminal renal failure].
Smirnov, AV, Nesterova, OB, Suglobova, ED, Golubev, RV, Vasil'ev, AN, Vasil'eva, IA, Verbitskaia, EV, Korosteleva, NIu, Kostereva, EM, Lebedeva, EB, et al
Terapevticheskii arkhiv. 2013;(1):69-75
Abstract
AIM: To evaluate the efficiency of using a succinate-containing dialysis solution (SCDS) in terminal renal failure patients treated with chronic hemodialysis (CHD). SUBJECTS AND METHODS Ninety patients from two hemodialysis units took part in the crossover study and were allocated to 2 groups. For 6 months, study group patients received CHD using SCDS and control group patients had CHD with a standard bicarbonate dialysis solution after 3-month washout period followed by decussation. The time course of changes in blood biochemical parameters, 24-hour ECG monitoring data, and quality of life indicators were estimated in the patients. RESULTS After using acidosuccinate during hemodialysis, there was a significant reduction in the predialysis serum level of inorganic phosphate, a calcium phosphate product, gamma-glutamyl transpeptidase, urea, and aldosterone as compared to the control group. The blood concentration of total protein was also increased. After 6-month administration of acidosuccinate, the patients showed reductions in systolic blood pressure, heart rate, and the frequency and duration of ST-segment depression episodes. There were positive changes in the quality of life of patients according to the KDQOL-SF questionnaire. CONCLUSION The use of SCDS in patients with CHD causes positive changes in a number of laboratory parameters and improves the physical and general status, and quality of life of patients.
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Desloratadine-montelukast combination improves quality of life and decreases nasal obstruction in patients with perennial allergic rhinitis.
Cingi, C, Oghan, F, Eskiizmir, G, Yaz, A, Ural, A, Erdogmus, N
International forum of allergy & rhinology. 2013;(10):801-6
Abstract
BACKGROUND The effects of desloratadine-montelukast combination on quality of life (QoL) and nasal airflow of patients with perennial allergic rhinitis (PAR) has not been reported. The objective of this work was investigate the efficacy of desloratadine-montelukast combination on nasal obstruction and health-related quality of life (HRQL) of patients with PAR. METHODS The patients with PAR (n = 40) were assessed using acoustic rhinometry (AcR) and Rhinoconjunctivitis QoL Questionnaire (RQLQ) before therapy. Desloratadine-montelukast fixed-dose combination treatment was applied to every patient once daily. The AcR and RQLQ score were reevaluated at the first and third months; and statistical comparison of pretreatment and posttreatment results was performed. RESULTS Nasal symptoms and signs such as itching, sneezing, discharge, congestion, and edema, and color change of turbinates have been decreased after treatment. In AcR, minimum cross-sectional area (MCA) measurements and volume results were increased after the treatment. Correlation was found between the volume results and nasal discharge and/or congestion in right nasal passages. In left nasal passages, statistical relation was observed between the MCA and itching and/or change of turbinate color (p < 0.05). A significant decrease in the overall RQLQ score was determined at the first and third months of therapy. The difference between scores at baseline and end of the first and third months for all domains was statically significant (p < 0.001). The treatment difference in change from the first month to the end of the third month was statistically significant (p < 0.05). CONCLUSION Desloratadine-montelukast combination therapy causes subjective and objective decrease in nasal obstruction, reduces the other symptoms of PAR and improves the disease-specific QoL.
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Effects of mometasone, fluticasone, and montelukast on bone mineral density in adults with asthma.
Maspero, J, Backer, V, Yao, R, Staudinger, H, Teper, A
The journal of allergy and clinical immunology. In practice. 2013;(6):649-55.e1
Abstract
BACKGROUND Associations of inhaled corticosteroids (ICS) with bone mineral density (BMD) loss have not been characterized consistently. OBJECTIVE This randomized, double-blind study assessed effects of mometasone furoate (MF) administered via dry powder inhaler on BMD of patients with persistent asthma. METHODS Adults with mild-moderate persistent asthma who did not receive ICS for ≥3 months were randomized to MF 400 μg once daily (QD) in the evening (pm), MF 200 μg QD pm, montelukast sodium (ML) 10 mg QD pm, or fluticasone propionate (FP) 250 μg twice daily. Included patients had 25-hydroxy vitamin D levels ≥15 ng/mL at baseline. All the patients received calcium and vitamin D supplements for daily use during the trial. Duplicate BMD scans were done at baseline, 6 months, and 1 year. The mean percentage change in lumbar spine (LS) BMD from baseline to end point for MF 400 μg versus ML 10 mg was the primary analysis. Changes from baseline in left total femur BMD and femoral neck BMD were secondary assessments. RESULTS At the end point, mean LS BMD increased 0.9% (MF 400 μg), 1.2% (ML), 0.7% (MF 200 μg), and 1.1% (FP), with no significant differences for MF 400 μg versus ML (-0.3% [95% CI, -1.01 to 0.27]) for LS BMD. No significant differences among treatments occurred for changes in left total femur BMD; all were slight increases. Changes in femoral neck BMD were 0.4% (MF 400 μg), -0.2% (ML), -0.2% (MF 200 μg), and -0.4% (FP); only the difference between MF 400 μg and FP was statistically significant (P = .044). CONCLUSION No detrimental effects on lumbar BMD were observed after up to 1 year of treatment with MF in comparison with ML for patients who received calcium and vitamin D supplements.
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RCT of montelukast as prophylaxis for upper respiratory tract infections in children.
Kozer, E, Lotem, Z, Elgarushe, M, Torgovicky, R, Cohen, R, Cohen, HA, Berkovitch, M
Pediatrics. 2012;(2):e285-90
Abstract
BACKGROUND Infections with viruses causing upper respiratory tract infection (URI) are associated with increased leukotriene levels in the upper airways. Montelukast, a selective leukotriene-receptor antagonist, is an effective treatment of asthma and allergic rhinitis. OBJECTIVE To determine whether prophylactic treatment with montelukast reduces the incidence and severity of URI in children. METHODS A randomized, double-blind, placebo-controlled study was performed in 3 primary care pediatric ambulatory clinics in Israel. Healthy children aged 1 to 5 years were randomly assigned in a 1:1 ratio to receive 12-week treatment with 4 mg oral montelukast or look-alike placebo. Patients were excluded if they had a previous history of reactive airway disease. A study coordinator contacted the parents by phone once a week to obtain information regarding the occurrence of acute respiratory episodes. The parents received a diary card to record any acute symptoms of URI. The primary outcome measure was the number of URI episodes. RESULTS Three hundred children were recruited and randomly assigned into montelukast (n = 153) or placebo (n = 147) groups. One hundred thirty-one (85.6%) of the children treated with montelukast and 129 (87.7%) of the children treated with placebo completed 12 weeks of treatment. The number of weeks in which URI was reported was 30.4% in children treated with montelukast and 30.7% in children treated with placebo. There was no significant difference in any of the secondary variables between the groups. CONCLUSIONS In preschool-aged children, 12-week treatment with montelukast, compared with placebo, did not reduce the incidence of URI.