montelukast and Bronchiolitis

Bronchiolitis is an acute inflammatory illness of the bronchioles common among infants and young children. It is often caused by the respiratory syncytial virus (RSV). Management of bronchiolitis varies between clinicians, reflecting the lack of evidence for a specific treatment approach. The leukotriene pathway has been reported to be involved in the pathogenesis of bronchiolitis. Leukotriene inhibitors such as montelukast have been used in infants and young children with bronchiolitis. However, the results from limited randomised controlled trials (RCTs) are controversial and necessitate a thorough evaluation of their efficacy for bronchiolitis in infants and young children.. To assess the efficacy and safety of leukotriene inhibitors for bronchiolitis in infants and young children.. We searched CENTRAL (2014, Issue 5), MEDLINE (1946 to April week 4, 2014), EMBASE (1974 to May 2014), CINAHL (1981 to May 2014), LILACS (1982 to May 2014), Web of Science (1985 to May 2014), WHO ICTRP and ClinicalTrials.gov (6 May 2014).. RCTs comparing leukotriene inhibitors versus placebo or another intervention in infants and young children under two years of age diagnosed with bronchiolitis. Our primary outcomes were length of hospital stay and all-cause mortality. Secondary outcomes included clinical severity score, percentage of symptom-free days, percentage of children requiring ventilation, oxygen saturation, recurrent wheezing, respiratory rate and clinical adverse effects.. We used standard Cochrane Collaboration methodological practices. Two authors independently assessed trial eligibility and extracted data, such as general information, participant characteristics, interventions and outcomes. We assessed risk of bias and graded the quality of the evidence. We used Review Manager software to pool results and chose random-effects models for meta-analysis.. We included five studies with a total of 1296 participants under two years of age hospitalised with bronchiolitis. Two studies with low risk of bias compared 4 mg montelukast (a leukotriene inhibitor) daily use from admission until discharge with a matching placebo. Both selected length of hospital stay as a primary outcome and clinical severity score as a secondary outcome. However, the effects of leukotriene inhibitors on length of hospital stay and clinical severity score were uncertain due to considerable heterogeneity between the study results and wide confidence intervals around the estimated effects (hospital stay: mean difference (MD) -0.95 days, 95% confidence interval (CI) -3.08 to 1.19, P value = 0.38, low quality evidence; clinical severity score on day two: MD -0.57, 95% CI -2.37 to 1.23, P value = 0.53, low quality evidence; clinical severity score on day three: MD 0.17, 95% CI -1.93 to 2.28, P value = 0.87, low quality evidence). The other three studies compared montelukast for several weeks for preventing post-bronchiolitis symptoms with placebo. We assessed one study as low risk of bias, whereas we assessed the other two studies as having a high risk of attrition bias. Due to the significant clinical heterogeneity in severity of disease, duration of treatment, outcome measurements and timing of assessment, we did not pool the results. Individual analyses of these studies did not show significant differences between the leukotriene inhibitors group and the control group in symptom-free days and incidence of recurrent wheezing. One study of 952 children reported two deaths in the leukotriene inhibitors group: neither was determined to be drug-related. No data were available on the percentage of children requiring ventilation, oxygen saturation and respiratory rate. Finally, three studies reported adverse events including diarrhoea, wheezing shortly after administration and rash. No differences were reported between the study groups.. The current evidence does not allow definitive conclusions to be made about the effects of leukotriene inhibitors on length of hospital stay and clinical severity score in infants and young children with bronchiolitis. The quality of the evidence was low due to inconsistency (unexplained high levels of statistical heterogeneity) and imprecision arising from small sample sizes and wide confidence intervals, which did not rule out a null effect or harm. Data on symptom-free days and incidence of recurrent wheezing were from single studies only. Further large studies are required. We identified one registered ongoing study, which may make a contribution in the updates of this review.

Topics: Acetates; Bronchiolitis; Cyclopropanes; Humans; Infant; Length of Stay; Leukotriene Antagonists; Quinolines; Randomized Controlled Trials as Topic; Sulfides

The influence of Mycoplasma pneumoniae (MP) infection on bronchiolitis remains unclear. Additionally, reports on the efficacies of leukotriene receptor antagonists in the treatment of bronchiolitis have been inconclusive.. Children with respiratory syncytial virus (RSV)-induced bronchiolitis were divided into two groups: RSV+MP group and RSV group. Each group was randomly divided into two subgroups: one received routine and placebo treatment, while the other received routine and montelukast treatment for 9 months. The cumulative numbers of wheezing episodes and recurrent respiratory tract infections were recorded. Blood parameters were determined.. Patients in the RSV+MP group exhibited an older average age, fever, more frequent flaky and patchy shadows in chest X-rays, more frequent extrapulmonary manifestations, and longer hospital stays compared with patients in the RSV group. Additionally, higher baseline blood eosinophil counts, eosinophil cationic protein (ECP), total immunoglobulin E (IgE), interleukin (IL)-4, IL-5, IL-4/interferon-γ ratios, leukotriene (LT) B4, and LTC4, and lower baseline lipoxin A4 (LXA4)/LTB4 ratios were observed in the RSV+MP group compared with the RSV group. Montelukast treatment decreased the cumulative numbers of recurrent wheezing episodes and recurrent respiratory tract infections at 9 and 12 months. This efficacy may be related to the montelukast-induced reductions in peripheral eosinophil counts, ECP and total IgE, as well as the montelukast-dependent recovery in T helper (Th) 1/Th2 balance and LXA4/LTB4 ratios in children with bronchiolitis.. RSV bronchiolitis with MP infection was associated with clinical and laboratory features that differed from those of RSV bronchiolitis without MP infection. Add-on therapy with montelukast for 9 months was beneficial for children with bronchiolitis at 9 and 12 months after the initiation of treatment.

Topics: Acetates; Bronchiolitis; Coinfection; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Infant; Leukotriene Antagonists; Male; Pneumonia, Mycoplasma; Prospective Studies; Quinolines; Respiratory Syncytial Virus Infections; Sulfides

To observe the effect of montelukast treatment on levels of serum leukotriene B4 and urinary leukotriene E4 in infants with bronchiolitis.. Seventy-five children who were diagnosed with bronchiolitis between June 2014 and December 2014 were randomly assigned into two groups, one with thirty-eight cases as the montelukast treatment group and another thirty-seven cases as the control group. All of the children were given routine medical treatment. The children in the montelukast treatment group were additionally given montelukast daily (4 mg once a day, for 7 days). The serum leukotriene B4 and urinary leukotriene E4 levels were measured using ELISA before and after treatment. The relationship between serum leukotriene B4 and urinary leukotriene E4 levels was analyzed by Peason correlation analysis.. After 7 days of treatment, the serum leukotriene B4 and urinary leukotriene E4 levels in the montelukast treatment and control groups were significantly reduced compared with before treatment (P<0.05). The montelukast treatment group showed significantly lower serum leukotriene B4 and urinary leukotriene E4 levels than the control group (P<0.05). The remission time of cough, wheezing and lung wheezes and the length of hospital stay in the montelukast treatment group were significantly shortened compared with the control group (P<0.05). There was a positive correlation between serum leukotriene B4 and urinary leukotriene E4 levels (r=0.723, P<0.05).. Montelukast has a reliable clinical curative efficacy for bronchiolitis in infants, possibly by decreasing serum leukotriene D4 and urinary leukotriene E4 levels.

Topics: Acetates; Bronchiolitis; Cyclopropanes; Humans; Infant; Leukotriene B4; Leukotriene E4; Quinolines; Sulfides

A pilot study (Bisgaard H; Study Group on Montelukast and Respiratory Syncytial Virus. A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis. Am J Respir Crit Care Med 2003;167:379-383) reported the efficacy of montelukast in post-respiratory syncytial virus (RSV) bronchiolitic respiratory symptoms.. To evaluate the efficacy and safety of montelukast, 4 and 8 mg, in treating recurrent respiratory symptoms of post-RSV bronchiolitis in children in a large, multicenter study.. This was a double-blind study of 3- to 24-month-old children who had been hospitalized for a first or second episode of physician-diagnosed RSV bronchiolitis and who tested positive for RSV. Patients (n = 979) were randomized to placebo or to montelukast at 4 or 8 mg/day for 4 weeks (period I) and 20 weeks (period II). The primary end point was percentage symptom-free days (%SFD; day with no daytime cough, wheeze, and shortness of breath, and no nighttime cough).. No significant differences were seen between montelukast and placebo in %SFD over period I: mean +/- SD for placebo and for montelukast at 4 and 8 mg were 37.0 +/- 30.7, 38.6 +/- 30.4, and 38.5 +/- 29.9, respectively. Least-squares mean differences (95% confidence interval) between montelukast (4 mg) and placebo and between montelukast (8 mg) and placebo were 1.9% (-2.9, 6.7) and 1.6% (-3.2, 6.5), respectively. Secondary end points were similar across treatments. Both doses were generally well tolerated. During the first two treatment weeks, average %SFD was approximately 29%. In post hoc analyses of patients (n = 523) with persistent symptoms (%SFD < or = 30% over Weeks 1-2), differences in %SFD were seen between montelukast and placebo over Weeks 3-24: difference were 5.7 (0.0, 11.3) for montelukast (4 mg) minus placebo and 5.9 (0.1, 11.7) for montelukast (8 mg) minus placebo.. In this study, montelukast did not improve respiratory symptoms of post-RSV bronchiolitis in children.

Topics: Acetates; Bronchiolitis; Child, Preschool; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Infant; Leukotriene Antagonists; Male; Pilot Projects; Quinolines; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Retrospective Studies; Severity of Illness Index; Sulfides; Treatment Outcome

Cysteinyl leukotrienes are implicated in the inflammation of bronchiolitis. Recently, a specific cysteinyl leukotriene receptor antagonist, montelukast (Singulair [MSD, Haarlem, Netherlands]), has been approved for infants in granule sachets.. Our goal was to evaluate the effect of montelukast on clinical progress and on cytokines in acute bronchiolitis.. This was a randomized, placebo-controlled, double-blind, parallel-group study in 2 medical centers. Fifty-three infants (mean age: 3.8+/-3.5 months) with a first episode of acute bronchiolitis were randomly assigned to receive either 4-mg montelukast sachets or placebo, every day, from hospital admission until discharge. The primary outcome was length of stay, and secondary outcomes included clinical severity score (maximum of 12) and changes in type 1 and 2 cytokine levels (including interleukin4/IFN-gamma ratio as a surrogate for the T-helper 2/T-helper 1 ratio) in nasal lavage.. Both groups were comparable at baseline, and cytokine levels correlated positively with disease severity. There were neither differences in length of stay (4.63+/-1.88 [placebo group] vs 4.65+/-1.97 days [montelukast group]) nor in clinical severity score and cytokine levels between the 2 groups. No differences in interleukin 4/IFN-gamma ratio between the 2 groups were seen. There was a slight tendency for infants in the montelukast group to recover more slowly than those in the placebo group (clinical severity score at discharge: 6.1+/-2.4 vs 4.8+/-2.2, respectively).. Montelukast did not improve the clinical course in acute bronchiolitis. No significant effect of montelukast on the T-helper 2/T-helper 1 cytokine ratio when given in the early acute phase could be demonstrated.

Topics: Acetates; Acute Disease; Bronchiolitis; Cross-Over Studies; Cyclopropanes; Cytokines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Delivery Systems; Female; Follow-Up Studies; Hospitalization; Humans; Infant; Infant, Newborn; Inflammation Mediators; Leukotriene Antagonists; Male; Probability; Prospective Studies; Quinolines; Severity of Illness Index; Statistics, Nonparametric; Sulfides; Treatment Outcome

The single-dose pharmacokinetics of montelukast 4-mg oral granules and tolerability of daily administration of 2 different doses of montelukast (4 mg and 8 mg given once daily for 7 days) versus placebo were evaluated in 12 infants 1 to 3 months of age with bronchiolitis or a history of bronchiolitis and asthma-like symptoms. The population area under the concentration-time curve estimate after a single 4-mg dose of montelukast was 13 195.7 +/- 2309.8 (standard error) ng.hr/mL, 3.6 times higher than historical values in infants 3 to 24 months of age. Six patients had 10 total clinical adverse experiences; none was considered serious or drug related. Three patients had transient drug-related increases in aspartate aminotransferase (montelukast 8 mg [n = 2]; placebo [n = 1]). Despite increased systemic exposure after administration of a single dose of montelukast 4-mg oral granules in infants 1 to 3 months of age compared with that in pediatric patients 3 to 24 months of age, administration of montelukast at 4 and 8 mg once daily for 7 days in 1- to 3-month-old infants was generally well tolerated.

Topics: Acetates; Anti-Asthmatic Agents; Area Under Curve; Asthma; Bronchiolitis; Child, Preschool; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Infant; Male; Nonlinear Dynamics; Powders; Quinolines; Sulfides

The single-dose population estimate of the area under the concentration-time curve (AUC(pop)) from time zero to infinity (AUC(0-infinity)), maximum plasma concentration (C(max)), and time to C(max) (t(max)) of montelukast 4-mg oral granules were investigated in infants aged 3 to 6 months. Montelukast concentrations were quantitated after a single 4-mg dose of montelukast oral granules. Pharmacokinetic parameters were determined using a population-based approach with a nonlinear mixed-effect, 1-compartment model with first-order absorption and elimination. Ninety-five percent confidence intervals for the AUC(pop) ratio (3 to 6 months/6 to 24 months) were determined. Safety and tolerability were assessed. Montelukast 4-mg oral granules in children 3 to 6 months of age yielded systemic exposure (AUC(pop) = 3644.3 +/- 481.5 ng x h/mL) similar to that observed in children aged 6 to 24 months (3226.6 +/- 250.0 ng x h/mL). Systemic exposure after a 4-mg dose of montelukast as oral granules is similar in children aged 3 to 6 months and 6 to 24 months.

Topics: Acetates; Anti-Asthmatic Agents; Bronchiolitis; Cyclopropanes; Double-Blind Method; Female; Humans; Infant; Leukotriene Antagonists; Male; Quinolines; Sulfides

Severe bronchiolitis is often associated with subsequent respiratory morbidity, mainly recurrent wheezing and asthma. However, the underlying immune mechanisms remain unclear. The main goal of this study was to investigate the association of nasal detection of periostin and thymic stromal lymphopoietin (TSLP) during severe bronchiolitis with the development of asthma at 4 years of age.. Observational, longitudinal, post-bronchiolitis, hospital-based, follow-up study. Children hospitalized for bronchiolitis between October/2013 and July/2017, currently aged 4 years, included in a previous study to investigate the nasal airway secretion of TSLP and periostin during bronchiolitis, were included. Parents were contacted by telephone, and were invited to a clinical interview based on a structured questionnaire to obtain information on the respiratory evolution. The ISAAC questionnaire for asthma symptoms for 6-7-year-old children, was also employed.. A total of 248 children were included (median age 4.4 years). The mean age at admission for bronchiolitis was 3.1 (IQR: 1.5-6.5) months. Overall, 21% had ever been diagnosed with asthma and 37% had wheezed in the last 12 months. Measurable nasal TSLP was detected at admission in 27(11%) cases and periostin in 157(63%). The detection of nasal TSLP was associated with the subsequent prescription of maintenance asthma treatment (p = 0.04), montelukast (p = 0.01), and the combination montelukast/inhaled glucocorticosteroids (p = 0.03). Admissions for asthma tended to be more frequent in children with TSLP detection (p = 0.07). In the multivariate analysis, adjusting for potential confounders, the detection of TSLP remained independently associated with chronic asthma treatment prescription (aOR:2.724; CI 1.051-7.063, p:0.04) and with current asthma (aOR:3.41; CI 1.20-9.66, p:0.02). Nasal detection of periostin was associated with lower frequency of ever use of short-acting beta2-agonists (SABA) (p = 0.04), lower prevalence of current asthma (p = 0.02), less prescription of maintenance asthma treatment in the past 12 months (p = 0.02, respectively). In the multivariate analysis, periostin was associated with lower risk of asthma at 4 years, independently of the atopic status (aOR:0.511 CI 95% 0.284-0.918, p:0.025).. Our results show a positive correlation between nasal TSLP detection in severe bronchiolitis and the presence of current asthma, prescription of asthma maintenance treatment and respiratory admissions up to the age of 4 years. By contrast, we found a protective association between nasal periostin detection and current asthma at 4 years, ever diagnosis of asthma, maintenance asthma treatment prescription, and respiratory admissions.

Topics: Asthma; Bronchiolitis; Child; Child, Preschool; Cytokines; Follow-Up Studies; Humans; Infant; Respiratory Syncytial Virus Infections; Thymic Stromal Lymphopoietin