montelukast and Bronchiolitis--Viral

Infants often develop reactive airway diseases subsequent to respiratory syncytial virus (RSV) bronchiolitis. Cysteinyl leukotrienes (cysLTs), a class of lipid mediators that have been implicated in the pathogenesis of allergic rhinitis and asthma, are released during RSV infection, thereby contributing to the pathogenic changes in airway inflammation. Many pediatric patients, especially those of very young age, continue to have recurrent episodes of lower airway obstruction after bronchiolitis treatment. This study was to systematically review and assessed the efficacy of montelukast for preventing wheezing in patients with post-bronchiolitis. The Cochrane library, PubMed, China National Knowledge Infrastructure (CNKI) periodical databases were screened for studies related to use of montelukast for preventing post-bronchiolitis wheezing published up to 31 December 2012. Randomized controlled trials (RCTs) and quasi-RCTs using montelukast alone as an active intervention in infants up to 24 months of age with post-bronchiolitis were selected. Two authors independently extracted data and assessed trial quality using the recommendations published by the Cochrane Collaboration. The meta-analyses were performed using the Cochrane statistical package RevMan5.0.0. Four trials, containing 1430 infants with confirmed diagnosis of acute bronchiolitis, were analyzed. Patients were administered montelukast at post-bronchiolitis. Three trials showed no effects of montelukast on reducing the incidence of recurrent wheezing risk ratios (RR = 0.78, 95% CI: 0.55-1.12, p = 0.17), while two trials found that montelukast did reduce the frequency of recurrent wheezing and another two trials demonstrated no effects of montelukast on symptom-free days. The pooled montelukast treatment group showed no significant effect on reducing the usage of corticosteroids, as compared to the placebo group (RR = 1.11, 95% CI: 0.85-1.44, p = 0.45). Two trials showed that montelukast significantly decreased serum eosinophil-derived neurotoxin levels, as compared to the control group. In general, the side effects of rash, vomiting, and insomnia caused by montelukast occurred in 1.5% of patients analyzed. The recent evidences indicate that montelukast may reduce the frequency of post-bronchiolitic wheezing without causing significant side effects but that it has no effects on decreasing incidences of recurrent wheezing, symptom-free days, or the associated usage of corticosteroid in post-bronchi

Topics: Acetates; Age Factors; Bronchiolitis, Viral; Chi-Square Distribution; Child, Preschool; Cyclopropanes; Humans; Infant; Infant, Newborn; Leukotriene Antagonists; Odds Ratio; Quinolines; Respiratory Sounds; Respiratory Syncytial Virus Infections; Risk Factors; Sulfides; Treatment Outcome

Topics: Acetates; Asthma; Bronchiolitis, Viral; Cyclopropanes; Cysteine; Humans; Infant; Infant, Newborn; Leukotriene Antagonists; Leukotrienes; Nasopharynx; Quinolines; Respiratory Syncytial Virus Infections; Risk Factors; Sulfides

Topics: Acetates; Acute Disease; Adrenal Cortex Hormones; Antiviral Agents; Bronchiolitis, Viral; Cromolyn Sodium; Cyclopropanes; Humans; Infant; Infant Welfare; Infant, Newborn; Leukotriene Antagonists; Morbidity; Prospective Studies; Quinolines; Respiratory Syncytial Virus Infections; Retrospective Studies; Sulfides

To investigate the effect of montelukast on eosinophil degranulation and recurrent wheezing episodes in post-respiratory syncytial virus (RSV) bronchiolitis.. Two hundred infants (age, 6-24 months) who were hospitalized with their first episode of acute RSV bronchiolitis were randomized in a double-blind, placebo-controlled, parallel comparison of 4-mg montelukast granules (RSV-MONT group) or matching placebo (RSV-PLC group) administered for 3 months. Serum eosinophil-derived neurotoxin (EDN) levels were measured (primary outcome), and recurrent wheezing was documented (secondary outcome) for 12 months. Comparisons were made with control subjects (control group, n = 50).. At the end of the 3-month treatment period, the RSV-PLC group (n = 71) exhibited significantly elevated EDN levels (P < .0001), and the RSV-MONT group (n = 79) showed significantly decreased EDN levels (P < .01) when compared with the initial levels. As a result, EDN levels in the 2 RSV groups significantly differed at this point (P < .0001) and remained different for the entire 12-month follow-up period. Cumulative recurrent wheezing episodes at 12 months were significantly lower in the RSV-MONT group (P = .039).. Montelukast treatment reduces eosinophil degranulation and is associated with a decrease in recurrent wheezing episodes in post-RSV bronchiolitis.

Topics: Acetates; Acute Disease; Bronchiolitis, Viral; Cell Degranulation; Cyclopropanes; Double-Blind Method; Eosinophil-Derived Neurotoxin; Eosinophils; Humans; Infant; Quinolines; Recurrence; Respiratory Sounds; Respiratory Syncytial Virus Infections; Sulfides

To evaluate the long-term effect of montelukast on symptoms of cough and wheeze following RSV bronchiolitis.. Fifty eight patients (aged < or = 24 months) hospitalized with a first episode of RSV bronchiolitis were enrolled in this double blind prospective randomized trial comparing montelukast (n = 31) vs placebo (n = 27).. During the 3-month treatment period, there were no statistical significant differences between the two groups for symptom-free days and nights (48.5 [interquartile range 33.0.0-66.0] for montelukast vs 57.0 [29.0-71.0] for placebo p = 0.415) nor disease-free days and nights (44.5 days [26.0-54.0] vs 53.0 [22.3-71.0]; p = 0.266). During the 1 year follow-up, there were 41 exacerbations in the montelukast group vs 54 exacerbations in the placebo group (p = 0.57). Time to first exacerbation was not different. Number of unscheduled visits and need to start inhaled steroids were comparable in the two groups.. Treatment with montelukast after hospital admission for RSV bronchiolitis in children younger than 2 years of age did not reduce symptoms of cough and wheeze. We cannot exclude that a subgroup of children may, however, benefit from this treatment.

Topics: Acetates; Bronchiolitis, Viral; Bronchodilator Agents; Chi-Square Distribution; Cough; Cyclopropanes; Double-Blind Method; Follow-Up Studies; Hospitalization; Humans; Infant; Prospective Studies; Quinolines; Respiratory Hypersensitivity; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Statistics, Nonparametric; Sulfides; Treatment Outcome

Infants often develop reactive airway disease after respiratory syncytial virus (RSV) bronchiolitis. Cysteinyl-leukotrienes (cys-LT) are released during RSV infection and may contribute to the inflammation. We hypothesized that a cys-LT receptor antagonist would ameliorate reactive airway disease subsequent to RSV bronchiolitis. One hundred and thirty infants who were 3 to 36 months old, hospitalized with acute RSV bronchiolitis, were randomized into a double-blind, parallel comparison of 5-mg montelukast chewable tablets or matching placebo given for 28 days starting within 7 days of symptom debut. Infants with a suspected history of asthma were excluded. One hundred sixteen infants provided diary card data for the treatment period. Median age was 9 months. Infants on montelukast were free of any symptoms on 22% of the days and nights compared with 4% of the days and nights in infants on placebo (p = 0.015). Daytime cough was significantly reduced on active treatment (p = 0.04). Exacerbations were significantly delayed from montelukast compared with placebo (p < 0.05). In conclusion, cys-LT antagonist treatment reduces lung symptoms subsequent to RSV bronchiolitis.

Topics: Acetates; Bronchiolitis, Viral; Cyclopropanes; Double-Blind Method; Female; Humans; Infant; Leukotriene Antagonists; Male; Quinolines; Respiratory Syncytial Virus Infections; Sulfides

We sought to identify predictors of asthma development following severe early childhood RSV bronchiolitis. Different definitions of asthma were also compared.. This longitudinal, observational study (N = 343) followed patients (<2 years old) from a placebo-controlled trial (N = 979) of montelukast after RSV bronchiolitis to identify clinical, demographic, or biochemical predictors of asthma, atopic disorders, and chronic asthma therapy use at 6 years of age (Clinical Trials Registry Number: NCT01140048). Asthma (primary definition) was based on parental identification of wheeze at 6 AND 12 months before 6 years of age; definitions based on physician diagnosis as well as parental identification of wheeze at 6 OR 12 months (to consider seasonal effect) were also assessed. Post-hoc analyses evaluated agreement among asthma diagnosis criteria.. Prevalence of asthma (primary definition by parental identification), asthma (physician diagnosis), atopic disorders, and chronic asthma therapy use (parental identification) was 6.1%, 22.4%, 36.2%, and 14.5%, respectively. Predictors for asthma (primary definition) included male gender, a relative with asthma, and RAST positive for dog dander; for physician diagnosis of asthma, high severity score for RSV bronchiolitis, high respiratory rate, and asthma diagnosis before enrollment. Predictors of atopic disorders included allergic rhinitis before enrollment, a relative with asthma, and the plasma biomarkers IL-5, IL-16, and IL-18. Predictors of chronic asthma therapy use included asthma diagnosis before enrollment and geographic region (Europe and Africa). Only 42% of patients with asthma (primary definition) also met the asthma definition by physician diagnosis and chronic asthma therapy use.. Among children with early RSV bronchiolitis, hereditary factors (i.e., having a relative with asthma) and RSV bronchiolitis severity were predictors of asthma and atopic disorders at 6 years of age. Of interest, there was poor agreement among the asthma definitions evaluated. Pediatr Pulmonol. 2016;51:1382-1392. © 2016 Wiley Periodicals, Inc.

Topics: Acetates; Animals; Anti-Asthmatic Agents; Asthma; Bronchiolitis, Viral; Child; Child, Preschool; Cyclopropanes; Dander; Dogs; Europe; Female; Humans; Hypersensitivity; Hypersensitivity, Immediate; Infant; Interleukin-16; Interleukin-18; Interleukin-5; Longitudinal Studies; Male; Medical History Taking; Prevalence; Prospective Studies; Quinolines; Respiratory Rate; Respiratory Sounds; Respiratory Syncytial Virus Infections; Rhinitis, Allergic; Risk Factors; Severity of Illness Index; Sex Factors; Sulfides

Respiratory syncytial virus (RSV) bronchiolitis in infants may be followed by the development of asthma-like symptoms. Age at first infection dictates consequences upon reinfection. Reinfection of mice initially exposed as neonates to RSV enhanced development of airway hyperresponsiveness (AHR), eosinophilic inflammation, and mucus hyperproduction. RSV lower respiratory tract disease is associated with activation of the leukotriene pathway.. To determine the effects of montelukast (MK), a cysteinyl leukotriene (cysLT) receptor antagonist, in primary and secondary RSV-infected newborn and adult mice.. BALB/c mice were infected with RSV at 1 week (neonate) or 6 to 8 weeks (adult) of age and reinfected 5 weeks later. MK was administered 1 day before the initial infection and through Day 6 after infection. Seven days after primary or secondary infection, airway function was assessed by lung resistance to increasing doses of inhaled methacholine; lung inflammation, goblet cell metaplasia, and cytokine levels in bronchoalveolar lavage fluid were monitored.. RSV infection induced cysLT release in bronchoalveolar lavage fluid. MK decreased RSV-induced AHR, airway inflammation, and increased IFN-gamma production in primary infected adult and neonatal mice. MK, administered during initial infection of neonates but not during secondary infection, prevented subsequent enhancement of AHR, airway eosinophilia, and mucus hyperproduction upon reinfection.. MK attenuated the initial responses to primary RSV infection in both age groups and altered the consequences of RSV reinfection in mice initially infected as neonates. These data support an important role for cysLT in RSV-induced AHR and inflammation.

Topics: Acetates; Animals; Animals, Newborn; Anti-Asthmatic Agents; Bronchiolitis, Viral; Bronchoalveolar Lavage Fluid; Cyclopropanes; Cysteine; Disease Models, Animal; Inflammation; Interferon-gamma; Leukotriene Antagonists; Leukotrienes; Mice; Mice, Inbred BALB C; Quinolines; Recurrence; Respiratory Hypersensitivity; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Sulfides

In this work we have evaluated the clinical responses of pneumovirus-infected mice to combination therapy with the antiviral agent, ribavirin, and the CysLT1 cysteinyl leukotriene receptor antagonist, montelukast. We observed substantial virus replication in our mouse model of pneumovirus infection and significant accumulation of cysteinyl leukotrienes in lung tissue, the latter detected at levels that correlate directly with granulocyte recruitment to the airways. While administration of the nucleoside analog, ribavirin, reduced virus replication approximately 2,000-fold, the clinical outcomes as measured by morbidity and mortality, in response to ribavirin monotherapy were indistinguishable from those of the no-treatment controls. Similarly, montelukast therapy alone did not reduce granulocyte recruitment nor did it improve the clinical outcome. However, combined therapy with ribavirin and montelukast resulted in a significant reduction in morbidity and a substantial reduction in mortality (50% survival at t = 14 days and onward, compared to 10-20% survival in response to montelukast alone or to ribavirin alone, respectively, p < 0.01). These findings define further the independent contributions made by virus replication and by the ensuing inflammatory response to the detrimental sequelae of pneumovirus infection in vivo.

Topics: Acetates; Animals; Antiviral Agents; Bronchiolitis, Viral; Cyclopropanes; Cysteine; Disease Models, Animal; Drug Therapy, Combination; Humans; Leukotriene Antagonists; Leukotrienes; Lung; Mice; Mice, Inbred C57BL; Murine pneumonia virus; Pneumovirus Infections; Quinolines; Ribavirin; Sulfides; Treatment Outcome; Virus Replication

Topics: Acetates; Bronchiolitis, Viral; Child, Preschool; Cyclopropanes; Humans; Quinolines; Respiratory Syncytial Virus Infections; Sulfides

Topics: Acetates; Bronchiolitis, Viral; Cyclopropanes; Humans; Leukotriene Antagonists; Quinolines; Respiratory Syncytial Virus Infections; Sulfides

Topics: Acetates; Bronchiolitis, Viral; Cyclopropanes; Humans; Leukotriene Antagonists; Quinolines; Respiratory Syncytial Virus Infections; Sulfides

Leukotrienes were found to be raised in respiratory syncytial virus bronchiolitis. Montelukast is a cysteinyl leukotrienes antagonist. We report our experience with the use of montelukast in three young children from 5-months to 20-months old. The first case was a 5-month-old boy with previous good health. He had prolonged respiratory distress secondary to adenovirus type 3 infection. The second case was a 20-month-old boy with bronchopulmonary dysplasia. He had respiratory syncytial virus and an adenovirus type 3 infection leading to prolonged wheeze. The third case was a 20-month-old girl with chronic lung disorder after an episode of severe E. coli pneumonia at 1 month old. She developed acute virus-negative severe wheeze after a few days of running nose and low-grade fever. All three cases responded poorly to inhaled steroids and bronchodilators. Addition of montelukast was associated with marked clinical improvement within 1 week. The three cases were very heterogeneous and differed from usual simple virus-induced acute bronchiolitis. The use of multiple drugs including montelukast did not enable any definite conclusions; however, the addition of montelukast was closely related to clinical improvement. Further studies in the use of montelukast in severe virus-induced bronchiolitis are warranted.

Topics: Acetates; Acute Disease; Age Factors; Bronchiolitis, Viral; Cyclopropanes; Female; Humans; Infant; Leukotriene Antagonists; Leukotrienes; Male; Quinolines; Respiratory Sounds; Sulfides; Treatment Outcome