-
The Journal of Allergy and Clinical... Jan 2013Allergic eye diseases are common and cause significant morbidity. Leukotrienes are implicated in the pathogenesis of seasonal and perennial allergic conjunctivitis (AC),... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Allergic eye diseases are common and cause significant morbidity. Leukotrienes are implicated in the pathogenesis of seasonal and perennial allergic conjunctivitis (AC), commonly seen in conjunction with allergic rhinitis, and in vernal keratoconjunctivitis and atopic keratoconjunctivitis.
OBJECTIVES
To assess the available evidence for an effect of leukotriene receptor antagonists (LTRAs) on the ocular symptoms of allergic eye diseases.
METHODS
Selected studies, identified with systematic review search methods, were single/double-blind, randomized, controlled trials that compared LTRAs with other common treatments.
RESULTS
Eighteen trials, using the LTRA montelukast (in AC only), were identified. Six studies were suitable for meta-analysis, in patients with seasonal AC [treated over a 2-week period, symptoms scored 0 (mild) to 3 (severe)]. These trials were at low risk of bias without significant heterogeneity. Six trials were analyzed and showed that montelukast improved patients' ocular symptoms to a greater extent than placebo, with a difference in mean change-from-baseline score of -0.10 (95% CI, -0.14 to -0.07; P < .00001). Three trials compared montelukast with oral antihistamine. The difference in mean change-from-baseline score was 0.08 (95% CI, 0.02 to 0.14; P = .007), in favor of antihistamines. Two trials compared montelukast and oral antihistamine with placebo. The difference in mean change-from-baseline score was -0.30 (95% CI, -0.38 to -0.21; P < .00001), in favor of combination treatment.
CONCLUSIONS
In seasonal AC LTRAs are more efficacious than placebo but less efficacious than oral antihistamines in adult patients. Clinical trials should be conducted to determine whether combination treatment with LTRA and oral antihistamine has a synergistic effect. Further research is required to clarify the role of LTRAs in other allergic eye diseases.
Topics: Adolescent; Adult; Anti-Asthmatic Agents; Child; Child, Preschool; Conjunctivitis, Allergic; Histamine Antagonists; Humans; Leukotriene Antagonists; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 24229824
DOI: 10.1016/j.jaip.2012.07.001 -
Pediatric Allergy and Immunology :... Mar 2014Infants often develop reactive airway diseases subsequent to respiratory syncytial virus (RSV) bronchiolitis. Cysteinyl leukotrienes (cysLTs), a class of lipid mediators... (Meta-Analysis)
Meta-Analysis Review
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-bronchiolitis patients. The small number of enrolled participants and the inability to pool all clinical outcomes precludes us from making solid recommendations.
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
PubMed: 24118637
DOI: 10.1111/pai.12124 -
The Cochrane Database of Systematic... Oct 2013In the treatment of children with mild persistent asthma, low-dose inhaled corticosteroids (ICS) are recommended as the preferred monotherapy (referred to as step 2 of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In the treatment of children with mild persistent asthma, low-dose inhaled corticosteroids (ICS) are recommended as the preferred monotherapy (referred to as step 2 of therapy). In children with inadequate asthma control on low doses of ICS (step 2), asthma management guidelines recommend adding an anti-leukotriene agent to existing ICS as one of three therapeutic options to intensify therapy (step 3).
OBJECTIVES
To compare the efficacy and safety of the combination of anti-leukotriene agents and ICS to the use of the same, an increased, or a tapering dose of ICS in children and adolescents with persistent asthma who remain symptomatic despite the use of maintenance ICS. In addition, we wished to determine the characteristics of people or treatments, if any, that influenced the magnitude of response attributable to the addition of anti-leukotrienes.
SEARCH METHODS
We identified trials from the Cochrane Airways Group Specialised Register of Trials (CAGR), which were derived from systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, AMED, and CINAHL; and the handsearching of respiratory journals and meeting abstracts, as well as the www.clinicaltrials.gov website. The search was conducted until January 2013.
SELECTION CRITERIA
We considered for inclusion randomised controlled trials (RCTs) conducted in children and adolescents, aged one to 18 years, with asthma, who remained symptomatic despite the use of a stable maintenance dose of ICS and in whom anti-leukotrienes were added to the ICS if they were compared to the same, an increased, or a tapering dose of ICS for at least four weeks.
DATA COLLECTION AND ANALYSIS
We used standard methods expected by The Cochrane Collaboration.
MAIN RESULTS
Five paediatric (parallel group or cross-over) trials met the inclusion criteria. We considered two (40%) trials to be at a low risk of bias. Four published trials, representing 559 children (aged ≥ six years) and adolescents with mild to moderate asthma, contributed data to the review. No trial enrolled preschoolers. All trials used montelukast as the anti-leukotriene agent administered for between four and 16 weeks. Three trials evaluated the combination of anti-leukotrienes and ICS compared to the same dose of ICS alone (step 3 versus step 2). No statistically significant group difference was observed in the only trial reporting participants with exacerbations requiring oral corticosteroids over four weeks (N = 268 participants; risk ratio (RR) 0.80, 95% confidence interval (CI) 0.34 to 1.91). There was also no statistically significant difference in percentage change in FEV₁ (forced expiratory volume in 1 second) with mean difference (MD) 1.3 (95% CI -0.09 to 2.69) in this trial, but a significant group difference was observed in the morning (AM) and evening (PM) peak expiratory flow rates (PEFR): N = 218 participants; MD 9.70 L/min (95% CI 1.27 to 18.13) and MD 10.70 (95% CI 2.41 to 18.99), respectively. One trial compared the combination of anti-leukotrienes and ICS to a higher-dose of ICS (step 3 versus step 3). No significant group difference was observed in this trial for participants with exacerbations requiring rescue oral corticosteroids over 16 weeks (N = 182 participants; RR 0.82, 95% CI 0.54 to 1.25), nor was there any significant difference in exacerbations requiring hospitalisation. There was no statistically significant group difference in withdrawals overall or because of any cause with either protocol. No trial explored the impact of adding anti-leukotrienes as a means to taper the dose of ICS.
AUTHORS' CONCLUSIONS
The addition of anti-leukotrienes to ICS is not associated with a statistically significant reduction in the need for rescue oral corticosteroids or hospital admission compared to the same or an increased dose of ICS in children and adolescents with mild to moderate asthma. Although anti-leukotrienes have been licensed for use in children for over 10 years, the paucity of paediatric trials, the absence of data on preschoolers, and the variability in the reporting of relevant clinical outcomes considerably limit firm conclusions. At present, there is no firm evidence to support the efficacy and safety of anti-leukotrienes as add-on therapy to ICS as a step-3 option in the therapeutic arsenal for children with uncontrolled asthma symptoms on low-dose ICS.
Topics: Acetates; Adolescent; Asthma; Child; Cyclopropanes; Drug Therapy, Combination; Humans; Leukotriene Antagonists; Quinolines; Randomized Controlled Trials as Topic; Sulfides
PubMed: 24089325
DOI: 10.1002/14651858.CD009585.pub2 -
Der Hautarzt; Zeitschrift Fur... Sep 2013In November 2012, the 4th International Consensus Meeting on Urticaria ("URTICARIA 2012") took place in Berlin with more than 300 participants. The international and the... (Review)
Review
[Diagnosis and therapy of chronic urticaria-what is expected from the revision and update of the international guidelines? A report of the public consensus conference "URTICARIA 2012"].
In November 2012, the 4th International Consensus Meeting on Urticaria ("URTICARIA 2012") took place in Berlin with more than 300 participants. The international and the German guidelines for the definition, classification, diagnosis and management of urticaria are currently being developed based on this meeting. At the time of publication of this article, the guidelines are in the final process of international coordination. The previous international guidelines were updated based on prepared questions as well as a systematic review of the literature by an expert panel. The individual aspects were then discussed with all participants and decided upon, based on the Delphi method with general discussion and open poll. Here, at least a 75 % agreement was required. The new consensus modifies the previous international guidelines on classification and diagnosis and especially on therapy. The treatment algorithm has been changed to a three step approach. The first step is a second generation H1 antihistamine in standard dosage. The second step is increasing the dose up to 4 times the standard dose. In the third step, additional treatment with omalizumab, cyclosporine A or montelukast is recommended as well as possibly systemic corticosteroids for a maximum of 7-10 days. H2 antihistamines and dapsone, which were included in the previous guideline as standard therapies, are no longer recommended for use by the updated and revised guidelines.
Topics: Allergy and Immunology; Chronic Disease; Dermatology; Histamine H1 Antagonists; Humans; Immunologic Factors; Internationality; Practice Guidelines as Topic; Urticaria
PubMed: 24022627
DOI: 10.1007/s00105-013-2628-8 -
JAMA Pediatrics Apr 2013Although the question of whether early diagnosis and treatment of pediatric allergic rhinitis (AR) improve disease control is important, a more crucial question is... (Review)
Review
IMPORTANCE
Although the question of whether early diagnosis and treatment of pediatric allergic rhinitis (AR) improve disease control is important, a more crucial question is whether we can evaluate the effect of treatment on disease control using an impairment-risk model.
OBJECTIVE
To conduct a systematic review evaluating application of a control model based on domains of impairment and risk (similar to that used for asthma) in pharmacotherapy for children with AR.
EVIDENCE ACQUISITION
We searched the MEDLINE and EMBASE databases (January 1, 1996, through May 31, 2012) for controlled studies lasting 2 weeks or longer in children with confirmed diagnoses of AR, including measures assessing impairment and/or risk of comorbid conditions.
RESULTS
Sixteen controlled clinical trials, including more than 3000 children (aged 2-18 years) with AR (seasonal, n = 2290; perennial, n = 800), met the study criteria. All medication classes improved impairment related to AR, but between-treatment comparisons were limited because of different assessments. Intranasal steroids improved risk outcomes associated with asthma and obstructive sleep apnea. Small single studies suggested possible effects of oral antihistamines on asthma and sleep-disordered breathing. No risk data were available for nasal antihistamines or montelukast sodium.
CONCLUSIONS
Treatment of AR, particularly with intranasal steroids, improves disease control in children by reducing disease-associated impairment and risk. All AR medications with proved efficacy probably improve impairment, paralleling symptom reduction. Intranasal steroids may reduce the likelihood of comorbidities that increase health care use. These observations, although limited by different protocols and outcomes measures among studies, support current practice recommendations. Studies that use standardized measures of impairment to permit better comparison and appropriate protocols for risk evaluation are needed.
Topics: Budesonide; Child; Comorbidity; Early Diagnosis; Glucocorticoids; Health Status Indicators; Humans; Quality of Life; Rhinitis, Allergic, Perennial; Sleep Apnea, Obstructive; Surveys and Questionnaires
PubMed: 23440263
DOI: 10.1001/jamapediatrics.2013.623 -
The Journal of Allergy and Clinical... Mar 2013Traditionally, asthma has been considered a disease that predominantly involves the large airways. Today, this concept is being challenged, and increasing evidence has... (Review)
Review
Traditionally, asthma has been considered a disease that predominantly involves the large airways. Today, this concept is being challenged, and increasing evidence has become available showing that abnormalities in the small airways also contribute to the clinical expression of asthma. The small airways can be affected by inflammation, remodeling, and changes in the surrounding tissue, all contributing to small-airways dysfunction. In this article we have performed a systematic review of the literature on the association between small-airways dysfunction and clinical signs and symptoms of asthma. This review shows that small-airways dysfunction associates with worse control of asthma, higher numbers of exacerbations, the presence of nocturnal asthma, more severe bronchial hyperresponsiveness, exercise-induced asthma, and the late-phase allergic response. Importantly, small-airways dysfunction can already be present in patients with mild asthma. Our review provides suggestive evidence that a better response of the small airways to inhaled steroids or montelukast associates with better asthma control. For this reason, an early recognition of small-airways dysfunction is important because it enables the physician to start timely treatment to target the small airways. It is important to develop simpler and more reliable tools (eg, questionnaires or bronchial provocation tests with small-particle stimuli) to assess the presence and extent of small-airways dysfunction in daily clinical practice.
Topics: Air Pollution; Allergens; Asthma; Bronchial Hyperreactivity; Exercise; Humans; Lung
PubMed: 23380222
DOI: 10.1016/j.jaci.2012.12.1567 -
Journal of Pediatric Health Care :... 2014Inhaled corticosteroids (ICS) are a first-line treatment for mild persistent asthma, but montelukast (MON) monotherapy also has been beneficial. The aim of this review... (Review)
Review
INTRODUCTION
Inhaled corticosteroids (ICS) are a first-line treatment for mild persistent asthma, but montelukast (MON) monotherapy also has been beneficial. The aim of this review is to evaluate current evidence comparing MON versus ICS monotherapy in pediatric patients.
METHOD
A systematic review was conducted of randomized controlled trials evaluating treatment of mild to moderate persistent asthma in which MON was compared with ICS monotherapy in children aged 2 to 18 years. PubMed, the Cumulative Index to Nursing and Allied Health Literature, and the Institute of Scientific Information's Web of Knowledge were searched using key words asthma, MON, and ICS. Studies that met inclusion criteria were appraised for quality.
RESULTS
Of 214 identified studies, eight met inclusion criteria and seven were deemed high quality. Study sample sizes ranged from 62 to 994, 88% were multi-site, and the average length of follow-up was 8.2 months. Asthma symptoms improved with both therapies. Four studies reported superiority of ICS compared with MON; the remaining studies showed no differences between therapies.
DISCUSSION
These results are consistent with the National Asthma Education and Prevention Program (2007) recommendation that ICS therapy should be first-line treatment in children with mild to moderate persistent asthma.
Topics: Acetates; Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Cyclopropanes; Humans; Quinolines; Sulfides
PubMed: 23312367
DOI: 10.1016/j.pedhc.2012.11.005 -
BMJ Clinical Evidence Apr 2011Bronchiolitis is the most common lower respiratory tract infection in infants, occurring in a seasonal pattern, with highest incidence in the winter in temperate... (Review)
Review
INTRODUCTION
Bronchiolitis is the most common lower respiratory tract infection in infants, occurring in a seasonal pattern, with highest incidence in the winter in temperate climates and in the rainy season in warmer countries. Bronchiolitis is a common reason for attendance at and admission to hospital.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of prophylactic interventions for bronchiolitis in high-risk children? What are the effects of measures to prevent transmission of bronchiolitis in hospital? What are the effects of treatments for children with bronchiolitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 59 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, bronchodilators (oral, inhaled salbutamol, inhaled adrenaline [epinephrine], hypertonic saline), chest physiotherapy, continuous positive airway pressure, corticosteroids, fluid management, heliox, montelukast, nasal decongestants, nursing interventions (cohort segregation, hand washing, gowns, masks, gloves, and goggles), oxygen, respiratory syncytial virus immunoglobulins, pooled immunoglobulins, or palivizumab (monoclonal antibody), ribavirin, or surfactants.
Topics: Acute Disease; Administration, Inhalation; Albuterol; Bronchiolitis; Bronchodilator Agents; Double-Blind Method; Epinephrine; Humans; Infant
PubMed: 21486501
DOI: No ID Found -
The Cochrane Database of Systematic... Jan 2011Obstructive sleep apnea (OSA) is characterized by partial or complete upper airway obstruction during sleep. Approximately 1% to 4% of children are affected by OSA, with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Obstructive sleep apnea (OSA) is characterized by partial or complete upper airway obstruction during sleep. Approximately 1% to 4% of children are affected by OSA, with adenotonsillar hypertrophy the most common underlying risk factor. Surgical removal of enlarged tonsils and adenoids is the most commonly used treatment for OSA. Given the perioperative risk of the intervention and an estimated recurrence rate of up to 20%, there has recently been an increased interest in non-surgical treatment modalities. As the enlarged adenoids and tonsils consist of hypertrophied lymphoid tissue, anti-inflammatory agents have been proposed as a useful non-invasive treatment option in children with OSA.
OBJECTIVES
To assess the efficacy of anti-inflammatory drugs for the treatment of OSA in children.
SEARCH STRATEGY
We identified trials using searches of the Cochrane Airways Group Specialized Register, MEDLINE (1950 to 2010), EMBASE (1988 to 2010), CINAHL (1982 to 2010), CENTRAL (1964 to 2010), Web of Science (1900 to 2010), LILACS (1982 to 2010) and International Pharmaceutical Abstracts (IPA) (1970 to 2010).
SELECTION CRITERIA
Randomized controlled trials (RCTs) comparing anti-inflammatory drugs against placebo, other anti-inflammatory drugs, or other treatment in children between one and 16 years with objectively diagnosed OSA (Apnea Hypopnea Index (AHI) ≥ 1/hour (h)).
DATA COLLECTION AND ANALYSIS
Both authors independently performed data extraction and quality assessment. It was not possible to combine data from the included studies; we summarized data in a narrative fashion.
MAIN RESULTS
We included three RCTs. The first study was a six-week parallel-group trial (25 participants, mean age 3.8 years, mean AHI 10.8/h) of intranasal fluticasone versus placebo showed a statistically significant effect of the drug on improving the AHI. The second study compared intranasal budesonide with placebo in a six-week cross-over trial (62 participants, mean age 8.2 years, mean AHI 3.7/h). The authors reported an advantage of the drug over placebo in reducing the AHI. However, the patients were not analyzed as randomized so the result must be interpreted with caution. No valid group comparisons were reported for the third trial (30 participants, oral montelukast versus placebo in a 12-week parallel-group trial), which has so far only been published as an abstract.
AUTHORS' CONCLUSIONS
A single small study has found a short-term beneficial effect on the AHI in children with mild to moderate OSA. However, long-term safety and efficacy data are not available yet. Further RCTs are needed to evaluate anti-inflammatory drugs for OSA in children.
Topics: Acetates; Administration, Intranasal; Administration, Oral; Androstadienes; Anti-Inflammatory Agents; Budesonide; Child; Child, Preschool; Cyclopropanes; Fluticasone; Humans; Quinolines; Randomized Controlled Trials as Topic; Sleep Apnea, Obstructive; Sulfides
PubMed: 21249687
DOI: 10.1002/14651858.CD007074.pub2 -
European Journal of Clinical... Sep 2010The objective of this study was to analyse inter-and intra-country quantitative and qualitative differences in anti-asthmatic prescriptions to children and adolescents. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The objective of this study was to analyse inter-and intra-country quantitative and qualitative differences in anti-asthmatic prescriptions to children and adolescents.
METHODS
A literature search was performed in EMBASE and MEDLINE to identify pharmaco-epidemiological studies published from January 1, 2000 to December 31, 2008 in which anti-asthmatic prescription prevalence in out-hospital children was measured. A meta-analytic weighted average and 95% confidence intervals of prescription prevalences were calculated using a random-effect(s) model. Inter- and intra-country quantitative and, where possible, qualitative prescribing patterns were compared and assessed.
RESULTS
Twelve studies were identified (ten from Europe, one from Canada and one from the USA), but epidemiological indicators varied widely, and only eight were suitable for meta-analysis. The data from these studies revealed inter-country quantitative differences in prescription prevalences in the overall population
CONCLUSIONS
This first overall analysis of anti-asthmatic utilization studies in out-of-hospital children indicates a wide variability in anti-asthmatic prescription prevalence. It also reveals that epidemiological evaluations should be improved by using homogeneous indicators and, in order to validate the use of anti-asthmatic prescription as a proxy of disease, the diagnosis of asthma should accompany the data of prescriptions within the same population.
Topics: Acetates; Adolescent; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Canada; Child; Cromolyn Sodium; Cyclopropanes; Drug Prescriptions; Ethanolamines; Europe; Fluocinolone Acetonide; Fluticasone; Humans; Italy; Prevalence; Quinolines; Salmeterol Xinafoate; Sulfides; United States
PubMed: 20533030
DOI: 10.1007/s00228-010-0845-y