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Beta2-agonists for exercise-induced asthma.

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Beta2-agonists for exercise-induced asthma.

Cochrane Database Syst Rev. 2013 Oct 2;10:CD003564

Authors: Bonini M, Di Mambro C, Calderon MA, Compalati E, Schünemann H, Durham S, Canonica GW

Abstract
BACKGROUND: It is well known that physical exercise can trigger asthma symptoms and can induce bronchial obstruction in people without clinical asthma. International guidelines on asthma management recommend the use of beta2-agonists at any stage of the disease. At present, however, no consensus has been reached about the efficacy and safety of beta2-agonists in the pretreatment of exercise-induced asthma and exercise-induced bronchoconstriction. For the purpose of the present review, both of these conditions are referred to by the acronymous EIA, independently from the presence of an underlying chronic clinical disease.
OBJECTIVES: To assess the effects of inhaled short- and long-acting beta2-agonists, compared with placebo, in the pretreatment of children and adults with exercise-induced asthma (or exercise-induced bronchoconstriction).
SEARCH METHODS: Trials were identified by electronic searching of the Cochrane Airways Group Specialised Register of Trials and by handsearching of respiratory journals and meetings. Searches are current as of August 2013.
SELECTION CRITERIA: We included randomised, double-blind, placebo-controlled trials of any study design, published in full text, that assessed the effects of inhaled beta2-agonists on EIA in adults and children. We excluded studies that did not clearly state diagnostic criteria for EIA.
DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by The Cochrane Collaboration.
MAIN RESULTS: We included 53 trials consisting of 1139 participants. Forty-eight studies used a cross-over design, and five were performed in accordance with a parallel-group design. Forty-five studies addressed the effect of a single beta2-agonist administration, and eight focused on long-term treatment. We addressed these two different intervention regimens as different comparisons.Among primary outcomes for short-term administration, data on maximum fall in forced expiratory volume in 1 second (FEV1) showed a significant protective effect for both short-acting beta-agonists (SABA) and long-acting beta-agonists (LABA) compared with placebo, with a mean difference of -17.67% (95% confidence interval (CI) -19.51% to -15.84%, P = 0.00001, 799 participants from 72 studies). The subgroup analysis of studies performed in adults compared with those performed in children showed high heterogeneity confined to children, despite the comparable mean bronchoprotective effect.Secondary outcomes on other pulmonary function parameters confirmed a more positive and protective effect of beta2-agonists on EIA compared with placebo. Occurrence of side effects was not significantly different between beta2-agonists and placebo.Overall evaluation of the included long-term studies suggests a beta2-agonist bronchoprotective effect for the first dose of treatment. However, long-term use of both SABA and LABA induced the onset of tolerance and decreased the duration of drug effect, even after a short treatment period.
AUTHORS' CONCLUSIONS: Evidence of low to moderate quality shows that beta2-agonists, both SABA and LABA, when administered in a single dose, are effective and safe in preventing EIA.Long-term regular administration of inhaled beta2-agonists induces tolerance and lacks sufficient safety data. This finding appears to be of particular clinical relevance in view of the potential for prolonged regular use of beta2-agonists as monotherapy in the pretreatment of EIA, despite the warnings of drug agencies (FDA, EMA) regarding LABA.

PMID: 24089311 [PubMed - as supplied by publisher]

Addition of anti-leukotriene agents to inhaled corticosteroids in children with persistent asthma.

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Addition of anti-leukotriene agents to inhaled corticosteroids in children with persistent asthma.

Cochrane Database Syst Rev. 2013 Oct 2;10:CD009585

Authors: Chauhan BF, Ben Salah R, Ducharme FM

Abstract
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.

PMID: 24089325 [PubMed - as supplied by publisher]

Asthma and risk of non-respiratory tract infection: a population-based case-control study.

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Asthma and risk of non-respiratory tract infection: a population-based case-control study.

BMJ Open. 2013;3(10):e003857

Authors: Bang DW, Yang HJ, Ryoo E, Al-Hasan MN, Lahr B, Baddour LM, Yawn BP, Juhn YJ

Abstract
OBJECTIVES: Asthmatics have increased risks of airway-related infections. Little is known about whether this is true for non-airway-related serious infections such as Escherichia coli bloodstream infection (BSI). We assessed whether asthma is associated with a risk of developing community-acquired E coli BSI.
DESIGN: The study was designed as a population-based retrospective case-control study.
SETTING: This population-based study was conducted in Olmsted County, Minnesota.
PARTICIPANTS: The study included 259 all eligible community-acquired E coli BSI cases in Olmsted County, MN between 1998 and 2007 and 259 birthday-matched, gender-matched and residency-matched controls.
PRIMARY AND SECONDARY OUTCOME MEASURES: Only community-acquired E coli BSI cases as the primary outcome was included. Asthma status as an exposure was ascertained by predetermined criteria. An adjusted OR and 95% CI for the association between asthma and risk of community-acquired E coli BSI was calculated using conditional logistic regression.
RESULTS: Of 259 eligible cases, 179 (69%) were women and mean age was 61±22 years. Of the 259 cases 37 (14%) and 16 (6%) of 259 controls had a prior history of asthma (adjusted OR 2.74; 95% CI 1.11 to 6.76; p=0.029). The population attributable risk of asthma for community-acquired E coli BSI was 9%. Although not statistically significant, there was a borderline association between having a history of food allergy and increased risk of community-acquired E coli BSI (6% vs 2%; adjusted OR 3.51; 95% CI 0.94 to 13.11; p=0.062).
CONCLUSIONS: Based on the findings of the current population-based, case-control investigation, a history of asthma may be associated with risk of community-acquired E coli BSI. The impact of asthma on risk of microbial infections may go beyond airways.

PMID: 24091424 [PubMed - as supplied by publisher]

Abnormal small airways function in children with mild asthma.

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Abnormal small airways function in children with mild asthma.

Chest. 2013 Oct 3;

Authors: Singer F, Abbas C, Yammine S, Casaulta C, Frey U, Latzin P

Abstract
ABSTRACT BACKGROUND: Small airways disease is a hallmark in adults with persistent asthma but little is known on small airways function in children with mild asthma and normal spirometry. We assessed ventilation heterogeneity, a marker of small airways function, using an easy tidal breath single-breath washout (SBW) technique in school-aged children with mild asthma and normal FEV1 and healthy age-matched controls.
METHODS: Primary outcome was the double-tracer gas phase III slope (SDTG), an index of ventilation heterogeneity in acinar airways derived from the tidal double-tracer gas SBW test. The second outcome was the nitrogen phase III slope (SN2), an index of global ventilation heterogeneity derived from the tidal nitrogen SBW test using pure oxygen. Triplicate SBW and spirometry tests were performed in healthy (n = 35) and asthmatic children (n = 31) at baseline and in asthmatic children after bronchodilation.
RESULTS: Acinar (SDTG) but not global (SN2) ventilation heterogeneity was significantly increased in asthma despite normal FEV1. SDTG was abnormal (≤-2 z-scores) in 11/31 asthmatic children, FEF25-75 in 3/31 and FEV1 in 0/31. After bronchodilaton, SDTG, SN2, and FEF25-75 and FEV1 significantly changed: Average (95% CI) change given as percentage from baseline was 36 (15-56)%, 38 (18-58)%, 17 (9-25)% and 6 (3-9)%, respectively.
CONCLUSION: Abnormal acinar ventilation heterogeneity in one third of children suggests that small airways disease may be present despite rare and mild asthma symptoms and normal spirometry. The easy tidal SBW technique has considerable potential as a clinical and research outcome in children with asthma.

PMID: 24091465 [PubMed - as supplied by publisher]

Is Asthma an Infectious Disease? New Evidence.

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Is Asthma an Infectious Disease? New Evidence.

Curr Allergy Asthma Rep. 2013 Oct 3;

Authors: Atkinson TP

Abstract
The pathogenetic mechanisms leading to asthma are likely to be diverse, influenced by multiple genetic polymorphisms as well as elements of the environment. Recent data on the microbiome of the airway have revealed intriguing differences between the number and diversity of microbial populations in healthy persons and asthmatics. There is convincing evidence that early viral infections, particularly with human rhinovirus and respiratory syncytial virus, are often associated with the development of chronic asthma and with exacerbations. Recent studies suggest that two unrelated types of atypical bacteria, Mycoplasma pneumoniae (Mpn) and Chlamydia pneumoniae, are present in the airways of a substantial proportion of the population, bringing up the possibility that the persistent presence of the organism may contribute to the asthmatic phenotype in a subset of patients. This review will examine the current data regarding a possible role for infection in chronic asthma with a particular focus on atypical bacterial infections.

PMID: 24091724 [PubMed - as supplied by publisher]

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