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Inhibiting Interleukin-4 and Interleukin-13 in Difficult-to-Control Asthma.

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Inhibiting Interleukin-4 and Interleukin-13 in Difficult-to-Control Asthma.

N Engl J Med. 2013 May 21;

Authors: Wechsler ME

Abstract
One of the most challenging aspects of the clinical management of asthma is determining how to treat patients whose condition is poorly controlled despite the use of inhaled glucocorticoids and long-acting beta-agonists (LABAs). Although most patients have a response to these treatments, it is estimated that asthma remains poorly controlled in as many as 20% of patients who use combination therapy.(1) Mainstays of the management of difficult-to-control asthma include increased adherence to treatment, avoidance of allergens and other exacerbating factors, and control of common coexisting conditions such as gastrointestinal reflux, postnasal drip, and sinusitis. Other adjuvant therapies currently available include . . .

PMID: 23688322 [PubMed - as supplied by publisher]

Adult Serum Cytokine Concentrations and the Persistence of Asthma.

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Adult Serum Cytokine Concentrations and the Persistence of Asthma.

Int Arch Allergy Immunol. 2013 May 14;161(4):342-350

Authors: Kandane-Rathnayake RK, Tang ML, Simpson JA, Burgess JA, Mészáros D, Feather I, Southey MC, Schroen CJ, Hopper J, Morrison SC, Giles GG, Walters EH, Dharmage SC, Matheson MC

Abstract
Background: Cytokines play a pivotal role in regulating the development and persistence of the inflammatory process in asthma. Our aim was to investigate whether asthma persistence or remission is associated with a specific cytokine profile. Methods: The Tasmanian Longitudinal Health Study followed participants from 7 to 44 years of age. Serum concentrations of interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10 and tumor necrosis factor-alpha (TNF-α) were measured at age 44 years. Participants were categorized into five phenotypes (early-onset noncurrent asthma, early-onset current asthma, late-onset noncurrent asthma and late-onset current asthma). Those who had never had asthma formed the reference group. Multivariable linear regression was used to compare serum cytokine concentrations between each phenotype and the reference group. Results: IL-10 concentrations were significantly lower in serum from the early-onset current asthma group than in the reference group (ratio of geometric means 0.58; 95% confidence interval 0.33-0.99; p = 0.048). IL-6 concentrations for the late-onset remitted group were also significantly lower than in the reference group (p = 0.009). The TNF-α concentrations were significantly lower for both early-and late-onset remitted asthma phenotypes when compared with the reference group. No associations were detected between serum concentrations of IL-4, IL-5 or IL-8 and these specific longitudinal asthma phenotypes. Conclusion: Our findings suggest a possible role for deficient IL-10 responses in the persistence of early-onset asthma. Lower IL-6 and TNF-α concentrations in serum from those with remitted asthma suggest that these proinflammatory cytokines may be actively suppressed during asthma remission.

PMID: 23689759 [PubMed - as supplied by publisher]

Potential of immunoglobulin a to prevent allergic asthma.

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Potential of immunoglobulin a to prevent allergic asthma.

Clin Dev Immunol. 2013;2013:542091

Authors: Gloudemans AK, Lambrecht BN, Smits HH

Abstract
Allergic asthma is characterized by bronchial hyperresponsiveness, a defective barrier function, and eosinophilic lower airway inflammation in response to allergens. The inflammation is dominated by Th2 cells and IgE molecules and supplemented with Th17 cells in severe asthma. In contrast, in healthy individuals, allergen-specific IgA and IgG4 molecules are found but no IgE, and their T cells fail to proliferate in response to allergens, probably because of the development of regulatory processes that actively suppress responses to allergens. The presence of allergen-specific secretory IgA has drawn little attention so far, although a few epidemiological studies point at a reverse association between IgA levels and the incidence of allergic airway disease. This review highlights the latest literature on the role of mucosal IgA in protection against allergic airway disease, the mechanisms described to induce secretory IgA, and the role of (mucosal) dendritic cells in this process. Finally, we discuss how this information can be used to translate into the development of new therapies for allergic diseases based on, or supplemented with, IgA boosting strategies.

PMID: 23690823 [PubMed - in process]

Best strategies to implement clinical pathways in an emergency department setting: study protocol for a cluster randomized controlled trial.

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Best strategies to implement clinical pathways in an emergency department setting: study protocol for a cluster randomized controlled trial.

Implement Sci. 2013 May 22;8(1):55

Authors: Jabbour M, Curran J, Scott SD, Guttman A, Rotter T, Ducharme FM, Lougheed MD, McNaughton-Filion ML, Newton A, Shafir M, Paprica A, Klassen T, Taljaard M, Grimshaw J, Johnson DW

Abstract
BACKGROUND: The clinical pathway is a tool that operationalizes best evidence recommendations and clinical practice guidelines in an accessible format for 'point of care' management by multidisciplinary health teams in hospital settings. While high-quality, expert-developed clinical pathways have many potential benefits, their impact has been limited by variable implementation strategies and suboptimal research designs. Best strategies for implementing pathways into hospital settings remain unknown. This study will seek to develop and comprehensively evaluate best strategies for effective local implementation of externally developed expert clinical pathways.Design/methods: We will develop a theory-based and knowledge user-informed intervention strategy to implement two pediatric clinical pathways: asthma and gastroenteritis. Using a balanced incomplete block design, we will randomize 16 community emergency departments to receive the intervention for one clinical pathway and serve as control for the alternate clinical pathway, thus conducting two cluster randomized controlled trials to evaluate this implementation intervention. A minimization procedure will be used to randomize sites. Intervention sites will receive a tailored strategy to support full clinical pathway implementation. We will evaluate implementation strategy effectiveness through measurement of relevant process and clinical outcomes. The primary process outcome will be the presence of an appropriately completed clinical pathway on the chart for relevant patients. Primary clinical outcomes for each clinical pathway include the following: Asthma---the proportion of asthmatic patients treated appropriately with corticosteroids in the emergency department and at discharge; and Gastroenteritis---the proportion of relevant patients appropriately treated with oral rehydration therapy. Data sources include chart audits, administrative databases, environmental scans, and qualitative interviews. We will also conduct an overall process evaluation to assess the implementation strategy and an economic analysis to evaluate implementation costs and benefits. DISCUSSION: This study will contribute to the body of evidence supporting effective strategies for clinical pathway implementation, and ultimately reducing the research to practice gaps by operationalizing best evidence care recommendations through effective use of clinical pathways.Trial registration: ClinicalTrials.gov: NCT01815710https://register.clinicaltrials.gov.

PMID: 23692634 [PubMed - as supplied by publisher]

Multifactorial intervention for children with asthma and overweight (Mikado): study design of a randomised controlled trial.

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In children, the prevalence's of both obesity and asthma are disconcertingly high. Asthmatic children with obesity are characterised by less asthma control and a high need for asthma medication. As the obese asthmatic child is becoming more common in the clinical setting and the disease burden of the asthma-obesity phenotype is high, there is an increasing need for effective treatment in these children. In adults, weight reduction resulted in improved lung function, better asthma control and less need for asthma medication. In children this is hardly studied.

The Mikado study aims to evaluate the effectiveness of a long term multifactorial weight reduction intervention, on asthma characteristics in children with asthma and a high body weight.

Methods/design: The Mikado study is a two-armed, randomised controlled trial. In total, 104 participants will be recruited via online questionnaires, pulmonary paediatricians, the youth department of the Municipal Health Services and cohorts of existing studies. All participants will be aged 6--16 years, will have current asthma, a Body Mass Index in the overweight or obesity range, and no serious comorbidities (such as diabetes, heart diseases). Participants in the intervention arm will receive a multifactorial intervention of 18 months consisting of sessions concerning sports, parental involvement, individual counselling and lifestyle advices including dietary advices and cognitive behavioural therapy. The control group will receive usual care. The primary outcome variables will include Forced Expiratory Volume in one second and Body Mass Index - Standard Deviation Score. Secondary outcomes will include other lung function parameters (including dynamic and static lung function parameters), asthma control, asthma-specific quality of life, use of asthma medication and markers of systemic inflammation and airway inflammation.

DISCUSSION: In this randomised controlled trial we will study the potential of a multifactorial weight reduction intervention to improve asthma-related outcome measures in asthmatic children with overweight. Moreover, it will provide information about the underlying mechanisms in the relationship between asthma and a high body weight in children. These findings can contribute to optimal management programs and better clinical guidelines for children with asthma and overweight.Trial registration: Clinicaltrial.gov NCT00998413.

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