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Current status of therapy with omalizumab in children.

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Current status of therapy with omalizumab in children.

Curr Opin Allergy Clin Immunol. 2014 Feb 14;

Authors: Baena-Cagnani CE, Gómez RM

Abstract
PURPOSE OF REVIEW: There are a considerable number of patients with moderate-to-severe uncontrolled asthma needing additional therapy. Omalizumab, an anti-IgE monoclonal antibody, improves control while reducing IgE-mediated airway inflammation and potentially interfering in the progressive remodeling process. The clinical implications are reductions in the required doses of inhaled steroids, a decrease in exacerbation number, and a reduction in emergency room visits and hospitalizations. In addition to its use in asthma, there is an increasing interest on the use of omalizumab for other uncontrolled IgE-mediated diseases, supported by the favorable risk-benefit background. The present review explores the most recent publications on the use of omalizumab for allergic asthma and other atopic conditions in children.
RECENT FINDINGS: Omalizumab has also shown efficacy in allergic rhinitis, and it is being investigated in the treatment of anaphylaxis, food allergy, atopic dermatitis, and chronic spontaneous urticaria, as well as cystic fibrosis and allergic bronchopulmonary aspergillosis. Despite the benefits shown so far, more data are needed for optimal use in these conditions, particularly looking at the safety issues that have to be confirmed.
SUMMARY: Confirmatory evidence on the efficacy and safety of omalizumab in children is reviewed, as well as newest fields of applicability in which IgE is involved in disease mechanism.

PMID: 24535142 [PubMed - as supplied by publisher]

Gut microbiota and allergic disease: new findings.

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Gut microbiota and allergic disease: new findings.

Curr Opin Clin Nutr Metab Care. 2014 Feb 15;

Authors: West CE

Abstract
PURPOSE OF REVIEW: Disturbed gut colonization patterns are proposed to be associated with the development of allergic disease.
RECENT FINDINGS: Studies using new systems biology methods confirm previous findings that early environmental exposures, for example cesarean delivery, are associated with disturbed gut colonization patterns and reduced microbial diversity. Low microbial diversity in infancy is also observed to precede onset of allergic disease. In a large population-based cohort study, probiotic consumption in pregnancy was associated with reduced risk of eczema and rhinoconjunctivitis in the child, but not asthma. The association between probiotics and rhinoconjunctivitis appeared stronger if both mother and child (from 6 months) consumed probiotics. Follow-up data from primary prevention studies with probiotics do not support a role for probiotics in asthma prevention. In meta-analyses, both prebiotics (high-risk infants only) and probiotics modestly reduce the eczema risk, but no other allergic manifestations. Their use is not generally recommended for prevention, or treatment, of allergic disease.
SUMMARY: Gut microbial patterns are associated with susceptibility to allergic disease, but the incomplete understanding of what constitutes a healthy gut microbiota that promotes tolerance, remains a challenge. Further understanding of gut microbial functions may pave the way for more effective allergy prevention and treatment strategies.

PMID: 24535216 [PubMed - as supplied by publisher]

The complex relationship between inflammation and lung function in severe asthma.

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The complex relationship between inflammation and lung function in severe asthma.

Mucosal Immunol. 2014 Feb 19;

Authors: Manni ML, Trudeau JB, Scheller EV, Mandalapu S, Elloso MM, Kolls JK, Wenzel SE, Alcorn JF

Abstract
Asthma is a common respiratory disease affecting ∼300 million people worldwide. Airway inflammation is thought to contribute to asthma pathogenesis, but the direct relationship between inflammation and airway hyperresponsiveness (AHR) remains unclear. This study investigates the role of inflammation in a steroid-insensitive, severe allergic airway disease model and in severe asthmatics stratified by inflammatory profile. First, we used the T-helper (TH)-17 cells adoptive transfer mouse model of asthma to induce pulmonary inflammation, which was lessened by tumor necrosis factor (TNF)-α neutralization or neutrophil depletion. Although decreased airspace inflammation following TNFα neutralization and neutrophil depletion rescued lung compliance, neither intervention improved AHR to methacholine, and tissue inflammation remained elevated when compared with control. Further, sputum samples were collected and analyzed from 41 severe asthmatics. In severe asthmatics with elevated levels of sputum neutrophils, but low levels of eosinophils, increased inflammatory markers did not correlate with worsened lung function. This subset of asthmatics also had significantly higher levels of TH17-related cytokines in their sputum compared with severe asthmatics with other inflammatory phenotypes. Overall, this work suggests that lung compliance may be linked with cellular inflammation in the airspace, whereas T-cell-driven AHR may be associated with tissue inflammation and other pulmonary factors.Mucosal Immunology advance online publication, 19 February 2014; doi:10.1038/mi.2014.8.

PMID: 24549277 [PubMed - as supplied by publisher]

Digital Asthma Self-Management Interventions: A Systematic Review.

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Digital Asthma Self-Management Interventions: A Systematic Review.

J Med Internet Res. 2014;16(2):e51

Authors: Morrison D, Wyke S, Agur K, Cameron EJ, Docking RI, Mackenzie AM, McConnachie A, Raghuvir V, Thomson NC, Mair FS

Abstract
BACKGROUND: Many people with asthma tolerate symptoms and lifestyle limitations unnecessarily by not utilizing proven therapies. Better support for self-management is known to improve asthma control, and increasingly the Internet and other digital media are being used to deliver that support.
OBJECTIVE: Our goal was to summarize current knowledge, evidenced through existing systematic reviews, of the effectiveness and implementation of digital self-management support for adults and children with asthma and to examine what features help or hinder the use of these programs.
METHODS: A comprehensive search strategy combined 3 facets of search terms: (1) online technology, (2) asthma, and (3) self-management/behavior change/patient experience. We undertook searches of 14 databases, and reference and citation searching. We included qualitative and quantitative systematic reviews about online or computerized interventions facilitating self-management. Title, abstract, full paper screening, and quality appraisal were performed by two researchers independently. Data extraction was undertaken using standardized forms.
RESULTS: A total of 3810 unique papers were identified. Twenty-nine systematic reviews met inclusion criteria: the majority were from the United States (n=12), the rest from United Kingdom (n=6), Canada (n=3), Portugal (n=2), and Australia, France, Spain, Norway, Taiwan, and Greece (1 each). Only 10 systematic reviews fulfilled pre-determined quality standards, describing 19 clinical trials. Interventions were heterogeneous: duration of interventions ranging from single use, to 24-hour access for 12 months, and incorporating varying degrees of health professional involvement. Dropout rates ranged from 5-23%. Four RCTs were aimed at adults (overall range 3-65 years). Participants were inadequately described: socioeconomic status 0/19, ethnicity 6/19, and gender 15/19. No qualitative systematic reviews were included. Meta-analysis was not attempted due to heterogeneity and inadequate information provision within reviews. There was no evidence of harm from digital interventions. All RCTs that examined knowledge (n=2) and activity limitation (n=2) showed improvement in the intervention group. Digital interventions improved markers of self care (5/6), quality of life (4/7), and medication use (2/3). Effects on symptoms (6/12) and school absences (2/4) were equivocal, with no evidence of overall benefits on lung function (2/6), or health service use (2/15). No specific data on economic analyses were provided. Intervention descriptions were generally brief making it impossible to identify which specific "ingredients" of interventions contribute most to improving outcomes.
CONCLUSIONS: Digital self-management interventions show promise, with evidence of beneficial effects on some outcomes. There is no evidence about utility in those over 65 years and no information about socioeconomic status of participants, making understanding the "reach" of such interventions difficult. Digital interventions are poorly described within reviews, with insufficient information about barriers and facilitators to their uptake and utilization. To address these gaps, a detailed quantitative systematic review of digital asthma interventions and an examination of the primary qualitative literature are warranted, as well as greater emphasis on economic analysis within trials.

PMID: 24550161 [PubMed - as supplied by publisher]

Shared clinician-patient decision-making about treatment of pediatric asthma: what do we know and how can we use it?

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Shared decision-making (SDM) is an emerging field that promises to improve healthcare. We aim to explore the concept of SDM, how it has been studied or applied in the treatment of asthma, and how it might be implemented to improve adherence and outcomes in pediatric asthma.

RECENT FINDINGS: Healthcare providers often fail to involve their patients in clinical decision-making by not presenting all available options, associated risks and benefits, in light of the patient's values, preferences, concerns, lifestyle, and perceived barriers to following various treatment regimens. It has been argued that SDM is preferable to a clinician-controlled approach and may improve patient outcomes (increase satisfaction with care, reduce decisional conflict and decisional regret, improve health-related quality of life, and increase decision-specific knowledge). This may be especially important in managing chronic conditions in which adherence to treatment regimen may increase if the patient was actively involved in the decision-making. In pediatrics, the decision process is further complicated by the clinician-parent(s)-child interaction. We found no studies on how to effectively involve and communicate with children at different developmental levels, or how to coalesce the parent and child's perspective to work as a unit.

SUMMARY: SDM has the promise to improve satisfaction with disease management, treatment adherence and patient-centered outcomes in pediatric asthma, but further research is needed to determine its effectiveness and to establish guidelines on how to implement SDM in the clinical setting and incorporate the input and preferences of all stakeholders' perspectives.

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