Quality of life associated with maternal anxiety disorder in Russian children and adolescents with food allergy.

BACKGROUND: Food allergy negatively impacts the quality of life (QoL) and has been associated with increased maternal anxiety. There is currently a lack of data assessing QoL of food-allergic children and adolescents in Russia. We aimed to evaluate the performance of the Food Allergy Quality of Life Questionnaire (FAQLQ) measures in a Russian sample of children, adolescents, and mothers and to investigate association between child QoL and maternal general anxiety. METHODS: FAQLQ and Food Allergy Independent Measures (FAIM) were translated to Russian to be completed by participants. Mothers also filled the General Anxiety Disorder (GAD-7) questionnaire. Reliability, construct, and discriminant validity of the FAQLQs and association between FAQLQ scores and general anxiety were assessed. RESULTS: A total of 142 participants completed FAQLQ and FAIM. In total, 126 mothers completed GAD-7 questionnaire. All FAQLQs showed excellent internal consistency (α > 0.94). The means for the FAQLQ-PF, FAQLQ-CF, and FAQLQ-TF varied according to the number of foods avoided, severity of symptoms, and FAIM and GAD scores (ηp2 0.40 P < .001). One in 5 mothers had GAD-7 score indicative of moderate-to-severe anxiety. Association strength between GAD and FAQLQ increased with age. GAD score was associated with FAQLQ-PF score, controlling for multiple confounders. CONCLUSION: The FAQLQ showed good reliability and validity in Russian. This study identified number of foods avoided and reported reaction severity being associated with greater QoL impairment in Russian children and adolescents affected by food allergy. The significant association found between general anxiety in parents and QoL in children and adolescents has practice, screening, and resource implications.

Short-term subcutaneous grass pollen immunotherapy under the umbrella of anti-IL-4: A randomized controlled trial.

BACKGROUND: Allergen immunotherapy is currently the only disease-modifying treatment available for allergic rhinitis and allergic asthma. OBJECTIVES: We sought to evaluate the induction of sustained tolerance to allergen when anti-IL-4 was combined with a suboptimal course of grass pollen subcutaneous immunotherapy (SCIT) using the allergen-induced skin late-phase response (LPR) and exploratory immune monitoring as surrogate markers of therapeutic response. METHODS: In this randomized, double-blind, 3-group parallel design trial, 37 participants with seasonal allergic rhinitis received suboptimal SCIT (30,000 standardized quality units) in combination with anti-IL-4 (VAK694) and suboptimal SCIT (30,000 standardized quality units) plus placebo antibody or double placebo (placebo SCIT and placebo antibody) restricted to 13 weeks before the grass pollen season. The primary end point was the size of the LPR at 12 months. Exploratory end points included measures of the immunomodulatory activity of treatment by using IL-4 and IL-10 FluoroSpot assays, flow cytometry of T cells, and measurement of IgE, IgG4, and facilitated antigen binding. RESULTS: Both active treatment arms led to a substantial and sustained reduction of the LPR with no additional suppression with addition of anti-IL-4. Treatment with anti-IL-4 and SCIT compared with SCIT alone led to a sustained reduction in allergen-specific IL-4-producing cell counts (P < .01). Both active treatment arms led to induction of dual IL-4/IL-10-producing cells during the pollen season. CONCLUSION: The combination of anti-IL-4 with SCIT provided no additional benefit over SCIT alone in suppressing the allergen-induced skin LPR. A larger trial is needed to assess whether the observed ex vivo downregulation of TH2 responses might translate into clinical benefit.

Recombinant allergen immunotherapy: clinical evidence of efficacy--a review.

Recombinant allergens for immunotherapy aim to overcome the problems of natural extracts as they can be produced in unlimited amounts with exact physiochemical and immunological properties. These can be modified to have more favourable characteristics including reduced IgE reactivity or enhanced immunogenicity. Different types of recombinant allergens have been evaluated in clinical phase II and III trials whilst others are currently under development. In this review, we identified double-blind, placebo-controlled randomised clinical trials assessing the efficacy and safety of various recombinant allergen preparations. The majority of studies have up to now focused on cat, grass, birch, ragweed and bee venom allergens. Some studies have shown some of these preparations to be effective and well tolerated. However, there are still outstanding issues regarding optimum doses, minimising side effects and long-term effects.

The Potential Role of Allergen Immunotherapy in Stepping Down Asthma Treatment.

For patients whose asthma is controlled and who have a low risk for future exacerbations, current guidelines recommend gradually stepping down pharmacotherapy to identify the lowest dose needed to maintain control. This review article will discuss the benefits and risks of step down in asthma management and the different strategies of achieving step down with particular focus on allergen immunotherapy (AIT). A literature search was conducted to identify studies that assessed the effect of AIT on asthma step down and evaluated this and asthma control as one of the outcomes. Six studies were identified: 2 subcutaneous and 4 sublingual AIT studies. Five studies assessed house dust mite-induced asthma, whereas 1 study focused on birch-induced seasonal asthma. Regarding house dust mite-induced asthma, the AIT studies reviewed suggest that individuals with moderate rather than mild asthma are the patients who are more likely to benefit from the addition of AIT for their asthma condition. The potential value of AIT is likely to be in enabling successful step down of the inhaled corticosteroid dose in Global Initiative for Asthma step 3 or 4. It is important to further explore this effect so that affected individuals can benefit from this treatment.

Subcutaneous Immunotherapy and Sublingual Immunotherapy: Comparative Efficacy, Current and Potential Indications, and Warnings--United States Versus Europe.

Subcutaneous immunotherapy and sublingual immunotherapy are effective for allergic rhinitis and allergic asthma and with some support for use in selected patients with atopic dermatitis. The sequence of immunologic responses is the same, irrespective of the route of administration, and similar disease modification has been demonstrated. However, there are differences between the two approaches. The most important is the greatly reduced likelihood of sublingual immunotherapy producing systemic reactions. There are major drawbacks for sublingual immunotherapy in regard to dosing. Finally, there is the question of relative clinical efficacy, with the currently available data favoring subcutaneous immunotherapy.

Prospective adherence to specific immunotherapy in Europe (PASTE) survey protocol.

BACKGROUND: Adherence to allergen immunotherapy is important for its effectiveness. There is currently limited data available on allergen immunotherapy adherence outside of clinical trials i.e. in real-life clinical practice. As part of a European Academy of Allergy and Clinical Immunology Immunotherapy Interest group initiative, we endeavoured to design a survey in order to prospectively evaluate adherence to subcutaneous and sublingual immunotherapy across different European countries. METHOD/DESIGN: The inclusion criteria for this prospective, multi-country survey were set as: adults, starting clinically indicated allergen immunotherapy for respiratory allergic disorders or Hymenoptera venom allergy. An online survey was designed in order to enrol participants and assess adherence to immunotherapy. Eight countries (Czech Republic, Georgia, Germany, Greece, Italy, Poland, Portugal, Spain) were selected to reflect different parts of Europe and differences in allergens and routes of immunotherapy administration. Each country has an allocated National co-ordinator that has identified local Allergy departments willing to enrol participants in this survey. Each participant will be followed up for a total of three years. In order to assess adherence, a 4-monthly follow-up form detailing any missed doses and reasons will be completed online. In case of a participant discontinuing treatment, reasons for this will be recorded. DISCUSSION: The use of online survey software has enabled us to make this survey a reality and reach clinicians in different countries. Forty-five centres have enrolled a total of over 1,350 participants. It is hoped that this prospective real life survey will enable us to gain a better understanding of reasons that affect adherence to subcutaneous and sublingual immunotherapy and assist in developing ways to improve this.

Sublingual allergen immunotherapy for respiratory allergies: what is new?

Sublingual immunotherapy (SLIT) is a disease-modifying treatment for respiratory allergies that has been used for many years in Europe and has also recently been approved for use in North America. Its use is thus likely to increase. There is more evidence available regarding SLIT efficacy and its good safety profile, making it an appealing treatment option. The majority of studies have mostly focused on grass pollens; however, there are now data available regarding efficacy for other allergens. This review will summarize recent findings from SLIT clinical trials for respiratory allergies, including efficacy, safety, post-discontinuation effects and use in different age groups. Grass pollen, tree pollen, house dust mite and ragweed SLIT studies will be evaluated.

Anaphylaxis: still a ghost behind allergen immunotherapy.

PURPOSE OF REVIEW: Allergen immunotherapy has been shown to be an effective treatment for respiratory allergies and Hymenoptera venom allergy. However, concern regarding its potential to cause anaphylaxis may limit its use. This review aims to assess whether anaphylaxis is still a worry when administering subcutaneous (SCIT) and sublingual immunotherapy (SLIT). RECENT FINDINGS: Retrospective surveillance surveys and one ongoing North American prospective study have helped to characterize the incidence and risk factors for fatal and nonfatal systemic reactions to SCIT. The latest rate of very severe, World Allergy Organization grade 4, systemic reactions was similar to the previously reported rates of near-fatal reactions, that is, 1 in 1 million injections. Regarding SLIT, no fatalities have been reported. Case reports of anaphylaxis in clinical practice and in some clinical trials have been described; however, given the number of doses administered daily throughout the world, the number is very small. SUMMARY: Identification of possible risk factors and the introduction of safety guidelines and practice parameters have enabled the reduction in immunotherapy related systemic reactions. However, it is important that clinicians remain vigilant when administering immunotherapy and should be prepared to provide emergency treatment if required.

Allergen immunotherapy: clinical outcomes assessment.

Assessment of clinical outcomes is essential to evaluate the efficacy of allergen immunotherapy, both in clinical trials and in daily clinical practice. "Primary outcomes" used in sublingual and subcutaneous immunotherapy trials include the measurement of symptoms, the use of concomitant medications, and/or a combination of both of these measures. "Secondary outcomes" that have been measured include individual symptom scores, provocation allergen tests, visual analog scales, and health-related quality of life assessments. Currently, there is a lack of consistency in the selection of outcome parameters used, which represents a major problem when comparing the same therapeutic intervention. In this review, we examined the different primary and secondary outcome parameters that have been used in clinical trials; reviewed recommendations by European and US guidelines, and allergy groups; and explored which outcomes may be applicable for use in clinical practice.

Comparability of subcutaneous and sublingual immunotherapy outcomes in allergic rhinitis clinical trials.

PURPOSE OF REVIEW: To conduct a qualitative comparison between the primary and secondary outcomes used in clinical trials of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) for allergic rhinitis. RECENT FINDINGS: Studies of SCIT and SLIT for allergic rhinitis published up to January 2012 were included in this systematic review. Different ways of defining primary and secondary outcome parameters in studies investigating specific immunotherapy are described. Whereas older studies often use the total symptom score and the total medication score individually for the primary efficacy analysis, more recent studies follow current international recommendations of applying the total combined score as primary outcome measure. Even wider is the range of secondary outcomes in clinical trials with few being validated or standardized. SUMMARY: As already recognized as a major concern in recent literature, standardized and validated primary endpoints are of paramount importance in order to improve the comparability of study results. The lack of consistency in the selection of primary outcome parameters represents a major problem when comparing the same therapeutic intervention. A main point of concern is the absence of validation data for those primary and secondary outcomes selected. In conclusion, the qualitative analysis of well powered studies confirms an urgent call from academics, regulatory agencies and the pharmaceutical industry for validated primary outcome parameters and standardized definitions.

An evidence-based appraisal of the surrogate markers of efficacy of allergen immunotherapy.

PURPOSE OF REVIEW: The assessment of clinical efficacy of immunotherapy in patients with respiratory allergy is highly affected by variability and lack of validated outcome measures such as symptom and medication scores. At the same time, there is a need to identify reliable predictive surrogate markers or biomarkers that may correlate with real clinical endpoints and lead to individually tailored immunotherapy treatment. RECENT FINDINGS: In-vivo markers, such as early and late skin reaction as well as immunological parameters such as IgE levels, IgG subclasses, mucosal IgA, lymphocyte subsets, cytokines and local and systemic inflammatory markers, have been proposed as potential surrogate markers. SUMMARY: Given the poor reproducibility and surrogacy to clinical outcomes shown in various clinical trials, the decreased availability in daily practice and anticipated high costs, an ideal surrogate marker is still not available to allergists.