Environmental peanut exposure increases the risk of peanut sensitization in high-risk children.

BACKGROUND: High household peanut consumption is associated with the development of peanut allergy, especially when peanut allergic cases are compared against atopic controls; thus, environmental peanut exposure (EPE) may be a risk factor for peanut sensitization and allergy. In this study, we explored the relationship between EPE and school-age peanut sensitization in a population-based cohort. METHODS: Maternal bed dust was collected postnatally, and EPE was quantified using a polyclonal peanut ELISA. Peanut sensitization was assessed by specific IgE to peanut extract and sIgE to peanut protein component allergens Ara h 1, 2 or 3 ≥ 0.35kU/L (primary peanut sensitization). Initial nested case-control analysis was performed comparing peanut-sensitized cases against high-risk controls (matched for parental atopy) (n = 411) using a conditional regression analysis. This was followed by whole cohort analysis (n = 1878) comparing EPE against peanut sIgE sensitization at ages 4 and 8 years using generalized estimating equations and against primary peanut sensitization at age 8 years using a logistic regression model. Finally, a subgroup analysis was performed comparing the impact of EPE in peanut-sensitized vs egg-sensitized, peanut-tolerant individuals using logistic regression analysis. Levels of EPE were compared between groups using the Mann-Whitney U test. RESULTS: In the nested case-control analysis, a higher level of EPE around birth was associated with peanut-specific IgE sensitization at age 4 years (OR=1.41, 95% CI:1.05-1.90) and primary peanut sensitization at age 8 years (OR=2.11, 95% CI:1.38-3.22) compared against high-risk controls. When the whole BAMSE cohort was assessed, EPE was no longer associated with peanut sensitization; however, on subgroup analysis, EPE was associated with primary peanut sensitization when compared against egg-sensitized peanut-tolerant controls with an adjusted odds ratio of 1.44 per unit EPE (95% CI:1.06-1.94). There was no significant interaction between EPE and FLG loss-of-function mutations, egg sensitization at age 4 years, infantile eczema or parental atopy on peanut sensitization. CONCLUSIONS: Higher levels of environmental exposure to peanut in the first few months of life appear to increase the probability of developing school-age peanut sensitization in atopic children (based on egg sensitization and parental atopy).

EAACI Guidelines on Allergen Immunotherapy: Allergic rhinoconjunctivitis.

Allergic rhinoconjunctivitis (AR) is an allergic disorder of the nose and eyes affecting about a fifth of the general population. Symptoms of AR can be controlled with allergen avoidance measures and pharmacotherapy. However, many patients continue to have ongoing symptoms and an impaired quality of life; pharmacotherapy may also induce some side-effects. Allergen immunotherapy (AIT) represents the only currently available treatment that targets the underlying pathophysiology, and it may have a disease-modifying effect. Either the subcutaneous (SCIT) or sublingual (SLIT) routes may be used. This Guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on AIT for AR and is part of the EAACI presidential project "EAACI Guidelines on Allergen Immunotherapy." It aims to provide evidence-based clinical recommendations and has been informed by a formal systematic review and meta-analysis. Its generation has followed the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included involvement of the full range of stakeholders. In general, broad evidence for the clinical efficacy of AIT for AR exists but a product-specific evaluation of evidence is recommended. In general, SCIT and SLIT are recommended for both seasonal and perennial AR for its short-term benefit. The strongest evidence for long-term benefit is documented for grass AIT (especially for the grass tablets) where long-term benefit is seen. To achieve long-term efficacy, it is recommended that a minimum of 3 years of therapy is used. Many gaps in the evidence base exist, particularly around long-term benefit and use in children.

Allergen immunotherapy for allergic rhinoconjunctivitis: A systematic review and meta-analysis.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis. To inform the development of clinical recommendations, we undertook a systematic review to assess the effectiveness, cost-effectiveness, and safety of AIT in the management of allergic rhinoconjunctivitis. METHODS: We searched nine international biomedical databases for published, in-progress, and unpublished evidence. Studies were independently screened by two reviewers against predefined eligibility criteria and critically appraised using established instruments. Our primary outcomes of interest were symptom, medication, and combined symptom and medication scores. Secondary outcomes of interest included cost-effectiveness and safety. Data were descriptively summarized and then quantitatively synthesized using random-effects meta-analyses. RESULTS: We identified 5960 studies of which 160 studies satisfied our eligibility criteria. There was a substantial body of evidence demonstrating significant reductions in standardized mean differences (SMD) of symptom (SMD -0.53, 95% CI -0.63, -0.42), medication (SMD -0.37, 95% CI -0.49, -0.26), and combined symptom and medication (SMD -0.49, 95% CI -0.69, -0.30) scores while on treatment that were robust to prespecified sensitivity analyses. There was in comparison a more modest body of evidence on effectiveness post-discontinuation of AIT, suggesting a benefit in relation to symptom scores. CONCLUSIONS: AIT is effective in improving symptom, medication, and combined symptom and medication scores in patients with allergic rhinoconjunctivitis while on treatment, and there is some evidence suggesting that these benefits are maintained in relation to symptom scores after discontinuation of therapy.

Effect of grass pollen immunotherapy on clinical and local immune response to nasal allergen challenge.

RATIONALE: Nasal allergen provocations may be useful in investigating the pathophysiology of allergic rhinitis and effects of treatments. OBJECTIVE: To use grass pollen nasal allergen challenge (NAC) to investigate the effects of allergen immunotherapy in a cross-sectional study. METHODS: We studied nasal and cutaneous responses in untreated subjects with seasonal grass-pollen allergic rhinitis (n = 14) compared with immunotherapy-treated allergics (n = 14), plus a nonatopic control group (n = 14). Volunteers underwent a standardized NAC with 2000 biological units of timothy grass allergen (equivalent to 1.3 µg major allergen, Phl p5). Nasal fluid was collected and analysed by ImmunoCAP and multiplex assays. Clinical response was assessed by symptom scores and peak nasal inspiratory flow (PNIF). Cutaneous response was measured by intradermal allergen injection. Retrospective seasonal symptom questionnaires were also completed. RESULTS: Immunotherapy-treated patients had lower symptom scores (P = 0.04) and higher PNIF (P = 0.02) after challenge than untreated allergics. They had reduced early (P = 0.0007) and late (P < 0.0001) skin responses, and lower retrospective seasonal symptom scores (P < 0.0001). Compared to untreated allergics, immunotherapy-treated patients had reduced nasal fluid concentrations of IL-4, IL-9 and eotaxin (all P < 0.05, 8 h level and/or area under the curve comparison), and trends for reduced IL-13 (P = 0.07, area under the curve) and early-phase tryptase levels (P = 0.06). CONCLUSIONS: Nasal allergen challenge is sensitive in the detection of clinical and biological effects of allergen immunotherapy and may be a useful surrogate marker of treatment efficacy in future studies.

Local and systemic effects of cat allergen nasal provocation.

BACKGROUND: Cat allergen is widely distributed in homes and schools; allergic sensitization is common. OBJECTIVE: To develop a model of cat allergen nasal challenge to establish dose-response and time-course characteristics and investigate local and systemic biomarkers of allergic inflammation. METHODS: Nineteen cat-allergic individuals underwent titrated nasal challenge, range 0.243 to 14.6 µg/mL Fel d1, and matched diluent-only provocation. Clinical response to 8 h was assessed by symptom scores and peak nasal inspiratory flow (PNIF). Nasal fluid was collected using polyurethane sponges and analysed by ImmunoCAP and multiplex assays. Whole blood flow cytometry for basophil surface CD63, CD107a, and CD203c was carried out at baseline and 6 h post-challenge. RESULTS: A dose-response to allergen was seen in symptom scores and PNIF, maximal at 10 000 BU/mL (4.87 µg/mL Fel d1), P < 0.0001 vs. diluent. Nasal fluid tryptase was elevated at 5 min after challenge (P < 0.05 vs. diluent); eotaxin, IL-4, -5, -9, and -13 were increased at 8 h (P < 0.05 to P < 0.0001 vs. diluent); TSLP was undetectable; IL-10, IL-17A, and IL-33 were unchanged compared to diluent challenge. Nasal fluid IL-5 and IL-13 correlated inversely with PNIF after challenge (IL-5, r = -0.79, P < 0.0001; IL-13, r = -0.60, P = 0.006). Surface expression of CD63 and CD107a was greater at 6 h than at baseline, both in the presence (both P < 0.05) and absence (CD63, P < 0.01; CD107a, P < 0.05) of in vitro allergen stimulation; no changes were seen on diluent challenge day. CONCLUSIONS: Cat allergen nasal challenge produces local and systemic Th2-driven inflammatory responses and has potential as a surrogate outcome measure in clinical trials.

Systematic review on the efficacy of fexofenadine in seasonal allergic rhinitis: a meta-analysis of randomized, double-blind, placebo-controlled clinical trials.

RATIONALE: Evidence-based medicine represents the effort to highlight the best intervention for patients, clinicians, and policy makers, each from their respective viewpoint, to solve a particular health condition. According to a recently diffused grading system of evidence and recommendations for medical interventions, efficacy and safety represent 2 of the most important features to consider, and data from meta-analyses of randomized controlled clinical trials (RCTs) is the strongest supporting demonstration. Fexofenadine has been used for its efficacy and safety in the treatment of allergic rhinitis (AR) for many years although no meta-analyses supporting its use currently exist. The aim of this study is to assess for the first time the efficacy and safety of fexofenadine in the treatment of AR by means of a meta-analytic analysis of existing RCTs. Since specific evidence should be provided to address recommendations in a pediatric population, the quality of the estimates of this subgroup analysis is assessed. METHODS: All double-blind, placebo-controlled randomized trials assessing the efficacy of fexofenadine in AR were searched for in OVID, Medline, and Embase databases up to December 2007. Outcomes were extracted from original articles; when this information was not available, the authors of each trial were contacted. Some graphics were digitalized. The RevMan 5 program was used to perform the analysis. GradePro 3.2.2 was used to assess the quality of the evidence for a pediatric population. RESULTS: Of 2,152 identified articles, 20 were potentially relevant trials. Eight studies satisfied the inclusion criteria and were included in the meta-analysis. The main reasons for exclusion were: unnatural exposure, strong study limitations, an atypical outcome measurement, a design for other outcomes, and not being a placebo-controlled, single-blind study. Seven trials investigated a mixed population of adults and children, 1 trial investigated only children, and 1 trial only adults. In 1,833 patients receiving fexofenadine (1,699 placebo), a significant reduction of the daily reflective total symptom scores (TSS) (SMD ­0.42; 95% CI ­0.49 to ­0.35, p < 0.00001) was found. Positive results were also found for morning instantaneous TSS and individual nasal symptom scores (sneezing, rhinorrhea, itching, and congestion). The safety analysis did not show a significant difference in reported adverse events (AE) between the active and placebo treatment groups (OR = 1.03; 95% CI 0.87­1.22, p = 0.75). A very low heterogeneity between the studies was detected, so a fixed-effects model was used. The mean quality level of the included trials was medium. Specific information for a pediatric population may be assumed with a moderate quality of evidence from only 1 study and with a low quality of evidence, mainly due to indirectness, from the others. CONCLUSIONS: This study has 5 major strengths: it represents the first attempt to evaluate the efficacy and safety of fexofenadine in the treatment of AR by means of a meta-analysis of RCTs; there was consistency between positive results in terms of efficacy in TSS and in individual symptoms; a large population was studied; there was an irrelevant interstudy heterogeneity, and the AE frequency was similar in both groups. All of these values encourage the recommendation of fexofenadine for AR. Further research focused on the benefits and disadvantages for a pediatric population is needed.

Sublingual immunotherapy for allergic conjunctivitis: Cochrane systematic review and meta-analysis.

BACKGROUND: Allergic conjunctivitis (AC) is a common manifestation and represents an important co-morbidity of allergic rhinitis (AR). Sublingual immunotherapy (SLIT) is an effective and safe treatment for nasal symptoms of AR; its effectiveness is however less well established for ocular symptoms. OBJECTIVES: To evaluate the effectiveness of SLIT in reducing ocular symptoms, the need for ocular treatments and the threshold exposure for conjunctival immediate allergen sensitivity (CIAS). METHODS: We searched eight databases up to January 2010. We included only randomized controlled trials (RCT), double-blind and placebo-controlled evaluating the efficacy of SLIT in patients with symptoms of allergic rhinoconjunctivitis (ARC) or AC. Primary outcome measures were total ocular symptom scores, individual ocular symptoms scores (itchy eyes, eye redness, watery eyes, swelling eyes), eye drops use and CIAS. Meta-analysis was undertaken using RevMan 5 software. RESULTS: From 811 abstracts that were screened, 109 studies were reviewed in their full text version. Forty two trials including 3958 participants (n=2011 SLIT and n=1947 placebo) had data suitable for inclusion in the meta-analysis. SLIT induced a significant reduction on both total ocular symptom scores (SMD: -0.41; 95%CI: -0.53 to -0.28; I(2) : 59%) and individual ocular symptoms scores [red (-0.33; -0.45 to -0.22), itchy (-0.31; -0.42 to -0.20) and watery eyes (-0.23; -0.34 to -0.11)] compared with placebo. Participants in the SLIT group showed an increase in the threshold dose for the CIAS (SMD: 0.35; 0.00-0.69). No significant reduction was observed on eye drops use (SMD: -0.10; -0.22 to 0.03). CONCLUSIONS AND CLINICAL RELEVANCE: SLIT is effective in reducing total and individual ocular symptom scores in subjects with ARC or conjunctivitis. No significant reduction was observed in ocular eye drops use.

Search engine as a diagnostic tool in difficult immunological and allergologic cases: is Google useful?

BACKGROUND: Web search engines are an important tool in communication and diffusion of knowledge. Among these, Google appears to be the most popular one: in August 2008, it accounted for 87% of all web searches in the UK, compared with Yahoo's 3.3%. Google's value as a diagnostic guide in general medicine was recently reported. The aim of this comparative cross-sectional study was to evaluate whether searching Google with disease-related terms was effective in the identification and diagnosis of complex immunological and allergic cases. METHODS: Forty-five case reports were randomly selected by an independent observer from peer-reviewed medical journals. Clinical data were presented separately to three investigators, blinded to the final diagnoses. Investigator A was a Consultant with an expert knowledge in Internal Medicine and Allergy (IM&A) and basic computing skills. Investigator B was a Registrar in IM&A. Investigator C was a Research Nurse. Both Investigators B and C were familiar with computers and search engines. For every clinical case presented, each investigator independently carried out an Internet search using Google to provide a final diagnosis. Their results were then compared with the published diagnoses. RESULTS: Correct diagnoses were provided in 30/45 (66%) cases, 39/45 (86%) cases, and in 29/45 (64%) cases by investigator A, B, and C, respectively. All of the three investigators achieved the correct diagnosis in 19 cases (42%), and all of them failed in two cases. CONCLUSION: This Google-based search was useful to identify an appropriate diagnosis in complex immunological and allergic cases. Computing skills may help to get better results.

Efficacy of mometasone furoate nasal spray in the treatment of allergic rhinitis. Meta-analysis of randomized, double-blind, placebo-controlled, clinical trials.

RATIONALE: Several randomized, double-blind, placebo-controlled clinical trials have demonstrated the efficacy of mometasone furoate nasal spray (MFNS) in the treatment of allergic rhinitis (AR) thus allowing for a meta-analysis to determine the overall treatment effect. METHODS: A comprehensive search of the MEDLINE, LILACS, SCOPUS, and the Cochrane Library databases up to 31 October, 2007 was carried out. Randomized, double-blind, placebo-controlled, clinical trials evaluating the efficacy of MFNS in patients with AR compared to placebo were included. Total nasal symptom scores (TNSS), individual nasal symptoms, total non-nasal symptom scores (TNNSS) and nasal airflow were analysed as the standardized mean difference (SMD). Meta-analysis was performed with the random or the fixed effect models depending on heterogeneity, by using revman 5 software. DATA SYNTHESIS: Sixteen of the 113 identified articles met the inclusion criteria. For MFNS efficacy on TNSS, 2998 participants were analysed: 1534 received MFNS and 1464 placebo. Mometasone furoate nasal spray was associated with a significant reduction in TNSS (SMD -0.49, 95% CI: -0.60 to -0.38; P < 0.00001; I(2) = 50.1%). A significant effect on SMD for nasal stuffiness/congestion (-0.41; 95% CI: -0.56 to -0.27), rhinorrhoea (-0.44; 95% CI: -0.66 to -0.21), sneezing (-0.40; 95% CI: -0.57 to -0.23) and nasal itching (-0.39; 95% CI: -0.53 to -0.25) was also demonstrated. Mometasone furoate nasal spray treated subjects also showed a significant reduction in TNNSS (-0.30; 95% CI: -0.43 to -0.18). The proportion of patients with adverse events was similar for MFNS and placebo (0.99; 95% CI: 0.81-1.20; P = 0.91). CONCLUSIONS: This meta-analysis provides a level Ia evidence for the efficacy of MFSN in the treatment of AR vs placebo. Adverse events frequency was similar in both groups.

Efficacy of desloratadine in the treatment of allergic rhinitis: a meta-analysis of randomized, double-blind, controlled trials.

The objective of the study is to assess the efficacy of the nonsedating antihistamine, desloratadine, in the treatment of allergic rhinitis (AR). A search of MEDLINE, EMBASE, LILACS, and CINAHL databases was undertaken from January, 1966 to May, 2006. Double-blind, randomized, controlled studies of desloratadine in the treatment of AR in adult patients were carried out. The measured outcomes included the total symptoms score, the total nasal symptoms score, nasal airflow, and inflammatory markers (nasal eosinophils, nasal interleukin-4). The analysis included the calculation of standardized mean difference (SMD). A total of 57 studies were analyzed, and 13 randomized, double-blind, controlled trials were included in the meta-analysis. The trials included 3108 subjects who had completed studies involving desloratadine. There was significant heterogeneity among the study results, because of differing study methodologies. Desloratadine was associated with significant reductions in total symptoms scores (SMD -1.63; 95% CI -2.75 to -0.51; P = 0.004) and total nasal symptoms score (SMD -0.66; 95% CI -0.91 to -0.42; P < 0.001), when compared with placebo. Analysis of objective data on nasal blockage demonstrated a significant improvement in nasal airflow with desloratadine, when compared with placebo (SMD 0.32; 95% CI 0.10 to 0.55; P = 0.005). A benefit favoring desloratadine over placebo in terms of nasal eosinophil levels was also noted in the analysis. This meta-analysis confirms the reduction of AR symptoms and improvement in nasal airflow seen in individual studies of desloratadine. Objective improvements in nasal airflow, total symptoms, and total nasal symptoms seen with desloratadine are supported by Ia evidence.

Changes in the cell wall accompanying drying and maturation determine the ease of isolation of protoplasts from wheat aleurone layers.

Cell walls of aleurone tissue of developing wheat grains (25 days post anthesis) are degraded by cellulase to give a good yield of protoplasts. As grains become older the aleurone cell walls become increasingly resistant to cellulase, which is completely ineffective on 45-day old material. Resistance to cellulase is provoked even in aleurone cells of young grains by enforced drying of the grains to 12% water content. This suggests that the decreasing effectiveness of cellulase that occurs as grains develop and mature may be caused partly by the natural loss of water.Resistance to degradation by the aleurone cell walls of older or dried grains is to a large extent overcome by the addition of hemicellulase and xylanase to the digestion mixture but completely if acetyl esterase is also included. Changes involving hemicelluloses and xylans are therefore implicated in the effects of drying or maturation, including acetylation processes especially in grains which are almost mature. Arising from these findings a method has been developed for obtaining a high yield of protoplasts from aleurone layers of mature wheat grains, having a high viability and response to gibberellic acid.