Showing papers in "Allergy in 2009"

Grading quality of evidence and strength of recommendations in clinical practice guidelines. Part 1 of 3. An overview of the GRADE approach and grading quality of evidence about interventions.

Abstract: The GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach provides guidance to grading the quality of underlying evidence and the strength of recommendations in health care. The GRADE system's conceptual underpinnings allow for a detailed stepwise process that defines what role the quality of the available evidence plays in the development of health care recommendations. The merit of GRADE is not that it eliminates judgments or disagreements about evidence and recommendations, but rather that it makes them transparent. This first article in a three-part series describes the GRADE framework in relation to grading the quality of evidence about interventions based on examples from the field of allergy and asthma. In the GRADE system, the quality of evidence reflects the extent to which a guideline panel's confidence in an estimate of the effect is adequate to support a particular recommendation. The system classifies quality of evidence as high, moderate, low, or very low according to factors that include the study methodology, consistency and precision of the results, and directness of the evidence.

EAACI/GA(2)LEN/EDF/WAO guideline: management of urticaria.

Abstract: This guideline, together with its sister guideline on the classification of urticaria (Zuberbier T, Asero R, Bindslev-Jensen C, Canonica GW, Church MK, Gimenez-Arnau AM et al. EAACI/GA(2)LEN/EDF/WAO Guideline: definition, classification and diagnosis of urticaria. Allergy 2009;64: 1417-1426), is the result of a consensus reached during a panel discussion at the Third International Consensus Meeting on Urticaria, Urticaria 2008, a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2)LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO). As members of the panel, the authors had prepared their suggestions regarding management of urticaria before the meeting. The draft of the guideline took into account all available evidence in the literature (including Medline and Embase searches and hand searches of abstracts at international allergy congresses in 2004-2008) and was based on the existing consensus reports of the first and the second symposia in 2000 and 2004. These suggestions were then discussed in detail among the panel members and with the over 200 international specialists of the meeting to achieve a consensus using a simple voting system where appropriate. Urticaria has a profound impact on the quality of life and effective treatment is, therefore, required. The recommended first line treatment is new generation, nonsedating H(1)-antihistamines. If standard dosing is not effective, increasing the dosage up to four-fold is recommended. For patients who do not respond to a four-fold increase in dosage of nonsedating H(1)-antihistamines, it is recommended that second-line therapies should be added to the antihistamine treatment. In the choice of second-line treatment, both their costs and risk/benefit profiles are most important to consider. Corticosteroids are not recommended for long-term treatment due to their unavoidable severe adverse effects. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).

Sub-lingual immunotherapy: World Allergy Organization Position Paper 2009.

Abstract: Co-Authors: Wahiduzzaman Akhanda, Raul Castro Almarales, Ignacio Ansotegui, Floriano Bonifazi, Jan Ceuppens, Tomás Chivato, Darina Dimova, Diana Dumitrascu, Luigi Fontana, Constance HKatelaris, Ranbir Kaulsay, Piotr Kuna, Dèsirée Larenas-Linnemann, Manolis Manoussakis, Kristof Nekam, Carlos Nunes, Robyn O’Hehir, José M Olaguibel, Nerin Bahceciler Onder, JungWon Park, Alfred Priftanji, Robert Puy, Luis Sarmiento, Glenis Scadding, Peter Schmid-Grendelmeier, Ester Seberova, Revaz Sepiashvili, Dirceu Solé, Alkis Togias, Carlo Tomino, Elina Toskala, Hugo Van Beever, Stefan Vieths*

Global map of the prevalence of symptoms of rhinoconjunctivitis in children: The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three

Abstract: Background: Phase One of the International Study of Asthma and Allergies in Childhood (ISAAC) measured the global patterns of prevalence and severity of symptoms of rhinoconjunctivitis in children in 1993–1997. Methods: International Study of Asthma and Allergies in Childhood Phase Three was a cross-sectional survey performed 5–10 years after Phase One using the same methodology. Phase Three covered all of the major regions of the world and involved 1 059 053 children of 2 age groups from 236 centres in 98 countries. Results: The average overall prevalence of current rhinoconjunctivitis symptoms was 14.6% for the 13- to 14-year old children (range 1.0–45%). Variation in the prevalence of severe rhinoconjunctivitis symptoms was observed between centres (range 0.0–5.1%) and regions (range 0.4% in western Europe to 2.3% in Africa), with the highest prevalence being observed mainly in the centres from middle and low income countries, particularly in Africa and Latin America. Co-morbidity with asthma and eczema varied from 1.6% in the Indian sub-continent to 4.7% in North America. For 6- to 7-year old children, the average prevalence of rhinoconjunctivitis symptoms was 8.5%, and large variations in symptom prevalence were also observed between regions, countries and centres. Discussion: Wide global variations exist in the prevalence of current rhinoconjunctivitis symptoms, being higher in high vs low income countries, but the prevalence of severe symptoms was greater in less affluent countries. Co-morbidity with asthma is high particularly in Africa, North America and Oceania. This global map of symptom prevalence is of clinical importance for health professionals.

Update on the evaluation of hypersensitivity reactions to betalactams

Abstract: Hypersensitivity reactions to betalactams (BLs) are classified as immediate or nonimmediate The former usually appear within 1 h of drug-intake and are mediated by specific IgE-antibodies Nonimmediate reactions are those occurring more than 1 h after drug-intake, and they can be T-cell mediated The diagnostic evaluation of allergic reactions to BLs has changed over the last 5 years, for several reasons Major and minor determinants are no longer commercially available for skin testing in many countries In immediate allergic reactions, the sensitivity of skin testing and immunoassays is decreasing and new in vitro methods, such as the basophil activation test, are gaining importance for diagnosis For nonimmediate reactions, skin testing appears to be less sensitive than previous results, although more studies need to be carried out in this direction Nevertheless, the drug provocation test is still necessary for diagnosis

GA(2)LEN skin test study I: GA(2)LEN harmonization of skin prick testing: novel sensitization patterns for inhalant allergens in Europe.

Abstract: BACKGROUND: Skin prick testing is the standard for diagnosing IgE-mediated allergies. However, different allergen extracts and different testing procedures have been applied by European allergy centres. Thus, it has been difficult to compare results from different centres or studies across Europe. It was, therefore, crucial to standardize and harmonize procedures in allergy diagnosis and treatment within Europe. AIMS: The Global Asthma and Allergy European Network (GA(2)LEN), with partners and collaborating centres across Europe, was in a unique position to take on this task. The current study is the first approach to implement a standardized procedure for skin prick testing in allergies against inhalant allergens with a standardized pan-European allergen panel. METHODS: The study population consisted of patients who were referred to one of the 17 participating centres in 14 European countries (n = 3034, median age = 33 years). Skin prick testing and evaluation was performed with the same 18 allergens in a standardized procedure across all centres. RESULTS: The study clearly shows that many allergens previously regarded as untypical for some regions in Europe have been underestimated. This could partly be related to changes in mobility of patients, vegetation or climate in Europe. CONCLUSION: The results of this large pan-European study demonstrate for the first time sensitization patterns for different inhalant allergens in patients across Europe. The standardized skin prick test with the standardized allergen battery should be recommended for clinical use and research. Further EU-wide monitoring of sensitization patterns is urgently needed.

Effector and regulatory mechanisms in allergic contact dermatitis

Abstract: Allergic contact dermatitis (ACD), one of the commonest occupational diseases, is a T-cell-mediated skin inflammation caused by repeated skin exposure to contact allergens, i.e. nonprotein chemicals called haptens. Allergic contact dermatitis, also referred to as contact hypersensitivity, is mediated by CD8+ T cells, which are primed in lymphoid organs during the sensitization phase and are recruited in the skin upon re-exposure to the hapten. Subsets of CD4+ T cells endowed with suppressive activity are responsible for both the down-regulation of eczema in allergic patients and the prevention of priming to haptens in nonallergic individuals. Therefore, ACD should be considered as a breakdown of the skin immune tolerance to haptens. Recent advances in the pathophysiology of ACD have demonstrated the important role of skin innate immunity in the sensitization process and have revisited the dogma that Langerhans cells are mandatory for CD8+ T-cell priming. They have also introduced mast cells as a pivotal actor in the magnitude of the inflammatory reaction. Finally, the most recent studies address the nature, the mode and the site of action of the regulatory T cells that control the skin inflammation with the aim of developing new strategies of tolerance induction in allergic patients.

Impact of peanut allergy on quality of life, stress and anxiety in the family

Abstract: Background: Peanut allergy (PA) is known to impact on quality of life (QoL) of the sufferer, but little research has focused on all family members. We therefore sought to establish the impact of PA on QoL and reported anxiety of children with clinically confirmed PA, their parents and older siblings. Methods: Forty-six families, who had a child with PA, completed QoL (PedsQLTM or WHOQOL-BREF), anxiety (SCAS or STAI) and perceived stress (PSS) scales. PA children completed a PA specific QoL questionnaire (Pediatr Allergy Immunol 2003;14:378). Parents and sibling also completed QoL proxy questionnaires for the PA child (PedsQLTM, Pediatr Allergy Immunol 2003;14:378). Results: Mothers rated their own psychological (P < 0.01) and physical (P < 0.05) QoL significantly worse than fathers rated theirs, and had higher scores than fathers for anxiety (P < 0.05) and stress (P < 0.001). Children with PA had significantly poorer physical health-related QoL (P < 0.05), QoL within school (P < 0.01) and general QoL (P < 0.05) than their siblings did, and greater separation anxiety (P < 0.05). The majority of differences were between girls with PA and female siblings. Mothers felt that there was a greater impact on QoL for their PA child, compared with that reported by siblings, fathers or the PA children themselves (P < 0.01). Conclusions: Mothers report that they have significantly poorer QoL and suffer more anxiety and stress than fathers do; this inter-parental difference may be an important feature of family stress caused by PA. Siblings have a similar view of how QoL affects the PA child as the PA child does, while mothers may possibly overestimate this impact.

Skin testing in patients with hypersensitivity reactions to iodinated contrast media – a European multicenter study

Abstract: BACKGROUND: Iodinated contrast media cause both immediate and nonimmediate hypersensitivity reactions. The aim of this prospective study was to determine the specificity and sensitivity of skin tests in patients who have experienced such reactions. METHODS: Skin prick, intradermal and patch tests with a series of contrast media were conducted in 220 patients with either immediate or nonimmediate reaction. Positive skin tests were defined according to internationally accepted guidelines. Seventy-one never-exposed subjects and 11 subjects who had tolerated contrast medium exposure, served as negative controls. RESULTS: Skin test specificity was 96-100%. For tests conducted within the time period from 2 to 6 months after the reaction, up to 50% of immediate reactors and up to 47% of nonimmediate reactors were skin test positive. For immediate reactors, the intradermal tests were the most sensitive, whereas delayed intradermal tests in combination with patch tests were needed for optimal sensitivity in nonimmediate reactors. Contrast medium cross-reactivity was more common in the nonimmediate than in the immediate group. Interestingly, 49% of immediate and 52% of nonimmediate symptoms occurred in previously unexposed patients. Many of these patients were skin test positive, indicating that they were already sensitized at the time of first contrast medium exposure. CONCLUSIONS: These data suggest that at least 50% of hypersensitivity reactions to contrast media are caused by an immunological mechanism. Skin testing appears to be a useful tool for diagnosis of contrast medium allergy and may play an important role in selection of a safe product in previous reactors.

GA2LEN skin test study II: clinical relevance of inhalant allergen sensitizations in Europe

Abstract: BACKGROUND: Skin prick testing is the standard for diagnosing IgE-mediated allergies. A positive skin prick reaction, however, does not always correlate with clinical symptoms. A large database from a Global Asthma and Allergy European Network (GA(2)LEN) study with data on clinical relevance was used to determine the clinical relevance of sensitizations against the 18 most frequent inhalant allergens in Europe. The study population consisted of patients referred to one of the 17 allergy centres in 14 European countries (n = 3034, median age = 33 years). The aim of the study was to assess the clinical relevance of positive skin prick test reactions against inhalant allergens considering the predominating type of symptoms in a pan-European population of patients presenting with suspected allergic disease. METHODS: Clinical relevance of skin prick tests was recorded with regard to patient history and optional additional tests. A putative correlation between sensitization and allergic disease was assessed using logistic regression analysis. RESULTS: While an overall rate of >or=60% clinically relevant sensitizations was observed in all countries, a differential distribution of clinically relevant sensitizations was demonstrated depending on type of allergen and country where the prick test was performed. Furthermore, a significant correlation between the presence of allergic disease and the number of sensitizations was demonstrated. CONCLUSION: This study strongly emphasizes the importance of evaluating the clinical relevance of positive skin prick tests and calls for further studies, which may, ultimately, help increase the positive predictive value of allergy testing.

EAACI/GA(2)LEN task force consensus report: the autologous serum skin test in urticaria.

Abstract: Injection of autologous serum collected during disease activity from some patients with chronic spontaneous urticaria (CU) into clinically normal skin elicits an immediate weal and flare response. This observation provides a convincing demonstration of a circulating factor or factors that may be relevant to the understanding of the pathogenesis and management of the disease. This test has become known as the autologous serum skin test (ASST) and is now widely practised despite incomplete agreement about its value and meaning, the methodology and the definition of a positive response. It should be regarded as a test for autoreactivity rather than a specific test for autoimmune urticaria. It has only moderate specificity as a marker for functional autoantibodies against IgE or the high affinity IgE receptor (FcepsilonRI), detected by the basophil histamine release assay, but high negative predictive value for CU patients without them. It is usually negative in other patterns of CU, including those that are physically induced. Positive ASSTs have been reported in some subjects without CU, including those with multiple drug intolerance, patients with respiratory allergy and healthy controls, although the clinical implications of this are uncertain. It is essential that failsafe precautions are taken to ensure that the patient's own serum is used for skin testing and aseptic procedures are followed for sample preparation and handling. CU patients with a positive ASST (ASST(+)) are more likely to be associated with HLADR4, to have autoimmune thyroid disease, a more prolonged disease course and may be less responsive to H1-antihistamine treatment than those with a negative ASST (ASST(-)) although more evidence is needed to confirm these observations conclusively.

Serum 25‐hydroxyvitamin D and IgE – a significant but nonlinear relationship

Abstract: Background: Hormonal vitamin D system affects the determination of T-cell responses. It is unknown if there is an association between vitamin D status and allergic conditions. Our aim was to investigate differences in serum IgE concentrations by vitamin D status [measured by 25(OH)D] and by a genetic variation in a key vitamin D activation enzyme (CYP27B1) previously shown to be associated with type 1 diabetes. Methods: 9377 participants in the 1958 British birth cohort completed a biomedical assessment at 45 years of age ; 7288 eligible participants had data on 25(OH)D and IgE, with 6429 having further information on CYP27B1 genotype (−1260C>A). Results: There was a nonlinear association between 25(OH)D and IgE (P-value for curvature = 0.0001). Compared with the reference group with the lowest IgE concentrations [25(OH)D 100–125 nmol/l], IgE concentrations were 29% higher (95% CI 9–48%) for participants with the 25(OH)D 135 nmol/l (adjusted for sex, month, smoking, alcohol consumption, time spent outside, geographical location, social class, PC/TV time, physical activity, body mass index and waist circumference). CYP27B1 genotype was associated with both 25(OH)D (difference for A vs. C allele: 1.88%, 95% CI 0.37–3.4%, P = 0.01) and IgE concentrations (−6.59%, −11.6% to −1.42%, P = 0.01). Conclusions: These data suggest that there may be a threshold effect with both low and high 25(OH)D levels associated with elevated IgE concentrations. The same CYP27B1 allele that is protective of diabetes was associated with increased IgE concentrations.

The effects of selected probiotic strains on the development of eczema (The PandA study)

Abstract: Background: Modification of the intestinal microbiota by administration of probiotic bacteria may be a potential approach to prevent allergic disease. We aimed to study primary prevention of allergic disease in high-risk children by pre- and postnatal supplementation of selected probiotic bacteria. Methods: In a double-blind, randomized, placebo-controlled trial, a mixture of probiotic bacteria selected by in-vitro experiments (Bifidobacterium bifidum, Bifidobacterium lactis, and Lactococcus lactis; Ecologic® Panda) was prenatally administered to mothers of high-risk children (i.e. positive family history of allergic disease) and to their offspring for the first 12 months of life. Results: Parental-reported eczema during the first 3 months of life was significantly lower in the intervention group compared with placebo, 6/50 vs 15/52 (P = 0.035). After 3 months, the incidence of eczema was similar in both groups. Cumulative incidence of parental-reported eczema at 1 and 2 years was 23/50 (intervention) vs 31/48 (placebo) and 27 (intervention) vs 34 (placebo), respectively. The number needed to treat was 5.9 at age 3 and 12 months and 6.7 at age 2 years. The intervention group was significantly more frequently colonized with higher numbers of Lc. lactis. Furthermore, at age 3 months, in vitro production of IL-5 (146 pg/ml vs 72 pg/ml; P = 0.04) was decreased in the probiotic-group compared with the placebo-group. Conclusions: This particular combination of probiotic bacteria shows a preventive effect on the incidence of eczema in high-risk children, which seems to be sustained during the first 2 years of life. In addition to previous studies, the preventive effect appears to be established within the first 3 months of life.

Grading quality of evidence and strength of recommendations in clinical practice guidelines: Part 2 of 3. The GRADE approach to grading quality of evidence about diagnostic tests and strategies.

Abstract: The GRADE approach to grading the quality of evidence and strength of recommendations provides a comprehensive and transparent approach for developing clinical recommendations about using diagnostic tests or diagnostic strategies. Although grading the quality of evidence and strength of recommendations about using tests shares the logic of grading recommendations for treatment, it presents unique challenges. Guideline panels and clinicians should be alert to these special challenges when using the evidence about the accuracy of tests as the basis for clinical decisions. In the GRADE system, valid diagnostic accuracy studies can provide high quality evidence of test accuracy. However, such studies often provide only low quality evidence for the development of recommendations about diagnostic testing, as test accuracy is a surrogate for patient-important outcomes at best. Inferring from data on accuracy that using a test improves outcomes that are important to patients requires availability of an effective treatment, improved patients' wellbeing through prognostic information, or - by excluding an ominous diagnosis - reduction of anxiety and the opportunity for earlier search for an alternative diagnosis for which beneficial treatment can be available. Assessing the directness of evidence supporting the use of a diagnostic test requires judgments about the relationship between test results and patient-important consequences. Well-designed and conducted studies of allergy tests in parallel with efforts to evaluate allergy treatments critically will encourage improved guideline development for allergic diseases.

Successful oral tolerance induction in severe peanut allergy

Abstract: Background: Peanut allergy is common, potentially severe and rarely resolves causing impaired quality of life. No disease-modifying treatment exists and there is therefore a need to develop a therapeutic intervention. Aims of the study: The aim of this study was to investigate whether peanut oral immunotherapy (OIT) can induce clinical tolerance to peanut protein. Methods: Four peanut-allergic children underwent OIT. Preintervention oral challenges were performed to confirm clinical allergy and define the amount of protein required to cause a reaction (dose thresholds). OIT was then administered as daily doses of peanut flour increasing from 5 to 800 mg of protein with 2-weekly dose increases. After 6 further weeks of treatment, the oral challenge was repeated to define change in dose threshold and subjects continued daily treatment. Results: Preintervention challenges confirmed peanut allergy and revealed dose thresholds of 5–50 mg (1/40–1/4 of a whole peanut); one subject had anaphylaxis during challenge and required adrenaline injection. All subjects tolerated immunotherapy updosing to 800 mg protein and i.m. adrenaline was not required. Each subject tolerated at least 10 whole peanuts (approximately 2.38 g protein) in postintervention challenges, an increase in dose threshold of at least 48-, 49-, 55- and 478-fold for the four subjects. Conclusions: We demonstrated a substantial increase in dose threshold after OIT in all subjects, including the subject with proven anaphylaxis. OIT was well tolerated and conferred protection against at least 10 peanuts, more than is likely to be encountered during accidental ingestion.

A multicentre study assessing the prevalence of sensitizations in patients with asthma and/or rhinitis in China.

Abstract: Background: The prevalence of sensitization in patients with asthma and rhinitis in mainland China remains unclear. Objective: Our aim was to estimate the prevalence of allergy in patients with respiratory allergic diseases such as asthma and/or rhinitis attending respiratory clinics within mainland China. The study also investigated regional and annual differences in the prevalence and pattern of sensitization among the patients in China. Method: A cross-sectional survey was performed in 6304 patients suffering from asthma and/or rhinitis in 17 cities from 4 regions of China. Patients completed a standardized questionnaire asking for the presence of respiratory and allergic symptoms. They also underwent skin prick tests with 13 common aeroallergens. Results: Among the 6304 patients, 4545 (72.1%) had at least one positive skin prick reaction. The overall prevalence of positive skin prick responses was 59.0% for Dermatophagoides farinae, 57.6% for Dermatophagoides pteronyssinus, 40.7% for Blomia tropicalis, 16.1% for American cockroach, 14.0% for dog, 11.5% for Blatella germanica, 11.3% for Artemisia vulgaris, 10.3% for cat, 6.5% for Ambrosia artemisifolia, 6.3% for mixed mould I, 4.4% for mixed mould IV, 3.5% for mixed grass pollen and 2.2% for mixed tree pollen. Sensitizations to common allergens varied widely between geographical areas and demonstrated unique pattern in patients by stratification with age groups, with asthma and/or rhinitis. Severity of rhinitis and asthma was significantly correlated with skin index of reactivity to Artemisia vulgaris, Ambrosia artemisifolia and to D. pteronyssinus, D. farinae and Blomia tropicalis respectively (P < 0.001). Positive reactivity to the tested allergens and concomitant reactivity to multiple allergens including to house dust mites and Blomia tropicalis was markedly increased in patients with both asthma and rhinitis. Conclusion: House dust mites were the most prevalent allergens in patients with asthma and/or rhinitis in China. There were significant differences in patterns of sensitizations in patients from different geographical areas, age groups as well as asthma and/or rhinitis.

Randomized double‐blind, placebo‐controlled trial of sublingual immunotherapy with a Pru p 3 quantified peach extract

Abstract: Background: Peach allergy is highly prevalent in the Mediterranean area; it is persistent and potentially severe, and therefore a prime target for immunotherapy We aimed to study the efficacy and safety of sublingual immunotherapy (SLIT) with a peach extract quantified in mass units for Pru p 3, the peach lipid transfer protein Methods: Randomized, double-blind, placebo-controlled (DBPC) clinical trial The main efficacy outcome was the change in the response to a DBPC food challenge (DBPCFC) with peach Secondary efficacy outcomes were the changes in skin prick test (SPT), and in specific immunoglobulin E (IgE) and IgG4 to Pru p 3 Tolerance was assessed with a careful recording of adverse events Results: After 6 months of SLIT, the active group tolerated a significantly higher amount of peach (three- to ninefold), presented a significant decrease (53 times) in SPT, and a significant increase in IgE and IgG4 to Pru p 3 No significant changes were observed within the placebo group Statistically significant inter-group differences were only observed in the SPT and IgG4 responses No serious adverse events were reported Systemic reactions were mild, and observed with a similar frequency in both groups Local reactions were significantly more frequent in the active group (three times) and 95% of them restricted to the oral cavity Conclusion: In this first exploratory clinical trial, SLIT for peach allergy seems to be a promising therapeutic option that could modify the clinical reactivity of the patients to peach intake and the underlying immunological response with a good tolerance

The efficacy of sublingual immunotherapy for house dust mites respiratory allergy: results of a GA2LEN meta-analysis.

Abstract: Recent meta-analyses documented the efficacy and safety of sublingual immunotherapy (SLIT) in patients with allergic rhinitis (AR) and asthma (AA). Although SLIT appeared globally effective, the sub-analyses for single allergens provided uncertain results. This study is aimed to investigate the efficacy of SLIT with house dust mite (HDM) extracts in AR and AA through an updated reassessment of randomized controlled trials. Electronic databases were searched up to March 31, 2008, for randomized DBPC trials, assessing the efficacy of SLIT in AR and AA due to HDM sensitization. Outcomes were symptom scores and rescue medications use. For AR, eight studies fulfilled the selection criteria. A significant reduction in symptoms of AR (SMD −0.95; CI 95%−1.77 to −0.14 P = 0.02) was found in 194 patients (adults and children) receiving SLIT compared to 188 receiving placebo. For AA, with nine studies, similar results were found for symptoms (SMD −0.95; CI 95%−1.74 to −0.15 P = 0.02) in 243 patients (adults and children) receiving SLIT compared to 209 receiving placebo. A reduction in rescue medication use was found for AR (SMD −1.88; CI 95%−3.65 to −0.12 P = 0.04) in 89 patients, and AA (SMD −1.48; CI 95%−2.70 to −0.26 P = 0.02) in 202 patients. A relevant inter-study heterogeneity was detected. Promising evidence of efficacy for SLIT, using mite extract in allergic patients suffering from AR and AA, are herein shown. These findings suggest that more data are needed, derived from large-population-based high quality studies, and corroborated by objective outcomes, mainly for AA.

Respiratory virus induction of alpha-, beta- and lambda-interferons in bronchial epithelial cells and peripheral blood mononuclear cells.

Abstract: Background Respiratory viruses, predominantly rhinoviruses are the major cause of asthma exacerbations. Impaired production of interferon-beta in rhinovirus infected bronchial epithelial cells (BECs) and of the newly discovered interferon-lambdas in both BECs and bronchoalveolar lavage cells, is implicated in asthma exacerbation pathogenesis. Thus replacement of deficient interferon is a candidate new therapy for asthma exacerbations. Rhinoviruses and other respiratory viruses infect both BECs and macrophages, but their relative capacities for alpha-, beta- and lambda-interferon production are unknown. Methods To provide guidance regarding which interferon type is the best candidate for development for treatment/prevention of asthma exacerbations we investigated respiratory virus induction of alpha-, beta- and lambda-interferons in BECs and peripheral blood mononuclear cells (PBMCs) by reverse transferase-polymerase chain reaction and enzyme-linked immunosorbent assay. Results Rhinovirus infection of BEAS-2B BECs induced interferon-alpha mRNA expression transiently at 8 h and interferon-beta later at 24 h while induction of interferon-lambda was strongly induced at both time points. At 24 h, interferon-alpha protein was not detected, interferon-beta was weakly induced while interferon-lambda was strongly induced. Similar patterns of mRNA induction were observed in primary BECs, in response to both rhinovirus and influenza A virus infection, though protein levels were below assay detection limits. In PBMCs interferon-alpha, interferon-beta and interferon-lambda mRNAs were all strongly induced by rhinovirus at both 8 and 24 h and proteins were induced: interferon-alpha>-beta>-lambda. Thus respiratory viruses induced expression of alpha-, beta- and lambda-interferons in BECs and PBMCs. In PBMCs interferon-alpha>-beta>-lambda while in BECs, interferon-lambda>-beta>-alpha. Conclusions We conclude that interferon-lambdas are likely the principal interferons produced during innate responses to respiratory viruses in BECs and interferon-alphas in PBMCs, while interferon-beta is produced by both cell types.

Hymenoptera venom allergy: analysis of double positivity to honey bee and Vespula venom by estimation of IgE antibodies to species‐specific major allergens Api m1 and Ves v5

Abstract: Background: In patients with hymenoptera venom allergy diagnostic tests are often positive with honey bee and Vespula venom causing problems in selection of venoms for immunotherapy. Methods: 100 patients each with allergic reactions to Vespula or honey bee stings and positive i.e. skin tests to the respective venom, were analysed for serum IgE to bee venom, Vespula venom and crossreacting carbohydrate determinants (CCDs) by UNICAP (CAP) and ADVIA Centaur (ADVIA). IgE-antibodies to species specific recombinant major allergens (SSMA) Api m1 for bee venom and Ves v5 for Vespula venom, were determined by ADVIA. 30 history and skin test negative patients served as controls. Results: By CAP sensitivity was 1.0 for bee and 0.91 for Vespula venom, by ADVIA 0.99 for bee and 0.91 for Vespula venom. None of the controls were positive with either test. Double positivity was observed in 59% of allergic patients by CAP, in 32% by ADVIA. slgE to Api m1 was detected in 97% of bee and 17% of Vespula venom allergic patients, slgE to Ves v5 in 87% of Vespula and 17% of bee venom allergic patients. slgE to CCDs were present in 37% of all allergic patients and in 56% of those with double positivity and were more frequent in bee than in Vespula venom allergic patients. Conclusions: Double positivity of IgE to bee and Vespula venom is often caused by crossreactions, especially to CCDs. IgE to both Api m1 and Ves v5 indicates true double sensitization and immunotherapy with both venoms.

A specific mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides induces a beneficial immunoglobulin profile in infants at high risk for allergy.

Abstract: Background: It has been suggested that human breast milk oligosaccharides play a role in the development of the immune system in infants, and may consequently inhibit the onset of allergy. A specific prebiotic mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (GOS/FOS) has been shown to reduce the incidence of atopic dermatitis (AD) at 6 months of age in infants at risk for allergy. Aim of the study: This study was aimed to analyze the effect of GOS/FOS on the immune response in these infants. Methods: In a double-blind randomized placebo-controlled study, infants received a hypoallergenic whey formula with either 8 g/l GOS/FOS in a 9 : 1 ratio (IMMUNOFORTIS™) or 8 g/l maltodextrine (placebo) for 6 months. At 3 months of age, children were vaccinated with Hexavac against a.o. diphteria, tetanus, polio (DTP). At 6 months of age, plasma samples were collected from 84 infants (verum group n = 41, placebo group n = 43). Levels of total immunoglobulins (Ig) and of cow's milk protein (CMP-) and DTP-specific Ig were measured. Results: GOS/FOS supplementation led to a significant reduction in the plasma level of total IgE, IgG1, IgG2 and IgG3, whereas no effect on IgG4 was observed. CMP-specific IgG1 was significantly decreased. DTP-specific Ig levels were not affected. Conclusions: This study shows that GOS/FOS supplementation induces a beneficial antibody profile. GOS/FOS reduces the total Ig response and modulates the immune response towards CMP, while leaving the response to vaccination intact. This suggests that oral GOS/FOS supplementation is a safe method to restrain the atopic march.

Increased metal allergy in patients with failed metal-on-metal hip arthroplasty and peri-implant T-lymphocytic inflammation.

Abstract: Background: In 16 patients with revised metal-on-metal arthroplasty and peri-implant lymphocytic inflammation, we verified the role of metal hypersensitivity by patch testing (PT) and lymphocyte transformation test (LTT). Methods: In the 16 patients with lymphocyte dominated periprosthetic inflammation, allergy history was obtained by a questionnaire, specific serum IgE to aeroallergens was measured to assess atopy, PT to standard and metal series was performed and metal sensitivity was further assessed by LTT using blood mononuclear cells. Results: Revision surgery was performed because of pain (8/16), osteolysis (4/16), dislocation (3/16) and loosening of the stem (1/16). Histological examination showed perivascular infiltrates of T lymphocytes, high endothelial venules, fibrin exudation and accumulation of macrophages with drop-like inclusions. Five patients had a history of cutaneous metal allergy and atopy was found in 25% of the patients. In 13/16 patients (81%), systemic metal sensitivity was found based on PT and/or LTT. Patch test reactions were seen in 11/16 patients (69%; partly multiple reactions/patient): 7/16 to Cobalt (Co), 7/16 to Chromium (Cr), 4/16 to Nickel (Ni), and one each to Molybdenum (Mo) and Manganese (Mn). Ten of 16 patients (62%) showed enhanced LTT reactivity to metals: 7/16 to Ni, 7/16 to Co, 5/16 to Cr, 5/16 to Mo and 4/16 to Mn. Conclusions: The lymphocyte dominated peri-implant inflammation may well reflect an allergic hyper-reactivity in these patients, given the high rate of concomitantly found metal allergy. Despite the overall incidence of metal implant allergy being low, allergic reactions should be included as differential diagnosis in failed metal-on-metal arthroplasty.

Adrenaline for the treatment of anaphylaxis: cochrane systematic review

Abstract: Background: Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death. Adrenaline is recommended as the initial treatment of choice for anaphylaxis. Objectives: To assess the benefits and harms of adrenaline in the treatment of anaphylaxis. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1), MEDLINE (1966 to March 2007), EMBASE (1966 to March 2007), CINAHL (1982 to March 2007), BIOSIS (to March 2007), ISI Web of Knowledge (to March 2007) and LILACS (to March 2007). We also searched websites listing ongoing trials: http://www.clinicaltrials.gov/, http://www.controlledtrials.com and http://www.actr.org.au/ and contacted pharmaceutical companies and international experts in anaphylaxis in an attempt to locate unpublished material. Randomized and quasi-randomized controlled trials comparing adrenaline with no intervention, placebo or other adrenergic agonists were eligible for inclusion. Two authors independently assessed articles for inclusion. Results: We found no studies that satisfied the inclusion criteria. Conclusions: On the basis of this review, we are unable to make any new recommendations on the use of adrenaline for the treatment of anaphylaxis. In the absence of appropriate trials, we recommend, albeit on the basis of less than optimal evidence, that adrenaline administration by intramuscular injection should still be regarded as first-line treatment for the management of anaphylaxis.

Adherence rate to inhaled corticosteroids and their impact on asthma control.

Abstract: Background: Poor asthma control is associated to high morbidity. The objective of this study was to assess the association between adherence rates to beclomethasone dipropionate (BDP) and the degree of asthma control. Methods: A cohort concurrent study was carried out for 12 months with 122 asthmatic patients, aged 3–12 years, randomly selected in a pediatric pulmonology outpatient clinic, who received BDP free of charge. Adherence rates were verified by pharmacy records. Clinical control was assessed through a scoring system comprised four variables (nocturnal and morning symptoms, limitation of physical activities and exacerbations). Total score was 16 points. Patients whose score was below or equal to two were considered controlled (group 1), and patients whose score was above or equal to three were considered uncontrolled (group 2). For patients able to perform spirometry, we considered as controlled the patients with forced expiratory volume in 1 s (FEV1) equal to or above 80% of the predicted value, and as uncontrolled the patients with FEV1 below 80%. Results: Fewer than half (40.3% maximum) of the 122 patients maintained asthma control. Median adherence rate of groups 1 and 2 were 85.5% and 33.8%, (P < 0.001) in the 4th month, 90.0% and 48.0% (P < 0.001) in the 8th month and 84.4% and 47.0% in the 12th month (P < 0.001), respectively. Conclusion: In all periods, there were statistically significant differences in adherence rates for maintaining or not maintaining the asthma control. Optimal asthma control entailed adherence rate higher than 80%. Strategies for reducing asthma morbidity should include a regular monitoring of adherence to inhaled steroids.

Negativization rates of IgE radioimmunoassay and basophil activation test in immediate reactions to penicillins.

Abstract: Background: Skin test sensitivity in patients with immediate allergy to penicillins tends to decrease over time, but no information is available concerning in vitro tests. We analysed the negativization rates of two in vitro methods that determine specific immunoglobulin E (IgE) antibodies, the basophil activation test using flow cytometry (BAT) and the radioallergosorbent test (RAST), in immediate allergic reactions to penicillins. Methods: Forty-one patients with immediate allergic reactions to amoxicillin were followed up over a 4-year period. BAT and RAST were performed at 6-month intervals. Patients were randomized into groups: Group I, skin tests carried out at regular intervals; Group II, skin tests made only at the beginning of the study. Results: Differences were observed between RAST and BAT (P < 0.01), the latter showing earlier negativization. Considering different haptens, significant differences for the rate of negativization were only found for amoxicillin (P < 0.05). Comparisons between Groups I (n = 10) and II (n = 31) showed a tendency to become negative later in Group I with RAST. Conclusions: Levels of specific IgE antibodies tended to decrease over time in patients with immediate allergic reactions to amoxicillin. Conversion to negative took longer for the RAST assay, although the differences were only detected with the amoxicillin hapten. Skin testing influenced the rate of negativization of the RAST assay, contributing to maintenance of in vitro sensitivity. Because of the loss of sensitivity over time, the determination of specific IgE antibodies to penicillins in patients with immediate allergic reactions must be done as soon as possible after the reaction.

The German version of the chronic urticaria quality‐of‐life questionnaire: factor analysis, validation, and initial clinical findings

Abstract: Background: Chronic urticaria (CU) is a common skin disorder that causes a substantial burden on patients’ quality-of-life (QoL). The aim of this work was to generate and validate a German version of the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) and to provide reference assessments of QoL. Methods: The Italian CU-Q2oL was translated into German and administered to 157 CU patients. They also completed two well-established general dermatology QoL questionnaires, the Dermatology Life Quality Index (DLQI) and Skindex-29. Factor analysis was used to identify scales of the German CU-Q2oL. Correlation to the DLQI and Skindex-29 was used for validation. Multiple linear regression was used to determine which patient characteristics were associated with which dimensions of QoL. Results: The factor analysis identified six scales of the German CU-Q2oL: functioning, sleep, itching/embarrassment, mental status, swelling/eating, and limits looks, which accounted for 70% of the data variance. Five of these six scales showed good internal consistency, and another five demonstrated convergent validity. On a percentile scale, they had these median CU-Q2oL scores: 29 functioning, 44 sleep, 50 itching/embarrassment, 50 mental status, 31 swelling/eating, 31 limits looks. Disease severity significantly predicted scores on all scales. Age predicted functioning, sleep, itching/embarrassment, and swelling/eating. Sex predicted itching/embarrassment and limits looks. Conclusion: This study yielded a robust validation of the German version of the CU-Q2oL. It confirmed previous studies that CU has a clinically meaningful burden on QoL, especially for sleep and mental health, and that women are more severely affected by pruritus. The German CU-Q2oL should be widely adopted in clinical research on the treatment of CU.

Decreased FOXP3 protein expression in patients with asthma

Abstract: Background: T-regulatory cells (T(reg)) are important in balancing immune responses and maintaining peripheral tolerance. Current evidence suggests that asthma is characterized by a relative deficiency in T(reg), allowing T helper 2 cells to expand. In this study, we aimed to evaluate circulating T(reg), defined by the protein FOXP3, in both control subjects and patients with stable asthma. Methods: Peripheral blood mononuclear cells (PBMC) of control (n = 14) and asthmatic patients (n = 29) were labeled for CD4, CD25, and intracellular FOXP3 and analyzed using flow cytometry. In CD3/CD28 stimulated PBMC, the effects of dexamethasone on the transcription factors T-bet, GATA-3, FOXP3, and RORc2 and representative cytokines were studied. Results: In control subjects and asthmatic patients, numbers of peripheral blood CD4(+)CD25(high) and CD4(+)CD25(high)FOXP3(+) T-cells were similar. However, FOXP3 protein expression within CD4(+)CD25(high) T-cells was significantly decreased in asthmatic patients. There was a tendency for increased FOXP3 expression within CD4(+)CD25(high) T-cells in glucocorticosteroid-treated patients when compared to steroid-naive asthmatic patients. In stimulated PBMC, dexamethasone treatment increased the anti-/proinflammatory transcription ratios of FOXP3/GATA-3, FOXP3/T-bet, and FOXP3/RORc2. Conclusion: Asthmatic patients have decreased FOXP3 protein expression within their CD4(+)CD25(high) T(reg). Our findings also suggest that treatment with inhaled glucocorticosteroids in asthmatics might increase this FOXP3 protein expression within the CD4(+)CD25(high) T-cell population.

Allergic rhinitis and the common cold – high cost to society

Abstract: To cite this article: Hellgren J, Cervin A, Nordling S, Bergman A, Cardell LO. Allergic rhinitis and the common cold – high cost to society. Allergy 2010; 65: 776–783. Abstract Background: The common cold and allergic rhinitis constitute a global health problem that affects social life, sleep, school and work performance and is likely to impose a substantial economic burden on society because of absence from work and reduced working capacity. This study assesses the loss of productivity as a result of both allergic rhinitis and the common cold in the Swedish working population. Methods: Four thousand questionnaires were sent to a randomized adult population, aged 18–65 years, in Sweden, stratified by gender and area of residence (metropolitan area vs rest of the country). The human capital approach was used to assign monetary value to lost productivity in terms of absenteeism (absence from work), presenteeism (reduced working capacity while at work) and caregiver absenteeism (absence from work to take care of a sick child). Results: Thousand two hundred and thirteen individuals responded, response rate 32%. The mean productivity loss was estimated at 5.1 days or € 653 per worker and year, yielding a total productivity loss in Sweden of € 2.7 billion a year. Of the total costs, absenteeism (44%) was the dominant factor, followed by presenteeism (37%) and caregiver absenteeism (19%). Poisson regression analyses revealed that women, people in the 18–29 year age group, and respondents with ‘doctor-diagnosed asthma’ reported more lost days than the rest of the group. Conclusion: In Sweden, the cost of rhinitis is € 2.7 billion a year in terms of lost productivity. A reduction in lost productivity of 1 day per individual and year would potentially save € 528 million.

The definition and diagnostic testing of physical and cholinergic urticarias – EAACI/GA2LEN/EDF/UNEV consensus panel recommendations

Abstract: The recommendations for the definition and diagnosis presented in this position paper are the result of a panel consensus meeting held in December 2008 in Berlin. This consensus meeting was a joint initiative of EAACI (European Academy of Allergology and Clinical Immunology) Dermatology Section, the EU-funded network of excellence, GA2LEN (Global Allergy and Asthma European Network), the EDF (European Dermatology Forum) and UNEV (urticaria network e.V.). The aim of these recommendations is to improve the diagnosis and management of patients with physical urticaria or cholinergic urticaria and to promote research and a better understanding of these diseases. Our recommendations used the paper produced by a 1996 expert meeting (1) and they acknowledge the latest changes in our understanding of physical urticarias and cholinergic urticaria as well as the recent development of novel diagnostic tools. In addition, this consensus paper highlights areas of need for further research.

Blockade of CCR4 in a humanized model of asthma reveals a critical role for DC-derived CCL17 and CCL22 in attracting Th2 cells and inducing airway inflammation.

Abstract: Background: As Th2 type lymphocytes orchestrate the cardinal features of allergic asthma, inhibiting their recruitment to the lungs could be of therapeutic benefit. Although human Th2 cells express the CCR4 chemokine receptor and increased production of CCR4 ligands has been found in asthmatic airways, studies in animals have reached contradictory conclusions on whether blocking this pathway would be beneficial. Objective: As a lack of efficacy might be due to differences between mouse and man, we readdressed this question using a humanized severe combined immunodeficiency model of asthma. Methods: Mice received peripheral blood mononuclear cells from house dust mite (HDM) allergic asthmatic patients and then underwent bronchial challenge with HDM. Results: This resulted in marked allergic inflammation and bronchial hyper-reactivity. Administration of CCR4 blocking antibody abolished the airway eosinophilia, goblet cell hyperplasia, IgE synthesis and bronchial hyperreactivity. In this chimeric system, human CD11c+ dendritic cells (DCs) were the predominant source of CCR4 ligands, suggesting that DC-derived chemokines attract Th2 cells. In separate experiments using human DCs, in vitro exposure to HDM of DCs from HDM allergic patients but not healthy controls caused CCL17 and CCL22 release that resulted in chemoattraction of polarized human Th2 cells in a CCR4-dependent way. Conclusions: Taken together, our data provide proof of concept that CCR4 blockade inhibits the salient features of asthma and justify further clinical development of CCR4 antagonists for this disease.