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The methodology of randomized clinical trials is essential for the critical assessment and registration of therapeutic interventions. The CONSORT (Consolidated Standards of Reporting Trials) statement was developed to alleviate the problems arising from the inadequate reporting of randomized controlled trials. The present article reflects on the items that we believe should be included in the CONSORT checklist in the context of conducting and reporting trials in allergen-specific immunotherapy. Only randomized, blinded (in particular blinding of patients, health care providers, and outcome assessors), placebo-controlled Phase III studies in this article. Our analysis focuses on the definition of patients’ inclusion and exclusion criteria, allergen standardization, primary, secondary and exploratory outcomes, reporting of adverse events and analysis. [ABSTRACT FROM AUTHOR]

Immunotherapy has been used extensively for 80 years as a specific treatment of allergy. In the last decade, the clinical practice of immunotherapy has changed markedly in certain parts of Europe. In southern Europe immunotherapy still represents the cornerstone of allergy treatment, while in Scandinavia and Great Britain a large number of allergic patients receive immunotherapy. In spite of the fact that a large number of recently published, wee-performed clinical trials have documented the evidently beneficial effect of immunotherapy, the decrease is probably caused by a combination of some degree of uncertainty as to the clinical efficacy, the risk of side effects, and the introduction of potent new drugs for prophylactic treatment of allergic diseases. With the overall aim of improving the safety of immunotherapy and making it more convenient to patients, routes other than the subcutaneous administration of allergens have been investigated.

Abstract: While desired for the cure of allergy, regulatory immune cell subsets and nonclassical Th2‐biased inflammatory mediators in the tumour microenvironment can contribute to immune suppression and escape of tumours from immunological detection and clearance. A key aim in the cancer field is therefore to design interventions that can break immunological tolerance and halt cancer progression, whereas on the contrary allergen immunotherapy exactly aims to induce tolerance. In this position paper, we review insights on immune tolerance derived from allergy and from cancer inflammation, focusing on what is known about the roles of key immune cells and mediators. We propose that research in the field of AllergoOncology that aims to delineate these immunological mechanisms with juxtaposed clinical consequences in allergy and cancer may point to novel avenues for therapeutic interventions that stand to benefit both disciplines. [ABSTRACT FROM AUTHOR]

Allergic diseases in animals are increasingly gaining importance in veterinary practice and as research models. For intradermal testing and allergen immunotherapy, a good knowledge of relevant allergens for the individual species is of great importance. Currently, the knowledge about relevant veterinary allergens is based on sensitization rates identified by intradermal testing or serum testing for allergen-specific IgE; crude extracts are the basis for most evaluations. Only a few studies provide evidence about the molecular structure of (particularly) dust mite, insect and mould allergens in dogs and horses, respectively. In those species, some major allergens differ from those in humans. This position paper summarizes the current knowledge about relevant allergens in dogs, cats and horses. [ABSTRACT FROM AUTHOR]

While both the incidence and general awareness of food allergies is increasing, the variety and clinical availability of therapeutics remain limited. Therefore, investigations into the potential factors contributing to the development of food allergy (FA) and the mechanisms of natural tolerance or induced desensitization are required. In addition, a detailed understanding of the pathophysiology of food allergies is needed to generate compelling, enduring, and safe treatment options. New findings regarding the contribution of barrier function, the effect of emollient interventions, mechanisms of allergen recognition, and the contributions of specific immune cell subsets through rodent models and human clinical studies provide novel insights. With the first approved treatment for peanut allergy, the clinical management of FA is evolving toward less intensive, alternative approaches involving fixed doses, lower maintenance dose targets, coadministration of biologicals, adjuvants, and tolerance‐inducing formulations. The ultimate goal is to improve immunotherapy and develop precision‐based medicine via risk phenotyping allowing optimal treatment for each food‐allergic patient. [ABSTRACT FROM AUTHOR]

Most extracts used in hyposensitization (immunotherapy) are complex and ill- defined mixtures of a large number of' non-antigenic and antigenic components, only a few of the latter being of significance for allergy and allergen specific immunotherapy. A new purified and well-characterized allergen preparation from timothy pollen is now available, and it has been shown to be superior to the cor- responding crude aqueous extract in the diagnosis of IgE-mediated human allergy to timothy pollen. This paper describes the results of hyposensitization for 2 years, with the purified preparation and the crude extract compared. The changes in in vivo and in vitro tests following this treatment in 40 patients with allergic rhinitis due to grass pollen are reported. Both patient groups showed a significant decrease in clinical symptom scores when compared with a control group during the grass pollen season. For all groups the symptom scores correlated well with atmospheric pollen counts. Nasal challenge tests showed a significant increase in nasal tolerance to timothy pollen after 2 years of treat- merit, but nasal tolerance was unchanged in the control group. Nasal function as a criterion for evaluating the effect of specific hyposensitization is discussed. Serum concentrations of timothy pollen-specific IgE antibodies showed a significant decrease for the group treated with the purified preparation and a slighter and non-significant reduction for the other treated group. There was no significant change in total serum IgE levels. The results indicate that the purified preparation is preferable to the crude aqueous extract in hyposensitization. [ABSTRACT FROM AUTHOR]

This article presents information on the evaluation of changes in skin sensitivity by means of skin tests. Skin sensitivity to allergens and histamine can vary spontaneously, or as a consequence or specific immunotherapy, the use of antihistamines or other drugs, and other circumstances. The principle of standardization by skin tests is based on the dose-response relationship of allergen, derived by melting the wheal size produced by different concentrations of the allergen. Most authors evaluating changes in skin sensitivity reactivity.

The article presents information on treatment of patients allergic to house dust mites. In the treatment of patients allergic to house dust mites two different principles can be applied; symptomatic or specific treatment. The symptomatic treatment includes medicamental treatment and the elimination of now specific irritants, while specific treatment includes elimination of allergens and immunotherapy. In case of bronchial asthma, the purpose of therapy is to keep patients free of symptoms and provide normal lung functioning. It is important neither to undertreat nor overtreat and this means variable and individual pharmacotherapy.

The article focuses on the standardization of biological methods in clinical work in allergy. For several allergens in the IgE-dependent systems, biological and laboratory methods are available which correlate fairly well with each other when adequately performed and which are suggested should be used together to express the total diagnostic potency of allergen extracts. The specificity of the skin test for quantitation of the total allergenic activity of extracts for diagnosis appears to be accepted. Similar standardization of allergen preparations meant for immunotherapy is, however, likely to raise a quite lively debate.

The article focuses on the analysis and standardization of allergen extracts intended for therapeutic use. Over the past decade, many papers and international meetings have been devoted to establishing methods and requirements for analysis and standardization of allergen extracts. In fact, manufacturers and control authorities are in demand to produce procedures enabling precise and viable quantitation of allergenic activity as well as analysis of extracts. Such an approach would allow physicians to prescribe uniformly labeled extracts of known quality and guarantee therapeutic procedures.

Abstract: The accurate assessment and communication of the severity of acute allergic reactions are important to patients, clinicians, researchers, the food industry, and public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach, and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore, there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that work across the range of allergenic triggers and address the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data‐driven method that is informed by clinical and patient experience and other stakeholders’ perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that are clinically meaningful and are useful for allergy healthcare professionals and researchers, and (ii) a three‐grade‐based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice. [ABSTRACT FROM AUTHOR]

Abstract: Background: The European Academy of Allergy and Clinical Immunology (EAACI) is developing guidelines for allergen immunotherapy (AIT) for the management of allergic rhinitis, allergic asthma, IgE‐mediated food allergy and venom allergy. To inform the development of clinical recommendations, we undertook systematic reviews to critically assess evidence on the effectiveness, safety and cost‐effectiveness of AIT for these conditions. This study focusses on synthesizing data and gaps in the evidence on the cost‐effectiveness of AIT for these conditions. Methods: We produced summaries of evidence in each domain, and then, synthesized findings on health economic data identified from four recent systematic reviews on allergic rhinitis, asthma, food allergy and venom allergy, respectively. The quality of these studies was independently assessed using the Critical Appraisal Skills Programme tool for health economic evaluations. Results: Twenty‐three studies satisfied our inclusion criteria. Of these, 19 studies investigated the cost‐effectiveness of AIT in allergic rhinitis, of which seven were based on data from randomized controlled trials with economic evaluations conducted from a health system perspective. This body of evidence suggested that sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) would be considered cost‐effective using the (English) National Institute for Health and Clinical Excellence (NICE) cost‐effectiveness threshold of £20 000/quality‐adjusted life year (QALY). However, the quality of the studies and the general lack of attention to characterizing uncertainty and handling missing data should be taken into account when interpreting these results. For asthma, there were three eligible studies, all of which had significant methodological limitations; these suggested that SLIT, when used in patients with both asthma and allergic rhinitis, may be cost‐effective with an incremental cost‐effectiveness ratio (ICER) of £10 726 per QALY. We found one economic modelling study for venom allergy which, despite being based largely on expert opinion and plausible assumptions, suggested that AIT for bee and wasp venom allergy is only likely to be cost‐effective for very high‐risk groups who may be exposed to multiple exposures to venom/year (eg bee keepers). We found no eligible studies investigating the cost‐effectiveness of AIT for food allergy. Conclusions: Overall, the evidence to support the cost‐effectiveness of AIT is limited and of low methodological quality, but suggests that AIT may be cost‐effective for people with allergic rhinitis with or without asthma and in high‐risk subgroups for venom allergy. We were unable to draw any conclusions on the cost‐effectiveness of AIT for food allergy. [ABSTRACT FROM AUTHOR]

Background The European Academy of Allergy and Clinical Immunology ( EAACI) is in the process of developing the EAACI Guidelines on Allergen Immunotherapy ( AIT) for the management of insect venom allergy. To inform this process, we sought to assess the effectiveness, cost-effectiveness and safety of AIT in the management of insect venom allergy. Methods We undertook a systematic review, which involved searching 15 international biomedical databases for published and unpublished evidence. Studies were independently screened and critically appraised using established instruments. Data were descriptively summarized and, where possible, meta-analysed. Results Our searches identified a total of 16 950 potentially eligible studies; of which, 17 satisfied our inclusion criteria. The available evidence was limited both in volume and in quality, but suggested that venom immunotherapy ( VIT) could substantially reduce the risk of subsequent severe systemic sting reactions ( OR = 0.08, 95% CI 0.03-0.26); meta-analysis showed that it also improved disease-specific quality of life (risk difference = 1.41, 95% CI 1.04-1.79). Adverse effects were experienced in both the build-up and maintenance phases, but most were mild with no fatalities being reported. The very limited evidence found on modelling cost-effectiveness suggested that VIT was likely to be cost-effective in those at high risk of repeated systemic sting reactions and/or impaired quality of life. Conclusions The limited available evidence suggested that VIT is effective in reducing severe subsequent systemic sting reactions and in improving disease-specific quality of life. VIT proved to be safe and no fatalities were recorded in the studies included in this review. The cost-effectiveness of VIT needs to be established. [ABSTRACT FROM AUTHOR]

Background The safety and tolerability of a mite allergoid subcutaneous allergen immunotherapy ( SCIT) product was previously established. The aim of this study (EudraCT number: 2011-000393-61) was to find the optimally safe and effective allergoid dose by evaluating several dosages in patients with house dust mite ( HDM)-induced allergic rhinoconjunctivitis ( ARC) using a titrated nasal provocation test ( TNPT). Methods In total, 290 adult ARC patients (148 females; 142 males) with established HDM allergy and with a positive TNPT were randomized to receive placebo or mite allergoid SCIT 6667, 20 000, 50 000 or 100 000 AUeq/ml for 12 months. Patients were updosed weekly, followed by monthly maintenance dosing. The primary study endpoint comprised the clinical response to TNPT after 12 months of treatment. Secondary endpoints included response to TNPT after 6 months, PNIF measurements, symptom and medication scores during the last 8 weeks of treatment, serum immunoglobulins and safety assessments. Results After 12 months, a dose-response was observed showing statistically significant improvements in the TNPT with SCIT concentrations of ≥20 000 AUeq/ml, while no significantly different outcomes were reached after 6 months. Specific serum IgG and IgG4 levels were dose dependently increased. In the highest dose group, more treatment-emergent adverse events were observed compared with the lower dose groups. Conclusion In this mite allergoid SCIT dose finding study in HDM-induced ARC, concentrations of ≥20 000 AUeq/ml showed both immunological effects and clinical efficacy in the TNPT compared with placebo. The risk-benefit ratio favours 20 000 AUeq/ml and 50 000 AUeq/ml strengths for further clinical development. [ABSTRACT FROM AUTHOR]

This document is the result of a consensus on the mechanisms of exercise-induced anaphylaxis (EIAn), an unpredictable and potentially fatal syndrome. A multidisciplinary panel of experts including exercise physiologists, allergists, lung physicians, paediatricians and a biostatistician reached the given consensus. Exercise-induced anaphylaxis (EIAn) describes a rare and potentially fatal syndrome in which anaphylaxis occurs in conjunction with exercise. The pathophysiological mechanisms underlying EIAn have not yet been elucidated although a number of hypotheses have been proposed. This review evaluates the validity of each of the popular theories in relation to exercise physiology and immunology. On the basis of this evidence, it is concluded that proposed mechanisms lack validity, and it is recommended that a global research network is developed with a common approach to the diagnosis and treatment of EIAn in order to gain sufficient power for scientific evaluation. [ABSTRACT FROM AUTHOR]

Background Although many patients with allergic rhinoconjunctivitis have symptoms due to sensitization with more than one pollen allergen, and mixed pollen extracts are widely used for allergen immunotherapy in practice, there are few published trials. Methods We performed a 2-year multicentre, double-blind, placebo-controlled trial of subcutaneous immunotherapy with mixed depigmented-polymerized birch and grass pollen extract in 285 patients with allergic rhinoconjunctivitis symptomatic during both birch and grass pollen seasons. Primary outcome was combined symptom and medication score (SMS) assessed by daily visual analogue scales (VAS). Analysis included a placebo-based analysis examining the effect of treatment only on days when placebo patients were symptomatic. Results There was a significant reduction in median SMS for actively treated patients (median 5.70 (interquartile range 2.62-10.02) compared with 7.07 (3.47-10.71) for placebo, P = 0.0385). Rhinitis quality-of-life scores were significantly better for active compared with placebo, and other secondary endpoints were not significantly different. Placebo-based analysis showed a 33.7% reduced SMS at year 2 for active treatment compared with placebo on days when placebo patients were symptomatic. Both birch pollen- and grass pollen-specific IgG4 increased with active treatment. Conclusions This study shows efficacy of mixed pollen extracts for immunotherapy for patients symptomatic to both birch and grass pollen allergens. The relatively modest effect may reflect 50% dose reduction for each allergen in the mixture. It supports VAS for symptom assessment and placebo-based analysis as useful for the analysis of immunotherapy trials. The safety of modified extracts may allow study of mixed extracts without dose reduction to improve efficacy. [ABSTRACT FROM AUTHOR]

To cite this article: Calderón MA, Simons FER, Malling H-J, Lockey RF, Moingeon P, Demoly P. Sublingual allergen immunotherapy: mode of action and its relationship with the safety profile. Allergy 2012; 67: 302-311. Abstract Allergen immunotherapy reorients inappropriate immune responses in allergic patients. Sublingual allergen immunotherapy (SLIT) has been approved, notably in the European Union, as an effective alternative to subcutaneous allergen immunotherapy (SCIT) for allergic rhinitis patients. Compared with SCIT, SLIT has a better safety profile. This is possibly because oral antigen-presenting cells (mostly Langerhans and myeloid dendritic cells) exhibit a tolerogenic phenotype, despite constant exposure to danger signals from food and microbes. This reduces the induction of pro-inflammatory immune responses leading to systemic allergic reactions. Oral tissues contain relatively few mast cells and eosinophils (mostly located in submucosal areas) and, in comparison with subcutaneous tissue, are less likely to give rise to anaphylactic reactions. SLIT-associated immune responses include the induction of circulating, allergen-specific Th1 and regulatory CD4+ T cells, leading to clinical tolerance. Although 40-75% of patients receiving SLIT experience mild, transient local reactions in the oral mucosa, these primary reactions rarely necessitate dose reduction or treatment interruption. We discuss 11 published case reports of anaphylaxis (all nonfatal) diagnosed according to the World Allergy Organization criteria and relate this figure to the approximately 1 billion SLIT doses administered worldwide since 2000. Anaphylaxis risk factors associated with SCIT and/or SLIT should be characterized further. [ABSTRACT FROM AUTHOR]

To cite this article: Blank S, Seismann H, Michel Y, McIntyre M, Cifuentes L, Braren I, Grunwald T, Darsow U, Ring J, Bredehorst R, Ollert M, Spillner E. Api m 10, a genuine A. mellifera venom allergen, is clinically relevant but underrepresented in therapeutic extracts. Allergy 2011; 66: 1322-1329. Abstract Background: Generalized systemic reactions to stinging hymenoptera venom constitute a potentially fatal condition in venom-allergic individuals. Hence, the identification and characterization of all allergens is imperative for improvement of diagnosis and design of effective immunotherapeutic approaches. Our aim was the immunochemical characterization of the carbohydrate-rich protein Api m 10, an Apis mellifera venom component and putative allergen, with focus on the relevance of glycosylation. Furthermore, the presence of Api m 10 in honeybee venom (HBV) and licensed venom immunotherapy preparations was addressed. Methods: Api m 10 was produced as soluble, aglycosylated protein in Escherichia coli and as differentially glycosylated protein providing a varying degree of fucosylation in insect cells. IgE reactivity and basophil activation of allergic patients were analyzed. For detection of Api m 10 in different venom preparations, a monoclonal human IgE antibody was generated. Results: Both, the aglycosylated and the glycosylated variant of Api m 10 devoid of cross-reactive carbohydrate determinants (CCD), exhibited IgE reactivity with approximately 50% of HBV-sensitized patients. A corresponding reactivity could be documented for the activation of basophils. Although the detection of the native protein in crude HBV suggested content comparable to other relevant allergens, three therapeutical HBV extracts lacked detectable amounts of this component. Conclusion: Api m 10 is a genuine allergen of A. mellifera venom with IgE sensitizing potential in a significant fraction of allergic patients independent of CCD reactivity. Thus, Api m 10 could become a key element for component-resolved diagnostic tests and improved immunotherapeutic approaches in hymenoptera venom allergy. [ABSTRACT FROM AUTHOR]

Background: Treatment of allergic rhinitis with subcutaneous allergen immunotherapy is effective in terms of reductions in symptoms and seasonal use of reliever medication. Its effect on quality of life (QoL), reflecting the impact of symptoms on work/school performance and leisure activities is, however, important and often overlooked. Aims of the study: To assess effect on QoL of specific immunotherapy with two doses of Alutard SQ® Phleum pratense in patients with moderately to severe seasonal allergic rhinoconjunctivitis inadequately controlled by standard drug therapy. Methods: Double-blind, randomized, placebo-controlled study of 410 patients with seasonal allergic rhinoconjunctivitis. Participants were randomized (2 : 1 : 1) to receive Alutard SQ® P. pratense (ALK-Abelló) at maintenance doses of 100 000 SQ-U (203 subjects), 10 000 SQ-U (104 subjects) or placebo (103 subjects) given by subcutaneous injections. The groups were well matched for demographics and baseline symptoms. Quality of life was assessed using the Rhinoconjunctivitis Quality of Life Questionnaire which covers seven domains of health before and in the peak of the pollen season. Results: While all domain scores were significantly improved when comparing 100 000 SQ-U with placebo, two domain scores were significantly improved when comparing 10 000 SQ-U with placebo. When comparing 100 000 SQ-U with 10 000 SQ-U, four domain scores were significantly improved. Conclusion: Treatment with Alutard SQ® significantly improved the seasonal QoL of patients suffering from allergic rhinoconjunctivitis. The improvement was more pronounced and wider ranging in patients who received the higher 100 000 SQ-U maintenance dose. [ABSTRACT FROM AUTHOR]

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a rare variant of severe asthma resulting from hypersensitivity to Aspergillus fumigatus (Asp f) present in the airways. Aims of the study: We analyzed the expression of a panel of six chemokine receptors (CCR3, CCR4, CCR8, CCR5, CXCR3 and CXCR4) on total blood CD4+ T cells and Asp f-specific-T cells in ABPA patients. We hypothesized that chemokine receptor pattern on T cells differs between ABPA patients, non-ABPA allergic asthmatics sensitized to Dermatophagoides pteronyssinus (Der p) or Phleum pratense (Phl p) and healthy controls. Methods: We used the fluorescent dye PKH26, a membrane bound marker, to identify accumulated proliferating (cell-sorted PKH26low) CD4+ T cells in response to allergens (Asp f, Der p, Phl p) or recall antigens (PPD and TT). Chemokine receptor expression was analyzed by flow cytometry on proliferating CD3+ CD4+ PKH26low cells. Results: Stimulation of CD4+ T cells with the relevant allergen resulted in different patterns of chemokine receptor expression in ABPA and non-ABPA allergic asthmatics. Upon Asp f exposure, proliferating CD4+ T cells from ABPA patients down-regulated the expression of CCR4 and CXCR3 while CCR4 and CXCR3 were up-regulated in allergen-specific T cells from non-ABPA allergic asthmatics. Considering each group of patients, the pattern of chemokine receptors expressed on proliferating allergen-specific CD4+ T cells was similar to that expressed by recall antigen-specific T cells. Conclusions: The down-regulation of CCR4 and CXCR3 after allergen exposure in Asp f-specific T cells seems to be a characteristic feature of ABPA patients and requires further evaluation. [ABSTRACT FROM AUTHOR]

Background: Evaluation of the efficacy of allergen-specific immunotherapy (IT) with pollen extracts is complicated by annual variation in pollen intensity. Our study aimed to evaluate the efficacy of birch and grass IT, taking into consideration these variations. Methods: After 1 year of observation, 52 patients with rhinoconjunctivitis and allergy to birch as well as grass pollen were allocated to double-blinded clustered IT with aluminum-adsorbed extract produced from either birch (Betula verrucosa) pollen or grass (Phleum pratense) pollen. After 1 year of treatment, the patients continued IT with their original extract and also received the other extract. During the three consecutive pollen seasons, the rhinoconjunctivitis symptom score and the use of antihistamines, eye-drops, and oral prednisolone were recorded. Longitudinal data analysis was used to investigate the relation between different pollen counts and the magnitude of clinical efficacy. Results: An effect of IT was found on symptom score, antihistamine intake, and eye-drop use for both birch and grass (P values <0.05). The mean reduction in symptom score/medication by IT ranged from 24% to 95%, depending on mean seasonal pollen counts. A minimum mean seasonal grass-pollen count of 20–30 pollen grains m3 was required for the efficacy of grass IT to emerge. Conclusions: A model was developed for evaluation of efficacy in longitudinal IT studies, taking the differences in annual pollen counts into consideration. The model showed a significant beneficial role of pollen IT in rhinoconjunctivitis patients allergic to birch and grass pollen. [ABSTRACT FROM AUTHOR]

Provides information on local immunotherapy. Types of local immunotherapy; Concept behind the experimental evidence of local administration of allergen extracts on airway mucosa; Allergen extracts, formulations, and duration of treatment.

The article discusses the functions of recombinant allergens in the diagnosis and treatment of atopic allergy. It highlights the allergen-specific monitoring of immunoglobulin antibodies against allergens in childhood including the characterization of cross-reactions in accordance with the molecular structures of allergens. It also discusses several approaches to the production of new molecules for the treatment of birch-pollen allergy.

The increase in prevalence of allergic disorders which supposedly has occurred during the last few decades has happened despite the widespread use of pharmacologic therapy with both an ever increasing armoury of drugs and the more judicious application of allergen-specific immunotherapy in some countries. Allergy is usually considered to be an immunologic dysfunction leading to a severe local inflammatory response or to more serious systemic effects. Such effects are brought about by contact with allergens which., during prior exposure of the patient have induced particular elevated specific immune responses, in most cases, of the IgE isotype.

Sensitization to the house-dust mite is one of the most important risk factors for asthma, and a dose-response relationship between exposure to house-dust-mite allergens and asthma as well as asthma severity has been shown by several authors. The likelihood of mite-allergen exposure varies according to geographic conditions. To prevent exacerbation and deterioration, of established allergic disease, treatment of symptoms and inflammation should if possible, be combined with allergen avoidance. A broad range of mite-avoidance measures are theoretically possible, and this article reviews possible strategies.

We studied the protein-stabilizing properties of sucrose, in the extraction medium, on the composition and stability of ryegrass (Lolium perenne) pollen extracts. The effect of 0.5 M and 1 M sucrose was assessed in the presence and absence of 0.5% phenol, which is commonly used as a disinfectant in industrially prepared allergenic extracts. In the absence of phenol, sucrose improves the stability of extracts during storage, but it has little influence on the extraction process. In the presence of 0.5% phenol, however, both the quality of fresh extracts and the stability are greatly improved by 0.5 M and by 1 M sucrose, as shown by electrophoresis, immunoblotting, and RAST-inhibition experiments. The protection afforded by sucrose against the degrading effect of phenol is particularly evident for the major allergen Lol p 1 and for a set of basic allergens. In this respect, sucrose has been found to be superior to glycerol. on an equimolar basis. One may envisage the use of 0.5 M sucrose in allergenic extracts for intradermal testing and immunotherapy. [ABSTRACT FROM AUTHOR]

The effect of topically applied (10 μl) nedocromil sodium (NS) and sodium cromoglycate (CS) on the plasma extravasation induced by local application of ovalbumin (5%, 10 μl) into the respiratory nasal mucosa of sensitized guinea pigs pretreated with the neutral endopeptidase inhibitors, phosphoramidon, was studied. Topical NS (220 nmol, 10 μl) reduced by 57% the Evans blue dye extravasation caused by local application of ovalbumin into the nasal mucosa, whereas CS (220 nmol, 10 μl) was without effect. The tachykinin NK1 receptor antagonist CP-99994 (2 mumol/kg, i.v.) reduced by 45% the plasma extravasation induced by antigen challenge. The combination of NS and CP-99994 did not increase further the inhibition caused by NS alone. Plasma extravasation evoked by instillation of bradykinin (50 nmol), which causes this response by releasing tachykinins from sensory nerves, was markedly reduced by NS, but not by CS. Plasma extravasation evoked by installation of substance P, which acts directly on the endothelial cells, was not affected by NS. We conclude that the reduction by NS of the plasma extravasation induced by antigen challenge in the nasal mucosa of sensitized guinea pigs is due to the inhibition of tachykinin release from sensory nerve endings. [ABSTRACT FROM AUTHOR]

The aim of our investigation was to obtain a well-characterized active apple extract suitable for both in vivo and in vitro diagnostics by a technically simple method. For this purpose, apple extracts were prepared by homogenization in potassium phosphate buffer or by precipitation in organic solvents and resolubilization in potassium phosphate buffer in the presence or in the absence of enzyme inhibitors. These extracts were comparatively investigated by means of SDS- PAGE, two-dimensional electrophoresis, immunoblotting, RAST inhibition, and prick test. The in vitro investigations indicated that extracts prepared by precipitation in organic solvents (diacetone alcohol) at -20°C have a higher allergen activity than those prepared by extraction in aqueous solutions. From the in vivo tests (prick test), it was concluded that application of inhibitors of cytoplasmic enzymes (phenol oxidases, peroxidases, proteases) already during extraction is an essential precondition for active prick test solutions. Correspondingly, the extract obtained by solvent precipitation in the presence of enzyme inhibitors appeared to be most suitable for clinical application. [ABSTRACT FROM AUTHOR]

This presentation reviews recent progress in knowledge of (i) molecular biology and immunology of allergens and (ii) the methods for the modulation of allergen-specific immune response, with special emphasis on our grass pollen allergens, particularly Pao p IX AL, used as a model. The last few years have seen tremendous progress in molecular characterization of allergens, leading to synthesis of a number of recombinant allergens. Furthermore, studies of the structure-activity relationship of allergens have led to the delineation of the epitopes of these allergens and of widespread cross-reactivities among diverse allergens. In view of the requirement for extensive pre-clinical studies, the application of the recombinant allergens and epitopes in the clinical realm has just begun. Studies in murine systems suggest that these allergens and/or their epitopic peptides downregulate allergen-specific immune responses de novo. The potential and drawbacks of the recombinant allergens and peptides for improving the existing immunotherapeutic approaches and for developing new approaches to specific immunotherapy are discussed. [ABSTRACT FROM AUTHOR]

The variation in skin prick test (SPT ) results was evaluated clinically during terfenadine treatment in 39 adult patients with pollen rhinitis. A change in the perceived state of the patient as regards sensitization to a specific pollen allergen or atopic constitution was judged to be clinically important. A randomized, double-blind, crossover design was used, comprising 2 weeks on terfenadine 120 mg once a day and 2 weeks on placebo. SPT for two pollen allergens and histamine (10 mg/ml) were evaluated at the start of the study and at the end of each period. When SPT was used as a discovery test and liberal definitions were applied, predictive values for a positive test were 100%. 1-Sensitivity ranged between 10 and 54% with substantially lower values when a histamine wheal reaction was noted. The inhibitory effect of terfenadine was detectable 2 weeks after withdrawal as a reduction in the median of the mean diameter for the histamine-induced wheal response of 1 mm (0-1.5). The data implied that a positive SPT is reliable when liberal definitions are adopted for sensitization and atopy; a negative SPT is presumably reliable when the measurement artifact is considered and the wheal reaction to histamine is detectable. [ABSTRACT FROM AUTHOR]

Assessment of efficacy in immunotherapy trials is difficult: a number of parameters can be measured; these may give conflicting results and it is not clear which best represents the, clinical state. We therefore derived a Clinical Index (CI), by combining five individual parameters-diary card symptom score, visual analogue symptom score, drug score, nasal challenge and skin prick test-by rank analysis. The CI has been used to. express the results in a trial of house dust mite (D. pteronyssinus) immunotherapy for allergic rhinitis, comparing two active treatments, Pharmalgen® and Allpyral®, with placebo. The derived index correlated well with all parameters measured. Correlations between the five individual parameters were variable: with the exception of the skin test, good correlations were seen, each parameter correlating with two or three of the others, but the visual analogue showed the closest association with other parameters. Results from a single parameter taken alone could be misleading, e.g. in the Allpyral group, nasal challenge improved significantly, but symptoms assessed either by visual analogue or diary card score did not. The CI showed significant improvement in the Pharmalgen group but not in the Allpyral group. The CI gave a more reliable measure of outcome than individual parameters. [ABSTRACT FROM AUTHOR]

Allergen has previously been shown to induce a continuous increase in local dermal blood flow after a prick test in allergic subjects, whereas histamine induced, initially, similar peak increases in blood flow of much shorter duration. Blood flow changes induced by histamine and allergen have now been evaluated (i) after pretreatment with a local corticosteroid cream, clobetasole-17-propionate; (ii) after oral administration of the H1-antihistamine loratadine; and (iii) after oral pretreatment with the the alpha1-adrenoceptor agonist pseudoephedrine. Blinded placebo-controlled designs were used in the substudies. Laser doppler flowmetry was used for non-invasive recording of changes in local blood flow intermittently for 24 h after the topical corticosteroid, 6 h for the substudies on loratadine and pseudoephedrine. The size of the immediate weal and flare reactions, as well as late phase reactions, were also determined. Pretreatment with clobetasole-17-propionate cream on the skin for 1 week prior to prick tests did not affect the blood flow response elicited by histamine or allergen, in either the initial part (up to 1 h) or the protracted 24 h determinations. The size of the weal and flare reactions decreased. Loratadine and pseudoephedrine did not reduce the initial allergen-induced increase in blood flow, while lower blood flow compared with placebo pretreatment was noted for the protracted (1–6 h) determinations. Blood flow changes after histamine were unaffected. The histamine-induced weal and flare was inhibited by loratadine more effectively than the corresponding allergen-induced reaction. The weal and flare reactions after histamine and allergen were not changed after pseudoephedrine. The late dermal reaction expressed as the size of the erythema and/or induration present 6 h after allergen prick tests was reduced with pretreatment with loratadine as well as after pseudoephedrine when compared with placebo. The results from these pharmacological experiments suggest that pretreatment with potent topical corticosteroids had no effect on changes in dermal blood flow, while H1-antihistainines and α1-adrenoceptor agonists appear to have a direct effect on the vessels in a local allergic reaction. [ABSTRACT FROM AUTHOR]

The aim of the study was to determined whether IgG antibodies from patients on specific immunotherapy could inhibit skin test reactivity of allergens when mixed with them prior to testing. In a preliminary double-blind study, mite extracts were incubated with glycero-saline solution or non-specific IgG and used in testing 15 patients. Wheal and flare diameters produced with the two mite extracts did not differ significantly. In a second double-blind study with 15 other patients, skin tests using mite extracts incubated with either non-specific IgG or specific IgG showed significantly decreased diameters when mite extracts were preincubated with specific IgG. This result, in vivo, confirms the antigen neutralizing capacity of specific IgG demonstrated in vitro. [ABSTRACT FROM AUTHOR]

The article reports on the treatment of allergy patients by pharmacologically symptomatic treatment and immunotherapy (IT). Immunotherapy has been practiced for almost 80 years. The efficacy has been documented. Treatment of Type I allergic conditions--particularly hay fever-- with IT is not of recent origin. In 1921 it was demonstrated that serum from allergic patients contains a factor that may transfer allergen reactivity to the skin of an unsensitized subject. In spite of clinical improvernent on IT, no reduction of sensitizing antibodies in serum occurred. Many strategies have been followed in order to improve IT.

Twenty-six pollen-allergic subjects partidpated in a double-blind, placebo-controlled trial of the protective effect of the calcium antagonist. verapamil. on allergen-provoked nasal symptoms. Intranasal verapamil. 1 mg. had a weak protective effect in that "tickling score" was 22% lower (P < 0.01) and the number of sneezes 29% lower (nonsignificant) alter verapamil as compared with placebo pretreatment. There were no differences with regard to nasal blockage or discharge. It is concluded that the verapamil spray used, cannot be recommended for clinical trials, but that further investigations of other formulations of calcium antagonists are justified In order to analyse the potential role of this type of drugs in the treatment of allergic rhinitis. [ABSTRACT FROM AUTHOR]

The effects of immunotherapy by intranasal insufflation of Lolium perenne allergens modified with glutaraldehyde (Glu-Rye) was tested by a stratified placebo-controlled trial in 16 adult subjects with hay fever. The purpose of this pilot study was to determine whether the treatment could reduce nasal sensitivity to allergen in provocation tests. Modification of the allergen was shown to include polymerization and reduced allergenicity, but retained immunogenicity. Nasal sensitivity to unmodified L. perenne allergens was measured by threshold-type quantitative nasal challenge and posterior rhinometry for measurement of nasal airway resistance. In challenge tests after a 10-week course of intranasal preseasonal treatment with Glu-Rye, nasal sensitivity was reduced, but this effect was not maintained when testing was repeated 9 months after treatment. Post-seasonal serum levels of IgE antibodies to L. perenne were also not significantly affected by the treatment. [ABSTRACT FROM AUTHOR]

Background: Since the majority of allergic patients are polysensitized, it is often necessary to prescribe immunotherapy with multiple allergens. It is crucial to know if the administration of multiple allergens with sublingual immunotherapy (SLIT) increases the risk of side-effects in children. Methods: Consecutive children with respiratory allergy because of pollens, receiving SLIT for multiple or single allergens were followed-up in a postmarketing survey. Inclusion criteria were those for prescribing SLIT according to guidelines. Parents recorded in a diary card the side-effects (eye symptoms, rhinitis/ear itching, asthma, oral itching/swelling, nausea, vomiting, abdominal pain, diarrhoea, urticaria, angioedema and anaphylaxis). The side-effects were graded as mild, moderate and severe. Results: Four hundred and thirty-three children (285 male, age range 3–18 years) receiving SLIT were surveyed. Of them, 179 received a single extract, and 254 multiple allergens. The total number of doses given was 40 169 (17 143 with single allergen). Overall, 178 episodes were reported. Of them, 76 occurred with the single allergen (42.46% patients, 4.43/1000 doses) and 102 (40.3% patients, 4.42/1000 doses) with multiple allergens ( P = NS). 165 episodes (92.5%) were mild and self-resolving and were equally distributed in the two groups. In 13 cases, the events were judged of moderate severity and medical advice was required. Three patients discontinued SLIT, despite the local side-effects being mild. No emergency treatment was required at all. Conclusion: The use of multiple allergens for SLIT does not increase the rate of side-effects in children. [ABSTRACT FROM AUTHOR]

The article discusses that immunotherapy with insect venom is well documented and more widely accepted than immunotherapy with other allergens. Although the therapeutic principles are the same immunotherapy with insect venom differs from other forms of immunotherapy: Immunologically the injected allergens might stimulate differently and clinically the symptoms leading to immunotherapy are often much more dramatic and dangerous. On the other hand the spontaneous course of the disease will in more than 50% lead to less severe reactions to future stings. Especially in children the prognosis is good.