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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.

To evaluate difference in clinical efficacy, side effects, in vivo and in vitro parameters, 25 patients allergic to Yellow Jacket were treated with clustered immunotherapy using either 7 or 14 days interval between dusters. Twenty-one patients completed the 6 months' treatment period and four were withdrawn due to adverse reactions (2 cases of anaphylactic shock). Sixteen patients were challenged by in-hospital sting and the clinical efficacy was complete. Local side effects were observed in the majority of patients, but only rarely limited the course of immunotherapy. Skin sensitivity estimated as the venom concentration eliciting a wheal equal to histamine HCl 0.1 mg/ml using intradermal test was significantly reduced after 6 months of treatment. Specific IgE showed an initial increase, thereafter declining to pretreatment levels. IgG subclasses were determined by a triple antibody assay. Only subclasses 1 and 4 showed response. Subclass 4 showed a steady increase contrary to subclass 1 which decreased after reaching maintenance dose. No unambiguous relation between either the absolute value or the change of IgG1 and IgG4 at the time of challenge was observed in the patients who tolerated a sting. Furthermore, the IgG response was not correlated to the cumulative dose of venom administered. No simple regulatory function of IgG subclasses in the skin and IgE response was found, and the occurrence of local side effects did not seem to be determined by IgG antibodies. We conclude that clustered immunotherapy with Yellow Jacket venom is highly effective and that the frequency of side effects is acceptable. Neither the IgE nor the IgG response is significantly different with a 7- and 14-day interval between dusters, indicating that a protective dose of venom might be reached within 1 month. [ABSTRACT FROM AUTHOR]

Thirty-two patients with previous systemic allergic reaction to yellow jacket stings were randomly allocated to three groups receiving immunotherapy with different preparations of yellow jacket venom: 1) extract adsorbed to aluminium hydroxide (Alutard®-SQ), 2) Pharmalgen® extract or 3) non-adsorbed extract from Allergologisk Laboratorium (ALK aq.). Regular examinations showed a decrease in skin prick test size in nearly all patients. Specific IgE-antibody (RAST and CRIE scores) showed a similar, but not significant tendency to decrease in all three groups. Specific IgG-antibody increased considerably in the Alutard group only; after 2 years, however, no difference could be detected between the three groups. During dose increase, patients treated with ALK aq. generally had smaller local reactions to injections than those treated with Pharmalgen. Few systemic reactions occurred in all three groups. Nineteen patients treated for 2½-3½ years were challenged in-hospital with stings from yellow jackets. No systemic and only minor local reactions occurred. Consequently, with the dose regimens applied all three extracts seem effective even though no common changes in either specific IgE or IgG could be demonstrated. [ABSTRACT FROM AUTHOR]

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]

Background: Native allergen extracts or chemically modified allergoids are routinely used to induce allergen tolerance in allergen‐specific immunotherapy (AIT), although mechanistic side‐by‐side studies are rare. It is paramount to balance optimal dose and allergenicity to achieve efficacy warranting safety. AIT safety and efficacy could be addressed by allergen dose reduction and/or use of allergoids and immunostimulatory adjuvants, respectively. In this study, immunological effects of experimental house dust mite (HDM) AIT were investigated applying high‐dose HDM extract and low‐dose HDM allergoids with and without the adjuvants microcrystalline tyrosine (MCT) and monophosphoryl lipid A (MPL) in a murine model of HDM allergy. Methods: Cellular, humoral, and clinical effects of the different AIT strategies were assessed applying a new experimental AIT model of murine allergic asthma based on physiological, adjuvant‐free intranasal sensitization followed by subcutaneous AIT. Results: While low‐dose allergoid and high‐dose extract AIT demonstrated comparable potency to suppress allergic airway inflammation and Th2‐type cytokine secretion of lung‐resident lymphocytes and draining lymph node cells, low‐dose allergoid AIT was less effective in inducing a potentially protective IgG1 response. Combining low‐dose allergoid AIT with MCT or MCT and dose‐adjusted MPL promoted Th1‐inducing mechanisms and robust B‐cell activation counterbalancing the allergic Th2 immune response. Conclusion: Low allergen doses induce cellular and humoral mechanisms counteracting Th2‐driven inflammation by using allergoids and dose‐adjusted adjuvants. In light of safety and efficacy improvement, future therapeutic approaches may use low‐dose allergoid strategies to drive cellular tolerance and adjuvants to modulate humoral responses. [ABSTRACT FROM AUTHOR]

A computer program for the analysis of differences or changes in skin sensitivity has been developed. It is based on parallel line assays and its main features are its ability to conduct a validation process which ensures that the data from skin tests conform to the conditions imposed by the analysis which is carried out (regression, parallelism, etc.), the estimation of the difference or change iii skin sensitivity, and the determination of the 95% and 99% confidence intervals of this estimation. This program is capable of managing data from independent groups, as well as paired data, and it may be applied to the comparison of allergen extracts, with the aim of determining their biologic activity, as well as to the analysis of changes in skin sensitivity appearing as a consequence of treatment such as immunotherapy. [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 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.

Allergic reaction to stinging insects is one of the more dramatic allergic diseases. The combination of sudden pain, acute onset of reactions, and knowledge of sting-induced fatalities will often make the victim seek medical advice. Judged from the rather low mortality rate reported, emergency treatment is often sufficient to manage such cases. `the effect has uniformly been confirmed, and during the period when the need for immunotherapy in general was debated and safety regulations in some countries led to a reduction in the use of this kind of treatment, the need for venom immunotherapy was not questioned among specialists.

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]

In the past years, several investigators have demonstrated the existence of local nasal responses in some patients with typical allergic rhinitis symptoms but without atopy and have defined a new phenotype called local allergic rhinitis ( LAR) or 'entopy'. In a percentage of LAR subjects, the upper airway disease is also associated with lower airway symptoms. After the description of this phenotype, the differential diagnosis between LAR and nonallergic rhinitis ( NAR) has become a challenge for the clinician. To correctly identify LAR patients is of high importance for treatment and management of these patients, and for an appropriate inclusion of patients in clinical trials and genetics studies. The treatment of LAR patients, in contrast with NAR, is oriented to allergen avoidance and specific treatment. Allergen immunotherapy, the aetiological treatment for allergic respiratory diseases, has demonstrated to be an effective and safe treatment in LAR, increasing immunological tolerance, and reducing the clinical symptoms and the use of medication. In this article, the important and novel aspects of LAR in terms of mechanisms, diagnosis and treatment will be discussed. Also, the involvement of the lower airway and the potential role of IgE in the bronchial disease will be also reviewed. [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]

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]

Background: In immunotherapy trials, primary and secondary endpoints often focus on average symptom and medication scores during the pollen season or on days with low symptoms and low medication use. Thus, there is a need for endpoints describing the treatment effect on the most troublesome days in the pollen season. Aims of the study: A possible additional efficacy endpoint, days with severe symptoms during the pollen season, was investigated using data from a multicentre, double- blind, randomized, placebo-controlled trial of the SQ-standardized grass allergy immunotherapy tablet (AIT) (Grazax, Phleum pratense, 75 000 SQ-T/2,800 BAU, ALK, Hørsholm, Denmark). Methods: The trial included 634 subjects (NGrass AIT = 316; NPlacebo = 318) with grass pollen-induced rhinoconjunctivitis. Six different definitions of a day with severe symptoms were suggested. The number of days with severe symptoms was analysed and odds ratios were calculated. Results: The number and percentage of days with severe symptoms differed between definitions, but overall the analysis of days with severe symptoms showed consistent results (odds ratios: 2.0-3.4) for the different definitions. All definitions showed a reduced risk of having days with severe symptoms in the grass AIT group when compared to the placebo group. Conclusions: Days with severe symptoms during the pollen season is a relevant additional efficacy endpoint, which can be used in immunotherapy trials to support the clinical interpretation of commonly used efficacy endpoints. [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]

Specific Immunotherapy for respiratory allergy is used since about one century and there is now solid documentation of its efficacy. Nevertheless, the methods and experimental designs used in clinical trials are quite heterogeneous and there is no unanimously accepted methodological standard. Many studies are planned with study designs that may not confirm the clinical value of SIT as an effective treatment to reduce disease severity. To ensure that patients are treated based on sound scientific evidence and to minimize the risk of misusing limited financial resources for scientific studies, the World Allergy Organization (WAO) convened a group of experts to provide guidelines for the methodology of future immunotherapy studies. This document summarizes the recommendations for study design, patients’ selection, appropriate outcomes and statistical treatment to be used in planning and performing clinical trials with specific immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Sublingual immunotherapy (SLIT) is effective and safe in the treatment of allergic rhinitis. However, there is no meta-analysis in asthma treatment. Methods: The clinical efficacy of SLIT for asthma was evaluated through a systematic review with meta-analysis. MEDLINE (1966–2005), EMBASE (1974–2005), LILACS (1982–2005), and the Cochrane Library were searched for related literature in any language. Randomized-controlled clinical trials (RCT) on SLIT in asthma treatment for adults and children were selected. From 119 citations, 25 studies with 1706 patients were included in this meta-analysis. For each report, quality scores were assigned and data were extracted in relation to the outcomes analyzed: asthmatic symptoms, use of asthma medications, lung function, and bronchial provocation. Results: According to the Jadad quality method, 64% of the studies were assigned scores of 4 or 5. Immunotherapy was seen to significantly reduce asthma severity when parameter compositions were all analyzed by categorical outcomes. There was a nonsignificant reduction in asthma symptoms when analyzed using standardized mean differences. No severe reactions were observed. Conclusions: This meta-analysis found that SLIT is beneficial for asthma treatment albeit the magnitude of the effect is not very large. Moreover, it is a safe alternative to the subcutaneous route. More RCT with standardization of symptom scores and medications are needed in order to contribute further to this subject. [ABSTRACT FROM AUTHOR]

Using Medline we identified 39 placebo-controlled, double-blind sublingual immunotherapy (SLIT) studies providing symptom–medication score. These were retrospectively evaluated for evidence of clinical efficacy and quality of study presentation. Clinical efficacy was estimated according to statistical significance and graded as: unequivocal efficacy (statistically significant difference from placebo in both symptom and medication scores or the combined score), which was observed in 28% of studies, possible efficacy (significant improvement in either symptom or medication scores) seen in 33%, and no efficacy (no statistical difference between active treatment and the placebo group), as found in 38% of studies. Generally, studies were limited by the number of patients, showed a high frequency of withdrawals, a short duration of treatment, and insufficient data on randomization. The magnitude of efficacy additional to placebo treatment must be >20% in order to justify the treatment. This review concludes that future SLIT studies should be planned in accordance with international recommendations in order to be conclusive. [ABSTRACT FROM AUTHOR]

Background: Systemic side-effects of venom immunotherapy (VIT) represent a considerable problem in the treatment of patients allergic to Hymenoptera venom. We examined the hypothesis whether basophil responsiveness might be connected with the adverse reactions to VIT. Methods: Basophil surface expression of activation marker CD63 induced by different concentrations of honeybee and wasp venom (0.1 and 1 μg/ml) was measured by flow cytometry in 34 patients with history of systemic anaphylactic reactions to Hymenoptera sting just before rush honeybee or wasp VIT. Results: Eleven of 34 patients had systemic anaphylactic reaction (Mueller grades I–III) and one patient a large local reaction to VIT. In those 12 patients, median percentage of activated basophils after stimulation with VIT-specific venom in concentration of 0.1 μg/ml was 99% (range: 17–195) of value reached with stimulation with 1 μg/ml. Side-effects occurred in all patients with 0.1/1 ratios over 92% (eight of 12). In contrast, in 22 patients with no side-effects, the median 0.1/1 ratio was 25% (range: 2–92). These concentration-dependent activation ratios were significantly different between the groups with and without side reactions ( P < 0.0001). We also show significant positive correlation of the occurrence/clinical grade of the side-effects with individual ratios of CD63 basophil response ( r = 0.73, P < 0.0001). Conclusion: The results suggest that increased basophil sensitivity to allergen-specific in vitro stimulation is significantly associated with major side-effects of VIT. [ABSTRACT FROM AUTHOR]

Sublingual-swallow immunotherapy (SLIT) is an accepted treatment for allergic rhinitis but its optimal dosage is scantly investigated. We studied the dose dependence of clinical efficacy and immunological response to SLIT by administering two different dosages of the same allergen in rhinitic children monosensitized to grass pollen.Seventy-one patients with comparable age and symptoms were randomized to receive SLIT by the same grass pollen extract from Stallergénes (Antony, France), 40 of them with the 100 IR and 31 with the 300 IR extract. All patients recorded diary cards for symptoms, medications and side-effects of the treatment, and had measurements of specific IgE and IgG4 in serum by the CAP System FEIA (Pharmacia, Uppsala, Sweden) and in nasal secretion by anin situincubation method with the same reagents of CAP System FEIA.Symptom/medication scores during the pollen season were significantly higher in patients treated with the lower dosage compared with those treated with the 300 IR dosage. Side-effects occurred with a comparable rate (25.8%vs27.5%) in the two groups. Serum-specific IgE and IgG4 had no significant changes after 3 months of SLIT in both groups, while a significant seasonal increase of nasal IgE (P = 0.015) and IgG4 (P = 0.019) was found only in patients treated with the lower dosage.A rise of specific IgG4 and a blunting of seasonal increase of specific IgE in serum was repeatedly reported during subcutaneous immunotherapy (SCIT) with pollen extracts. Our findings show such blunting of specific nasal IgE along with a low symptom/medication score in patients treated with SLIT with the higher dosage, but not a concomitant rise of specific nasal IgG4. This suggests a local immunological effect of SLIT, different from systemic mechanisms of SCIT. [ABSTRACT FROM AUTHOR]

The use of immunotherapy in asthmatic children is still controversial. Sublingual immunotherapy (SLIT) may represent an advance, due to the good safety profile, but little is known about its effects on lung function and nonspecific bronchial responsiveness. The aim of this study was to assess the effects of SLIT on these parameters, in children with Parietaria pollen-induced asthma. Thirty children with asthma solely due to Parietaria who participated in a previous randomized, placebo-controlled trial with SLIT were studied: pulmonary function test and methacholine challenge were carried out at baseline in winter 1999 (out season), during the 1999 season (before randomization), and during the 2001 season. Before randomization, there was a significant fall in methacholine provocation concentration during the pollen season vs baseline in both groups (SLIT group 9.78 ± 5.95 mg/ml vs 3.37 ± 2.99 mg/ml; placebo 8.70 ± 6.25 mg/ml vs 2.44 ± 2.25 mg/ml; P = .005). In the second pollen season, the response to methacholine returned to baseline values in the active group (9.10 ± 7.7 mg/ml; P = NS vs baseline), whereas in the placebo group a significant increase in reactivity was still present (2.46 ± 2.26; P = 0.008 vs baseline). No significant difference in FEV1 and FEF25−75 between the two groups was observed at all times. Our data show that SLIT abrogates the seasonal bronchial hyperreactivity in children with asthma due to Parietaria. This may be regarded as an indirect evidence of the effect on bronchial inflammation. [ABSTRACT FROM AUTHOR]

Background: For the immunotherapy of Hymenoptera venom allergy various preparations and treatment protocols are in use. However, controlled studies making direct comparisons of the efficacy and safety of different regimens are rare.) Objective: To assess prospectively different venom immunotherapy (VIT) protocols using an aqueous or an aluminium hydroxide adsorbed allergen preparation for the treatment of honeybee venom (HBV) allergy. Methods: Sixty-five HBV allergic patients (42 males, 23 females; aged 17-75 years) with a history of systemic anaphylactic reactions (SARs) to honeybee stings were treated according to three different regimens. During the incremental phase, patients in group A ( n = 21) or B ( n = 21) received an aqueous preparation according to a rush protocol. Patients in group C ( n = 23) were treated with conventional ('slow') VIT using an aluminium hydroxide adsorbed depot preparation. The maintenance dose was 100 μg venom in all groups. Maintenance treatment in group A was performed with the aqueous preparation administered every 4 weeks, whereas in groups B and C the depot preparation was administered every 8 weeks (group B) or every 4 weeks (group C). A sting challenge test with a living honeybee was performed in 49 patients, 6-12 months after reaching the maintenance dose. Another seven patients were stung accidentally by a honeybee ('field sting'). Results: Treatment with the aqueous preparation evoked large local reactions more frequently than the depot preparation in the dose increase phase [53/693 (7.6%) vs 8/206 (3.9%); P = 0.059] and also in the course of maintenance therapy [85/172 (49.4%) vs 58/478 (12.1%); P < 0.001]. During the dose increase phase, systemic side-effects seemed to occur more frequently in patients on rush VIT with the aqueous preparation compared to patients initially treated with the conventional schedule using the depot preparation [13/42 (31.0%) vs 3/23 (13.0%); not significant). When re-stung by the culprit insect, SARs were observed in 3/20 patients (15.0%) in group A, 2/18 (11.1%) in group B and 3/18 (16.7%) in group C (not significant). Conclusion: The aluminium hydroxide adsorbed HBV preparation caused fewer large local reactions than the aqueous preparation. The therapeutic efficacy of the three treatment protocols did not differ. [ABSTRACT FROM AUTHOR]

Background: Recent studies showed that injection specific immunotherapy (SIT) with birch pollen extract greatly reduces or cures the associated apple allergy in a large proportion of birch pollen-allergic patients. However, the long-term efficacy of SIT for apple allergy has not been assessed. Objective: To evaluate the duration of the effect of injection SIT with birch pollen extract on apple allergy in birch pollen-allergic patients. Methods: Thirty birch pollen-allergic patients showing both the clinical disappearance of apple allergy and a negative SPT with fresh apple at the end of their injection SIT course were followed-up at 12-month intervals from 6 months after SIT was stopped. Apple tolerance as well as SPT was assessed on all occasions. Fifty-seven birch pollen-allergic subjects without apple allergy and not submitted to SIT regularly followed-up for the onset of oral allergy syndrome (OAS) were used as controls. Results: The overall prevalence of OAS after 30 months of follow-up did not differ between patients and controls. Although most patients became re-sensitized to apple by SPT over time, >50% of them were still able to tolerate eating the fruit at the 30-month follow-up visit. Conclusion: Although most patients show a ‘natural’, gradual propensity to apple re-sensitization (a consequence of prolonged and repeated inhalation of birch pollen responsible for primary sensitization?), the clinical effects of injection SIT on food allergy seem rather long lasting. [ABSTRACT FROM AUTHOR]

Background: There is only very limited documentation of the efficacy and safety of high-dose subcutaneous birch pollen immunotherapy (IT) in double-blind, placebo-controlled (DBPC) studies. Birch pollen is a major cause of allergic morbidity in northern Europe and in eastern parts of North America. Methods: Thirty-five patients with severe rhinoconjunctivitis (hay fever) to birch pollen were allocated to double-blinded clustered IT with a depot birch pollen extract (Betula verrucosa ) or placebo injections. Seven patients in each group had concomitant self-reported seasonal asthma. Treatment was conducted as a clustered regimen and was performed in a specialist unit. Symptom scores from nose, eyes, and lungs, and use of oral and topical antihistamines, beta-2-agonists, and oral corticosteroids were recorded daily during the season of 2000. Sensitivity to allergen provocation in skin, conjunctiva, and nasal mucosa was measured before and after 10 months of treatment. Post-seasonal assessment of symptom severity was performed using a simple questionnaire. Results: IT reduced the symptom score for both rhinoconjunctivitis and asthma (P -values < 0.05), total medication score (P < 0.02) and use of oral antihistamines (P < 0.01). IT reduced specific conjunctival sensitivity (P < 0.05), skin prick test, and especially cutaneous late-phase response diameters (P < 0.00001), and increased general well-being on post-seasonal evaluation (P < 0.01). IT was safe, with side-effects at the same level as placebo. Conclusions: High-dose, subcutaneous IT is efficacious and safe in patients with severe birch pollen rhinoconjunctivitis and asthma. Background: There is only very limited documentation of the efficacy and safety of high-dose subcutaneous birch pollen immunotherapy (IT) in double-blind, placebo-controlled (DBPC) studies. Birch pollen is a major cause of allergic morbidity in northern Europe and in eastern parts of North America. Methods: Thirty-five patients... [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.

Discusses studies on the mechanisms of specific immunotherapy (SIT) for allergic diseases. Effect of long-term immunotherapy on the late-phase reaction induced by allergens in the nasal and bronchial mucosa and in the skin; Association between immunotherapy and immunoglobulins; Targets of SIT, including antigen-presenting cells.

Thirty-one adult patients with asthma caused by house-dust mites (HDM) were included in this placebo-controlled, double-blind study to evaluate the efficacy and safety of specific immunotherapy (SIT) with biologically standardized extracts of HDM. The specific diagnosis was confirmed by skin prick tests, specific IgE, and bronchial provocation tests with HDM allergens. The patients were randomized to receive active treatment with extracts of either Dermatophagoides pteronyssinus (Dpt) or D. farinae (Dfa) (Alutard® SO, ALK, Denmark) or placebo injections. Twenty-three patients completed the study. After 1 year of treatment, we found a clinically important and significant reduction in both asthma medicine consumption (inhaled steroids 38% and beta 2-agonists 46%) and symptom score (57%) in the actively treated group, but not the placebo group. These findings were confirmed by a significant decrease in skin and bronchial sensitivity to HDM in the active group. Additionally, there was a significant difference in the patients' scores for effect in favor of the actively treated group. Total IgE and specific IgE to HDM showed no significant changes before and after treatment for either group. Spirometric lung-function measurements showed a significant increase in forced expiratory volume in 1 s (FEV1) from 85% before to 89% of predicted values after treatment for the actively treated group. Peak-flow measurements at home showed no significant changes during the study. It is concluded that allergen SIT is an effective treatment in adult patients suffering from asthma due to HDM. [ABSTRACT FROM AUTHOR]

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.

According to the maximum tolerated dose (MTD) achieved, we assessed the changes in clinical and laboratory parameters, induced by specific immunotherapy (SIT), in a group of 43 asthmatic patients sensitized to Dermatophagoides pteronyssinus, over a period of 18 months. A standardized extract (100 Bu/ml; 40 μg/ml of Der p 1; 20 μg/ml of Der p 2) was used. The patients were divided into two groups: the high-dose immunotherapy (HDI) group (MTD ≥= 4 μg Der p I) and the conventional immunotherapy (CI) group (MTD < 4 μg Der p 1). Changes in clinical severity index, medication, and symptom scores; in cutaneous and conjunctival reactivity; and in the levels of specific IgE, IgG, IgG1, and IgG4 to D. pteronyssinus (Der p 1 and Der p 2) were measured (ELISA monoclonal antibodies). Safety was monitored according to the EAACI guidelines. The range of the MTD was 0.8-16 μg of Der p 1. Ninety percent of the patients tolerated a dose of 3.2 μg, but only 18% of the patients reached a maintenance dose of 16 μg. The medians of the accumulated dose were 197 μg of Der p 1 for the HDI group, and 50 μg for the CI group. Conjunctival and cutaneous reactivity was significantly lowered (P< 0.001) after SIT, as were the clinical severity score and medication score in both groups, without significant differences between the groups, except for cutaneous reactivity. Levels of specific IgE decreased significantly (P< 0.01) in both groups, again without significant differences between the groups. The range of the increase in medians of specific IgG, IgG1, and IgG4 was 4.4-120-fold for the HDI group and 3-24-fold for the CI group (P< 0.01). The increase in the levels of Der p 1 and Der p 2 IgG4 were correlated to the changes in cutaneous and conjunctival reactivity (P< 0.01). These results show that a maintenance dose of 3.2 μg Der p 1 (8 BU) can induce pronounced clinical and immunologic changes with an excellent safety profile. [ABSTRACT FROM AUTHOR]

The article focuses on the systemic hypersensitivity reactions to allergy by hymenoptera venom. The reactions to this allergy are due to an IgE-mediated, immediate-type allergy. Since the late 1970s, immunotherapy with hymenoptera venoms has been available for treatment of allergic patients. The procedure is highly effective: about 80-100% of those who formerly had reacted systemically do not do so when re-stung after treatment has been initiated. The classical diagnostic tools in this allergy are history, skin tests, and estimation of allergen-specific IgE serum antibodies. The sting challenge is generally accepted as a method to evaluate the efficacy of immunotherapy.

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]

Grass pollen immunotherapy is effective, although efficacy must be balanced against side-effects. In a double-blind, placebo-controlled trial of 40 adult patients with summer hay fever, immunotherapy with a depot grass pollen extract (Phleum pratense, Alutard SQ) reduced symptoms and medication requirements with an acceptable minimal level of side-effects (31). The original placebo group, as well as the actively treated group. have now received active immunotherapy in an open fashion for a further 3 years. An important question was whether continued injection treatment was accompanied by maintained clinical improvement. By analysis of diary symptoms, rescue medication, and visual analogue scores during the pollen season, we show that efficacy was maintained throughout the 3-4- year study period. Clinical improvement was accompanied by a sustained and marked decrease in immediate conjunctival allergen sensitivity and a further significant decrease in the size of the allergen-induced late cutaneous response. In contrast, an initial decrease in the allergen-induced immediate cutaneous response was not maintained at 3-4 years. Of the patients, 37/40 completed the first year, 33/40 the second year. and 32/40 the third year of treatment. Patients dropped out for reasons other than the outcome of immunotherapy. During a total of 2598 injections, five immediate systemic reactions were observed, all during the induction (not maintenance) phase, and all occurred within 10 mm of injection and responded promptly to adrenaline. Grass pollen immunotherapy is effective and safe, provided it is performed on carefully selected patients by trained physicians with immediate access to resuscitative measures. [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]

Fifty-eight patients with well-documented history of seasonal rhinoconjunctivitis caused by grass pollens were. allocated randomly on a double-blind basis to receive either sublingual therapy with a solution of purified, standardized allergen preparation (Stallerg&egravenes) or a matched placebo for 17 weeks. The assessment of the effect of oral immunotherapy, done with drops of five-grass allergen extract, was on the clinical symptoms and on the medication score of the authorized rescue treatments. The actively treated patients had significantly (P < 0.05 to P < 0.01) fewer symptoms of rhinitis (sneezing and rhinorrhea) and of conjunctivitis (redness and tears) during the pollen season than the placebo group. Consumption of nasal solution of sodium cromoglycate and of betamethasone and dexchlorpheniramine was significantly less in the desensitized group (P < 0.01). Side-effects were negligible. This studs concludes that perlingual immunotherapy with grass pollen extract in grass-pollen-sensitive seasonal hay fever and conjunctivitis patients is effective, easy to perform inexpensive, and safe. [ABSTRACT FROM AUTHOR]

Immunotherapy (IT) was performed for 12 months with a purified and standardized preparation of Dermatophagoides farinae. Twenty adults with rhinoconjunctivitis sensitive to house-dust mite were given IT, and a similar group of 11 patients served as open controls. A total of 512 injections were given. Twenty-eight episodes of allergic side-effects occurred, 13 general and 15 local, most of them during the initial incremental dose period. No severe reactions started later than 30 min after the injection. One patient suffered anaphylactic shock. In this patient, specific antibodies fell immediately, followed by an increase within 1 week. The therapy group improved significantly in relation to the open controls in patients' subjective evaluation of symptoms (P < 0.028) and skin (P < 0.0001) and conjunctival (P < 0.001) sensitivity. Specific IgE increased in controls (P < 0.0001) but not in IT-treated patients during the "mite season"; that is, there was a significant difference in change during the observation period (P < 0.0001). There was also a difference in change of specific IgG between the groups during the first 4-5 months and the whole year (P < 0.0001), but not from 4-5 months to 12 months. In contrast to changes in antibody titer (IgG, P = 0.04), changes in conjunctival (P < 0.01) and especially skin sensitivity (P < 0.005) correlated well with subjective improvement. This implies that the skin prick test and the conjunctival test can be recommended for follow-up of IT. Furthermore, we recommend that changes in skin sensitivity be expressed as change in allergen concentration either inducing the same wheat response before and after IT as evaluated by parallel-line bioassay, or inducing the same wheal response before and after IT as that induced by histamine tested at the same time. Finally, our findings support the hypothesis of a switch from IgE + to IgE - during successful IT. [ABSTRACT FROM AUTHOR]

A double-blind, placebo-controlled study of immunotherapy was conducted in 19 patients with grass-pollen hay fever to evaluate the efficacy and safety of a formalinized depot grass allergoid. The patients were assessed before and during IT by clinical (symptom-medication scores during the grass- pollen season, specific nasal and skin reactivity) and immunological (specific IgE, IgG, IgG1 and IgG4 antibodies) parameters. High doses of grass allergoid, corresponding to a cumulative pre-seasonal dosage of 46,050 PNU, were administered, with only one systemic reaction. The actively treated patients had significantly lower symptom-medication scores than placebo (p < 0.01) during the month of May and showed a significant decrease in specific skin (p < 0.01) and nasal (p < 0.05) reactivity, and a significant early increase in specific IgE (p < 0.01), IgG (p < 0.0005), IgG1 (p < 0.001) and IgG4 (p < 0.05), with a subsequent decrease of IgE and IgG1. No differences were detected in any of these parameters in the placebo group. A correlation was found between high IgG4/IgG1 ratio and the specific skin reactivity decrease (r = 0.691, p < 0.05), whereas a high IgG4/IgG1 ratio was associated with higher symptom-medication scores (r = 0.654, p < 0.05). Possible explanations of these apparent discrepancies are proposed. [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]

The article focuses on prevention and treatment of occupational allergic diseases. It includes evaluation of immunological and respiratory status in swine farmers, prevention of allergic reactions in chronic hemodialyzed patients by suppression of putative allergenic parameters during the dialysis session, altered monocyte/macrophage function due to exposure to suspended diesel exhaust particles, green coffee bean dust as a cause of occupational asthma, screening of latex allergy in nurses, immunotherapy follow-up by re-sting in honeybee venom allergic patients, etc.

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.

Patients allergic to pollen from alder, birch and hazel were hyposensitized during a 3-year period with either birch pollen extract alone (n = 24) or a mixture of one or more of alder, birch and hazel pollen extracts (n = 27). The effect of the treatment was evaluated by RAST and tandem crossed-radioimmunoelectrophoresis (tandem-CRIE). The patient' specific IgE response to the major allergens of alder (Aln g I), birch (Bet v I) and hazel (Cor a I and Cor a II), as measured by tandem-CRIE, and the total specific IgE response, measured by RAST, decreased significantly (Pc < 0.05) during immunotherapy, irrespective of the extract used during the treatment. There was no significant difference (Pc < 0.05) between the two treatment groups. The results obtained indicate either that birch pollen extract alone is adequate in the treatment of the studied patient group or the patients had been sensitized towards birch pollen alone. [ABSTRACT FROM AUTHOR]

The IgE-response was evaluated by skin prick test, bronchial provocation test and RAST in a 1-year placebo-controlled double-blind immunotherapy study. Eleven adult asthmatics were treated with a Cladosporium allergen preparation and 11 comparable patients received histamine placebo. The bronchial sensitivity (PC20) decrease > 0.5 log step in &frac811; (73%) Cladosporium-treated versus &frac311; (27%) in the placebo group. Corresponding figures for skin prick test sensitivity was 10/11 (91%) and &frac111; (9%) respectively. Circulating IgE showed a temporary boost in the Cladosporium group and then values approaching the pretreatment value. Only minimal and insignificant changes were found in the placebo-treated patients. Changes in IgE-reactivity were not related to allergen dose, clinical efficacy or to the occurrence of side effects. Some interrelation between changes in skin prick test, bronchial provocation test and RAST was found indicating a differentiated effect of immunotherapy on various IgE compartments. In spite of the pathogenetic role of IgE in allergic diseases, changes in IgE-reactivity do not seem directly involved in the mechanisms underlying the clinical efficacy of immunotherapy but might be of importance in a complex interaction with other immunological parameters. [ABSTRACT FROM AUTHOR]

This double-blind immunotherapy trial in children, using a purified and standardized Cladosporium herbarium preparation, has shown that children with mould asthma and/or rhinoconjunctivitis, responded to immunotherapy with a decrease in specific IgE and a significant increase in specific IgG. There was a marked increase in the ratio specific IgG/specific IgE as a result of active treatment, IgE-CRIE radiostaining patterns showed no pronounced changes after 10 months' actives treatment and no "new sensitivities" could be detected in the studied patients. IgG-CRIE radiostaining, primarily directed towards the important allergens, was significantly increased in the active group and particularly towards Ag-12 (partially identical to a previously described major allergen in Cladosporium herbarium, Ag-54). Children treated with histamine placebo showed no change in antibody patterns during 10 months of treatment. [ABSTRACT FROM AUTHOR]

Monomethoxy polyethylene glycol (mPEG) modified honey bee venom (HBV) immunotherapy (IT) has been studied in 14 patients allergic to honey bee venom. Doses could be increased more rapidly and higher doses were reached compared to regular venom immunotherapy. No general side effects were seen, although large local swellings were found somewhat more often than with regular HBV. Most patients could easily be switched from the modified to the unmodified venom. Eight patients experienced and tolerated field stings. Skin testing showed decreased allergenicity of the mPEG-HBV. The mean HBV-specific IgE level was below pre-treatment level already after only 6 weeks of IT. The HBV-specific IgG response was very good. [ABSTRACT FROM AUTHOR]