New approaches for developing biomarkers of hormonal contraceptive use.

To identify biomarkers of hormonal contraceptive (HC) use in urine and saliva, we conducted a pilot study with 30 women initiating levonorgestrel (LNG) containing combined oral contraceptives (COCs) or depot medroxyprogesterone acetate (DMPA) (15/group). Based on established COC pharmacokinetics, we collected serum and urine samples before COC ingestion and during Days one and three of use, or before DMPA injection and on Days 21 and 60 post-injection. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure serum/urine LNG and MPA. LNG was undetectable at baseline (specificity 100%); post ingestion, most urine samples had detectable LNG levels (sensitivity: 80% 6 h post Dose one, 93% 6 h post Dose three). We used a DetectX LNG immunoassay kit and showed 100% sensitivity measuring urine LNG. Urine MPA levels were undetectable in 14/15 women at baseline (specificity 91%); post-injection all urine samples had detectable MPA levels (sensitivity: 100% days 21 and 60). Results suggest urine sampling can be used to identify a biomarker of LNG and MPA use. Based on evidence from other steroidal hormonal studies showing changes affecting the transcriptome profile of saliva at 24 h, we used the same (COC, DMPA) timepoints to collect saliva. We performed transcriptome analysis and detected several differentially expressed genes in DMPA users' saliva on Days 21 and 60 compared to baseline; none among COC users. We plan further research of differential gene expression in saliva as a HC biomarker of DMPA use, and will explore longer periods of COC use and saliva collection times, and application of microRNA sequencing to support using saliva as a COC biomarker.

Dipeptidyl peptidase IV of the Vespa velutina nigrithorax venom is recognized as a relevant allergen.

BACKGROUND: Vespa velutina nigrithorax (VVN), typically known as the Asian yellow-legged wasp, has been one of the most significant invasive species in western Europe since 2010. Currently, VVN has become the most prevalent cause of Hymenoptera anaphylaxis in the north and northwestern Spain. For this reason, it is crucial to diagnose anaphylaxis cases in the acute moment for carrying out the best available treatment as soon as possible. OBJECTIVE: To achieve a complete understanding of the venom allergen composition that will help to develop efficient diagnostics and immunotherapy treatments on the basis of this venom. METHODS: In this study, autochthonous VVN venom was obtained and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, isoelectric focusing, followed by a mass spectrometry analysis. In addition, the allergenic sensitization profile of patients diagnosed with allergy to VVN in the Allergology Service of Navarra University Hospital between the years 2017 and 2020 was studied by immunoblotting and specific IgE (ImmunoCAP, Thermo Fisher Scientific, Uppsala, Sweden). RESULTS: Two new allergens (dipeptidyl peptidase IV and serin protease) were identified in the autochthonous VVN venom, and their identity was confirmed by liquid chromatography-mass spectrometry analysis. The study by ImmunoCAP using sera from 12 patients who had a systemic reaction after a VVN sting revealed groups 5 and 1 as predominant allergens (92% and 34%, respectively). Furthermore, the immunoblotting assay recognized dipeptidyl peptidase IV (50%) in the sera of these patients. CONCLUSION: Serine protease and the dipeptidyl peptidase IV are components of the VVN venom, and the latter is an allergen recognized in the studied population.

Changes in the Sensitization Pattern to Alternaria alternata Allergens in Patients Treated with Alt a 1 Immunotherapy.

Alternaria alternata is the most important allergenic fungus, with up to 20% of allergic patients affected. The sensitization profile of patients sensitized to A. alternata and how it changes when treated with immunotherapy is not known. Our objective is to determine the allergen recognition pattern of allergic patients to A. alternata and to study its association to the parameters studied in a clinical trial recently published. Sera of 64 patients from the clinical trial of immunotherapy with native major allergen Alt a 1 were analyzed by immunoblotting; 98. 4% of the patients recognized Alt a 1. The percentage of recognition for Alt a 3, Alt a 4, and/or Alt a 6, Alt a 7, Alt a 8, Alt a 10 and/or Alt a 15 was 1.6%, 21.9%, 12.5%, 12.5%, and 12.5% respectively. Of the 64 patients, 45 (70.3%) only recognized Alt a 1 among the allergens present in the A. alternata extract. Immunotherapy with Alt a 1 desensitizes treated patients, reducing their symptoms and medication consumption through the elimination of Alt a 1 sensitization, which is no longer present in the immunoblotting of some patients. There may be gender differences in the pattern of sensitization to A. alternata allergens, among others.

Integration of in vitro allergy test results and ratio analysis for the diagnosis and treatment of allergic patients (INTEGRA).

The introduction of molecular diagnosis into routine clinical practice has substantially improved the diagnosis and management of allergic patients by allowing clinicians to precisely identify the allergenic molecule responsible for immunoglobulin E (IgE)-mediated allergies. However, it can be challenging to accurately interpret the results of molecular assays, partly due to the limited evidence base. In this context, a panel of experts with extensive experience in interpreting in vitro measures of total and serum specific IgE reviewed the available scientific evidence. After this review, the panel selected a series of representative case studies to demonstrate how determination of specific and total IgE values and the relationship between them (ratio analysis) can add value to the diagnostic process by more precisely defining the patient's sensitization profile. Finally, the experts developed a series of recommendations on the clinical application of ratio analysis to optimize and complement the classical approach to allergy diagnosis.

Validation of novel recipes for masking peanuts in double-blind, placebo-controlled food challenges.

BACKGROUND: Double-blind, placebo-controlled oral food challenges are the gold standard in food allergy diagnosis. Nevertheless, proper masking of peanuts is particularly complex owing to their intense flavor and odor. Thus, it is important to use validated recipes to ensure their adequate masking during oral food challenges. OBJECTIVE: To design and validate recipes containing masked peanuts for double-blind, placebo-controlled oral food challenges. METHODS: Two types of products (cookies and a custard­type dessert) containing the masked peanuts and other ingredients with low allergenic potential were designed and validated. For this purpose, of the 24 initial cookie recipes and 12 initial custard recipes developed, those that did not exhibit significant differences in their texture were selected for sensory validation. RESULTS: Similarity triangle tests were performed using a panel of 36 selected tasters, enabling the validation of 1 pair of cookie recipes and 1 pair of custard-type dessert recipe, both with low allergenic potential and suitable for those with celiac disease and for vegans. CONCLUSION: The validated recipes are of clinical and research interest because they allow to confirm a peanut allergy and detect a wide range of tolerated threshold doses, which makes it possible to provide specific indications for each patient.

Oral immunotherapy in severe cow's milk allergic patients treated with omalizumab: Real life survey from a Spanish registry.

BACKGROUND: Oral immunotherapy is a frequent treatment for the management of food allergies, but adverse events (AE) are common. This study assessed the outcome of cow's milk oral immunotherapy (MOIT) in severe cow`s milk-allergic patients treated with omalizumab in a real-life setting. METHODS: OmaBASE was a national, multicenter, open, and observational registry that collected clinical, immunologic, and treatment from patients with food allergy receiving omalizumab. RESULTS: Data derived from 58 patients aged 10.3 years (IQR 6.3-13.2) and median milk-specific IgE 100 kUA /L at the start of omalizumab treatment. Most had experienced anaphylaxis by accidental exposures (70.7%) and had asthma (81.0%). Omalizumab in monotherapy induced tolerance to ≥6000 mg of cow's milk protein (CMP) to 34.8% of patients tested by oral food challenge. Omalizumab combined with MOIT conferred desensitization to ≥6000 mg of CMP to 83.0% of patients. Omalizumab withdrawal triggered more AE (P = .013) and anaphylaxis (P = .001) than no discontinuation. Anaphylaxis was observed in 36.4% of patients who discontinued omalizumab, and more in those with sudden (50.0%) rather than progressive (12.5%) discontinuation. At database closure, 40.5% of patients who had completed follow-up tolerated CMP without omalizumab (7.2% 1500-4500 mg; 33.3% ≥6000 mg). CONCLUSION: Milk oral immunotherapy initiated under omalizumab allows the desensitization of subjects with severe cow's milk allergy even after omalizumab discontinuation. However, discontinuation of omalizumab can lead to severe AE and should be carefully monitored.

Recent Advances in Allergen-Specific Immunotherapy as Treatment for Allergic Asthma: A Practical Overview.

The Global Initiative for Asthma Report updated in 2019 stated that potential benefits of allergen immunotherapy (AIT), compared to pharmacological and avoidance options, must be weighed against the risk of adverse effects and the inconvenience and cost of the prolonged course of therapy in asthma. Thus, with the aim of clarifying some aspects with regard to the possible use of AIT in allergic asthma treatment armamentarium, a group of expert allergists from the Spanish Allergy and Clinical Immunology Scientific Society (SEAIC), particularly from the Immunotherapy and Asthma Interest Groups developed a frequently asked questions in clinical practice. This document updates relevant topics on the use of AIT in asthma and could facilitate physician clinical decisions and improve health outcomes for individual patients.

Decision-making for pediatric allergy immunotherapy for aeroallergens: a narrative review.

There has been exciting progress in diagnosis and in the treatment of allergic patients. The objective of this review is to summarize the most relevant contributions in the past 10 years with a special focus on the pediatric population allergic to aeroallergens and provide the most relevant references and practical issues for the decision-making. Current guidelines on allergy diagnosis recommend a thorough clinical history as the first step, followed by allergen extract testing using an in vivo prick test and/or an in vitro specific IgE test. Molecular diagnosis is recommended when previous tests are inconclusive. In practice, the most important factors to decide the AIT treatment are the actual intensity and duration of the patient's symptoms and the availability of appropriate AIT products for the patient's sensitization profile at high allergen concentrations and with confirmed efficacy and safety from clinical trials. This document summarizes outstanding references for allergic immunotherapy decision-making and provides summary tables and figures analyzing the most important factors related to the decision for allergen immunotherapy and the safety risks related. The experts concluded that AIT is efficacious and safe for the treatment of allergic patients that is available for the most frequent aeroallergens.What is Known:• The prevalence of allergic asthma and rhinitis in children has increased in recent decades.• The efficacy and safety of allergen immunotherapy has been shown in multiple studies and systematic reviews.What is New:• This document summarizes outstanding references for allergic immunotherapy decision-making and provides summary tables and figures analyzing the most important factors related to the decision for allergen immunotherapy and the safety risks related. Recommendations of expert authors for the decision of the patients more suitable for allergen immunotherapy are included.

Double-blind, randomized, placebo-controlled trial of allergen-specific immunotherapy with the major allergen Alt a 1.

BACKGROUND: There have been few studies conducted on the efficacy and safety of specific immunotherapy with allergen extracts of fungi compared with other allergen extracts, and there are no data on the major allergen Alt a 1 of the fungus Alternaria alternata. OBJECTIVES: We sought to evaluate the efficacy and safety of subcutaneous immunotherapy with 2 different doses of Alt a 1 in patients with rhinoconjunctivitis caused by sensitization to A alternata. METHOD: We performed a multicenter, randomized, double-blind, placebo-controlled trial with Alt a 1 administered subcutaneously in patients with allergic rhinoconjunctivitis with or without controlled asthma aged 12 to 65 years. Three groups were included: the placebo group and active groups receiving 0.2 or 0.37 µg of Alt a 1 per dose. The main end point was the combined symptom and medication score. Secondary end points were cutaneous reactivity and serum IgE and IgG4 levels to Alt a 1. Recorded adverse reactions were graded according to World Allergy Organization criteria. RESULTS: There were significant reductions in the combined symptom and medication score for the 0.37-µg dose of Alt a 1 compared with placebo at 12 months of treatment. Reduced cutaneous reactivity and IgE levels, together with increased IgG4 levels, were demonstrated for the 2 active groups versus the placebo group. A similar safety profile was found for both active groups compared with the placebo group. No serious adverse drug reactions were reported. CONCLUSION: Immunotherapy with Alt a 1 was efficacious and safe, reducing the symptoms and medication consumption associated with rhinoconjunctivitis after only 1 year of treatment. The clinical benefits were associated with reduced skin reactivity and specific IgE levels and increased IgG4 levels.

Quality standards for allergen immunotherapy clinics in Spain: consensus document

BACKGROUND: Allergen immunotherapy clinics (AITCs) in Spain differ widely in terms of structure, organization, resources, and portfolio of services. Therefore, it is essential to unify treatment criteria and define quality standards for the most complex AITCs. OBJECTIVE: To establish a series of recommendations that make it possible to guarantee quality and safety in the administration of immunotherapy and define quality standards for the most complex AITCs. METHODS: This project began with an online survey of 65 allergy departments/units throughout Spain in 2013. Next, a 2-phase consensus process was carried out. In the first phase, 10 experts defined and agreed on the standards using the RAND/UCLA Appropriateness method; in the second, the agreements were validated by means of a 2-round Delphi consultation with 84 experts. RESULTS: Consensus was reached on minimum safety and quality criteria in the administration of allergen immunotherapy, and 2 levels of highly complex AITCs were defined: accredited AITCs and accredited AITCs with excellence. Consensus was also reached on quality standards and accreditation criteria for both levels. CONCLUSIONS: This project is pioneering in terms of its purpose (the definition of quality standards for AITCs) and of the use of structured participation techniques (combination of the RAND/UCLA and Delphi methods). It enabled the design of minimum standards for quality and safety in administering AIT, as well as quality criteria for accreditation of AITCs supported by a broad panel of experts from the Spanish Society of Allergology and Clinical Immunology

ANTECEDENTES: Las unidades de inmunoterapia (UIT) en España son muy diferentes en cuanto a estructura, organización, recursos y cartera de servicios. Por ello, resulta esencial homogeneizar criterios de actuación y definir estándares de calidad para las UIT de mayor complejidad. OBJETIVO: Establecer recomendaciones que permitan garantizar la calidad y seguridad en la administración de la inmunoterapia y definir estándares de calidad para las UIT de mayor complejidad. MÉTODOS: Proyecto iniciado (año 2013) con una encuesta on-line a 65 servicios o unidades de alergología de toda España. Posteriormente, se desarrolló un proceso de consenso en dos fases. En la primera, diez expertos definieron y consensuaron los estándares mediante el método RAND/UCLA; en la segunda, los acuerdos se validaron mediante una consulta Delphi a dos rondas con 84 expertos. RESULTADOS: Se consensuaron criterios mínimos de seguridad y calidad en la administración de inmunoterapia con alérgenos (ITA) y se definieron dos niveles de UIT de mayor complejidad: las UIT acreditadas (UITA) y las UIT acreditadas con excelencia (UITAE), consensuándose también los estándares de calidad y criterios de acreditación para ambos niveles. CONCLUSIONES: Proyecto pionero en su objetivo - definición de estándares de calidad de UIT- y en el empleo de técnicas de participación estructuradas -combinación de los métodos RAND/UCLA y Delphi-. El resultado es la definición de unos mínimos de calidad y seguridad para administrar ITA, y un conjunto de criterios de calidad para la acreditación de las UIT que cuenta con el respaldo de un amplio panel de expertos de la SEAIC

Efficacy and effectiveness of omalizumab in the treatment of childhood asthma.

INTRODUCTION: Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E, a mediator involved in the clinical manifestations of allergic asthma. Evidence for its efficacy and safety in the treatment of moderate-to-severe allergic asthma is based primarily on studies in adolescents and adults. However, there is increasing evidence of its utility in children with allergic asthma aged 6-12 years. Areas covered: This article reviews efficacy, safety, and effectiveness of omalizumab in the treatment of moderate-to-severe allergic asthma in children aged 6-12 years in clinical trials and in studies in clinical practice. Pharmacoeconomic aspects of its use among this population and the positioning of omalizumab in pediatric asthma management guidelines are also discussed. Additionally, an algorithm for the management of poorly controlled severe pediatric asthma in children older than 6 years is proposed. Electronic databases, such as PubMed, were searched for terms Asthma and Omalizumab and for asthma management guidelines. Expert commentary: Add-on omalizumab is an effective maintenance therapy in children aged 6-12 years with poorly controlled moderate-to-severe allergic asthma treated with medium-high inhaled corticosteroids doses and inhaled long-acting ß2-agonists. Omalizumab appears safe in children in both clinical trials and real-life setting and may be cost-effective.

The European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI): A paediatric assessment.

BACKGROUND: Safety data on 'real-life' allergen immunotherapy (AIT) in children and adolescents is usually extrapolated from studies in adults. METHODS: Patients aged 18 or under initiating aeroallergen AIT were evaluated in a prospective European survey. Patient profiles and systemic reactions (SRs) were recorded. Descriptive, univariate and multivariate analyses were used to identify risk factors for SRs. RESULTS: A total of 1563 patients (mean ± SD age: 11.7 ± 3.9 years; rhinitis: 93.7%; asthma: 61.5%; polysensitization: 62.5%) and 1578 courses of AIT were assessed. Single-allergen AIT was administered in 89.5% of cases (n = 1412; mites: 49%; grass pollen: 25.8%; tree pollen: 8.7%; Alternaria: 4.6%; dander: 0.8%; weed pollen: 0.6%). Subcutaneous AIT (SCIT) was used in 71.4% (n = 1127) of the treatments, including 574 (50.9%) with natural extracts. Sublingual AIT (SLIT) was used for the remaining 451 treatments (drops: 73.8%; tablets: 26.2%). The mean ± SD follow-up period was 12.9 ± 3.3 months. The estimated total number of doses was 19,669 for SCIT and 131,550 for SLIT. Twenty-four patients (1.53%) experienced 29 SRs. Respiratory (55.7%) and skin symptoms (37.9%) were most frequent. Anaphylaxis was diagnosed in 3 SRs (10.3%), and adrenaline was administered in 2 of these cases. In a univariate analysis, the risk of SRs was lower in mite-sensitized patients and higher in cases of pollen polysensitization (>3), grass pollen extracts and the use of natural extracts (vs. allergoids). CONCLUSIONS: In a real-life paediatric setting, AIT is safe. SRs are infrequent and generally not severe. Pollen polysensitization, grass pollen extracts and natural extracts (vs. allergoids) were risk factors for AIT-associated SRs.

Optimal duration of allergen immunotherapy in children with dust mite respiratory allergy.

BACKGROUND: Subcutaneous immunotherapy (SCIT) discontinuation data in children remain scarce. OBJECTIVE: We sought for differences in the clinical efficacy of 3 vs. 5 yr of SCIT in children with dust mite respiratory allergy. METHODS: We performed a 5-yr, phase IV prospective study. After the first year, the patients were randomized to 3 (IT3) or 5 yr of treatment (IT5). Efficacy was assessed at 3rd and 5th year by symptom and medication scores and visual analog scales (VAS). Skin tests with common allergens and in vitro assessments were also performed. RESULTS: Eighty-one children (mean age: 9 yr) were randomly assigned to 3 (IT3: 41) or 5 yr (IT5: 40) of immunotherapy. After 3 years, rhinitis global scores decreased in IT3 (44%; p = 0.002) and in IT5 (50%; p = 0.001). Asthma global, symptom and medication scores decreased by 100% in IT3 (p = 0.001) and IT5 (p = 0.001). VAS scores also diminished significantly (IT3: 70%, p = 0.001; IT5: 62.5%; p = 0.001). At 5th year, global rhinitis scores were reduced an additional 30% in IT5 children. Comparisons between both groups did not show differences in rhinitis (p = 0.055), asthma global scores (p = 0.948) or VAS scores at 5th year. Twenty percent of IT5 (p = 0.002) and 7% of IT3 children (p = 0.705) developed new sensitizations. At 5th year, sIgG4 determinations decreased in IT3 without significant variations in IT5. CONCLUSIONS: Three years of SCIT induced significant improvement in children with dust mite respiratory allergy, but a 5-yr course added clinical improvement in rhinitis.

Efficacy and safety of sublingual tablets of house dust mite allergen extracts in adults with allergic rhinitis.

BACKGROUND: Preliminary studies have suggested the efficacy of sublingual tablets of house dust mite (HDM) extracts in adults with allergic rhinitis. OBJECTIVES: We sought to assess the efficacy and safety of 2 doses of HDM sublingual tablets over 1 treatment year and the subsequent immunotherapy-free year. METHODS: Adults with HDM-associated allergic rhinitis were randomized in a double-blind, placebo-controlled study to receive 500 index of reactivity (IR) tablets, 300IR tablets, or placebo administered once daily for 1 year and were followed for the subsequent year. The primary efficacy variable was the Average Adjusted Symptom Score over the year 1 primary period (ie, October 1 to December 31). Symptoms and rescue medication scores, onset of action, patient-reported outcomes, and safety were secondary variables. The same end points were evaluated during the immunotherapy-free year. The primary efficacy end point was analyzed by using analysis of covariance. RESULTS: Five hundred nine participants were randomized, and 427 continued in the immunotherapy-free year. Both the 500IR and 300IR HDM sublingual tablets significantly reduced mean Average Adjusted Symptom Scores compared with placebo by -20.2% (P = .0066) and -17.9% (P = .0150), respectively. Efficacy of both doses was maintained during the treatment-free follow-up phase. The onset of action was at 4 months. Participants' global evaluation of treatment success was significantly higher in the 500IR and 300IR groups compared with the placebo group (P = .0206 and P = .0001, respectively). Adverse events were generally application-site reactions. There were no reports of anaphylaxis. CONCLUSIONS: Twelve months of treatment with 500IR and 300IR sublingual tablets of HDM allergen extracts was efficacious and well tolerated. Efficacy was maintained during the treatment-free follow-up year.

Diagnosis and allergen immunotherapy treatment of polysensitised patients with respiratory allergy in Spain: an Allergists' Consensus.

BACKGROUND: Polysensitisation is common in patients with respiratory allergy in Spain. Selection of the best allergen immunotherapy (AIT) is difficult in polysensitised patients. The present study was designed to help allergists better identify relevant allergens in these patients and to improve the selection of AIT in Spain. METHODS: Sixty-two Spanish allergists answered a survey containing 88 items divided into four groups: 1) general approach to polysensitised subjects; 2) sensitisation profile involving mite, animal dander and moulds; 3) grass and olive pollen co-sensitisation, and 4) other pollen polysensitisation profile (weed and tree pollen). The Delphi method was used. RESULTS: A consensus was achieved for 83% of items (92%, 81%, 83% and 73% of the four groups analysed, respectively). Only polysensitised patients with clinical relevance should be considered polyallergic. A detailed medical history (clinical symptoms and medication) together with a profound knowledge of allergens present in the patient's environment are essential for diagnosis. Skin prick tests (SPTs) are not adequate to decide the clinical relevance of each allergen. Serum specific IgE against allergen sources adds value to SPT but molecular diagnosis, when possible, is strongly recommended, especially in pollen-allergic patients. Specific allergen challenge tests are difficult to perform and not recommended for daily practice. Regarding AIT composition, up to three allergens can be used in the same vaccine, but only related allergens may be mixed. In some cases more than one vaccine may be needed. CONCLUSION: Some criteria have been established to improve diagnosis and AIT prescription in polysensitised patients.

Safety evaluation of rapid build-up schedules with IR-standardized allergen extracts for subcutaneous immunotherapy of allergic respiratory diseases.

INTRODUCTION: The conventional schedule used in specific subcutaneous immunotherapy (SCIT) is a slow treatment that often leads to poor compliance or discontinuation of treatment. These disadvantages have led to design administration schedules that shorten the build-up phase without increasing the adverse reactions rate. AREAS COVERED: This report reviews the available scientific documentation of the safety profile of build-up schedules for SCIT with Alustal Rapid® (a suspension of standardized allergen extracts adsorbed on aluminum hydroxide gel for specific immunotherapy) in the treatment of IgE-mediated rhinitis, conjunctivitis and bronchial asthma to inhaled allergens. EXPERT OPINION: Cluster and shortened conventional schedules may offer a safe method of SCIT for the treatment of respiratory allergy and reduce the inconvenience associated with conventional schedules by reaching the maintenance dose in less time and with fewer visits; thereby this method could reduce discontinuation rates and increase compliance.

Comparison of conventional and component-resolved diagnostics by two different methods (Advia-Centaur/Microarray-ISAC) in pollen allergy.

BACKGROUND: Component-resolved diagnostics (CRD) has recently been introduced into clinical allergology. OBJECTIVE: The aim of this study was to assess the contribution that this new diagnostic technique makes to conventional diagnosis in patients with pollen allergy, comparing CRD with conventional technologies, and to compare 2 CRD methods, Advia-Centaur and Microarray-ISAC. METHODS: Serum samples from 120 pollen-allergic patients were obtained. Immunoglobulin (Ig) E to total extracts (CAP System) and individual allergens using both CRD methods were determined. RESULTS: The 3 diagnostic methods were in agreement in 62.5% of cases. In 30%, the CRD modified the conventional diagnosis either by detecting new relevant sensitizations (mainly to Olea) or by ruling out clinically irrelevant sensitizations caused by panallergens. The main differences between the 2 CRD methods were the deficiency in the ISAC version we used (ISAC-CRD-89) to detect sensitizations to Salsola and Plantago and that Advia-Centaur did not detect sensitizations to cypress. For all allergens except for Par j 1, a significant association in the frequency of sensitization was seen with the 2 CRD techniques and good agreement when comparing the results of the 2 methods in all cases. Significant correlation was found in the concentration of specific IgE in the 2 techniques for the most prevalent allergens in our setting. The results of the different profilins analyzed using Microarray-ISAC were superimposable although somewhat lower in the case of Phl p 12. CONCLUSIONS: Component-resolved diagnostics modified the conventional diagnosis in 30% of cases. The results from the 2 CRD methods showed good agreement and correlation for most allergens.

Three years of specific immunotherapy may be sufficient in house dust mite respiratory allergy.

BACKGROUND: Specific immunotherapy (SIT) duration for respiratory allergy is currently based on individual decisions. OBJECTIVE: To evaluate the differences in clinical efficacy of SIT as a result of the duration between the current recommended limits (3-5 years). METHODS: A 5-year prospective, controlled clinical trial of SIT blind until the first year and randomization to a 3-year (IT3) or 5-year (IT5) course was conducted. Of the 239 patients with respiratory allergy caused by D pteronyssinus initially included, 142 completed 3 years of SIT with good compliance. Twenty-seven controls were included at the third year. Efficacy of SIT after 3 (T3) and 5 (T5) years was assessed by using clinical scores, visual analog scales (VASs), rhinitis (RQLQ) and asthma (AQLQ) quality of life questionnaires, skin tests, and serum immunoglobulins. RESULTS: At T3, significant reductions were observed in rhinitis (44% in IT3 and 50% in IT5; P < .001), asthma (80.9 % in IT3 and 70.9% in IT5; P < .001) scores, VAS (P < .001 in both), RQLQ (P < .001 in both) and AQLQ (P < .001 in both). At T5, the clinical benefit was maintained in both groups, and IT5 patients presented additional decreases (19%; P = .019) in rhinitis scores. At Tf, specific IgG(4) measurements were lower in IT3 (P = .03) without detecting differences in IT5. An increase in asthma score of 133% was the only difference observed in controls. CONCLUSION: Clinical improvement is obtained with 3 years of D pteronyssinus SIT. Two additional years of SIT add clinical benefit in rhinitis only.

Assessment of short-term changes induced by a Dermatophagoides pteronyssinus extract on asthmatic patients. Randomised, double-blind, placebo-controlled trial.

BACKGROUND: Once the optimal dose is reached, subcutaneous immunotherapy [SCIT] with mite extract is capable of reducing symptoms and the need for rescue medication. OBJECTIVE: To assess the capacity of a subcutaneous extract of mites [D. pteronyssinus] to bring about a reduction in concomitant medication as well as in vivo and in vitro changes in just 2-3 months of treatment in patients with allergic asthma. METHODS: A total of 45 patients with persistent mild-moderate allergic asthma due to sensitisation to D. pteronyssinus were included in a multi-centre, double-blind, placebo-controlled trial. Length of treatment was 4 months. After a period for adjusting medication in order to classify asthma severity appropriately, patients were commenced on treatment of 400 or 800 g/day of budesonide as concomitant medication. RESULTS: After 4 months of treatment there were no significant changes in the budesonide dose between the active group and the placebo group. In the active group there was a significant difference between active and placebo group in sIgG4 [p=.0003], as well as a significant increase in the cutaneous tolerance index [2.81, CI 95%: 1.29 - 7.48, which was significant with a Confidence Interval of 95%]. These changes were not observed in the placebo group. CONCLUSION: After just 4 months of treatment, SCIT was capable of inducing in vivo and in vitro changes, but these changes were not reflected in improved clinical outcome within the first 4 months of therapy.