SQ HDM sublingual immunotherapy tablet for the treatment of HDM allergic rhinitis and asthma improves subjective sleepiness and insomnia: an exploratory analysis of the real-life CARIOCA study.

BACKGROUND AND OBJECTIVE: There are still gaps in the knowledge regarding the effectiveness of house dust mite (HDM) sublingual immunotherapy (SLIT) on allergic rhinitis (AR) and asthma (AA)-associated sleep disorders. A non-interventional study was conducted to assess the effect of the Standardized quality (SQ) HDM SLIT-tablet on safety and symptoms in adults with HDM respiratory allergies. The aim was to describe the status of insomnia and daytime sleepiness in AR and/or AA patients treated with the SQ HDM SLIT-tablet. METHODS: This was a 12-month multicenter, longitudinal and prospective study. Participants started the SQ HDM SLIT-tablet for moderate-to-severe HDM AR, persistent despite the use of symptom-relieving medication; or HDM AA not well controlled by inhaled corticosteroids and associated with mild-to-severe HDM AR. Sleep symptoms were measured using the Insomnia Severity Index (ISI) questionnaire and the Epworth Sleepiness Scale (ESS). RESULTS: A total of 1,526 adult patients were enrolled and 1,483 were included in the analysis. At baseline, 41.5% of patients reported sleep disorders: 77.0% of them had insomnia and 28.9% suffered from excessive daytime sleepiness. Insomnia was significantly more frequent among patients with uncontrolled AR (83.1%) than those with controlled AR (52.6%) (p<0.0001). Over time, 48.3% and 59.7% of patients reported an improvement greater than the minimal clinically important difference on the ISI and ESS scales respectively. CONCLUSION: In patients with HDM AR and/or asthma associated sleep disorders, an improvement in subjective insomnia and sleepiness was observed after one year of treatment with the SQ HDM SLIT-tablet in a real-life setting.

Essential oils: what is the clinical tolerance in asthmatic patients?

Essential oils in air-spray form are being more and more used for several purposes, even by allergic and asthmatic patients. Available data on the potentially dangerous effects of volatile organic compounds and terpenes contained in essential oils are scarce, and sometimes difficult to compare. Through the present work, we evaluated the clinical tolerance of asthmatic patients exposed to compounds emitted by an essential oils spray, and compared previous and new data available in the scientific literature, focusing on the aspects that may influence clinical results.

Action Plan to Ensure Global Availability of Adrenaline Autoinjectors.

Adrenaline (epinephrine) is the first-line treatment for anaphylaxis and, therefore, is listed as an essential medication for the treatment of anaphylaxis by the World Health Organization (WHO). However, the availability of adrenaline autoinjectors (AAI) for use as first-aid treatment is limited to only 32% of all the world's 195 countries, most of which are high-income countries. The key issues leading to the lack of availability of AAIs include cost, national regulations, lack of regional evidence on the value of epinephrine, and limited accurate data about the epidemiology of anaphylaxis. For these reasons, regional and international allergy academies support initiatives to narrow these gaps. Our WHO Collaborating Centre is deeply involved in this process. This document aims to serve as a baseline to ensure the following: (1) adequate access to affordable autoinjectors for all patients/societies; and (2) the development of disease-/patient-specific approaches. Therefore, we propose a 5-step action plan that aims to gather accurate epidemiological data on anaphylaxis and autoinjector consumption, confirm partnerships, strengthen awareness, and include AAIs in the WHO Model List of Essential Medicines. These aspects should be considered in combination. A prioritized research agenda should encapsulate all these steps within the framework a global initiative against anaphylaxis. More than calling for universal availability of autoinjectors for optimal management of anaphylaxis, we propose an action plan as the baseline for a global initiative against anaphylaxis. We strongly believe that combined efforts will ensure a strong public health and societal approach that will lead to optimal care of allergic patients and best practices in allergology.

Epidemiological Data on Anaphylaxis in French Emergency Departments.

BACKGROUND: Although anaphylaxis has been considered a priority public health issue in the world allergy community, epidemiological data on morbidity and mortality remain suboptimal. We performed the first multicenter epidemiological study in French emergency departments (EDs). The study covered 7 EDs over a period of 1 year. The objectives were to identify areas that are amenable to change and to support ongoing national and international efforts for better diagnosis, management, and prevention of anaphylaxis. METHODS: Ours was a descriptive study based on data routinely reported to French institutional administrative databases from 7 French public health institutions in the Lorraine region between January and December 2015. Data were collected based on the anaphylaxisrelated codes of the International Classification of Diseases (ICD)-10, and cases were clinically validated as anaphylaxis. RESULTS: Of the 202 079 admissions to the EDs, 4817 had anaphylaxis-related codes; of these, 323 were clinically validated as anaphylaxis. Although 45.8% were severe, adrenaline was prescribed in only 32.4% of cases. Of the 323 cases, 57.9% were subsequently referred for an allergy work-up or evaluation (after or during hospitalization), and 17.3% were prescribed autoinjectable epinephrine. CONCLUSION: Our results highlight an urgent need for improved public health initiatives with respect to recognition and treatment of anaphylaxis. We flag key problems that should be managed in the coming years through implementation of national and international actions.

Prevalence of self-reported drug hypersensitivity reactions among Lithuanian children and adults.

INTRODUCTION AND OBJECTIVES: Drug hypersensitivity reactions (DHRs) are the adverse effects of drugs that, when taken at doses generally tolerated by normal subjects, clinically resemble allergy. We aimed to assess the prevalence of self-reported DHRs among Lithuanian children and adults and to identify possible risk factors. MATERIALS AND METHODS: A cross-sectional survey of a population visiting their general practitioners in Vilnius and Kaunas regions of Lithuania was performed. Thirty-five questions on drug allergy symptoms, in addition, food, pollen allergy and family history were included. RESULTS: 3222 (60.0%) children and 2148 (40.0%) adults were included in the study. 7.9% of children and 13.8% of adults reported a DHR for at least one drug (p<0.001). 69.8% of children and 47.3% of adults, who indicated DHRs, had skin symptoms. Rate of anaphylaxis was similar in both groups (about 10%). 4.5% of children and 7.3% of adults had DHRs induced by antibiotics and this was the most implicated group of drugs. Significant self-reported risk factors for DHRs were family history of DHRs (OR=6.007, 95%CI 4.756-7.587), pollen allergy (OR=2.0, 95%CI 1.573-2.544), food allergy (OR=1.92, 95%CI 1.505-2.448), female gender (OR=1.439, 95%CI 1.187-1.744) and age (OR=1.017 in favour of adults, 95%CI 1.013-1.021). CONCLUSIONS: The prevalence of self-reported DHRs in Lithuania is higher among adults than children. Drug-induced skin reactions were the predominant symptom in both groups. Besides female gender and age, a positive family history of DHR and presence of pollen or food allergy may be associated with DHR.

What can we learn in drug allergy management from World Health Organization's international classifications?

Drug hypersensitivity reactions (DHRs) represent growing health problem worldwide, affecting more than 7% of the general population, and represent an important public health problem. However, knowledge in DHRs morbidity and mortality epidemiological data is still not optimal and international comparable standards remain poorly accessed. Institutional databases worldwide increasingly use the WHO International Classification of Diseases (ICD) system to classify diagnoses, health services utilization, and death data. The misclassification of disorders in the ICD system contributes to a lack of ascertainment and recognition of their importance for healthcare planning and resource allocation. It also hampers clinical practice and prevention actions. To further inform the allergy community and to ensure that the revision process is transparent as advised in the WHO ICD-11 revision agenda, we report the advances and use of the pioneering "Drug hypersensitivity" subsection of ICD-11 and implementation in the WHO International Classification of Health Interventions (ICHI). The new classification addressed to DHRs will enable the collection of more accurate epidemiological data to support quality management of patients with drug allergies and better facilitate healthcare planning and decision-making and public health measures to prevent and reduce the morbidity and mortality attributable to DHRs.

Current practice of allergy diagnosis and the potential impact of regulation in Europe.

In the European Union (EU), the regulatory framework regarding diagnostic allergen extracts is currently in the process of being implemented at the national level. Due to these regulations, the initial and periodic renewal expenses for the registration of diagnostic allergen extracts may render extract production unprofitable. Consequently, many extracts may be at risk of removal from the market. The current survey, which was conducted by a task force of the European Academy of Allergy and Clinical Immunology, aimed to assess the current practice of allergy diagnosis in Europe. This survey revealed that skin tests continue to be the main diagnostic procedure and are used as the first option in almost two-third of all types of allergic diseases and in 90% of individuals suffering from respiratory allergies. Therefore, there is a need to ensure the availability of high-quality allergen extracts to maintain the common diagnostic procedures used by EU professionals. To reach this goal, it is necessary to align efforts and establish active partnerships between manufacturers, relevant scientific societies, consumer organizations and authorities to maintain the availability of these diagnostic tools.

Perspectives in allergen immunotherapy: 2017 and beyond.

The Future of the Allergists and Specific Immunotherapy (FASIT) workshop provides a regular platform for global experts from academia, allergy clinics, regulatory authorities and industry to review developments in the field of allergen immunotherapy (AIT). The most recent meeting, held in February 2017, had two main themes: advances in AIT and hot topics in AIT from the regulatory point of view. The first theme covered opportunities for personalized AIT, advances in adjuvants and delivery systems, and the development of new molecules and future vaccines for AIT. Key topics in the second part of the meeting were the effects of the enactment of European Directive 2001/83 on the availability of allergens for therapy and diagnosis across the EU, the challenges of conducting Phase 3 studies in the field, the future role of allergen exposure chambers in AIT studies and specific considerations in performing AIT studies in the paediatric population. Finally, the group highlighted the forthcoming EAACI guidelines and their particular importance for the standardization of practice in the treatment of allergies. This review presents a comprehensive insight into those panel discussions and highlights unmet needs and also possible solutions to them for the future.

Treatment of allergic rhinitis using mobile technology with real-world data: The MASK observational pilot study.

BACKGROUND: Large observational implementation studies are needed to triangulate the findings from randomized control trials as they reflect "real-world" everyday practice. In a pilot study, we attempted to provide additional and complementary insights on the real-life treatment of allergic rhinitis (AR) using mobile technology. METHODS: A mobile phone app (Allergy Diary, freely available in Google Play and Apple App stores) collects the data of daily visual analog scales (VAS) for (i) overall allergic symptoms, (ii) nasal, ocular, and asthma symptoms, (iii) work, as well as (iv) medication use using a treatment scroll list including all medications (prescribed and over the counter (OTC)) for rhinitis customized for 15 countries. RESULTS: A total of 2871 users filled in 17 091 days of VAS in 2015 and 2016. Medications were reported for 9634 days. The assessment of days appeared to be more informative than the course of the treatment as, in real life, patients do not necessarily use treatment on a daily basis; rather, they appear to increase treatment use with the loss of symptom control. The Allergy Diary allowed differentiation between treatments within or between classes (intranasal corticosteroid use containing medications and oral H1-antihistamines). The control of days differed between no [best control], single, or multiple treatments (worst control). CONCLUSIONS: This study confirms the usefulness of the Allergy Diary in accessing and assessing everyday use and practice in AR. This pilot observational study uses a very simple assessment (VAS) on a mobile phone, shows novel findings, and generates new hypotheses.

Daily allergic multimorbidity in rhinitis using mobile technology: A novel concept of the MASK study.

BACKGROUND: Multimorbidity in allergic airway diseases is well known, but no data exist about the daily dynamics of symptoms and their impact on work. To better understand this, we aimed to assess the presence and control of daily allergic multimorbidity (asthma, conjunctivitis, rhinitis) and its impact on work productivity using a mobile technology, the Allergy Diary. METHODS: We undertook a 1-year prospective observational study in which 4 210 users and 32 585 days were monitored in 19 countries. Five visual analogue scales (VAS) assessed the daily burden of the disease (i.e., global evaluation, nose, eyes, asthma and work). Visual analogue scale levels <20/100 were categorized as "Low" burden and VAS levels ≥50/100 as "High" burden. RESULTS: Visual analogue scales global measured levels assessing the global control of the allergic disease were significantly associated with allergic multimorbidity. Eight hypothesis-driven patterns were defined based on "Low" and "High" VAS levels. There were <0.2% days of Rhinitis Low and Asthma High or Conjunctivitis High patterns. There were 5.9% days with a Rhinitis High-Asthma Low pattern. There were 1.7% days with a Rhinitis High-Asthma High-Conjunctivitis Low pattern. A novel Rhinitis High-Asthma High-Conjunctivitis High pattern was identified in 2.9% days and had the greatest impact on uncontrolled VAS global measured and impaired work productivity. Work productivity was significantly correlated with VAS global measured levels. CONCLUSIONS: In a novel approach examining daily symptoms with mobile technology, we found considerable intra-individual variability of allergic multimorbidity including a previously unrecognized extreme pattern of uncontrolled multimorbidity.

The Allergic Rhinitis and its Impact on Asthma (ARIA) score of allergic rhinitis using mobile technology correlates with quality of life: The MASK study.

Mobile technology has been used to appraise allergic rhinitis control, but more data are needed. To better assess the importance of mobile technologies in rhinitis control, the ARIA (Allergic Rhinitis and its Impact on Asthma) score ranging from 0 to 4 of the Allergy Diary was compared with EQ-5D (EuroQuol) and WPAI-AS (Work Productivity and Activity Impairment in allergy) in 1288 users in 18 countries. This study showed that quality-of-life data (EQ-5D visual analogue scale and WPA-IS Question 9) are similar in users without rhinitis and in those with mild rhinitis (scores 0-2). Users with a score of 3 or 4 had a significant impairment in quality-of-life questionnaires.

Validation of the MASK-rhinitis visual analogue scale on smartphone screens to assess allergic rhinitis control.

BACKGROUND: Visual Analogue Scale (VAS) is a validated tool to assess control in allergic rhinitis patients. OBJECTIVE: The aim of this study was to validate the use of VAS in the MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) app (Allergy Diary) on smartphones screens to evaluate allergic rhinitis symptoms and disease control. METHODS: Each user filled 4 different VAS measuring overall, nasal, ocular, and asthma symptoms at least once. Following COSMIN guidelines, we evaluated internal consistency, (Cronbach's alpha coefficient and test-retest), reliability (intraclass correlation coefficients), sensitivity, and acceptability of the MASK-Rhinitis VAS. RESULTS: Between 1 August 2015 and 31 July 2016, the app was used 14 612 times in 15 countries. A total of 1225 users used it more than once, during the evaluated period. The tool resulted to be statistically satisfactory, showing excellent internal consistency (Cronbach's test > 0.84, test-retest > 0.7), reliability (>0.9), and acceptability. In addition, the tool had a good sensitivity when users (n = 521) answered the VAS twice in less than 3 hours. CONCLUSIONS AND CLINICAL RELEVANCE: The MASK-rhinitis VAS is a reliable and valid tool to assess allergic control on smartphone screens, at the population level.

Clinical benefits of treatment with SQ house dust mite sublingual tablet in house dust mite allergic rhinitis.

Treatment with SQ (standardised quality) house dust mite sublingual tablet for 1 year resulted in a decreased probability of having an allergic rhinitis (AR) exacerbation day (from 11% [placebo] to 5% [SQ house dust mite sublingual tablet]) and an increased probability of having a mild AR day (from 16% [placebo] to 34% [SQ house dust mite sublingual tablet]).

Optimal step doses for drug provocation tests to prove beta-lactam hypersensitivity.

BACKGROUND: Drug provocation tests (DPT) are commonly performed as part of ß-lactam (BL) allergy workup, in case of negative skin tests (ST) and in the absence of contraindications. The recommendations of learned societies have created a frame for DPT performance, but protocols vary widely between centres, generating various hypothesis-driven protocols (i.e. empirical dosing, driven by both safety concerns and practical aspects). METHODS: The primary objective of this retrospective analysis was to detect eliciting dose thresholds (reactive doses) during BL DPT, using the survival analysis method, in order to suggest optimal step doses. Our secondary objective was to evaluate the safety of our 30-min incremental 1-day protocol. The study included all the patients explored in the Allergy Unit of the University Hospital of Montpellier (France), between September 1996 and July 2015 for a suspicion of drug hypersensitivity reaction to BLs, with negative ST and positive DPT. RESULTS: During the study period, 182 positive DPT (accounting for 171 hypersensitive patients) were analysed. We identified eliciting thresholds, and we suggest the following steps for DPT to BLs: 5-15-30-50% of daily therapeutic dose (with additional lower steps for index reactions of anaphylaxis). We confirm the safety of 1-day protocol for immediate and mild nonimmediate reactors, for both children and adults, with a surveillance period of 2 h after the last administered dose, and a prolonged surveillance after discharge of 48 h. CONCLUSION: This data-driven approach in designing DPT protocols is a step forward in improving DPT standardization, starting with the most frequently tested drugs, BL antibiotics.

Decreasing the undernotification of anaphylaxis deaths in Brazil through the International Classification of Diseases (ICD)-11 revision.

BACKGROUND: In 2012, an analysis of the Brazilian mortality database demonstrated undernotification of anaphylaxis deaths due, at least in part, to difficult coding under the International Classification of Diseases (ICD)-10. This work triggered a cascade of strategic international actions supported by the Joint Allergy Academies and the ICD World Health Organization (WHO) representatives to update the classifications of allergic disorders for the ICD-11 revision. These efforts have resulted in the construction of the new 'Allergic and hypersensitivity conditions' section under the 'Disorders of the Immune system' chapter. OBJECTIVE: To analyze the capacity of the new ICD-11 revision to capture anaphylaxis deaths. METHODS: We re-estimated the anaphylaxis deaths that occurred in Brazil during the period 2008 to 2010, utilizing this new framework and the database of the Brazilian mortality information system that had initially been extracted in May 2011. However, in 2016, a manual review of each of the 3638 records was performed. RESULTS: We identified 639 anaphylaxis deaths, of which 95% were classified as 'definitive anaphylaxis deaths'. In contrast to the 2012 published data, we found a higher number of cases; moreover, all 606 definitive anaphylaxis deaths would be considered as underlying causes of death utilizing the ICD-11 revision. CONCLUSION: This study is the first example of how the new 'Allergic and hypersensitivity conditions' section of the forthcoming ICD-11 can improve the quality of official vital statistics data and the visibility of an important public health concern. This research will facilitate comprehensive, comparable population-based epidemiologic data collection on anaphylaxis.

Field-testing the new anaphylaxis' classification for the WHO International Classification of Diseases-11 revision.

BACKGROUND: To consolidate the new classification model addressed to the allergic and hypersensitivity conditions according to the International Classification of Diseases (ICD)-11 revision timeline, we here propose real-life application of quality assurance methodology to evaluate sensitivity and accuracy of the 'Anaphylaxis' subsection. METHODS: We applied field-testing methodology by analysing all the consecutive inpatients' files documented as allergies from the University Hospital of Montpellier electronic database for the period of 1 year. The files clinically validated as being anaphylaxis were manually blind-coded under ICD-10 and current ICD-11 beta draft. The correspondence of coding and the impressions regarding sensibility were evaluated. RESULTS: From all 2318 files related to allergic or hypersensitivity conditions, 673 had some of the anaphylaxis ICD-10 codes; 309 files (46%) from 209 patients had anaphylaxis and allergic or hypersensitivity comorbidities description. The correspondence between the two coders was perfect for 162 codes from all 309 entities (52.4%) (Cohen-kappa value 0.63) with the ICD-10 and for 221 codes (71.5%) (Cohen-kappa value 0.77) with the ICD-11. There was a high agreement regarding sensibility of the ICD-11 usability (Cohen-kappa value 0.75). CONCLUSION: We here propose the first attempt of real-life application to validate the new ICD-11 'Anaphylaxis' subsection. Clearer was the improvement in accuracy reaching 71.5% of agreement when ICD-11 was used. By allowing all the relevant diagnostic terms for anaphylaxis to be included into the ICD-11 framework, WHO has recognized their importance not only to clinicians but also to epidemiologists, statisticians, healthcare planners and other stakeholders.

Costs of perennial allergic rhinitis and allergic asthma increase with severity and poor disease control.

BACKGROUND: Perennial allergic rhinitis (PAR) represents a global and public health problem, due to its prevalence, morbidity, and impact on the quality of life. PAR is frequently associated with allergic asthma (AA). Costs of PAR with or without AA are poorly documented. OBJECTIVE: Our study aimed to detail medical resource utilization (MRU) and related direct cost for PAR, with or without concomitant AA, in France. METHODS: Using Electronic Health Records (EHRs), we identified in 2010 two cohorts of PAR patients, based on General Practitioners' diagnoses and prescribing data, with and without concomitant AA. For each patient, the EHRs were linked to corresponding claims data with MRU and costs during years 2011 to 2013. Predefined subgroup analyses were performed according to severity of PAR and level of AA control. RESULTS: The median annual cost reimbursed by social security system for a patient with PAR, and no AA was 159€ in 2013. This varied from 111€ to 188€ depending on PAR severity. For patients with PAR and concomitant AA, the median annual cost varied between 266€ and 375€, and drug treatment accounted for 42-55% of the costs, depending on asthma control. CONCLUSION: This study linking diagnoses from EHRs to claims data collected valid information on PAR management, with or without concomitant AA, and on related costs. There was a clear increase in costs with severity of PAR and control of AA.

European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI): a real-life clinical assessment.

BACKGROUND: Outside clinical trials, data on systemic reactions (SRs) due to allergen immunotherapy (AIT) are scarce. METHODS: A prospective, longitudinal, web-based survey of 'real-life' respiratory allergen immunotherapy (AIT) clinical practice was conducted in France, Germany and Spain. SRs were recorded and coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and risk factors associated with SRs were identified. RESULTS: A total of 4316 patients (corresponding to 4363 ongoing courses of AIT) were included. A total of 109 SRs were recorded, and 90 patients (2.1%) presented at least one SR. Most of the SRs occurred in subcutaneous allergen immunotherapy (SCIT) (89%, n = 97). The most frequently reported symptoms were urticaria, rhinitis, dyspnoea and cough. Respiratory symptoms appeared before skin symptoms. Most SRs occurred during the up-dosing phase (75.8%) and were mild in severity (71.6%). Intramuscular adrenaline was administered in 17 SRs, but only 65% of these were subsequently classified as anaphylaxis. Independent risk factors for SRs during SCIT were as follows: the use of natural extracts (odds ratio, OR) [95% confidence interval (CI)] = 2.74 [1.61-4.87], P = 0.001), the absence of symptomatic allergy medications (1.707 [1.008-2.892], P = 0.047), asthma diagnosis (1.74 [1.05-2.88], P = 0.03), sensitization to animal dander (1.93 [1.21-3.09], P = 0.006) or pollen (1.16 [1.03-1.30], P = 0.012) and cluster regimens (vs rush) (4.18 [1.21-14.37], P = 0.023). A previous episode of anaphylaxis increased the risk for anaphylaxis in SCIT (OR [95% CI] = 17.35 [1.91-157.28], P = 0.01). CONCLUSION: AIT for respiratory allergy is safe, with a low number of SRs observed in real-life clinical practice. A personalized analysis of risk factors could be used to minimize SRs.

Defining pollen exposure times for clinical trials of allergen immunotherapy for pollen-induced rhinoconjunctivitis - an EAACI position paper.

BACKGROUND: Clinical efficacy of pollen allergen immunotherapy (AIT) has been broadly documented in randomized controlled trials. The underlying clinical endpoints are analysed in seasonal time periods predefined based on the background pollen concentration. However, any validated or generally accepted definition from academia or regulatory authorities for this relevant pollen exposure intensity or period of time (season) is currently not available. Therefore, this Task Force initiative of the European Academy of Allergy and Clinical Immunology (EAACI) aimed to propose definitions based on expert consensus. METHODS: A Task Force of the Immunotherapy and Aerobiology and Pollution Interest Groups of the EAACI reviewed the literature on pollen exposure in the context of defining relevant time intervals for evaluation of efficacy in AIT trials. Underlying principles in measuring pollen exposure and associated methodological problems and limitations were considered to achieve a consensus. RESULTS: The Task Force achieved a comprehensive position in defining pollen exposure times for different pollen types. Definitions are presented for 'pollen season', 'high pollen season' (or 'peak pollen period') and 'high pollen days'. CONCLUSION: This EAACI position paper provides definitions of pollen exposures for different pollen types for use in AIT trials. Their validity as standards remains to be tested in future studies.

Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: an EAACI Position Paper.

BACKGROUND: Allergen immunotherapy (AIT) is an effective treatment for allergic rhinoconjunctivitis (AR) with or without asthma. It is important to note that due to the complex interaction between patient, allergy triggers, symptomatology and vaccines used for AIT, some patients do not respond optimally to the treatment. Furthermore, there are no validated or generally accepted candidate biomarkers that are predictive of the clinical response to AIT. Clinical management of patients receiving AIT and efficacy in randomised controlled trials for drug development could be enhanced by predictive biomarkers. METHOD: The EAACI taskforce reviewed all candidate biomarkers used in clinical trials of AR patients with/without asthma in a literature review. Biomarkers were grouped into seven domains: (i) IgE (total IgE, specific IgE and sIgE/Total IgE ratio), (ii) IgG-subclasses (sIgG1, sIgG4 including SIgE/IgG4 ratio), (iii) Serum inhibitory activity for IgE (IgE-FAB and IgE-BF), (iv) Basophil activation, (v) Cytokines and Chemokines, (vi) Cellular markers (T regulatory cells, B regulatory cells and dendritic cells) and (vii) In vivo biomarkers (including provocation tests?). RESULTS: All biomarkers were reviewed in the light of their potential advantages as well as their respective drawbacks. Unmet needs and specific recommendations on all seven domains were addressed. CONCLUSIONS: It is recommended to explore the use of allergen-specific IgG4 as a biomarker for compliance. sIgE/tIgE and IgE-FAB are considered as potential surrogate candidate biomarkers. Cytokine/chemokines and cellular reponses provided insight into the mechanisms of AIT. More studies for confirmation and interpretation of the possible association with the clinical response to AIT are needed.