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Background : MP- AzeFlu (azelastine/fluticasone propionate in one spray) is the most effective allergic rhinitis (AR) treatment available. Its effect on asthma control in co- morbid patients is unknown. We examined whether MP- AzeFlu altered asthma control in patients with AR and asthma. Method : This pre- post historical cohort study, carried out using the Optimum Patient Care Database, included patients aged ≥12 years from UK general practice with active asthma in the year before MP- AzeFlu initiation. Active asthma was defined as a recorded diagnosis, with ≥ 1 prescription for reliever or controller inhaler in the year prior to and including the initiation date. The primary endpoint was change in number of acute respiratory events (i.e. an exacerbation or an antibiotic course for a respiratory event) between baseline and outcome years. Study outcomes were assessed by Wilcoxon signed rank test or McNemar ' s test. Results : 1,188 patients were included (average age: 47 yrs; 58.4% female). Most were prescribed intranasal corticosteroids (60.4%) and Inhaled corticosteroid (ICS)/long- acting β2 - agonist (59.3%) at baseline. MP- AzeFlu initiation was associated with significantly fewer acute respiratory events ( P = .013). Significantly more patients had well- controlled asthma in the year after MP- AzeFlu initiation ( P = .004). These asthma control benefits were noted despite significant reduction in short- acting β2 - agonist (SABA) dose ( P 2 SABA puffs/week ( P < .001) and the average ICS dose remaining stable (64.0% of patients) or reduced (20.4% of patients). Conclusion : MP- AzeFlu initiation is associated with reduced acute respiratory events, improved asthma control and reduced SABA and maintenance ICS dose in patients with AR and asthma. This study was funded by BGP Products Operations GmbH (A Mylan Company).

In order to summarize recent research on the prevention of allergies—particularly asthma—and stimulate new activities for future initiatives, a virtual workshop sponsored by the EAACI Clemens von Pirquet foundation and EUFOREA was held in October 2021. The determinants of the “allergic march” as well as the key messages from intervention studies were reviewed by an international faculty of experts. Several unmet needs were identified, and a number of priorities for future studies were proposed.

Background The Dermatophagoides pteronyssinus molecule Der p 23 is a major allergen whose clinical relevance has been shown in cross‐sectional studies. We longitudinally analysed the trajectory of Der p 23‐specific IgE antibody (sIgE) levels throughout childhood and youth, their early‐life determinants and their clinical relevance for allergic rhinitis and asthma. Methods We obtained sera and clinical data of 191 participants of the German Multicentre Allergy Study, a prospective birth cohort. Serum samples from birth to 20 years of age with sIgE reactivity to Der p 23 in a customised semiquantitative microarray were newly analysed with a singleplex quantitative assay. Early mite exposure was assessed by measuring the average content of Der p 1 in house dust at 6 and 18 months. Results Der p 23‐sIgE levels were detected at least once in 97/191 participants (51%). Prevalence of Der p 23 sensitisation and mean sIgE levels increased until age 10 years, plateaued until age 13 years and were lowest at age 20 years. Asthma, allergic rhinitis (AR) and atopic dermatitis (AD) were more prevalent in Der p 23‐sensitised children, including those with monomolecular but persistent sensitisation (11/97, 11%). A higher exposure to mites in infancy and occurrence of AD before 5 years of age preceded the onset of Der p 23 sensitisation, which in turn preceded a higher incidence of asthma. Conclusions Der p 23 sensitisation peaks in late childhood and then decreases. It is preceded by early mite exposure and AD. Asthma and AR can occur in patients persistently sensitised to Der p 23 as the only mite allergen, suggesting the inclusion of molecular testing of Der p 23‐sIgE for subjects with clinical suspicion of HDM allergy but without sIgE to other major D.pt. allergens.

In vitro immunoglobulin E (IgE) tests can be better standardized if based on molecules rather than extracts. However, singleplex screening tests for respiratory or food allergies are still based on extracts only.To validate a novel singleplex IgE screening test for respiratory allergies, based on a mix of major allergenic molecules Der p 1, Der p 2, Fel d 1, Can f 1, Can f 2, Can f 3, Can f 5, Bet v 1, Phl p 1, and Art v 1 (Molecular SX01, NOVEOS, HYCOR, USA), and requiring only four microliters (μl) of serum.We examined six subsets of sera from participants of the German Multicenter Allergy Study (MAS) birth cohort enrolling 1314 newborns during 1990: (1) monosensitized (n = 58); (2) polysensitized (n = 24); (3) nonsensitized, with total IgE levels above (n = 24) or (4) below (n = 24) 300 kU/L; (5) sensitized to milk and/or egg but not to airborne allergens (n = 24); and (6) sera of children aged ≤5 years at their earliest IgE monosensitization to airborne allergens (n = 41). Sera were analyzed with the novel molecular SX01 test (NOVEOS) and with three categories of comparators: ImmunoCAP Phadiatop SX01, extracts, and molecules of D. pteronyssinus, cat, dog, grass, and birch. Sensitivity, specificity, positive and negative predictive values were calculated. Quantitative interrelationships were determined using Spearman's rank-order correlation coefficient and Bland-Altmann plots.The molecular SX01 test predicted the outcome of IgE tests based on molecules, extracts, or Phadiatop in 188 (96.4%), 171 (87.7%), and 171 (87.7%) of the 195 sera, respectively. Accordingly, sensitivity was 93.5%, 89.0%, and 82.4%, whereas specificity was 100%, 97.6%, and 96.1% when compared with molecular, extract, and Phadiatop tests, respectively. Inconsistent outcomes were largely confined to sera with IgE-Ab levels around the cutoff value of 0.35 kU/L, except for 5/195 (2.5%) sera, containing high levels of IgE to Phl p 5 and/or Alt a 1 only. IgE levels measured by the molecular SX01 test and with IgE tests to molecules, extracts, and Phadiatop were highly correlated (rho 0.90; p .001), (rho 0.87, p .001), (rho 0.84, p .001), respectively. The novel molecular SX01 test detected IgE-Ab in 27/28 (sensitivity 96.4%) of the sera of preschool children at their earliest IgE sensitization to the same molecules.Our study validates the prototype of a novel category of IgE test, based on molecular mixes. The test's rather good precision and accuracy in early screening IgE sensitization to airborne allergens in German children may be further improved by adding a few other molecules, such as Phl p 5 and Alt a 1.

Background The Grazax Asthma Prevention (GAP) trial has recently demonstrated significant reductions in the odds of asthma symptoms or medication use in patients treated with SQ® grass SLIT-tablet relative to placebo, both in combination with allergy and asthma pharmacotherapy. The objective of the present analysis was to evaluate the cost-effectiveness of SQ grass SLIT-tablet relative to placebo in children with AR from the perspective of a German healthcare payer. Methods A cost-utility model was developed in Microsoft Excel (Microsoft Corporation, Redmond, WA, USA) to evaluate the cost-utility of SQ grass SLIT-tablet in combination with pharmacotherapy versus pharmacotherapy alone in patients with AR. Transition probabilities were derived from the GAP trial, and costs were taken from a real-world insurance database analysis. Future costs and effects were discounted at 3% per annum, and extensive deterministic and probabilistic sensitivity analyses were performed. Results Over a 10-year time horizon, the base case analysis showed an increase in overall treatment costs of €897 per child being treated with SQ grass SLIT-tablet relative to pharmacotherapy alone. The increased treatment costs were accompanied by an improvement in patient quality of life of 0.10 quality-adjusted life years (QALYs) yielding an ICER of €8978 per QALY gained, falling well below a willingness-to-pay threshold of €17,800 per QALY gained. The base case results were insensitive to changes in all individual model parameters. Discussion Improvements in quality of life with the SQ grass SLIT-tablet would be accompanied by only a modest increase in costs over a 10-year time horizon, with the SQ grass SLIT-tablet therefore representing excellent value for money from the German healthcare payer perspective.

International audience; Introduction: Allergen bioavailability underpins the efficacy and safety of SLIT tablets. Three product-related factors are likely to influence this: tablet potency, formulation and sublingual holding time.Areas covered: Tablet formulation determines the rate and extent of solubilized allergen release. Using validated in vitro dissolution assays, the two licensed grass pollen SLIT tablets are shown to release ≥85% of their total allergenic activity within several minutes. Sublingual holding time affects the contact duration between solubilized allergens and sublingual tissue. Maximal uptake of allergens by sublingual tissue requires ~5 minutes, with little uptake occurring within the first minute. A higher potency tablet with longer sublingual holding time would provide higher bioavailability, while faster rates of allergen release in vitro are unlikely to translate to a greater increase in bioavailability. Differences in dissolution times cannot serve as a surrogate of in vivo bioavailability, and are not related to differences in efficacy at the marketed tablet dosages. Rapid in vitro dissolution is likely not a key requirement for inducing a potent immune response.Expert opinion: In vitro dissolution cannot predict the clinical efficacy of SLIT tablets but could be important in immune tolerance and safety. In addition, a discontinuous administration regimen may have benefits for adherence and cost without compromising efficacy.

Background It has previously been shown in an uncontrolled study that the IgE response to vaccine antigens is downregulated by co-vaccination with cellular Bordetella pertussis vaccine. Methods In the present study, we compared in a controlled trial the humoral immune response to diphtheria toxoid (D) and tetanus toxoid (T) in relation to co-vaccinated cellular or acellular B pertussis vaccine. IgE, IgG4, and IgG to D and T were analyzed at 2, 7, and 12 months of age in sera of children vaccinated with D and T (DT, N = 68), cellular (DTPw, N = 68), 2- or 5-component acellular B pertussis vaccine (DTPa2, N = 64; DTPa5, N = 65). Results One month after vaccination, D-IgE was detected in 10% sera of DTPw-vaccinated children, whereas vaccination in the absence of whole-cell pertussis resulted in 50%-60% IgE positivity. Six months after vaccination, the IgE antibody levels were found to be more persistent than the IgG antibodies. These diphtheria findings were mirrored by those for tetanus. Only minor differences between vaccine groups were found with regard to D-IgG and T-IgG. No immediate-type allergic reactions were observed. Conclusion Cellular (but not acellular) B pertussis vaccine downregulates IgE to co-vaccinated antigens in infants. We assume that the absence of immediate-type allergic reactions is due to the high levels of IgG antibodies competing with IgE antibodies.

International audience; The introduction of personalized medicine (PM) has been a milestone in the history of medical therapy, because it has revolutionized the previous approach of treating the disease with that of treating the patient. It is known today that diseases can occur in different genetic variants, making specific treatments of proven efficacy necessary for a given endotype. Allergic diseases are particularly suitable for PM, because they meet the therapeutic success requirements, including a known molecular mechanism of the disease, a diagnostic tool for such disease, and a treatment blocking the mechanism. The stakes of PM in allergic patients are molecular diagnostics, to detect specific IgE to single-allergen molecules and to distinguish the causative molecules from those merely cross-reactive, pursuit of patient's treatable traits addressing genetic, phenotypic, and psychosocial features, and omics, such as proteomics, epi-genomics, metabolomics, and breathomics, to forecast patient's responsiveness to therapies, to detect biomarker and mediators, and to verify the disease control. This new approach has already improved the precision of allergy diagnosis and is likely to significantly increase, through the higher performance achieved with the personalized treatment, the effectiveness of allergen immunotherapy by enhancing its already known and unique characteristics of treatment that acts on the causes.

Atopic dermatitis (AD) is a common skin disease during infancy, which imposes a considerable burden on patients, their families, and the society, requiring effective treatment options that result in rapid and sustained symptom relief. Additionally, early treatment may prevent the development of atopic comorbidities by restoring the skin barrier. Currently, topical standard-of-care for AD in infants includes emollients and topical corticosteroids (TCS) to treat and reduce the risk of flares. However, only few have been approved for infants and long-term maintenance therapy with TCS is not indicated due to potential local and systemic side effects, including skin atrophy. Accordingly, the recently updated European guidelines for treatment of AD recommend topical calcineurin inhibitors (TCIs) for long-term use, treatment of sensitive skin areas, and for use in the pediatric population. Evidence on the use of TCIs for infants has almost been exclusively collected for pimecrolimus, with >4000 infants evaluated in clinical trials, consistently confirming that pimecrolimus is a safe and effective treatment for infants with AD. Nevertheless, its use is still restricted in most countries to children above the age of 2 years due to initial and mostly theoretical safety concerns. Based on a careful review of the available evidence of clinical trials, post-marketing surveillance, and epidemiological studies, an Expert Panel of European dermatologists and pediatric allergologists concluded that these safety concerns are no longer valid. Therefore, pimecrolimus offers a safe and effective alternative to TCS in infants aged 3 months and above, and labeling restrictions in this age group are no longer justified.

International audience; Concerning development of medicinal products, children belong to a so-called "special population" for which additional legislation applies: Regulation (EC) No 1901/2006 on medicinal products for paediatric use sets up a system of requirements, rewards and incentives to ensure that medicinal products are researched, developed and authorized to meet the therapeutic needs of children. Allergen Immunotherapy (AIT) is believed to contain a strong potential for immunomodulatory effects inducing sustained clinical efficacy after cessation of treatment (disease modifying effect) and thereby may prevent the progression of the atopic march towards asthma manifestation. However, to this day only few data on long-term effects in general exist and even fewer in children. These are predominantly data from open studies, which are strongly influenced in their validity by the known placebo effect of AIT. Furthermore, there are no studies allowing for the conclusion that efficacy in adults are mirrored by a similar efficacy in children and thus, up to now, it is not possible to extrapolate data from adults to children. The Paediatric Committee (PDCO)-European Medicines Agency's (EMA) scientific committee responsible for activities on medicines for children-initiated a Multi-Stakeholder Meeting on AIT for Children held at the Paul-Ehrlich-Institut in Langen, Germany, to provide a platform for discussion and exchange of thoughts to this topic between allergy experts from academia, regulators and AIT-manufacturers. The consented meeting minutes, conclusions and participants are presented.

Spring and Summer 2020 are unique in that the challenges of care for those suffering from pollen allergy coincide with the COVID-19 pandemic. Several considerations are important to allow optimal care of allergic rhinitis (AR) and asthma and hence prevention of coronavirus spread through sneezing, rhinorrhoea, and coughing. This compact overview of recommendations by the EUFOREA expert teams on allergic airway diseases and allergen-specific immunotherapy (AIT) is based on investigation of the current COVID-19 literature in association with the key words above and shared clinical experience of the experts involved. It deals with similarities and differences between AR and coronavirus infection, specific recommendations for allergic disease care in the COVID-19 era, including guidance on AIT. ispartof: WORLD ALLERGY ORGANIZATION JOURNAL vol:13 issue:5 ispartof: location:United States status: published

Background: MP-AzeFlu (Dymista®; spray of azelastine/fluticasone propionate) is the most effective allergic rhinitis (AR) treatment available. Its effect on asthma outcomes in patients with AR and asthma is unknown. Methods: This pre-post historical cohort study, using the Optimum Patient Care Research Database, included patients aged ≥12 years, from UK general practice with active asthma (defined as a recorded diagnosis, with ≥1 prescription for reliever or controller inhaler) in the year before or at the initiation date. The primary study outcome was change in number of acute respiratory events (i.e. exacerbation or antibiotic course for a respiratory event) between baseline and outcome years. The effect size of MP-AzeFlu was quantified as the difference in % of patients that improved and worsened. Results: Of the 1,188 patients with AR and asthma included, many had a record of irreversible obstruction (67%), and uncontrolled asthma (70.4%), despite high mean daily doses of reliever/controller therapy and acute oral corticosteroid use, in the year pre-MP-AzeFlu initiation. MP-AzeFlu initiation was associated with fewer acute respiratory events (effect size (e) = 5.8%, p = 0.0129) and a reduction in daily use of short-acting β2-agonists, with fewer patients requiring >2 SABA puffs/week (e = 7.7% p

The allergist's community has recently celebrated 100 year of Allergen Immunotherapy (AIT). Unfortunately the implemention of this treatment is still impaired by some challenges. With the diversity of definitions, methodology and different allergen products used, research studies have produced conflicting outcomes. This has resulted in confusion about the benefits and risks of AIT amongst policymakers and professionals, as well as in the variable availability of AIT products, regulation and reimbursement policies globally. In 2015 EAACI initiated the AIT Guidelines project as part of the Presidential plan in order to settle the controversies. This article is protected by copyright. All rights reserved.

Specific allergen immunotherapy is considered a key candidate for a successful preventive intervention in atopic diseases. The strong association of atopic manifestations such as rhinitis and asthma with atopic sensitizations (specific serum IgE) provide a rationale for early intervention in childhood and adolescence.Currently, the documentation of the disease-modifying intervention effects is limited to the secondary prevention of asthma symptoms in children with allergic rhinoconjunctivitis. These effects appear to be rather allergen specific than nonspecific.Documentation on disease modification including a reduction of asthma symptoms in children, particularly with grass pollen tablets has become quite robust. It is not clear up to now, if the new onset of allergic sensitizations can be modified. So far data on primary prevention are not conclusive.

Background In early childhood, the allergen-specific IgG repertoire is mainly directed to animal and vegetable food molecules and infrequently to airborne molecules. It is unknown whether this early pattern is maintained throughout childhood. Objective To investigate the evolution of IgG and IgE responses to a broad panel of allergenic molecules from birth to age 10yrs. Methods We examined the sera collected between birth and age 10yrs from participants in the German Multicentre Allergy Study, a birth cohort born in 1990. The IgE (cut-off ≥0.30 ISU) and IgG (cut-off ≥0.10 ISU) responses to 35 genuine allergenic molecules were measured with a multiplex microarray approach (ImmunoCAP ISAC™). Results IgE responses were mostly directed against a restricted group of airborne molecules, with a sequence and prevalence hierarchy (Phl p 1 > Bet v 1 > Fel d 1 > Phl p 5 > Der p 2 > Der p 1) largely maintained over time. Conversely, the IgG repertoire was much broader, starting with animal foodborne, then spreading to vegetable foodborne and finally to airborne molecules. A strong and persistent IgG response to a given airborne molecule almost invariably preceded or accompanied an IgE response to that molecule. Conclusions The evolution of IgG and IgE responses throughout childhood differs widely at population level. IgG responses are mostly directed to animal food allergens while IgE responses are dominated by airborne allergens. However, a strong IgG response almost invariably precedes or accompanies the appearance of IgE to the same molecule in specifically sensitized subjects. This article is protected by copyright. All rights reserved.

Atopic dermatitis (AD) affects up to 20% of children worldwide and is an increasing public health problem, particularly in developed countries. Although AD in infants and young children can resolve, there is a well-recognized increased risk of sequential progression from AD to other atopic diseases, including food allergy (FA), allergic rhinitis, allergic asthma, and allergic rhinoconjunctivitis, a process referred to as the atopic march. The mechanisms underlying the development of AD and subsequent progression to other atopic comorbidities, particularly FA, are incompletely understood and the subject of intense investigation. Other major research objectives are the development of effective strategies to prevent AD and FA, as well as therapeutic interventions to inhibit the atopic march. In 2017, the Division of Allergy, Immunology, and Transplantation of the National Institute of Allergy and Infectious Diseases sponsored a workshop to discuss current understanding and important advances in these research areas and to identify gaps in knowledge and future research directions. International and national experts in the field were joined by representatives from several National Institutes of Health institutes. Summaries of workshop presentations, key conclusions, and recommendations are presented herein.

The seventh "Future of the Allergists and Specific Immunotherapy (FASIT)" workshop held in 2019 provided a platform for global experts from academia, allergy clinics, regulatory authorities and industry to review current developments in the field of allergen immunotherapy (AIT). Key domains of the meeting included the following: (a) Biomarkers for AIT and allergic asthma; (b) visions for the future of AIT; (c) progress and data for AIT in asthma and the updates of GINA and EAACI Asthma Guidelines (separated for house dust mite SCIT, SLIT tablets and SLIT drops; patient populations) including a review of clinically relevant endpoints in AIT studies in asthma; (d) regulatory prerequisites such as the "Therapy Allergen Ordinance" in Germany; (e) optimization of trial design in AIT clinical research; (f) challenges planning and conducting phase III (field) studies and the future role of Allergen Exposure Chambers (AEC) in AIT product development from the regulatory point of view. We report a summary of panel discussions of all six domains and highlight unmet needs and possible solutions for the future. ispartof: ALLERGY vol:74 pages:3-25 ispartof: location:Denmark status: published

Background Real-world evidence is sparse on the benefits of allergen immunotherapy [AIT; subcutaneous/sublingual immunotherapy (SCIT/SLIT)], the only disease-modifying intervention for allergic rhinitis (AR) with long-term efficacy. This real-life study evaluated the effect of six AITs (native pollen SLIT/SCIT, four allergoid SCITs) vs symptomatic medication use, on AR symptoms and asthma symptoms/onset, in patients with birch pollen-associated AR and/or asthma. Methods In this retrospective cohort analysis of a German longitudinal prescription database, AIT patients received >= 2 successive seasonal treatment cycles; non-AIT patients had >= 3 AR prescriptions in three seasons or previous month. Patients were matched for: index year, age, gender, main indication at index, number of seasonal cycles within treatment period, baseline AR/asthma treatment prescriptions. Multiple regression analysis compared prescription data in AIT and non-AIT groups as proxy for clinical status/disease progression. Results Up to 6 years of follow-up, significantly more AIT (65.4%) vs non-AIT (47.4%) patients were AR medication-free; odds ratio (OR) [95% confidence interval (CI)]: 0.51 [(0.48-0.54); P < 0.001] (28.6% covariate-adjusted reduction vs non-AIT; P < 0.001), and significantly more AIT (49.1%) vs non-AIT (35.1%) patients were asthma medication-free [OR (95% CI): 0.59 (0.55-0.65); P < 0.001] (32% reduction vs non-AIT; P < 0.001), or reduced existing asthma medication use (32% covariate-adjusted reduction vs non-AIT; P < 0.001). During treatment, new-onset asthma risk was significantly reduced in the AIT vs non-AIT group (OR: 0.83; P = 0.001). Conclusions Birch pollen AIT demonstrated real-world benefits up to 6 years post-treatment cessation through significantly reduced AR and asthma medication intake, and significantly decreased risk of new-onset asthma medication use on-treatment.

Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence-based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including health professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as on the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow up of patients. This article is protected by copyright. All rights reserved.

International audience; BACKGROUND:The allermix survey was conducted to gain insights into the most frequently diagnosed allergies worldwide, the use of allergen immunotherapy (AIT) in clinical practice, and to identify current clinical approaches for the management of polyallergic patients.METHODS:The survey was conducted in 19 countries worldwide during 2016. Clinicians currently prescribing AIT completed an online questionnaire, designed to gather data on their daily clinical practice, most commonly diagnosed and treated allergies among their patients, awareness and adherence to recommendations and guidelines on AIT, the AIT format(s) that they choose to prescribe, and management of polyallergic patients.RESULTS:Respondents (N = 1029) considered a clinical demonstration of safety and effectiveness, and quality and standardization of allergen extract, as key factors influencing their choice of which AIT formulation to prescribe. 98% of respondents reported managing polyallergic patients; 58% were treated with single-allergen AIT and 42% with multiple-allergen AIT. 74% of respondents were aware of latest AIT practice guidelines, while 67% had an awareness of recent recommendations for pharmaceutical manufacturers.CONCLUSION:These findings highlight the need for high-quality AIT products that are supported by robust efficacy and safety data, and address the treatment habits of allergy specialists in their real-life clinical practice.

Background Accessible markers to predict the development of atopic diseases are highly desirable but yet matter of debate. Objective We investigated the role of blood eosinophils at 4 weeks and 7 months of life and their association with developing atopic dermatitis (AD) in a birth cohort of children with atopic heredity. Methods Infant blood samples for eosinophil counts were taken from 559 infants at 4 weeks and from 467 infants at 7 month of life with at least one atopic parent. Elevation of blood eosinophils was defined as ≥ 5% of total leukocytes and the asscociation for the occurrence of AD was assessed by entering 2 × 2 tables and the odds ratios were estimated followed by hypothesis testing against the alternate working hypothesis: odds ratio 1. Survival analysis was carried out estimating the Kaplan-Meier product limit estimator from the life-time table of AD score and time to AD manifestation stratified by the eosinophil binary score. Results Elevated blood eosinophils observed at 4 weeks were significantly associated with the occurrence of AD in the whole cohort at the age of 7 months (p = 0.007), 1 year (p = 0.004), 2 years (p = 0.007) and 3 years (p = 0.006) of life. AD occurred app. 12 weeks earlier in infants with elevated blood eosinophils at 4 weeks of life. Blood eosinophil counts ≥5% at 7 months of life failed to show significance for AD; for eosinophils at 4.5% a significant association at 7 months (p = 0.005), and 1 year of life (p = 0.039), 2 years (p = 0.033) and 3 years (p = 0.034) was observed. Conclusion Elevated blood eosinophils at age 4 weeks have a predictive value for the onset of atopic dermatitis in infancy and early childhood in children with high risk for atopy. Early eosinophil counts may therefore be helpful for counseling parents to provide infant skincare but furthermore identify individuals for interventional trials aiming at allergy prevention.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Prevention of Allergic Disease. We seek to critically assess the effectiveness, cost-effectiveness, and safety of AIT in the prevention of allergic disease.METHODS: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesized.DISCUSSION: The findings from this review will be used to inform the development of recommendations for EAACI's Guidelines on AIT.

BACKGROUND: The role of tobacco smoke exposure in the development and persistence of asthma and rhinoconjunctivitis through childhood into adolescence is unclear. OBJECTIVES: We assessed the associations of parental smoking from fetal life through adolescence with asthma and rhinoconjunctivitis during childhood and adolescence. METHODS: We analyzed data for 10,860 participants of five European birth cohort studies from the Mechanisms of the Development of Allergy (MeDALL) consortium. Parental smoking habits and health outcomes (early transient, persistent, and adolescent-onset asthma and rhinoconjunctivitis) were based on questionnaires covering the period from pregnancy to 14-16 y of age. Data were combined and analyzed using a one-stage and two-stage individual participant data meta-analysis. RESULTS: Overall, any maternal smoking during pregnancy tended to be associated with an increased odds of prevalent asthma [adjusted odds ratio (aOR)=1.19 (95% CI: 0.98, 1.43)], but not prevalent rhinoconjunctivitis [aOR=1.05 (95% CI: 0.90, 1.22)], during childhood and adolescence. In analyses with phenotypes related to age of onset and persistence of disease, any maternal smoking during pregnancy was associated with early transient asthma [aOR=1.79 (95% CI: 1.14, 2.83)]. Maternal smoking of >/=10 cigarettes/day during pregnancy was associated with persistent asthma [aOR=1.66 (95% CI: 1.29, 2.15)] and persistent rhinoconjunctivitis [aOR=1.55 (95% CI, 1.09, 2.20)]. Tobacco smoke exposure during fetal life, infancy, childhood, and adolescence was not associated with adolescent-onset asthma or rhinoconjunctivitis. CONCLUSIONS: Findings from this combined analysis of five European birth cohorts strengthen evidence linking early exposure to tobacco smoke with asthma during childhood and adolescence. Children with high early-life exposure were more likely than unexposed children to have early transient and persistent asthma and persistent rhinoconjunctivitis. https://doi.org/10.1289/EHP2738.

BACKGROUND Interaction between respiratory multimorbidity and lung function has not been examined in longitudinal population studies. We aimed to assess the association of multimorbidity of asthma and rhinitis with lung function and bronchial hyperresponsiveness in comparison with single and no allergies from early school age to young adulthood. METHODS In 1990, the Multicenter Allergy Study birth cohort recruited 1314 newborns from 5 German cities. At 7, 13, and 20 years, we performed lung function and bronchial challenge tests. We assessed symptoms, medications, and doctor's diagnoses for asthma and rhinitis for 3 outcomes: current multimorbidity (both coexisting), asthma only, and rhinitis only. RESULTS From 7 to 20 years, multimorbidity prevalence more than doubled from 3.5% to 7.7%, current asthma only (without rhinitis co-occurring) decreased by half from 2.8% to 1.3%, and current rhinitis only (without asthma co-occurring) increased from 14.3% to 41.6%. Resting lung function parameters differed between allergic and asymptomatic participants but showed no considerable differences between the allergic phenotypes. Frequency and severity of bronchial hyperresponsiveness were particularly associated with multimorbidity. At the age of 20 years, participants with multimorbidity showed a clearly higher severity in hyperresponsiveness compared to participants who suffered only asthma (P = .049) or rhinitis (P = .008) or were asymptomatic (P

We present an overview of important results obtained during the first 20 years of the Multicenter Allergy Study (MAS), one of the first and longest-running population-based birth cohorts focusing on asthma and allergy.The MAS is an observational population-based allergy-risk enriched cohort of 1,314 newborns enrolled in Germany in 1990. Assessments of various lifestyle and environmental exposures took place at 19 points, including 9 clinical visits for physical examinations and biosampling up to age 20 years.A positive allergic family history was a strong predictor of asthma from childhood up to adulthood, more so for allergic multimorbidity than single allergic entities. For asthma prevalence, the early male preponderance shifted toward females during adolescence, leading to a sex-balanced distribution by age 20 years. Eczema prevalence switched toward a clear and persisting female predominance, whereas allergic rhinitis continued to affect more males up to age 20 years. The immunoglobulin (Ig) E antibody response to grass evolved in many allergic children from a simple, often mono- and oligomolecular to a polymolecular sensitization stage ("molecular spreading"). Indoor allergen exposure increased the risk for specific sensitization, which was linked to asthma and impaired lung function at early school-age. Moreover, the MAS birth cohort has made important contributions to the investigation of genetic factors in the manifestation of clinical subphenotypes and in the long-term temporal trajectory of allergic diseases.Follow-up assessments over 2 decades provided new insights into risk factors and predictors for eczema, rhinitis, and asthma up to adulthood to develop better prevention strategies.

The history of pediatric allergology (PA) in Europe is relatively youthful, dating back to 1984, when a small group of pediatricians founded the European Working Group on Pediatric Allergy and Immunology-later giving rise to ESPACI (European Society on Pediatric Allergology and Clinical Immunology). In 1990, the first dedicated journal, Pediatric Allergy and Immunology (PAI), was founded. There are striking differences across Europe, and even within European countries, in relation to the training pathways for doctors seeing children with allergic disease(s). In 2016, the EAACIClemens von Pirquet Foundation (CvP) organized and sponsored a workshop with the European Academy of Allergy and Clinical Immunology (EAACI) Pediatric Section. This collaboration focussed on the future of PA and specifically on education, research, and networking/ advocacy. The delegates representing many countries across Europe have endorsed the concept that optimal care of children with allergic diseases is delivered by pediatricians who have received dedicated training in allergy, or allergists who have received dedicated training in pediatrics. In order to meet the needs of children and families with allergic disease(s), the pediatric allergist is highly encouraged to develop several networks. Our challenge is to reinforce a clear strategic approach to scientific excellence to across our member base and to ensure and enhance the relevance of European pediatric research in allergy. With research opportunities in basic, translational, clinical, and epidemiologic trials, more trainees and trained specialists are needed and it is an exciting time to be a pediatric allergologist.

International audience; 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.

Background Allergy immunotherapy (AIT) is the only treatment for allergic rhinitis (AR) and/or allergic asthma (AA) with long-term efficacy. However, there are few real-life data on the progression of AR and/or AA in patients receiving AIT. Objectives To assess the real-world, long-term efficacy of grass pollen sublingual immunotherapy (SLIT) tablets in AR and their impact on asthma onset and progression. Methods In a retrospective analysis of a German longitudinal prescription database, AR patients treated with grass pollen SLIT tablets were compared with a control group not having received AIT. Multiple regression analysis was used to compare changes over time in rescue symptomatic AR medication use after treatment cessation, asthma medication use, and the time to asthma onset in the two groups. Results After applying all selection criteria, 2851 SLIT and 71 275 control patients were selected for the study. After treatment cessation, AR medication use was 18.8 percentage points lower (after adjustment for covariates, and relative to the pretreatment period) in SLIT tablet group than in the non-AIT group (P

Introduction Les donnees de delivrance de medicaments chez des patients atteints de rhinite et/ou asthme allergiques ont ete analysees afin d’evaluer l’impact d’une immunotherapie sublinguale (ITSL) aux pollens de bouleau sur l’evolution de l’asthme. Methodes En utilisant les donnees IQVIA de la base de donnees LRx allemande, 2 cohortes de patients souffrant de rhinite et/ou asthme allergiques ont ete comparees sur une periode totale de 9 ans : un groupe de 9001 patients traites par immunotherapie dont 838 par ITSL et un groupe temoin (45 005 patients). Cette sous-analyse porte sur la survenue d’un asthme chez des patients traites par ITSL sans antecedent de delivrance d’anti-asthmatique avant ITSL (via un modele de regression logistique ajuste sur differents criteres), et l’evolution des delivrances de medicaments de l’asthme chez les patients ayant deja ete traites (via un modele de regression lineaire ajuste sur differents criteres). Resultats Parmi les patients ITSL et les patients du groupe temoin, 634 (49,5 %) et 31 683 (70,4 %), respectivement, n’avaient pas d’antecedent de traitement pour asthme ; 61 (9,6 %) traites par ITSL et 4159 (13,1 %) temoins ont initie un traitement pour asthme. La probabilite d’initier un traitement anti-asthmatique est 34,5 % plus faible durant la periode de traitement dans le groupe ITSL que dans le groupe temoin (OR = 0,655 ; p = 0,013) et 22,6 % plus faible apres l’arret du traitement (OR = 0,774 ; p = 0,246) sur les 6 annees de suivi. Les resultats restent significatifs sur l’integralite de la periode de traitement et suivi (OR = 0,686, p = 0,006). Chez les patients ayant recu un anti-asthmatique avant la periode de traitement, on constate une reduction de l’evolution des prescriptions d’anti-asthmatiques de 41,2 % (p Conclusion Ces donnees suggerent un impact favorable d’un traitement d’immunotherapie sublinguale sur le risque d’initiation d’un traitement anti-asthmatique chez les patients identifies non asthmatiques et sur la charge therapeutique pour asthme, notamment pour ce qui concerne les delivrances de corticoides inhales, chez les patients identifies asthmatiques.