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Hirst pollen traps and operator pollen recognition are worldwide used by aerobiologists, providing essential services for the diagnosis and monitoring of allergic patients. More recently, semiautomated or fully automated detector systems have been developed, which facilitate prediction of pollen exposure and risk for the individual patient. In parallel, smartphone apps consisting of short questionnaires filled in daily by the patient/user provide daily scores, time trajectories, and descriptive reports of the severity of respiratory allergies in patients with pollen allergy. The usual scientific and clinical approach to this matter is to monitor the environment (pollen concentration) in order to predict the risk of symptoms (allergic rhinitis) in a population. We discuss here the opposite, contraintuitive possibility, that is, the use of e‐diaries to collect daily information of mono‐sensitized pollen‐allergic patients in order to predict the clinically efficient airborne exposure to a given pollen, area, and time period. In line with the "Patient as Sensor" concept, proposed in 2013 by Bernd Resch, the "allergic nose" may be used as a pollen detector in addition to existing calibrated hardware sensors, namely the pollen stations, thus contributing with individual measurements, sensations, and symptoms' perception. The target of this review is to present a novel concept of pollen monitoring based on "pollen‐detector" patients to inspire future cooperative studies aimed at investigating and hopefully validating our hypothesis. [ABSTRACT FROM AUTHOR]

The natural history of COVID‐19 caused by SARS‐CoV‐2 is extremely variable, ranging from asymptomatic or mild infection, mainly in children, to multi‐organ failure, eventually fatal, mainly in the eldest. We propose here the first model explaining how the outcome of first, crucial 10‐15 days after infection, depends on the balance between the cumulative dose of viral exposure and the efficacy of the local innate immune response (natural IgA and IgM antibodies, mannose‐binding lectin). If SARS‐CoV‐2 runs the blockade of this innate immunity and spreads from the upper airways to the alveoli in the early phases of the infections, it can replicate with no local resistance, causing pneumonia and releasing high amounts of antigens. The delayed and strong adaptive immune response (high‐affinity IgM and IgG antibodies) that follows, causes severe inflammation and triggers mediator cascades (complement, coagulation, and cytokine storm), leading to complications often requiring intensive therapy and being, in some patients, fatal. Low‐moderate physical activity can still be recommended. However, extreme physical activity and oral breathing with hyperventilation during the incubation days and early stages of COVID‐19 facilitates re‐inhalation and early direct penetration of high numbers of own virus particles in the lower airways and the alveoli, without impacting on the airway's mucosae covered by neutralizing antibodies ("viral auto‐inhalation" phenomenon). This allows the virus to bypass the efficient immune barrier of the upper airway mucosa in already infected, young, and otherwise healthy athletes. In conclusion, whether the virus or the adaptive immune response reaches the lungs first is a crucial factor deciding the fate of the patient. This "quantitative and time‐/sequence‐dependent" model has several implications for prevention, diagnosis, and therapy of COVID‐19 at all ages. [ABSTRACT FROM AUTHOR]

Mobile health is the "medical and public health practice supported by mobile devices, such as mobile phones, patient monitoring devices, personal digital assistants, and other wireless devices." For example, mobile apps (such as MASK‐Air, Allergy.Monitor, Pollen, and others) have proven useful in the management of patients with allergic rhinitis. These apps can be used in the context of broader clinical decision support systems (CDSS) for enhancing allergy‐related decisions and actions with pertinent, organized clinical knowledge and patient information to improve allergy care. A CDSS targeted to control rhinitis with drugs and other interventions guiding the patient in his/her self‐ and doctor‐driven management is currently being produced and investigated by the MACVIA network. Another one, called @IT‐2020, is targeted to support etiologic diagnostics and allergen immunotherapy (AIT) prescriptions for patients with seasonal allergic rhinitis. Intensive investigation is necessary to better define the advantages and limitations of mobile‐health technology in allergology and establish guidelines for their proper use in daily practice in the context of a rapidly evolving European regulatory environment. [ABSTRACT FROM AUTHOR]

The article discusses use of allergen‐specific immunotherapy (AIT) to cure allergic diseases by attacking their antigen‐specific immunologic mechanisms. Topics include better standardization of allergen products for diagnosis and therapy with molecular allergology, selection of molecules in order to identify genuine sensitization to the allergen, and producing recombinant molecules with hybrid technology.

Background: 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. Target: 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. Methods: 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. Results: 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. Discussion 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. [ABSTRACT FROM AUTHOR]

Allergen immunotherapy is a cornerstone in the treatment of allergic children. The clinical efficiency relies on a well‐defined immunologic mechanism promoting regulatory T cells and downplaying the immune response induced by allergens. Clinical indications have been well documented for respiratory allergy in the presence of rhinitis and/or allergic asthma, to pollens and dust mites. Patients who have had an anaphylactic reaction to hymenoptera venom are also good candidates for allergen immunotherapy. Administration of allergen is currently mostly either by subcutaneous injections or by sublingual administration. Both methods have been extensively studied and have pros and cons. Specifically in children, the choice of the method of administration according to the patient's profile is important. Although allergen immunotherapy is widely used, there is a need for improvement. More particularly, biomarkers for prediction of the success of the treatments are needed. The strength and efficiency of the immune response may also be boosted by the use of better adjuvants. Finally, novel formulations might be more efficient and might improve the patient's adherence to the treatment. This user's guide reviews current knowledge and aims to provide clinical guidance to healthcare professionals taking care of children undergoing allergen immunotherapy. [ABSTRACT FROM AUTHOR]

Background: There is growing interest both in testing IgE in nasal secretions (NS) and in molecular diagnosis of seasonal allergic rhinitis (SAR). Yet, the reliability of nasal IgE detection with the newest molecular assays has never been assessed in a large cohort of pollen allergic patients. Objective: To investigate with microarray technology and compare the repertoires of specific IgE (sIgE) antibodies in NS and sera of a large population of children and adults with SAR. Methods: Nasal secretions were collected with an absorbent device (Merocel 2000®, Medtronic) and a minimal dilution procedure from 90 children and 71 adults with SAR. Total IgE (tIgE) (ImmunoCAP, Thermo Fisher Scientific (TFS)) and sIgE antibodies against 112 allergen molecules (ISAC‐112, TFS) were measured in NS and serum. Results: Nasal sIgE was detectable in 68.3% of the patients. The detected nasal sIgE antibodies recognized airborne (88%), vegetable (10%), and animal food or other (<1%) allergen molecules. The prevalence and average levels of sIgE in NS and serum were highly interrelated at population level. A positive nasal sIgE antibody to a given molecule predicted the detection of the same antibody in the patient's serum with a specificity of 99.7% and a sensitivity of 40%. Conclusions: The concentration of sIgE is much lower in nasal secretions than in the serum. sIgE assays with very high analytical sensitivity and sampling methods with minimal dilution will be therefore needed to validate nasal secretions as alternative to serum in testing the sIgE repertoire. [ABSTRACT FROM AUTHOR]

Background Previous studies of serum total IgE (t-IgE) were not able to discriminate well-enough atopic from non-atopic subjects, that is, with or without serum-specific IgE antibodies to allergens. Objectives To model growth curves of the total IgE levels in children without atopic sensitization (hereafter defined as 'normal' t-IgE levels) and to test their usefulness in predicting atopic sensitization. Methods The German Multicentre Allergy Study ( MAS), a birth cohort with 1314 recruited newborns, began in 1990 and examined the participants until age 20 years. Total and specific IgE (t-IgE, s-IgE) were analyzed with a fluorescent enzyme immunoassay Immuno CAP ( TFS, Sweden) at ages 1, 2, 3, 5, 6, 7, 10, 13, and 20 years. Participants were classified as 'never atopic' if all their available serum samples had negative response (cutoff: <0.35 kUA/L) for s-IgE to the nine common foodborne and airborne allergenic extracts (milk, egg, soy, wheat, house dust mite, cat, dog, birch, and grass) tested in the MAS birth cohort. By contrast, participants were defined as atopic if they had, for at least at one available serum sample, s-IgE≥0.35 kUA/L to at least one allergenic extract tested. The evolution of t-IgE levels in the 'never atopic' children was described by growth curves, estimated by exploiting a quantile regression model. A 'reference' percentile, based on the t-IgE value measured at age 5 years, was assigned to each child with no IgE sensitization at that age. Upward deviations from the own 'reference' quantile of t-IgE in atopic and 'never atopic' children were calculated and a ROC analysis was used to identify the best cutoff point for predicting atopic sensitization. Results Overall, 1113 of 1314 children were included in this analysis. Of these, 469 were 'never atopic' and 644 atopic. Quantile trajectories of t-IgE levels in 'never atopic' subjects were stable from 5 years of age, increased to a plateau at age 10-13 years, and decreased slightly afterward. The onset of atopic s-IgE responses was characterized by an upward deviation of serum t-IgE levels from their 'reference' trajectory. T-IgE quantiles predicted the onset of atopy with high efficiency ( AUC>80%). ROC analysis showed that deviations from the t-IgE level 'reference' quantile above 0.32, 0.41, 0.42, 0.30, and 0.58 kU/L (log-units) at 6, 7, 10, 13, and 20 years of age, respectively, predicted an atopic sensitization. Conclusion The growth curves of 'normal' serum t-IgE concentrations were estimated in 'never atopic' children; for each individual who was non-atopic at 5 years of age a 'reference' quantile was identified that represented the individual's 'normal' level of t-IgE production. Upward deviations of observed t-IgE levels from the own 'reference' quantile, from 6 to 20 years of age, predicted at each year the occurrence of atopic sensitization. Clinical Implications The trajectory of t-IgE levels can be elaborated since age 5 years in non-atopic children. A child whose t-IgE levels are consistently higher than those predicted by his/her growth curve may have developed atopic sensitization. [ABSTRACT FROM AUTHOR]

Background There is a need to establish the effectiveness, cost-effectiveness, and safety of allergen immunotherapy ( AIT) for the prevention of allergic disease. Methods Two reviewers independently screened nine international biomedical databases. Studies were quantitatively synthesized using random-effects meta-analyses. Results A total of 32 studies satisfied the inclusion criteria. Overall, meta-analysis found no conclusive evidence that AIT reduced the risk of developing a first allergic disease over the short term ( RR = 0.30; 95% CI: 0.04-2.09) and no randomized controlled evidence was found in relation to its longer-term effects for this outcome. There was, however, a reduction in the short-term risk of those with allergic rhinitis developing asthma ( RR = 0.40; 95% CI: 0.30-0.54), with this finding being robust to a pre-specified sensitivity analysis. We found inconclusive evidence that this benefit was maintained over the longer term: RR = 0.62; 95% CI: 0.31-1.23. There was evidence that the risk of new sensitization was reduced over the short term, but this was not confirmed in the sensitivity analysis: RR = 0.72; 95% CI: 0.24-2.18. There was no clear evidence of any longer-term reduction in the risk of sensitization: RR = 0.47; 95% CI: 0.08-2.77. AIT appeared to have an acceptable side effect profile. Conclusions AIT did not result in a statistically significant reduction in the risk of developing a first allergic disease. There was, however, evidence of a reduced short-term risk of developing asthma in those with allergic rhinitis, but it is unclear whether this benefit was maintained over the longer term. We are unable to comment on the cost-effectiveness of AIT. [ABSTRACT FROM AUTHOR]

The so-called local allergic rhinitis ( LAR) has been proposed as a phenotype of rhinitis with Th2-driven prominent local allergic inflammation, nasal synthesis of specific IgE and a positive response to a nasal allergen provocation test, in the absence of 'systemic' atopy (negative skin prick test and serum allergen-specific IgE antibodies). To date, available data on LAR are mostly focused on adults. The purpose of this 'Rostrum' was to critically discuss data and implications of the ' LAR concept' in paediatrics. In the natural history of rhinitis due to IgE-mediated reactions triggered by exposure to allergens, a ' LAR' can be either the initial, transient stage of classical allergic rhinitis or a stable phenotype never evolving to 'systemic' IgE sensitization. Given the present difficulties in performing routinely nasal allergen provocation test in children, the development of sensitive and specific tests to detect IgE in the child's nasal secretions is a research priority. We suggest also the hypothetical role of allergen immunoprophylaxis or immunotherapy in LAR. Last, the term 'local allergic rhinitis' may be inappropriate, as rhinitis is always 'local', while IgE sensitization can be either 'local' or 'systemic'. [ABSTRACT FROM AUTHOR]

Background Many different symptom (medication) scores are nowadays used as measures of allergic rhinoconjunctivitis severity in individual patients and in clinical trials. Their differences contribute to the heterogeneity of the primary end-point in meta-analyses, so that calls for symptom (medication) score harmonization have been launched. Objective To prospectively compare six different severity scores for allergic rhinitis ( AR) against pollen counts at both population and individual levels. Methods Two groups of children with seasonal AR and grass pollen sensitization were recruited in Ascoli, Italy (n = 76) and Berlin, Germany (n = 29). Symptoms and drug intake were monitored daily for 40 and 30 days of the grass pollen season in 2011 (Ascoli) and 2013 (Berlin), respectively, through an Internet-based platform (AllergyMonitor™, TPS Production srl, Rome, Italy). From the gathered data, the informatics platform automatically generated one symptom score ( RTSS) and five symptom-medication scores ( RC- ACS©, ACS, RTSS[ LOCF], RTSS[ WC] and Ad SS). Values were then statistically normalized for reciprocal comparison and matched against the daily variations of local grass pollen counts (Spearman's rank correlation). Results The grass pollen counts were higher in Ascoli than in Berlin (peak values 194 vs. 59 grains/m3). At population level, the trajectories of the normalized average values of the six scores differed only slightly in both studies and correlated well with the pollen counts (ranges r2: 0.38-0.50 in Ascoli, 0.41-0.56 in Berlin). By contrast, in individual patients, trajectories of different scores were often quite heterogeneous. The RTSS[ WC] had a very low discriminatory power and generated in many patients long, flat horizontal segments. Conclusions Disease severity scores for seasonal AR, as evaluated via an Internet-based platform, tend to provide similar results at population level but can often produce heterogeneous slopes in individual patients. The choice of the disease severity score might have only a low impact on the outcome of a very large clinical trial, but it may be crucial in the management of individual patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Asthma and allergic diseases have become one of the epidemics of the 21st century in developed countries. Much of the success of other areas of medicine, such as infectious diseases, lies on preventive measures. Thus, much effort is also being placed lately in the prevention of asthma and allergy. This manuscript reviews the current evidence, divided into four areas of activity. Interventions modifying environmental exposure to allergens have provided inconsistent results, with multifaceted interventions being more effective in the prevention of asthma. Regarding nutrition, the use of hydrolyzed formulas in high-risk infants reduces the incidence of atopic dermatitis, while there is for now not enough evidence to recommend other dietary modifications, pre-biotics, probiotics, or other microbial products. Pharmacologic agents used until now for prevention have not proved useful, while there is hope that antiviral vaccines could be useful in the future. Allergen-specific immunotherapy is effective for the treatment of allergic patients with symptoms; the study of its value for primary and secondary prevention of asthma and allergy is in its very preliminary phases. The lack of success in the prevention of these disorders lies on their complexity, which involves many genetic, epigenetic, and environmental interactions. There is a need to identify target populations, involved mechanisms and interactions, and the best interventions. These must be effective, feasible, implementable, and affordable. [ABSTRACT FROM AUTHOR]