Background: In Europe, Omalizumab (anti-IgE) is indicated for the treatment of moderate/severe asthma, but not for IgE-mediated food allergy (FA). Objective: We prospectively assessed the impact of Omalizumab for efficacy, safety, and quality of life (FA-QoL) in patients with moderate/severe asthma and history of anaphylaxis to peanut, tree nuts, fish, egg, milk, and/or wheat. Methods: Food-allergic children (6-18yrs) with moderate/severe asthma underwent oral food challenges (OFCs) to establish the threshold of reaction to the culprit food(s) at baseline (T0) and at four-month intervals (T1, T2, T3) during their first year of treatment with Omalizumab. We recorded the number and severity of food-allergic reactions, Asthma Control Test (ACT), FA-QoL, and total IgE. Results: In 65 patients allergic to 107 foods, the No Observed Adverse Events Level (NOAEL) at T1 increased: 243- and 488-fold for raw and baked milk, respectively; 172 and 134-fold for raw and baked egg; 245-fold for hazelnut; 55-fold for peanut; 31-fold for wheat, and 10-fold for fish. Full tolerance was achieved in 66.4% of OFCs at T1, 58.3% at T2, and 75% at T3. Ninety-five foods were liberalized ad libitum in the diet of 55 patients; the remaining 12 were introduced by 10 patients at least in traces. Throughout the study, 40/65 children got a free diet. ACT increased from 17 (Q1-Q3:15-17) to 23.6 (Q1-Q3:23-25). The FA-QoL score in children ≤ 12 years decreased from 4.63±0.74 to 2.02±1.13, in adolescents from 4.68±0.92 to 1.90±1.50. Conclusions: Omalizumab allows safe reintroduction of allergenic foods. Trial registration number: ClinicalTrials.gov, NCT06316414

BACKGROUND: Characterization of disease endotypes will open a new window for the treatment of allergic rhinitis (AR). Herein we provide the first attempt to identify specific AR phenotypes/endotypes and/or any biomarker/predictor for specific treatment response based on local biological parameters. METHODS: This observational study was carried out in 142 patients with seasonal AR and 20 non-allergic controls. Total IgE levels, specific IgE to 112 allergenic molecules and 92 proinflammatory and immunologic proteins were measured in both serum and nasal secretions (NS). RESULTS: We found increased values of MCPs and MMPs in adults both in NS and serum when compared with pediatric patients (p<.05). MCPs and MMPs might represent two effective predictors of chronic inflammation. CXCL9, CXCL10, CXCL11, MCPs and MMP1 showed an upward trend both in serum and NS for patients with ≥ 3 comorbidities vs non-allergic controls(p<.05). These data suggest the involvement of these chemokines in the late phase of chronic allergic inflammation in the nose. Serum levels of IL-6, IL-8 and IL-10 (p<.05) were significantly higher in patients with AR+asthma compared to patients with different comorbidities. Conversely, serum levels of neurotrophin-3 values (p<.05) were significantly higher in those with AR+eczema vs other comorbidities groups. A subgroup of patients with a nasal hypersecretory state,called “hypersecreter endotype” was characterized by paediatric age, male gender, grass pollen sensitization and distributed among persistent, mild or moderate to severe cases of AR. CONCLUSIONS: Our study sets the groundwork for an AR endotypization at molecular level, which is highly desirable to deliver a patient-tailored approach.

Background Biological therapies relieve symptoms in allergic and inflammatory diseases so may also benefit people with IgE-mediated food allergy. We systematically reviewed the highest quality published evidence to inform forthcoming GA 2LEN guidelines. Methods We searched six bibliographic databases from 1946 to 30 September 2021 for randomised controlled trials, controlled clinical trials and quasi-randomised trials about biological monotherapy in people with IgE-mediated food allergy confirmed by oral food challenge. We found 3 trials with 118 participants. We used the GRADE approach. We summarised the findings narratively because studies were too heterogeneous to conduct meta-analysis. Results We included one randomised trial about etokimab, one about omalizumab and one about the discontinued TNX-901. All were in people with peanut allergy in the USA, mostly aged 13+ years. There were trends towards improved tolerance of peanut during treatment, with no increase in adverse events compared to placebo. However, we have very low certainty about the evidence. No trial reported on quality of life or cost-effectiveness. Conclusions Our review of the highest quality research found that there is not yet enough certainty of evidence to support offering etokimab or omalizumab widely for food allergy. Clinicians may consider the merits for individuals, but large randomised trials with standardised measures need to confirm the safety and efficacy and the most suitable candidates, doses and durations of treatment.

Background: Although well described in adults, there are scarce and heterogeneous data on the diagnosis and management of chronic urticaria (CU) in children (0-18 years) throughout Europe. Our aim was to explore country differences and identify the extent to which the EAACI/GA²LEN/EDF/WAO guideline recommendations for paediatric urticaria are implemented. Methods: The EAACI Taskforce for paediatric CU disseminated an online clinical survey among EAACI paediatric section members. Members were asked to answer 35 multiple choice questions on current practices in their respective centres. Results: The survey was sent to 2,773 physicians of whom 358 (13.8%) responded, mainly paediatric allergists (80%) and paediatricians (49.7%), working in 69 countries. For diagnosis, Southern European countries used significantly more routine tests (e.g., autoimmune testing, allergological tests, and parasitic investigation) than Northern European countries. Most respondents (60.3%) used a 2nd generation antihistamine as first- line treatment of whom 64.8% up dosed as a second- line. Omalizumab, was used as a second line treatment by 1.7% and third-line by 20.7% of respondents. Most clinicians (65%) follow EAACI/WAO/GA2LEN/EDF guidelines when diagnosing CU, and only 7.3% follow no specific guidelines. Some clinicians prefer to follow national guidelines (18.4%, mainly Northern European) or the AAAAI practice parameter (1.7%). Conclusions: Even though most members of the Paediatric Section of EAACI are familiar with the EAACI/WAO/GA2LEN/EDF guidelines, a significant number do not follow them. Also, the large variation in diagnosis and treatment strengthens the need to re-evaluate, update and standardize guidelines on the diagnosis and management of CU in children.

Background: Allergen immunotherapy(AIT) is the only disease-modifying treatment with long-term effects in patients with seasonal allergic rhinoconjunctivitis(SAR). Its efficacy depends on the precise identification of the pollen triggering symptoms. However, a diagnostic approach based on retrospective clinical history and sensitization to extracts often does not lead to unequivocal results. Objectives: To assess the usability and impact of a recently established algorithm for a potential clinical decision support system (@IT.2020-DSS) for pollen allergy and its diagnostic steps (including anamnesis, SPT, component resolved diagnosis, CRD, and real-time digital symptom recording, eDiary) on doctor’s AIT prescription decisions. Methods: After a concise educational training on the @IT.2020-DSS algorithm, 46 doctors (18allergy specialists, AS, and 28general practitioners, GP) expressed their hypothetical AIT prescription for 10 clinical index cases. Decisions were recorded repeatedly based on different steps of the support algorithm. The usability and perceived impact of the algorithm on individual clinical performance were evaluated. Results: The combined use of CRD and an eDiary increased the hypothetical AIT prescriptions, both among AS and GP (p<.01). AIT prescription based on anamnesis and SPT were heterogeneous but converged towards a consensus after the integration of CRD and eDiary information. Doctors considered the algorithm useful and recognized its potential in enhancing traditional diagnostics. Conclusions: The implementation of CRD and eDiary in the @IT2020-DSS algorithm improved consensus on hypothetical AIT prescription for SAR among AS and GP. The hypothesis, that a CDSS for etiological SAR diagnosis and AIT prescription may be useful in real-life clinical practice deserves further investigations.

Background This systematic review used the GRADE approach to compile evidence to inform an anaphylaxis guideline from the European Academy of Allergy and Clinical Immunology (EAACI). Methods We searched five bibliographic databases from 1946 to 20 April 2020 for studies about the diagnosis, management and prevention of anaphylaxis. We included 50 studies with 18,449 participants: 29 randomised controlled trials, seven controlled clinical trials, seven consecutive case series and seven case-control studies. Findings were summarised narratively because studies were too heterogeneous to conduct meta-analysis. Results It is unclear whether the NIAID/FAAN criteria or Brighton case definition are valid for immediately diagnosing anaphylaxis due to the very low certainty of evidence. Adrenaline is the cornerstone of first-line emergency management of anaphylaxis but, due to ethical constraints, little robust research has assessed its effectiveness . Newer models of adrenaline autoinjectors may slightly increase the proportion of people correctly using the devices and reduce time to administration. Face-to-face training for laypeople may slightly improve anaphylaxis knowledge and competence in using autoinjectors. Adrenaline prophylaxis prior to snake bite anti-venom may reduce anaphylaxis but the impact of prophylactic corticosteroids and antihistamines is uncertain. There was insufficient evidence about the impact of other anaphylaxis management strategies. Conclusions Anaphylaxis is a potentially life-threatening condition but, due to practical and ethical challenges, there is a paucity of robust evidence about how to diagnose and manage it.