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Allergy Quiz

109 Questions

1. After intranasal administration of sodium dodecyl sulfate, which epithelial cell-derived activator is found to be increased in the lungs by qPCR and ELISA? Look for the answer in the original article by Saito and colleagues.





Following intranasal administration of laundry detergent A (sodium dodecyl sulphate), an increase in IL-33 was detected in mice although TSLP and IL-25 levels did not increase by both qPCR and ELISA. Detergent A is thought to induce upregulation of IL-33 due to oxidative stress, triggering the activation of ILC2.

2. Exposure to high levels of particulate matter with aerodynamic diameters ≤2.5 micrometers (PM2.5) in children increases the frequency of which monocyte population? Check the answer by reading the original article by Movassagh and colleagues.




The study successfully demonstrated that classical monocytes (CD14+CD16+) are associated with increased PM2.5 exposure, related to a pro-inflammatory activity, whereas no differences were observed for intermediate monocytes (CD14+CD16+). In contrast, a reduction in non-classical monocytes (CD14−CD16+), mainly associated with anti-inflammatory activity, was observed.

3. According to the recent EAACI position paper published on Allergy related to digital biomarkers for allergic respiratory diseases and asthma, select one that is not a strength of digital biomarkers:





Digital and mHealth biomarkers are tools that could be of interest for clinical practice, as they allow the easy availability of large volumes of data, important for optimal decision-making, stratification, and patient monitoring. These biomarkers have several strengths, such as low associated costs. In addition, they allow for rapid automated and standardized data collection, which enables close patient follow-up. However, one of their most relevant limitations is the possibility of including biases in the data, leading to inaccurate or even incorrect classification of patients with unconfirmed diagnosis.

4. Among the novel therapies for food allergy, how many cases of anaphylaxis are estimated to occur during the administration of epicutaneous immunotherapy (EPIT). Access the data by reading the comprehensive review by Anasnostou et al. on “The future of food allergy: Challenging existing paradigms of clinical practice”.





During the administration of food allergen-specific immunotherapy (AIT), allergic reactions may occur, although depending on the specific AIT, the risk of anaphylaxis changes. The highest risk of anaphylaxis is approximately 14% during oral immunotherapy (OIT), although desensitization, is usually achieved within 6-12 months. In contrast, the risk of suffering an episode of anaphylaxis during epicutaneous immunotherapy (EPIT) is lower than during OIT (approximately 4%), although the desensitization occurs later, between 24 and 36 months. Similarly, desensitization during sublingual immunotherapy (SLIT) is achieved between 24 and 36 months, but the risk of anaphylaxis is rare.

5. Pharmacologic strategies currently approved for Allergic Rhinitis target immune cells and mediator molecules involved in allergic inflammation. Which is the mechanism of action of LRAs? Look for the answer in the original article by Luo Zhang and colleagues.





Cysteinyl leukotrienes trigger inflammation process by activating protein molecules known as CysLT1 receptors on the surface of bronchial smooth muscle cells and immune cells. Leukotriene receptor antagonists (LRAs) are able to bind the CysLT1 receptors and to inhibit cysteinyl leukotrienes’ pro-inflammatory activity.

6. In Allergic Rhinitis animal model, Mesenchymal Stem Cells (MSCs) effectively decreased the number of sneezes and nose rubbing and alleviated local inflammation in the nasal mucosa. Which are the MSCs immunomodulatory effects mainly detected? Check the answer by reading the original article by Luo Zhang and colleagues.





MSCs can enhance the action of T cells (Treg), restore immune balance of Th1/Th2 cells, promote the switch of M1 to M2 macrophages, restore epithelial barrier integrity, and regulate key cells and molecules of type 2 immune response. Mechanisms underlying the immunomodulatory effects of MSCs are associated with cell– cell contact, as well as extracellular vesicles and soluble factors.

7. Oral prednisone improves the inflammatory process caused by diphencyprone (DPCP) in delayed-type hypersensitivity reactions (DTH), as it showed a decrease in the International Contact Dermatitis Research Group (ICDRG) score and secondary hypersensitivity reaction (SHR) diameter compared to the placebo group. Related to this, what specific T-cell subpopulation seem to be involved in this improvement? You can find the answer by reading the original article by Mehta and colleagues.





Oral prednisone administration in DTH by DPCP improves clinical parameters of skin inflammation, as measured by decreases ICDRG score and SHR diameter. This improvement has been linked with to a reduction in activated TRM, specifically CD8+IFNγ+PD-1+ cells, which despite being a rare cell population, appears to be significantly involved in several inflammatory diseases. Interestingly, the frequency of other cell subpopulations such as Tc1, Tc2, Th17, Th1, Th2, or Tregs is not modified by the glucocorticoid administration.

8. Atopic dermatitis (AD) can initiate during childhood (pediatric-onset AD, POAD) or during adulthood (adult-onset AD, AOAD). Identifying the specific characteristics of each AD based on age of onset may be essential for the management of the disease, guiding specific therapeutic strategies. Compared to AOAD, which specific pathway is enriched in POAD-injured skin? You can find the correct answer by reading the original article by Facheris and colleagues.





Lesional skin in both POAD and AOAD, shows significant increases in Th1, Th2, Th22, and Th17 compared to nonlesional skin. Nevertheless, only Th17 is significantly increased in POAD lesional skin compared to AOAD. This is also accompanied by increased barrier dysfunction, with lower expression of terminal differentiation, lipid, and cell adhesion molecules. These results suggest that POAD may represent a different endophenotype from AOAD, with important implications for the management and treatment of AD.

9. Atopic dermatitis (AD) is a chronic inflammatory disease characterised by a complex pathogenesis and heterogeneous immune mechanisms. This makes it difficult to identify specific biomarkers, as well as to correctly treat and monitor AD patients. It is therefore important to better understand the immunological mechanisms of the disease. Among the mediators involved, CCL19 may represent a key molecule for the trafficking of different immune cells, such as dendritic cells or T cells, through the interaction with CCR7, in the leukocyte-infiltrated area lesions. In relation to CCL19, which specific cells are the most potent sources of CCL19 in leukocyte-infiltrated areas of lesioned skin in AD patients? You can find the answer by reading the original article by Mitatura and colleagues by clicking here.





Atopic dermatitis (AD) is a complex and heterogeneous chronic disease with skin involvement. The original article by Mitamura and colleagues nicely identified the resident tissue cells as well as the interaction between them in lesioned AD skin infiltrates. Moreover, they have shown that in AD-affected skin, COL18A1+ fibroblasts express high amount of CCL19, together with LAMP3+ DCs mainly in leukocyte-infiltrated area lesions compared to unaffected skin. These activated fibroblasts in AD infiltrates interact with antigen presenting cells, mainly DCs, through CCR7, and T cells, suggesting a fibroblast phenotype change between healthy and AD skin.

10. Asthma induced by allergen exposure is mainly mediated by Th2 cells with recruitment and involvement of other immune cells into the lungs such as neutrophils or eosinophils. Anti-CD3 has been shown to be effective in reducing the activity of immune cells in different diseases. Therefore, anti-CD3 could also be used to reduce lung inflammation from initial exacerbation and re-challenges with house dust mite (DHM) undergoing several asthma exacerbations. Which specific immune cells were reduced in bronchoalveolar lavage fluid (BALF) after treatment with anti-CD3 (F(ab′)2 fragment) during exposure to DHM and blocking exacerbations of asthmatic inflammation? Find the correct answer by reading the original article by Sethi and colleagues by clicking here.





Lung inflammation during asthma exacerbation is caused by the accumulation of different immune cells in lungs. During the secondary or even tertiary response to DHM, treatment with F(ab′)2 fragment of anti-CD3 reduces the number of CD4+T cells, correlating also with a reduced capacity for proliferation and cytokine release, together with a reduction in the number of eosinophils and neutrophils, thus improving the clinical symptoms of lung inflammation. This short-term treatment could be effective in treating patients with uncontrolled asthma. Interestingly, this treatment does not appear to be effective controlling long-term asthma exacerbations, probably due to the inability to completely block all memory CD4+ T cells in the lungs in response to DHM re-exposure.

11. Food emulsifiers, such as polysorbate 20 (P20, E432) and polysorbate 80 (P80, E433) can compromise the integrity of the intestinal barrier. In relation to this, which specific genes involved in cytokine-cytokine interaction are significantly upregulated in response to both P20 and P80 in monolayer cultured Caco-2-cells? You can find the correct answer by reading the original article by Ogulur and colleagues.





It has been shown that food emulsifiers such as polysorbate 20 (P20) and polysorbate 80 (P80) can damage the epithelial barrier, inducing epithelial inflammation at a concentration of 1%. Nevertheless, the study by Ogulur and colleagues showed that lower concentrations also have an impact on the epithelial barrier at a concentration of 0.05% after 24h of Caco-2 cells stimulation. Among their effects, a proinflammatory response has been associated with P20 and P80 stimulation, characterised by a differential expression of genes involved in signaling pathways related to cytokine-cytokine interactions. Specifically, IL4R gene expression is significantly increased in response to both P20 and P80 compared to unexposed Caco-2 cells, while IL1R1 gene expression is only increased with P20 and decreased with P80, while CCR1 is significantly increased only with P20, and IL2RG with P80.

12. Eosinophilic esophagitis (EoE) is a chronic inflammatory disease in response to food antigens. Janarthanam and colleagues studied the clonality of T-cell receptors (TCRs) from adults and children with active and non-active EoE and from healthy donors. Which of the following statements is correct? You can find the correct answer by reading the original article.





In children with active eosinophilic esophagitis (EoE), a reduced number of unique clonotypes was found compared to non-active EoE, although this difference was not observed in adults. In addition, a higher relative abundance of clonotypes compromising >1% was observed in children with active EoE. These measures correlated with the frequency of intraepithelial CD4+T cells. These results suggest increased T cell clonality in EoE in children, although this does not appear to be applicable to EoE in adults.

13. Locke and colleagues reviewed updates on the latest developments and highlights in food allergy. They nicely summarised the latest advances in the factors involved in the development of food allergy and natural tolerance, as well as new findings related to the epithelial barrier, the effect of emollient interventions and the immune mechanisms involved. Moreover, they evaluated novel immunotherapy strategies and the clinical management of food allergy. In relation to food allergen immunotherapy (AIT), what factors increase the risk of side effects during food AIT? Find the correct answer by reading the original article.





Factors affecting the safety and eligibility of allergen immunotherapy (AIT) need to be carefully evaluated on an individual basis. Many factors should be taken into account, such as controlled asthma and atopic comorbidity, patient age and socioeconomic status, as well as the AIT administration protocol. There are some factors that increase the risk of a side effect during AIT, such as high IgE levels, low threshold, gastrointestinal side effects, greater skin prick test reactivity or compatible history of anaphylaxis. On the other hand, low IgE levels, no history of asthma or anaphylaxis, or younger age at the start of AIT are factors favoring the safety of AIT.

14. Bastin and colleagues analysed the potential predictive serological biomarkers in response to epicutaneous immunotherapy (EPIT) with investigational Viaskin™ peanut 250ug (DBV712). After 12 months of treatment, which unique biomarker reported the best value for predicting the peanut protein eliciting dose (ED) with both ≥ 300 mg and ≥ 1000 mg? Find the correct answer by reading the original article.





The study conducted by Bastin and colleagues nicely demonstrated that epicutaneous immunotherapy (EPIT) with investigational Viaskin™ peanut 250ug (DBV712) modulates serum peanut sIgG4 and sIgE during 12 months of treatment. Results showed that, after 12 months of treatment, the peanut-specific IgG4/IgE ratio is the best biomarker for prediction with eliciting dose (ED) ≥300 mg, with an area under curve (AUC) of 69.5%, a negative predictive value (NPV) of 49% and a positive predictive value (PPV) of 80.6%; and with ED ≥1000 mg, an AUC of 69.9%, a NPV of 69.5% and a PPV of 81.8%, in both cases better than other potential biomarkers analysed such as peanut-sIgE, Ara h 1-sIgE, or Ara h 2-sIgE.

15. Related to food allergy/sensitization estimated prevalence in Europe in the past decade compared to the previous decade, which are the major changes in the past 10 years? Check the answer by reading the original article by Spolidoro and colleagues.





The prevalence of Food allergy (FA) confirmed by the gold standard diagnosis technique, the Food challenge (FC), has decrease in the last decade compared to 2000-2012 decade. For cow’s milk, the biggest change was observed for SPT sensitization, which increased more than 10 times between 2000–2012 (0.3%) and 2012–2021 (3.8%). For wheat, the biggest changes were lifetime prevalence of self-reported FA, which decreased from 3.6% vs. 1.4%, and an increase in the prevalence of sIgE positivity to wheat (3.9% vs 7.4%).

16. In difficult-to-treat asthma, specific “non- airway- centric profiles” have been identified. Which of the following features are characterized in specific “non- airway- centric profiles”? Look for the answer in the original article by Lin and colleagues.





Distinct trait profiles in difficult-to-treat asthma are associated with different clinical outcomes and treatment responsiveness to systematic assessment. Two “airway- centric profiles” were characterized by early-onset with allergic rhinitis and adult-onset with eosinophilia/chronic rhinosinusitis, respectively. Three “non- airway- centric profiles” exhibited either comorbid (obesity, vocal cord dysfunction, dysfunctional breathing) dominance, psychosocial (anxiety, depression, smoking, unemployment) dominance, or multi-domain impairment.

17. De novo synthesis of Synthetic glucocorticoid (GC) occurs in murine lung. In which part specifically? Check the answer by reading the original article by Merk and colleagues.





In the mouse model described by Merk and colleagues, de novo synthesis of bioactive glucocorticoid (GC) was shown to occur specifically in the large conducting airways, while GC reactivation occurred everywhere along the respiratory tree.

18. To improve care for Ukrainian refugees with allergies and skin diseases, UCRAID (Ukrainian Citizen and refugee electronic support in Respiratory diseases, Allergy, Immunology and Dermatology) has been launched, which aims to provide solutions to different communication problems between them and health professionals. Among the expected benefits of UCRAID, which of the following is not true? Check the answer by reading the review article by Bousquet and colleagues.





In the mouse model described by Merk and colleagues, de novo synthesis of bioactive glucocorticoid (GC) was shown to occur specifically in the large conducting airways, while GC reactivation occurred everywhere along the respiratory tree.

19. To improve care for Ukrainian refugees with allergies and skin diseases, UCRAID (Ukrainian Citizen and refugee electronic support in Respiratory diseases, Allergy, Immunology and Dermatology) has been launched, which aims to provide solutions to different communication problems between them and health professionals. Among the expected benefits of UCRAID, which of the following is not true? Check the answer by reading the review article by Bousquet and colleagues.





The UCRAID initiative provides a roadmap for improving care for Ukranian refugee patients with allergic and skin diseases. Among the expected benefits of the initiative, it will help to better understand the real barriers that Ukrainian refugees face with a person-centred care for chronic diseases. It also helps improve symptom management and treatment of refugees with asthma, rhinitis and urticaria using easy-to-use mHealth apps in their own language. It also reduces emergency visits and hospitalizations, saving costs, by engaging with healthcare professionals. Another potential benefit of UCRAID is that it can help refugees other than Ukrainians, and can be implemented to other pathologies such as COPD or cardiovascular diseases.

20. Drugs can interact with immune receptors in many different ways, and drug hypersensitivity reactions (DHRs) can be explained by the Hapten hypothesis and/or the p-i concept. An important feature of delayed-onset DHRs is characterized by the presence of eosinophilia, in approximately 50% of DHRs. In a recent review, eosinophilia in drug hypersensitivity (EOS-DH) has been linked to an “aberrant” TCR signalosome due to p-i stimulation resulting in high IL-5 production. Compared to drug hypersensitivity without eosinophilia, which of the following statements is not true regarding drug hypersensitivity and eosinophilia? Check the answer by reading the review article by Pichler and colleagues.





In some cases, drug hypersensitivity reactions (DHRs) have been associated with p-i stimulation, characterized by non-covalent binding of the drug with different immune receptors such as human leukocyte antigen (HLA) on antigen presenting cells (APCs) or T-cell receptors (TCRs) on CD4 and CD8 T-cells. A common feature of most delayed-onset DHRs is the involvement of eosinophils. Therefore, in this review, an IL-5-TCR signalosome via p-i interaction has been proposed as a potential mechanism explaining DHRs and eosinophilia, although it is not limited to DHRs. In contrast to p-i stimulation without eosinophilia (conventional stimulation), Lck is not associated to CD4/CD8 co-receptors, but TCR signaling has been linked to membrane-bound Lck, even in absence of CD4/CD8. Moreover, it has been hypothesized that IL-5 production is associated with delayed or reduced LAT (linker for activation of T cells) phosphorylation.

21. It is estimated that the healthcare sector contributes to approximately 4.4% to 10% of total greenhouse gas emissions, with a significant impact on the consumption of resources, such as consumables, water and electricity, which directly and indirectly impact on people’s health. To reduce their impact, different alternatives can be implemented from a One Health perspective. The use of inhalers to treat chronic respiratory diseases such as asthma or COPD has an important impact on carbon emission. Converting metered-dose inhalers (MDI) to dry-powder inhalers (PDI) could reduce the CO2 emitted into the atmosphere. How many kg of CO2e per year and patient would this strategy be estimated to save? Check the answer by reading the review article by Pali-Schöll and colleagues.





Health care professionals and researchers have a significant impact on the environment and climate change, in terms of greenhouse gas emissions, consumption of resources such as water, energy, as well as waste production. Several measures can be taken to reduce the environmental impact of health care professionals and researchers. One potential measure to reduce carbon impact is the conversion of metered-dose inhalers (MDI) to dry-powder inhalers (PDI) for treating asthma and COPD. This conversion is estimated to help save between 115 and 480kg CO2e per year and patient, depending on the intensity and type of therapy.

22. Although not yet applicable to the field of allergy, medical applications using artificial intelligence and machine learning appear to be relevant in the near future of clinical practice. Specifically, applications of artificial intelligence could be important for clinical research, such as diagnosis of allergic diseases, prediction of asthma exacerbations, hospitalizations, and disease management; fundamental research: heterogeneity and endotype discovery, pathways, and disease mechanisms; and drug and therapy development and precision medicine: treatment response and drug repurposing. Nevertheless, to create a reliable model, a structured modelling process is needed. Based on this, which of the following workflows is correct for developing a supervised machine learning model for disease risk? Check the answer by reading the review article by van Breugel and colleagues.





Although it is clear that the use of medical applications using machine learning and artificial intelligence is gaining relevance in recent years, it has not yet been applied to the allergy field. Moreover, the most relevant challenge of these technologies is to translate proofs-of-concepts into clinical practice, which require multidisciplinary collaborations between developers of algorithms, researchers, and clinicians, enabling the adaptation of algorithms to real healthcare. To achieve this, the design, creation, development, and validation of reliable models that can assist clinicians as decision support tools is essential. During the developing of a machine learning for predicting disease risk, it is essential to create an iterative feedback loop using different training, validation, tuning and test datasets. For this purpose, the proposed workflow is based on 1) feature engineering, 2) feature selection, 3) model selection and 4) hyperparameter tuning.

23. The COVID-19 pandemic caused by SARS-CoV-2 affects more than 700 million people and causes nearly 7 million deaths. Most people are asymptomatic or have mild symptoms, but some develop severe disease, although the pathophysiological mechanism driving this condition is not fully understood. It has been suggested that an impaired epithelial barrier function may increase the susceptibility to COVID-19 infection or even aggravate the inflammatory process. The original article by Yazici and colleagues sheds light on potential serum biomarkers, both related to inflammation and barrier damage, that may predict disease severity and progression. Among all the serum biomarkers analyzed, which pair is associated with both the degree of severity on hospital admission and disease progression?





Yazici and colleagues identified serum biomarkers related to immune and inflammatory response and disrupted epithelial barrier permeability, being good predictors for COVID-19 outcoming at the time of admission in hospitals and as predictors of COVID-19 moderate to severe disease progression to death. Among all, the chemokine CXCL10 and the TNF family member TRANCE are the two serum biomarkers associated with both COVID-19 grade of severity and disease progression. Combining these biomarkers with others can differentiate healthy donors vs. COVID-19 patients with 100% sensitivity, and mild from severe COVID-19 and disease progression with 88% sensitivity. These findings have important implications for clinical routine and could represent potential therapeutic targets.

24. Chronic rhinosinusitis (CRS) and asthma often co-exist, although there are no data to determine whether CRS is a risk factor for the development of asthma. The original article by Schwartz and colleagues analyzed the relationship between people with previous CRS and the risk developing new-onset asthma. In relation to this, which specific CRS variable was associated with an increased risk to develop new-onset asthma in the following year? Check the correct answer by reading the article





The longitudinal study conducted by Schwartz and colleagues demonstrated that prevalent chronic rhinosinusitis (CRS) is associated with the occurrence of asthma, based on both sinus computerized tomography (CT) scan reports and the use of two CRS diagnosis entries. Nevertheless, the strongest correlation between CRS and new asthma onset was obtained when CRS is based on a positive sinus CT scan, without adjustment for sinus surgery (2.2-fold increased risk of the diagnosis of new-onset asthma in the following year). However, the association between previous sinus surgery and asthma onset cannot be completely ruled out due to the small number of people with sinus surgery included in the study. These associations may have important clinical implications for asthma prevention.

25. Chronic rhinosinusitis with nasal polyps (CRSwNP) affects the quality of life of patients, and although dupilumab treatment has been shown to be effective in clinical trials, it has never been studied in real-life clinical practice. De Corso and colleagues therefore conducted a phase IV real-life, observational, retrospective, and multicenter study to determine the real benefit of Dupilumab treatment for CRSwNP. Related to this, and following the EPOS 2020 criteria at month 12, how many patients were excellent responders to the treatment? Check the correct answer by reading the article





The real-life study conducted by De Corso and colleagues has demonstrated the efficacy of 300mg of subcutaneous dupilumab by auto-injector every 2 weeks for the treatment of severe chronic rhinosinusitis with nasal polyps (CRSwNP). After 12 months, all parameters studied improved: nasal polyp endoscopic score (NPS) and Sino-nasal Outcome Test-22 (SNOT-22) fluctuations, Sniffin' Sticks test and smell visual analogue scale (VAS) scores fluctuations. Out of 648 patients and following EPOS2020 criteria, 69.6% of patients after 12-months of treatment were excellent, 27.3% moderate, 1.9% poor responders, and only 1.2% were non-responders. In conclusion, this real-life study has demonstrated the effectiveness of dupilumab 300mg for the treatment of severe CRSwNP.

26. A better understanding of the pathogenic pathways (endotypes) of allergic diseases allows a more detailed description of the diseases, being necessary the development of an updated nomenclature, from a pathomechanistic approach to a more established network of immunological and metabolic pathways, described by different biomarkers. Therefore, a new nomenclature is needed to better understand the aetiology, mechanism, prevention, diagnosis, and treatment of allergic diseases and hypersensitivity reactions. The recent EAACI position paper led by Marek Jutel, Ioana Agache, Cezmi Akdis and Beatrice Bilò provides a modern and updated nomenclature for allergic diseases. According to this new nomenclature, which specific cell subsets are mainly involved in type IVc (T3 immune response)? Check the correct answer by reading the article





The new nomenclature of allergic diseases proposed by Jutel and colleagues, represents an important step towards precision and personalised medicine, leading to improved diagnostic tools, therapeutical strategies, and management of allergic diseases. This new nomenclature is mainly based on disease mechanisms and endotypes rather than phenotypes. Among the cell-mediated-allergic diseases, 3 different subclasses can be described: 1. Type IVa reactions, with special involvement of Th1, ILC1, Tc1, and NK cells with participation of different cytokines and mediators such as IFN-y, TNF-a, granzyme B and perforin; 2. Type IVb reactions with involvement of Th2, ILC2, Tc2, and NK, and cytokines such as IL-4, IL-5, IL-9, IL-13, and IL-31; and 3. Type IVc reactions with special involvement of Th17, ILC3, and Tc17, and participation of IL-17, IL-22, and IL-23 cytokines.

27. Allergic asthma is one of the most common asthma phenotypes, from which asthmatic patients may benefit from allergen immunotherapy (AIT). Although AIT has been shown to provide long-term clinical benefits after the stop of the treatment, it remains unclear how to interpret the outcomes of AIT, especially in terms of asthma control. Different clinically applicable outcomes such as exacerbations, use of inhaled corticosteroids, symptom medication score, questionnaires, lung function evaluation, or biomarkers can be used to quantify this. Applicable to questionnaires (patient-reported outcome measures), which of the following is not correct? You can check the correct answer by reading the position paper by Kappen and colleagues.





Currently, there is no consensus on outcome measures for allergen immunotherapy (AIT) in allergic asthma. In the position paper by Kappen and colleagues, different outcome measures have been discussed, such as exacerbation rate, inhaled corticosteroids withdrawal, lung function, symptoms and use of rescue medication, questionnaires, nasal and bronchial challenge, allergen exposure chambers or biomarkers, all with advances and disadvantages. The main advantages of questionnaires (patient-reported outcome measures-PROMS) are that they allow assessment of the patient’s perspective on disease control, reflect exposure and improvement of symptoms that are not always directly related to asthma, and can be used in the research field, but also in clinical practice. The most important disadvantage of using questionnaires is that they have been considered secondary outcomes, as they are not included as primary endpoint parameters. Moreover, they might include biases and subjective parameters that cannot be controlled.

28. Intestinal helminths appear to elicit potential benefits to human hosts by reducing the risk of allergy and autoimmune diseases, as demonstrated in several epidemiological, preclinical, and clinical studies. Such a protective role seems to be related to the alteration of the intestinal mucus layer, its benefit in the human microbiome, increased epithelial permeability and microbial translocation. In relation to the intestinal barrier, IL-13 is a key cytokine that exerts an important influence on mucus response during helminth infections. Based on this, which of the following is correct? You can check the correct answer by reading the review article by Mules and colleagues.





Helminthic infection triggers the release of alarmins such as IL-25, IL-33, and TSLP during the early stages of infection. This increase triggers the production of IL-13 which plays an important role in mucus alterations. It causes goblet-cell hyperplasia, increasing the production of goblet-cell-derived proteins such as TFFs and RELM-β. It also increases the production of mucins such as MUC2 and MUC5ac and alters mucin glycosylation (sialylation and sulphation). All this modifies the properties of the mucus barrier. Moreover, IL-13 is a primary mediator of epithelial permeability, increasing it by reducing the expression of tight junction proteins in intestinal epithelial monolayers. Taken together, helminths seem to prevent and/or treat some pathologies such as allergies and autoimmune diseases. Nevertheless, further research is needed to determine whether helminth therapy could be used as a potential therapy to treat intestinal barrier function.

29. Dupilumab is a monoclonal antibody that blocks the IL-4/IL-13 receptor and has demonstrated effective in reducing severe asthma exacerbations, improving asthma control and lung function in patients with type 2 asthma. Nevertheless, its long-term impact in patients with moderate to severe asthma receiving high or medium doses of inhaled corticosteroids (ICs) remains unknown. In the TRAVERSE extension study, the improvement of different parameters such as exacerbation rate, asthma control questionnaires (ACQ-5 scores), ACQ-5 responder analysis, blood eosinophil counts, serum total IgE, or pre-bronchodilator FEV1 has been analysed. In relation to the latter, from what week after the start of the TRAVERSE study has an improvement in the pre-BD FEV1 been demonstrated in patients with both high- and medium-dose ICS? Check the correct answer by reading the original article by Pavord and colleagues.





The TRAVERSE study shed light on the long-term efficacy of dupilumab in patients with moderate/severe type 2 asthma receiving medium- or high-dose of inhaled corticosteroids (ICS). Treatment with dupilumab showed improvement in all parameters analyzed in both moderate and severe type 2 asthma in patients receiving high and medium doses of ICS. With respect to pre-bronchodilator FEV1 measurements, a rapid improvement was observed after dupilumab initiation in the TRAVERSE study at week 2 compared to baseline in the parent study. These results demonstrated the sustained long-term efficacy of dupilumab in patients with uncontrolled moderate or severe type 2 asthma despite the use of medium- or high-dose ICS.

30. Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intensely pruritic, recurrent eczematous lesions of relapsing course. AD is mainly driven by type-2 cytokines such as IL-4 and IL-13. Nevertheless, although both cytokines share many overlapping effector functions, some studies suggest that IL-13 rather than IL-4, is the dominant cytokine involved in AD. Therefore, Tralokinumab, a fully human IgG4 monoclonal antibody that specifically neutralizes IL-13, has been evaluated for the treatment of AD of different severities. Which of the following is not correct regarding the administration of Tralokinumab for the treatment of AD? Check the correct answer by reading the review by Simpson and colleagues.





Clinical trials with Tralokinumab for the treatment of moderate and severe atopic dermatitis (AD) have demonstrated significant improvement in AD symptoms and quality of life of patients while maintaining efficacy over time. From an immunological perspective, Tralokinumab, triggers a decrease in serum levels of IL-22, periostin, IgE, and CCL17, while increasing gene expression of skin barrier integrity markers such as CLDN8, FLG, ELOVL3, CLDN23, and LOR. In addition, an increase in microbial density is observed after Tralokinumab treatment, while Staphylococcus aureus abundance is reduced 10-fold compared to placebo. Overall, the monoclonal antibody Tralokinumab has been shown across different clinical trials to be an effective therapeutic option for patients with moderate and severe AD, although future studies are needed to identify and compare the most suitable therapeutic option for each AD patient.

31. Severe asthma is a heterogeneous disease characterized by different clinical and molecular phenotypes. Among them, the neutrophilic inflammatory phenotype is characterized by type-1 inflammatory pathways with sputum neutrophilia, while the eosinophilic phenotype is mainly characterized by type-2 inflammation. Due to the influence of the microbiome and its contribution to inflammation, it is important to characterize the airway composition and abundance of microbial species in asthmatic patients with different severities and phenotypes. In relation to this, which bacterial species is increased in eosinophilic asthma, mainly related to severe asthmatic patients who are smokers and ex-smokers? Check the correct answer by reading the original article by Versi and colleagues.





The study carried out by Versi and colleagues sheds light on the influence of different microbial species and the different severity, inflammatory and molecular phenotypes of asthma, by metagenomic analysis of sputum samples. This study has demonstrated that neutrophilic inflammation is associated with increased abundance of Haemophilus influenzae and Moraxella catarrhalis, while asthmatic patients with eosinophilic inflammation are associated with high abundance of Tropheryma whipplei. This species has also been associated with severe asthma in smokers and ex-smokers asthmatic patients. Nevertheless, further studies are needed to confirm the role of these species in asthmatic patients.

32. Food allergy is a major health problem, and its prevalence is increasing in recent decades. Therefore, a correct allergy diagnosis has a very important impact on patients' lives. The EAACI guideline on the diagnosis of IgE-mediated food allergy aims to provide guidance to healthcare professionals, focusing mainly on the clinical management of IgE-mediated food allergy. According to the meta-analysis performed in the guideline, what is the mean sensitivity and specificity of the determination of sIgE to the Ara h2 component? Check the correct answer by reading the EAACI guideline by Alexandra Santos and colleagues





In addition to skin prick testing and/or determination of sIgE to food extracts, the quantification of sIgE to food components is recommended, due its higher specificity compared to food allergen extracts, thus being useful to confirm a suggestive history of food allergy. Nevertheless, the sensitivity and specificity of the different extracts and components is variable. In the case of peanut sensitization, the usefulness of the measurement of sIgE to Ara h 2 reports higher % sensitivity and specificity (82% and 92% respectively) compared to the quantification of sIgE to peanut extract (81% and 83% respectively).

33. Eosinophils perform a wide range of biological activities, from the maintenance of health and homeostasis to the triggering of different diseases, thus being an important target cell population for the development of new therapies. In relation to eosinophils is asthmatic patients, which of the following statements is correct about the use of the monoclonal antibody Anti-IL-5R (benraluzumab)? Check the correct answer by reading the comprehensive review by Jesenak and colleagues.





Eosinophils are versatile cells with important functions during immune defense against different parasites such as helminths, viruses, bacteria or fungi, but they also have important roles in the maintenance of homeostasis and regulation of the immune response. Nevertheless, they are also involved in different pathologies such as asthma, allergic rhinitis and drug allergic reactions. In asthmatic patients, the use of anti-IL-5R monoclonal antibody (benralizumab) treatment reported a significant reduction in the number of mature eosinophils and eosinophil progenitors. A reduction of eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) was also observed, while an increase in the level of IL-5, eotaxin/CCL11 and eotaxin-2/CCL24 was detected.

34. Although IgE is the rarest isotype, its role as a key mediator in allergy and related diseases is clear. Although significant progress has been made in recent decades, several questions remain to be addressed about the mechanisms involved in cellular IgE response. In relation to IgE production, which combination of cytokines enhances IgE production? Check the correct answer by reading the review by Zhoujie Ding and colleagues





IL-4 is an essential cytokine for increasing IgE production, although its combination with other cytokines and mediators can both reduce and increase IgE production. The combination of IL-4 with neuritin produced by follicular T regulatory helper cells inhibits IgE production. On the other hand, IL-13 seems to have a minimal effect on IgE production, although it plays a relevant role in the affinity maturation of IgE. IL-21 has a pleiotropic role in IgE production, as it increases IgE production with high CD40 stimulation, but also limits IgE production when CD40 stimulation is low.

35. Autoimmunity is defined as the break of tolerance to self-antigens that causes organ-specific or systemic diseases. Some of them are characterized by the presence of autoreactive antibodies (AAb). Among all isotypes, IgG AAb are mostly pathogenic, but in recent years, the presence of IgE-AAb has also been linked to different autoimmune diseases, thus representing a potential therapeutic target for some autoimmune diseases. In relation to systemic lupus erythematosus, what is the estimated prevalence of autoreactive IgE against antinuclear antibodies? Check the correct answer by reading the review by Nicolas Charles and colleagues.





In recent decades, the presence of autoreactive IgE in systemic lupus erythematosus against antinuclear antigens, acting mainly on plasmacytoid dendritic cells and basophils, has been described. The estimated prevalence of autoreactive IgE against antinuclear antibodies in systemic lupus erythematosus varies between 48% and 65%. Due to the high prevalence of IgE AAb observed in the disease, IgE modulation or depletion may be considered an effective therapeutic strategy for these patients, although further research is needed.

36. Understanding the recognition of IgE and IgG antibodies to different epitopes of pollen allergens such as Bet v 1 in sensitised and non-sensitised subjects is essential to better understand the immunological process during an allergic reaction, but also because it sheds light on the effect of allergen-specific immunotherapy. Related to this, which Bet v 1 epitope is preferentially recognised by specific IgG1 and IgG4 from birch pollen allergic patients? Check the correct answer by reading the original article by Brazhnikov and colleagues.





The original article by Brazhnikov and colleagues shed light on the differential capacity of Bet v 1-sIgE and -sIgG to recognise different Bet v 1 epitopes. sIgE from birch pollen allergic patients recognises exclusively the complete folded Bet v1, whereas sIgG in addition to recognising the complete form, also recognises both Bet v 1 unfolded fragments. Indeed, in both allergic patients and non-allergic subjects, IgG1 and IgG4 antibodies preferentially recognise the non-conformational epitopes of Bet v 1, being the IgG levels specific for F1+F2 significantly higher than IgG levels for folded Bet v 1. These different recognition patterns may explain why allergen-specific IgG does not fully protect against allergic symptoms.

37. Two different subsets of circulating eosinophils can be distinguished based on the expression of surface markers such as CD62L, with inflammatory eosinophils (iEOs) expressing CD62Llow. The two subsets of Eos play different roles during tissue homeostasis and during inflammation such as in type 2 (eosinophilic) asthma. In relation to circulating eosinophils and type 2 asthma, which of the following clinical scores for asthma and nasal polyps does not correlate with % CD62Llow eosinophils in blood? Check the correct answer by reading the original article by Alessandra Vultaggio and colleagues





The results of the study by Alessandra Vultaggio and colleagues have demonstrated the correlation between CD62Llow inflammatory eosinophils (iEos) and clinical severity of asthma, using both the Asthma Control Test (ACT) and the Asthma Control Questionnaire-5 (ACQ5). Because the presence of nasal polyps is a frequent comorbidity in asthma, CD62Llow iEos percentage also correlates with Sinunasal Outcome Test-22 items (SNOT-22), while no correlation is found with Nasal Polyp Score (NPS). These results may indicate that the measure of circulating iEos, characterised by the expression of CD62Llow, could be an accurate biomarker for the risk of asthma exacerbations and non-control of type 2 asthma.

38. Atopic dermatitis (AD) is a chronic recurrent inflammatory skin disease that usually begins in childhood with a lower prevalence in adults (around 2-8%). Autoimmune responses against self-peptides have been described in AD and other skin-related diseases such as chronic spontaneous urticaria, bullous pemphigoid, and lupus erythematous. Of patients with AD and atopic comorbidities (type-2 diseases) and age group between 18 and 40 years, what is the % of highly positive cases of IgE autoantibodies against human keratinocytes? Check the correct answer by reading the original article by Inge Kortekaas Krohn and colleagues





The prevalence of IgE-mediated autoimmunity is mainly observed in the group of patients with atopic dermatitis (AD) and atopic comorbidities (type-2 diseases) in 16.4% of cases; in 9.6% of patients with only AD or atopic patients without AD; and in 2.7% of healthy controls. In addition, highly positive cases are only found in patients with AD + Type 2 (3.5%) and in patients with solely AD (0.9%). The prevalence of IgE-mediated autoimmunity changes during ageing, with the highest % of highly positive cases between 18-40 years (4.1%) in AD + Type 2 patients, and in solely AD patients (2.3%).

39. The cutaneous lymphocyte-associated antigen (CLA) is a cell surface molecule highly expressed on human memory T cells infiltrating the skin, although it is also expressed on other cell types such as T regulatory cells, or type 2 innate lymphoid cells (ILC)2 and ILC3. The involvement of CLA+ memory T cells in atopic dermatitis (AD) seems to be relevant, mainly because the expression of CLA allows cell migration to peripheral tissues and is also involved in T cell activation. In relation to CLA+ memory T cells, which of the following molecules has an increased expression in CD4+ and CD8+T cells from patients with AD? Check the correct answer by reading the review by Lídia Sans-de San Nicolàs and colleagues





The role of CLA+T cells in atopic dermatitis (AD) patients is clear, mainly due to their involvement in cell migration to peripheral tissues, together with the expression of other adhesion markers such as LFA-1, ICAM-1, VLA-4, CCR10, or CCR4. Moreover, in AD patients, CD4+ and CD8+CLA+T cells express higher levels of CD25, CD40L, HLA-DR, and ICOS, all of which are involved in the activation state of these cells. In addition, CLA+T cells express higher levels of cytokines such as IL-4, IL-5, IL-13, IL-9, IL-21, or IL-22. AD patients also also characterised by a higher frequency of CLA+Th2/Tc2 and CLA+Th22/Tc22 expansion, but not CLA+Th1/Tc1.

40. Sleep deprivation is associated with a cognitive impairment, characterised by reduced sustained attention, working memory, executive function and processing speed, with an increased risk of depression, infections and inflammatory disorders. Atopic dermatitis (AD) is characterised by chronic pruritic and erythematous dry skin, accompanied by scratching, which exacerbates itching and skin barrier breakdown, mainly at night, leading to sleep disturbance. Due to sleep deprivation, which specific transcription factor family proteins are activated? Check the correct answer by reading the review by Cameron and colleagues





AD has been associated with psychological disorders such as attention deficit, anxiety, depression, and hyperactive disorders, mainly during childhood and adolescence. These disorders can be linked with sleep perturbance, mainly associated with the itch-scratch cycle, leading to significant sleep disturbances. Poorer sleep quality has also been linked with an increased risk of infectious and inflammatory disorders. On this basis, sleep loss is associated with activation of inflammation, signal transducers and activation of transcription factors, such as those belonging to STAT and Nf-kB family proteins.

41. Mast cells are a versatile group of cells that exert homeostatic functions, but are also responsible for triggering different mast cell-dependent and mast cell -associated diseases, due to excessive activation and/or proliferation. These disorders do not have a curative therapy, although in recent decades different therapeutical strategies have emerged, aimed not only at conventional treatment for symptom control, but also at controlling mast cell activation, proliferation, signalling, degranulation or survival. In relation to therapeutical strategies, which of the following does not belong to the mast cell silencing strategy? Check the correct answer by reading the review by Martin Metz and colleagues





Mast cell silencing is an emerging mast cell therapeutic strategy with potential clinical relevance, as it may offer several advantages over other targeted strategies such as mast cell depletion, the use of mast cell activation antagonists, or through inhibition of mast cell mediators, mainly related to its higher selectivity and lower toxic effect. Several silencing strategies are currently being studied, mainly through interaction with Singlecs, by using anti-Singlec-8 monoclonal antibody, anti-Singlec-6 monoclonal antibody, or through the administration of CD200R agonist.

42. Tissue-resident memory T cells (TRM ) play a key role in protecting local tissues from recurrent infections or the development of neoplasic cells. Nevertheless, they also have undesirable effects in autoimmune, inflammatory and allergic diseases, such as allergic contact dermatitis. The use of corticosteroids is the reference treatment, although little is known about their specific effects in skin TRM population. Which of the following gene expression is downregulated in CD8+TRM following triamcinolone acetonide application? Check the correct answer reading the original article by Emi Ono and colleagues





The application of topical corticosteroids, and in particular triamcinolone acetonide, is effective in preventing skin symptoms by inhibiting the recruitment of skin TRM precursors and the reactivation of TRM. Nevertheless, they cannot prevent disease once the effector T cell has infiltrated the skin, nor prevent the expansion of TRM when the treatment is discontinued. When triamcinolone acetonide is administrated, CD8+TRM downregulates the expression of genes such as Ifng and Gzmb, related to TRM proliferation, while upregulating the expression of other genes related to the restriction of TRM proliferation such as Tsc22d3, Ptpn22, or Dusp2.

43. Environmental exposure is associated with susceptibility to allergic diseases and immune protection, mainly in early life, through functional reprogramming of the innate and adaptive immune systems. In relation to this, which of the following G protein-coupled receptors (GPCRs) is increased in children from rural compared to urban environments? Check the correct answer by reading the original article by Lunjani and colleagues





Specific environmental exposure drives important changes in immune cell gene expression, which influence in the subsequent incidence of inflammatory, autoimmune and allergic diseases, mainly related to urban vs. rural lifestyles. In this article, Lunjani and colleagues analysed the gene expression signature in rural, semi-rural, and urban groups of children with and without atopic dermatitis. They found a significant upregulation of genes in children exposed to rural environments related to modulation of activation, proliferation and antigen presentation pathways through different regulatory cytokines, inhibitory receptors and G protein-coupled receptors (GPCRs) such as the GPR17, associated with negative regulation of inflammatory cell recruitment and Th2/Th17 cytokine expression.

44. Most of the knowledge acquired regarding the pathomechanisms involved in atopic dermatitis (AD) is based on in skin biopsy studies. Nevertheless, skin biopses are associated with pain, scarring, and infection risk. In contrast, tape strips are minimally invasive, although few studies are available comparing both sample-obtaining techniques with full transcriptomic analysis. Related to this, which specific gene is differentially expressed in AD patients vs. controls detectable in biopsies, but not in tape-strips? Check the correct answer by reading the original article by Ester Del Duca and colleagues





Tape strips showed higher capacity to detect specific biomarkers in atopic dermatitis patients vs. controls in genes related to Th2 (IL-13) and Th17 responses, innate immunity (IL-8), Th1-related chemokines or negative regulatory markers such as IL-34. In contrast, hyperplasia-related cytokines and chemokines, including IL-22, are detected in biopsy samples rather than in tape-strips. These differences between the techniques could be explained by the nature of the sampling method, where biopsies capture all the skin layers, including epidermis, dermis, hypodermis and fat, whereas tape-strips only capture the upper epidermis and the granular layer.

45. Many patients with chronic spontaneous urticaria (CSU) use 2nd generation of non-sedating H1-antihistamine as first-line treatment on demand, rather than daily use. Nevertheless, little is known about how treatment schedule and updosing can influence outcomes. In relation to this, which of the following is not true about rupatadine treatment in patients with CSU? Check the correct answer by reading the original article by Karsten Weller and colleagues





The study by Weller and colleagues showed that, at the end of the follow-up period, daily rather than on-demand dosing of rupatadine does not provide a longer-term advantage after treatment, although appears to provide benefits while the patient is undergoing treatment. Additionally, two weeks of daily rupatadine treatment improves disease activity compared to on demand use. Moreover, rupatadine updosing increases the percentage of complete responders to 22%, although it doesn’t lead to a significant reduction in chronic spontaneous urticaria activity at the end of treatment.

46. Virus-like particles (VLPs) are novel useful platforms with potential use for the development of immunotherapeutic vaccines, such as for peanut allergy, by cross-linking the B cell receptor (BCR), inducing strong B cell activation, and simultaneously promoting T-follicular priming by antigen presenting cells, inducing an overall strong humoral response. In relation to the VLP-based vaccine against peanut allergy, which specific Toll-like receptors (TLRs) are stimulated following peanut VLP-based vaccination? Check the correct answer by reading the original article by Pascal S Krenger and colleagues.





Virus-like particles (VLPs)-based vaccine against peanut allergy can stimulate both TLR 3 and TLR 7, which may explain why, despite the lack of TLR 7 signalling, the vaccine remains immunogenic. Therefore, the RNA incorporation (prokaryotic versus eukaryotic), as well as nucleoside modifications are important factors for vaccine effectiveness. Moreover, the density of Ara h 2 antigens of VLP-vaccines seems to be relevant to the protective capacity of the vaccine, with relevance for the optimisation of existing VLP-based vaccines, or the development of new ones.

47. The Basophil activation test (BAT) is an in vitro test, with potential implications in clinical routine, although the lack of standardization hinders its inclusion, due to differences in protocols, cytometer settings, and interpretation of the results among other factors. On this basis, EAACI has set up a task force for BAT-External Quality Assurance (EQA) in which 7 round robins have been performed in up to 10 specialized laboratories. From the results obtained in this study, what is the standard deviation of the pre-activated samples compared to locally activated and analyzed samples? Check the correct answer by reading the EAACI Task Force Report by Pascal and colleagues.





Standardization of Basophil Activation Test (BAT) is an essential step that could allow its inclusion in clinical routine, of importance in obtaining reliable and comparable results in multicenter research studies. To move forward on this, EAACI has launched a task force to create the basis for a BAT-External Quality Assurance (EQA) with the performance of 7 round robins in up to 10 specialized laboratories. The results obtained in the Task Force indicated that the use of preactivated blood significantly reduces the variability of results (16.8%) compared to local activation and analysis of fresh samples (49.2%), with better results being obtained in the latter with EDTA-stabilized blood instead of heparin.

48. There is strong evidence of the harmful effects of air pollution on human health, affecting, among other things, the integrity of epithelial barriers, DNA damage, cell death response, or activation of inflammatory pathways. Nevertheless, indoor air quality has not received as much attention, despite the fact that humans spend more than 90% of their time indoors. Because of this unmet need, the SynAir-G project aims to reveal the interactions between pollutants that affect human health. In relation to the SynAir-G project, which of the following sentences is not correct? Check the correct answer by reading the review article by Nikolaos G. Papadopoulos and colleagues.





Although the harmful effect of air pollution on human health is well described, there is little information regarding the effect of indoor pollutants on humans, even though we spend most of our time indoors. This is even more relevant for children in concrete places such as schools. To shed light on this, the SynAir-G project has been launched, which through the use of different technologies will make it possible to monitor the effect of indoor pollution in children’s health. For this purpose, different data sources, such as questionnaires, sensors and potable dvices will be used to obtain quantitative data on indoor school environments. In addition, different interventions such as the effect of air filtering or green walls will also be evaluated, and other important factors, such as socioeconomic aspects will also be considered.

49. Estimating the prevalence of food allergy and sensitization to tree nut is an important step in determining the real burden of disease in the general population. Therefore, having up-to-date prevalence data is relevant, especially in those diseases, such as nut allergy, for which low data are available. The first systematic review with data about prevalence of food allergy and sensitization to tree nut in Europe was conducted in 2015, and an update has now been performed, including data on individual tree nuts. According to the updated systematic review, which self-reported allergy to tree nut has the highest prevalence in Europe? Check the correct answer by reading the review by Spolidoro and colleagues.





The systematic review by Spolidoro and colleagues updated the data on the prevalence of tree nut allergy and sensitization in Europe, including data from individual trees. Although the risk of bias in the studies analyzed is moderate and the data are sparse, making interpretation of results difficult, the highest prevalence of self-reported allergy to tree nuts was obtained with hazelnut (4.04%), followed by brazil nut (3.44%), almond (2.02%) and walnut (1.79%).

50. The incidence of food allergy has been increasing in recent decades, with major implications for patients' lives, affecting not only their health, but also the high costs associated with the disease for themselves and the consequent burden for healthcare systems. EAACI has recently updated the guidelines for the diagnosis and management of food allergy. On this basis, a systematic review has been published in order to synthesize the different diagnostic procedures with the aim of guiding clinicians to make the best diagnostic decision for each case. Based on the data from the systematic review, which of the following skin prick test has the best sensitivity and specificity values? Check the correct answer by reading the review article by Riggioni and colleagues.





Data from the updated systematic review support the use of skin prick test and sIgE determination for the diagnosis of food allergies, especially for peanut, hen’s egg, cow’s milk, hazelnut and cashew nut. Specifically, the highest values of sensitivity and specificity of skin prick test were obtained for the diagnosis of peanut (84% and 86% respectively), compared to egg white (78% and 83.8%), shrimps (62% and 90%) and cow’s milk (52% and 80%). Nevertheless, more research is needed to further validate these observations, mainly in those food allergies with less diagnostic data and studies available.

51. The role and deprivation of micronutrients have important implications in human health, as they have been linked to inflammation, increasing morbidity and mortality in a wide range of diseases. Determining the specific role of micronutrients in healthy, nutrient-deprived, or inflamed conditions, as well as the energy needs of specific cell populations, is important to better understand immunological processes and to develop strategies aimed at increasing the bioavailability of these nutrients. In relation to the metabolic demands of immune cells under inflammation, which of the following T cell subpopulations has the greatest demand for energy through the glycolysis pathway? Check the correct answer by reading the comprehensive review article by Roth-Walter and colleagues.





Energy demands vary depending on the specific cell population and inflammation process involved. Different pathways can be used to obtain energy depending on cell-type and environmental conditions, mainly through glycolysis, fatty acid oxidation, glutaminolysis, and oxidative phosphorylation. T cells, naïve T cells, T regulatory cells and memory T cells are mainly dependent on oxidative phosphorylation and aerobic fatty acid oxidation, whereas activated T cells (Th1, Th2, Th17) are, in addition, more dependent on glycolysis. Therefore, the type of food ingested may affect the T-cell response, with a ketogenic diet being better suited to promote non-inflammatory cells, whereas a diet rich in simple sugars promotes mainly the development of inflammatory cells.

52. The use of biologics revolutionized the management of asthma, due to their higher capacity to prevent loss of lung function and minimize the toxicity of some treatments such as those associated with oral corticosteroids. Although biologics have a greater ability to control asthma symptoms and reduce the frequency of acute exacerbations, less attention has been paid to achieving asthma remission. In relation to this, what percentage of clinical remission plus lung function improvement has been achieved for treatment of patients with severe asthma with mepolizumab after 12 months? Check the correct answer by reading the original article by Dennis Thomas and colleagues.





The use of biologics to achieve treatment-induced remission in severe asthma patients after 12 months of treatment is effective in 29.3% and 22.8% with mepolizumab and omalizumab respectively. Nevertheless, the percentage of severe asthma patients meeting both clinical remission and lung function criteria was 25.2% after treatment with mepolizumab, and 19.1% with omalizumab. Nevertheless, further studies are warranted to define asthma remission using specific biomarkers and considering longer-term follow-up.

53. The quality of maternal diet during and even before pregnancy has been linked with childhood wheezing and asthma. On this basis, prenatal exposure to suboptimal nutrients may affect the maturation of lungs, airways and immune system, with important implications for the development of asthma during childhood. Related to this, what reduction in the odds of belonging the early-childhood onset wheeze was observed in the highest quartile of maternal balanced diet score? Check the correct answer by reading the original article by Hitomi Okubo and colleagues.





Four different wheeze trajectories were defined in the present study, with the lower risk of early and transient and persistent wheeze trajectories being associated with the higher maternal balanced diet score compared with the never or infrequent wheeze trajectory. Therefore, a well-balanced maternal diet may mitigate wheezing symptoms and the development of asthma. In this study, a reduction in the odds of belonging to the early-childhood onset wheeze of 0.93 was observed in the highest quartile of maternal balanced diet score, whereas it was 0.94 in quartile 2, 0.97 in quartile 2, and 0.90 in quartile 4 for transient early wheeze. Nevertheless, further studies are needed to determine risk factors for each trajectory and to follow-up this cohort to define asthma risk.

54. Treatment strategies to prevent accidental exposures to peanut, which can trigger a fatal anaphylactic episode in allergic patients, are mainly based on oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT), although they are not risk exempt for patients. It is therefore necessary to develop new treatments with improved safety and efficacy. Regarding the ASP0892 vaccine for the treatment of peanut allergy, what peanut-specific IgE/IgG ratio was observed at baseline vs. day 211 after intradermal administration of 4mg of the vaccine? Check the correct answer by reading the original article by Brian C. Ferslew and colleagues.





Data derived from the phase 1 study demonstrated that administration of ASP0892 vaccine for the treatment of peanut allergy is safe in both adults and adolescents. Immunologically, treatment with the vaccine modestly increased sIgG levels compared to baseline and placebo group. Specifically, on day 211, IgE/IgG ratio decreased compared to baseline in the ASP0892 1mg intradermal (3.24 vs. 1.81); ASP0892 4mg intradermal (5.02 vs. 1.44); and ASP0892 4mg intramuscular (5.61 vs. 3.91) groups, but not in the placebo group (1.82 vs. 1.40). Although an increase in peanut-sIgG4 was also observed in the vaccinated groups, no clinical significance was observed. Although the safety of the ASP0892 vaccine has been determined, moderate immune modulation was reported, with some improvements therefore necessary, such as those related to vaccine stability and administration, cellular uptake, alternative delivery devices and/or treatment duration and dosing.

55. Food-grade titanium dioxide (fg-TiO2) is a common food additive that can cross the placental barrier. Accumulation of fg-TiO2 can affect gut homeostasis in early life, altering susceptibility to oral tolerance or food allergy. In the mouse model performed by Mohammad Issa and colleagues, long-term exposure from perinatal life to diet enriched with fg-TiO2 has different consequences related to alteration of the epithelial barrier, changes in the immune system, altered metabolism and gut dysbiosis. Regarding changes in immune cells, which of the following cell populations is downregulated after perinatal exposure to fg-TiO2? Check the correct answer by reading the original article by Mohammad Issa and colleagues





The effect of fg-TiO2 on the local and systemic immune system of male mice after perinatal exposure results in an increase in the percentage of monocytes, conventional dendritic cells and T cells, both CD4+ and CD8+ cells. Nevertheless, a reduction in the % of natural killer cells has also been observed. For the first time, an altered frequency of immune cells in both local tissues and peripheral blood has been observed in young male mice perinatally exposed to fg-TiO2, in addition to other alterations such as changes in the integrity of epithelial barrier or establishment of the microbiota, having an important effect in the development of food allergy or oral tolerance in early life.

56. The use of telemedicine (TM) has increased in recent decades, with the increased use of technology during the 21st century. The use of TM was promoted mainly during the COVID-19 pandemic. In this regard, some studies have demonstrated the usefulness of TM in clinical practice, although it seems that it cannot completely replace face-to-face visits. In the EAACI position paper by Sylwia Smolinska and colleagues, the terminology of TM, its advantages, disadvantages and unmet needs were discussed. Based on this, which of the following definitions is not correct? Check the correct answer answer by reading the EAACI position paper by Smolinska and colleagues





Telemedicine is a part of telehealth, defined as the use of remote clinical services including the diagnosis and treatment of patients through telecommunication technology. Telemedicine can be divided into different services, such as teleconsultation, telediagnosis, tele-education, telescreening, teletriage, telesurgery, or teleassistance. Teleconsultation is defined as: “a synchronous or asynchronous delivery model of telemedicine between two or more geographically separated healthcare providers”, while teletriage is defined as the tecnology used to supplement or replace elements of the patient interaction. It involves screening patients remotely to determine the patient's condition and required care

57. Recent publications have outlined the importance of supporting the transition to self-management of adolescents with allergic conditions. However, no synthesis of the evidence based on the use and impact of telehealth interventions for this purpose has been conducted to date. A systematic review by Meg O’Sullivan and colleagues was conducted to evaluate the impact of telehealth interventions and explore their language use and implementation. Eighteen articles were included, reporting on 15 interventions. Based on their observations, which type of interventional content was included in all studies? Check the correct answer by reading the original article by O’Sullivan and colleagues:





All interventions (n = 15) featured behavioural content, mainly technique skill in administering medications such as inhalers or adrenaline auto-injectors and adherence promotion. Although all interventions included behavioural content, surprisingly not all included educational content. Of the five interventions that did not, three were evaluated in a mixed-methods or qualitative study, and participants in all of these commented explicitly on its' absence. Therefore, this review consolidates the necessity of educational content in self-management support. Psychosocial content (discussing emotions, stress and promoting communication with family and peers about one's condition) and healthcare navigational issues (promoting asking HCPs questions, knowing when to seek medical help) were also addressed in few interventions.

58. Pyrrole–imidazole polyamides (PIPs) have been studied for their potential to target specific genes and pathways for therapeutic purposes. Based on recent research, what was one of the observed therapeutic effects of PIPs targeting the human TGF-β1 promoter? Check the correct answer by reading the original article by Bai and colleagues:





Studies have shown that PIPs targeting the human TGF-β1 (hTGF-β1) promoter can significantly suppress both the activity of the TGF-β1 promoter and the expression of TGF-β1 mRNA and protein in human cells. A series of studies also proved that using PIPs that specifically target the transcription of TGF-β1 could exhibit promising therapeutic potential in attenuating progressive renal diseases, reducing carotid artery stenosis following angioplasty, treating alkali-induced corneal burns, minimizing skin hypertrophic scars, alleviating liver fibrosis, and mitigating encapsulating peritoneal sclerosis in rat models.

59. Allergic rhinitis is one of the most frequent chronic diseases among children and adolescents. Despite its high prevalence, not many studies have been conducted with the aim of analyzing the natural course of allergic rhinitis during the transition from childhood to young adulthood. To shed light on these aspects, Magnus Lindqvist and colleagues carried out a prospective study, following the same children for more than 20 years. In terms of their results, in what % and age group did the authors observe the highest rate of disease remission? Check the correct answer by reading the original article by Lindqvist and colleagues





The prospective study by Lindqvist and colleagues followed the natural course of pollen-induced allergic rhinitis in more than 1,000 children and young adults over 20 years. Overall, they observed a low rate of disease remission, with 75% of children with allergic rhinitis still suffering from it at 24 years of age. Nevertheless, between the ages of 16 and 24 years is the period with the highest remission of the disease (21.5%), compared to a rate of 0% between the ages 4 and 8 years, and 11.4% between the ages of 8 and 16 years. These results indicate that the transition from children to young adults is the most dynamic period of the disease.

60. Pollen allergy patterns are relatively homogeneous within Central and Northern European countries. However, no study broadly assessed the features of seasonal allergic rhinitis (SAR) across different Southern European countries with a standardized approach. This original article by Stephanie Dramburg and colleagues aimed to describe sensitization profiles and clinical phenotypes of pollen allergic patients in nine Southern European cities with a uniform methodological approach. The spectrum of diversity in IgE profiles among the study population ranged from a clear predominance of single allergen sources to a high degree of poly-sensitization in other study centers. Overall, which was the most important seasonal airborne allergen source? Check the correct answer by reading the original article by Dramburg and colleagues





Overall, the most important seasonal airborne allergen source was grass pollen, an observation matching the results of previous studies in different regions of Southern Europe. Another frequent elicitor of SAR symptoms in the Mediterranean basin is olive pollen. In this study, olive pollen ranged among the top three sensitizers being the second most important allergen source after grasses at population level. The increasing importance of cypress allergy in the Mediterranean region is also highlighted, with the observation of three general patterns: (i) mono-sensitization to cypress (Marseille, Istanbul); (ii) cypress as part of (broad) poly-sensitization (Rome, Tirana, Athens, Valencia, Ismir); and (iii) almost no relevant cypress pollen sensitization (Porto, Messina). Sensitization to pellitory was mostly observed in poly-sensitized patients, with the exception of Messina. A natural consequence of the heterogeneous profiles and trends toward poly-sensitization in Mediterranean countries is the need for cost- and time-efficient multiplex IgE testing for pollen allergic patients.

61. The evaluation of clinical outcomes in food allergen immunotherapy (AIT) trials is crucial for understanding the effectiveness of treatments for milk, egg, and peanut allergies. The article by Pablo Rodriguez del Rio and colleagues is important because it highlights key efficacy measures such as desensitization, sustained unresponsiveness, and changes in allergen thresholds assessed by Oral Food Challenges (OFC). The review identifies significant heterogeneity in these outcomes, emphasizing the need for standardized protocols to improve the evaluation and comparison of AIT efficacy. Which of the following outcomes were commonly evaluated in these food allergen immunotherapy trials? Check the correct answer by reading the original article by Rodríguez del Río and colleagues:





A total of 63 manuscripts met inclusion criteria, corresponding to 23, 21 and 22 studies of milk, egg and peanut AIT, respectively. The most common AIT efficacy outcome was desensitization, mostly defined as tolerating a maintenance phase dose, or reaching a particular dose upon successful exit oral food challenge (OFC). However, a large degree of heterogeneity was identified regarding the dose quantity defining this outcome. Sustained unresponsiveness and patient-reported outcomes (e.g. quality of life) were explored less frequently, and to date have been most rigorously described for peanut AIT versus other allergens. Change in allergen threshold assessed by OFC remains the most common efficacy measure.

62. Dupilumab (anti-IL-4Rα-mab) is used for the treatment of atopic dermatitis (AD). A common side effect of this therapy in AD is dupilumab-associated ocular surface diseases (DAOSD) like conjunctivitis or keratitis. Thormann et al. examined tear fluids of patient treated with dupilumab to understand the cause of DAOSD. The authors hypothesize two possible factors that influence the development of DAOSD. One is the shift of cytokine pattern from Th2/Th17 toward Th1/Th17 under dupilumab therapy. What is the second possible explanation for DAOSD that was mentioned in the article? Check the correct answer by reading the original article by Thormann and colleagues.





Dupilumab inhibits the function of IL-13 by blocking the IL-4Rα receptor. Thus, inhibiting IL-13 may result in a depletion of goblet cells followed by decreased mucin secretion, disturbed antigen passage from the ocular surface to dendritic cells in the stroma. Mice that lack conjunctival goblet cells were shown to develop epithelial barrier disruption and an inflammation characterized by increased numbers of CD11c+ and CD11b+ antigen presenting cells, IL-12+ macrophages and dendritic cells, IFN-γ+ and IL-17+ T cells, expression of proinflammatory cytokines, such as IL-1α, IL-1β, and TNF-α, but downregulation of Muc5ac. The proliferation and function of goblet cells are inhibited, resulting in decreased mucus production and barrier dysfunction similar to that in dry eye disease.

63. Allergic rhinitis (AR) is a prevalent disease characterized by an aberrant type-2 response to aeroallergens. In addition to traditional treatments for AR, which have been primarily aimed at reducing AR symptoms, recent evidences may support the use of allergen-specific immunotherapy (AIT) to reduce symptoms and medication use. Nevertheless, the utility of biologics as monotherapy or in combination with other therapies such as AIT for the treatment of AR has not yet been fully investigated. Matthew F. Wipperman and colleagues conducted a study to further investigate the transcriptomic effect on nasal epithelial cells following treatment of AR with dupilumab, subcutaneous immunotherapy (SCIT), and dupilumab + SCIT. In this regard, which of the following genes was only downregulated by the SCIT + Dupilumab combination treatment? Check the correct answer by reading the original article by Wipperman and colleagues





The transcriptomic signature of allergic rhinitis (AR) in nasal epithelial cells following treatment with dupilumab, subcutaneous immunotherapy (SCIT), and dupilumab + SCIT has revealed that treatment with dupilumab, and dupilumab + SCIT reduces AR symptoms. This is not achieved with SCIT alone, probably due to the short treatment course, which is unable to modulate AR symptoms in the short term. In this regard, the combination of SCIT + dupilumab treatment induced elevated downregulation of genes related to inflammation compared to the placebo group in a greater extent than with dupilumab alone or SCIT treatment. Some of these downregulated genes are GCNT4, DPP4, CDH26, SERPINB4, or CMYA5, whereas dupilumab treatment only downregulated POSTN, and SCIT only downregulated LGALS7.

64. Allergen immunotherapy (AIT) is rapidly evolving and brings a huge benefit to patients suffering from allergic conditions. Zemelka-Wiacek et al. shared the latest development in AIT in their article and proposed several novel methods to improve patient stratification and AIT management. Randomized controlled trials (RCT) and real-world evidence (RWE) from real-world data (RWD) are common trial designs. What is the advantage of RWE studies compared to RCT that the authors emphasize in the article regarding clinical trials in AIT? Check the correct answer by reading the original article by Zemelka-Wiacek and colleagues.





RCTs and RWE complement each other in several ways. RCTs are considered the gold standard for determining a treatment's efficacy because they control for confounding variables through randomization and maintain strict protocols for treatment administration. RWE studies provide evidence from larger, more diverse and unselected patient populations, and the treatment is given under routine clinical conditions. This means RWE can capture a broader range of patient experiences, from different demographics to those with comorbidities, thus providing insights into how a treatment performs in ‘real-life’ conditions. Because RWD is observational, it may not be possible to establish a clear cause-effect relationship as in RCTs. Furthermore, RWD can capture the effectiveness of AIT in reducing healthcare costs and the rates of adherence to therapy, areas often not covered in RCTs.

65. Tezelumab is a monoclonal antibody that specifically blocks the activity of thymic stromal lymphopoietin (TSLP), an alarmin produced by airway epithelial cells, highly associated with asthma onset and persistence. Different studies have demonstrated the efficacy of tezepelumab in controlling asthma progression and exacerbation. The usefulness of tezepelumab in allergic and eosinophilic asthma has been reviewed in a recent article by Marco Caminati et al. In this regard, what percentage reduction in the number of exacerbations was observed with treatment for 52 weeks with tezepelumab 210 mg with a baseline blood eosinophil count of at least 300 cells/uL? Check the correct answer by reading the review article by Marco Caminati and colleagues.





Tezepelumab is a monoclonal antibody that selectively blocks the activity of thymic stromal lymphopoietin (TSLP), and its efficacy has been demonstrated through different randomized trials for threating allergic, eosinophilic, non-allergic, and non-eosinophilic asthma. Accross different studies, treatment for 52 weeks with tezepelumab 210 mg has been shown to be effective in reducing the annualized asthma exacerbation rate (AAER) by up to 71% with a baseline blood eosinophil count of at least 300 cells/uL compared to the placebo group, while a 63% reduction was obtained when the baseline blood eosinophil count is at least 150 cells/uL, 77% with at least 500-750 cells/uL, and 74% with at least 1000 cells/uL.

66. Over the past decade, studies have reported a significant increase in anaphylaxis presentation among children in developed countries, particularly food-induced anaphylaxis. The Asia-Pacific Research Network for Anaphylaxis (APRA), established by the Asia Pacific Academy of Pediatric Allergy, Respirology and Immunology (APAPARI), is a prospective paediatric anaphylaxis registry that employs a standardized methodology for data collection across all participating Asian countries. This study, conducted by the APRA, aimed to highlight the patterns and elicitors of pediatric anaphylaxis in this region, in comparison with the rest of the world, and to identify the adequacy of anaphylaxis management. Based on their observations, which of the following sentences is false? Check the correct answer by reading the original article by Leung and colleagues:





In the evaluated cohort, biphasic reactions occurred in 16 (2.2%) cases. Upon discharge, 229 (32%) cases were given follow-up appointments at specialist allergy clinics, and 296 (41%) were prescribed adrenaline autoinjectors or prefilled syringes upon discharge. Overall, the top 3 triggers of anaphylaxis were food (62%), idiopathic causes (22%), and drugs (10%). Insect venom-induced anaphylaxis was uncommon in Asia, with only eight cases reported in Bangkok and one in Singapore. Regarding severity, when food anaphylaxis was analyzed independently, most reactions were classified as Grade 4 (61%) by the oFASS-5 scores, followed by Grade 3 (21%) and Grade 5 (18%).

67. In studying the effects of propionate on atopic dermatitis (AD) in mouse models, Yao Xu and colleagues explored how propionate impacts various symptoms of AD, including itch and inflammation. The findings provide insights into which specific types of itch were influenced by propionate treatment. Which of the following was NOT found to be significantly reduced by propionate in the study's atopic dermatitis mouse model? Check the correct answer by reading the original article by Xu and colleagues:





The study noted that propionate markedly reduced scratching induced by histamine, chloroquine, and compound 48/80, but not 5-HT ("but not 5-HT (p = 84), compared with vehicle control"). This indicates that while propionate was effective against certain pruritogens, it did not significantly reduce itch caused by 5-HT.

68. Abrocitinib, a Janus kinase inhibitor, is approved for the treatment of moderate-to-severe atopic dermatitis (AD). Abrocitinib 200mg showed a good clinical efficacy compared to placebo with more patients achieving EASI-90. Guttman-Yassky et al. investigated the gene expression on skin biopsies under abrocitinib therapy and association with clinical markers. They found that S100A8, S100A9 and S100A12 are significantly reduced under abrocitinib treatment in AD patients. How does the JAK1-inhibition influence the expression of these proinflammatory proteins? Check the correct answer by reading the original article by Guttman-Yassky and colleagues.





Although S100A8, S100A9, and S100A12 expression is induced by both Th22 cytokine (IL-22) and Th17 cytokine (IL-17) signaling in AD skin, IL-22 acts via JAK1 signaling, whereas IL-17 does not. Therefore, abrocitinib, a JAK1 inhibitor, likely reduced S100A8, S100A9, and S100A12 expression by inhibiting IL-22 signaling. Interestingly, dupilumab has also been shown to decrease expression of S100A8, S100A9, and S100A12 in AD skin, and downregulation of S100A8 and S100A12 is strongly correlated with improvements in EASI score at week 16. The mechanism behind this downregulation is likely to differ from that observed with abrocitinib; one hypothesis is that dupilumab-mediated inhibition of IL-4 precludes activation of the IL-4Rα/γc heterodimer, suppressing Th2 cell differentiation and TARC synthesis. Decreased production of TARC decreases Th22 cell recruitment to lesional skin, suppressing the expression of Th22-related genes, such as S100A8 and S100A9.

69. Chronic rhinosinusitis (CRS) is a persistent inflammatory disorder of the nasal and sinus mucosa, that affects approximately 15% of the general population. Although CRS, with or without polyps, is complex, data suggest that epithelial barrier dysfunction, impaired mucociliary clearance, disordered immune response and excessive tissue remodelling are involved in its pathogenesis. In recent years, the role of tight junction, proteins located between epithelial cells, appears to play a central role in the integrity, polarity, recovery and differentiation of epithelial cells. Based on our current knowledge of the expression of different thigh junctions in different cell models, which of the following statements is correct? Check the correct answer by reading the review article by Zhi-Qun Huang and colleagues.





One of the most important features of Chronic RhinoSinusitis (CRS) with or without polyps is the increased permeability between nasal epithelial cells, which is affected by different factors such as pathogens, allergens, pollutants... Therefore, understanding the mechanisms underlying epithelial barrier dysfunction is essential for diagnosis, management and treatment strategies. The review article by Zhi-Qun Huang and colleagues summarises original and published data on the role of different tight junction proteins and their expression at different stages of epithelium formation using different cell models. Specifically, gene expression of ZO-2 and claudin-7 peaks at day 7, whereas expression of CRB3, RHOA, and MKI167 gradually decreases over time, mainly because they are more associated with proliferation, being therefore inactivated in mature cells. In contrast, occludin increases slightly with time, and claudin-3 and -10 expression gradually increases with time from their total absence during the first days of epithelium formation.

70. Despite numerous global clinical trials demonstrating the effectiveness and safety of subcutaneous immunotherapy (SCIT) for house dust mite-induced allergic rhinitis (AR), a significant proportion of patients exhibit insufficient responses. Consequently, there is an urgent need to identify biomarkers capable of predicting the effectiveness of SCIT. This original article by Nan Wang and colleagues aimed to identify potential efficacy predictors of a 12-month SCIT treatment, by analysing baseline demographic data and immune signatures in adult patients with HDM-induced AR. A multivariate prediction model for SCIT responsiveness allowed for the identification of important biomarkers as independent predictors. Which of the following variables was not an independent predictor? Check the correct answer by reading the original article by Wang and colleagues:





To establish a robust prediction model for SCIT responsiveness in the Tongji cohort, the authors performed multivariate logistic regression analysis using the eight variables that showed significant associations with SCIT response in the univariate analysis. From this analysis, the authors identified sIgE/tIgE ratio, TFR/TFH2 cell ratio, and CD23+ BSM cell frequency as independent and significant predictors of clinical response to SCIT. Despite being identified as an important predictor in random forest modelling and univariate logistic regression analysis, CD23+ BNSM cell frequency was not included in the multivariate logistic regression model.

71. The regulation of immune response genes in the skin plays a crucial role in determining whether an individual exposed to p-phenylenediamine (PPD), a common allergen in hair dyes, will develop allergic contact dermatitis (ACD) or remain clinically tolerant. This study by Sanne S. Meisser and colleagues highlights significant differences in gene expression profiles between allergic and asymptomatic (non-responder) individuals. Which of the following findings was observed in the study regarding the immune response to PPD in the skin? Check the correct answer by reading the original article by Meisser and colleagues:





The study found that PPD exposure induced up-regulation of immune response genes in both non-responders and allergic individuals. "PPD affected the regulation of immune response genes in both non-responders and allergic individuals," and "There was significant overlap between differentially expressed immune response genes in the groups with 139 genes being shared among all groups". The study further elaborates on the involvement of T cell activation and other immune pathways, demonstrating that PPD exposure leads to a complex immune response in both groups.

72. Accumulation of senescent cells due to inflammaging is a common pathogenic hallmark of chronic allergic and inflammatory diseases in old age such as atopic dermatitis, late-onset severe asthma and chronic obstructive pulmonary disease (COPD). In their review, Roth-Walter et al. summarized the role of senescent cells, inflammaging and future therapeutic targets relevant to chronic allergic and inflammatory lung responses. Several pharmacological approaches have been investigated to counteract senescence. Senolytic and senomorphic drugs are currently being studied in preclinical and clinical trials. What are senomorphic drugs? Check the correct answer by reading the original article by Roth-Walter and colleagues.





Different pharmacological approaches to contrast senescence have been investigated. Senolytic and senomorphic drugs are promising approaches for targeting the aging process, and they are currently being investigated in preclinical and clinical studies. Senolytic drugs are compounds that selectively induce death in senescent cells. Senomorphic drugs, on the other hand, do not directly kill senescent cells but instead alter the SASP of these cells. Main approaches are either the introduction of potent radical scavenger/anti-inflammatory agents, such as fisetin and quercetin; or blocking signaling pathways for inflammatory cytokine synthesis with agents such as dasinitb, or improving respiration (OXPHOS) in mitochondria and ATP synthesis with sulforaphane.

73. The impairment of the epithelial barrier of skin, gut and respiratory tract has a major impact on the occurrence and progression of inflammatory and allergic conditions. Epithelial barrier dysfunction has multiple causes, such as exposure to pollution, cleaning products, ultra-processed food, the impact of climate change; microbiome alterations, as well as genetic and epigenetic factors. Therefore, it is of great importance to identify specific biomarkers as well as therapeutic targets for epithelial dysfunction. Regarding investigational biological therapies for epithelial-driven diseases, which of the following monoclonal antibodies selectively targets the IL-33 receptor? Check the correct answer by reading the review article by Berni-Canani and colleagues:





Epithelial barrier dysfunction is relevant in the onset and progression of inflammatory and allergic disorders. The identification of specific biomarkers as well as potential therapeutic targets for epithelial dysfunction are essential steps in the diagnosis and management of these patients. Currently, a large number of treatments with biologics have been approved for a wide range of diseases such as asthma, atopic dermatitis (AD), or eosinophilic esophagitis (EoE), and many more targeting different immune receptors, alarmins and cytokines are under investigation. In relation to these, itepekimab, that targets IL-33, is in phase 3 study for asthma. Cendakimab, an anti-IL-13 in phase 3 trial for the treatment of EoE and in phase 2 for AD, while lebrikizumab, also targeting IL-33, is being investigated for AD (phase 3 trial). Astegolimab is a monoclonal antibody specially targeting the IL-33 receptor (IL-33R), in phase 2 trial for allergic asthma.

74. The EAACI-EANO Position Paper discusses the complex relationship between allergic diseases and glioma. Allergic disorders stem from a Th2-biased immune response and have varied phenotypes, genotypes, and endotypes. Gliomas, on the other hand, are the most common type of brain tumour, with diverse classifications based on molecular biomarkers. Emerging research in AllergoOncology explores the potential for allergic diseases to influence glioma risk, with some epidemiological studies suggesting an inverse association. However, this connection is not fully understood, particularly in relation to glioma subtypes and the role of specific immune responses. One hypothesis within the paper suggests that allergic diseases might decrease glioma risk by affecting tumour microenvironment factors. Which of the following statements about the relationship between allergies and glioma risk is incorrect? Check the correct answer by reading the review article by Turner and colleagues:





75. Alpha-gal syndrome (AGS is a syndrome of tick-acquired mammalian meat allergy. It is mediated by IgE antibodies against the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal), and can also involve reactions to visceral organs, dairy, gelatin and other products, including medications sourced from non-primate mammals. Its characteristics have been extensively covered in this review article by Jeffrey Wilson and colleagues. Aside from tick bites, other risk factors have been reported by some groups to be associated with alpha-gal sensitization and AGS. Which of the following sentence is incorrect? Check the correct answer by reading the review article by Wilson and colleagues:





Aside from tick bites, ABO blood group status is arguably the most thoroughly investigated risk factor, with several studies indicating that individuals with the B antigen blood group may have some protection against sensitization and/or the development of the clinical syndrome. However, those with the B blood group may still develop alpha-gal syndrome (AGS). While cat ownership has been suggested as a potential risk factor for alpha-gal sensitization, this has not been consistently supported by other studies. The role of pre-existing atopy as a risk factor for AGS is still uncertain. Lastly, in less developed regions, parasites other than ticks, such as Ascaris, might contribute to alpha-gal IgE sensitization, though whether this significantly causes symptomatic AGS is still to be determined.

76. Malassezia is the most abundant fungal genus in the skin microbioma. It is controlled by the skin immune system via IL-17. Ruchti et al. investigated the interaction between the host and Malassezia in atopic dermatitis, the most common skin disorder associated with Malassezia. Malassezia is unable to synthesize lipids, which is why they live in lipid-rich areas such as sebaceous hair follicles. What mechanism is dysregulated in atopic dermatitis and therefore supports fungal growth? Check the correct answer by reading the original article by Ruchti and colleagues:





Given its lack of fatty acid synthase, Malassezia relies on the acquisition of lipids from the host by means of lipases, phospholipases, and sphingomyelinases. We detected increased expression of MpFAA1, a key fungal gene implicated in fatty acid uptake, activation and consequently in fungal growth in the MC903-treated skin (Figure 6G). Likewise, we found the fungal phospholipase A2 activating gene MpPLAA to be upregulated (Figure 6G). Phospholipases are involved in the acquisition of fatty acids from the host environment and their production and activity is enhanced in M. pachydermatis isolates from dogs with dermatitis or otitis, emphasizing their relevance for Malassezia fitness in the atopic skin. Together, these findings suggest that by increasing its lipid uptake machinery Malassezia may benefit from the altered lipid environment in the barrier-impaired skin, which provides a growth advantage.

77. Atopic dermatitis (AD) is a common disease affecting both adults and children, characterized by recurrent eczematous skin lesions, pruritus and sensitive dry skin, which significantly impairs the quality of life of patients. A deeper understanding of the endotype and phenotype of the disease, as well as the identification of specific biomarkers could allow identifying the best treatment to a particular patient in the context of personalized medicine. In the last decades, new lines of treatments, biologics and oral janus kinase inhibitors (JAKi), have been approved, and have demonstrated their short- and long-term efficacy and safety. In this regard, which of the following treatments showed the best short-term efficacy as monotherapy for AD? Check the correct answer by reading the review article by Svenja Müller and colleagues:





Atopic dermatitis (AD) is a common disease with important implications for patients’ quality of life. Treatment of the disease has changed dramatically in recent years due to the approval of new therapies, mainly those involving biologics and janus kinase inhibitors (JAKi) that target a wide variety of immune receptors, cytokines and alarmins, opening up the therapeutic options for AD patients in the context of personalized medicine. Many of these treatments have already been approved, while others are now under investigation. In the case of those already approved, their safety and short- and long-term efficacy have been demonstrated by different studies and clinical trials. In this context, the treatment as monotherapy that has shown the best short-term efficacy in AD is upadacitinib 30 mg (odds ratio (OR) = 18.90), followed by dupilumab 300 mg each 2 weeks (OR=9.25), tralokinumab 300 mg (OR = 2.95) and baricitinib 2 mg (OR = 2.76).

78. This study explored the use of skin tape-strips to evaluate transcriptomic biomarkers in children with moderate and severe allergic asthma. Tape-strips, a minimally invasive method, were used to collect skin samples from children with asthma and healthy controls, uncovering significant downregulation in genes related to epidermal barrier function and immune response pathways. The study identified specific biomarkers that correlated with lung function and asthma severity. Which of the following statements about the findings of the study is correct? Check the correct answer by reading the article by Del Duca and colleagues:





The correct answer is D) All of the above. This information can be found throughout the study, including the sections discussing epidermal barrier dysfunction, the correlation of biomarkers with lung function and asthma severity, and the two-gene classifier achieving 100% accuracy.

79. Atopic dermatitis (AD) is a chronic pruritic inflammatory skin condition characterized by disrupted skin barrier function and immune dysregulation. Children with AD often experience multiple co-morbidities, including food allergies (FA). In particular, early onset and severe AD are significant risk factors for the development of FA in children. The skin plays a vital role in providing barrier protection, sensory regulation and immune and thermal homeostasis. On healthy skin, there is a diverse skin microbial community, with a fine equilibrium among pathogens, commensal organisms and the immune system. However, in children with AD, this skin microbiome is altered. The mechanistic pathways involved in the development of AD and FA in children, as well as the role of the skin microbiome in pediatric AD and FA, are comprehensively reviewed in this article by Elizabeth Tham and colleagues. In healthy neonates, which of the following bacteria has an incorrect prevalence in skin microbiome? Check the correct answer by reading the review article by Tham and colleagues:





Exposure to the external environment during early life can influence host-microbe interactions that impact skin health and the development of atopic diseases. Variations in skin physiology during the neonatal period and infancy affect the patterns of skin microbiota colonization. In healthy neonates, the skin microbiome is primarily dominated by Bacillota (formerly Firmicutes), including genera like Staphylococcus and Streptococcus, with fewer Actinomycetota (formerly Actinobacteria), such as Cutibacterium and Corynebacterium.

80. Atopic dermatitis (AD) is a common skin disease that significantly affects the quality of life of patients. Environmental factors such as ultraviolet radiation, toxins, allergens, temperature or humidity have a significant effect on AD. Therefore, it is expected that due to climate change, exposure to recurrent and extreme climatic hazards may affect people in specific locations, altering the onset, management, and worsening of AD. In this regard, a recent review by the International Eczema Council addresses this issue, analyzing the most relevant climatic hazards and their influence on AD. Based on this, which of the following research gaps were identified on the impact of climate change on AD? Check the correct answer by reading the review article by Sheng-Pei Wang and colleagues:





Human exposure to climatic hazards has a major impact on atopic dermatitis (AD), affecting the onset, course, and worsening of disease symptoms through factors that affect the disease through biological mechanisms: alteration of the immune system or impairment of epithelial barrier integrity; environmental mechanisms: increase of mold, dust, pollen or pollution; and psychosocial mechanisms: stress, migration or access to health care facilities. All of these mechanisms affecting AD, are especially important in locations where the effect of global warming and climate change are more pronounced such as in the tropics. Although the data regarding the effect of climatic hazards and AD are clear, the International Eczema Council identifies some research gaps and future perspectives, such as the need to integrate as many climate risks as possible into studies, to examine AD in terms of incidence, prevalence and follow-up, to include data from different parts of the world, to integrate basic mechanisms and epidemiological data, and to consider specific differences depending on population or vulnerability.

81. Retinoic acid, the main metabolite of vitamin A has the ability to regulate inflammation and oxidative stress, key factors during an allergic response. It has been described that different proteins have the capacity to form complexes with micronutrients, thus modifying their interaction with the immune system, as is the case of Alt a 1, the major allergen of Alternaria alternata. Which of the following statements is not correct regarding in vitro stimulation of PBMCs with Alt a 1 loaded with retinoic acid (holo-Alt a 1) or not (apo-Alt a 1)? Check the correct answer by reading the original article by Aila Fakhimahmadi and colleagues:





The study by Aila Fakhimahmadi and colleagues has demonstrated the ability of retinoic acid, the main metabolite of vitamin A, to form complexes with Alt a 1, the major allergen of Alternaria alternata. Because of the capacity of retinoic acid to modulate the immune system, the authors conjugated Alt a 1 with retinoic acid (holo-Alt a 1) or not (apo-Alt a 1), to determine the potential immunomodulatory role of this micronutrient. After stimulation of PBMCs with both compounds, they have observed that holo-Alt a 1 compared to apo-Alt a 1 significantly decreases the release of cytokines such as IL-6, TNFα, and IL-10, while decreasing the overall frequency of monocytes, also reducing their maturation state. Moreover, it increases the frequency of plasma cells (CD19+CD27+CD38+), mainly related to IgA production, although it decreases the frequency of T regulatory cells and impairs their activation.

82. In rhinitis and asthma, a few mHealth apps have been validated. These apps have a high potential for improving person-centered care, especially in allergen immunotherapy (AIT). Perspectives in this regard have been formulated in a recent ARIA-EAACI position paper, published by Oliver Pfaar and colleagues. Regarding the MASK-air app and AIT, which of the following sentences is incorrect? Check the correct answer by reading the reading the original article by Pfaar and colleagues:





Using MASK-air app, a cohort of 1970 users (13-26 years) and a total of 13454 days were evaluated. AIT was associated with improved school productivity, which was not observed for rhinitis medication. Additionally, real-world data suggests that AIT is associated with a lesser burden of symptoms in patients using antiallergic medication compared to comparators without AIT. In another study, VAS global allergy symptoms and work as well as e-CSMS were analysed in users receiving sublingual AIT (SLIT) or subcutaneous AIT (SCIT) and in those with no AIT. Obtained data confirmed the clinical efficacy of AIT regarding the need for antiallergic medication. In users under SLIT, days with AIT were associated with better AR control than days without AIT. These rapid clinical effects may be related to rapid and short-lasting cell downregulation (desensitization), particularly in basophils and mast cells.

83. Food allergy (FA) starts in patients’ early life and brings a heavy burden on the quality of life. Preventive strategies are important for the control of FA. Peng et al. developed a directed acyclic graph (DAG) to map causal relationships of relevant factors for the development of childhood food allergy. According to the DAG online application by Peng et al. (http://dagitty.net/dags.html?id=8J8AWP), what are the confounding factors, when we set “formula feeding” as an exposure variable? Check the correct answer by reading the original article by Peng and colleagues:





According to the web application provided by the authors, the confounding factors of exposure to “formula feeding” are breastfeeding, region/outdoor environment and socioeconomic status. Formula feeding mediates infants’ weight gain, complementary feeding, GERD/antacid use, atopic dermatitis/eczema in the pathway to food allergy.

84. The paper “Quality control of allergen products with mass spectrometry part I: Positioning within the EU regulatory framework” by Jelena Spiric and colleagues discusses the use of mass spectrometry (MS) in the standardisation and regulation of allergen products. While MS holds great potential, its current role in regulatory frameworks is limited but evolving. Which of the following statements about the application of MS in allergen product regulation is incorrect? Check the correct answer by reading the the review article by Jelena Spiric and colleagues:





The incorrect statement is B. The European Pharmacopoeia (Ph. Eur.) does not mandate the use of MS in all allergen product batch release tests. While MS is mentioned in regulatory guidelines, it is not required as a standard method, and manufacturers have the discretion to choose suitable methods for their products. This can be found in the discussion on the regulatory framework and current applications of MS within the EU regulatory environment in the paper.

85. Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a non-immediate hypersensitivity reaction affecting multiple organs. During the acute phase of the reaction, the ocular surface can be severily damaged, which can lead to chronic complications. Nevertheless, little is known about the underlying mechanisms. In a recent article, tear proteomics using mass spectrometry has been performed to better understand the molecular mechanism involved in ocular complications in SJS/TEN patients. In this regard, which of the following proteins was less expressed in the tears of SJS/TEN patients compared to those of healthy donors? Check the correct answer by reading the original article by Madhuri Amulya Koduri and colleagues:





The study by Amulya Koduri and colleagues compares the tear proteasome between SJS/TEN patients with chronic ocular complications and healthy donors. They have observed that several proteins were highly expressed in the lacrimal gland secretion tears of SJS/TEN patients compared to healthy donors, such as interleukin-36γ (IL-36γ), interleukin-8 (IL-8), or proteinase-3/ myeloblastin (PRTN3). Nevertheless, proteasome analysis showed a significant reduction in the expression of some proteins, such as proline-rich protein 4 (PRR4), in SJS/TEN patients compared to healthy donors.

86. Intralymphatic immunotherapy (ILIT) represents a promising novel approach treating allergic diseases. However, no standardized procedures or recommendations have been established or reported. This original article, published by Stephan Flory and colleagues, aimed to provide a critical appraisal of ILIT as a method of allergen immunotherapy and to deliver practical recommendations for accurate ILIT. Regarding the safety of ILIT injections, which of the following is not true? Check the correct answer by reading by reading the review article by Flory and colleagues:





In 141 out of 180 ILIT sessions (78%), no AE were reported within the 1 day of release. There were seven (4%) reports of chest tightness and no urticaria. All local reactions could be treated with oral antihistamines. No serious adverse events (AEs) were reported after ILIT. When analysing AEs as a function of the grading system for injections, the authors observed significantly (p = .009) more AEs in patients that received injections of poor quality (scores 1–2) as compared to patients with no AEs.

87. Preventive allergen immunotherapies (pAIT) in children show a good therapeutic efficacy in reducing existing symptoms and medication scores. Dwivedi et al. summarized the current use of pAIT in primary, secondary and tertiary prevention as well as in different allergens. For which type of allergen did pAIT show the best results in preventing development of asthma? Check the correct answer by reading the original article by Fritz and colleagues:





HDM pAIT is most commonly studied. Still, definitive evidence on its preventive benefits is missing. Reasons for this may be heterogeneous allergen composition and doses, discrepancies in the perennial exposure, and a low number of high-quality randomised studies. Favourable evidence from randomised studies on grass and/or tree pollen based pAIT is available for preventing asthma development in children with AR/C. Preventive effects of AIT with other allergen types are inconclusive.

88. The paper “Helminth induced monocytosis conveys protection from respiratory syncytial virus infection in mice” by Matthew O. Burgess and colleagues describes the immune mechanisms through which Heligmosomoides polygyrus infection helps protect against RSV. Which of the following statements about the role of H. polygyrus-induced immune responses is correct? Check the correct answer by reading the article by Matthew O. Burgess and colleagues:





The correct answer is B. The expansion of circulatory monocytes is both necessary and sufficient for H. polygyrus-induced protection against RSV, as shown by experiments involving monocyte depletion and transfer. This can be found in the results section discussing the role of monocytes in antiviral protection.

89. Pollen negatively affects the quality of life of a large number of allergic and/or asthmatic patients, among other pathologies. Therefore, pollen forecast is an important tool to reliable predict daily pollen concentrations in an extended geographical area, crucial for the daily management of pollen allergy symptoms, helping to improve the quality of life of patients. Computational intelligence can help to obtain more accurate pollen prediction models than traditional regression models. In this regard, which of the following parameters is the most important variable for predicting daily pollen concentrations using a deep learning (DL) model? Check the correct answer by reading the original article by László Makra and colleagues:





Pollen concentration forecasting is essential for the management of pollen allergic symptoms in asthmatic and allergic patients, which is important for improving their quality of life. In this regard, László Makra and colleagues created forecasting models using computational intelligence with deep learning and CatBoost in 23 cities worldwide. Both models have overall better predictive values for pollen concentrations than previous studies, with the best predictive parameter being the total past daily pollen concentration, followed by the future 2m temperature, past 2m temperature, past soil temperature at 28–100 cm depth, and past soil temperature in 0–7 cm depth.

90. increasing public health problem worldwide. Immunomodulatory treatments that could potentially change the course of FA have been investigated. These include allergen-specific immunotherapy (AIT) and monoclonal antibodies directed to key factors, such as IgE, IL-33, or the IL4/IL13-receptor. A systematic review, published by Carmen Riggioni and colleagues, was carried out to inform the development of clinical recommendations on the treatment of IgE-mediated FA with biologics and/or IT for the update of the EAACI guidelines. Overall, in which type of food allergy immunotherapy was the protective effect higher? Check the correct answer by reading the review article by Riggioni and colleagues:





The protective effect in food allergy was higher for OIT than other modalities of IT, namely EPIT and SLIT, where evidence was available, and higher for peanut allergy than for cow's milk or egg allergies. With SCIT, the available evidence is very limited.

91. Allergy has been linked to other disorders, such as cardiovascular diseases like atherosclerosis, due to the inflammatory process and metabolic disorders caused by allergic reactions. Nevertheless, the specific relationship between allergic disorders, metabolic changes and atherosclerosis remains poorly understood. In this regard, what specific lipid profile is increased in sensitized allergic mice 3 days after allergen challenge compared to naive mice? Check the correct answer by reading the original article by Nieves Fernández-Gallego and colleagues:





Recent studies have associated allergic disorders and metabolic changes, specifically, lipid metabolism, and other pathologies such as cardiovascular diseases like atherosclerosis. The study by Nieves Fernández-Gallego and colleagues showed an increase in serum triglyceride levels in sensitized allergic mice 3 days after allergen challenge, but not in other lipid parameters such as total cholesterol, free cholesterol, or LDL/HDL ratio. These changes are independent of the diet and T cells, with an IgG-mediated pathway being sufficient to trigger this increase. This new data supports the relationship between allergic disorders and atherosclerosis through changes in lipid profile, mainly related to increased serum triglyceride.

92. The role of eosinophils in airway inflammation and asthma pathogenesis is well established, with raised eosinophil counts in blood and sputum associated with increased disease severity and risk of asthma exacerbation. Conversely, there is also preliminary evidence suggesting antiviral properties of eosinophils in the airways. These dual roles for eosinophils are particularly pertinent as respiratory virus infections contribute to asthma exacerbations. This review, published by Rupani et al, discusses the pathological and antiviral roles of eosinophils in asthma and exacerbations. Regarding the known features of eosinophilic response to influenza in asthma discussed in the article, which of the following sentences is incorrect? Check the correct answer by reading the original article by Rupani and colleagues:





Influenza viruses account for up to 25% of asthma exacerbation cases during the influenza season. Influenza exposure was associated with upregulation of both T1 and T2 inflammatory pathways, as demonstrated by IFN-γ upregulation, and IL-5 and IL-13 upregulation, respectively. Changes in IL-5 and IL-13 were paralleled by an enhanced presence of eosinophils. Additionally, an in vitro study highlighted eosinophils’ antiviral activity – it was found that human eosinophils adhered to influenza and respiratory syncytial virus (RSV) before internalizing and inactivating them. Information regarding increased TGF-β release from eosinophils was found in studies related to epithelial rhinoviral infection, and not influenza.

93.The paper “Quality control of allergen products with mass spectrometry part I: Positioning within the EU regulatory framework” by Jelena Spiric and colleagues discusses the use of mass spectrometry (MS) in the standardisation and regulation of allergen products. While MS holds great potential, its current role in regulatory frameworks is limited but evolving. Which of the following statements about the application of MS in allergen product regulation is incorrect? Check the correct answer by reading the review article by Jelena Spiric and colleagues:





The incorrect statement is B. The European Pharmacopoeia (Ph. Eur.) does not mandate the use of MS in all allergen product batch release tests. While MS is mentioned in regulatory guidelines, it is not required as a standard method, and manufacturers have the discretion to choose suitable methods for their products. This can be found in the discussion on the regulatory framework and current applications of MS within the EU regulatory environment in the paper.

94. The 4th Davos Declaration was developed during the Global Allergy Forum in Davos with a focus on advancing research, treatment and management of atopic dermatitis. Traidl-Hoffmann et al. summarized the current knowledge about atopic dermatitis and formulated research goals for improving the quality of healthcare globally, ensuring equitable treatment for patients worldwide. Which statement is not a research goal in the diagnosis and therapy of atopic dermatitis according to the 4th Davos Declaration? Check the correct answer by reading the original article by Traidl-Hoffmann and colleagues:





The incorrect statement is “B”. The 4th Davos Declaration stated the following research goals for diagnosis and therapy in atopic dermatitis:
1. Identifying variations
2. Analyzing the impact of diverse definitions
3. Developing global standards
4. Enhancing patient-centered care
5. Cross-cultural collaboration and education

95. Interleukin-5 (IL-5) is an important cytokine involved in eosinophil maturation, activation, proliferation, migration and survival. Nevertheless, IL-5 is also involved in additional mechanisms beyond its direct effect on eosinophils. Kathleen M. Buchheit and colleagues reviewed the role of IL-5 beyond eosinophil-associated inflammation, as well as its clinical implications in type-2 inflammation. In this regard, which of the following pathways does IL-5 directly influence? Check the correct answer by reading the original article by Kathleen M. Buchheit and colleagues:





Interleukin-5 (IL-5) is a type 2 cytokine that directly influences the maturation, activation, proliferation, migration and survival of eosinophils, with relevant implications in inflammatory diseases related to these cells. However, IL-5 also directly influences different inflammatory processes, targeting a wide variety of cell types through the presence of functional IL-5R, such as mast cells, basophils, plasma cells, neutrophils or fibroblasts. In this regard, and beyond eosinophils, IL-5 plays a direct role in mast cell and basophil survival, IgE production by plasma cells, neutrophil activation, fibroblast activation and proliferation, and vascular remodeling. Understanding the direct and indirect effects of IL-5 beyond its influence on eosinophils will be essential to optimize treatments for specific patients.

96. Oral immunotherapy (OIT) is an emerging treatment for food allergy that is effective at inducing desensitization and remission. Particularly, randomized placebo-controlled trials have shown that peanut OIT is highly effective. However, it has been associated with increased adverse events and anaphylaxis with OIT as compared to allergen avoidance, and uncertainty regarding quality-of-life improvement. Few studies have examined outcomes following OIT beyond 12 months post-treatment, and there are no direct comparisons of the risks and benefits of desensitization versus remission outcomes following peanut OIT in the longer term. This long-term trial, conducted by Loke et al, is a follow-up of the probiotic and peanut oral immunotherapy (PPOIT)-003 study. Peanut ingestion, reactions, and health-related quality of life (HRQOL) were monitored prospectively. Outcomes at 1-year and 2-years post-treatment were examined by treatment group and by post-OIT clinical outcome (remission, desensitization without remission [DWR], allergic). Regarding the results of this trial and current evidence, which of the following sentences is incorrect? Check the correct answer by reading the original article by Loke and colleagues:





Participants who achieved remission after treatment with either PPOIT or OIT reported significant and clinically meaningful improvements in health-related quality of life (HRQOL), which continued through the second year post-treatment. A decline in adherence to daily treatment among desensitized patients over time is notable, as the PALISADE-ARC004 open-label follow-on study found that skipping daily doses led to a loss of desensitization and an increase in reactions compared to those who continued daily dosing. However, high-quality evidence is still lacking on whether extending desensitization therapy over a longer period can achieve sustained remission. Additionally, peanut reaction rates decreased across all treatment and clinical outcome groups over time, with particularly low reaction rates among remission participants (28% in the first year, 16% in the second year) - significantly lower than the typical 45%–55% rate of accidental reactions in children with peanut allergies in real-world settings.

97. The paper “Helminth induced monocytosis conveys protection from respiratory syncytial virus infection in mice” by Matthew O. Burgess and colleagues describes the immune mechanisms through which Heligmosomoides polygyrus infection helps protect against RSV. Which of the following statements about the role of H. polygyrus-induced immune responses is correct? Check the correct answer by reading the article by Matthew O. Burgess and colleagues:





The correct answer is B. The expansion of circulatory monocytes is both necessary and sufficient for H. polygyrus-induced protection against RSV, as shown by experiments involving monocyte depletion and transfer. This can be found in the results section discussing the role of monocytes in antiviral protection.

98. There are various biomarkers to assess IgE-mediated peanut allergy (PA) in children. Foong et al. compared biomarkers for peanut allergy in PA children and peanut sensitized but tolerant (PS) children. Which biomarker was significantly higher in the PS group compared to the PA group? Check the correct answer by reading the original article by Foong and colleagues:



The correct answer is “C”. Comparison of peanut IgG4 and peanut-specific IgG4:IgE ratios between PA and PS children revealed significantly higher peanut-specific IgG4:IgE ratios in the PS group compared to the PA group at 12 months (276.9 vs. 35.9, p < .01), 36 months of age (1214.9 vs. 20.9, p < .001) and at the 7–12 years time point (490.6 vs. 11.3, p < .001). This was also reflected in the subgroup analysis, with the children who did not have PA because they outgrew it or never had it, as they had significantly higher peanut-specific IgG4:IgE ratios compared to those who had persistent or new PA at 12 months (p < .01), 36 months (p < .001) and 7–12 years (p < .001) time points.

99. Mepolizumab (anti-IL5) and benralizumab (anti-IL5R) are useful biologics for reducing exacerbations and symptom burden in severe eosinophilic asthma, as both block the IL5 pathway, which is essential for eosinophil growth, maturation and migration. Nevertheless, as each biologic targets a different element of the pathway, a differential effect may also be observed depending on the specific eosinophil subtype studied. In this regard, select the correct statement about mepolizumab/benralizumab and eosinophils. Check the correct answer by reading the original article by Michael Fricker and colleagues:





Although both mepolizumab and benralizumab are biologics targeting the IL5 pathway, which is essential for eosinophil differentiation, maturation, migration and survival, each targets different elements (directly against IL-5 or against IL5R), affecting the eosinophil population differently. In addition to the inflammatory role of eosinophils in severe eosinophilic asthma, the importance of homeostatic eosinophils has arisen mainly in relation to modulation of the airway inflammatory response. The article by Michael Fricker and colleagues showed that mepolizumab specifically reduces the number of inflammatory eosinophils, also affecting their survival and maintaining the number of homeostatic eosinophils, while benralizumab reduces both subtypes.

100. Exposure to toxic substances, introduced into our daily lives during industrialization and modernization, can disrupt the epithelial barriers in the skin, respiratory, and gastrointestinal systems, leading to microbial dysbiosis and inflammation. Athletes and physically active individuals are at increased risk of exposure to agents that damage the epithelial barriers and microbiome, and their extreme physical exercise exerts stress on many organs, resulting in tissue damage and inflammation. This review, published by Kistler et al, discusses the detrimental impact of toxic agents on epithelia, while bringing a new perspective on the factors affecting the health and performance of athletes and physically active individuals. What is a significant risk factor for respiratory epithelial barrier damage in athletes? Check the correct answer by reading the original article by Kistler and colleagues:





Chlorination by-products in swimming pools impair the respiratory epithelial barrier, as evidenced by increased transepidermal water loss after swimming sessions. This exposure contributes to the high prevalence of asthma and respiratory allergies among swimmers, making it a significant risk factor.

101. The study by Jabeen and colleagues provides a species-level metagenomic and proteomic analysis of the airway microbiome and associated immune responses in severe asthma. By using long-read nanopore sequencing on sputum samples, the researchers characterise the presence of dominant respiratory pathogens. The pathogen-dominant microbiome correlates with neutrophilic inflammation, elevated type-1 cytokines, and altered immune regulatory factors, providing new insights into the “treatable traits” of severe asthma. Aside from the key findings, which of the following sentences is incorrect? Check the correct answer by reading the the full article by Jabeen and colleagues:





The incorrect option is B. The study clearly states that Haemophilus influenzae was the most prevalent dominant pathogen (10 cases), followed by Moraxella catarrhalis and Streptococcus pneumoniae (4 cases each).

102. Dupilumab has shown high efficacy in treating patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, the long-term effectiveness of this novel biologic medication is still unknown. Huber et al. evaluated the 3-year impact of sustained dupilumab therapy in CRSwNP. Which endpoint measure improved even more from 6 months to 36 months of dupilumab treatment in CRSwNP patients? Check the correct answer by reading the original article by Patrick Huber and colleagues:





The correct statement is “D”. NPS showed a further statistically significant improvement to 0.7 ± 1.1 (p < .05) after 36 months compared to the 12-month time point. SNOT-22 score improved but not significant after 36 months to 18.0 ± 15.0. A subsequent decline of IgE to 36 ± 39.4 was observed after 36 months, although this reduction did not achieve statistical significance. At the 36-month time point, the blood eosinophil count remained consistent at 0.5 ± 0.5, comparable to the count observed at the beginning of therapy (p = .24).

102. Exposure to dust particles, especially particulate matter (PM), has relevant adverse effects on human health, mainly affecting the respiratory and cardiovascular systems. To study these adverse effects on airway epithelial cells, different cellular in vitro models have been widely used worldwide. In addition, the use of microfluidic platforms allows for efficient control and emulation of dynamic forces in the airways. Based on the CALU-3 cell line, which of the following genes is highly downregulated after PM2.5 exposure under dynamic conditions in the airway epithelial barrier (AEB)-­on-­a-chip? Check the correct answer by reading the original article by Ozlem Goksel and colleagues:





Exposure to PM2.5 significantly affects the integrity of airway epithelial barrier, which has an impact on the onset and worsening symptoms of respiratory diseases such as allergies, COPD and other cardiovascular diseases, among others. Experiments by Ozlem Goksel and colleagues have demonstrated the inflammatory response and barrier integrity using a cellular model with Calu-3 cells, and an airway epithelial barrier (AEB)-­on-­a-chip, a useful microfluidic-based platform for simulating dynamic forces in the body. They observed that exposure to PM2.5 increased expression levels of proinflammatory genes, such as IL6, TNF-α, and CD80, while other anti-inflammatory genes, such as CD206, decreased when comparing dynamic to static conditions.

103. The study by Beerweiler et al. explores the immune-regulatory effects of farm-dust stimulation on blood-derived immune cells in children with allergic asthma (AA) and healthy controls (HC). Based on their results, which immune cell population is exclusively upregulated in allergic asthmatic (AA) children upon in vitro farm-dust stimulation? Check the correct answer by reading the full article by Beerweiler and colleagues:





The correct answer is C) CD4+ T-Cells. This information is located in the “Results” section under “Following in vitro farm-dust stimulation, adaptive T- and B-cells were increased while innate cell numbers were decreased in both phenotypes.” It states that “CD4+ T-cells were exclusively elevated in allergic asthmatics (AA).”

104. Moderate-late preterm-born infants experience more frequent and severe respiratory tract infections and wheezing compared to term-born infants. Decreasing the risk on respiratory tract infections and wheezing in this group is vital to improve quality of life and reduce medical consumption during infancy, but also to reduce the risk on asthma and COPD later in life. The review by van Duuren et al., elaborates on risk factors and preventative measures concerning respiratory tract infections and wheezing in preterm-born infants, exploring their impact on the immune system and microbiome. Which of the following is a major risk factor for respiratory infections in preterm infants? Check the correct answer by reading the original article by van Duuren and colleagues:





Early exposure to antibiotics significantly increases the risk of respiratory infections in preterm infants by disrupting gut microbiota development. This leads to a decrease in beneficial bacteria like Bifidobacterium, which plays a key role in regulating immune responses through metabolites like short-chain fatty acids. Early antibiotic exposure also causes pro-inflammatory immune activation and impairs development of regulatory T cells, which are essential for maintaining immune homeostasis.

105. Severe bronchiolitis is associated with childhood asthma development. Several risk factors have been identified for post-bronchiolitis asthma development. However, protective factors against asthma development are still unclear in high-risk children. Wojciech Feleszko and colleagues analysed exposure to residential surrounding greenness in the US severe bronchiolitis cohort. Which parameters were analysed to assess surrounding greenness? Check the correct answer by reading the original article by Feleszko and colleagues:





The correct answer is “A”. The primary exposures consisted of the Normalized difference vegetation index (NDVI) and chlorophyll index (CI) green levels within a small (100 m [meters]) and a large (500 m) radius around the residential address at index hospitalization. The study analyzed the NDVI and CI green levels both as continuous and as categorical variables.

106. Eosinophilic asthma is a severe phenotype, driven by type 2 cytokines with a key role of eosinophils. Therefore, treatments targeting the IL-5 pathway, a cytokine essential for controlling eosinophil differentiation, survival and activation, represent useful strategies to treat this phenotype. On this basis, mepolizumab and reslizumab target IL-5, while beralizumab targets IL-5R. Although they all block the same pathway, there are differences due to their different mechanism of action. In this regard, which of the following statements is correct? Check the correct answer by reading the review article by David J. Jackson and colleagues:





Mepolizumab (anti IL-5) and Benralizumab (anti IL-5R) are monoclonal antibodies targeting the IL-5 pathway, which is essential for the activation, survival and differentiation of eosinophils, the key players in eosinophilic asthma. Although both antibodies target the same pathway, there are important differences due to different mechanisms of action. Mepolizumab does not affect other cytokines involved in eosinophil activation and reduces 50-86% of eosinophils in sputum and blood. At the same time, benralizumab blocks all eosinophil activation pathways, resulting in almost complete eosinophil depletion. Nevertheless, no significant differences in safety, remission rates or lung function have been observed.

107. Irizar et al. investigated the effects of early life air pollution on the development of allergic rhinitis (AR) through DNA methylation and gene expression in the nasal mucosa. Their study of 505 participants found that air toxics such as acrylic acid, phosphine, antimony compounds and benzyl chloride increased the odds of AR. The molecular effects included changes in DNA methylation and expression of genes linked to respiratory ciliary function, mast cell activation, and inflammation. Which gene was identified as playing a key role in mast cell activation and mediating the effect of acrylic acid on allergic rhinitis? Check the correct answer by reading the full article by Irizar and colleagues:





The correct answer is B) RHOH. This information is in the “Results” section under “Mediation by methylation and/or gene expression.” It states that acrylic acid mediates its effect on AR through the expression of RHOH, which is essential for mast cell activation and degranulation.

108. Allergic fungal rhinosinusitis (AFRS) is a severe phenotype of chronic rhinosinusitis with nasal polyposis (CRSwNP). AFRS is associated with immunopathogenic fungal-induced type 2 inflammation. Barrier dysfunction has been suggested to play a role in facilitating fungal colonization and proliferation. Connell et al. investigated the bacterial and fungal microenvironment of AFRS. Which fungal genus was significantly less abundant in AFRS compared to non-fungal CRSwNP in the internal transcribed spacer (ITS) next generation sequencing (NGS)? Check the correct answer by reading the original article by Connell and colleagues:





The correct answer is “D”. For ITS analysis, 25/61 swabs met the reads threshold (16 AFRS, 9 NF). The dominant fungal genus in both AFRS and NF was Malassezia. Significantly higher Malassezia MRA was identified in NF compared with AFRS (AFRS = 45.0%, NF = 84.9%, p < .0001). Malassezia was one of only 3 genera with MRA >1% in NF. In AFRS, 6 fungi were identified with MRA >1%, including Curvularia (AFRS = 18.5%, NF = 0%, p = .06) and Aspergillus (AFRS = 16.8%, NF = 0%, p = .09).

109. Galactose α-1,3-galactose (alpha-Gal) syndrome, a delayed type I redmeat (RM) allergy based on the production of specific IgE antibodies(sIgE) to the oligosaccharide alpha-Gal, is a unique entity. This algorithm, published by Darsow et al., aims to clarify diagnosis and treatment of this allergic disease. According to the diagnostic algorithm for alpha-Gal syndrome, which of the following is a necessary step for confirming the diagnosis? Check the correct answer by reading the original article by Darsow and colleagues:





The diagnostic algorithm emphasizes the need to demonstrate specific IgE to alpha-Gal (e.g., using alpha-galactosylated bovine thyroglobulin) as a key step in confirming the diagnosis. While skin prick tests with fresh meat extracts can be used, they often show weak positivity and are not considered definitive for diagnosing alpha-Gal syndrome. An elimination diet may be part of management but is not sufficient for diagnosis without additional testing. Oral challenges are part of the diagnostic process, but they are performed cautiously with cooked meat and cofactors to ensure patient safety