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Allergy Quiz

38 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%).