Potential of molecular based diagnostics and its impact on allergen immunotherapy

Molecular based in vitro technologies greatly changed the diagnostic approaches in allergy. At present, sensitization profiles can be dissected according to IgE subsets, which are specific for genuine or cross-reacting components and potentially dangerous or virtually harmless components. The identification of IgE in components with specific characteristics has a direct impact on the accuracy of the diagnosis (indeed, it is possible at present to not only identify the allergen derived from a given allergen source but also the family of molecules to which the patient is sensitized), on the prognosis of the patient's allergy, and on the prevention activities to be implemented. More interestingly, during the last few years, and thanks to the tools of molecular diagnostics, the indications for Allergen Immunotherapy (AIT) have also be modified, and novel strategies for the selection of the allergens to be administered have been better defined. Indeed, protocols indicating how Molecular Based Diagnosis (MBD) can be used to identify the best AIT approach have been recently published. In this review, the rationale for the use of MBD tools is discussed, and the recent strategies for the choice of allergens to be used in AIT are reported

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Adherence issues related to sublingual immunotherapy as perceived by allergists

Objectives: Sublingual immunotherapy (SLIT) is a viable alternative to subcutaneous immunotherapy to treat allergic rhinitis and asthma, and is widely used in clinical practice in many European countries. The clinical efficacy of SLIT has been established in a number of clinical trials and meta-analyses. However, because SLIT is self-administered by patients without medical supervision, the degree of patient adherence with treatment is still a concern. The objective of this study was to evaluate the perception by allergists of issues related to SLIT adherence. Methods: We performed a questionnaire-based survey of 296 Italian allergists, based on the adherence issues known from previous studies. The perception of importance of each item was assessed by a VAS scale ranging from 0 to 10. Results: Patient perception of clinical efficacy was considered the most important factor (ranked 1 by 54% of allergists), followed by the possibility of reimbursement (ranked 1 by 34%), and by the absence of side effects (ranked 1 by 21%). Patient education, regular follow-up, and ease of use of SLIT were ranked first by less than 20% of allergists. Conclusion: These findings indicate that clinical efficacy, cost, and side effects are perceived as the major issues influencing patient adherence to SLIT, and that further improvement of adherence is likely to be achieved by improving the patient information provided by prescribers. © 2010 Scurati et al, publisher and licensee Dove Medical Press Ltd

Male osteoporosis and hymenoptera venom anaphylaxis [Osteoporosi maschile e anafilassi da imenotteri]

Mastocytosis is one of the rare causes of unexplained osteoporosis, above all in males. On the other hand, a strict association between severe systemic reactions after hymenoptera sting and mastocytosis was recently demonstrated. Here we report a case of unexplained severeosteoporosis with multiple vertebral fractures in a 48 years old male, which also suffered an anaphylactic reaction afterhymenoptera sting. Among laboratory tests performed to clarify the cause of osteoporosis, serum tryptaseconcentrations were determined. The value of tryptase was 43.6 \u3bcg/L, four times higher than the upper reference limit.Skin did not show abnormalities; bone marrow vertebral biopsy was not valuable, but bone marrow aspirate from iliaccrest demonstrated the presence of atypical mast cells expressing CD25; D816V mutation of KIT gene was alsoidentified. These findings, in association with an increase of serum tryptase concentrations, fulfil all minor criteriarequested for the diagnosis of systemic mastocytosis. Osteoporosis treatment with zolendronate and vitamin Dsupplementation was started, but later, for the persistence of bone pain, therapy with -interferon was added. This caseconfirms that an unexplained osteoporosis, especially if associated with hymenoptera sting systemic reaction, requiresexclusion of a systemic mastocytosis

Urban air pollution and climate change: "The Decalogue: Allergy Safe Tree" for allergic and respiratory diseases care

Background: According to the World Health Organization, air pollution is closely associated with climate change and, in particular, with global warming. In addition to melting of ice and snow, rising sea level, and flooding of coastal areas, global warming is leading to a tropicalization of temperate marine ecosystems. Moreover, the effects of air pollution on airway and lung diseases are well documented as reported by the World Allergy Organization. Methods: Scientific literature was searched for studies investigating the effect of the interaction between air pollution and climate change on allergic and respiratory diseases. Results: Since 1990s, a multitude of articles and reviews have been published on this topic, with many studies confirming that the warming of our planet is caused by the "greenhouse effect" as a result of increased emission of "greenhouse" gases. Air pollution is also closely linked to global warming: the emission of hydrocarbon combustion products leads to increased concentrations of biological allergens such as pollens, generating a mixture of these particles called particulate matter (PM). The concept is that global warming is linked to the emission of hydrocarbon combustion products, since both carbon dioxide and heat increase pollen emission into the atmosphere, and all these particles make up PM10. However, the understanding of the mechanisms by which PM affects human health is still limited. Therefore, several studies are trying to determine the causes of global warming. There is also evidence that increased concentrations of air pollutants and pollens can activate inflammatory mediators in the airways. Our Task Force has prepared a Decalogue of rules addressing public administrators, which aims to limit the amount of allergenic pollen in the air without sacrificing public green areas. Conclusions: Several studies underscore the significant risks of global warming on human health due to increasing levels of air pollution. The impact of climate change on respiratory diseases appears well documented. The last decades have seen a rise in the concentrations of pollens and pollutants in the air. This rise parallels the increase in the number of people presenting with allergic symptoms (e.g., allergic rhinitis, conjunctivitis, and asthma), who often require emergency medical care. Our hope is that scientists from different disciplines will work together with institutions, pharmaceutical companies and lay organizations to limit the adverse health effects of air pollution and global warming

Allergic Reactions to COVID-19 Vaccines: Risk Factors, Frequency, Mechanisms and Management

Conventional vaccines have been widely studied, along with their risk of causing allergic reactions. These generally consist of mild local reactions and only rarely severe anaphylaxis. Although all the current COVID-19 vaccines marketed in Europe have been shown to be safe overall in the general population, early post-marketing evidence has shown that mRNA-based vaccines using novel platforms (i.e., lipid nanoparticles) were associated with an increased risk of severe allergic reactions as compared to conventional vaccines. In this paper we performed an updated literature review on frequency, risk factors, and underlying mechanisms of COVID-19 vaccine-related allergies by searching MEDLINE and Google Scholar databases. We also conducted a qualitative search on VigiBase and EudraVigilance databases to identify reports of "Hypersensitivity" and "Anaphylactic reaction" potentially related to COVID-19 vaccines (Comirnaty, Spikevax, Vaxzevria and COVID-19 Janssen Vaccine), and in EudraVigilance to estimate the reporting rates of "Anaphylactic reaction" and "Anaphylactic shock" after COVID-19 vaccination in the European population. We also summarized the scientific societies' and regulatory agencies' recommendations for prevention and management of COVID-19 vaccine-related allergic reactions, especially in those with a history of allergy

Mild/Moderate Asthma Network in Italy (MANI): a long-term observational study

Objective The prevalence of asthma in Italy is estimated to be around 4%; it affects approximately 2,000,000 citizens, and up to 80-90% of patients have mild-to-moderate asthma. Despite the clinical relevance of mild-to-moderate asthma, longitudinal observational data are very limited, including data on disease progression (worsening vs. improvement), the response to treatment, and prognosis. Studies are needed to develop long-term, observational, real-life research in large cohorts. The primary outcomes of this study will be based on prospective observation and the epidemiological evolution of mild and moderate asthma. Secondary outcomes will include patient-reported outcomes, treatments over time, disease-related functional and inflammatory patterns, and environmental and life-style influences. Methods This study, called the Mild/Moderate Asthma Network of Italy (MANI), is a research initiative launched by the Italian Respiratory Society and the Italian Society of Allergology, Asthma and Clinical Immunology. MANI is a cluster-based, real world, cross-sectional, prospective, observational cohort study that includes 20,000 patients with mild-to-moderate asthma. (ClinicalTrials.gov Identifier: NCT04796844). Results and conclusion Despite advances in asthma care, several research gaps remain to be addressed through clinical research. This study will add important new knowledge about long-term disease history, the transferability of clinical research results to daily practice, the efficacy of currently recommended strategies, and their impact on the burden and evolution of the disease

Effectiveness and safety of dupilumab in patients with chronic rhinosinusitis with nasal polyps and associated comorbidities: a multicentric prospective study in real life

Biologics are currently one of the main treatment options for a number of diseases. The IgG4 monoclonal antibody dupilumab targets the Interleukin-4 receptor alpha chain, thus preventing the biological effects of the cytokines IL-4 and IL-13, that are essential for the Th2 response. Several controlled trials showed that dupilumab is effective and safe in patients with atopic dermatitis (AD), severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), thus resulting in approval by regulatory agencies. Aim of the study was to evaluate the efficacy and safety of dupilumab in adult patients with CRSwNP stratified by common overlapping comorbid conditions

Effectiveness and safety of dupilumab in patients with chronic rhinosinusitis with nasal polyps and associated comorbidities: a multicentric prospective study in real life

Background: Biologics are currently one of the main treatment options for a number of diseases. The IgG4 monoclonal antibody dupilumab targets the Interleukin-4 receptor alpha chain, thus preventing the biological effects of the cytokines IL-4 and IL-13, that are essential for the Th2 response. Several controlled trials showed that dupilumab is effective and safe in patients with atopic dermatitis (AD), severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), thus resulting in approval by regulatory agencies. Aim of the study was to evaluate the efficacy and safety of dupilumab in adult patients with CRSwNP stratified by common overlapping comorbid conditions. Methods: We performed a multicenter, observational, prospective study enrolling adult patients with severe CRSwNP who had started dupilumab treatment in the context of standard care from January 2021 to October 2021. Data were collected from twentynine Italian secondary care centers for allergy and clinical immunology, all of which were part of the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). A number of efficacy parameters were used. Patient data were compared using the Wilcoxon test for paired data. All statistical analyses were performed with SPSS version 20 (IBM, Armonk, NY, USA). Results: In total, 82 patients with nasal polyposis were identified. A significant improvement was detected for all the applied efficacy parameters, i.e. 22-item Sino-Nasal Outcome Test (SNOT-22) and bilateral endoscopic nasal polyp score (NPS) scores for CRSwNP, Rhinitis Control Scoring System (RCSS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores for allergic perennial rhinitis, Forced Expiratory Volume in the 1st second (FEV1) and Asthma Quality of Life Questionnaire (AQLQ) scores for asthma, Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI) scores for AD. A non-significant improvement was also obtained in the Urticaria Activity Score over 7 days (UAS7) for chronic spontaneous urticaria. Treatment with dupilumab was well tolerated. Conclusions: These data suggest that dupilumab treatment in patients suffering from CRSwNP and associated comorbidities may be suitable. Such outcome, although confirmation by trials is warranted, suggests the possibility to treat different disorders with a single therapy, with favorable effects especially under the cost-effectiveness aspect