The Global Initiative for Asthma (GINA) provides the most comprehensive and frequently updated guidelines for the management of asthma. The primary aim of guidelines is to bridge the gap between research and current medical practice by presenting the best available evidence to aid clinical decision-making, thereby improving patient outcomes, quality of care, and cost-effectiveness. Guidelines are particularly useful in situations where scientific evidence is limited, multiple treatment options exist, or there is uncertainty about the best course of action. However, due to variations in healthcare system structures, many countries have developed their own local guidelines for the management of asthma. Adoption of GINA recommendations into local guidelines has been uneven across different countries, with some embracing the changes while others continue to follow older approaches. This review article will explore the impact of the noteworthy changes in GINA guidelines, particularly in the 2019 version, on local guidelines and some of the challenges associated with implementing them.

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Allergen-specific immunotherapy (AIT) is a proven efficacy treatment for allergic rhinitis (AR), asthma, and Hymenoptera venom allergy, but its use in food allergy (FA) is still under investigation. Because some efficacy and safety concerns still remain, biologic drugs, including omalizumab and dupilumab, have been studied as an adjunctive therapy to AIT for these conditions. In this article, the evidence supporting the use of monoclonal antibodies (mAbs) as an add-on therapy to AIT for FA, AR, asthma, and Hymenoptera venom allergy has been reviewed. The review will delve into the mechanisms of action of different mAbs, their efficacy, and how they can be integrated into personalized medicine approaches to treat allergic diseases. Furthermore, future research areas will be considered. Evidence suggests that omalizumab in combination with AIT may be a beneficial option for respiratory allergies or food desensitisation, especially during the escalation or build-up phase, when adverse events are more frequent. Currently, there is a small number of well-structured clinical trials in Hymenoptera venom allergy, and the available data consist mainly of single-case reports that provide information of limited value. Dupilumab has been studied as adjunctive therapy in patients with respiratory and FAs. Clinical trials are ongoing to evaluate the efficacy of dupilumab as monotherapy or as an adjunct to oral immunotherapy (OIT) in peanut allergy. Other studies are investigating the use of dupilumab in patients with multiple FAs and as an adjunct to milk OIT. Overall, mAbs have the potential to improve outcomes in various allergic conditions when used as an add-on to AIT, especially during the build-up phase. Further research is needed to fully understand their optimal dosing and duration of treatment, as well as to identify which patients may benefit the most from these therapies.

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It is well known that adolescent patients often have less than optimal outcomes. Adolescence is a time of much transition, physically, emotionally, and socially all of which have effects on asthma management and outcomes. Pubertal changes affect asthma, but mostly it is the move towards independence from the parents, peer pressures, stigma of illness, and adherence issues that cause the issue. It is thus important to learn to treat the patient directly, wherein currently often children are treated through the parent, to ensure success.

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Asthma is a respiratory disease affecting more than 300 million people around the world. Airflow obstruction and inflammation due to asthma usually involve large airways, but recently small airway involvement (internal diameter < 2 mm) has been shown to represent one of the main determinants of asthma and asthma control. In fact, compared to large airway involvement, small airway dysfunction (SAD) has been demonstrated across all the asthma severity in the majority of patients, as assessed with Global Initiative for Asthma (GINA) steps. Clinically, SAD is associated with, among other features, exercise-induced bronchoconstriction, asthma-related night awakenings, obesity/overweight, more severe airway hyperresponsiveness, worse asthma control, and more severe exacerbations. Impulse oscillometry (IOS), a forced oscillation technique (FOT) requiring less effort than spirometry from the patients, demonstrated to accurately measure SAD in children and adults. The fall in resistance from 5 Hz to 20 Hz (R5–R20), which is the most used index for the resistance of peripheral airways, is how SAD is usually identified by IOS. Other crucial parameters measured by IOS are the reactance at 5 Hz (X5), reflecting elastic recoil of the peripheral airways, the resonant frequency (Fres), which is the frequency at which the inertial properties of the airway and the capacitance of the lung periphery are equal, and the reactance area (AX), reflecting the elastic properties of the lung periphery. In this mini review, the latest findings on the utility of IOS to identify SAD and the associations between SAD and clinical features in adult asthmatic patients were addressed.

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Steroid-resistant asthma (SRA) is clinically significant, approximately 10–15% of individuals with asthma do not exhibit a positive response to standard treatments. While this subset represents a relatively small proportion of asthma patients, severe refractory asthma places a substantial burden on healthcare resources and contributes significantly to illness and death. Additionally, the quality of life of patients is greatly affected by the adverse effects of excessive steroid consumption, there is a need to identify individuals who do not react well to steroid medication and the ongoing difficulties of these asthma patients in controlling their diseases, which have a large socio-economic impact. The current short article reviews the common molecular mechanisms responsible for steroid resistance in asthma patients.

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The incidence of asthma, a heterogeneous inflammatory disease affecting over 300 million people worldwide, continues to increase in developed countries. Human epithelial cells (ECs) express the alarmin-type cytokine thymic stromal lymphopoietin (TSLP) following tissue injury triggered by several environmental insults, which include allergens, smoke, pollutants, or other irritants. Furthermore, TSLP has an emerging but well-documented pathogenic role in asthma. TSLP has been called a “master switch” of allergic inflammation at the epithelial-dendritic cell (DC) interface, where it supports T helper 2 (Th2) inflammatory polarization and promotes the maintenance of Th2 memory responses. Therefore, targeting TSLP/TSLP-mediated signaling may represent an attractive therapeutic strategy for asthma. Several studies of anti-TSLP drugs are ongoing; the first-in-class anti-TSLP monoclonal antibody (mAb) tezepelumab, the immunoglobulin G1 antibody fragment CSJ117, or TSLP-traps [a combination of anti-interleukin-13 (anti-IL-13) and anti-TSLP mAbs] all represent promising new treatment approaches. This article reviews the characteristics of TSLP and discusses the treatment of severe asthma through TSLP-associated mechanisms.

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Lettuce allergy is uncommon and usually attributed to lipid transfer protein (LTP) sensitization. Most LTP-sensitized patients present with heterogeneous symptoms not only to lettuce, but to a large number of other foods and pollen allergens, including peaches, apples, Platanus, and mugwort, with peach LTP being considered as the primary sensitizer. The case of a medical student with a history of lettuce allergy investigated by skin prick tests (SPTs) and oral food challenge (OFC) is presented in this report. SPTs showed sensitization exclusively to lettuce and not to any other known cross-reacting allergens, which contrasts with previous literature and highlights the uniqueness of this case. During OFC, the patient developed generalized symptoms including abdominal discomfort, bilateral tinnitus, facial flushing, generalized itching, and urticaria. No cardiopulmonary compromise was observed at the time, and the reaction was managed with oral antihistamines. More sophisticated molecular analysis is required to identify the patient’s sensitization profile; however, SPTs and OFCs remain the most practical clinical approach. Lettuce allergy deserves further attention and investigation.

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Coronavirus disease 2019 (COVID-19) pandemic was a great challenge for healthcare professionals globally and also for allergists/immunologists. The Pegaso low-care COVID center's experience in managing a low-care center for COVID-19 patients was reported, trying to bring out the relevance of this type of structure in reducing the length of stay of patients in high-care settings with the consequent effect of avoiding the collapse of major hospitals. The experience of managing a low-care setting with a day hospital service inside emphasizes, even more, the role of the allergists/immunologists during the COVID-19 pandemic contributing to keeping the medical staff's specialty in a strategic role in the battle against this common enemy. Sharing all the information on public health organizations is crucial to cope in the best possible way with the present and future challenges.

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Eosinophilic granulomatosis with polyangiitis (EGPA) is a multiorganic syndrome that affects the cardiovascular, neurologic, renal, and gastrointestinal systems with an incidence ranging from 0 case to 67 cases per one million person-years, and its pathophysiology remains unknown. It is believed that genetic factors, the environment, and changes in immune system function contribute to the development of EGPA, overlapping the immune mechanisms of vasculitides and the pathologic mechanisms in eosinophilic syndromes. This disease is commonly divided into two phenotypes depending on the presence of antineutrophil cytoplasmic antibodies (ANCA). ANCA-positive patients usually have more vasculitic manifestations like peripheral neuropathy, purpura, renal involvement, and biopsy-proven vasculitis. The keystone of EGPA therapy is systemic corticosteroids (CS) as monotherapy or in combination with other immunosuppressive treatments, and recently the efficacy of eosinophil-targeted biotherapy, anti-interleukin-5 (IL-5), has been shown to be efficacious in EGPA. Although this phenotype/phase distinction has not yet had an impact on the current treatment strategies, emerging targeted biotherapies under evaluation could lead to a phenotype-based approach and personalised treatment regimens for EGPA patients. The present review describes the new therapeutical approaches with biological drugs for EGPA.

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A case report of fish allergy is exposed. The responsible allergen was fish collagen, and there was no sensitization to parvalbumin (main fish allergen). The patient acquired collagen sensitization by occupational exposition, not by ingestion.

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The advent of biological drugs has opened up new therapeutic possibilities in the field of eosinophilic gastro-intestinal diseases (EGIDs). EGIDs are chronic inflammatory diseases of the gastrointestinal tract unrelated to drugs or infections, and eosinophilic esophagitis (EoE) is the most frequent form. EGIDs are complex disorders, which pathogenesis is still partially unknown. The diagnosis of EGIDs relies on the combination of different data, such as clinical manifestations, laboratory tests, endoscopic, and histological data. The gold standard at present is the histological examination obtained from biopsies under endoscopic guidance, but the diagnostic criteria for each disorder are still not fully defined, and few clinical scores are validated, for all these reasons, conducting clinical trials on EGIDs is challenging. The dietary approach remains currently a first-line treatment, despite its efficacy being influenced by patients’ compliance. Exclusion diets, nevertheless, involve potential nutritional deficiencies. Two of the pivotal pharmacological therapies for the treatment of EGIDs are proton pump inhibitors (PPIs), especially for EoE, and systemic or topical steroids. Long-term corticosteroid therapies are, however, associated with even severe side effects, so steroid-sparing therapies are needed to achieve the same results, in the last years monoclonal antibodies have been studied. To date, dupilumab is the only approved biological drug for EoE therapy, but many others are currently being tested in clinical trials also for the other forms of EGIDs. This work presents a complete review of the role of biological drugs in EGIDs to date, systematically structured by pathology.

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Asthma is a chronic condition characterized by inflammation throughout the entire bronchial airways. Recent findings suggest that ventilation inhomogeneity and small airway dysfunction (SAD) play a particularly significant role in asthma development and clinical manifestations. Obesity is a considerable risk factor for asthma development and morbidity in children and adults. A growing body of evidence suggests that SAD is linked to more severe asthma and poor asthma control in obese patients. However, the knowledge about the relationship between peripheral airway compromise and obesity in asthma is limited, mainly because of the historical lack of access to non-invasive assessment methods for studying SAD. Conventional lung function measurements, like spirometry, cannot accurately assess small airway function. However, in recent years, new specialized tests available in outpatient settings have been found to distinguish SAD from large airway obstruction more accurately compared to spirometry. Therefore, understanding the degree of peripheral airway implication in the underlying pathology is critical for effective asthma control and therapeutic decisions. This review highlights recent findings on the impact of SAD on asthma patients who are obese. Additionally, it explores how new diagnostic methods, such as impulse oscillometry (IOS), may be used in outpatient settings to detect small airway impairment in obese asthma at an early stage, potentially leading to improved asthma treatment.

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Non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) is characterized by adult-onset asthma, chronic rhinosinusitis with nasal polyps (CRSwNPs), and aspirin/NSAID hypersensitivity, presenting recurrent asthma exacerbation and poor clinical outcomes. Patients with NERD have heterogeneous clinical phenotypes/endotypes, and the management of NERD remains challenging. Dysregulation of arachidonic acid (AA) metabolism and persistent eosinophilic airway inflammation are the major pathogenic mechanisms in the upper and lower airways of NERD. To date, increased levels of urinary leukotriene E4 (uLTE4) [a terminal metabolite of the lipoxygenase (LOX) pathway] have been the most relevant biomarker for NERD. It is demonstrated that mast cells, platelets, and epithelial cells can amplify upper and lower airway inflammation in NERD, and several potential biomarkers based on these complicated and heterogeneous mechanisms have been suggested. This review summarizes potential biomarkers for application in the management of NERD.

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In Europe, allergen products from different manufacturers can be labeled using the same unit with yet different definitions of that unit, which may cause confusion, as is the case for the index of reactivity (IR). In this context, house dust mite (HDM) Staloral 300 IR/mL, from Stallergenes Greer, and HDM Osiris 300 IR/mL, from ALK-Abelló, were characterized in vitro. Qualitatively, namely in terms of protein and allergen profiles, the two products were similar. Quantitatively, and despite the same 300 IR/mL labeling, the two products were shown to have different biological potencies, with HDM Staloral 300 IR/mL displaying a 2.4 times higher total allergenic activity (TAA) than HDM Osiris 300 IR/mL. This higher biological potency of HDM Staloral 300 IR/mL was paralleled by higher allergen and protein contents, namely 1.5 times more Der p 1 and Der f 1, 3.0 times more group 2 allergens, 2.7 times more Der p 23, and 1.8 times more protein. In contrast, HDM Staloral 300 IR/mL was shown to contain far fewer culture medium-derived proteins than HDM Osiris 300 IR/mL.

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Nutritional therapy through exclusive enteral nutrition (EEN) is successful with Crohn’s disease (CD), but most patients relapse when returning to a normal diet. Personalized and sustainable diets over time have not been tried. This pioneering case report shows the successful response to the use of a skin prick test (SPT) with a 0.5 mm cutoff and a combination of parameters to guide the diet of a child with CD, ensuring continued remission and a regular diet over a follow-up period of 3 years. The 5-year-old patient had a history of chronic diarrhea. Laboratory showed anemia, hypoalbuminemia, high erythrocyte sedimentation rate (ESR), and fecal calprotectin (FCP) > 2,100 µg/g. Endoscopies revealed duodenal ulcer scar and ulcerative pancolitis. Simple endoscopic score for CD score (SES-CD) = 16 (severe). Pathology showed CD. EEN started with a polymeric formula, later moving to an elemental formula due to a suboptimal response. Medication included prednisolone, mesalazine, azathioprine, and methotrexate. Foods were introduced guided by the SPT and included 54 protein extracts from food tested every 3–4 months. The patient has clinical and histological remission despite having lamb, turkey, eggs, cereals (including wheat), and fish in his diet. FCP has been measured with every change in diet and maintained at < 100 µg/g with the reintroduction of food, with the exception of fish and eggs which, despite a negative SPT, gave mild symptoms and raised FCP to 223 µg/g. Both eggs and fish were successfully reintroduced (FCP < 100 µg/g) after 7 and 11 months respectively from failed reintroduction. This innovative approach based on SPT and strict clinical and follow-up inflammatory markers can potentially ensure remission, reintroducing foods with objective parameters, and improving the patient’s quality of life.

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