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.

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.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that primarily affects the barrier function of the skin in patients. The condition has been documented to cause xerosis in patients from birth onwards. In order to protect the skin barrier in AD, it is of the utmost importance to moisturize the skin. Moisturizers and emollients play a pivotal role in the prevention and treatment of AD. Concordantly, the use of moisturizers and emollients can facilitate the reduction in the necessity for the application of topical treatments such as corticosteroids. An understanding of the use of moisturizers and emollients, in conjunction with an appreciation of the pathophysiology of the skin barrier, will prove invaluable in the treatment of AD.

Allergen-specific immunotherapy for inhalant allergies, using allergen extracts of proven value, is highly effective in selected patients with allergic rhinoconjunctivitis and allergic asthma. Both subcutaneous and sublingual immunotherapy (SLIT) have been shown to modify the underlying cause of the disease, with long-term clinical benefits that persist for years after their discontinuation. Real-world studies have confirmed the long-term efficacy of allergen immunotherapy in allergic rhinitis (AR) and asthma and shown a reduction in the incidence of lower respiratory tract infections. Sublingual house dust mite (HDM) immunotherapy has been suggested to improve innate antiviral immunity—a likely explanation for this finding. Based on robust randomized controlled trials, the Global Initiative for Asthma (GINA) guideline has incorporated the use of SILT for the treatment of adults with HDM-driven asthma and concomitant AR, with sub-optimal control, regardless of the use of low-to-high doses of inhaled corticosteroids, as long as the patient’s forced expiratory volume in 1 second (FEV₁) is > 70%.

Asthma is one of the most common respiratory diseases in humans throughout the world. The illness continues to be the most prevalent cause of respiratory morbidity and affects both adults and children. Asthma is mainly caused by microbes, especially the species of Aspergillus. It causes continuous irritation and distracts the mental attention of the patient, leading to physical weakness and depression resulting in immune-compromised conditions. Asthmatic patients need careful attention and continuous treatment. Taking into account its major effects on patients’ quality of life, the challenging nature of the therapy, and side effects of the novel therapeutic strategies that influence the clinical course of asthma are required to be considered before finally deciding the course of treatment. Children with asthma and wheezing are frequently sustained by a type-2 immune response. In addition, people with wheezing and asthma can be identified by the presence of digestive and respiratory tract dysbiosis. Therefore, oral probiotics could be used as an additional asthmatic medication to manage asthma, but the decision should be constantly monitored by specialized persons. During the last two decades, the importance of probiotics in the treatment of various ailments has been realized and several researches are being conducted to find out the impact of healthy gut microbiome on the management of various diseases including asthma.

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.

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.

Asthma is the most common chronic disease during childhood. While most of characteristic structural changes in asthma have been identified in the large airways, there is a growing recognition of peripheral airway dysfunction as a crucial factor in the development of asthma. This dysfunction is a defining feature in adults with persistent asthma. However, little is known about the contribution of small airway impairment in children with asthma due to the relatively low sensitivity of conventional lung function tests, such as spirometry. Recently, new diagnostic tools that are sensitive to both large and small airway function and inflammation have been introduced in clinical practice. The most widely studied of these tools in preschool and school-aged children is impulse oscillometry (IOS). This review addresses the latest findings on the usefulness of IOS in identifying small airway dysfunction, predicting the risk of uncontrolled asthma, and ultimately improving the diagnosis and management of asthma in children.

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.

Seaweed, a rich source of bioactive compounds, has gained increasing attention for its potential therapeutic applications in allergy and inflammation. This review examines the current scientific literature investigating the effects of seaweed derived food and diet factors on allergic and inflammatory conditions. Seaweed is abundant in polysaccharides, peptides, polyphenols, and fatty acids, which possess anti-inflammatory, antioxidant, and immunomodulatory properties. These bioactive compounds have the capacity to modulate immune responses and mitigate allergic reactions, rendering seaweed a promising candidate for the development of functional foods and dietary interventions targeting allergy and inflammation. Explorations into the effects of seaweed consumption on allergic conditions such as allergic rhinitis, asthma, and atopic dermatitis have shown encouraging results. Factors found in seaweed have the potential to alleviate symptoms, reduce inflammation, and boost immune function in allergy sufferers. Furthermore, inquiries into the effectiveness of diets incorporating seaweed in preventing and managing chronic inflammatory conditions like inflammatory bowel disease and rheumatoid arthritis have been undertaken. The mechanisms underlying the therapeutic effects of seaweed derived compounds are being unraveled, revealing their ability to modulate immune cell activity, regulate cytokine production, inhibit inflammatory mediators, and promote gut microbiota balance. Understanding these molecular mechanisms is crucial for targeted interventions and the identification of specific bioactive compounds responsible for the observed therapeutic effects. Seaweed derived food and diet factors hold significant promise as natural interventions for the prevention and management of allergic and inflammatory conditions. However, further research is required to establish the optimal dosage, formulation, and long-term effects of seaweed-based interventions. Additionally, clinical trials are necessary to validate their efficacy and safety in diverse patient populations. This review emphasizes the therapeutic potential of seaweed derived compounds and underscores the importance of incorporating seaweed into dietary strategies to combat allergy and inflammation.

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.

Eosinophilic gastrointestinal diseases (EGIDs) are a group of chronic conditions, characterized by an excessive accumulation of eosinophils in various areas of the mucosal of the gastrointestinal (GI) tract. EGIDs encompass a spectrum of diseases, including eosinophilic esophagitis (EoE), eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC), each affecting different segments of the GI tract. The pathogenesis of EGIDs is multifaceted and involves an intricate interplay between genetic predisposition, environmental triggers, and dysregulated immune responses. Although the exact etiology behind EGIDs is not fully understood, it is clear that they are immune-mediated, with eosinophils having a central role in inflammation and tissue damage of GI mucosal. Clinical manifestations depend on the organ that is affected by the disease and on the depth of the eosinophil infiltration of the bowel wall. They range from mild discomfort to severe dysphagia, abdominal pain, malnutrition, and growth failure, particularly in pediatric cases. Regarding EGID management, it is a challenging issue to achieve clinical and histologic remission using pharmacotherapy and dietary elimination. Corticosteroids and proton pump inhibitors can be selected as an effective first-line treatment for certain patients and six-food elimination diet (6-FED) has been proven effective in inducing remission. Furthermore, biologic therapies have emerged as essential tools in controlling eosinophilic-driven inflammation. This review focuses on the complex pathogenesis and treatment of these inflammatory diseases, especially EoE.

Food allergy is characterized by an abnormal immune reaction that occurs reproducibly upon exposure to a specific food. This immune response can lead to a variety of symptoms, the prevalence of food allergies has increased in recent decades, most likely due to environmental factors that likely play a role in the expression of genetic susceptibility. Recent understanding of the immunopathogenesis of allergic diseases has suggested that these atopic diseases may be due to monogenic mutations associated with inborn errors of immunity (IEI). Aspects to be assessed in suspected IEI involve the onset of atopic disease within the initial months of life, the progression of the condition, and the response to conventional therapy. A prospective study was conducted on 385 patients admitted to the clinic with suspected immunodeficiency. Most children were referred for recurrent respiratory infections, but almost half had concurrent atopy (44%), atopy and autoimmunity (3%), autoimmunity (6%) and malignancy (1%). The results of the study underline the importance of the allergic phenotype and suggest that children with more severe allergic diseases should be screened for possible underlying inborn defects of immunity. If a congenital disorder of immunity is suspected, comprehensive immunologic testing is required, and genetic testing is essential to identify the specific genetic abnormalities. Molecular diagnosis provides a comprehensive understanding of congenital immune disorders, allowing tailored interventions and personalized surveillance strategies.

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.

Allergic and immunologic skin diseases are becoming increasingly common and this requires clinicians to be able to recognize and diagnose them. A joint meeting (GET TOGETHER 2022) of the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC) and the Italian Society of Allergological, Occupational and Environmental Dermatology (SIDAPA) aimed to review the current knowledge on the differential diagnosis of contact dermatitis, atopic dermatitis, hereditary angioedema, urticaria, and cutaneous mastocytosis. The most important aspects to take into consideration when faced with a new cutaneous manifestation are the clinical features of the lesions, their distribution, age of onset, and comorbidities/aggravating factors. The document does not aim to provide an exhaustive and comprehensive description of all allergic and immunologic skin diseases. Instead, it should be a reference tool for the clinician who is faced with the onset of a new skin manifestation and its differential diagnosis.

Chronic rhinosinusitis (CRS) is an inflammatory disorder of the paranasal sinuses and the nasal cavity lasting longer than 12 weeks. This disease is a common clinical syndrome with significant monetary burden due to the high costs of medical visits, diagnostic tests, medications, and surgical therapies. CRS without nasal polyposis (CRSsNP) is the most common subtype of CRS, accounting for about 70% of all patients. Other subtypes include CRS with nasal polyposis (CRSwNP) and allergic fungal rhinosinusitis (AFRS). CRSwNP has the worldwide prevalence of 2% to 4% and is often accompanied by type 2 inflammation and asthma as a comorbid condition. Pediatric chronic sinusitis is distinct from adult chronic sinusitis and is currently considered an infectious process, characterized by persistent inflammation representing an exaggerated immune response to an external stimulus. The medical and surgical management of CRS has been remarkably modified in the past two decades. The aim of this study was to present an update on CRS based on the recent years’ literature.

There are no plausible arguments to consider that the best evidence-based asthma treatment should be different in low- and middle-income countries (LMICs). A few decades ago, the recognition of asthma as an inflammatory disease of the airways positioned the inhaled corticosteroids (ICS) as the cornerstone of the treatment of this disease, maintaining bronchodilators, especially the short-acting beta-agonists (SABA), as symptom-reliever medications for use as needed. However, adherence to regular use of ICS is very low, especially in LMICs, favoring the overuse of SABA, which has been related to an excess of exacerbations and mortality. Recently, the Global Initiative for Asthma (GINA) strategy has recommended the mandatory use of ICS every time a bronchodilator is used as needed (for symptoms relief), whether only as needed or with a background of regular dose of ICS, and has named it: anti-inflammatory reliever (AIR) therapy. This form of therapy, which has been related to a significant reduction of asthma exacerbations, is very attractive for LMICs where patients do not have guaranteed a proper medical follow-up and the access to on-the-counter medications is high. However, the implementation of AIR therapy in LMICs will face many of the already recognized barriers for the diagnosis and treatment of asthma in these countries, especially related to limited access to care in very different health systems, low education level of patients and communities, insufficient health personnel training in asthma in primary care, the unfordable cost of medications, and the lack of political commitment. This review analyzes some of these challenges and strategies for facing them in LMICs.

Multiple chemical sensitivity (MCS) is an unexplained acquired medical condition that includes multiple, vague, recurrent, and non-specific symptoms in different organs. They are attributed to exposures to various and structurally unrelated environmental chemicals at concentration levels that are well tolerated by the majority of people and normally considered not to have toxic effects in humans. The aim of this review is to examine the multiple explanatory hypotheses for the pathophysiology of MCS: genetic, metabolic, neurological, immunological, and psychological. Several publications suggest a neurological and immunological activation. However, this neurological and immunological hyperresponse is not always observed when performing challenge tests. This suggests that behavioral conditioning could be an important mechanism in the pathogenesis of MCS. Even if psychiatric conditions appear not to be a major cause of MCS, in the case of genuine psychiatric disease, psychotherapeutic therapy is mandatory. Because of the complexity of the pathophysiology, there is no specific drug to treat MCS. However, the use of cognitive behavioral therapy is encouraged, as it has a significant positive impact on patients’ perception of their illness.