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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Desensitization (DSZ) or oral tolerance induction is increasingly used in children who do not outgrow their food allergies. Off-label omalizumab (OMZ) is used as adjuvant therapy for those with severe reactions, but there is little information on outcomes when OMZ is withdrawn. The long-term outcome in a group of children with severe milk or egg allergy who had undergone an OMZ-assisted DSZ procedure is here described. Clinical data from 21 children from the time they started DSZ until database closure were retrospectively collected, to assess the appearance of symptoms and response to clinical decisions under real-life conditions. Patients received OMZ before, during, and after the DSZ procedure itself and OMZ was subsequently discontinued. The scheduled treatment protocol had to be changed in almost all patients due to reactions or individual needs. Three of 21 patients had to prematurely abandon the procedure due to DSZ failure. The other 18 patients were able to tolerate the target dose of food, but nine of them developed symptoms when eating the food 1.5 to 6 months after stopping OMZ. These patients underwent a second course of OMZ-assisted DSZ, which was successful in six, but three had a second relapse 3 to 8 months after stopping OMZ and decided to quit. OMZ-assisted DSZ failed in almost a third of patients with severe allergy even after a second course of OMZ, almost 40% had a successful outcome with one course of OMZ, while almost a third required a second course. Relapses of symptoms occurred up to six months after stopping OMZ.

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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.

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Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and paranasal sinuses. Eosinophilic inflammation is described as a common endotype. The anti-interleukin-5 (IL-5) antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe CRSwNP when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, therapy monitoring and follow-up documentation are required, and therapy discontinuation has not been adequately established yet. In this paper, recommendations for monitoring the course and efficacy of therapy as well as for reviewing the duration and possible termination of therapy are provided. For this purpose, a literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching MEDLINE, PubMed, and the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including October 2022 were considered. Based on the international literature and previous experience, recommendations for follow-up, adherence to therapy intervals and possible therapy breaks, as well as termination of therapy when using mepolizumab for the indication CRSwNP in the German health care system are given by an expert panel on the basis of a documentation sheet.

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Coronavirus disease 2019 (COVID-19) was declared a global pandemic by the World Health Organization (WHO) in March 2020. Despite the availability of therapies and the adoption of security measures, the most effective method to fight COVID-19 remains the induction of immunity through vaccines. Scientific communities have developed several types of COVID-19 vaccines since the beginning of the pandemic, including those with innovative messenger RNA (mRNA) technology. Patients with a history of allergic reactions may have an increased risk of hypersensitivity reactions to COVID-19 vaccines. Therefore, it is important that these patients are evaluated by an allergist to help monitor immediate-type adverse reactions and identify what vaccine component may elicit an allergic reaction. Various strategies have been suggested to prevent hypersensitivity reactions, including performing skin tests or in vitro tests before vaccination in high-risk patients, administering a different vaccine for the second dose in subjects reporting adverse reactions to the first dose, fractional dosing, or pretreating with anti-immunoglobulin E (IgE) monoclonal antibody. The scope of this review is to evaluate, through current evidence available in the literature, the accuracy of skin testing to the excipients of COVID-19 vaccines, especially polyethylene glycol (PEG) and polysorbate, in predicting allergic reactions to vaccination, despite the existing discordance of data and approaches to the question from the various clinical experiences, as to permit the safe administration of COVID-19 vaccines to populations around the globe.

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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.

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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%.

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Respiratory changes are often associated with anxiety disorders, particularly panic disorder (PD). Individuals experiencing PD are subjected to unexpected panic attacks, marked by overwhelming anxiety and fear, leading to a variety of autonomic and respiratory symptoms. PD patients have increased sensitivity to carbon dioxide (CO₂). In response to respiratory stimulants like CO₂, patients with PD tend to hyperventilate and panic, triggering the activation of an excessively reactive fear network. While their respiratory physiology may appear normal, the presence of subtle breathing abnormalities and other functions related to bodily homeostasis. This fear network, comprising the hippocampus, medial prefrontal cortex, amygdala, and its connections to the brainstem, seems to be hypersensitive in PD’s patients. This review aims to present a comprehensive overview of the current landscape on the link between PD and respiratory disorders. In July 2023 a literature search was undertaken for articles examining the relationship between PD, respiratory disorders, and psychological implications. Multiple databases were searched: PubMed, PubMed Central, PsycINFO, Web of Science, Elsevier Journal, Health & Medical Collection, and Springer. The analysis of six studies focused on the correlation between PD and asthma revealed important links between these two disorders. Anxiety and panic can have significant impacts on the manifestation and aggravation of asthma. Furthermore, the review indicates that psychological therapeutic approaches, in particular cognitive-behavioral therapy, may represent a valid intervention to improve clinical outcomes in patients suffering from both disorders. Future investigations in this field may help highlight new intervention strategies in the psychological area to help individuals with PD decrease concomitant asthma, significantly improving their quality of life.

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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.

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Recent data has resulted in an interest in the metabolic shift in cellular metabolism to aerobic glycolysis, increased reactive oxygen species (ROS), and mitochondrial dysfunction associated with asthma. There has been a push to better understand the immune and metabolic changes in allergy to improve understanding of disease pathology and treatment. Aerobic glycolysis seen in epithelial cells in asthma promotes chronic inflammation and the production of inflammatory cytokines. Asthma epithelial cells share a number of features proposed in the stages of cancer initiation including aerobic glycolysis and increased apoptosis with proliferation, all within a chronic inflammatory microenvironment. Metabolic reprogramming in malignant cells has been widely investigated since the glycolytic characteristics were first described last century. It is still debated whether these metabolic changes are the cause or consequence of carcinogenesis and oncogenic cell-selective pressures. Although historic results have been conflicting, recent data has found an increased lung cancer risk in asthma patients, independent of risk factors. A review of emerging research on the metabolic changes seen in asthma helps us to propose a pathway between the initiation of aerobic glycolysis and the selective pressures of the epithelial microenvironment and resulting malignant transformation risk.

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