Asthma is a common chronic inflammatory disease of the airways that affects more than 330 million people globally. Severe asthma, despite being 5–10% of the total asthmatic population presents significant morbidity and high cost due to health care utilization. The management of severe asthma has dramatically changed with the use of biologics. However, biologics have been approved only for patients with severe asthma with type-2 mediated inflammation. Eosinophils are central in the T2 inflammatory process in asthma and this stands true for the severe form of the disease as well. In this review, we discuss basic insights into the pathogenesis of severe asthma related to eosinophilic inflammation and the pivotal role of T2 cytokines which have also become along with eosinophils the target of biologics. Novel biologics such as tezepelumab have demonstrated efficacy regardless of the blood eosinophil count and have shown promise for T2 low asthma, although to a lesser degree.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Glucagon-like peptide-1 (GLP-1) is a hormone that regulates blood glucose levels and is produced by the enteroendocrine glands in the large and small intestines in response to the consumption of foods that contain carbohydrates, fats, and proteins. When GLP-1 is secreted, it acts on the pancreas to increase insulin production and secretion, while decreasing pancreatic glucagon secretion in order to lower serum glucose. However, GLP-1 also regulates metabolism through the gut-brain axis. While GLP-1 is primarily produced in the gut and released into the bloodstream, small quantities of it can also be synthesized in distinct areas of neurons located in the hindbrain. Recent studies have proposed that GLP-1 receptor (GLP-1R) agonists (GLP-1RAs) may protect against neuroinflammatory diseases. GLP-1RAs may also be a therapeutic target for asthma as animal models show that these drugs reduce allergen-induced airway inflammation, as the GLP-1R is expressed on lung epithelial and endothelial cells. There is a notable association between insulin resistance and the onset of asthma, particularly among obese people, with this association suggesting that metabolic dysfunction may play a role in asthma development. There is also evidence that there may be a link between asthma pathobiology and neuroinflammation, suggesting that GLP-1 and its analogs may regulate neuroinflammatory pathways that contribute to asthma pathogenesis. Interest is growing, though research remains limited, in how inflammation in the nervous system and lung might be linked. This review will explore how GLP-1R signaling could inhibit interdependent inflammation in both the lung and nervous system. This review will first focus on the inflammation that is known to exist in asthma, then pivot to the current state of neural regulation of asthma, and finally speculate on how GLP-1RA signaling could inhibit both neural and lung inflammation in asthma treatment.

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.

Atopic dermatitis (AD) represents the most common inflammatory skin disease with a highly intricated immune fingerprint. Until recently, AD management mostly relied on topical corticosteroids, calcineurin inhibitors, and systemic immunosuppressants, with a range of safety and tolerability concerns including toxicity, drug interactions, and contraindications. With the onset of biologics, safer and more targeted therapeutics have become available, displaying various degrees of success in treating AD, but not yet able to meet all the needs of AD patients. Some of the challenges encountered included variability of responses among patients, long-term safety, and limited access due to prohibitive costs. As the pathophysiology of AD has been increasingly understood within the last years, new approaches are explored, leading to an unprecedented diversification of therapeutic options to address these hurdles. This review highlights current immunotherapeutic strategies developed towards AD, whether already in the clinical pipeline or still in preclinical exploration.

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder affecting millions worldwide, with significant variations in clinical presentation influenced by socioeconomic, racial, and environmental factors. This review explores the current understanding of AD pathophysiology, emphasizing immune dysregulation, epithelial barrier dysfunction, and the role of cytokines, particularly interleukin (IL)-4 and IL-13, in disease progression. Safety and efficacy concerns limit traditional corticosteroids, phototherapy, and systemic immunosuppressants, prompting interest in innovative therapies. New biologic agents, including monoclonal antibodies (mAbs) and Janus kinase (JAK) inhibitors (JAKis), target specific immune pathways, promising outcomes in moderate-to-severe AD cases. Biologics like dupilumab and emerging JAKis have shown substantial efficacy and safety in clinical trials, with notable reductions in inflammation and pruritus. However, these advancements present challenges, including hypersensitivity risks and the high costs of biologics, underscoring the need for further research on long-term safety and accessibility. The shift toward precision medicine in AD management marks a significant evolution, with future approaches likely to integrate targeted therapies alongside multidisciplinary care to enhance patient outcomes and quality of life (QoL).

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.

Food protein-induced enterocolitis syndrome (FPIES) is an allergic disorder that manifests as reproducible gastrointestinal symptoms within hours of ingestion of the causative food, which can progress to dehydration and hypotension. Historically, FPIES has been recognized as a disease affecting the pediatric population but it can also develop de novo in adults. The pathophysiology is not well understood; however, the local adaptive immune system and gene expression linked to innate immune activation are implicated. Adult-onset FPIES has some differences with pediatric FPIES. Vomiting may be absent, while abdominal pain is the most common manifestation. A clear predominance in women occurs, being seafood the most common trigger, although many other foods have also been implicated. Diagnosis of adult-onset FPIES is based on a thorough clinical history but in many cases, it should be followed by an oral food challenge (OFC), due to the absence of vomiting in some patients and the lack of confirmatory diagnostic test. The first-line treatment for acute FPIES reactions is fluid replacement, by the oral route in mild to moderate reactions or via the intravenous route in severe reactions. Ondansetron may be effective in shortening the duration of emesis. Management of patients after diagnosis includes dietary advice and follow-up with supervised OFC at regular intervals to monitor for resolution. Tolerance to the trigger food in children is commonly achieved, a finding not so common in adult-onset FPIES. The aim of this article is to review the most important current concepts in epidemiology, pathophysiology, diagnosis, and management of FPIES.