Severe pediatric asthma is a very challenging type of asthma for both physicians and patients. Precision medicine in severe pediatric asthma has undergone important developments in recent years. This therapeutic approach requires an adequate diagnosis and clinical phenotyping of patients and is useful for predicting the prognosis and response to treatment in this type of patient. This article summarizes the scientific information of the last five years in the diagnosis of severe pediatric asthma, focusing on topics such as genetic markers, biomarkers, lung function, radiological techniques, and bronchoscopy.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by a compromised epidermal barrier and heightened immunoglobulin E (IgE) levels, often associated with filaggrin (FLG) gene mutations. Genetic factors like FLG mutations and environmental influences, including microbial exposure and pollutants, contribute to the disease’s progression, leading to itchy, inflamed skin. AD frequently coexists with allergic conditions, severely affecting the quality of life. The disease’s pathogenesis involves complex interactions between genetic predispositions, immune responses, and environmental triggers. Despite advances, the development of effective treatments remains challenging due to an incomplete understanding of how FLG mutations influence immune pathways and the variability in AD presentation. Current biomarkers are insufficient to fully capture disease complexity or predict therapeutic responses, highlighting the need for novel biomarkers and personalized approaches. Emerging therapies such as chimeric antigen receptor (CAR)-T cell therapy, stem cell therapy, and regenerative medicine show promise in addressing AD’s root causes. This review explores key aspects of AD pathogenesis, focusing on epidermal barrier dysfunction, immune mechanisms, and the need for innovative therapeutic strategies to improve patient outcomes.

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.

A granulomatous vasculitis of the medium and large vessels, giant cell arteritis (GCA) is a persistent, idiopathic condition. The overlapping phenotypes of this condition include conventional cranial arteritis and extra-cranial GCA, also known as large-vessel GCA. Vascular problems linked with considerable vessel involvement may partly be caused by delayed diagnosis, emphasizing the necessity of early detection and the fast beginning of appropriate therapy. The cornerstone of treatment for GCA is glucocorticoids, but using them for an extended period has numerous, often severe, side effects. We aim to explore the most recent literature on GCA therapies to investigate the current and potential therapeutic options for induction and maintaining treatment in GCA. By now, only tocilizumab is approved for GCA treatment, but several other biological drugs may be efficient and safe for GCA patients, like abatacept, baricitinib and upadacitinib, mavrilimumab, secukinumab, ustekinumab, and anakinra.

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.

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.

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.

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.

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.

Bronchiectasis is a heterogeneous chronic lung disease, characterised by irreversible dilatation of the airways and attributed to a wide spectrum of other underlying conditions, usually underdiagnosed and inadequately treated with a high burden for both the patients and the healthcare system. The way bronchiectasis is viewed by physicians has drastically changed over the last decades, with the topic of eosinophilia in the context of the disease being one of the substantially highlighted. Eosinophilia was traditionally considered as a means for distinguishing bronchiectasis from asthma, whereas bronchiectasis was primarily associated with neutrophilic inflammation. However, eosinophilic bronchiectasis is nowadays identified as a distinct disease endotype and is associated with a specific clinical course and response to treatment. Further research is needed to better characterise this endotype and improve its personalised investigation and management in daily clinical practice.

This review delves into the complex role of 12/15-lipoxygenase (12/15-LOX) in asthma pathogenesis, focusing on its contributions to mitochondrial dysfunction, oxidative stress, epithelial injury, and airway remodeling. We provide new insights into potential therapeutic strategies aimed at improving asthma management. Additionally, we examine the pro-inflammatory functions of interleukin-4 (IL-4) and its regulatory mechanisms that upregulate 12/15-LOX, leading to increased oxidative stress and airway remodeling. Key interventions such as vitamin E, esculetin, and baicalein are highlighted for their potential to inhibit 12/15-LOX activity, reduce oxidative stress, and restore mitochondrial function. Vitamin E suppresses IL-4 transcription, reducing 12/15-LOX expression and its inflammatory metabolites, while esculetin and baicalein directly inhibit 12/15-LOX, mitigating inflammation and oxidative damage. These antioxidants also promote mitochondrial biogenesis, protect mitochondrial DNA, and enhance respiratory efficiency, contributing to improved cellular metabolism and reduced apoptosis. This comprehensive approach emphasizes the therapeutic potential of targeting 12/15-LOX pathways to alleviate asthma symptoms and improve patient outcomes, paving the way for novel treatment strategies that significantly enhance asthma therapy.

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).

Chronic rhinosinusitis (CRS) is a prevalent and burdensome condition worldwide, characterized by inflammation of the paranasal sinuses. Ideally, instead of treating CRS, we would identify ways to prevent the development of this chronic condition. Occupational exposures may be an excellent target for prevention. Occupational exposures have been shown to play a critical role in the pathogenesis of multiple lower airway diseases, such as asthma, silicosis, asbestosis, and hypersensitivity pneumonitis. However, evidence for the association between occupational exposures and the development of upper airway disease, like CRS, is less well-defined. This manuscript examines the association between occupational exposures and CRS. A scoping review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines identified 19 relevant studies. The populations examined and the methods and criteria used for defining CRS diagnosis and occupational variables significantly varied between the studies. Diagnosis of CRS was most often determined by self-reported symptoms or medical record review. Occupational variables ranged from employment status to occupation type to specific exogenous compounds encountered. Overall, substantial evidence demonstrates a general association between occupational exposures and CRS diagnosis; however, limitations in study methodologies, including variations in CRS diagnostic criteria, occupational exposures, assessment methods, and populations, hinder drawing more specific conclusions. Moving forward, rigorous research methodologies and standardized criteria are essential to draw conclusions supported by multiple studies. Critical components of future studies should include large, diverse populations, use of consensus CRS diagnostic criteria, and inclusion of many specific and quantitatively defined exposures. Ultimately, such efforts can help inform preventative measures and interventions for CRS, thus mitigating the burden of CRS on individuals and populations worldwide.

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.

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.

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.