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.

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.

Asthma is a complex inflammatory airway disease affecting a significant global population, spanning from childhood through adulthood. Despite advances in treatment modalities, a significant subset of patients, approximately 10%, grapple with severe asthma, characterized by increased healthcare utilization and diminished quality of life. Tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), offers promising therapeutic potential. TSLP is a protein released by a variety of cells, with a predominance of epithelial cells, in reaction to plenty of stimuli, such examples as viruses, aeroallergens, and others. Its action is upstream and pertains to initiating numerous subsequent innate and adaptive immune reactions, contributing to the continuation of asthma pathophysiological processes. Tezepelumab’s unique efficacy spans diverse severe asthma phenotypes, significantly reducing exacerbation rates across eosinophilic and non-eosinophilic subtypes. Its favorable safety profile and clinically meaningful improvements in asthma control, accompanied by reductions in cytokine levels and baseline biomarkers, underscore its broad impact on asthma inflammation. Its efficacy, irrespective of type 2 (T2) endotype, reinforces the idea that TSLP blockade broadly inhibits pathways crucial to asthma pathophysiology, rather than narrowly focusing on individual downstream factors, as previous biological treatments have. This review discusses the rationale for TSLP blockade and the efficacy of tezepelumab in severe asthma using data from key trials.

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.

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.

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 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.

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.

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.

In recent decades, atopic diseases, such as atopic dermatitis (AD), allergic asthma (AA), allergic rhinitis (AR), and food allergy (FA) have been estimated rapidly increasing in prevalence. These diseases are characterized by the presence of specific immunoglobulin E (sIgE) and often relate to each other and develop in sequence (the so-called “atopic march”). AD may be the first early manifestation in infants followed by FA often within the first year of life. Moreover, AD is a risk factor for developing sensitization to airborne allergens later in life that can cause clinical manifestations of AA and AR. According to the dual-allergen exposure hypothesis, allergic sensitization to food allergens is promoted through cutaneous exposure, rather than the oral route. Moreover, there is evidence that exposure to food allergens, in particular peanuts, in the airway would also lead to food sensitization. The most frequent route of sensitization for inhalant allergens is still debated. Of note, a recent case report supports the development of sensitization to cat dander through a cat bite. Our review aims to provide an overview of current knowledge and unmet needs in the pathophysiology of respiratory and FAs.

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.

As a novel respiratory viral infection, coronavirus disease 2019 (COVID-19) has influenced asthma in unpredictable ways. In the post-COVID era, there is a need to review asthma care and the new challenges and opportunities that are presented. Long COVID is a new and complex syndrome that has arisen. Treatable traits (TTs) have already been developed to address complex asthma and can be adapted to manage long COVID. Consumers are seeking more information on and answers to what to expect with a dual diagnosis of asthma and COVID-19. People with asthma identify a strong need for research into COVID and asthma. Completion of a national survey (n = 593) resulted in a list of research themes. From these, participants prioritized 10 asthma research themes. Among the top 10 asthma research priorities, the theme of COVID and asthma was ranked as the second priority in the overall rank list. Addressing these issues has the potential to improve global asthma health.