Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness, variable airflow obstruction, and persistent inflammation. While its pathophysiology is well established, growing evidence highlights significant sex-based differences in its prevalence, severity, and treatment response. Epidemiological studies indicate that asthma is more common in prepubertal boys but shifts toward a female predominance after puberty, with adult women experiencing higher morbidity and greater healthcare utilization. These disparities suggest a crucial role for sex hormones, genetic predisposition, and epigenetic regulation in asthma pathogenesis. Sex hormones modulate immune responses, contributing to disease progression. Estrogen enhances type 2 inflammation, increases eosinophilic infiltration, and upregulates IL-4 and IL-13 expression, leading to greater airway hyperreactivity in women. Additionally, progesterone fluctuations correlate with perimenstrual asthma exacerbations, while testosterone appears to exert a protective effect by dampening Th2-driven inflammation and airway remodeling. These hormonal influences contribute to sex-specific asthma phenotypes and treatment responses. Genetic and epigenetic factors further shape sex-related differences in asthma. The X chromosome harbors immune-regulatory genes, including TLR7 and TLR8, which amplify inflammatory responses in females. The sex-dependent expression of IL13 and ORMDL3 influences eosinophilic inflammation and airway remodeling. Epigenetic modifications, such as DNA methylation and microRNA regulation, further impact immune activation and corticosteroid responsiveness. For instance, Let-7 miRNAs modulate IL-13 expression, contributing to sex-specific inflammatory profiles. Environmental factors, including air pollution, obesity, and diet, interact with hormonal and genetic influences, exacerbating sex disparities in asthma severity. Obesity-related metabolic dysfunction promotes systemic inflammation, airway remodeling, and steroid resistance, disproportionately affecting women. Given these complex interactions, sex-specific approaches to asthma management are essential. Personalized treatment strategies targeting hormonal pathways, immune regulation, and metabolic health may improve outcomes for both men and women with asthma. Future research should focus on sex-based therapeutic interventions to optimize disease control and mitigate healthcare disparities.

Background: In its severe form, where possible, asthma is treated using biological drugs in order to reduce, as much as possible, the use of systemic steroids. Mepolizumab is effective for severe asthma based on key outcomes such as exacerbation and steroid dependence. Its efficacy in terms of the criteria for clinical remission in the short and long term has become of interest. Objective: We aimed to evaluate the effect of mepolizumab in the achievement of clinical remission after 3 years of administration. Methods: In this study, 71 patients who continued mepolizumab for 3 years were assessed for clinical remission according to six different published sets of remission criteria. Results: According to the criteria, 39–52% of patients experienced complete remission in the first year, increasing to 51–73% at 3 years. By classifying patients according to partial and complete remission criteria, proposed by the SANI, we observe 22% of patients in partial remission at one year, achieving complete remission after three years. The baseline factors associated with earlier remission were a higher FEV1, if we consider classifications requiring an FEV1 ≥ 80%, a low OCS dose, and low FeNO levels, in the patients requiring FEV1 stabilization. Conclusions: Clinical remission is possible for patients treated with mepolizumab. The observations at three years compared with the first year indicated that the factors negatively affecting remission delayed rather than prevented it. Earlier treatment could increase the chances of remission.

Hypereosinophilic syndrome (HES) encompasses a heterogeneous and complex group of different subtypes within the wider group of hypereosinophilic disorders. Despite increasing research interest, several unmet needs in terms of disease identification, pathobiology, phenotyping, and personalized treatment remain to be addressed. Also, the prospective burden of non-malignant HES and, more in general, HE disorders is currently unknown. On a practical note, shortening the diagnostic delay and the time to an appropriate treatment approach probably represents the most urgent issue, even in light of the great impact of HES on the quality of life of affected patients. The present document represents the first action that the Italian Society of Allergy, Asthma, and Clinical Immunology (SIAAIC) has finalized within a wider project aiming to establish a collaborative national network on HES (InHES—Italian Network on HES) for patients and physicians. The first step of the project could not but focus on defining a common language as well as sharing with all of the medical community an update on the most recent advances in the field. In fact, the existing literature has been carefully reviewed in order to critically integrate the different views on the topic and derive practical recommendations on disease identification and treatment approaches.

Dupilumab is currently approved for the treatment of Type 2 severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Few studies have specifically reported on dupilumab efficacy on asthma outcomes as a primary objective in a real-life setting, in patients with and without CRSwNP. Our study aimed to explore the efficacy of dupilumab on functional, inflammatory, and patient-reported outcomes in asthma patients across different disease phenotypes and severity, including mild-to-moderate asthma coexisting with CRSwNP. Data from 3, 6, and 12 months follow-up were analyzed. Asthma (FEV1%, Tiffeneau%, ACT, FeNO, oral steroid use, exacerbation rate, and blood eosinophilia) and polyposis (SNOT22, VAS, NPS) outcomes showed a rapid (3 months) and sustained (6 and 12 months) significant change from baseline, despite most of the patients achieving oral steroid withdrawal. According to the sensitivity analysis, the improvement was not conditioned by either the presence of polyposis or severity of asthma at baseline. Of note, even in the case of milder asthma forms, a significant further improvement was recorded during dupilumab treatment course. Our report provides short-, medium-, and long-term follow-up data on asthma outcomes across different diseases phenotypes and severity, contributing to the real-world evidence related to dupilumab efficacy on upper and lower airways T2 inflammation.

Sex and gender play a critical role in allergic diseases, influencing immune response, clinical phenotypes, treatment strategies, outcomes, and health-related quality of life. Despite mounting evidence across multiple studies examining sex/gender differences in a multitude of allergic diseases, most address isolated conditions, not taking into consideration the vast interplay of hormonal, genetic, immunological, and sociocultural factors and their unique consequences for clinicians and researchers. With this position paper, we aim to assess currently available evidence on the sex- and gender-specific characteristics of the most common allergic diseases, providing an overview of present knowledge and future areas of improvement for clinicians and researchers. This position paper was developed by the Società Italiana di Allergologia, Asma ed Immunologia Clinica (SIAAIC): a panel of experts who conducted a literature review focusing on sex and gender differences across major allergic diseases. A consensus-based approach was employed to assess the immunological, clinical, and therapeutic implications of available evidence, offering a recommendation for researchers and clinicians alike. Data highlights marked differences driven by sex and gender in disease prevalence, immune pathways, clinical phenotype and severity, as well as therapeutic outcomes. Female patients appear to show a higher prevalence of Th2-driven ailments, autoimmune overlap, and allergic drug reactions, whereas males are more likely to experience fatal anaphylaxis and severe mastocytosis. Sex hormones can modulate multiple immune pathways leading to mast cell activation, antibody production, and cytokine expression, thus contributing to divergent disease trajectories. In conclusion, sex and gender are a key determinant in allergic diseases, and their integration in future research is essential to develop a tailored approach to treatment. Efforts should prioritise the identification of sex- and gender-specific biomarkers, therapeutic strategies, and equitable access to healthcare services. A sex- and gender-aware approach could potentially improve outcomes, optimise treatment strategies, and address current gaps in allergy practice.

Hypereosinophilic syndrome (HES) is a heterogeneous group of disorders characterised by persistent hypereosinophilia associated with organ damage. Due to its rarity and heterogeneity in its clinical presentation, HES remains underdiagnosed or misdiagnosed, often leading to delayed diagnosis and irreversible organ damage. The complexity of HES diagnosis is even more complicated due to the absence of standardised criteria. Moreover, the lack of structured referral pathways among specialists, including allergists, clinical immunologists, haematologists, and rheumatologists, further hinders optimal patient care. To address these challenges, the Italian National Hypereosinophilic Syndrome (INHES) Network aimed to enhance the diagnosis, management, and research of HES. INHES objectives also include connecting specialised centres, facilitating data collection on HES and eosinophilic-associated conditions, and improving healthcare standards through consensus guidelines. To do this, INHES has created a web-based platform called “Phleos” to develop a comprehensive referral map, ensuring timely and appropriate patient access to expert care. Phleos is a web-based datasheet, per GDPR regulations, to systematically collect anonymised clinical data, including absolute eosinophil counts, organ involvement, laboratory parameters, instrumental assessments, and treatments. A structured classification system enables differentiation among idiopathic, lymphocytic, myeloid, familial, reactive, and overlap forms of HES. Moreover, the platform integrates standardised diagnostic pathways and treatment protocols to harmonise patient care across participating centres. The INHES Network aims to mitigate diagnostic delays, optimise therapeutic decision-making, and advance research in eosinophilic disorders by fostering interdisciplinary collaboration and establishing a unified framework. This initiative represents a crucial step toward a cohesive national strategy, ultimately improving clinical outcomes for HES patients in Italy.