Fabiana Furci

Background: Precision medicine targets clinical remission, but traditional symptom-based frameworks often ignore the biological pathways driving the disease. Adequate T2 biomarker interpretation is crucial to identify phenotypes where FeNO reflects epithelial barrier distress. We investigated the “clinical-biological gap” through the analysis of six groups to distinguish profiles of symptomatic resilience from biological insensitivity to corticosteroids. Methods: Real-world study of 292 patients stratified into six groups based on BEC (≥250 cells/microL), FeNO (≥25 ppb), and IgE (≥100 kU/L). ACT, BMI, FEV1, comorbidities, and therapeutic burden were analyzed. Results: The EoS+ IgE+ group showed “symptomatic resilience”: apparent clinical control (54.5% ACT ≥ 20) supported by a critical pharmacological burden (90% salbutamol, 80% OCS ≥ 7.5 mg). The Triple Positive and EoS+ FeNO+ groups depicted “Maximum Steroid Insensitivity,” characterized by poor control despite maximal ICS/OCS regimens. FeNO could appear like the primary driver of instability, reflecting a trajectory of oxidative stress not altered by steroids. Conclusions: T2 biomarkers provide a unique prognostic value unidentifiable by standard clinical assessment. FeNO monitoring unmasks silent distress in resilient patients and identifies the “therapeutic wall” in refractory profiles. Therefore biological remission could represents the only effective target to modify the natural history of the disease.

Food allergy is an increasingly prevalent global health condition characterized by immune-mediated reactions to dietary antigens and a substantial clinical burden. Growing understanding of IgE-mediated mechanisms has highlighted the central role of type 2 inflammation, effector-cell activation, and impaired immune regulation. These advances have prompted the development of disease-modifying therapies beyond allergen avoidance. This narrative review summarizes recent advances in the therapeutic management of IgE-mediated food allergy. A structured PubMed search was performed to identify clinical trials, randomized studies, and meta-analyses published within the last five years. Both allergen-specific and non-allergen-specific interventions were evaluated. Current evidence supports oral immunotherapy as the most effective strategy for increasing reaction thresholds and inducing desensitization in peanut, milk, and egg allergies. However, safety concerns remain, and sustained unresponsiveness after treatment discontinuation is achieved inconsistently. Sublingual and epicutaneous immunotherapy show improved safety but lower efficacy. Modified allergen approaches, including baked milk and processed peanut products, may improve tolerability and facilitate immune modulation in selected patients. Biologic therapies, particularly anti-IgE agents, demonstrate efficacy both alone and when combined with immunotherapy. Emerging approaches include peptide vaccines, DNA immunization, microbiome-targeted interventions, and early dietary modulation. These strategies may improve durable immune tolerance through personalized, mechanism-based therapeutic approaches. Future progress will depend on optimizing safety, identifying predictive biomarkers, and integrating multimodal approaches to achieve durable immune tolerance.

Allergen immunotherapy (AIT) represents the only disease-modifying treatment currently available for IgE-mediated allergic diseases. Traditionally employed to alleviate symptoms and reduce pharmacological dependence, AIT is now being reconsidered within a broader and more ambitious therapeutic framework: the induction of long-term clinical remission. In the field of allergic diseases, the concept of disease control has recently been integrated with that of clinical remission. This review discusses the evolving concept of remission in allergic disorders, particularly allergic rhinitis and allergic asthma, in patients treated with AIT. Starting from the definition of clinical remission, this review aims to analyze the evidence supporting this concept and explore potential tools for clinical application in allergic patients treated with AIT, the only causal therapy.

Atopic dermatitis (AD) is a common inflammatory skin disorder which presents with recurrent eczematous lesions and itching. Its pathophysiology is complex and multifactorial. Alterations in cell-mediated immune responses, barrier dysfunction, environmental aspects and IgE-mediated hypersensitivity are all involved. This review aims to provide the clinician with an update on the impact that Th2 inflammation can have on growth and osteoimmunology. The potential adverse or protective effects brought on by the many therapies administered in this condition are also considered. Moreover, through this analysis, we aim to show how, by inhibiting the IL-4 and IL-13 signaling pathways—fundamental in the T helper 2 (Th2) immune axis and in AD pathogenesis—dupilumab may exert a protective role on growth and osteoimmunology in moderate-to-severe AD, particularly in young patients. This focus is essential for the correct, safe management of patients with Th2 inflammation.

In recent years, the role of sexual hormones in the pathogenesis and progression of various diseases has progressively being established, which attempts to explain immune dimorphism. Whether physiological or pathological, variations in hormones influence the inflammatory response and adaptive systems to control increased productions of reactive oxygen species, reactive nitrogen species, and free radicals. Primary allergic respiratory and skin diseases were taken into consideration, and possible biomarkers of oxidative stress related to sex differences in the onset and development of atopic diseases were analyzed. Understanding how these variables interact with each other, and evaluating the possible common targets, lays the foundation for the development of tailored therapies with an eye to precision medicine.

Photodynamic therapy is a non-ionizing radiation treatment that utilizes a photosensitizer in combination with light to produce singlet oxygen. This singlet oxygen induces anti-cancer effects by causing apoptotic, necrotic, or autophagic cell death in tumor cells. Currently, photodynamic therapy is employed in oncology to treat various cancers. In the presence of oxygen, this non-invasive approach leads to direct tumor cell death, damage to microvasculature, and the induction of a local inflammatory response. These effects allow photodynamic therapy to be effective in treating early-stage tumors, extending survival in cases where surgery is not feasible, and significantly improving quality of life. In this paper, we provide a state of the art on cytomolecular mechanisms and associated pathways involved in photodynamic therapy. By integrating these mechanistic insights with the most recent advancements in nanotechnology, this phototherapeutic approach has the potential to become a prevalent treatment option within conventional cancer therapies, enhancing its application in precision medicine.

Asthma is a chronic inflammatory disease with the main anti-inflammatory drugs for better disease control being steroids or corticosteroids. The use of steroids in asthma patients, in particular in uncontrolled asthma patients, is associated with an increased risk of osteoporosis and fragility fractures. A single oral corticosteroid course increases the risk of osteoporosis and the continual use of inhaled corticosteroids is correlated over time to an increased risk for both bone conditions. With the use of new, available biologic therapies for asthma, perhaps even anticipating the times of their use in therapeutic management, in the current guidelines and with targeted strategies of prevention it may be possible to improve asthma management, preventing some comorbidities, such as osteoporosis.

Background: Conventional vaccines rarely cause severe allergic reactions. However, the rapid development and approval of COVID-19 vaccines left limited initial data on their adverse reactions, particularly in individuals with a history of allergy. The aim of this study was to assess and compare the safety profile of different doses and brands of COVID-19 vaccines in subjects with a history of allergy vs. those without a history of allergy. Methods: From February 2021 to February 2023, a web-based prospective study gathered vaccinee-reported outcomes using electronic questionnaires across eleven European countries. Baseline and up to six follow-up questionnaires captured data on vaccinee demographics, as well as both solicited and unsolicited adverse reactions. Results: Overall, 3476 vaccinees with a history of allergy were matched with 13,872 vaccinees from the general population at the first vaccination cycle and were included in the analysis. A total of 825 vaccinees with a history of allergy who had received a booster dose, matched to 3297 vaccinees from the general population, were included in the analysis. Higher rates of ADRs occurred after the first vaccination cycle compared to after the booster dose (64–91% vs. 56–79%). However, most reported ADRs were solicited and not serious, and no case of anaphylaxis was reported. Women and vaccinees with a history of allergy reported ADRs more frequently than men and the matched controls, respectively. Compared to other COVID-19 vaccines, a higher proportion of vaccinees experiencing at least one ADR following their first vaccination cycle was observed with Comirnaty and Vaxzevria. Statistically significant differences were observed among the study cohorts for median TTO after the second dose, and for median TTR following the first vaccination cycle and booster dose (p < 0.001). Conclusions: Typically, any drug or vaccine use carries a risk of severe allergic reactions, yet the benefits of vaccination generally outweigh these potential risks, as shown with the COVID-19 vaccines.

Asthma is a chronic inflammatory disease for which the main anti-inflammatory drugs for better disease control are steroids or corticosteroids. The use of steroids in asthma patients, in particular in uncontrolled asthma patients, is associated with an increased risk of osteoporosis and fragility fractures. A single oral corticosteroids course increases the risk of osteoporosis and continual use of inhaled corticosteroids is correlated over time to an increased risk for both bone conditions. With the use of new, available biologic therapies for asthma, perhaps even anticipating the times of their use in what are the steps of therapeutic management, in the current guidelines and with targeted strategies of prevention it may be possible to improve asthma management, preventing some comorbidities, such as osteoporosis.

Vitamin C is a water-soluble vitamin introduced through the diet with anti-inflammatory, immunoregulatory, and antioxidant activities. Today, this vitamin is integrated into the treatment of many inflammatory pathologies. However, there is increasing evidence of possible use in treating autoimmune and neoplastic diseases. We reviewed the literature to delve deeper into the rationale for using vitamin C in treating this type of pathology. There is much evidence in the literature regarding the beneficial effects of vitamin C supplementation for treating autoimmune diseases such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA) and neoplasms, particularly hematological neoplastic diseases. Vitamin C integration regulates the cytokines microenvironment, modulates immune response to autoantigens and cancer cells, and regulates oxidative stress. Moreover, integration therapy has an enhanced effect on chemotherapies, ionizing radiation, and target therapy used in treating hematological neoplasm. In the future, integrative therapy will have an increasingly important role in preventing pathologies and as an adjuvant to standard treatments.