Martina Ottoni

Background: Allergic rhinitis (AR) affects up to 50% of adults globally. This study was undertaken to evaluate cumulative incidence of chronic rhinosinusitis (CRS) in patients with AR and to investigate the association between CRS and clinical features of AR, sensitization patterns, concomitant atopic comorbidities and AR severity. Method: This retrospective, observational, multicenter study included consecutive adult patients with a diagnosis of AR without CRS at first assessment. Data covering clinical information from AR onset to the last follow-up were collected. Results: Out of the 198 patients included (54.0% female, median age at AR diagnosis 19 years old, IQR 11–30), CRS developed in 65.2% of patients during follow-up. Among those who developed CRS, 51.2% had radiological confirmation, and 31.0% were diagnosed with CRS with nasal polyposis (CRSwNP). Multivariate analysis revealed no independent predictors of CRS at the time of AR diagnosis (Hazard ratio (HR) with [95% confidence intervals (CI)] 1.24 [0.68–2.25], age at AR diagnosis (per year change) 1.00 [0.98–1.02], atopic morbidities 1.81 [0.8–4.11], and polysensitization 0.76 [0.8–1.58]). At last follow up (median 19 [IQR 9-29] years from AR diagnosis), AR was moderate-persistent in 47.4%. Patients with CRSwNP have a higher proportion of asthma (77.5% vs 43.8%, p=0.0005) and ASA hypersensitivity (27.5% vs. 5,6%, p=0.0010) as compared to CRSsNP. Overall, only CRS was independently associated to moderate-persistent AR at last follow-up (HR 2.90 [1.51, 5.56]). Conclusion: Almost two-thirds of subjects with AR develop CRS during the disease course. Years after AR diagnosis, CRS is the only independent factor associated with moderate-persistent AR, increasing almost three times its risk.

The concept of united airway disease (UAD) highlights the bidirectional relationship between inflammatory disorders of the upper airways—such as allergic rhinitis and chronic rhinosinusitis with or without nasal polyps (CRSwNP/CRSsNP)—and lower airway diseases, most notably asthma. This paradigm is supported by epidemiological, embryological, and immunological evidence demonstrating that airway inflammation represents a single, interconnected process rather than isolated compartmental pathology. Central to many UAD phenotypes is type 2 (T2) inflammation, driven by cytokines including IL-4, IL-5, and IL-13, and mediated by effector cells such as eosinophils and group 2 innate lymphoid cells (ILC2s). Epithelial barrier dysfunction often serves as the initiating trigger for this shared inflammatory cascade by production of TSLP, IL-25 and IL-33. Optimal diagnosis and management of UAD require an integrated, multidisciplinary framework. Clinical evaluation remains essential for patient characterization but must be complemented by pheno-endotypic assessment using imaging (CT), allergy testing, biomarker profiling (FeNO, blood eosinophils, IgE), and pulmonary function testing (spirometry, impulse oscillometry). Therapeutic strategies are layered, targeting both symptom control and inflammation across airway compartments. Standard approaches include intranasal and inhaled corticosteroids as well as saline irrigations, while severe T2-high disease increasingly benefits from biologic therapies (anti-IL-5/IL-5R, anti-IL-4R, anti-TSLP), which reduce dependence on systemic corticosteroids and surgical interventions such as endoscopic sinus surgery (ESS). Emerging precision-medicine models, particularly the “treatable traits” approach, further underscore the need to view the airway as a unified system. Collectively, these insights reinforce the clinical imperative of addressing upper and lower airway disease as a continuum, ensuring that inflammation in one district is neither overlooked nor treated in isolation.

The diagnosis and management of UAD require an integrated, multidisciplinary approach. Diagnostic strategies combine clinical evaluation, imaging (CT), allergy testing, biomarker measurement (such as FeNO, blood eosinophils, IgE), and pulmonary function testing (spirometry, IOS) to phenotype the disease. Therapeutic management is stratified and aims to control inflammation and symptoms in both compartments. Cornerstones include topical corticosteroids (intranasal and inhaled) and saline irrigations. For severe forms, especially T2-high, targeted biologic therapies (anti-IL-5/IL-5R, anti-IL-4R, anti-TSLP) have revolutionized treatment, reducing dependence on oral corticosteroids and the need for surgical interventions (like endoscopic sinus surgery, ESS). Adopting a "treatable traits" approach is emerging as a key strategy for precision medicine in UAD.

Given their nutritional features and environmental sustainability, black soldier fly (Hermetia illucens) larvae are currently being considered in Europe for commercialization as human food. The primary goal of this study is the determination of in vitro IgE-cross-reactivity to recombinant tropomyosin (_HITPM) and arginine kinase (_HIAK) of H. illucens in subjects sensitized to crustaceans and/or mites. Dot blot assays for recombinant _HITPM were carried out with the sera of 48 subjects, 30 sensitized to crustaceans (Cr+) and/or house dust mites (HDM+) (STUDY group) and 18 non-sensitized (CTRL group). A higher rate of IgE-reactivity to recombinant _HITPM was found in the STUDY group compared to non-sensitized controls (73% vs. 44%; p 0.066). No significant relationship was achieved upon dot blot assays for _HIAK. No relevant association between a positive history of food reactions and immunoreactivity to _HITPM and to _HIAK was reported (15% in _HITPM+ vs. 6% in _HITPM-, p NS; 28% in _HIAK+ vs. 50% in _HIAK-, p NS), contrary to the _HITPM+Cr+HDM+ subset (50% vs. 0%, p 0.022). Considering the wide overlap of pan-allergens within the Arthropoda phylum, concerns about allergenic potential due to the eventual consumption of H. illucens-enriched foods might be valid. Therefore, targeted studies involving basophil activation tests, skin prick tests, and a double-blind placebo-controlled oral food challenge using H. illucens are needed.

The demographic increase, environmental concerns, and heightened awareness about health has led Western countries to consider edible sources previously overlooked. The novelty of these sources implies a scarce knowledge about their allergenicity. This review has the purpose of offering an arranged view about the allergenicity of different categories of novel foods, such as edible insects, new plant-based foods and microalgae, by exploring cross-reactivity and common traits with other food allergies but also specific peculiarities. A particular regard is reserved to the framework in Western countries. Increasing efforts have been directed in the last years to identify dangerous cross-reactive allergens in novel foods, i.e. tropomyosin. On the other hand, eventual primary sensitizations should also be considered, especially for idiopathic anaphylaxis. In view of the partial knowledge about the allergenic potential of the novel sources, the education of the patient on this topic (particularly those with known food allergies), and an appropriate labeling of product's packages may reveal helpful to minimize the risk.

Eosinophilic esophagitis (EoE) is a multifaceted disease characterized by a wide heterogeneity of clinical manifestations, endoscopic and histopathologic patterns, and responsiveness to therapy. From the perspective of an effective approach to the patient, the different inflammatory mechanisms involved in the pathogenesis of EoE and biologics, in particular monoclonal antibodies (mAbs), targeting these pathways are needed. Currently, the most relevant is dupilumab, which interferes with both interleukin (IL)-4 and IL-13 pathways by binding IL-4 receptor α, and is the only mAb approved by the European Medicine Agency and US Food and Drug Administration for the treatment of EoE. Other mAbs investigated include mepolizumab, reslizumab, and benralizumab (interfering with IL-5 axis), cendakimab and dectrekumab (anti-IL-13s), tezepelumab (anti-TSLP), lirentelimab (anti-SIGLEG-8), and many others. Despite the undeniable economic impact of biologic therapies, in the near future, there will be room for further reflection about the opportunity to prescribe biologic agents, not only as a last-line therapy in selected cases such as patients with comorbidities involving common pathways. Although recent findings are very encouraging, the road to permanent success in the treatment of EoE is still long, and further studies are needed to determine the long-term effects of mAbs and to discover new potential targets.

Background. Allergen-specific immunotherapy (AIT) is the only disease-modifying therapy for allergic conditions, resulting in a long-lasting tolerance beyond the duration of the treatment. Due to the strong relationship between the effectiveness, its optimal duration (at least three years) and the observation of the correct administration protocol, appropriate adherence to the plan of treatment represents a critical factor for the therapeutical success of AIT. Methods. Analysis of studies about the rate of adherence in subcutaneous and sublingual immunotherapy, which are the main routes of administration of AIT. Results. There are different causes leading to a premature interruption of the therapy or to it being incorrectly carried out; the most reported include erroneous expectations of the effectiveness and the adverse effects, economic issues, inconvenience and unrelated clinical conditions. Conclusions. An attentive analysis of the main causes of dropouts may be useful to improve the management of these patients and to develop new strategies for a personalized approach. These strategies should be dynamic, involving attentive communication between the physician and the patient about all the possible criticalities, especially in the initial phase of the therapy, and facilitating, as much as possible, access to healthcare providers over the course of the maintenance phase, including by exploiting technological tools.