Non-allergic rhinitis is a frequent yet underdiagnosed cause of chronic nasal symptoms, including nasal congestion, rhinorrhoea, and upper airway hyperreactivity. Its pathophysiology involves neurogenic dysregulation, leading to excessive mucus production and vasodilation. While medical therapy remains first-line, some patients experience persistent symptoms requiring surgical intervention. This review outlines key surgical options for refractory non-allergic rhinitis: inferior turbinate (IT) reduction, vidian neurectomy, and posterior nasal nerve (PNN) ablation. IT reduction-performed using cold instruments, radiofrequency, laser, coblation, or microdebrider-remains the cornerstone treatment for nasal obstruction, offering durable symptom relief with low complication rates. Vidian neurectomy effectively reduces rhinorrhoea but carries risks of ocular dryness and transient facial numbness, limiting its indication to severe, refractory cases. PNN interventions, including cryotherapy, cold-instrument techniques, and radiofrequency, provide a minimally invasive, outpatient alternative that selectively targets nasal parasympathetic and sensory fibers while sparing lacrimal innervation, yielding significant and lasting symptom improvement. Surgical management of non-allergic rhinitis is effective and safe when tailored to symptom profile, anatomy, and prior medical treatment response. Advances in endoscopic and minimally invasive approaches have reduced complications, establishing these procedures as integral options in comprehensive non-allergic rhinitis care.

Systemic glucocorticosteroids (sGCS) are widely used in the treatment of chronic inflammatory airway diseases such as rhinitis, rhinosinusitis and asthma. It is well-known that systemic use is linked to multiple adverse effects (AEs) both in the short- and the long-term. However, less is known about the safety of multiple short courses of sGCS. Currently there is no established agreement on the acceptable cumulative exposure to sGCS, considering the potential for various AEs. This systematic review and meta-analysis evaluated sGCS-related AEs in both upper and lower inflammatory airway disease, with a particular focus on short- and long-term risks. We further evaluated whether a dose-response relationship existed between the daily and cumulative dosages of sGCS and the occurrence of those AEs. Our meta-analysis confirmed that cumulative dosages between 500 mg and 1 g prednisolone-equivalent significantly increase the risk of most AEs, with risks increasing with incremental dose. These findings underscore the importance of: (a) judicious sGCS prescription and need for steroid stewardship, due to their potential for short- and long-term complications, occurring even with repeated short courses, and (b) prioritization of steroid-sparing approaches (e.g., biologicals) to avoid reaching a cumulative dose of 500 mg.

The sense of smell, with its extensive evolutionary history, is highly prone to disorders that can have a profound impact on daily life. Anosmia affects approximately 5% of the population, with an additional 15% exhibiting reduced olfactory function. The prevalence of olfactory dysfunction (OD) varies by population and age group, and standardized testing reveals a broad range of impacts. OD includes various causes, most commonly aging, inflammation of the olfactory epithelium, upper respiratory tract infections (URTI), traumatic brain injury, and neurological conditions. The recent COVID-19 pandemic has highlighted the association between viral infections and olfactory dysfunction, with severe hyposmia/anosmia being an early marker of infection. Despite its importance, the assessment of olfactory function remains inconsistent across clinical practices. Psychophysical smell tests, while vital for diagnosis and patient management, are underutilized, especially outside of specialized centers. Standardized testing methods are crucial for objective diagnosis, but significant challenges, including test variability, lack of comparability, and healthcare reimbursement issues, persist. The European Academy of Allergy and Immunology (EAACI) advocates for improvements in the quality and standardization of chemosensory assessments. Future efforts must prioritize education, incentives for better testing, and the integration of digital tools to expand access to olfactory testing and diagnosis in remote or quarantine situations. However, office-based testing remains irreplaceable, even with advancements in telemedicine.

Chronic rhinosinusitis (CRS) and asthma are prevalent conditions that often coexist. These diseases share common inflammatory mechanisms, such as T-helper cell 2 (T2)-high inflammation, driven by interleukin (IL)-4, IL-5, and IL-13 cytokines. The frequent comorbidity between CRS, especially CRS with nasal polyps (CRSwNP), and asthma exacerbates disease severity, impairs quality of life, and complicates treatment. Patients with NSAID-exacerbated respiratory disease (N-ERD) represent a severe phenotype of this disease, characterized by the coexistence of CRSwNP, asthma, and NSAID hypersensitivity, which poses unique therapeutic challenges. This EAACI Task Force explores the shared risk factors, including genetic predispositions, epithelial barrier dysfunction, microbiome dysbiosis, underlying CRS, and asthma. It also evaluates current therapeutic strategies such as biologics, aspirin therapy after desensitization (ATAD), and endoscopic sinus surgery (ESS). Biologics have shown their effectiveness and safety in the treatment of asthma and CRS. Dupilumab, mepolizumab, depemokimab, and omalizumab have emerged as transformative therapies, particularly for patients with severe type 2 inflammation. Tezepelulumab is effective for both T2-high and T2-low asthma and CRSwNP. Itepekimab has shown its effect in asthma and is under investigation for CRSwNP. Omalizumab is effective in allergic asthma and CRSwNP. ATAD provides an additional disease-modifying approach for N-ERD, though patient adherence and tolerability remain critical challenges. ESS significantly improves asthma control, reduces medication use, and enhances sinonasal outcomes, particularly in severe asthma cases; however, these patients often need recurring surgeries. Despite these advances, treatment outcomes vary based on individual phenotypes and endotypes, underscoring the need for personalized approaches. The report highlights gaps in the literature, such as the lack of head-to-head trials comparing biologics, ATAD, and surgery. Future research should focus on refining treatment algorithms, identifying biomarkers for treatment selection, and assessing long-term outcomes to optimize care for patients with CRS, asthma, and N-ERD.

Recently, we have uncovered overexpression of gasdermin B (GSDMB), driven by rs7216389 SNP in the 17q21 locus, as driving gene of asthma pathophysiology. However, the direct impact of this genetic dysregulation on the airway mucosa remains poorly studied. Effect of overespression of GSDMB in normal human bronchial epithelial (NHBE) cells, stimulated with interferons (IFNγ, IFNα, IFNλ2) for the viral response, or inflammasome inducers (dsDNA, LPS + nigericin) for the bacterial response, was analyzed by qPCR, LDH assays, FLICA analysis, and alarmin ELISAs. Interferons upregulated GSDMB and CXCL10, but inflammasome activation did not induce GSDMB-dependent pyroptosis. GSDMB overexpression neither triggered spontaneous nor inflammasome-mediated pyroptosis, indicating reliance on IFN signaling and lytic cell death in viral, but not bacterial, infections. These findings suggest GSDMB dysregulation impairs interferon responses and cell lysis during viral infections in asthma, identifying it as a promising therapeutic target. Future research should explore GSDMB gene modulation and therapies targeting antiviral defense molecules, such as interferons, to restore mucosal immunity and alleviate asthma symptoms in children with the 17q21 risk allele. Supported by the German Center of Lung Research (DZL) funded by the Federal Ministry of Education and Research (BMBF), the Bavarian State Office for Health and Food Safety (LGL; K1-2497-GLB-20-V4) of the Bavarian State Ministry of Health and Care and by grants from Deutsche Forschungsgemeinschaft RTG2668 (Project A5, Project-ID: 435874434) to C.B. Schmidt-Weber. Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)

Background: The skin prick test (SPT) is the gold standard for diagnosing sensitization to inhalant allergies. The Skin Prick Automated Test (SPAT) device was designed for increased consistency in test results, and captures 32 images to be jointly used for allergy wheal detection and delineation, which leads to a diagnosis. Materials and Methods: Using SPAT data from 868 patients with suspected inhalant allergies, we designed an automated method to detect and delineate wheals on these images. To this end, 10,416 wheals were manually annotated by drawing detailed polygons along the edges. The unique data-modality of the SPAT device, with 32 images taken under distinct lighting conditions, requires a custom-made approach. Our proposed method consists of two parts: a neural network component that segments the wheals on the pixel level, followed by an algorithmic and interpretable approach for detecting and delineating the wheals. Results: We evaluate the performance of our method on a hold-out validation set of 217 patients. As a baseline we use a single conventionally lighted image per SPT as input to our method. Conclusion: Using the 32 SPAT images under various lighting conditions offers a considerably higher accuracy than a single image in conventional, uniform light.

The skin prick test (SPT) is the gold standard for diagnosing allergic sensitization to aeroallergies. The Skin Prick Automated Test (SPAT) device has previously demonstrated reduced variability and more consistent test results compared to manual SPT. The current study aims to develop and validate an artificial intelligence (AI) assisted readout method to support physicians in interpreting skin reactions following SPAT. To train the AI algorithm, 7812 wheals (651 patients) are manually labeled. To validate the AI measurement, the longest wheal diameter of 2604 wheals (217 patients) is measured by the treating physician and compared to the AI measurement. In addition, AI-assisted readout is validated on a separate test cohort of 95 patients (1140 wheals). We demonstrate that the AI measurements of the longest wheal diameter exhibit a strong correlation with the physician's measurements. The AI algorithm shows a specificity of 98·4% and sensitivity of 85·0% in determining positive or negative test results in the validation cohort. In the test cohort, physicians adjust 5·8% of AI measurements, leading to a change in the test interpretation for only 0·5% of cases. AI-assisted readout significantly reduces inter- and intra-observer variability and readout time compared to manual physician measurements. Altogether, the AI-assisted readout method demonstrates high accuracy, with minimal misclassification of test results. Adding AI to SPAT further improves standardization across the SPT process, significantly reducing observer variability and time to readout.

BACKGROUND:Allergen-specific immunotherapy (AIT) is a disease-modifying therapy and is effective to reduce the symptoms of grass pollen-allergy. The airway epithelium of these patients releases inflammatory mediators including type-2 cytokines, which are associated with cellular processes involved in the symptomatic response of the affected tissue. Aim of the study was to identify epithelial biomarkers indicating AIT progress. METHODS:In an exploratory, observational allergy cohort, we longitudinally phenotyped 56 grass pollen-allergic patients undergoing AIT for over three years and 18 controls using nasal secretions at critical time windows during therapy to assess peak-season responses along the course of therapy. Type-2 cytokine protein levels were analyzed using the high-sensitivity multiplex electrochemiluminescence mesoscale technique. RESULTS:The type-2 cytokines CCL26 and POSTN oscillated seasonally, in contrast to TSLP and IL-33. However, only POSTN was reduced over the three-year AIT progression. In addition to POSTN, IL-24 and IL-37 levels were continuously reduced during AIT, while IFN-g and CCL27 were increased. Compared to healthy individuals, AIT did not restore healthy secretion levels but rather induced a novel homeostasis CONCLUSION: Nasal secretions trace the epithelial response during different phases of AIT. We demonstrate that AIT only partially controls the epithelial type 2 cytokine CCL26, which also adapts to seasonal changes, while POSTN and IL-24 are potential indicators of therapy success. Therefore, nasal secretions represent a promising, non-invasive tool for monitoring seasonal progress of AIT.

Background Omalizumab (Xolair®​; Novartis) is a recombinant IgG1 monoclonal antibody that selectively binds to human IgE and is approved for the treatment of allergic asthma, chronic spontaneous urticaria, and chronic rhinosinusitis with nasal polyps. Since its approval, the use of Omalizumab has been investigated in clinical studies for food allergies, atopic dermatitis, and eosinophilic gastritis. However, no approval exists for these indications. Allergen immunotherapy (AIT) is the only causal therapy used for allergic rhinitis (AR) and asthma. Systemic side effects are rare but can limit therapy.

BACKGROUND:Extracellular vesicles (EVs) have been implicated in the pathogenesis of asthma, however, how EVs contribute to immune dysfunction and type 2 airway inflammation remains incompletely understood. We aimed to elucidate roles of airway EVs and their miRNA cargo in the pathogenesis of NSAID-exacerbated respiratory disease (N-ERD), a severe type 2 inflammatory condition. METHODS:EVs were isolated from induced sputum or supernatants of cultured nasal polyp or turbinate tissues of N-ERD patients or healthy controls by size-exclusion chromatography and characterized by particle tracking, electron microscopy and miRNA sequencing. Functional effects of EV miRNAs on gene expression and mediator release by human macrophages or normal human bronchial epithelial cells (NHBEs) were studied by RNA sequencing, LC-MS/MS and multiplex cytokine assays. RESULTS:EVs were highly abundant in secretions from the upper and lower airways of N-ERD patients. N-ERD airway EVs displayed profoundly altered immunostimulatory capacities and miRNA profiles compared to airway EVs of healthy individuals. Airway EVs of N-ERD patients, but not of healthy individuals induced inflammatory cytokine (GM-CSF and IL-8) production by NHBEs. In macrophages, N-ERD airway EVs exhibited an impaired potential to induce cytokine and prostanoid production, while enhancing M2 macrophage activation. Let-7 family miRNAs were highly enriched in sputum EVs from N-ERD patients and mimicked suppressive effects of N-ERD EVs on macrophage activation. CONCLUSION:Aberrant airway EV miRNA profiles may contribute to immune dysfunction and chronic type 2 inflammation in N-ERD. Let-7 family miRNAs represent targets for correcting aberrant macrophage activation and mediator responses in N-ERD.

Introduction Type-2 biologics allow for successful treatment of patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). Eosinophils have been established as a reliable biomarker of type-2 disease and enable the differentiation of inflammatory patterns in CRSwNP. Aim of this study was to evaluate, whether peripheral blood eosinophilia before initiation of therapy with type-2 biologics allows assesment of response to treatment in patients with CRSwNP.

Severe chronic rhinosinusitis with nasal polyps (CRSwNP), a form of diffuse bilateral (usually type 2) CRS, is a debilitating disease with a significant impact on quality of life (QoL). With novel knowledge and treatment options becoming available, there is a growing need to update or revise key definitions to enable communication across different specialties dealing with CRS, and to agree on novel goals of care in CRSwNP. The European Forum for Research and Education in Allergy and Airway diseases (EUFOREA) and EPOS expert members discussed how to measure treatment responses and set new treatment goals for CRSwNP. In this paper a consensus on a list of definitions related to CRSwNP is provided: control, remission, cure, recurrence/exacerbation, treatable traits, remodeling, progression, and disease modification. By providing these definitions, the involved experts hope to improve communication between all stakeholders involved in CRSwNP treatment for use in routine care, basic and clinical research and international guidelines aimed to harmonize and optimize standard of care of patients with CRSwNP in the future.

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.