Sven F. Seys

Background: The SYNAPSE phase 3 study demonstrated that mepolizumab significantly improves nasal polyp score (NPS), quality of life and symptom severity in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Objective: We aimed to evaluate mepolizumab effectiveness in a real‐world cohort from 12 tertiary centers in 6 European countries. Methodology: A retrospective analysis was conducted in 110 CRSwNP patients (comorbid asthma: 86.4%). CRS‐related outcomes were analyzed at baseline, 24 and 52 weeks of mepolizumab. Treatment response was evaluated based on EUFOREA 2021 criteria. Results: Significant improvements in NPS, Sinonasal Outcome Test‐22 (SNOT‐22), and visual analog scale (VAS) symptom scores were observed at 24 and 52 weeks compared to baseline. Further improvement between weeks 24 and 52 was observed for NPS and SNOT‐22. Asthma Control Test (ACT) also improved significantly by week 24 (ACT score ≥ 20: 64.5%). At least one response criterion (change in SNOT‐22 ≥ 8.9, NPS ≥ 1, VAS total sinus symptoms ≥ 20, VAS nasal blockage ≥ 20, VAS loss of smell ≥ 20) was met by 85.6% and 78.7% of patients at 24 and 52 weeks, respectively. A more stringent composite response (SNOT‐22 < 30, NPS < 4, VAS total sinus symptoms < 50, and VAS nasal blockage < 50) was achieved in 18.3% and 44.6% of patients at 24 and 52 weeks, respectively. Conclusion: Mepolizumab demonstrated clinically meaningful benefits in a real‐world CRSwNP population, with nearly half of patients achieving a beneficial composite treatment response by week 52. Notably, progressive improvements between weeks 24 and 52 underscore the value of prolonged therapy and the importance of evaluating treatment response at one year.

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: Primary chronic rhinosinusitis (CRS) can be classified based on the sinuses involved and the dominant endotype of the mucosal inflammation. Since the introduction of type 2 targeted biologics as treatment option for CRS, assessment of the inflammatory status has gained importance in CRS patients. We here aimed to characterize CRS patients with and without elevated markers of type 2 inflammation.Methods: CRS patients who visited the outpatient ENT clinic in one of the 10 tertiary centers in 7 European countries were invited to use the Galenus Health mobile application for the monitoring of their disease.Results: CRS patients (n = 281) were stratified according to blood eosinophil counts or BEC (< 150 cells/μL: 21.6% of patients, ≥ 150 cells/μL: 78.4%; < 250 cells/μL: 36.3%, ≥ 250 cells/μL: 63.7%) and serum total IgE (< 100 IU/mL: 59.9%, ≥ 100 IU/mL: 40.1%). BEC and serum total IgE did not correlate well (Spearman r = 0.06; p = 0.39). CRS patients with BEC ≥ 150 cell/μL or ≥ 250 cells/μL, respectively, showed increased NPS, SNOT‐22, VAS for total CRS symptoms, loss of smell, nasal blockage, runny nose compared to patients with BEC below 150 or 250 cells/μL. CRS patients with increased serum total IgE (≥ 100 IU/mL) did not show differences in the outcome parameters compared to patients with levels below 100 IU/mL. CRS patients with asthma (58.9%) showed increased SNOT‐22 and VAS loss of smell compared to patients without asthma.Conclusions: A significant proportion of CRS patients exhibit a type 2 endotype, characterized by blood eosinophilia (78%), increased serum total IgE (40%) and/or concomitant asthma (59%). Our results underline the usefulness of eosinophils as a marker of type 2 inflammation and severity but challenge the utility of serum total IgE since it does not correlate with any of the markers of severity.

Introduction Asthma is a heterogenous disease shaped by different inflammatory pathways. The aim is to investigate transcriptomic profiles in asthmatic patients and associate these with inflammation, airway damage and lung function. Methods Adult asthma patients attending the outpatient pneumology clinic in our tertiary center, underwent diagnostic sputum induction and upon consent remaining sputum RNA was used for bulk RNA-sequencing (n = 56) coupled with unsupervised clustering. A retrospective analysis of comorbidities was performed. Sputum cytokine mRNA levels were determined via qPCR. Airway damage markers were determined in sputum supernatant Results Unsupervised clustering subdivided all asthmatic patients in one of three clusters. Cluster 1 contained most of the pauci-granulocytic asthma patients in whom oxidative stress was upregulated and TLR-signalling and several cytokine pathways down-regulated. Cluster 2 had upregulated S100 family signalling pathway genes, was mostly associated to type 2 inflammation with elevated sputum eosinophils, epithelial damage, IL-4 mRNA levels and allergy. Asthma patients in cluster 3 had worse lung function, upregulated inflammatory genes, increased sputum neutrophils and calprotectin levels. Conclusion Three different asthma clusters could be identified bridging over the classical type 2/non-type 2 classification. Clinical trial ClinicalTrials.gov Identifier: NCT01224938 registered on 19 October 2010.

The skin prick test (SPT) is the gold standard for identifying allergic sensitization in individuals suspected of inhalant allergy. A novel device, SPAT or Skin Prick Automated Test, that enables more standardized allergy testing has been developed. Previous research has shown reduced intra-subject variability of histamine wheals by SPAT. This study aimed to evaluate within-test agreement (% of patients with consistent test results) to detect sensitization to common inhalant allergens when a SPT is executed automated by SPAT or by manual SPT (SPMT) procedure. The 110 volunteers prospectively enrolled underwent both SPAT and SPMT with 3 pricks of house dust mite, timothy grass and birch, 2 pricks of histamine and 1 prick of glycerol. The proportion of consistent (3x positive - 3 x negative) and inconsistent (2x positive/negative - 1x positive/negative) test results were analysed. The proportion of inconsistent test results was significantly lower in the SPAT compared to the SPMT group. The delta histamine to control pricks was significantly higher in SPAT compared to SPMT group. Coefficient of variation was lower in SPAT compared to SPMT for house dust mite, timothy grass, birch pollen. Visual analogue scale for discomfort was significantly lower in SPAT compared to SPMT group. SPAT showed a 34% reduction in the number of inconsistent test results compared to manual SPT with common inhalant allergens. Patient experience is significantly improved when an allergy test is performed by SPAT compared to a manual SPT.

Background: The skin prick test (SPT) is the gold standard for identifying allergic sensitization in individuals suspected of having an inhalant allergy. Recently, it was demonstrated that SPT using a novel skin prick automated test (SPAT) device showed increased reproducibility and tolerability compared to the conventional SPT, among other benefits.Objective: This study aimed to evaluate prick location bias using the novel SPAT device.Methods: A total of 118 volunteers were enrolled in this study and underwent SPATs with histamine (nine pricks) and glycerol control (one prick) solutions on the volar side of their forearms. Imaging of the skin reactions was performed using the SPAT device, and the physician determined the longest wheal diameter by visually inspecting the images using a web interface. Prick location bias was assessed along the medial vs. lateral and proximal vs. distal axes of the forearm.Results: In total, 944 histamine pricks were analyzed. Four medial and four lateral histamine pricks were grouped, and wheal sizes were compared. The longest wheal diameters were not significantly different between the medial and lateral prick locations (p = 0.41). Furthermore, the pricks were grouped by two based on their position on the proximal–distal axis of the forearm. No significant difference was observed among the four groups of analyzed prick locations (p = 0.73).Conclusion: The prick location on the volar side of the forearm did not influence wheal size in SPAT-pricked individuals.

Over the past years, eosinophils have become a focus of scientific interest, especially in the context of their recently uncovered functions (e.g. antiviral, anti‐inflammatory, regulatory). These versatile cells display both beneficial and detrimental activities under various physiological and pathological conditions. Eosinophils are involved in the pathogenesis of many diseases which can be classified into primary (clonal) and secondary (reactive) disorders and idiopathic (hyper)eosinophilic syndromes. Depending on the biological specimen, the eosinophil count in different body compartments may serve as a biomarker reflecting the underlying pathophysiology and/or activity of distinct diseases and as a therapy‐driving (predictive) and monitoring tool. Personalized selection of an appropriate therapeutic strategy directly or indirectly targeting the increased number and/or activity of eosinophils should be based on the understanding of eosinophil homeostasis including their interactions with other immune and non‐immune cells within different body compartments. Hence, restoring as well as maintaining homeostasis within an individual's eosinophil pool is a goal of both specific and non‐specific eosinophil‐targeting therapies. Despite the overall favourable safety profile of the currently available anti‐eosinophil biologics, the effect of eosinophil depletion should be monitored from the perspective of possible unwanted consequences.