Despite the need for immediate treatment during acute allergic reactions (AARs), many patients do not consistently carry medication. A new mouth-dissolving dexamethasone film offers a portable, easily administered alternative to corticosteroid tablets. This non-randomized, open-label, low-interventional real-world trial assessed satisfaction (accessibility and safety/security) with the mouth film versus betamethasone tablets in adults prescribed tablets for moderate to severe AARs at a Swedish primary care center. Over six months, participants had access to both treatments and reported monthly via an electronic diary; qualitative responses were converted to Likert scales where applicable. Of 50 enrolled, 44 provided diary data (mean age 50 years, 74% female, 58% had an epinephrine autoinjector). In total, 189 responses were collected: 98% stated that the participant was satisfied or very satisfied with mouth film accessibility versus 58% for tablets (mean Likert scores 3.5-3.7 vs. 2.5-2.8; p < 0.001). A higher feeling of safety with the mouth film versus tablets was reported in 78% of responses and improved medication carriage compliance in 77%. At six months, 69% preferred the film. Of 18 AARs in total reported by 13 participants, the mouth film was chosen for treatment of 16 (11 participants); in 94%, the mouth film was found immediately accessible, and in 94%, the efficacy was rated as good or very good. In conclusion, the mouth film improved perceived accessibility, safety/security, and medication-carriage compliance compared with tablets for the treatment of AARs.

Purpose:Time to biologic initiation for the treatment of severe asthma (SA) is affected by many factors, including ease of access to biologics, which is often subject to approval by regulatory authorities and reimbursement criteria by relevant agencies. We investigated the association between ease of biologic access (using the biologic accessibility score [BACS] as a proxy) and post-biologic asthma outcomes, including remission. Methods:This ecological study, using data from CHRONICLE (a US severe asthma registry), the International Severe Asthma Registry (ISAR), and the Optimum Patient Care Research Database (OPCRD), included patients with SA from 21 countries. Associations at the country level, between BACS, a composite score of prescription criteria for biologics in SA, and the proportion of patients with a favorable asthma outcome 1-year post-biologic in each setting (ie ISAR country or in the CHRONICLE or OPCRD datasets) were tested. Several definitions of favorable outcome were used, including proportion of patients who achieved clinical remission (defined using 2, 3 and 4 domains), experienced no exacerbations, had well- or partly controlled asthma, a percent predicted forced expiratory volume in 1 second (ppFEV1) or percent predicted peak expiratory flow rate (ppPEFR) ≥80%, and no long-term oral corticosteroid (LTOCS) use. Results:A total of 9,183 patients were included. A higher BACS (as a proxy of easier access to biologics) was associated with a higher likelihood of achieving clinical remission (p≤0.001), no exacerbations (p<0.001), well- or partly controlled asthma (p=0.047), a ppFEV1 or ppPEFR ≥80% (p=0.004), and no need for LTOCS (p=0.045) 1 year post-biologic initiation. Conclusion:Easier access to biologics for patients with SA, a prerequisite for shorter time-to-initiation, was associated with a greater probability of achieving clinical remission and other favorable asthma outcomes. Initiating biologics earlier in the asthma disease course may help unlock greater therapeutic potential in SA. These findings warrant confirmation in additional studies to further establish the causal relationship between biologic accessibility, timing of initiation, and clinical outcomes in SA.

BACKGROUND:The objective was to assess how preferences for a self-dissolving dexamethasone mouth film versus conventional tablets for acute allergic reactions may vary according to population characteristics and the level of outcome knowledge for the intervention (i.e., ex ante, interim, and ex post). METHODS:We used preference data from two studies: a questionnaire study with a choice between mouth film and tablets based on a description of the mouth film (ex ante), and a clinical trial with ratings of accessibility and perceived security when the mouth film was available (interim) or used for acute allergic reactions (ex post). Associations between preferences and participant characteristics (demographics and clinical history) were analyzed using logistic regression models. RESULTS:Preference for the mouth film over tablets remained strong as outcome information increased from ex ante to ex post and was consistent across study populations. Higher relative preference was associated with female sex, longer disease duration, older age, and prior severe reactions, whereas satisfaction with current treatment and regular allergy check-ups were linked to weaker relative preference. CONCLUSIONS:Preference for the mouth film over tablets was stable, but the degree of preference may depend on characteristics that influence sensitivity to treatment challenges in acute situations.

BACKGROUND:The progression from mild-to-moderate to severe asthma remains unclear. This study aimed to assess the risk of progression following the first asthma exacerbation in mild-to-moderate asthma and to identify risk factors and high-risk patient profiles. METHODS:This was an observational cohort study based on Danish data from the Nordic Dataset for Asthma Research collaboration platform. Adult patients with mild-to-moderate asthma experiencing their first asthma exacerbation were identified between 2000 and 2018 and followed prospectively for 5 years for the development of severe asthma according to European Respiratory Society (ERS) / American Thoracic Society (ATS) guidelines. Baseline risk factors for progression to severe asthma were assessed using multivariable logistic regression models, and risk of progression was evaluated across specific patient profiles. RESULTS:Among 99 748 patients with mild-to-moderate asthma experiencing the first asthma exacerbation, 4.1% progressed to severe asthma within 5 years. Risk factors included baseline age 40-49 years (odds ratio [OR] = 1.62; 95% CI, 1.49-1.77), experiencing an exacerbation despite medium-dose inhaled corticosteroid (ICS) use (OR = 3.72; 95% CI, 3.39-4.09), high use of short-acting beta agonist (OR = 1.76; 95% CI, 1.64-1.90), ≥2 respiratory infections (OR = 1.61; 95% CI, 1.49-1.73), and blood eosinophil counts ≥ 0.6 × 109/L (OR = 1.97; 95% CI, 1.47-2.61). A patient aged 40-49 years with late-onset eosinophilic asthma, treated with medium-dose ICS and with recurrent respiratory infections, had a 30.4% 5-year risk of progressing to severe asthma. CONCLUSION:In patients with mild-to-moderate asthma experiencing their first asthma exacerbation, few (4.1%) patients overall progressed to severe asthma within 5 years, but specific high-risk patient profiles faced risks of up to 30%. Whether early recognition can modify this risk warrants further investigation.

Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by airway remodeling, including emphysema and fibrosis. Proteoglycans and their glycosaminoglycan (GAG) chains are key components of the extracellular matrix and may be altered as the disease advances. This study analyzed lung tissue from COPD patients (GOLD stages II-III and IV), non-COPD smokers, and non-smokers to assess proteoglycan and GAG changes. While LC-MS revealed no alterations in chondroitin/dermatan sulfate (CS/DS) or heparan sulfate (HS) proteoglycan core proteins, the total GAG level increased in GOLD II-IV patients. HS displayed increased N- and 2-O-sulfation in GOLD IV, while CS/DS levels and 4-O-sulfation were enhanced across GOLD II-IV. These findings were supported by transcriptomic data indicating upregulation of CHST11, the main CS/DS 4-O-sulfotransferase. In line with previous findings, TGF-β signaling was shown to be enriched in COPD patients and to regulate the CHST11 expression. These results were confirmed by TGF-β stimulation of lung fibroblasts showing increased CS/DS levels, 4-O-sulfation, and CHST11 expression. In conclusion, COPD is associated with disease-stage-specific changes in GAG sulfation, particularly enhanced CS/DS 4-O-sulfation that is likely to be driven by TGF-β. These alterations may contribute to extracellular matrix remodeling and represent potential targets for therapeutic intervention to mitigate disease progression.

BACKGROUND:Asthma severity is influenced by complex immunologic and environmental factors. While allergic asthma is linked to increased susceptibility to respiratory infections, the combined role of allergy and antibiotic-treated infections in progression to severe asthma has not been fully evaluated. OBJECTIVE:To evaluate whether allergic asthma and recurrent respiratory infections (RRI) requiring antibiotics are associated with increased risk of developing severe asthma. METHODS:We conducted a registry-based cohort study using Swedish national registry data. Adults with mild-to-moderate asthma were identified in 2014 (baseline) based on prescription records and absence of severe disease indicators. During a two-year exposure window (2015-2016), RRI was defined as ≥ 2 antibiotic prescriptions for lower respiratory tract infections. The outcome was development of severe asthma during 2017-2019, based on ERS/ATS treatment criteria. Allergic asthma was defined by ≥ 2 prescriptions for anti-allergic medications at baseline. RESULTS:Among 113,393 patients, 24,692 (21.8%) had allergic asthma. RRI occurred more frequently in allergic versus non-allergic asthma (7.5% vs. 5.9%, p < 0.001). A total of 869 patients (0.77%) developed severe asthma. Incidence was higher in those with RRI and highest among patients with both allergic asthma and RRI (2.0%), corresponding to a relative risk of 3.47 (95% CI: 2.49-4.83) versus patients with neither exposure. Results were consistent after adjustment for age, sex and comorbidities. CONCLUSION:Allergic asthma and antibiotic-treated respiratory infections were independent and additive predictors of severe asthma progression. These findings support a clinically actionable risk profile and may inform targeted preventive strategies in asthma management.

Protein profiling of whole cells can accurately define cell subsets specific to disease identity and/or severity. Preserving whole cells on cytospin slides is common practice but is often used only for differential counts. Here we ran two studies and successfully applied a high-plex protein panel using the NanoString GeoMx, quantifying up to 47 proteins (of immune, cell death, and MAPK signalling markers) in bronchoalveolar lavage (BAL) cytospins from the four major cell types: macrophages, neutrophils, type-2 granulocytes and lymphocytes. Despite the small sample size for this feasibility study, several significant differences between disease and controls within several BAL cell types for both the asthma cohort (n=21) and the COPD cohort (n=20) were found. Overall, we believe applying this method can maximise biomarker discover of any precious preserved cytospin clinical samples and that the significant disease specific cell subsets discovered during the method testing are worthy of future investigation. ### Competing Interest Statement The authors have declared no competing interest. Crafoord Foundation, https://ror.org/02hwwbr17, 2021-2023 Sanofi Type2 Innovation, 2020 Royal Physiographic Society of Lund: Endowments for the Natural Sciences, Medicine and Technology, 2023 Swedish Asthma and Allergy Association, https://ror.org/042ha6j15 Interreg ÖKS, NYPS20201002 The Swedish Heart and Lung Foundation

Chronic respiratory diseases (CRDs) remain 1 of the leading causes of preventable morbidity and disability worldwide, affecting up to one-third of the total Western population in 2025. Recognizing the substantial burden of inflammatory airway diseases such as asthma, COPD, chronic rhinosinusitis, and respiratory allergy, the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) organized the symposium "Shaping the Future of Respiratory Care" in April 2025 in Brussels, Belgium, at the occasion of the 10-year jubilee. Featuring keynote speakers from the World Health Organization and EUFOREA, this initiative had the following aims: (1) promoting dialogue on translating innovations into daily clinical practice; (2) encouraging collaboration between the different stakeholders in the respiratory field; and (3) defining strategic priorities to transform respiratory care and arrest the CRD epidemic over the next decade. The symposium highlighted the importance of moving toward predictive, preventive, and patient-centered medicine, while supporting value-based health care systems to improve long-term patient outcomes. This report summarizes the main insights and strategic directions discussed at the meeting.

Abstract Pulmonary vascular remodelling is common in patients with chronic obstructive pulmonary disease (COPD). Vascular endothelial growth factors (VEGFs) are key mediators in angiogenesis and vascular remodelling and exist in different isoforms. VEGF-A is the most potent angiogenic member binding to VEGF receptor 2 (VEGFR2). There are, however, few studies on other isoforms, as VEGF-C, and its receptor VEGFR3 in COPD and subsequent impact of cAMP therapies on VEGF isoforms. Our aim was to evaluate the VEGF isoform synthesis in primary distal lung fibroblasts from control subjects (non-smokers (n=6) and ex-smokers (n=4), and COPD subjects with GOLD stage II (n=4) or GOLD stage IV (n=6), and the expression of VEGFR2 and VEGFR3 in human lung tissue. Primary lung fibroblasts were exposed to the cAMP generating therapies formoterol, iloprost, or roflumilast, the adenylyl cyclase activator forskolin or to transforming growth factor (TGF)-b1. VEGF isoforms were evaluated with ELISA. VEGF-C release was not significantly altered by TGF-β1, in contrast to the increased levels of VEGF-A, in all fibroblasts. VEGF-C was significantly decreased by iloprost, forskolin and formoterol, whereas VEGF-A was significantly increased by iloprost and forskolin, with differences in release pattern between and within fibroblasts from control and COPD subjects. Exposure to VEGF-C specifically towards VEGFR3 decreased proliferative rate in human lung fibroblasts and bronchial epithelial cells. VEGFR2 and VEGFR3 were both present in parenchymal lung tissue and VEGFR2 in pulmonary blood vessels. in both healthy and COPD, whereas there was elevated expression of VEGFR3 in bronchial epithelium. In conclusion, TGF-β1 and cAMP generating compounds have significant effects on VEGF-C and VEGF-A synthesis, which appear dysregulated in lung fibroblasts from ex-smokers and patients with COPD. Increased VEGFR3 expression in the bronchial epithelium in lung tissue, and studies into their functional impact, warrants further investigations.

AbstractBackgroundSeasonal allergic rhinitis (AR) impacts public health by affecting work productivity and quality of life. The Swedish tree pollen season starts in February with alder and hazel pollination, followed by birch and ends with oak in May. Systemic corticosteroids are often prescribed when topical treatments fail, despite limited evidence supporting their efficacy.ObjectiveTo compare the effectiveness of prednisolone tablets versus antihistamine tablets in reducing symptoms and medication usage in patients with moderate to severe tree pollen‐induced AR.MethodsThis interventional single‐center, double‐blinded randomized trial included 34 patients. Treatment was initiated, and symptoms were registered during the tree pollen season. The two groups received either prednisolone tablets (20 mg) or ebastine tablets (20 mg) for 7 days. Treatment effects were evaluated by comparing daily symptom scores, use of topical medication, and a combined symptom‐medical score between the groups. Quality of life was recorded at the start and after 3 weeks.ResultsBoth interventions demonstrated efficacy in enhancing quality of life metrics. The area under the curve (AUC) for the combined symptom severity and medication usage score averaged 34.0 (SD = 19.1, 95% CI = 24.5–43.4) in the group treated with prednisolone. This was marginally lower than the control group, with an AUC of 32.6 (SD = 13.2, 95% CI = 25.6–39.7). The difference was not statistically significant (p = 0.80). Both groups exhibited only mild adverse events, which were statistically comparable in frequency and severity.ConclusionsPrednisolone tablets did not show superior efficacy over antihistamine tablets in reducing symptoms or medication usage in tree pollen‐induced AR. These results suggest that systemic corticosteroids may not provide additional benefits over antihistamines, and clinicians should prioritize individualized treatment based on patient preferences and tolerability.

Background: Asthma characterization using blood eosinophil count (BEC) (among other biomarkers and clinical indices) is recommended in severe asthma (SA), but the masking effect of oral corticosteroids (OCS), makes this challenging. Aim: Our aim was to explore the effect of OCS use (both intermittent [iOCS] and long-term [LTOCS]) prior to biologic initiation on SA phenotype and biomarker profile in real-life and to characterize the burden of SA among patients prescribed LTOCS by biomarker profile. Methods: This was a registry-based cohort study, including data from 23 countries collected between 2003 and 2023 and shared with the Internatonal Severe Asthma Registry (ISAR). Patients with SA were categorized into 3 cohorts, those with: (i) no prescription for OCS, (ii) prescription(s) for iOCS (ie, ≤90 days in previous 12-months, usually short courses for exacerbations), and (iii) prescriptions for LTOCS (ie, >90 days in previous 12-months). Biomarker distribution (ie, BEC, fractional exhaled nitric oxide [FeNO], and total Immunoglobulin E [IgE]) were quantified in the year prior to biologic initiation in patients with SA according to OCS prescription pattern. Phenotypes were characterized for those prescribed LTOCS according to BEC cut-off (<150 and ≥ 150 cells/μL). Results: Of 4305 patients included, 5.0% (n = 215), 54.1% (n = 2330) and 40.9% (n = 1760) were prescribed no OCS, iOCS, and LTOCS, respectively. The BEC distribution varied by prescription pattern and LTOCS dose (<5 mg to ≥20 mg/day); BEC was <150 cells/μL in 28.6% (n = 369/1288) of LTOCS patients, compared to 19.5% (n = 284/1460) of iOCS patients and 14.0% (n = 21/150) of those in the no OCS group. Median BEC was also significantly lower in the LTOCS versus the iOCS group (310 vs 400 cells/μL; p < 0.001). A similar pattern was noted for IgE, but not FeNO. Among LTOCS patients with BEC <150 cells/μL, 39.9% experienced ≥4 exacerbations, 75.1% had uncontrolled asthma symptoms and 55.9% had evidence of persistent airflow obstruction (compared with 40.9%, 76.2% and 59.5% of those with BEC ≥150 cells/μL, respectively). Conclusions: OCS, whether prescribed intermittently or long term, affect BEC distribution potentially leading to heightened risk of phenotype misclassification and influencing subsequent treatment decisions. FeNO appears to be less susceptible to OCS-induced suppression. Disease burden was high for those in the LTOCS group and was high independent of dose and BEC. Our findings highlight the importance of considering OCS use, even intermittent use, when characterizing SA, and suggests the need for earlier phenotyping and alternative treatment strategies for LTOCS patients with low BEC.

Although Chronic Obstructive Pulmonary Disease (COPD) is generally considered a progressive condition with limited reversibility, recent data suggests potential for lung function improvement with exercise. Mechanistic insights into exercise-induced benefits remain limited, but in vitro models offer promise for understanding cellular and molecular changes. This study aims to elucidate the mechanisms behind lung tissue regeneration in COPD through adapted exercise training as well as validating advanced lung function tests, such as Impulse Oscillometry (IOS) and Airspace Dimension Assessment (AiDA) for improved detection of early physiological /structural changes and predicting clinical outcomes. This is the protocol of a multicenter, hypothesis-generating, single-arm study exploring the mechanisms for lung regeneration in subjects with COPD induced by exercise. The exercise protocol includes supervised and individually tailored moderate-intensity aerobic- and muscle strengthening exercise, performed three times per week for 12 weeks. Eighty sedentary adults with a clinically stable COPD will be recruited at two study sites. Included participants will be assessed at baseline and at 12 weeks by comprehensive pulmonary function testing (including spirometry, IOS, body plethysmography, diffusing capacity of the lung, single breath nitrogen wash-out, AiDA, questionnaires, physical capacity performance (including 6-minutes walking test (6MWT), one-minute sit-to-stand test, and cardiopulmonary exercise testing (CPET)), and collection of blood and urine samples and bronchoscopy. A mid-intervention assessment at week 6 will include medication use, health status, questionnaires, spirometry, and blood sampling. Understanding the molecular and cellular activities related to lung function induced by exercise provides insights into repair pathways, challenges the notion of irreversible lung damage in COPD, and paves the way for improved management strategies with potential identification of biomarkers and pharmacological interventions. ClinicalTrials.gov ID NCT06335992 (Registration date 2024-03-28).

BACKGROUND:Asthma with low levels of type 2 (T2) biomarkers is poorly understood. OBJECTIVE:To characterize severe asthma phenotypes and compare changes in asthma outcomes from pre- to postbiologic treatment along a gradient of T2 involvement. METHODS:This was a registry-based cohort study including data from 24 countries. Biomarker distribution (blood eosinophil count, fractional exhaled nitric oxide, and IgE) was quantified before biologic initiation. Clusters were identified using a 5-component Gaussian finite mixture model and phenotypically characterized. Changes in asthma and health care utilization outcomes between 1-year pre- and postbiologic initiation were compared between clusters and by biologic class. RESULTS:Among 3675 patients, 5 biomarker clusters were identified along a gradient of T2 involvement: cluster A with the lowest T2 involvement (16.4%), cluster B (20.4%), cluster C (22.9%), cluster D (30.3%), and cluster E with the highest T2 involvement (10.0%). In multivariable analysis, biologic use was associated with improved outcomes in all clusters but tended to be better at the higher end of the T2 spectrum. For example, patients in cluster C had a significantly greater increase in forced expiratory volume in 1 second compared with cluster A (difference 0.16 L [95% confidence interval: 0.08, 0.25]; P < .001). The odds of uncontrolled asthma were approximately 0.6 for all clusters compared with cluster A. Overall, exacerbation rates were lower, and greater improvements in lung function and asthma control were noted for anti-IL-5/5 receptor (R) (but not anti-IgE or anti-IL-4Rα) for all clusters compared with cluster A. CONCLUSION:T2-targeting biologics have utility in the management of asthma with low T2 involvement, but more effective therapies are needed. Further research is warranted to identify specific pathogenic pathways at the lower end of the T2 spectrum that can be effectively targeted by biologics.

Asthma is a common, multifaceted respiratory disease with a major impact on quality of life. Despite increased insights into mechanisms underlying various asthma phenotypes and endotypes and the availability of targeted biologic treatment options, the disease remains uncontrolled in a substantial proportion of patients with risk of exacerbations, requiring systemic corticosteroids, and with progressive disease. Current international guidelines advocate for a personalized management approach to patients with uncontrolled severe asthma. The European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) asthma expert panel was convened to discuss strategies to optimize asthma care and to prevent systemic corticosteroid overuse and disease progression. In this meeting report, we summarize current concepts and recommendations and provide a rationale to implement personalized asthma management at earlier stages of the disease. The ultimate goal is to move away from the current one-size-fits-most concept, which focuses on a symptom-driven treatment strategy, and shift toward a phenotype- and endotype-targeted approach aimed at curbing the disease course by improving clinical outcomes and preserving health-related quality of life. Herein, we provide a consensus view on asthma care that advocates a holistic approach and highlight some unmet needs to be addressed in future clinical trials and population studies.