People living with COPD are frequently inadequately treated due to underdiagnosis or misdiagnosis. The aim of this study was to evaluate the real-world performance of the beclomethasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) fixed triple combination formulated in a dry powder inhaler (DPI) in improving symptoms, lung function, and adherence in moderate to severe COPD patients uncontrolled on dual therapies. We conducted a non-interventional, open-label, single-arm, multicenter, prospective study across 19 outpatient centers in Slovenia. The primary objective was to measure symptom improvement with the COPD Assessment Tool (CAT). A total of 359 patients with moderate to severe COPD (97% classified as GOLD E, frequent exacerbators) were followed for 24 weeks. There was a significant 6-point reduction in the CAT score after switching from dual therapies to BDP/FF/G inhalation powder (95% CI: -7.0 to -5.5; p < 0.0001). FEV1 increased by 110 mL (95% CI: 90-130; p < 0.0001) and FVC by 95 mL (95% CI: 65-120; p < 0.0001), reaching a statistically significant improvement of 2.5 percentage points in the FEV1/FVC quotient. The net improvement in dyspnea severity was 50.9% (95% CI 44.7%-57.2%), as assessed using the modified Medical Research Council (mMRC) Scale. Treatment adherence improved significantly after 6 months of triple therapy. In our cohort, switching uncontrolled moderate-to-severe COPD patients from dual therapy to BDP/FF/G fixed triple inhalation powder led to significant improvements in symptoms, lung function, dyspnea, sleep quality, and treatment adherence.

Sarcoidosis is a systemic disorder driven by genetic predisposition, environmental exposures, and immune dysregulation, resulting in the formation of noncaseating granulomas across multiple organs. In cardiac sarcoidosis (CS), immune cell infiltration of the myocardium, epicardium, and endocardium may lead to conduction disturbances, ventricular arrhythmias, and heart failure. While overt cardiac involvement was historically considered rare, affecting only 5% of sarcoidosis patients, the wider availability and improved sensitivity of contemporary cardiac imaging have revealed a substantially higher burden, with cardiac involvement reaching up to 55% in selected, systematically screened populations. Current diagnostic approaches for CS, including endomyocardial biopsy (EMB), cardiovascular magnetic resonance (CMR), and fluorine-18 fluorodeoxyglucose–positron emission tomography (FDG-PET), offer valuable insights but are restricted by high costs, invasiveness, and limited sensitivity and specificity. These challenges, together with the disproportionate contribution of cardiac involvement to sarcoidosis-related mortality, underscore the need for innovative, non-invasive, and widely accessible diagnostic strategies. Emerging evidence suggests that novel serum biomarkers and genomic studies hold promise for transforming the diagnostic landscape of CS. Biomarkers may provide accessible, cost-effective tools to complement established diagnostic methods, while genetic insights could identify individuals at higher risk for cardiac involvement and stratify patients based on disease phenotype. This review examines current evidence on serum biomarkers and genetic studies in CS diagnosis, identifies critical knowledge gaps, and proposes future directions aimed at advancing diagnostic precision and improving clinical outcomes.

IntroductionDupilumab, an IL-4Rα antagonist that blocks IL-4/IL-13 signalling, is used in severe eosinophilic asthma to improve clinical control and suppress type 2 inflammation.MethodsWe evaluated the clinical and systemic immunologic effects of dupilumab, focusing on type 2 biomarkers, total and aeroallergen-specific IgE, and FcεRI (High affinity IgE receptor) - expressing cells. Thirty-three adults with severe eosinophilic asthma were enrolled and followed up for 12 months in two Slovenian centres. Clinical assessments, spirometry, FeNO (Fractional exhaled nitric oxide), ACT (Asthma Control Test) scores, complete blood counts, total IgE, aeroallergen-specific IgE, and FcεRI expression on basophils were measured at baseline and at 1.5, 3, 6, and 12 months.ResultsTwenty-seven patients completed follow-up and were included in the final analysis. Dupilumab treatment resulted in significant improvement in ACT (p = 0.0221), FEV1 (p = 0.0139) and reduction in exacerbations requiring OCS (oral corticosteroid) (p < 0.0001). FeNO declined by 78 %, total IgE by 83%, and aeroallergen-specific IgE by 65% with consistent reductions across perennial and seasonal allergens. Circulating eosinophils increased transiently, whereas basophils increased by 39%.ConclusionsDupilumab demonstrated sustained clinical improvement in patients with severe eosinophilic asthma, accompanied by broad immunologic modulation. Concurrent reductions in FeNO, total IgE, and aeroallergen-specific IgE indicate upstream inhibition of IL-4/IL-13-mediated inflammation, suggesting modulation of the underlying type 2 inflammatory network.

Background Peak Inspiratory Flow (PIF) is a critical determinant of dry powder inhaler (DPI) effectiveness in managing patients with Chronic Obstructive Pulmonary Disease (COPD). Suboptimal PIF may compromise drug delivery and clinical outcomes. Objective To evaluate the association between repeated PIF measures and disease exacerbations, hospitalisations, and symptom burden in patients with stable COPD. Methods In this multi-country, observational cohort, 415 participants aged ≥40 years with confirmed COPD and a smoking history underwent PIF measurements at their prescribed inhaler's resistance, and low-, and high-resistance levels using the In-Check DIAL G16. Clinical assessments occurred at 3 months (Follow-Up 1, FU1) and 6 months (Follow-Up 2, FU2) including spirometry, COPD Assessment Test (CAT) scores, medication use, and exacerbation/hospitalisation rates. Results At FU1, 29.4% (n=113/384) had typical suboptimal PIF and 28.6% (n=108/377) remained suboptimal at FU2. Participants with suboptimal PIF were more often female and current smokers, with consistently poorer lung function across both visits: lower FEV1 (% predicted: 33.7±9.1% versus 45.7±9.2%, p=0.01), actual FVC and inspiratory capacity were observed. Suboptimal PIF significantly predicted moderate (p=0.03) and severe (p=0.01) exacerbations, was associated with higher hospitalisation risks (p=0.05), and with greater use of short-acting beta agonist, oral corticosteroid, and triple therapy. Conclusions Suboptimal PIF is a stable, clinically meaningful marker of worse COPD outcomes and may guide more personalised inhaler selection.

Background: Hypereosinophilia, defined as a peripheral blood eosinophil count greater than 1.5 × 109/L, can arise from allergic, infectious, autoimmune, or malignant conditions. In solid tumors, it is rare and most often linked to mucin-secreting carcinomas, while on extremely rare occasions, it accompanies signet ring cell carcinoma, a highly aggressive form of adenocarcinoma. Case Presentation: A 64-year-old woman presented with dyspnea and hypereosinophilia (2.9 × 109/L). She was admitted with suspected eosinophilic pneumonia, but extensive testing was inconclusive. After bone marrow biopsy, her condition deteriorated; histology revealed metastatic signet ring cell carcinoma. PET/CT showed skeletal metastases without apparent local recurrence, although colonoscopy could not be performed to definitively rule it out. Retrospective review uncovered a 2 mm rectal polyp with signet ring cell carcinoma (SRCC) removed two years earlier. Peripheral eosinophilia progressively increased from 0.16 × 109/L ten months earlier to a peak of 4.29 × 109/L one month prior to admission. She died four weeks after discharge. Conclusions: To the best of our knowledge, this case represents one of the smallest reported primary colorectal SRCC lesions (2 mm) presenting with disseminated disease and paraneoplastic hypereosinophilia as the first diagnostic clue. Monitoring peripheral blood eosinophil counts may provide additional insight into disease activity and prognosis in solid tumors.

INTRODUCTION:Patients with chronic obstructive pulmonary disease (COPD) use dry powder inhalers (DPIs) for disease management. DPI effectiveness relies on the patient's peak inspiratory flow (PIF), which may not always be optimal. We conducted an observational multicentre, prospective, real-life cohort study to determine the prevalence of suboptimal PIF in patients with COPD. METHODS:415 participants (11%, n=47 women, mean age=70±8.7 years, mean forced expiratory volume in 1 s (predicted %)=48.1%) recruited from 17 international centres had baseline PIF recorded with an In-Check Dial device at three resistance levels: (1) low, (2) high and (3) the participant's maintenance device. We also recorded PIF from participants as they would do at home to verify their proper inhalation technique. Participants underwent spirometry and completed questionnaires (COPD Assessment Test (CAT), Test of Adherence to Inhalers (TAI)-12). RESULTS:Of the 415 participants, 18% of DPI users (n=75) exhibited suboptimal values of PIF (as typical PIF <than what was required for tested inhalers in the study) when evaluated across DPI resistance groups ranging from low (R1) to high (R5) resistance, compared with 14% of participants (n=60) using devices without resistance (R0). Additionally, 14% of study participants were incapable of producing an optimal PIF or unwilling to do so (27%), impacting medication effectiveness. Participants with suboptimal PIF values had higher mean total CAT score (17.7±7) compared with those with optimal PIF values (12.1±7.6). When assessed globally, 37% (n=56) of participants with suboptimal PIF values did not adhere to treatment, highlighting the need for improved patient education and support. CONCLUSION:Suboptimal PIF is common in COPD, requiring regular assessment and tailored inhalers. TRIAL REGISTRATION NUMBER:NCT04606394. Encepp EUPAS34689.

Background There are limited data on optimal management of chronic lung allograft dysfunction (CLAD). We aimed to describe the variability of diagnostic and therapeutic practices in Europe. Methods A structured questionnaire was sent to 71 centres in 24 countries. Questions were related to contemporary clinical practices for workup, monitoring and treatment of CLAD. The number of lung transplant procedures and patients in follow-up were collected. Results 44 centres (62%) responded from 20 countries, representing 74% of European activity. The prevalence of CLAD was estimated at 9.1 cases per million population (25th and 75th percentiles of 4.4, 15.7). Preferred initial workup for probable CLAD consisted of chest computed tomography (CT) (inspiratory 91% and expiratory 74%), donor-specific antibody (DSA) measurement (86%), bronchoalveolar lavage (BAL) (85%) and transbronchial biopsy (81%). For monitoring of definite CLAD, inspiratory CT (67%), DSA (61%) and BAL (43%) were preferred. Body plethysmography was unavailable for 16% of cases. Prophylaxis was based on preventing infections (cytomegalovirus 99%, inhaled antibiotics 70% and antifungals 65%), tacrolimus-based immunosuppression (96%), azithromycin (72%) and universal proton pump inhibitor treatment (84%). First-line treatment of CLAD was based on azithromycin (82%) and steroid augmentation (74%). Photopheresis was used in 26% of cases. Conclusion Current European practice CLAD detection is based on spirometry, inspiratory CT and DSA, with limited access to plethysmography and expiratory CT. Prophylactic treatment is based on azithromycin, tacrolimus-based immunosuppression and treatment of risk factors. No single treatment strategy is universally used, highlighting the need for an effective treatment of CLAD. The preferred first-line strategy is azithromycin and steroid augmentation.

Chronic respiratory disorders are the third leading cause of mortality globally. Consequently, there is a continuous pursuit of effective therapies beyond those currently available. The therapeutic potential of the glucagon-like peptide-1 (GLP-1) and the glucose-dependent insulinotropic polypeptide/GLP-1 (GIP/GLP-1) receptor agonists extends beyond the regulation of glycemia, including glucometabolic, cardiovascular, and renal effects, rendering them viable candidates, due to their mechanisms of action, for the possible treatment of respiratory disorders. This manuscript aims to provide a comprehensive evaluation of the evidence on potential direct (cellular) and indirect (metabolic) actions of GLP-1 and GIP/GLP-1 receptor agonists within the pulmonary systems. In addition, it examines their efficacy in addressing prevalent respiratory disorders, specifically chronic obstructive pulmonary disease (COPD), asthma, pneumonia, obstructive sleep apnea, pulmonary hypertension, lung cancer, and lung transplantation. Finally, the manuscript seeks to identify potential avenues for further focused research in this field.

Common inflammatory ground links obesity, insulin resistance, and asthma. As recognition of their interplay, one worsening the natural course of the other, is recognised, questions remain about how to adequately address them altogether to improve clinical outcomes. The present manuscript sheds light on the problem, describing possible pathophysiological links, clinical views, and therapeutic challenges, raising questions about what remains to be done, and calling for multidisciplinary treatment of these patients to detect diseases early and adequately address them before they become full-blown and deteriorate their health and quality of life.

Introduction: It has been suggested that Aspergillus fumigatus sensitization (AFS) in severe asthma patients is associated with increased risk of progressive lung damage and worse clinical outcomes (Denning DW et al, ERJ 2006). Despite this, real-world clinical data on patients with AFS are limited. Aims and objectives: To compare clinical, functional, inflammatory and radiographic characteristics between AFS and non-AFS in a Slovenian cohort of severe asthma patients. Methods: Of 75 patients included in the Slovenian section (site University Medical Centre Ljubljana) of the ERS Severe Asthma Registry (SHARP), 15 (20%) had AFS assessed by either skin prick test or specific IgE to Aspergillus. Demographics, maintenance oral corticosteroid (OCS) use, severe asthma exacerbation (SAE) rate, FEV1, total IgE, blood eosinophils, exhaled NO, and radiology data were were compared cross-sectionally between AFS and non-AFS patients. Results: AFS patients had higher serum IgE (median 403 IU/ml; IQR 234-892 IU/ml) vs non AFS patients (median 145 IU/ml; IQR 67-367 IU/ml; p=0.008) and higher prevalence of bronchiectasis (8 (53%) vs 9 (18%), respectively (p=0.005)). There were no significant differences between AFS and non AFS patients in maintanance OCS use (p=0.17), FEV1 % predicted (p= 0.28), level of exhaled NO (p= 0.19), level of blood eosinophils (p=0.70) and SAE/year (p=0.49). Conclusion: The higher prevalence of bronchiectasis in AFS severe asthma patients confirms previous data, but this is not true for FEV1 and maintenance OCS use. These results call for larger-scale multinational research into this under-recognised comorbidity, which the pan-European SHARP consortium can provide.

Congenital extrahepatic portocaval shunt (CEPS) is a rare condition in which a rare congenital vascular anomaly of the portal system is present. CEPS may manifest as pulmonary arterial hypertension (PAH). When diagnosed and treated early, PAH can be reversible. We report a case of a previously asymptomatic woman, who manifested with severe pulmonary hypertension during pregnancy and was consequently diagnosed with CEPS. After unsuccessful medical treatment, urgent lung transplantation was done.

BACKGROUND: Lung transplantation (LTx) can be considered for selected patients suffering from COVID-19 acute respiratory distress syndrome (ARDS). Secondary sclerosing cholangitis in critically ill (SSC-CIP) patients has been described as a late complication in COVID-19 ARDS survivors, however, rates of SSC-CIP after LTx and factors predicting this detrimental sequela are unknown. METHODS: This retrospective analysis included all LTx performed for post-COVID ARDS at 8 European LTx centers between May 2020 and January 2022. Clinical risk factors for SSC-CIP were analyzed over time. Prediction of SSC-CIP was assessed by ROC-analysis. RESULTS: A total of 40 patients were included in the analysis. Fifteen patients (37.5%) developed SSC-CIP. GGT at the time of listing was significantly higher in patients who developed SSC-CIP (median 661 (IQR 324-871) vs 186 (109-346); p = 0.001). Moreover, higher peak values for GGT (585 vs 128.4; p < 0.001) and ALP (325 vs 160.2; p = 0.015) were found in the 'SSC' group during the waiting period. Both, GGT at the time of listing and peak GGT during the waiting time, could predict SSC-CIP with an AUC of 0.797 (95% CI: 0.647-0.947) and 0.851 (95% CI: 0.707-0.995). Survival of 'SSC' patients was severely impaired compared to 'no SSC' patients (1-year: 46.7% vs 90.2%, log-rank p = 0.004). CONCLUSIONS: SSC-CIP is a severe late complication after LTx for COVID-19 ARDS leading to significant morbidity and mortality. GGT appears to be a sensitive parameter able to predict SSC-CIP even at the time of listing. (C) 2022 The Author(s). Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation.

We report a case of human Dirofilaria repens infection in a woman in Slovenia who had concomitant pleural and subcutaneous manifestations of the infection. This case report illustrates the clinical course of a severe symptomatic parasitic infection that had multisystemic manifestations.

Izhodišča: Presaditev pljuč je zahtevna metoda zdravljenja za izbrane bolnike z napredovalo pljučno boleznijo. Naraščanje števila primernih kandidatov in standarizacija posega sta v letu 2018 omogočila vzpostavitev transplantacijskega centra v UKC Ljubljana. Prispevek poroča o prvih rezultatih. Metode: Opravili smo analizo lastnega registra bolnikov. Rezultate smo primerjali s skupino bolnikov, ki so jim pred tem opravili presaditev v AKH Dunaj. Rezultati: Med 15. 9. 2018 in 15. 9. 2021 smo opravili 37 presaditev pljuč (od tega pri 13 ženskah). Indikacije so bile KOPB (n = 13, 35 %), pljučne fibroze (n = 7, 19 %), cistična fibroza (n = 5, 14 %), kovidna pljučnica (n = 4, 11 %), bronhiektazije (n = 3, 8 %), pljučna hipertenzija (n = 2, 5 %), limfangioleiomiomatoza (n = 1, 3 %), pomanjkanje alfa-1-antitripsina (n = 1, 3 %) in bronhiolitis (n = 1, 3 %). V primerjavi s prejšnjo skupino bolnikov, napotenih v AKH Dunaj (71 bolnikov, od tega 35 žensk), je bil delež bolnikov s KOPB višji (35 % in 16 %, p = 0,019), bolniki pa so bili starejši (mediana [razpon], 59 [14–68] in 43 [4–58] let, p = 0,001). 76 % darovanih pljuč ni ustrezalo standardnim merilom (30 % darovalcev je bilo starejših od 55 let, 22 % jih je imelo infiltrate na rentgenogramu pljuč, 24 % pa ni izpolnjevalo enega od ostalih meril), v 43 % pa je bila potrebna redukcija velikosti, kar pa ni vplivalo na primarno odpoved presadka. Kratkoročno preživetje je bili podobno v obeh skupinah (1-letno preživetje v UKC Ljubljana 89 % [95 % CI 78–99 %] in v AKH Dunaj 83 % [95 % CI 74–92 %]). Zaključek: Prvi rezultati kažejo, da so zgodnji izidi po presaditvi pljuč primerljivi pri bolnikih, ki so imeli presaditev v UKC Ljubljana ali v AKH Dunaj.