University Clinic of Pulmonary and Allergic Diseases Golnik

Hereditary angioedema (HAE) is a rare, potentially life-threatening disorder characterised by recurrent episodes of localised oedema caused by bradykinin overproduction. Accurate epidemiological data are essential for optimising diagnosis and treatment, particularly in underrepresented regions such as the Baltic states. This study aimed to examine the prevalence, clinical characteristics, genetic variants, and treatment accessibility for patients with HAE in the Baltic states of Estonia, Latvia, and Lithuania. This retrospective study included HAE patients diagnosed according to the WAO/EAACI 2021 criteria between 2004 and 2024. Demographic, clinical, and genetic data were collected and evaluated. Descriptive statistical analysis was performed using Jamovi (version 2.3). A total of 78 patients were identified in Estonia (n=30), Latvia (n=12) and Lithuania (n=36) from 2004 till 2024. In Lithuania, 7 patients had died and 3 were lost to follow-up, resulting in 26 patients remaining under active observation. While the total number of HAE cases identified across the three countries was reported, detailed clinical data and analyses were limited to the 68 patients who were alive and actively followed at the time of data collection. Estonia exhibited the highest point prevalence (2.19 per 100, 000), while Latvia had the lowest (0.65). The median diagnostic delay was longest in Latvia (24 years) and shortest in Estonia (9.5 years). SERPING1 gene pathogenic variants predominated. Estonia had the broadest availability of treatments, whereas Latvia had restricted access to modern therapies. Considerable variation exists in HAE prevalence, diagnosis, and treatment across the Baltic states. Estonia exemplifies best practices, while Latvia remains underserved. Regional collaboration and standardised care protocols are urgently needed.

Background: Triple therapy (long-acting muscarinic antagonists (LAMAs), long-acting beta agonists (LABAs) and inhaled corticosteroids (ICSs)) is a recommended treatment for moderate-to-severe asthma at GINA Steps 4 and 5. However, little is known about the acceptance and use of triple therapy in everyday practice. The EU-LAMA Survey assessed specialists’ knowledge and views on triple therapy in daily practice. Methods: A 19-question survey was administered to 630 pulmonologists, allergologists, general practitioners, and internal medicine specialists in Poland (58%), Greece (27%), Sweden (6.3%), Slovenia (5.4%), and Austria (3.7%) using a dedicated online platform and computer-assisted web interviews. Results: The majority of the physicians were pulmonologists (59%), followed by allergologists (15.7%). For uncontrolled asthma at GINA Step 4, 81% of the respondents preferred increasing the ICS dose to the maximum level, whereas 76% opted to add LAMAs to medium-dose ICSs. At GINA Step 5, 79% of the respondents chose LAMAs first, followed by biological therapy (51%). Oral corticosteroids were favored over increasing the ICS dose and adding LAMAs. Triple therapy was mostly administered in one inhaler (70% and 82% at GINA Steps 4 and 5, respectively). Barriers to the use of LAMAs included a lack of reimbursement (31%), unclear guidelines (24%), lack of experience (18%), insufficient evidence (13%), fear of step-up regimens (10%), and the ease of increasing ICS doses (9%). Conclusion: Many physicians continue to rely on oral corticosteroids at GINA Steps 4 and 5 and infrequently refer patients to triple therapy or biological treatments at GINA Step 5.

<bold>Introduction:</bold> Patients with chronic obstructive pulmonary disease (COPD) may be predisposed to Aspergillus-related disease and sensitization (AS), which has been linked to exacerbations and poorer clinical outcomes. This study aimed to evaluate the prevalence of Aspergillus (AS) and Candida sensitization (CS), as well as fungal IgG positivity, in stable COPD patients and explore their associations with clinical outcomes. <bold>Methods:</bold> This cross-sectional study included consecutive COPD patients at the University Clinic Golnik, Slovenia in 2024 undergoing multidisciplinary team intervention due to uncontrolled dyspnea or frequent exacerbations. Patients underwent predefined laboratory and functional testing. AS and CS were defined as AfIgE and CaIgE >0.35 kUA/L. Aspergillus IgG >40 kUA/L (AFpoz) and Candida IgG >150 kUA/L (CApoz) indicated fungal IgG positivity. <bold>Results:</bold> The study included 76 patients (age 70.2 ± 7.7 years, 54% male), with a mean FEV1% of 46.6 ± 20.8% and eNO of 19.5 ± 18.3 ppb. Blood eosinophil levels were 190 ± 147 cells/µL, and total IgE 151.8 ± 237. Mean CAT score was 17.0 ± 7.9, with 30% experiencing poorly controlled symptoms and 70% frequent exacerbations. Mean IgG levels for Aspergillus fumigatus and Candida albicans were 26.1 ± 32.9 mg/L and 61.2 ± 45.3 mg/L, respectively. The prevalence of AS was 6.1%, CS 6.2%, AFpoz 15.8%, and CApoz 7.4%. AFpoz correlated significantly with FEV1% (r=0.276, p=0.038), but AS, CS, and CApoz showed no correlation with FEV1%. None of the fungal markers were associated with frequent exacerbations. <bold>Conclusion:</bold> The prevalence of AS and CS was relatively low in this COPD cohort, and neither sensitization nor fungal IgG positivity was linked to frequent exacerbations.

Cold urticaria (ColdU) is characterized by wheals, angioedema, or both, which are triggered by exposure to cold. A subset of patients experiences cold-induced anaphylaxis (ColdA), a potentially life-threatening systemic reaction. The pathogenesis of ColdU remains incompletely understood, but mast cell activation plays a central role. Most hypotheses are decades old and require further investigations. ColdU and ColdA are clinically diagnosed and typically supported by cold stimulation testing (CST). However, standard CST methods may yield negative results despite a clear clinical history. ColdU is classified into typical and atypical forms based on CST responses. ColdA occurs more frequently in patients with mucosal angioedema involving the oropharynx. It is most commonly triggered by full-body cold exposure, such as swimming. Diagnostic workup should include a detailed history, CST, and evaluation for underlying conditions, particularly in patients with clinical signs and symptoms extending beyond the skin. First-line treatment involves second-generation H1-antihistamines, often needed at increased doses for disease control. Omalizumab has shown efficacy in clinical trials and case reports for refractory cases. Adrenaline is the first-line therapy for ColdA; high-risk patients should be prescribed autoinjectors and receive proper training in their use. This review provides an overview of the pathophysiology, classification, diagnostic procedures, and management of ColdU and ColdA, emphasizing clinical variability and unmet research needs.

Hereditary α-tryptasemia (HαT)—a genetic trait caused by increased α-tryptase-encoding typtase alpha/beta-1 (TPSAB1) copy number—is associated with adult mastocytosis. The primary objective was to assess the association between α-tryptase and pediatric mastocytosis. We also want to evaluate whether the KIT p.D816V mutation in peripheral blood leukocytes (PBLs) reliably predicts systemic mastocytosis (SM) in children. A prospective cohort of 68 children from a referral center in Slovenia with cutaneous mastocytosis (CM) underwent tryptase genotyping by droplet digital PCR and examination for KIT p.D816V in PBL using a sensitive PCR test. A significant majority of patients (57 of 68; [83.8%]) had at least one α-tryptase-encoding gene; none had HαT. 7 of the 68 (10.3%) who were positive for KIT p.D816V in PBL, one fulfilled diagnostic criteria for indolent SM, and another was diagnosed with monoclonal mast cell activation syndrome. One of those individuals had an increased basal serum tryptase (BST) level (14.5 ng/mL). We found a high presence of germline α-tryptase in children with CM, but not HαT. By employing sensitive examination for KIT p.D816V in PBL, in combination with clinical data and other examinations, our study suggests that KIT p.D816V in PBL may indicate systemic disease in children with CM.