Gül Karakaya

Objective: Although hypersensitivity reactions to oral iron preparations are rare, they are clinically challenging as they can limit treatment options for iron deficiency anemia. Data on cross-reactivity between different oral iron formulations are limited, and guidance on safe switching strategies is insufficient. This study aimed to define the clinical characteristics of patients with suspected oral iron hypersensitivity and to evaluate the tolerance of alternative oral iron preparations using supervised oral provocation testing. Materials and Methods: We retrospectively analyzed 18 adult patients who presented to a tertiary allergy clinic with a history of hypersensitivity to an oral iron preparation between June 2011 and June 2025. Alternative oral iron formulations were selected based on differences in iron valence ferrous (Fe²⁺) and ferric (Fe³⁺) and ligand or complex structure. Oral provocation tests were performed using graded protocols. Results: The cohort included 17 females and 1 male with a mean age of 42.7 ± 9.5 years. Most reactions were attributed to ferrous (Fe²⁺) salts (77.8%), whereas ferric (Fe³⁺) salts accounted for 22.2% of the culprit oral iron formulations. The most frequent symptom was skin symptoms (77.8%), followed by angioedema or mucosal involvement (38.9%), systemic or vasovagal-like symptoms (27.8%), and gastrointestinal complaints (11.1%). Three patients experienced clinically anaphylactic reactions. Alternative iron formulations were selected by altering the iron oxidation status and/or ligand structure. All oral provocation tests with alternative preparations, including extended provocation protocols, were negative (100%), indicating excellent tolerance and a low probability of clinically significant cross-reaction. Conclusion: In patients suspected of having oral iron hypersensitivity, switching to an alternative oral iron preparation with a different oxidation state and/or ligand by performing provocation tests appears to be a safe and effective strategy. These findings support that hypersensitivity reactions are more closely related to formulation-specific components than to iron itself, and offer a practical approach to maintaining oral iron therapy.

Background: Donidalorsen, a prekallikrein-directed antisense oligonucleotide indicated for prophylaxis of hereditary angioedema (HAE) attacks in patients aged ≥ 12 years, demonstrated efficacy and acceptable safety in the phase 3, placebo-controlled OASIS-HAE trial (NCT05139810). Here, we report 1-year results from the corresponding open-label extension (OLE) cohort of the OASISplus study (NCT05392114). Methods: OASISplus included patients who rolled over from OASIS-HAE. Patients who received donidalorsen 80 mg or placebo subcutaneously every 4 weeks (Q4W) in OASIS-HAE received donidalorsen Q4W in OASISplus. Patients who received donidalorsen 80 mg or placebo every 8 weeks (Q8W) in OASIS-HAE received donidalorsen Q8W or Q4W, if not attack-free in the final 8 weeks of OASIS-HAE. The primary endpoint was safety (ie, incidence of treatment-emergent adverse events [TEAEs]). Secondary endpoints included the monthly rate of HAE attacks and Angioedema Quality of Life (AE-QoL). Results: The OLE cohort included 83 patients (Q4W, n=69 [83%]; Q8W, n=14 [17%]). Of these, 75 (90.4%) completed Year 1, and 6 patients receiving donidalorsen Q8W in OASIS-HAE switched to the Q4W dosing group in the OLE. Median donidalorsen exposure was 392.3 days. From Weeks 0 to 52, reductions in mean HAE attack rate from OASIS-HAE baseline were 94% (Q4W) and 95% (Q8W), and patients reported clinically meaningful improvements in mean AE-QoL total score at Week 52 (Q4W, 28.1 points; Q8W, 26.7 points). Twenty-two (27%) patients reported treatment-related TEAEs; none were serious, and injection-site reactions were the most frequently reported. Conclusion: Donidalorsen demonstrated sustained reductions in HAE attack rate, improvements in QoL, and an acceptable safety profile after 1 year of treatment.

Background : This study aimed to comprehensively define the clinical profile of elderly patients with hereditary angioedema (HAE) caused by C1 esterase inhibitor (C1INH) deficiency and/or dysfunction (HAE-C1INH). Furthermore, it sought to reveal age-related differences in disease expression and management by comparing these patients with their younger counterparts. Methods: In this retrospective study, seventy-six patients were included. All patients had been diagnosed with HAE-C1INH. Results: A total of 9 (12%) patients were ≥65 years, 7 (77%) of whom were female. The median age at the time of diagnosis was higher in the elderly group, whereas the median age at the first symptom was similar. There was a significant delay in diagnosis time in the elderly group. Hypertension was the most frequent comorbidity among elderly patients. The median number of angioedema attacks in the last year was 6, and similar to 10 in patients < 65 years. Angioedema control in the last three months was lower in older patients. The rate of laryngeal edema was similar in patients < 65 years and older patients. The use of short-term prophylaxis (STP) was higher in the elderly group. The most commonly used treatment for acute attacks was pdC1-INH. Two patients in the elderly group did not benefit from danazol. No adverse events with icatibant, pdC1-INH, danazol were encountered among patients. Conclusions: Compared to patients younger than 65 years of age, annual attack rates were similar, whereas elderly patients had lower angioedema control for the last three months. The use of STP rates was higher among elderly patients.

Objective: To investigate the relationship between angioedema (AE) attacks and dental procedures in patients with hereditary angioedema (HAE) and to identify potential risk factors. Patients and Methods: Patients diagnosed with HAE between 1999 and 2024 at a tertiary adult allergy clinic were retrospectively reviewed for dental procedures and AE attacks. Results: Of 102 HAE patients, 74 were included after excluding 28 with incomplete data. Dental procedures were performed in 47 patients (63.5%), totaling 85 interventions, most commonly tooth extractions (50.6%), restorations (34.1%), and root canal treatments (11.8%). Preprocedural prophylaxis was administered in 46 cases (54.1%), primarily with plasma-derived C1-inhibitor (pdC1-INH) (n = 36), followed by danazol (n = 7) and icatibant (n = 3). A total of 17 AE attacks (20%) were recorded, all involving the oropharyngeal region. Prophylaxis significantly reduced attack rates (p = 0.022), with no significant difference between pdC1-INH and danazol (p = 0.572). In the pdC1-INH group, attack rates were similar for 500 IU and 1000 IU doses (11.1% vs. 14.8%, p = 0.781). Conclusion: Preprocedural prophylaxis reduced AE attack frequency in dental procedures, with similar outcomes for pdC1-INH and danazol. Similar results were also observed between 500 IU and 1000 IU pdC1-INH.

Considerable overlaps exist between asthma phenotypes and the clinical significance of these overlaps remains undetermined. The objective of this study is to analyze the characteristics of asthma overlap phenotypes using data from the Turkish Adult Asthma Registry (TAAR). This cross-sectional registry study included 2053 adult patients (74.8% female) with asthma. Overall, 39.3% (n = 697) had allergic-eosinophilic (AE), 26.0% (n = 461) had allergic-non-eosinophilic (ANE), 21.3% (n = 377) had non-allergic-eosinophilic (NAE), and 13.4% (n = 237) had non-allergic-non-eosinophilic (NANE) asthma. Severe asthma exacerbations and emergency department (ED) visits were more frequent in the AE (28.3%, 31.2%, respectively) and NAE groups (36.0%, 34.0%, respectively) than in the ANE (14.3%, 20.6%, respectively) and NANE groups (12.6%, 16.7%, respectively) (p < 0.001). FEV1 values were significantly lower in the AE group than in the ANE and NANE groups (p < 0.001, p = 0.048, respectively) and in the NAE group than in the ANE group (p < 0.001). Risk factors for poor asthma control included living in rural areas, asthma-related ED visits, FEV1 < 60% in the NAE; being overweight, chronic rhinosinusitis, oral corticosteroids use, age < 40 years in the NANE; FEV1 < 80% in the AE; and severe asthma exacerbations, ED visits for AE and ANE groups. The considerable overlap between allergic and eosinophilic asthma phenotypes has clinical implications as increased rates of asthma exacerbations and healthcare utilization. The clinical heterogeneity among asthma phenotypes based on a single biomarker highlights the importance of multidimensional asthma phenotyping.

Objectives: It is aimed to assess how physicians use chest imaging in asthma and the relationship between the pathological findings and related disease characteristics in the radiological imaging of asthmatic patients. Background: The daily practice of imaging and its contribution to the management of asthma are not well defined. It is common to use radiological imaging to investigate pathologies that cause respiratory symptoms and to evaluate differential diagnoses in asthma patients. In this study, as a subanalysis of the Turkish Adult Asthma Registry, radiological findings and outcomes of asthmatic patients were examined. Methods: Between March 2018 and March 2022, the data of asthma patients in 36 secondary and tertiary health care centers was recorded using a web-based application. Patients with chest X-ray, computed thorax tomography, and paranasal sinus tomography data in the asthma database were statistically evaluated for sub-analysis. Results: The study included 2053 patients. Chest X-rays were taken in the majority of the cases (n:1739; 84.7%). Computed thorax tomography was performed in 869 (42.3%) patients and paranasal sinus tomography in 388 (18.9%) patients. The most common pathological findings on chest X-rays of asthmatic patients were increased bronchovascular branching and dirty lung appearance, whereas they were linear atelectasis, and bronchial wall thickening on computed thorax tomography bronchiectasis. Soft tissue in the sinuses and nasal polyps were the most common pathological findings in paranasal sinus tomography. Pathological findings were much more common in the radiological evaluations of patients with eosinophilic and allergic phenotypes and in patients with severe asthma. Conclusion: The radiological findings of asthma vary depending on the phenotype and severity of the disease. Patients with asthma, particularly those in the high-risk group, should be evaluated from a radiological perspective.

The obese-asthma phenotype has gradually increased in the last few years. We aimed to assess the differences between obese and non-obese patients with asthma. This research is a subanalysis of the Turkish Adult Asthma Registry (TAAR). Clinical presentation, disease control, severity, and demographics of obese and non-obese (lean, normal-weight, overweight) patients were compared. The obesity rate in TAAR was 32.2% (n = 619/1919; 18-83 years; 527 F/92 M). Patients with asthma and obesity had higher rates of childhood obesity, longer symptom duration, later onset of asthma, and more severe asthma. These patients were more likely to be female, older, less educated, and live in rural areas. Patients with obesity had more scheduled visits and emergency visits compared with non-obese patients, but similar asthma control, oral corticosteroid use, hospitalizations, intensive care unit admissions, and unscheduled visits. They also had a higher frequency of T2-high but lower frequency of possible T2-low phenotypes compared with normal-weight asthmatics. The risk of severe asthma in patients with obesity was 6.04 times higher for allergic than non-allergic patients and 3.58 times higher for the T2-high phenotype than for possible T2-low phenotypes. A one-unit increase in the asthma control test reduced the risk of severe asthma by 22%. A good definition of this phenotype is important to ensure that appropriate treatment strategies are implemented to achieve the control goal. We also believe that prevention of childhood obesity is an effective and pivotal strategy to achieve the goal of asthma control.

Evaluation of Risk Factors Causing Diagnostic Delay in Non-steroidal Anti-inflammatory Drug-exacerbated Respiratory Disease - Thoracic Research and Practice

Introduction: Primary immunodeficiencies (PIDs) are rare diseases in which chronic pulmonary diseases are common. Chronic pulmonary complications affect the long-term survival of these patients. The aim of this study was to evaluate the accompanying lung diseases and respiratory functions in adult PID patients in the Turkish population. Materials and Methods: Patients’ files who applied to the immunology clinic between 2015 and 2020 were evaluated retrospectively. The respiratory system was evaluated by physical examination, and if necessary, computed tomography, chest radiography, and pulmonary function test (PFT) were performed. The diagnosis of PIDs was based on the European Society of Immunodeficiency’s (ESID) criteria. Results: A total of 186 patients were included in the study. The median age of the patients was 38 years. The distribution of the diseases included in the study in order of frequency is: Common Variable Immunodeficiency (CVID) (47.8%), Severe Combined Immunodeficiency (SCID) (22.6%), Selective IgA deficiency (SIgAD) (10.8%), X-Linked Agammaglobulinemia (XLA) (10.2%), Chronic Granulomatous Disease (CGD) (8.6%). The most common findings on chest radiology were bronchiectasis (37.1%), parenchymal nodule (32.8%), ground glass opacity (31.2%), lymphadenopathy (24.7%), fibrotic changes (24.8%), reticular opacities (23.7%) and bronchial wall thickening (23.1%). PFT’s results were lower in patients with CGD. Bronchiectasis (37.1%), asthma (22%), and tuberculosis (9.7%) were the most common lung complications. Conclusion: We think that the frequency of other lung complications, especially asthma and bronchiectasis, is higher in adult patients with PIDs, and patient management is poor as there are no guidelines for the follow-up, diagnosis, and treatment of pulmonary complications.