Paediatrics III

302002, 302032, 302035, 302064, 302068

Adult Congenital Heart Disease, CFTR Modulator, Cystic Fibrosis - lung inflammation, lung clearance index, Paediatric Allergology, Paediatric Cardiology, and Paediatric Pulmonology

Clinical and basic research into paediatric cardiomyopathies and univentricular heart patients. Evaluation of risk factors for early vascular ageing. Clinical research into the prevention of food allergies and participation in European registry studies on primary ciliary dyskinesia and interstitial lung disease in children. Clinical and basic research into mutation-specific CFTR modulator therapies in CF patients. Clinical and basic research into CFTR-associated dysfunction in CF patients.

We provide high-quality regional and transregional patient care at the University Hospital of the Medical University Innsbruck together with the regional clinics of the Tyrol: Landeskrankenhaus Innsbruck/Universitätskliniken. We provide paediatric cardiac surgery and predefined interventional procedures in close collaborating with our partners at the Kinderherzzentrum Wien. Patient care is one of our core tasks, beside clinical and basic research.

Cardiology

Omics-analysis in patients with complex congenital heart disease

Miriam Michel, Alexander Höller, Sabine Scholl-Bürgi, Daniela Karall

FWF-funded project bound to the Tenure Track position for Pediatric Cardiology (metabolic cardiodiagnostics) (KLIF1036, NCT04764305). The project focuses on molecular regulatory processes in patients with complex congenital heart palliated and Fontan circulation, esp. on translational multi-omics regulatory analysis with network establishment aiming at risk stratification for the development of Fontan-associated comorbidities (https://fontanology.org/) (doi: 10.3390/ijms25105416, doi: 10.1038/s41598-020-65852-x). We are hoping to expand the binational study to a multinational multicentre study with the aim of implementing a European registry on omics research in these patients and to implement interventional study arm on the use of middle chain triglycerides in these patients (doi: 10.3390/metabo13080932).

Natural history and peri- and postnatal management of prenatally suspected/diagnosed cardiovascular scenarios:

Miriam Michel, in collaboration with the Department of Obstetrics and Gynaecology (Irene Mutz-Dehbalaie et al.) and the Department of Paediatrics II (Michaela Höck)

Research is focussing on the incidence, natural history, postnatal recurrence and management of foetal cardiac tachy- and bradyarrhythmia; on the incidence, natural history and management of foetal cardiac masses, focusing on the role of transplacental mTOR inhibitor treatment; and on

foetuses with suspected aortic coarctation, where we are investigating prenatal risk-stratification, perinatal management and outcome over the first year of life. We are also considering the implications of foetal atrial septal aneurysm on the development of left-sided cardiac structures; studying the natural history of prenatally diagnosed ventricular septal defects; and analysing the role of advanced 3D- and 4D- foetal echocardiographic techniques on the accuracy of the detection of congenital cardiac malformations.

Early Vascular Ageing in the YOUth – the EVA4YOU study

Johannes Nairz, Ursula Kiechl-Kohlendorfer

We are undertaking a single-centre observational study on adolescents to determine predictors of the early steps of the formation of atherosclerosis and to quantify their influence on the intima media thickness of the carotid artery and the aorta and on the pulse-wave velocity. The study includes a  long-term follow-up with a focus on cardio- and cerebrovascular events.

Cystic Fibrosis

Inflammatory processes in cystic fibrosis lung disease

Teresa Fuchs, Anja Siedl, Katharina Niedermayr, Johannes Eder, Dorothea Appelt

We are investigating inflammatory processes and their relationships with clinical parameters and therapies that play a crucial part in the development of cystic fibrosis lung disease. We are aiming to understand how inflammatory mechanisms contribute to disease progression and to identify potential therapeutic targets.

Early diagnosis of lung disease and individualized therapy

Dorothea Appelt, Teresa Fuchs, Katharina Niedermayr

Our scientific approach emphasizes regular assessments of lung function using the multiple breath washout (MBW) procedure, with the Lung Clearance Index measured from early infancy. This allows early diagnosis and assessment of the extent of lung involvement, such as ventilation inhomogeneity. The results of MBW measurements contribute to the development of innovative therapeutic strategies, which are being investigated in clinical trials. In collaboration with the Royal Brompton Hospital and Imperial College, we are qualitatively validating the measurements to ensure their accuracy and reliability.

Translational research project: CFTR function parameters

Katharina Niedermayr, Dorothea Appelt

The Cystic fibrosis centre is assessing CFTR function using methods such as the sweat test, nasal potential difference measurements (NPD) in vivo and intestinal current measurements (ICM) ex vivo on rectal mucosal biopsies. This final techniques allows not only the confirmation/exclusion of an inconclusive clinical/genetic diagnostic situation (e.g. screening positive but inconclusive diagnosis) in CF but also the monitoring of drugs on a patient-specific basis.

AI for analysis of chest CT scans in cystic fibrosis

Dorothea Appelt

The Erasmus MC Rotterdam has developed an accurate automated method to assess structural lung damage using chest CT scans . Recently advances in Artificial Intelligence (AI) have enabled the fully automated analysis of the scans, allowing the reliable evaluation of large datasets. We are contributing chest CT scans obtained during routine clinical care and the AI techniques are providing us with more information on structural lung damage.

Exploring mental health and resilience in cystic fibrosis patients

Dorothea Appelt, Johannes Eder

In collaboration with the Department for Medical Psychology Innsbruck, we are collecting longitudinal data on mental health and studying the resilience of our cystic fibrosis patients, aiming at improving our understanding of the psychological challenges throughout the course of the disease. In collaboration with the AKH Vienna, we are also investigating the mental health of young children who are starting CFTR modulator therapy. The early identification of and support for psychological challenges can strengthen patients’ resilience, positively influencing both disease management and therapy outcomes.

Pulmology

Allergen immunotherapy for single and multiple food allergies – real-life study on the introduction of AIT in the University Hospital for children and adolescents with food allergy in Innsbruck

Teresa Fuchs, Monika Kofler, Maria Schutz, Anna Beliveau, Thomas Eiwegger, Katharina Herzog, Anna Zschocke

In 2024, we introduced multi-nut oral immunotherapy for children aged nine months to 18 years and have integrated this treatment into a real-life study. The placebo arm includes children receiving standard care, where parents opt not to proceed with therapy. Using a novel adaptive platform trial design, we are aiming to evaluate the therapy’s impact on desensitization rates and sustained unresponsiveness—assessed through oral food challenges—as well as on the rates of side effects, on treatment burden and on quality of life. Our study protocol allows the integration of newly approved therapies, such as epicutaneous and sublingual immunotherapy. We will also analyse immunological markers, including allergen-specific immunoglobulin levels, basophil activation, cytokine profiles and skin-prick test responses.

Evaluation of the implementation of the basophil activation Test (BAT) in the routine clinical care of children and adolescents with food allergy

Anna Zschocke, Daniela Reider, Norbert Reider

The Basophil Activation Test (BAT) has demonstrated particularly high specificity for most allergens and can help reduce the need for multiple oral food challenges (OFCs) in cases where the diagnosis remains uncertain after history-taking and first-line testing. BAT is now recommended as a diagnostic tool to support clinical decision-making. The use of BAT in routine clinical practice is currently limited. In 2024, the Allergy Department of the Innsbruck University Clinic for Dermatology, Venereology and Allergy established a Basophil Activation Test (BAT) for clinical practice. We have now integrated the test into our diagnostic workflow and are evaluating its effectiveness in reducing the need for oral food challenges, minimizing the use of adrenaline pens during these challenges and lowering the overall cost of the diagnosis of food allergy.

Topic: Prevention of food allergies in infants

Anna Zschocke, Katharina Herzog, Maria Schütz

In a randomized placebo-controlled trial led by Prof. Kerstin Beyer, Charité Berlin, small amounts of four highly allergenic foods will be introduced into the diet of infants with eczema at 4-8 months of age to promote the development of oral tolerance. We hope that the approach will fill gaps in our knowledge of allergy prevention and will contribute to the update of prevention guidelines.

Topic: Evaluation of smartphone spirometry and body plethysmography to diagnose bronchial asthma in children (ESUBAK)
Anna Zschocke, Anna Beliveau

The diagnosis of asthma in childhood and adolescence requires objective evidence for reversible obstruction of the airways, which comes from spirometry. Should the spirometry be normal, as is often the case, a bronchial provocation test is required. A viable alternative may be the use of smartphone spirometry, which can be used in everyday life. We are undertaking a study in which we give children and adolescents aged 5 to 16 years with clinical suspicion of asthma a smartphone spirometer for four weeks. They use the device to perform lung function measurements routinely in everyday life and when acute symptoms occur. At the same time, we give them an assessment, as recommended by current guidelines, in the pediatric pulmonology outpatient clinic, with bronchial provocation and body plethysmography.

Cardiology

• Michel M, Renaud C, Chiu-Man C, Gross G, Jaeggi E. Postnatal recurrence and transesophageal inducibility of prenatally treated fetal supraventricular tachycardia. Heart Rhythm. 2022 Aug;19(8):1343-1349. doi: 10.1016/j.hrthm.2022.04.013. Epub 2022 Apr 21. PMID: 35462052.
• Nairz J, Messner A, Kiechl SJ, Winder B, Hochmayr C, Granna J, Egger AE, Griesmacher A, Geiger R, Knoflach M, Kiechl-Kohlendorfer U; Early Vascular Ageing in the YOUth (EVA4YOU) Study Group. Prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and its association with arterial stiffness in adolescents: Results from the EVA4YOU study. PLoS One. 2024 Nov 27;19(11):e0314585. doi: 10.1371/journal.pone.0314585. PMID: 39602440; PMCID: PMC11602044.
• Nairz J, Messner A, Kiechl SJ, Winder B, Hochmayr C, Egger AE, Griesmacher A, Geiger R, Griesmaier E, Pechlaner R, Knoflach M, Kiechl-Kohlendorfer U; Early Vascular Ageing in the YOUth (EVA4YOU) Study Group. Determinants of non-alcoholic fatty liver disease in young people: Maternal, neonatal, and adolescent factors. PLoS One. 2024 Feb 22;19(2):e0298800. doi: 10.1371/journal.pone.0298800. PMID: 38386674; PMCID: PMC10883560.
• Renaud D, Höller A, Michel M. Potential Drug-Nutrient Interactions of 45 Vitamins, Minerals, Trace Elements, and Associated Dietary Compounds with Acetylsalicylic Acid and Warfarin-A Review of the Literature. Nutrients. 2024 Mar 26;16(7):950. doi: 10.3390/nu16070950. PMID: 38612984; PMCID: PMC11013948.
• Michel M, Renaud D, Schmidt R, Einkemmer M, Laser LV, Michel E, Dubowy KO, Karall D, Laser KT, Scholl-Bürgi S. Altered Serum Proteins Suggest Inflammation, Fibrogenesis and Angiogenesis in Adult Patients with a Fontan Circulation. Int J Mol Sci. 2024 May 16;25(10):5416. doi: 10.3390/ijms25105416. PMID: 38791454; PMCID: PMC11121818.

Pulmonology und Allergology

• Stelzig O, Mühlegger B, Zschocke A, Kiechl-Kohlendorfer U, Griesmaier E. Neonatal meconium aspiration syndrome associated with ABCA3 gene mutation and mycoplasma infection: a case report. BMC Pediatr. 2025 Jan 9;25(1):22. doi: 10.1186/s12887-024-05369-8. PMID: 39789505; PMCID: PMC11715936.
• Raidt J, Riepenhausen S, Pennekamp P, Olbrich H, Amirav I, Athanazio RA, Aviram M, Balinotti JE, Bar-On O, Bode SFN, Boon M, Borrelli M, Carr SB, Crowley S, Dehlink E, Diepenhorst S, Durdik P, Dworniczak B, Emiralioğlu N, Erdem E, Fonnesu R, Gracci S, Große-Onnebrink J, Gwozdziewicz K, Haarman EG, Hansen CR, Hogg C, Holgersen MG, Kerem E, Körner RW, Kötz K, Kouis P, Loebinger MR, Lorent N, Lucas JS, Maj D, Mall MA, Marthin JK, Martinu V, Mazurek H, Mitchison HM, Nöthe-Menchen T, Özçelik U, Pifferi M, Pogorzelski A, Ringshausen FC, Roehmel JF, Rovira-Amigo S, Rumman N, Schlegtendal A, Shoemark A, Sperstad Kennelly S, Staar BO, Sutharsan S, Thomas S, Ullmann N, Varghese J, von Hardenberg S, Walker WT, Wetzke M, Witt M, Yiallouros P, Zschocke A, Ziętkiewicz E, Nielsen KG, Omran H. Analyses of 1236 genotyped primary ciliary dyskinesia individuals identify regional clusters of distinct DNA variants and significant genotype-phenotype correlations. Eur Respir J. 2024 Aug 8;64(2):2301769. doi: 10.1183/13993003.01769-2023. PMID: 38871375; PMCID: PMC11306806.

Cystic Fibrosis

• Appelt D, Fuchs T, Eder J, Niedermayr K, Siedl A, Ellemunter H. Monitoring ETI effects over 1.7 years in an infant treated in utero, via breast milk and granules by repeated faecal elastase measurements. J Cyst Fibros. 2025 Jan 28:S1569-1993(25)00012-8. doi: 10.1016/j.jcf.2025.01.012. Epub ahead of print. PMID: 39880765.
• Fuchs T, Vasiliadis A, Zlamy M, Siedl A, Niedermayr K, Appelt D, Gasser V, Eder J, Ellemunter H. Cytokines Measured in Nasal Lavage Compared to Induced Sputum in Patients with Mild Cystic Fibrosis. Int J Mol Sci. 2024 Oct 15;25(20):11081. doi: 10.3390/ijms252011081. PMID: 39456863; PMCID: PMC11507901.
• Fuchs T, Zlamy M, Zöggeler T, Appelt D, Niedermayr K, Siedl A, Gasser V, Eder J, Ellemunter H. Detection of cytokines in nasal lavage samples of patients with cystic fibrosis: comparison of two different cytokine detection assays. BMC Pulm Med. 2024 Jun 19;24(1):286. doi: 10.1186/s12890-024-03103-9. PMID: 38890643; PMCID: PMC11186286.
• Fuchs T, Appelt D, Ellemunter H. Long-Term Assessment of Antibody Response to COVID-19 Vaccination in People with Cystic Fibrosis and Solid Organ Transplantation. Vaccines (Basel). 2024 Jan 18;12(1):98. doi: 10.3390/vaccines12010098. PMID: 38250911; PMCID: PMC10819632.

Appelt D, Steinkamp G, Sieber S, Ellemunter H. Early and sustained improvements of lung clearance index from two to sixteen weeks of elexacaftor/tezacaftor/ivacaftor therapy in patients with cystic fibrosis-a real world study. Front Pharmacol. 2023 Mar 8;14:1125853. doi: 10.3389/fphar.2023.1125853. PMID: 36969845; PMCID: PMC10030732.

Cystic Fibrosis

• Research Award “Continued Research Capacity (“CRC”)”awarded by the Cystic Fibrosis Foundation, Bethesda, USA, through the European Cystic Fibrosis Society. This award reflects multi-year funding.
• Wissenschaftliche Projektförderung durch die Österreichische Gesellschaft für Kinder- und Jugendheilkunde Österreich (ÖGKJ), 2023.

Cystic Fibrosis

• Jane Davies, Chris Short LCI Core Facility London, Imperial College, Royal Brompton & Harfield Imperial College London, United Kingdom
• Lutz Nährlich Gießen, Universitätsklinikum Giessen und Marburg GmbH, Funktionsbereich Päd. Pneumologie und Allergologie, Giessen, Germany
• Daan Caudri, Erasmus MC University Medical Centre Rotterdam, Lung Analysis Lab, Rotterdam, the Netherlands
• Saskia Gruber, Univ. Klinik für Kinder- und Jugendheilkunde, Klinische Abteilung für Pädiatrische Pulmologie, Allergologie und Endokrinologie, AKH Wien