Paediatrics III

3002002, 3002032, 302035, 302064, 302068

Adult Congenital Heart Disease, CFTR Modulator, Cystic Fibrosis, 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 and basic research into mutation-specific CFTR modulator therapies in CF patients. Clinical research into the prevention of food allergies and participation in European registry studies for primary ciliary dyskinesia and interstitial lung disease in children.

We provide high-quality regional and transregional patient care at the University Hospital of the Medical University Innsbruck together with the regional clinics of 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 in addition to clinical and basic research.

Metabolomics in Congenital Heart Disease

Miriam Michel

Interest has recently grown in the assessment of Fontan patient metabolism. As well as reported abnormalities in the glucose metabolism of Fontan patients, their handling of lipids is the best studied area to date, with significant changes especially in the cholesterol and lipoprotein pathways. We are investigating whether study of the metabolism of amino acids and proteins – in addition to the metabolism of glucose and lipids – could improve understanding the mechanisms of Fontan circulation sequelae. Using a targeted metabolomics approach, we determine the serum concentrations of multiple analytes derived from the metabolism of amino acids and lipids in a homogeneous group of adult Fontan patients with good systemic function of the morphologic left ventricle of good function, good exercise capacity and no Fontan-associated liver disease or major collateral formation. We compare these values with those of age-matched healthy controls. By means of mass spectrometry-based assessment of amino acids, we have proved that the method is appropriate and that, in comparison with controls, Fontan patients exhibit a distorted amino acid and phospholipid metabolome, which indicates altered cell signalling, energy metabolism and inflammation.

Foetal Arrythmias

Miriam Michel

Postnatal antiarrhythmic treatment of foetal supraventricular tachycardia (SVT) by risk-based postnatal management strategies

Early Vascular Ageing in the YOUth – EVA4YOU Study

Johannes Nairz, Ursula Kiechl-Kohlendorfer

Single-centre observational study on adolescents to determine predictors of the early steps of the formation of atherosclerosis and to quantify their influence on Intima-Media-Thickness of the carotid artery and the aorta as well as the Pulse-Wave Velocity including long-term follow-up with a special focus on cardio- and cerebrovascular events.

Heart Failure in Children

Irena Odri Komazec

PANORAMA and PANORAMA-OLE trial. Treatment of acute venous thromboembolism in children. DIVERSITY trial. Cardiomyopathy in genetic diseases – individual, targeted therapy (such as dilatative cardiomyopathy in propionic acidaemia, hypertrophic cardiomyopathy in RASopathy). Arrhythmias in children.

Cystic Fibrosis

For the Cystic Fibrosis Centre (CFCI) longitudinal clinical research plays a crucial role in this multisystem disease. This includes early diagnosis of pulmonary changes, as lung involvement in cystic fibrosis still determines disease progression and survival likelihood. The goal in newly diagnosed infants is to prolong and delay the progression of the disease through early diagnosis and therapy. In older patients with preserved lung function, innovative lung function measurements are used to detect disease-specific changes in the lungs or deterioration caused by them at an early stage. Additionally, we contribute to the European and German Cystic Fibrosis Registry with data from our patients to allow multicentre analysis with high patient numbers. Our research team also investigates Cystic Fibrosis Transmembrane Regulator (CFTR) modulator therapies to address the basic defect of cystic fibrosis and is involved in international multi-centre clinical trials. The research of mutation-specific therapies is dedicated to identifying the individual therapy effect by means of CFTR biomarkers; methods include sweat test, ICM (intestinal short circuit current) and NPD (nasal potential difference) measurements. ICM is performed in our own laboratory on biopsied rectal mucosa. This concept is an expression of the bench-to-bedside approach of the CFCI.

Cystic Fibrosis: Early Diagnosis and Individualised Therapy

Katharina Niedermayr, Dorothea Appelt, Helmut Ellemunter

Our scientific approach focuses on regular lung function measurements (multiple breath gas washout procedure) with determination of the Lung Clearance Index beginning at early infancy, which allows early determination of the diagnosis and the extent of lung involvement i.e. lung inhomogeneity. The results of MBW measurements enable the development of innovative therapeutic strategies and are being investigated in clinical trials. In cooperation with the Royal Brompton Imperial College, the measurements are qualitatively verified.

Translational Research Project: CFTR Function Parameters

Katharina Niedermayr, Dorothea Appelt, Teresa Fuchs, Helmut Ellemunter

Cystic Fibrosis: Nasal Potential difference measurements (NPD) are performed in vivo and ex vivo on rectal mucosal biopsies to measure CFTR activity. This ex vivo technique 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 testing of drugs on a patient-specific basis. CFTR functional testing especially with ICM enables us to test the therapy effect in CF patients and thus individualise therapy. In a Horizon 2020 project in cooperation with the University of Utrecht, Holland, intestinal biopsies of patients with very rare mutations were grown and preserved in a biobank. These intestinal organoids are used to test novel CFTR-modulators (and combinations) ex vivo without having to administer CFTR modulator drugs to the patient beforehand.

Topic: Prevention of food allergies in infants

Anna Zschocke, Katharina Herzog, Maria Schütz

In a randomised placebo controlled trial led by Prof. Kerstin Beyer, Charité Berlin, small amounts of four highly allergenic foods will be introduced to the diet of infants with eczema at 4-8 months of age in order to promote oral tolerance development. With this approach, we hoped to close the gaps in the knowledge of allergy prevention. With the information gained, we will contribute to the information necessary to update current prevention guidelines.

Topic: Evaluation der Smartphone-Spirometrie und der Bodyplethysmographie zur

Anna Zschocke, Anna Beliveau

Diagnosestellung eines Asthma bronchiale im Kindesalter (ESUBAK): Vergleich mit den European Respiratory Society Clinical Practice Guidelines (Ethic approval pending)
The diagnosis of asthma in childhood and adolescence is challenging. One difficulty in diagnosing bronchial asthma is that the symptoms can vary greatly. This can lead to investigations for the clarification of suspected bronchial asthma being performed in symptom-free intervals without pathological abnormalities becoming apparent. One approach to make symptom variability measurable is smartphone spirometry, which is suitable for everyday use.

In this study, children and adolescents aged 5 to 16 years with clinical suspicion of asthma are given a smartphone spirometer for a period of four weeks. This is used to perform routine lung function measurements in everyday life and when acute symptoms occur. At the same time, a routine assessment is sent to the pulmonology outpatient clinic. This is based on the diagnostic algorithm of the European Respiratory Society Clinical Practice Guideline, but also includes the performance of a body-plethysmography, which is widely used in German-speaking countries. However, body-plethysmography requires expensive equipment and its usefulness in asthma diagnostics has only been investigated and confirmed for adults so far.

The aim of this study is to evaluate smartphone spirometry and body-plethysmography for asthma diagnosis in children and adolescents based on all these measurement results.

Cardiology

• Gande N, Pechlaner R, Bernar B, Staudt A, Stock K, Hochmayr C, Geiger R, Kiechl-Kohlendorfer U, Knoflach M; Early Vascular Aging (EVA) Study Group. Cardiovascular health behaviors and associations of sex, age, and education in adolescents – Results from the EVA Tyrol study. Nutr Metab Cardiovasc Dis. 2021 Apr 9;31(4):1286-1292. doi: 10.1016/j.numecd.2020.11.002. Epub 2020 Nov 10. PMID: 33558093.
• Kiechl SJ, Staudt A, Stock K, Gande N, Bernar B, Hochmayr C, Winder B, Geiger R, Griesmacher A, Egger AE, Pechlaner R, Kiechl S, Knoflach M, Kiechl-Kohlendorfer U. Diagnostic Yield of a Systematic Vascular Health Screening Approach in Adolescents at Schools. J Adolesc Health. 2022 Jan;70(1):70-76. doi: 10.1016/j.jadohealth.2021.10.019. PMID: 34930573.
• Blessing M, Körperich H, Barth P, Michel M, Dubowy O, Forreiter S, Laser KT. Influence of Respiration on Collateral Flow in the Fontan Population Using Real-time Phase-contrast Cardiovascular Magnetic Resonance: Collateral Flow Does Not Protect the Ventricle From Volume Deficiency and Diastolic Dysfunction. J Thorac Imaging. 2022 Oct 18. doi: 10.1097/RTI.0000000000000684. Epub ahead of print. PMID: 36317937.
• 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.
• Michel M, Laser KT, Dubowy KO, Scholl-Bürgi S, Michel E. Metabolomics and random forests in patients with complex congenital heart disease. Front Cardiovasc Med. 2022 Oct 5;9:994068. doi: 10.3389/fcvm.2022.994068. PMID: 36277761; PMCID: PMC9581308.

Cystic Fibrosis

• Mainz JG, Arnold C, Wittstock K, Hipler UC, Lehmann T, Zagoya C, Duckstein F, Ellemunter H, Hentschel J. Ivacaftor Reduces Inflammatory Mediators in Upper Airway Lining Fluid From Cystic Fibrosis Patients With a G551D Mutation: Serial Non-Invasive Home-Based Collection of Upper Airway Lining Fluid. Front Immunol. 2021 May 5;12:642180. doi: 10.3389/fimmu.2021.642180. PMID: 34025651; PMCID: PMC8131546.
• Ellemunter H, Dumke M, Steinkamp G. Arm muscle area for the longitudinal assessment of nutritional status in paediatric patients with cystic fibrosis – A single centre experience. J Cyst Fibros. 2022 Mar;21(2):e122-e128. doi: 10.1016/j.jcf.2021.10.006. Epub 2021 Oct 30. PMID: 34728152.
• Appelt D, Steinkamp G, Ellemunter H. Cancer in Cystic Fibrosis: Do Not Neglect Gynecologic Cancers. Chest. 2022 May;161(5):e325-e326. doi: 10.1016/j.chest.2022.01.055. PMID: 35526906.
• Niedermayr K, Gasser V, Rueckes-Nilges C, Appelt D, Eder J, Fuchs T, Naehrlich L, Ellemunter H. Personalized medicine with drugs targeting the underlying protein defect in cystic fibrosis: is monitoring of treatment response necessary? Ther Adv Chronic Dis. 2022 Aug 5;13:20406223221108627. doi: 10.1177/20406223221108627. PMID: 35959505; PMCID: PMC9358561.
• Pariano M, Puccetti M, Stincardini C, Napolioni V, Gatticchi L, Galarini R, Renga G, Barola C, Bellet MM, D’Onofrio F, Nunzi E, Bartoli A, Antognelli C, Cariani L, Russo M, Porcaro L, Colombo C, Majo F, Lucidi V, Montemitro E, Fiscarelli E, Ellemunter H, Lass-Flörl C, Ricci M, Costantini C, Giovagnoli S, Romani L. Aryl Hydrocarbon Receptor Agonism Antagonizes the Hypoxia-driven Inflammation in Cystic Fibrosis. Am J Respir Cell Mol Biol. 2023 Mar;68(3):288-301. doi: 10.1165/rcmb.2022-0196OC. PMID: 36252182.

Pulmonology

• FDA warning montelukast 03.2020-Statement of the Austrian working group of pediatric pulmonology and allergology.
• Zschocke A, Horak F, Eber E, Frischer T, Simma B, Stetzl W, Riedler J, Szépfalusi Z, Zacharasiewicz A.Wien Klin Wochenschr. 2022 Jan;134(1-2):86-88. doi: 10.1007/s00508-021-01981-1. Epub 2021 Dec 13.PMID: 34904177
• Do Not Miss Acute Diffuse Panbronchiolitis for Tree-in-Bud: Case Series of a Rare Lung Disease. Raedler J, Hoelz H, Zschocke A, Loeffler-Ragg J, Paolini M, Ley-Zaporozhan J, Griese M.Diagnostics (Basel). 2022 Jul 7;12(7):1653. doi: 10.3390/diagnostics12071653.PMID: 35885557
• Asthma bei Kindern – State of the Art Sepfalusi Z, Zschocke A, Kainz K Österreichische Ärztezeitung 11.2022

Paediatric Cardiology

• Metabolomic remodeling in Fontan patients: a Metabolomics study. Tiroler Wissenschaftsfoerderung; UNI-0404/2016; Principal investigator: Miriam Michel. (PI is actively holding the funding since 2018)
• Stoffwechseluntersuchungen bei Patienten mit angeborenen Herz- und Gefaesserkrankungen. Medizinischer Forschungsfonds Tirol; grant no. 327; Principal investigator: Miriam Michel. (PI is actively holding the funding since 2020)
• Maternal hyperoxygenation in the fetus with heart disease. Erwin-Schroedinger-fellowship-grant; J-4466; Principal investigator, fellow: Miriam Michel. (PI is actively holding the funding since 2020)

Cystic Fibrosis

• Research Award “Continued Research Capacity (“CRC”)”awarded by the Cystic Fibrosis Foundation, Bethesda, USA, through the European Cystic Fibrosis Society to CFCI. This award reflects multi-year funding.

Paediatric Cardiology

• Centre of Congenital Heart Defects, Heart and Diabetes Centre Northrhine-Westphalia, Bad Oeynhausen, Ruhr-University Bochum, Germany (K.T. Laser, K.-O. Dubowy)
• Division of Pediatric Cardiology, Labatt Family Heart Centre, The Hospital for Sick Children, Toronto, Canada (E. Jaeggi, M. Seed)
• Biocrates Life Sciences AG, Innsbruck, Austria (S. Ledinger)
• Sciomics GmbH, Neckargemuend, Germany (R. Schmidt)

Cystic Fibrosis

• Jane Davies LCI Core Facility London, Imperial College, Royal Brompton & Harfield Imperial College London, United Kingdom
• Elena K. Schneider-Futschik, NHMRC Peter Doherty Fellow,Cystic Fibrosis Pharmacology Laboratory, Department of Pharmacology & Therapeutics, School of Biomedical Sciences, University of Melbourne, Australia
• Lutz Nährlich Gießen, Universitätsklinikum Giessen und Marburg GmbH, Funktionsbereich Päd. Pneumologie und Allergologie, Giessen, Germany
• Kors van der Ent, University Medicial Center Utrecht, the Netherlands
• Alexander Möller, Pädiatrie, pädiatrische Pneumologie, Schlafmedizin (SSSSC), Universitäts-Kinderspital Zürich – Eleonorenstiftung, Zürich, Schweiz
• Merlijn Bonte, Harms Tiddens, Erasmus MC University Medical Centre Rotterdam, Lung Analysis Lab, Rotterdam, the Netherlands
• Kate Hayes, European Cystic Fibrosis Society (ECFS) –CTN (Clinical Trial Network) The Wellcome Trust-Wolfson NI Clinical Research Facility, Queen’s University Belfast, Northern Ireland

Paediatric Pulmonology and Allergology

• Kirsten Beyer, Department Pediatric Pneumology, Immunology and Intensive Care, Charité – University Medicine, Berlin
• Heymut Omran, University Hospital Münster, Germany
• Matthias Griese, Dr. von Hauner Children’s Hospital, Division of Pediatric Pneumology, Ludwig-Maximilians-University, University Hospital Munich, Germany
• Angela Zacharasiewicz,, Klinik Ottakring, Wien Ernst Eber, Medizinische Universitäts Kinderklinik, Graz