Academic Center for Respiratory Infections

Last updated: 365 days ago.

Our aim is to be a national and international leading centre for the treatment of acute and chronic respiratory airway infections in children and adults. We aim to become a European Reference Centre for Bronchiectasis (ERN) and Cystic Fibrosis. This can further increase our participation in national and international research trials and strengthen our already existing national and international collaborations for patient care , research and education.

We aim to deliver the highest quality in patient care. In research the focus is directed at the prevention of infectious exacerbations and the improvement of diagnostic methods. In this area of research the described national and international collaborations are crucial, as well as the translation of basic research to clinical trials and vice versa

Academic Center of Excellence

Research Activities

The ACE Respiratory infections performs research focused on prevention, treatment, inflammation and diagnostic methods in pulmonary infectious diseases. The research is multidisciplinary combining fundamental research with clinical studies. These studies are performed with intensive internal, national and international collaborations.

An overview of our current investigator-initiated studies highlighting these collaborations is as follows: Prospective randomized controlled trial investigating inhalation antibiotics in ventilator-associated pneumonia is performed by the depts of pulmonary medicine, laboratory of pulmonary medicine and ICU of the Erasmus MC and the University Hospital Clinic Barcelona. Prospective randomized controlled trial investigating eradication of microorganisms causing COPD exacerbations, microbiome and inflammation starting in 2017 and performed by the departments of pulmonary medicine and microbiology of the Erasmus MC, Amphia Hospital and Oxford University.

New diagnostic tool for Mycoplasma pneumoniae respiratory infection. A collaboration of basic scientists and clinician scientists of the departments of Pediatrics, and Immunology of the Erasmus MC and the University of Salamanca, Spain Alternative approaches are pursued in collaborations between Laboratory of Pediatrics, Med Microbiology and Virosciences of the ErasmusMC and Children's hospital; Zürich, Switserland. Mechanisms of immune evasion by RSV are investigated in collaboration with Dept Pediatrics and Radboud UMC, Nijmegen

The STRAP -Study: implementation of a validated decision rule to target antibiotic prescription in children with suspected community acquired pneumonia. Collaboration of epidemiologists, and clinician scientists from the Erasmus MC, and paediatricians from 6 hospitals in center/SouthWest Netherlands (a.o. the Haga ziekenhuis, St Elizabeth ziekenhuis, and Maasstad ziekenhuis).

A collaborative study with the University of Zurich on circulating antibody-secreting cells during Mycoplasma pneumoniae infection in childhood performed by basic scientists from the departments of pediatric infectious diseases Erasmus MC and University of Zurich. Respiratory virus infections in immunocompromised patients: assessing the need for early therapeutic intervention. A collaboration between the departments of Pulmonary Medicine, Hematology and Viroscience.

A ZONMW project goed gebruik geneesmiddelen has been submitted. The aim of the project is to improve personalized medicine in patients with COPD exacerbations by using biomarker-guided treatment.

A new research project, in collaboration with the Academic Center for Rare Immunological Disease (RIDC), has been initiated in the field of primary immunodeficiency disease. Main objective of this study is to establish dietary intake and potential deficiencies of macro- and micronutrients which were found to interact with immune function in descriptive and in vitro studies, in patients with primary antibody deficiencies and bronchiectasis. Moreover, we aim to investigate correlations between serum levels of nutrients of patients and disease severity.

A second collaborative research project between the AC Respiratory Infections and AC RIDC focusses on treatment of granulomatous complications in patients with primary antibody deficiencies.

Type of

Collaborations

These studies are performed with intensive internal, national and international collaborations. University Hospital Clinic Barcelona. Amphia Hospital and Oxford University. University of Salamanca, Spain, Children’s hospital; Zürich, Switserland. 6 hospitals in center/SouthWest Netherlands (a.o. the Haga ziekenhuis, St Elizabeth ziekenhuis, and Maasstad ziekenhuis).

Educational

Contributions

Educational programs play a major role in this ACE, which provides education for all academic degrees. To give more insight into our activities + feedback, we summarized them as follows:

Jaar 2 / Thema 2.B / Deel 3 
Pulmonary manifestations of infectious and immune diseases HC.1 Lower airway infections Menno van der Eerden Feedback: Duidelijke dia's en goede opbouw. De informatiedichtheid was goed. Afrondende casus op het einde was prettig. Oordeel: goed HC.3 Multiresistant Tuberculosis Marleen Bakker Feedback: Goede structuur en goede informatiedichtheid. Didactisch vaardige docent. Oordeel: goed PD.7 Cystic fibrosis and recurrent airway infections Marleen Bakker Feedback: Heel erg leerzaam en mooi om te horen hoe het dagelijks leven is voor een CF-patiënt. Oordeel: goed ZO.2 Cases. Fever, coughing, dyspnea Menno van der Eerden en Machteld Felz Feedback: Uitdagende casus. Leerzaam dat de DD uit verschillende tracti komt. Oordeel: voldoende
 Master / Jaar 1 / Thema M.1.B Dyspnea, Coughing ZO.3 Microbiology en infections Marielle Pijnenburg en Menno van der Eerden Feedback: Goed ZO. Duidelijke opbouw en relatie met kliniek. Fijn dat eerst de theorie aan bod komt en dat de student daarna zelf kan oefenen met casuïstiek. Mariëlle Pijnenburg: BA2B12 PD.8 Een kind met koorts en dyspnoe Feedback nog niet ontvangen Study Clinical Technology (LUMC/TU Delft/Erasmus MC) HC. COPD and lower airway infections Menno van der Eerden Feedback: nog niet ontvangen Wendy Unger (Lab of pediatrics): - Core-teacher research master Infection&Immunity. - Mol Med Course for PhD and post-docs: lecture on "Respiratory tract infections by Mycoplasma pneumoniae". Feedback: eye-opener, clear. Lecture was evaluated with a 7.9. Virgil Dalm (dept of Immunology) is involved in Research Masters Infection and Immunity & Molecular Medicine, Board Member Clinical Research Master, Involved in education in medical training bachelor and masters, mainly 2nd en 3rd year, involved in the development and organization of minor Evil Paradise (Immunology), involved in minor immunodeficiencies. Teaching Respiratory Infections (MvdE) to AIOS Pulmonology, Immunology, ICU, fellows pulmonary infectious diseases (one fellow from Ghent University Hospital) Education for Medical Specialists, AIOS Pulmonary medicine and PhD's: Marielle Pijnenburg (dept pediatric pulmonology): ERS summer school paediatric respiratory diseases, lectures about Non-CF bronchiectasis and Primary Ciliary Dyskinesia Winnifred van Lankeren (dept Radiology): organizes educational sessions for AIOS and Radiology specialists in imaging of pulmonary infectious diseases International Masterclass Respiratory Infections in Barcelona organized by Menno van der Eerden (dept of pulmonary medicine) with prof Antoni Torres, professor in pulmonary medicine from Hospital Clinic Barcelona. Feedback: This course has been evaluated in 2016 as very good with an average of 9. International Masterclass COPD Exacerbations in Oxford organized by Menno van der Eerden with prof Ian Pavord, professor in pulmonary medicine from Oxford University Hospital. Feedback: This course has been evaluated in 2016 as very good with an average of 9. National Masterclass Tuberculosis in Rotterdam organized by Marleen Bakker, (dept of pulmonary medicine) pulmonologist of the Erasmus MC. 
Feedback: This course has been evaluated in 2015 with an average of 8.5 National Symposium New Insights into Pulmonary Infectious Diseases organized each two year by Menno van der Eerden. No feedback present Annemarie van Rossum Managing/coordinating courses/programmes 2016 - present University of Oxford, tutor and examination assessor for the postgraduate MSc program Pediatric Infectious Diseases (chair prof. A. Pollard, University of Oxford) 2016 - present Eureka translational Medicine network, member of the educational committee for the yearly 8 day course (chair prof J. Hafler, Yale School of Medicine) 2016 - present Workgroup leader Infections and host response. Postgraduate school Molecular Medicine Erasmus MC University Medical Center Rotterdam, the Netherlands 2016 - present Organizing Committee of the yearly 3 days Oxford University course Hot Topics in Infections and Immunity in children. 2012 - 2016 Co-founder and course director (with prof. dr. L. Bont, UMC Utrecht) Hot topics in Airway Diseases. Yearly post graduate course for paediatricians.

A national ACE congress has been organized in lantaren Venster in October 2018

Patient

Care Activities

  • Tuberculosis and Cystic Fibrosis is labeled 100% academic according to Robijn. This ACE is already recognized as "topreferente zorg centrum" by the NFU, which means that there are highly multidisciplinary facilities to enable the best possible care for patients with rare and/or complex and/or exceptional pulmonary infectious diseases for which no standard treatments can be applied. The ACE is asked and accordingly applied to become an European Centre of Reference (ERN) for non-CF bronchiectasis and a separate ERN for Cystic Fibrosis together with the Sophia Children Hospital.
  • The departments of pediatric pulmonology and pediatric infectious diseases started a multidisciplinary outpatient clinic for patients with recurrent respiratory infections/ Non- CF bronchiectasis (NCFB) in 2016. In this clinical care pathway, prospective data will be collected on all patients visiting this clinic for future research purposes.
  • The dept of pulmonary medicine has a standard of care/ clinical pathway operational for non- CF bronchiectasis, in which multidisciplinary teams are involved.
  • Until now we are not participating in the program "Value based Health Care", but are eager to participate in this very promising program. For the ERN Non-CF bronchiectasis we agreed to measure the following outcome parameters: Mortality; % of patients investigated with CT,immunoglobulins and aspergillus serology; % taught Chest clearance. We will start measuring these outcome measures from 2017, and can monitor them in 2018. Furthermore we are actively involved in the participation of an European database registry for Non-CF bronchiectasis, called EMBARC. Also we participate in a national database for Cystic Fibrosis.
  • Clinical audits from the NVALT (Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose) in 2010 and 2014 and Internal audits from the Erasmus MC in 2014 and 2016 have been performed and only minor comments were raised. A plan was written, executed and evaluated in response to these comments, with good outcome.
  • With our latest publication in Lancet Resp Med, patients with recurrent COPD exacerbations are recommended to start with maintenance macrolide treatment to prevent new exacerbations. With the current prospective study to inhalation antibiotics in ventilator-associated pneumonia we are investigating new treatment options to improve the cure rate in this condition.
  • The STRAP trial includes implementation of a clinical decision rule for children with fever in emergency care, as a result of previous research (Nijman et al, BMJ 2013;346:f1706 doi: 10.1136/bmj.f1706, Kerkhof et al, PlosOne 2015; 10: e0127620. Doi: 10.1371/journal.pone.0127620)
  • A multidisciplinary outpatient clinic was established between the departments of pulmonology and internal medicine for patients with primary immunodeficiencies. Most patients with primary antibody deficiencies also suffer from pulmonary complications (approximately 90%). Therefore we set up this outpatient clinic, to increase efficacy in care and patient satisfaction. Patients undergo pulmonary function tests and CAT-scan of the lungs, including visits at the department of pulmonary medicine and internal medicine, clinical immunology on the same day and patients will be discussed between pulmonologist and internist on the same day.

  • A transition outpatient clinical has been established in collaboration with the AC RIDC for transfer of patients from the Sophia Children's hospital to the adult outpatient clinics. Pulmonologists, internists, paediatricians and dedicated nurse practitioners are involved in this transition outpatient clinic.

Societal Relevance to Research, Education and Patient Care

  • Respiratory Infections are within the WHO top 5 mortality rate due to diseases worldwide. The ACE can contribute to the awareness of respiratory infections and the use of appropriate diagnostic and treatment options. Especially the appropriate use of adequate antibiotics is an important issue, as well as the prevention by vaccination.
  • National Guidelines: Non-CF bronchiectasis, to be presented at the end of 2016. Menno van der Eerden, Virgil Dalm Treatment of tuberculosis. Marleen Bakker Tuberculosis en TNF-a antagonists. Marleen Bakker Mycobacterial diagnostics. Marleen Bakker Diagnostics and treatment of uncomplicated pneumonia in hospitalized children. Pieter Fraaij Recurrent airway infections in Children. Gertjan Driessen Fever in emergency care in children 0-16 years (NVK), Rianne Oostenbrink
  • The ACE is actively involved in the curriculum Pulmonary manifestations of infectious and immune diseases
  • The innovational contribution of the ACE to research: basic research aiming to find novel, accurate diagnostics to discern bacterial from viral infection as well as infectious from colonizing bacteria (Lab of pediatrics).
  • Prevention: Acute COPD exacerbations impose a large burden on health care costs. In our latest publication in Lancet Resp Med, patients with frequent exacerbations are recommended to start with maintenance macrolide treatment. Also, alternative strategies should be developed to prevent new exacerbations. One of these strategies could be directed at eradicating the bacterial causative agent of an exacerbation. This will be investigated in a prospective study starting in 2017 in collaboration with Oxford University Hospital.
  • We have a standard of care operational for non-CF bronchiectasis

Viability of Research, Education and Patient Care

  • The ACE respiratory Infections is composed of medical disciplines which collaborate intensively with each other, sharing knowledge continuously in multidisciplinary meetings, internal symposia and at a National Symposium about New Insights into Respiratory Infections in Rotterdam. The ages of the leading investigators of this ACE vary from 37 years to 54 years old. International working experience
  • Menno van der Eerden: 2006 Pulmonary infectious disease fellowship, Groote Schuur. Hospital, Cape town, South Africa. International publications
  • Said MA, et al, van der Eerden MM, Vila-Corcoles A, Watt JP. Estimating the burden of pneumococcal pneumonia among adults: a systematic review and meta-analysis of diagnostic techniques. PLoS One. 2013;8(4)
  • Cillóniz C, Torres A, Niederman M, van der Eerden M, Chalmers J, Welte T, Blasi F. Community-acquired pneumonia related to intracellular pathogens. Intensive Care Med. 2016 Jun 8
  • Antoni Torres, Nelson Lee, Jordi Vila and Menno Van der Eerden. Diagnosis of pneumonia in the molecular age. Submitted for publication to Eur Respir J.
  • Nijman, R.G., et al., Clinical prediction model to aid emergency doctors managing febrile children at risk of serious bacterial infections: diagnostic study. BMJ, 2013. BMJ2013;346:f1706 doi: 10.1136/bmj.f1706.
  • de Vos-Kerkhof E, Roland D, de Bekker-Grob E, Oostenbrink R, Lakhanpaul M, Moll HA. Clinicians' overestimation of febrile child risk assessment. Eur J Pediatr (2016) Apr;175 (4):563-572.
  • Oostenbrink, R., et al., Children with fever and cough at emergency care: diagnostic accuracy of a clinical model to identify children at low risk of pneumonia. Eur J Emerg Med, 2013. 20:p. 273-80
  • Kerkhof, E., et al., The Predictive Value of the NICE "Red Traffic Lights" in Acutely Ill Children. PLoS One, 2014. 9(3): p. e90847
  • Verbakel, J.Y., et al., How well do clinical prediction rules perform in identifying serious infections in acutely ill children across an international network of ambulatory care datasets? BMC Med, 2013. 11(1): p. 10. International conferences Menno van der Eerden
  • 2009-2010 Organizing Intensive Tropical Medicine course, Blantyre, Malawi
  • June 2011-2016 Organizing Masterclass Respiratory infections in Barcelona with professor Antoni Torres, pulmonary physician University, Hospital Clinic, Barcelona, Spain
  • April 2016 Organizing Masterclass Exacerbations of COPD in Oxford with Professor Ian Pavord, pulmonary physician, University Hospital of Oxford, England Recent lectures
  • February 2015 Presentation in Educational symposium for Spanish pulmonary Physicians Barcelona
  • February 2015 Presentation in International symposium on pulmonary infections, Leuven
  • July 2016 Presentation in 1st World Bronchiectasis Conference Hannover
  • September 2016: Presentation in European Respiratory Society congress London Rianne Oostenbrink, recent lectures
  • European society pediatric infectious diseases congress , Brighton 2016 May
  • European society for emergency medicine congress , Vienna September 2016
  • Congress of European academic pediatric society, Geneva, October 2016 Annemarie van Rossum, recent lectures 2016 University of Oxford/ESPID course: Hot topics in infection and immunity in children. 2015 37th Conference of German and Swiss pediatric Pulmonologists. Mycoplasma pneumoniae, update on diagnostic and therapeutic boundaries. Basel March 7 2015 2014 7th Danish Paediatric Infectious Diseases Symposium, September 26-27th, 2014 Comwell Klarskovgaard, Korsør, Denmark. Mycoplasma pneumoniae respiratory tract infections: does treatment help?
  • Talent identification: - Wendy Unger follows the Female Career Development (FCD) program this year, and has followed an "European Molecular Biology Organization" (EMBO) leadership course for junior PI's (EMBO Heidelberg) - Rianne Oostenbrink has followed: Leiderschap door samenspel in 2016 (VENA) and a course for management and leadership, Erasmus MC in 2012 - Menno van der Eerden will follow het "Persoonlijk leiderschapsprogramma for Medical Specialists" at the 2nd half of 2016. - Marielle Pijnenburg: FCD in 2011 - Mireille van Westreenen: has followed a "Persoonlijk leiderschapsprogramma" - Annemarie van Rossum: FCD and leiderschapscursus voor afdelingshoofden.2007 Erasmus MC klinisch fellowship, 2008 ZonMW (Dutch Scientific Organization, NWO) Clinical Fellowship and 2008 Fellowship award of the European Society of Pediatric Infectious Diseases. 2012 International Investigator Award of the Infectious Diseases Society of America, special honor of the Pediatric Infectious Diseases Society of America
  • Review and monitoring of trials will be performed by research Thema Thorax
  • A bibliometric network analysis is not yet available

Key and relevant publications of the last five years

  • van der Eerden MM. Antibiotics for Community-Acquired Pneumonia in Adults.N Engl J Med. 2015 Aug 13;373(7):683
  • Nijman, R.G., et al., Clinical prediction model to aid emergency doctors managing febrile children at risk of serious bacterial infections: diagnostic study. BMJ, 2013. BMJ;346:f1706 doi: 10.1136/bmj.f1706
  • Uzun S, Djamin RS, Kluytmans JA, Mulder PG, van't Veer NE, Ermens AA, Pelle AJ, Hoogsteden HC, Aerts JG, van der Eerden MM. Azithromycin maintenance treatment in patients with frequent exacerbations of chronic obstructive pulmonary disease: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2014 May;2(5):361-8
  • Spuesens EB, Fraaij PL, Visser E, Hop WC, van Adrichem L, Weber F, Moll HA, Berger MY, van Rijsoort-Vos T, van Belkum A, Schutten M, Diepstraten-Pas S, Oster-haus ADME, Hartwig NG, Vink C, Van Rossum AMC. Carriage of Mycoplasma pneumoni-ae in the upper respiratory tract of symptomatic and asymptomatic children. PLoS Med. 2013;10(5):e1001444.
  • Paats MS, Bergen IM, Hanselaar WE, van Zoelen EC, Verbrugh HA, Hoogsteden HC, van den Blink B, Hendriks RW, van der Eerden MM. T helper 17 cells are involved in the local and systemic inflammatory response in community-acquired pneumonia.Thorax. 2013 May;68(5):468-74
  • Paats MS, Bergen IM, Hanselaar WE, Groeninx van Zoelen EC, Hoogsteden HC,Hendriks RW, van der Eerden MM. Local and systemic cytokine profiles in nonsevere and severe community-acquired pneumonia. Eur Respir J. 2013 Jun;41(6):1378-85
  • Paats MS, Bergen IM, Hoogsteden HC, van der Eerden MM, Hendriks RW. Systemic CD4+ and CD8+ T-cell cytokine profiles correlate with GOLD stage in stable COPD. Eur Respir J. 2012 Aug; 40 (2):330-7
  • van Riel D, Leijten LM, van der Eerden M, Hoogsteden HC, Boven LA, Lambrecht BN, Osterhaus AD, Kuiken T. Highly pathogenic avian influenza virus H5N1 infects alveolar macrophages without virus production or excessive TNF-alpha induction.PLoS Pathog. 2011 Jun;7(6)
  • Moesker FM, van Kampen JJ, van der Eijk AA, van Rossum AM, de Hoog M, Schutten M, Smits SL, Bodewes R, Osterhaus AD, Fraaij PL. Human bocavirus infection as a cause of severe acute respiratory tract infection in children. Clin Microbiol Infect. 2015 Oct;21(10):964.e1-8
  • van der Eerden MM, Boersma WG. Single versus combination antibiotic therapy in adults hospitalised with community-acquired pneumonia Thorax. 2013 Nov;68(11):1068

PhD theses of the last five years

  • The T Helper 17 Lineage in Pulmonary Diseases. Marthe Paats. 2012
  • Characterisation and prevention of exacerbations in frequently exacerbating patients with COPD. Sevim Uzun. 2014
  • F.M. Moesker. Severe Acute Virus Infections in pediatric patients. Erasmus University Rotterdam. July 6 2016
  • EBM Spuesens. Colonization and infection by Mycoplasma pneumoniae of the respiratory tract in children. September 13 2016.
  • Improving Diagnostic strategies for predicting serious bacterial infections in children with fever. RG Nijman. Erasmus MC, Rotterdam, 2014
  • Remco Djamin. The effect of long term macrolide therapy in COPD exacerbations with frequent exacerbations.2017

Non-scientific publications related to the ACE

Principal coordinator(s)