annual report 2015 - umcg · 4 introduction the groningen research institute for asthma and copd...
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Groningen Research Institute for Asthma and COPD
Annual Report 2015
UMCG
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Content Mission statement ................................................................................................................. 3
Introduction ........................................................................................................................... 4
Perspectives .......................................................................................................................... 7
The year 2015 in review ........................................................................................................ 9
Highlights ........................................................................................................................... 9
Prizes/Awards ...................................................................................................................10
Visitors ..............................................................................................................................10
Special Topics ......................................................................................................................12
Special Topic 1 .................................................................................................................12
Special Topic 2 .................................................................................................................14
Special Topic 3 .................................................................................................................18
Special Topic 4 .................................................................................................................22
Departments .........................................................................................................................25
Members 2015 ………………………………………………………………………………………27
International collaboration 2015 ............................................................................................29
Seminar program 2015 .........................................................................................................32
Research meetings 2015 ......................................................................................................34
Brainstorm sessions 2015 ....................................................................................................37
Research projects 2015 ........................................................................................................38
Publications 2015 .................................................................................................................46
Dissertations .....................................................................................................................46
Publications SCI journals ..................................................................................................47
Publications in Dutch ........................................................................................................62
Books/Book chapters ........................................................................................................63
Contributions to other research institutes ..........................................................................63
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Mission statement
The mission of GRIAC is the multidisciplinary translational study of obstructive airway and pulmonary diseases and healthy ageing
Program leaders:
Prof. dr. Reinoud Gosens and Prof. dr. Gerard H.Koppelman Visiting address: University Medical Center Groningen Hanzeplein 1 NL-9713 GZ Groningen Website: www.griac.nl
Secretariat: Ms. H. Boering, Dept. Pediatric Pulmonology and Pediatric Allergology Beatrix Children’s Hospital University Medical Center Groningen Hanzeplein 1 P.O. Box 30.001 NL-9700 RB Groningen Phone: 31-50-361 1423 Fax: 31-50-361 1704 Email: [email protected] and [email protected]
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Introduction The Groningen Research Institute for Asthma and COPD (GRIAC) is dedicated to research on obstructive and pulmonary diseases on the edge of clinical and fundamental research. The main theme of GRIAC is unravelling the underlying mechanisms of the development, progression and remission of airway obstruction, allergy and airway hyperresponsiveness, their mutual interactions, and their relevance to treatment. These phenomena are important risk factors for the development of asthma and COPD and crucial characteristics in their clinical pictures. GRIAC operates within the research framework of the University Medical Center Groningen, which has a central focus on healthy ageing and the Faculty of Science of the University of Groningen, which has a focus on molecular life and health. GRIAC is part of the governmentally accredited organization GUIDE (Groningen University Institute for Drug Exploration) which is embedded in the Groningen School of Medical Sciences (GSMS). Participating departments The multidisciplinary and translational research of GRIAC is the result of an intensive collaboration between the researchers of GRIAC, consisting of our members from different disciplines. The disciplines involved are allergology, experimental pulmonology and inflammation research, epidemiology, general practice, molecular pharmacology, pathology, paediatric pulmonology and paediatric allergology, pulmonology and respiratory insufficiency. GRIAC recently added new members from the department of Clinical Pharmacy and from ERIBA, the European Research Institute for the Biology of Aging. Collaboration is based on freedom, equivalence and consensus. Extensive collaboration exists with Departments of Dermatology, Gastroenterology, Genetics, Haematology, Medical oncology and Transplantation. Furthermore, collaboration exists with the Department of Analytical Biochemistry (University Center for Pharmacy).
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Research program GRIAC defines ‘obstructive airway and pulmonary disease’ in relation to healthy ageing, as its main topic, which is reflected in our mission statement. Research projects have to fit within this research topic, describing the projects in their mutual cohesion. The tuning of projects and development into a program is the responsibility of the program leaders of GRIAC, in exchange with the Scientific Board of the Institute. GRIAC operates within the University Medical Center Groningen (UMCG) and its overarching research theme “Healthy Ageing”, and partially within the Groningen Research Institute of Pharmacy (GRIP), with a focus on Molecular Life and Health. Research within GRIAC focuses on the main challenges of obstructive airway and pulmonary disease: • Identifying risk factors for the development, progression and remission of disease • Identifying disease-related genes, gene pathways, gene functionality and gene regulation • Unravelling the pathophysiology of allergen-, environmental- and smoke- induced disease, in humans, animal models, and in vitro cell systems • Unravelling the effects of disease-related inflammation on lung function, hyperresponsiveness and remodeling of large and small airways • Defining new targets for drug intervention and evaluation of intervention strategies • Development of noninvasive or less invasive tools to assess severity of disease and effects (and side effects) of treatment. Scope of research These challenges are investigated particularly in asthma and COPD, resulting in integrated subprograms on: 1. Epidemiology and genomics 2. Molecular Medicine: Pathophysiology and pathogenesis of chronic lung disease and drug target identification. 3. Clinical Medicine: Assessment, modulation of and intervention in disease severity, progression and remission Epidemiology and genomics The longstanding expertise in identifying risk factors and the availability of large, prospective, long-term follow up of patient-based and population-based cohorts (such as LifeLines) and the collaboration with the Department of Genetics enables extensive sub-programs, including exposomics, (epi)genome-wide association, genome-wide interactions and transcriptome sequencing studies.This has resulted in identification of numerous novel genetic loci related to asthma and COPD onset and progression. Proteomic and lipidomic research has led to identification of disease susceptibility and progression markers. GRIAC has a longstanding collaboration with the proteomics facility, and recently incorporated its first member from the European Research Institute on the Biology of Ageing (ERIBA), strengthening its focus on bioinformatic analyses of integrated genomic datasets. Molecular medicine GRIAC is actively engaged in studies linking clinical outcomes to pathophysiology, also on a molecular basis. Often based on outcomes from and also involving omics studies, the functionality of genes and proteins in disease is studied using molecular approaches in cells and tissues from patients, in cell lines and in animal models. In vivo and in vitro silencing and overexpression of genes are now established techniques that are operational at the UMCG and GRIP, including the development of knock out and transgenic mouse models, and the use of RNA interference and pharmacological modulation of cells and tissue slices. Fundamental to this line of research is the exploration of intracellular and intercellular pathways and interactions relevant for tissue repair, disease development, progression and remission, as well as for the exploration of novel drug targets.
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Clinical medicine Patient-centered research is at the heart of GRIAC. Our translational research approach includes large-scale clinical management in primary care, clinical and intervention studies in allergy, food allergy, asthma and COPD. Because it is moving towards precision medicine in obstructive and pulmonary disease, GRIAC is in an excellent position to incorporate genomic markers in intervention studies. GRIAC is actively engaged in the development of clinical questionnaires for disease diagnosis and monitoring of disease control. Pulmonary rehabilitation and novel bronchoscopic intervention techniques are evaluated for the treatment of COPD. How we collaborate Every two weeks GRIAC organises research meetings for the whole institute in which both internal and external speakers are invited to venture new ideas and to challenge the audience. This constitutes also the forum in which different types of research are being presented to all members of GRIAC. Members of GRIAC participate in very different aspects of asthma and COPD research, ranging from epidemiology, clinical allergology, pulmonology, pharmacology, and general practice to basic research in genetics, proteomics, tissue studies, cell cultures and animal models. Lively discussions always take place. To enhance collaboration and stimulate new areas of research, GRIAC organises twice yearly a research retreat and monthly “brainstorm sessions” on a specific topic. These brainstorm sessions are used to stimulate novel ideas for multidisciplinary research, and to discuss publication ideas for high impact journals. During the GRIAC retreat the members of the Board of directors, scientific staff and post-docs of GRIAC discuss future perspectives and new developments in research and explore potential new collaborations within their research, based on international developments in the field. During and after the research meeting investigators can discuss their grant proposals with the staff members, who are expert in a particular field. Finally, there are weekly meetings for junior researchers and staff members. At these meetings there is ample time for discussion on choosing the appropriate study design, the set-up of research protocols, analyses and interpretation of results of research, and for preparation and improvements in concepts of abstracts, and oral and poster presentations at international meetings. Introductory lectures are provided in lung function measurements, laboratory techniques, genetic research and so on. We aim to make our PhD students familiar with these research techniques. These weekly GRIAC meetings aim to teach the understanding of different aspects of the approach towards research on asthma and COPD in the various disciplines involved in GRIAC in order to improve the level of interdisciplinary research. PhD courses in epidemiology, statistics and genetic data analyses are being organised for members of GRIAC and others interested as well. Organisation Two program leaders lead the Institute. They have the following tasks:
Representatives in GSMS and GUIDE
Contacts with the UMCG
Contacts with the University of Groningen
Policy preparation for KNAW, FMW, UMCG and University of Groningen
Preparing propositions for research development The coordinators are advised extensively by the Board of GRIAC, consisting of senior members of the participating departments, who all have their own specific expertise. This board advises in all aspects of research. The board meets once monthly to exchange ideas and prepare policies.
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Perspectives Asthma and COPD research takes place in a lively and rapidly changing field. New developments will encompass the functional genomics (including exposomics, lipidomics and proteomics) of asthma and COPD. We envisage that integration of the – omics techniques will provide novel insight into the disease networks that lead to these obstructive airway diseases. Within each sub-program, specific research goals are complemented with an overarching emphasis on healthy ageing, drug development, societal impact and the relevance of infrastructure. As listed below, this GRIAC approach has resulted in important achievements in past years and in new targets to work on for the future. The strategic sub-programs • Epidemiology and genomics: Study approaches integrating epidemiological and genomic techniques are customary at GRIAC. Epidemiological studies encompassing endogenous, environmental and lifestyle risk factors, in general and patient-based population and from the prenatal phase to mature age. Genomic studies are performed at the level of genetics, epigenetics, gene expression and function, molecular mechanisms and gene-gene and gene-environment interactions in disease development, progression, remission, and severity, as well as disease intervention (pharmacogenomics), and these are integrated with proteomic approaches. • Molecular Medicine: The focus here is on role of allergens, smoking and other lifestyle factors in pathophysiology and pathogenesis of environment-induced diseases including asthma and COPD. In vivo studies in humans and animal models (including transgenerational models) using mice and unrestrained guinea pigs are used to identify disease mechanisms and drug targets. Investigations include lung function techniques and studies of blood, tissues and/or cells derived from airways or lungs. Furthermore, in vitro studies assess cellular activation, adhesion and interactions with other cell types and with their environment, including the extracellular matrix. Signaling pathways and the function of susceptibility genes that were identified in the epidemiology and genomics subprogram are studied in cells and tissue explants (e.g. lymphocyte subsets, epithelial cells, fibroblasts, intact airway and smooth muscle preparations). Interactions between different cell types are studied by using cells obtained from sputum induction and nasal brushings as well as airway wall and lung tissue obtained by bronchoscopy, surgical biopsy or surgical resection. • Clinical Medicine: Assessment, modulation and intervention in disease severity, progression and remission: Disease outcome assessment is being studied with techniques such as exhaled breath analyses and small airway dysfunction. In addition, validated questionnaires on quality of life, drug side effects, hyperresponsiveness and symptoms are developed for diagnostic purposes as well as outcome assessment. Interventions can be at the level of cell cultures, animal models and clinical studies with targeted therapy. Output, visibility and (external) funding Productivity of GRIAC is at present overall very good and the whole GRIAC institute was graded “excellent”in its most recent Mid Term Review. Results in internal medicine and basic science have been published in top peer reviewed journals and patents have also been filed. GRIAC members have been urged to focus on publication strategy and brainstorm sessions have been organized to even further improve the impact of scientific output. Asthma and COPD are highly prevalent in the general population, and thus focussing on these two syndromes is appropriate and has a high societal relevance. At current the priority of the institute is ranging from cellular models to the underlying disease models to the clinic (translational research) with transdisciplinarity as a major feature. The national and international academic reputation of the senior GRIAC members can be weighted at its merits judging the invitations to address international congresses and their
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prominent roles in various national and international research and professional societies and working groups in addition to their role in EU collaborations. In 2014, the Expertscape Website graded GRIAC amongst the top institutes in Europe in relation to asthma and COPD. Moreover, since several of these GRIAC members are relatively young and proven to develop their high potential in their specific research field (e.g. epidemiology, pediatric and adult pulmonology, and molecular pharmacology), GRIAC can face its future with confidence. We will continue to invest in the training of young scientists in the field of obstructive airways and pulmonary disease, with a focus on multidisciplinary translational research. Given the true interdisciplinary nature of the institute, we feel confident that ongoing close collaboration of GRIAC members who share their in-depth knowledge of specific research fields in asthma and COPD will keep the institute at the internationally acknowledged level of excellence in the future, and that they will be able to generate sufficient resources to finance this research. We have shifted our focus from smaller (University Medical Centers) towards larger (inter)national and interdisciplinary research grants (Lung foundation consortium grants, NWO TOP grants, European funding) as well as personal grants (VENI, VIDI, VICI and ERC grants). Within the U4 collaboration of the Universities of Groningen, Ghent, Göttingen and Uppsala, international collaborations are ongoing for PhD students to stay at 2 or 3 of these universities for an international PhD project.
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The year 2015 in review
All contributions to the scientific work in GRIAC are important and highly appreciated. It cannot be stressed enough that all the scientific output and results obtained are only possible due to the contribution of every single person who works within our research institute. Nevertheless, without disrespect to the work of members who are not specifically mentioned, we like to highlight some topics that drew particular attention in 2015.
Highlights
During the American Thoracic Society Conference (May 2015) in Denver, USA, two GRIAC researchers received a prestigious award:
Prof. D.S. Postma received the Trudeau Medal from the American Thoracic Society. This award recognizes lifelong major contributions to the prevention, diagnosis and treatment of lung disease through leadership in research, education or clinical care.
Prof. H. Meurs received the Joseph R. Rodarte Award from the American Thoracic Society assembly on respiratory structure and function. This award is designated for an established investigator who has made distinguished contributions in the fields of respiratory medicine or physiology.
We congratulate Prof. Postma and Prof. Meurs with this excellent achievement.
In relation to the thesis defences of Dr. M. de Vries, Dr. K. Kumawat, Dr. L.E.M. Kistemaker, Dr. E. van der Wiel and Dr. L. Franciosi minisymposia were organized. Speakers at these symposia were all national and international leading researchers. Dr. B.N. Melgert, Dr. R. Gosens, Dr. D.J. Slebos and Dr. I.H. Heijink were promoted to associate professors. The GRIAC researchers Prof. D.S. Postma, Prof. B.N. Melgert, and Dr. M.N. Hylkema organized, in collaboration with Prof. P. Sterk (AMC) and Dr. G.J. Braunstahl (St Franciscus Hospital), the conference ‘Een leven lang longen’ in Almere. During this conference scientists and patients gave input on the main themes to be selected for the ‘National Program Lung Research’. The conference was very well attended. GRIAC researcher Prof. H.M. Boezen, chair of the ERS working group on Genetics and environment, organized together with the secretary of this group Prof T, Sigsgaard (DK) a two day ERS research seminar in Estoril, Portugal, entitled Genetics, epigenetics and exposomics: novel methods to study gene-by-environment interactions. A faculty of experts and a selected group of actively participating researchers met and discussed state-of-the-art and novel research approaches in the field of epigenetics and exposomics. Dr. J.K. Burgess and Dr. A. Dolga were appointed as Rosalind Franklin Fellows (assistant professor) at the departments of Pathology and Medical Biology/section Medical Biology and Molecular Pharmacology, respectively. GRIAC members are actively involved in the 7 Task Forces of the Netherlands Respiratory Society that will give input to the National Roadmap for Respiratory Research.
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Two of the three ‘Longfonds’ consortium grants for 2015 were awarded to projects lead by GRIAC principal investigators:
Section Treatment: Does high baseline oxidative stress cause macrophages to dysfunction during exacerbations in COPD and asthma? Prof. B.N. Melgert (UMCG/GRIAC), Dr. R. Lutter (AMC), Dr. F.O. Martinez (Oxford), Prof. H.A.M. Kerstjens (UMCG/GRIAC) Section Lung Repair: Mesenchymal stem cell deficiencies in emphysema: finding the right niche for alveolar repair. Prof. I.H. Heijink (UMCG/GRIAC), Dr. N.H.T. ten Hacken (UMCG/GRIAC)
In addition, three junior investigator grants from the ‘Longfonds’ were awarded to GRIAC researchers (Dr. M. Duiverman, Dr. L.E.M. Kistemaker, Dr. S.D. Pouwels). See ‘special topic 4’ for a short description of the projects. Dr. B.N. Melgert, in collaboration with Prof. A. Casini, filed a European patent entitled: Gold (III) compounds as tartrate-resistant acid phosphatase inhibitors, and the therapeutic uses thereof. Date: September 29, 2015. European Patent application No. EP15187373.4
Prizes/Awards
N. Tania, MSc won a poster award at the American Thoracic Society conference in Denver H. Tasena, MSc won the NRS Young Investigators Presentation award E. Osei, MSc won the NC3R best oral presentation award at the YIM meeting in London Dr. J.N.G. Oude Elberink won the ‘One day wonder’- award, an award for excellent teaching from the Medical Faculty of the University of Groningen Dr. L.E.M. Kistemaker won the 2nd prize in the Van Swinderen PhD thesis prize competition of the University of Groningen.
Visitors
Prof. Dr. E.R. Bleecker, Wake Forest School of Medicine, Winston-Salem, USA. February 11, 2015. Prof. Dr. D.A. Meyers, Wake Forest School of Medicine, Winston-Salem, USA. February 11, 2015. Prof. Dr. R. Penn, Thomas Jefferson University, Philadelphia, USA. February 20, 2015. Prof. Dr. P. Hiemstra, Leiden University Medical Center, Leiden. February 20, 2015. Prof. Dr. A. Halayko, University of Manitoba, Winnipeg, Canada. March 6, 2015. Prof. Dr. W. Kummer, Justus-Liebig-University, Giessen, Germany. March 6, 2015. Prof. Dr. T. Sigsgaard, Aarhus University, Aarhus, Denmark. June 22, 2015 Prof. S. Anderson, University of Sydney, Sydney, Australia. June 30, 2015.
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Prof. Dr. D.E. Davies, University of Southamptom, Southampton, UK. July 1, 2015. Prof. Dr. C. Lloyd, Imperial College, London, UK. July 1, 2015. Prof. A. Kalergis, Pontificia Universidad Católica de Chile, Chile. September 4, 2015. Dr. G.T.M. Wagenaar, Leiden University Medical Center, Leiden. September 10, 2015. Prof. Dr. D. Knight, University of Newcastle, Newcastle, Australia. October 1, 2015. Prof. Dr. L. Han, Academy of Military Medical Sciences, Beijing, China. November 3, 2015. Dr. F.O. Martinez, Oxford University, Oxford, UK. November 16, 2015. Prof. Dr. C. Gonzalez-Billault, Universidad de Chile, Santiago, Chile. November 23, 2015.
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Special Topics
Special Topic 1
FRESH AIR: increasing awareness and research capacity in the battle against indoor
air pollution in Uganda, Kyrgyz Republic, Vietnam and Greece Frederik van Gemert, Thys van der Molen
Department of General Practice
While tobacco smoking is widely recognized as the main risk factor for developing chronic obstructive lung diseases, far less attention has been paid to other causes of lung diseases such as biomass smoke and ambient air pollution. Especially in low and middle income countries, these factors seem to play a major, but often overlooked, role.
Figure 1: Indoor cooking
During his many travels in Africa, GRIAC researcher and GP Frederik van Gemert became aware of this issue and in 2010 he set out the first studies to gain more insight in the scope of the problem in Africa. Initially, a systematic literature review was performed, followed by a pilot field study in Masindi, a rural district of Uganda. Soon, there was enough reason to start a follow-up study and in 2012 indeed a larger study was initiated including almost 600 patients from 30 different villages in Masindi. It was found that in this rural district of Uganda, COPD starts early in life, with many patients having spirometry confirmed COPD before their 40s. In addition to high smoking prevalence in men, biomass smoke was identified as a major health threat to men and women in rural areas of Uganda. In 2015, the results were published in The Lancet Global Health and gained much media attention. In order to raise more awareness, alongside this success, the FRESH AIR program was developed and extended beyond the borders of Uganda. FRESH AIR is a program that focuses on prevention, treatment, impact and awareness of chronic lung diseases in four countries worldwide, including Uganda, Kyrgyz Republic, Vietnam and Greece. The FRESH AIR philosophy is based on the sharing and transfer of knowledge across borders. Using implementation science, the project aims to build research capacity on a local level. In 2015, the European Union funded this program with a €3 million Horizon 2020 grant. GRIAC members prof. dr. Thys van der Molen, dr. Job van Boven and dr. Frederik van Gemert were part of the consortium of 15 parties, including representatives from all four countries, Leiden University and several European respiratory societies (IPCRG, ECC, ELF, NCSCT).
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Figure 2: Performing spirometry in Masindi, Uganda
So far, considerable progress has already been made in Uganda. On Monday November 23 2015, the inaugural meeting of the Makerere University Lung Institute took place. The Lung Institute has been created to act as a centre of excellence for research into the prevention, diagnosis and care of respiratory diseases in Uganda and beyond, using the concept of the GRIAC institute in Groningen. Director of the newly established Lung Institute will be local pulmonologist and GRIAC PhD candidate dr. Bruce J. Kirenga. Notably, prof. dr. Thys van der Molen was installed as co-Chair of the Board of Governors and Trustees, and Frederik van Gemert as co-Chair of the Institute Technical Board.
Besides FRESH AIR, one of the Institute’s first planned projects will be the African Severe Asthma Program (ASAP). In ASAP, three universities in Kenya, Ethiopia, and Uganda will collaborate to include about 2,000 patients with asthma and to investigate whether providing these often very symptomatic patients with basic treatment alters clinical outcomes. Another goal is phenotyping and genotyping the therapy resistant severe asthma population, aiming to find new leads for asthma diagnosis and treatment in this region. Also for ASAP, the Makerere Lung Institute will closely collaborate with GRIAC. The collaboration includes training and exchange of pulmonologists, technicians, and research staff. Notably, the institute is also aiming to educate primary care physicians working in the rural areas of Uganda on treatment of asthma and COPD. Recently, these milestones in the East African region have been highlighted by a publication in The Lancet Global Health blog.
In 2016, GRIAC researchers Frederik van Gemert and Bruce Kirenga are expected to complete their PhD theses (under supervision of prof. dr. Thys van der Molen), both focusing on chronic lung diseases in Africa.
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Special Topic 2
Endobronchial valves for emphysema without interlobar collateral ventilation (The
STELVIO trial)1
Karin Klooster, Nick.H.T. ten Hacken, Jorine E. Hartman, Huib A.M. Kerstjens, Eva M. van
Rikxoort, Dirk-Jan Slebos
Department of Pulmonology
New England Journal of Medicine 2015;373:2325-35.
Background Bronchoscopic lung volume reduction with the use of one-way endobronchial valves has emerged as a potential treatment for patients with severe emphysema. This treatment was previously investigated in the randomized, controlled Endobronchial Valve for Emphysema Palliation Trial (VENT),2 which showed significant but moderate improvements in forced expiratory volume in 1 second (FEV1). Post-hoc analyses of the VENT data suggested that endobronchial valve treatment might be more effective in patients who had a complete fissure (as compared with an incomplete fissure) between the lobe that was targeted for treatment and the adjacent lobe on high-resolution computed tomography scan and when endobronchial valve treatment resulted in complete occlusion of the target lobe.2 A complete fissure on CT scan is a surrogate finding for the absence of interlobar collateral ventilation; if there is collateral ventilation, an occluded lobe can be reinflated through its collaterals.3 It is difficult to assess the completeness of the fissure on CT scan in order to predict the absence of collateral ventilation, with considerable interobserver variation.4 Temporary bronchoscopic lobar occlusion, achieved by inflation of a balloon catheter in the lobar bronchus, is another way to assess collateral ventilation. We conducted a randomized, controlled study, called STELVIO, to examine the effectiveness of endobronchial valve treatment in patients with severe emphysema in whom the absence of collateral ventilation had been proved. The STELVIO trial has been designed to serve the needs of our patients with severe emphysema, understanding that endobronchial valve therapy using best responder criteria has a potential as a treatment for these patients. This trial has not been designed as an industry invoked ‘Investigational Device Exemption’ trial, but resembles routine daily clinical care for this patient group. This trial ‘Endobronchial valves for emphysema without interlobar collateral ventilation’ is a 100% investigator initiated and driven trial. The trial, has been financially supported by a grant (no. 171101008, to University Medical Center Groningen)from The Netherlands (government) Organization for Health Research and Development ZonMw, The Hague, the Netherlands, and innovation funding by the University Medical Center Groningen, the Netherlands. Methods This was a randomized, controlled study comparing endobronchial valve treatment with standard medical care, with crossover at 6 months to endobronchial valve treatment for patients assigned to standard medical care. Patients with emphysema who were older than 35 years of age and had stopped smoking more than 6 months earlier were eligible for the study if they had a post-bronchodilator FEV1 that was less than 60% of the predicted value, total lung capacity that was more than 100% of the predicted value, and residual volume that was more than 150% of the predicted value, with a score on the modified Medical Research Council (mMRC) scale of more than 1. An additional criterion for eligibility was a lobe that was determined to be a target for treatment, with a complete or nearly complete fissure between the target lobe and the adjacent lobe as visually judged on CT scan. The main exclusion criteria were evidence of collateral ventilation in the target lobe and failure to achieve lobar occlusion with endobronchial valves.
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Collateral ventilation was assessed by means of the Chartis system (Figure 1B, Pulmonx, USA).5 Briefly, during bronchoscopy while the patient was under conscious sedation (with the administration of propofol and remifentanil), the target lobar airway was temporarily occluded by means of a balloon catheter, which blocks inspiratory flow but allows expiratory flow. A continuous expiratory flow through the catheter indicates collateral ventilation, and a flow gradually declining to zero indicates no collateral ventilation. The one-way endobronchial valve (Figure 1A, Zephyr® Pulmonx USA) was used as study device and was delivered with the use of a flexible endobronchial valve delivery catheter (Pulmonx Corporation, Redwood City, CA, USA) during a bronchoscopy. The treatment lobe was intended to be completely occluded with endo-bronchial valve placement. Achieving lobar occlusion was verified via bronchoscopy immediately after finishing valve placement. In this study, the bronchoscopy was performed either under conscious sedation or under general anesthesia with a flexible bronchoscope. Following recovery from anesthesia, patients stayed in the hospital at least one night for observation.
Figure 1A-D. A) one-way endobronchial valve (cartoon); B) Chartis balloon assessing collateral flow from the right lower lobe; C) one-way endobronchial valve in situ during expiration; D) one-way endobronchial valve in situ during inspiration.
Primary outcome measures were improvements from baseline to 6 months in FEV1, forced vital capacity, and distance on 6 minute walk test in the EBV group as compared with the control group. Secondary outcome measures, among patients who completed the study, were improvements from baseline to 6 months in FEV1, forced vital capacity, distance on 6 minute walk test, the total score on the St. George’s Respiratory Questionnaire (SGRQ),the score on the Clinical COPD (chronic obstructive pulmonary disease) Questionnaire (CCQ), and the total volume of the treated lobe on inspiratory CT scan. Clinical response was defined on the basis of established minimal clinically important differences from baseline. Safety data were collected during the study. Results The study was conducted between June 2011 and November 2014. In this study 680 patients were recruited of which 84 patients were initially included for baseline testing and bronchoscopy. Of these patients, 16 were excluded because they had collateral ventilation (13 patients) or because the airway anatomy was not suitable for endobronchial valve placement (3 patients), resulting in a total of 68 patients who underwent randomization. Based on these data approximately 10% of the patients with advanced COPD will potentially qualify for endobronchial valve treatment in the end.
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The remaining 68 patients (mean age, 59±9 years; 46 were women) were randomly assigned to the EBV group (34 patients) or the control group (34 patients). At baseline, the FEV1 and FVC were 29±7% and 77±18% of the predicted values, respectively, and the distance on 6 minute walk test was 374±86 meter.Intention-to-treat analyses showed significantly greater improvements in the EBV group than in the control group from baseline to 6 months: the increase in FEV1 was greater in the EBV group than in the control group by 140 ml (95% confidence interval [CI], 55 to 225), the increase in FVC was greater by 347 ml (95% CI, 107 to 588), and the increase in the distance on 6 minute walk test was greater by 74 meter (95% CI, 47 to 100) (P<0.01 for all comparisons). Analyses of data for patients who completed the study (25 patients in the EBV group and 33 in the control group) showed significant improvements in the secondary outcome measures from baseline to 6 months in the EBV group as compared with the control group: the increase in FEV1 was greater in the EBV group than in the control group by 191 ml (95% CI, 109 to 272), the increase in forced vital capacity was greater by 442 ml (95% CI, 215 to 668), and the increase in the 6 minute walk distance was greater by 106 meter (95% CI, 80 to 133) (P<0.001 for all between-group comparisons); improvements were also seen in SGRQ scores, with a 14.7-point greater reduction in the EBV group than in the control group (95% CI, -21.8 to -7.6; P<0.001), and in CCQ scores, with a 0.74-point greater reduction in the EBV group than in the control group (95% CI, -1.20 to -0.27; P = 0.002). See figure 2. In 7 of the 34 patients in the EBV group (21%), the endobronchial valves were associated with unacceptable adverse events and had to be removed. There were 23 serious adverse events in the EBV group, as compared with 5 in the control group (P<0.001). In the EBV group, treatment-related serious adverse events included pneumothorax (in 18% of patients), other events requiring valve replacement (in 12% of patients) or valve removal (in 15% of patients), and 1 death due to end-stage COPD with respiratory failure 58 days after treatment. We found that endobronchial valve treatment in patients with emphysema and a proven absence of interlobar collateral ventilation provided a measurable clinical benefit, with significantly improved lung function, exercise capacity, and quality of life, as compared with usual care. The reduction in lung volume with subsequent positive outcomes was accompanied by adverse effects, mainly pneumothorax, which was managed by means of regular care (including chest-tube drainage) but sometimes required repeated bronchoscopy. The endobronchial valves were retained throughout the 6 month study period in 79% of the initially treated patients.
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Figure 2. Secondary outcomes among the patients who completed the study. Shown are secondary outcomes among patients who completed the study, according to the assigned study group (endobronchial valve group or control group). Horizontal lines represent the minimal clinically important difference (MCID) for the following outcomes: forced expiratory volume in 1 second (FEV1), an increase of 100 ml; 6 minute walk distance (6MWD), an increase of 26 meter; SGRQ score, a reduction of 4 points, CCQ score, a reduction of 0.4 points; and residual volume (RV),a reduction of 430 ml. T bars indicate 95% confidence intervals. FVC denotes forced vital capacity. References
1. Klooster K, ten Hacken NH, Hartman JE, Kerstjens HA, van Rikxoort EM, Slebos DJ. Endobronchial Valves
for Emphysema without Interlobar Collateral Ventilation. N Engl J Med. 2015;373:2325-35.
2. Sciurba FC, Ernst A, Herth FJ, et al. A randomized study of endobronchial valves for advanced emphysema.
N Engl J Med 2010;363:1233-44.
3. Herth FJ, Noppen M, Valipour A, et al. Efficacy predictors of lung volume reduction with Zephyr valves in a
European cohort. Eur Respir J 2012;39:1334-42.
4. Koenigkam-Santos M, Puderbach M, Gompelmann D, et al. Incomplete fissures in severe emphysematous
patients evaluated with MDCT: incidence and interobserver agreement among radiologists and
pneumologists. Eur J Radiol 2012;81:4161-6.
5. Herth FJ, Eberhardt R, Gompelmann D, et al. Radiological and clinical outcomes of using Chartis to plan
endobronchial valve treatment. Eur Respir J 2013;41:302-8.
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Special Topic 3
Accelerated lung ageing in COPD: A lung tissue gene expression signature
Maaike de Vries, Alen Faiz, Dirkje S. Postma, Wim Timens, Maarten van den Berge and Corry-Anke Brandsma
Departments of Pathology and Medical Biology and Pulmonology Chronic Obstructive Pulmonary Disease (COPD) is a chronic and progressive inflammatory lung disease, characterized by persistent airflow limitation (1). COPD patients suffer from severe respiratory symptoms leading to a high economic and social burden (1) and COPD is now the third leading cause of death worldwide (WHO 2015). The current pharmacological treatment of COPD is only symptomatic and does not inhibit the progressive decline in lung function that is so characteristic for the disease. Since the underlying pathophysiology of COPD still remains largely unknown, identification of new therapeutic targets is difficult. Hence, novel approaches to find these targets are urgently needed. Ageing can be considered as a gradual, progressive loss of homeostasis, resulting in increased risk of disease or death (2). Acceleration of the ageing process has been indicated to be involved in the pathogenesis of several chronic degenerative diseases, including COPD (3). The ageing lung is characterized by loss of lung function and tissue elasticity, alveolar enlargement and inflammation. These features are all observed in the lungs of COPD patients as well, but not congruent to their actual age (3)(4). In addition, several other markers of ageing were found to be increased in COPD. For example, shortening of telomere length was demonstrated in circulating lymphocytes of COPD patients (5)(6) and the expression of senescence-associated β-galactosidase activity has been shown to be increased in fibroblasts of COPD patients compared with controls (7). These findings offer new insights in the pathogenesis of COPD as a disease of accelerated lung ageing, which may lead to novel therapeutic approaches. But even though the evidence for a role of lung ageing in COPD is increasing, not much is currently known about the genes underpinning this accelerated lung ageing. Therefore, the aim of our study is to create a lung tissue gene expression signature for the ageing lung and identify key genes that are involved in abnormal lung ageing in COPD. To create a lung tissue gene expression signature for the ageing lung, we took advantage of our well-established, unique lung tissue gene expression dataset (8). This dataset contains complete mRNA profiles of 1197 subjects undergoing lung resection or transplantation surgery at one of the participating centers in Groningen, Quebec and Vancouver. By using linear regression analysis for the confounders gender, smoking status and disease in the three separate cohorts followed by a meta-analysis, we associated gene expression with age of the individuals. We found 1598 genes being higher expressed with increasing age and 1156 genes lower expressed with increasing age and a heatmap summarizing these results is shown in Figure 1. Of these genes, Ectodysplasin A2 Receptor (EDA2R), involved in the DNA damage response, was most significantly increased with age. Microsomal Glutathione S-Transferase 1 (MGST1), involved in the detoxification and the defense response to oxidative stress, was most significantly decreased with age.
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Figure 1: Heatmap of genes differentially expressed with increasing age in lung tissue.
The heatmap shows differentially expressed genes with increasing age at FDR < 0.0001 in lung tissue for the three cohorts from Groningen, Quebec and Vancouver. Each probe set is shown separately and for several genes more than one probe set was found to be significant different. Relative increased gene expression is indicated in red, while relative decreased gene expression is indicated in blue. Genes increased expressed with age are shown in the upper part of the heatmap, genes decreased expressed with age are shown in the lower part of the heatmap.
Next, we performed pathway analysis using GeneNetwork (9) to identify biological processes to get more insight in the relevance of the differentially expressed genes to the ageing individual. For the genes that are increased expressed with age, processes involved in calcium signaling and immune response were significantly enriched. Genes decreased expressed with age were found to be enriched for several processes involved in lung development and cell-cell contacts. The data described above demonstrate that gene expression in lung tissue considerably changes with age and point towards genes that are important to lung ageing. However, it does not specifically address genes that may underlie accelerated lung ageing in COPD. Therefore, we took the gene expression analysis one step further and assessed which genes change differentially with age between individuals with and without COPD. From the whole database, we selected 311 COPD patients and 270 non-COPD controls within the 3 cohorts. By performing an age*COPD interaction analysis, we revealed 69 genes to be differentially expressed with age in COPD patients compared to non-COPD controls. Of the 39 genes increased expressed with age in COPD, Deoxyribonuclease I-Like 3 (DNASE1L3), engaged in the complement activation cascade, was most significantly increased expressed with age. KIAA1462, known to be involved in angiogenesis and blood vessel development, was the gene most significantly decreased expressed with age of a total of 30 decreased expressed genes.
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Figure 2: Pathway enrichment of extracellular matrix interaction. (A) Gene set enrichment analysis shows enrichment of genes whose expression levels significantly decreases among genes whose expression decreases with age in COPD. Genes are ranked from left to right based on their expression in the age*COPD interaction analysis in selected COPD patients and non-COPD controls. The position of each vertical bar indicates the position of a gene whose expression is associated with the ECM receptor interaction within the ranked list. The height of the bar represents the running gene enrichment analysis enrichment scores. (B-D) Expression of respectively COL6A3, COL3A1 and COL4A1 with age in COPD patients (red) and non-COPD controls (blue). Subsequent pathway analysis demonstrated that the extracellular matrix (ECM)-receptor interaction pathway was most significantly enriched among the genes that showed a negative interaction (Figure 2A). This indicates that the expression of ECM-related genes is decreased with age in COPD patients compared to the expression in non-COPD controls. ECM is fundamental to the function and structure of the lung. The ECM family comprises over 300 proteins, however, the three main components are elastic fibers, collagens and glycosaminoglycans (10). It is therefore of interest that three collagen genes COL6A3, COL3A1 and COL4A1 are amongst the core enriched genes in this ECM-receptor interaction pathway (Figure 2B, C and D, respectively). In conclusion, we identified a strong gene expression signature for the ageing lung and showed that biological processes like lung development and immune responses are associated with the ageing lung. We found a total of 69 genes differentially expressed with age in COPD patients compared to non-COPD controls and we suggest that the genes involved in extracellular matrix processes might play and important role in accelerated ageing
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in COPD. Since extracellular matrix proteins are mainly produced by pulmonary fibroblasts, it is of high interest to further explore the contribution of fibroblasts to lung ageing. References
(1) From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2015. Available from: http://www.goldcopd.org/. .
(2) Ito K, Barnes PJ. COPD as a disease of accelerated lung aging. Chest 2009 Jan;135(1):173-180.
(3) Mercado N, Ito K, Barnes PJ. Accelerated ageing of the lung in COPD: new concepts. Thorax 2015 May;70(5):482-489.
(4) Fletcher C, Peto R. The natural history of chronic airflow obstruction. Br Med J 1977 Jun 25;1(6077):1645-1648.
(5) Savale L, Chaouat A, Bastuji-Garin S, Marcos E, Boyer L, Maitre B, et al. Shortened telomeres in circulating leukocytes of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2009 Apr 1;179(7):566-571.
(6) Albrecht E, Sillanpaa E, Karrasch S, Alves AC, Codd V, Hovatta I, et al. Telomere length in circulating leukocytes is associated with lung function and disease. Eur Respir J 2014 Apr;43(4):983-992.
(7) Kanaji N, Basma H, Nelson A, Farid M, Sato T, Nakanishi M, et al. Fibroblasts that resist cigarette smoke-induced senescence acquire profibrotic phenotypes. Am J Physiol Lung Cell Mol Physiol 2014 Sep 1;307(5):L364-73.
(8) Brandsma CA, van den Berge M, Postma DS, Jonker MR, Brouwer S, Pare PD, et al. A large lung gene expression study identifying fibulin-5 as a novel player in tissue repair in COPD. Thorax 2015 Jan;70(1):21-32.
(9) Fehrmann RS, Karjalainen JM, Krajewska M, Westra HJ, Maloney D, Simeonov A, et al. Gene expression analysis identifies global gene dosage sensitivity in cancer. Nat Genet 2015 Feb;47(2):115-125.
(10) Humphrey JD, Dufresne ER, Schwartz MA. Mechanotransduction and extracellular matrix homeostasis. Nat Rev Mol Cell Biol 2014 Dec;15(12):802-812.
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Special Topic 4
Granted projects in 2015
In 2015, three junior investigator grants from the ‘Longfonds’ were awarded to GRIAC researchers. The summaries of these granted proposals are outlined below.
The RAGE receptor: A key molecule in lung tissue damage and repair during emphysema.
Simon D. Pouwels Chronic Obstructive Pulmonary Disease (COPD) is a severe and progressive lung disease characterized by both bronchitis and emphysema. COPD is caused by chronic exposure to noxious gases and particles, like cigarette smoke. Emphysema is the irreversible destruction of alveolar tissue for which no good treatment options are currently available. Current treatment is mainly focused at reducing symptoms and the number of exacerbations. Therefore, the Dutch Lung Foundation has prioritized research aimed at the development of novel treatment options inducing lung tissue regeneration. Here, we will investigate the role of the Receptor for Advanced Glycation End-products (RAGE) in lung tissue damage and repair during emphysema. RAGE is a multi-ligand membrane-bound receptor that belongs to the immunoglobulin superfamily and is mainly expressed in the lungs. Upon activation, NFκB-dependent pro-inflammatory effects are elicited. However, RAGE signaling is also important in cellular migration, invasion and adhesion. Several of the RAGE ligands, e.g. HMGB1, S100A8/9 and LL-37, belong to the group of Damage Associated Molecular Patterns (DAMPs), endogenous molecules that are released upon cellular damage and immunogenic cell death, which upon release activate Pattern Recognition Receptors, e.g. RAGE, subsequently inducing a pro-inflammatory innate immune response. Previously, we and others have shown that the levels of RAGE-activating DAMPs are increased systemically and in lung fluid during COPD compared to smoking and non-smoking controls and are even further increased during COPD exacerbations. Furthermore, also the expression of RAGE itself is increased in structural lung cells and cells of the innate immune system during COPD, together suggesting that RAGE signaling is increased in COPD. Next to the membrane-bound form of RAGE also free circulating soluble (sRAGE) exists, which acts as a decoy receptor for RAGE. It inhibits RAGE signaling by binding and therefore inactivating circulating RAGE ligands and by binding to membrane-bound RAGE which inhibits essential RAGE dimerization. In COPD patients the levels of this anti-inflammatory sRAGE are decreased and these levels significantly correlate to the severity of emphysema. In mouse studies the role of RAGE in emphysema was further described, as mice overexpressing RAGE spontaneously develop emphysema and RAGE knock-out mice were significantly protected against smoke- and elastase-induced emphysema. Lastly, the gene encoding RAGE, AGER, has been identified as a susceptibility gene for COPD. Therefore, our hypothesis is that RAGE is a key molecule in tissue damage during emphysema and that intervention in the RAGE-signaling pathway reduces the progression of tissue damage and potentially induces lung tissue regeneration. Here, we will use state-of-the-art in vitro, in vivo and ex vivo techniques to elicit the therapeutic potential of RAGE inhibition for emphysema. In vitro, we will investigate the function of RAGE in wound healing, inflammation, barrier function, cell death and differentiation using alveolar epithelial cells and several laboratory techniques, including flow cytometry, ELISA, scratch assays, qRT-PCR, fluorescent microscopy and Electric Cell-substrate Impedance Sensing (ECIS). Furthermore, we will test the effect of intra-nasal RAGE-ligand application on airway inflammation and lung tissue damage in mice susceptible and non-susceptible for emphysema. Lastly, we will test the therapeutic potential of RAGE inhibitors on lung tissue regeneration using a murine emphysema model and a 3D-ex vivo lung tissue culture model. Together these data will provide novel insight in the role of RAGE-
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signaling in tissue damage during emphysema and indicate whether RAGE inhibition is a potential novel treatment option for emphysema patients inducing lung tissue regeneration. This project will be executed by Simon D. Pouwels in collaboration with Prof. Dr. Irene H. Heijink at the laboratory of Experiment Pulmonology and Inflammation Research (EXPIRE) at the department of medical biology and pathology in the UMCG, Groningen, The Netherlands and in collaboration with Prof. Dr. Oliver Eickelberg at the Comprehensive Pneumology Center in the Helmholtz Zentrum München, Germany. Simon D. Pouwels is a member of the Groningen Research Institute for Asthma and COPD (GRIAC).
High-intensity nocturnal non-invasive ventilation in COPD patients with chronic hypercapnic respiratory failure: where to start and with whom?
Marieke Duiverman
Increasingly more patients with chronic obstructive pulmonary disease (COPD) have chronic hypercapnic respiratory failure (CHRF) for which there are limited treatment options. Application of long-term non-invasive ventilation (NIV) in stable COPD patients has recently been shown to improve survival and quality of life when applied with sufficiently high inspiratory pressures and adequate backup breathing frequencies. However, for a broader implementation of this costly treatment in a potentially large group of severe COPD patients, important issues have to be solved. First, we need to reconsider the current inpatient NIV initiation, which despite tight titration on arterial blood gases, does not always lead to good patient compliance, is inconvenient for patients and is expensive. Secondly, we know that not all COPD patients with CHRF benefit from chronic NIV, but we do not know predictors of a favourable response in individual patients. Aims of the study 1) To investigate whether home initiation of chronic NIV in stable COPD patients with
CHRF is non-inferior to inpatient initiation. 2) To investigate predictors of a favourable response to chronic NIV in COPD patients with
CHRF.
Study design and patients Sixty-two COPD patients with a NIV indication, a sufficient social network at home, without severe cardiac comorbidities, will be randomised to receive the usual inpatient NIV initiation or home initiation. The home initiation will be performed with the use of telemedicine. Furthermore, in these patients and in all other COPD patients initiated on chronic NIV in the Netherlands will be characterised in order to analyse how differences in baseline parameters are related to changes in health-related quality of life. Therefore, patient demographics, data on lung function as well as measures of respiratory muscle activity, arterial blood gases, comorbidities, inflammatory blood markers and anxiety and depressions scores will be collected in a central database. Neuronal remodeling: a novel perspective on airway hyperresponsiveness in asthma
Loes Kistemaker Long-acting anticholinergic drugs have recently been established as effective bronchodilators in asthma (1). This underscores the importance of the cholinergic tone in asthma, which is the predominant driver of neurally mediated bronchoconstriction. It is generally accepted that cholinergic tone is increased in asthma (2). However, the mechanisms underlying an increased cholinergic tone have only partly been resolved and it is unknown how chronic asthma affects airway nerve structure. I hypothesize that airway nerves undergo changes in asthma, including changes in phenotype and isotype, termed as remodeling of airway nerves, or neuronal remodeling (figure 1). I aim to investigate the nature of neuronal remodeling in asthma in detail and hypothesize that this is driven by neurotrophins; mediators which exhibit neuronal growth activity. A particularly interesting neurotrophin in
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asthma pathogenesis is brain-derived neurotrophin factor (BDNF) (3). BNDF expression is upregulated in asthma and there are genetic associations of the BDNF gene with asthma. A clear link exists between neurotrophins and an increased cholinergic tone, however, it is unknown whether BDNF drives neuronal remodeling in asthma (4). I hypothesize that neuronal remodeling is a characteristic feature of asthma, which is driven by BDNF, and contributes to airway hyperresponsiveness, airway inflammation, and airway remodeling; all core features of asthma (figure 1). To investigate this hypothesis, I have the unique opportunity to study this both in animal models of allergic asthma and in human tissues. Neuronal remodeling in these tissues will be characterised and a gene expression signature of neuronal remodeling in asthma will be defined. Furthermore, I will investigate the role of BDNF in neuronal remodeling using a knock-in model of mice with impaired BDNF signaling. Finally, I will determine the functional consequences of neuronal remodeling on airway hyperresponsiveness, airway inflammation, and airway remodeling. Understanding the mechanisms that drive an increased cholinergic tone may lead to improved treatment for asthma patients.
References
(1) Kerstjens HA, Casale TB, Bleecker ER, Meltzer EO, Pizzichini E, Schmidt O, Engel M, Bour L, Verkleij CB, Moroni-Zentgraf P, Bateman ED. Tiotropium or salmeterol as add-on therapy to inhaled corticosteroids for patients with moderate symptomatic asthma: two replicate, double-blind, placebo-controlled, parallel-group, active-comparator, randomised trials. Lancet Respir Med 2015;3:367-376.
(2) Kistemaker LE, Gosens R. Acetylcholine beyond bronchoconstriction: roles in inflammation and remodeling. Trends Pharmacol Sci 2015;36:164-171.
(3) Prakash YS, Martin RJ. Brain-derived neurotrophic factor in the airways. Pharmacol Ther 2014;143:74-86.
(4) Braun A, Lommatzsch M, Neuhaus-Steinmetz U, Quarcoo D, Glaab T, McGregor GP, Fischer A, Renz H. Brain-derived neurotrophic factor (BDNF) contributes to neuronal dysfunction in a model of allergic airway inflammation. Br J Pharmacol 2004;141:431-440.
Figure 1. I hypothesize that there are changes in parasympathetic nerve architecture in asthma, leading to an increased cholinergic tone. This contributes to airway hyperresponsiveness (AHR), airway inflammation, and airway remodeling. Brain derived neurotrophin factor (BDNF) plays a central role in mediating these effects. CNS: central nervous system; ACh: acetylcholine.
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Departments Dept. Epidemiology University Medical Center Groningen Hanzeplein 1 P.O. Box 30.001 NL-9700 RB Groningen Phone 31-50-361 0739 Fax 31-50-361 4493 Principal Investigators: Prof. Dr. H.M. Boezen, Dr. J.M. Vonk Dept. General Practice University of Groningen, Faculty of Medical Sciences A. Deusinglaan 1 NL-9713 AV Groningen Phone 31-50-363 2963 Fax 31-50-363 2964 Principal Investigators: Prof. Dr. T. van der Molen, Dr. B.M.J. Flokstra – de Blok Associate Principal Investigator: Dr. J.W.H. Kocks Dept. Internal Medicine, div. Allergology University Medical Center Groningen Hanzeplein 1 P.O. Box 30.001 NL-9700 RB Groningen Phone: 31-50-361 2976 Fax: 31-50-3121576 Principal Investigator: Dr. J.N.G. Oude Elberink Dept. Pathology and Medical Biology, div. Medical Biology University Medical Center Groningen Hanzeplein 1 P.O. Box 30.001 NL-9700 RB Groningen Phone: 31-50-361 8043 Fax: 31-50-361 9911 Principal Investigators: Prof. Dr. H.I. Heijink, Dr. M.C. Nawijn, Dr. J.K. Burgess University Centre for Pharmacy University of Groningen A. Deusinglaan 1 NL-9713 AV Groningen Phone 31-50-363 3197 Fax: 31-50-363 6908 Principal Investigators: Prof. Dr. M. Schmidt, Prof. Dr. H. Meurs, Prof. Dr. R. Gosens, Prof. Dr. B.N. Melgert, Dr. A.M. Dolga Dept. Pathology and Medical Biology University Medical Center Groningen Hanzeplein 1 P.O. Box 30.001 NL-9700 RB Groningen Phone: 31-50-361 4684 Fax: 31-50-363 2510 Principal Investigators: Prof. Dr. W. Timens, Dr. M.N. Hylkema, Dr. C.A. Brandsma
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Dept. Pediatric Pulmonology and Pediatric Allergy Beatrix Children’s Hospital, University Medical Center Groningen Hanzeplein 1 P.O. Box 30.001 NL-9700 RB Groningen Phone: 31-50-361 1107 Fax: 31-50-361 1704 Principal Investigators: Prof. Dr. G.H. Koppelman, Prof. Dr. A.E.J. Dubois, Dr. B.L. Rottier, Dr. A. Sprikkelman Dept. Pulmonary Diseases and Tuberculosis University Medical Center Groningen Hanzeplein 1 P.O. Box 30.001 NL-9700 RB Groningen Phone: 31-50-361 3532 Fax: 31-50-361 9320 Principal Investigators: Prof. Dr. D.S. Postma, Prof. Dr. H.A.M. Kerstjens, Dr. M. van den Berge, Dr. N.H.T. ten Hacken, Dr. D.J. Slebos Working group on Respiratory Insufficiency University Medical Center Groningen Hanzeplein 1 P.O. Box 30.001 NL-9700 RB Groningen Phone: 31-50-361 3235 Fax: 31-50-361 9320 Principal Investigator: Dr. P.J. Wijkstra
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Members 2015
Other scientific staff
Berge van den M., MD, PhD Brandsma C.A., PhD Burgess J.K., PhD Diamant Z., PhD, Prof. Dolga A.M., PhD Flokstra-de Blok B.M.J., PhD Guryev V., PhD Hacken ten N.H.T., MD, PhD Kocks J.W.H., MD, PhD
Melgert B.N, PhD, Prof. Nawijn M.C., PhD Rottier B.L., MD, PhD Slebos D.J., MD, PhD Sprikkelman A.B., MD, PhD Touw D.J., PhD, Prof. (associate member) Vrijlandt E.J.L.E., MD, PhD Wempe J.B, MD, PhD Willemse B.W., MD, PhD
Post-docs
Boven van J.F.M., PharmD, PhD Robbe-Gonçalves Dias Pereira P., PhD Faiz A. PhD Schokker S., PhD Faria Coimbra Lichtenfels de A.J., PhD Tsiligianni I., MD, PhD Hartman J.E., PhD Velde van der J.L., MD, PhD Jong de C., PhD Vermeulen C.J., PhD Jong de K., PhD de Vries M., PhD Kistemaker L.E.M., PhD Wright D.B., PhD Ng-Blichfeldt, J-P, PhD Xu C., PhD Riemersma R.A., MD, PhD PhD students
Alma H.J., MSc, MD/PhD student Kruk D.M.L.W., MSc Altenburg W.A., MSc Klijnsma M., MD Berkhof, F., MSc Klooster K. Boorsma C.E., MSc Koopmans T., MSc Boudewijn I., MD Metting E.I., MSc Cao J.J., MSc Meyer, K. Msc. Carpaij O., MD Nieuwenhuis M.A.E., MSc Cox C., MSc Ong J., MSc van Dijk E., MSc Osei E., MSc Dijk F.N., MD Pettersson M.E., MD/PhD student Draijer C., MSc van der Plaat D.A., MSc Fattahi F., MSc Poppinga W., MSc Faura Tellez G., MSc Pouwels S.D., MSc Florez-Sampedro L., MSc Rozeveld D., MSc Franciosi L., MSc Saleh-Langenberg J., MD/PhD student Geffen van W., MD Spanjer A.I.R., MSc Gemert van F.A., MD Song, J., MSc Ginkel van C.D., MD/PhD student Tania N., MSc Han B., MSc Tasena H., MSc
Scientific Board
Boezen H.M., PhD, Prof Dubois A.E.J., MD, PhD, Prof Gosens, R., PhD, Prof Heijink H.I., PhD, Prof Hylkema M.N., PhD Kerstjens H.A.M., MD, PhD, Prof Koppelman G.H., MD, PhD, Prof Meurs H., PhD, Prof
Molen van der T., MD, PhD, Prof Oude Elberink J.N.G., MD, PhD Postma D.S., MD, PhD, Prof Schmidt M., PhD, Prof Timens W., MD, PhD, Prof Vonk J.M., PhD Wijkstra P.J., MD, PhD
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Han X., MSc Vos B.J.P.R., MD/PhD student Hazenberg A. de Vries G.E., MSc Hesse L., MSc van der Wiel E., MD Imkamp K., MD Zeng X., MSc Kennedy Feitosa E., MSc Zijlstra J., MD Ketelaar M., MD/PhD student Zuo H., MSc Kirenga B.J., MD
Other research staff Augustijn S. Koops H. Beusekamp B. Kukler J. Beverdam H.R. Laan van der-Boers A. Bladder G. Leever M. Blokzijl J. Lodewijk M. Bos I. S.T Menzen M. Bouwman J. Niemeijer A., MSc Brouwer S. Nijboer-Brinksma S. Brouwer U. Noordhoek J. Bruin de H.G. Oeseburg D.S. Bruins Slot F.J. Oomkes-Pilon A.M. Dijkstra A.H. Oosterom H. Eems van der M.R. Rakers J.A. Elzinga C.R.S. Reinders-Luinge M. Gras R. Rijkom van B. Heijst van E.C.M. Smaalen van M. Heuving M.E. Smidt-Huizinga H.D.M. Homan A.A.J. Smit M. Horst E.W. Star-Kroesen M. Jonge de O.R.M. Swierenga M. Jonker M.R. Wedzinga A. Kooistra W. Zuidhof A.B Klok P. Zwart G.
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International collaboration 2015 (As far as related to joint projects and publications in 2015)
Prof. I. Adcock Imperial College London London, UK
Prof. S. Andreas Georg-August University Göttingen, Germany
Prof. J. Antó IMIM, CREAL Barcelona, Spain
Prof. E. Bateman University of Cape Town Cape Town, South Africa
Prof. R. Beasley Medical Research institute of New Zealand
Wellington, New Zealand
Dr. C. Bidan University of Grenoble Grenoble, France
Prof. E.R. Bleecker Wake Forest School of Medicine Winston Salem, USA
Dr. B. Bohle Medical University of Vienna Vienna, Austria
Dr. J. Bourke Monash University Melbourne, Australia
Dr. Y. Bossé Université de Laval Quebec, Canada
Prof. J. Bousquet INSERM Villejuif, France
Dr. K. Bracke University Hospital of Ghent Ghent, Belgium
Prof. G. Brusselle University Hospital of Ghent Ghent, Belgium
Prof. A. Bush Imperial College London, UK
Prof. A. Casini Cardiff University Cardiff, UK
Dr. M. Cho Harvard Medical School Boston, USA
Dr W. Chrzanowski University of Sydney Sydney, Australia
Prof. R. Dahl Odense University Hospital Odense, Denmark
Prof. D. Davies University of Southampton Southampton, UK
Dr. A. DunnGalvin Cork University Cork, Ireland
Dr. C. Ehrhardt Trinity College Dublin Dublin, Ireland
Dr. G. Fejer University of Plymouth Plymouth, UK
Prof. B.K. Fleischmann University of Bonn Bonn, Germany
Prof. J. Fonseca University of Porto Porto, Portugal
Prof. M. Gjomarkaj University of Palermo Palermo, Italy
Prof. Dr. C.M. Greene Royal College of Surgeons in Ireland Dublin, Ireland
Dr. T.L. Hackett University of British Columbia Vancouver, Canada
Prof. A.J. Halayko University of Manitoba
Winnipeg, Canada
Prof. L. Han Academy of Military Medical Sciences Beijing, China
Prof P.M. Hansbro
University of Newcastle
Newcastle, Australia
Prof. A.J. Henderson
University of Bristol Bristol, UK
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Prof. F. Herth University of Heidelberg Heidelberg, Germany
Prof. J.C. Hogg University of British Columbia Vancouver, Canada
Dr. J.W. Holloway University of Southampton Southampton, UK
Prof. J.O. Hourihane Cork University Cork, Ireland
Prof. C. Janson Uppsala University Uppsala, Sweden
Prof. D. Jarvis Imperial College London London, UK
Prof. G. Joos University Hospital of Ghent Ghent, Belgium
Prof. M. Kamya Makerere University Kampala, Uganda
Prof D. Knight University of Newcastle Newcastle, Australia
Prof. L. Kobzik Harvard School of Public Health Boston, USA
Prof. M. Königshoff Helmholtz Center Munich München, Germany
Dr. R. Korstanje The Jackson Laboratory Bar Harbor, USA
Dr. S. Krauss-Etschmann
Research Center Borstel Borstel, Germany
Prof. B.N. Lambrecht University Hospital of Ghent Ghent, Belgium
Dr. M. Lenburg Boston University School of Medicine Boston, USA
Dr. S. London National Institute of Environmental Health Sciences (NIEHS)
North Carolina, USA
Dr. H. Maarsingh Palm Beach Atlantic University West Palm Beach, USA
Dr. K. Malakauskas Lithuanian University of Health Sciences
Kaunas, Luthuania
Dr. F.O. Martinez Oxford University Oxford, UK
Dr. T. Mauad Sao Paolo University Sao Paolo, Brasil
Dr. E. Melén Karolinska Institute Stockholm, Sweden
Prof. D.A. Meyers Wake Forest School of Medicine Winston Salem, USA
Dr. M. Miravitlles Hospital Universitari Vall d’Hebron Barcelona, Spain
Prof. L.C. de Moraes Sobrino Porto
State University of Rio de Janeiro Rio de Janeiro, Brazil
Prof. B. Oliver Woolcock Institute Sydney, Australia
Prof. P.D. Pare University of British Columbia Vancouver, Canada
Prof. M. Peters-Golden University of Michigan Medical School Michigan, USA
Prof. E. Pizzichini Universidade Federal de Santa Catarina
Florianópolis, Brasil
Prof. D. Price University of Aberdeen Aberdeen, UK
Prof. N. Probst-Hensch Swiss Tropical and Public Health Institute
Basel, Switzerland
Dr. B.A. Raby Harvard Medical School Boston, USA
Dr. H.K. Reddel University of Sydney Sydney, Australia
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Dr. M. Rojas University of Pittsburgh Pittsburgh, USA
Prof M. Roth University Hospital Basel, Switzerland
Prof. F. van Roy Flemish Institute of Biotechnology Ghent, Belgium
Prof. I. Sabroe University of Sheffield Sheffield, UK
Prof. S. dos Santos Valenca
Federal University of Rio de Janeiro
Rio de Janeiro, Brazil
Dr. I. Sayers
University of Nottingham Nottingham, UK
Dr. M. Schuler University of Wuerzburg Wuerzburg, Germany
Dr. K. Schultz Klinik Bad Reichenhall Bad Reichenhall, Germany
Dr. J. Schwarze University of Edinburgh Edinburgh, UK
Prof. F. Sciurba University of Pittsburgh Medical Centre Pittsburgh, PA, USA
Prof. T. Sigsgaard Aarhus University Aarhus, Denmark
Dr. P. Shah Royal Brompton Hospital London, UK
Prof. E. Silverman Harvard Medical School Boston, USA
Prof. D.D. Sin University of British Columbia Vancouver, Canada
Dr. J.B. Soriano University of Madrid Madrid, Spain
Prof. L. Sorokin University of Münster Münster, Germany
Dr. A. Spira Boston University School of Medicine Boston, USA
Dr. K. Steiling Boston University School of Medicine Boston, USA
Prof. M. Tobin University of Leicester Leicester, UK
Prof. T. Troosters University of Leuven Leuven, Belgium
Prof. N. Tzanakis University of Crete Heraklion, Greece
Prof. N. Viacheslaev University of Göttingen Göttingen, Germany
Prof. M. Weatherall University of Otago Wellington, New Zealand
Dr M. Weckmann University of Luebeck Luebeck, Germany
Prof. S.T. Weiss Harvard Medical School Boston, USA
Prof. J. Wess National Institute of Health Bethesda, USA
Prof E.S. White University of Michigan Ann Arbor, USA
Prof W. Windisch Lungenklinik Merheim, Kliniken der Stadt Köln, Universität Witten/Herdecke
Köln, Germany
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Seminar program 2015
Date Speaker Title 06-01-2015 M. de Vries
Expire, Pathology & Medical Biology, UMCG
Pim1 kinase: a double-edged sword? The divergent role of Pim1 kinase in the airway epithelium
20-01-2015 Prof. G.H. Koppelman
Pediatric Pulmonology UMCG
Asthma genetics and epigenetics: from gene discovery to novel disease mechanisms
03-02-2015 Prof. R. Gosens
Molecular Pharmacology UMCG
Functional interactions of LAMA’s with corticosteroids and PDE-4 inhibitors: a pharmacologist’s perspective
17-02-2015 Dr. E. Tufvesson
Lund University Sweden
Clinical characterization and genetic analyses in COPD
03-03-2015 Prof. T. van der Molen
General Practice UMCG
Allergy, asthma and COPD research in primary care in Groningen – where can we meet?
17-03-2015 E. Osei
Pathology and Medical Biology, UMCG
The role of aberrant epithelium-fibroblast communication in COPD pathogenesis
07-04-2015 Dr. M. van Zelm
Erasmus MC Rotterdam
Human IgE+ B cells are derived from T cell-dependent and T cell-independent pathways
05-05-2015 Dr. J. Roukema
Radboud University Nijmegen
A virtual asthma clinic for children, first results of a randomized multicenter study
16-06-2015 Dr. G. Kar
European bioinformatics institute, Welcome trust Sanger institute, Genome campus Hinxton, Cambridge, UK
Chromatin status and stochasticity in gene expression
01-09-2015 Dr. J. van Boven
General Practice UMCG
Enhancing adherence in patients with COPD
15-09-2015 D. Pouwels
Expire, Pathology & Medical Biology, UMCG
DAMPs: endogenous danger signals that play a crucial role in the pathophysiology of COPD
06-10-2015 Prof. H.M. Boezen
Epidemiology Ethnic differences in the prevalence of respiratory disease and genetic make-up
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UMCG Date Speaker Title 20-10-2015 J. Song
Pathology UMCG
Epigenetics and airway epithelial cell differentiation
03-11-2015 Prof. L. Han
Academy of military medical sciences Beijing, China
Aspergillus fumigatus alters the airway epithelium integrity: a fresh view on players of the actin cytoskeleton dynamics
17-11-2015 K. Klooster
Pulmonology UMCG
Bronchial valves for emphysema without interlobar collateral ventilation
01-12-2015 Dr. A. Faiz
Expire, Pathology & Medical Biology, Pulmonology UMCG
Cause and effect: Genetic susceptibility to cigarette smoke and the influence on chromosomal stability
15-12-2015 Dr. M. Hylkema
Pathology & Medical Biology UMCG
Prenatal programming by maternal smoking during pregnancy: impact on the future lung
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Research meetings 2015 Date Speaker Title
06-01-2015 Gerard Koppelman Pediatric Pulmonology GRIAC-chair
Introduction to GRIAC
13-01-2015 Bing Han
Molecular Pharmacology
The role of novel pharmacological compounds in airway inflammation and hyperreactivity
20-01-2015 Anita Spanjer
Molecular Pharmacology
A role of the Frizzled-8 receptor in inflammation and remodeling in COPD
27-01-2015 All ERS abstracts 03-02-2015 Karolin Meyer
Pathology Update on prenatal smoke exposure in mice
10-02-2015 Emmanuel Osei
Pathology & Medical Biology, Experimental Pulmonology and Inflammation Research
Crosstalk between lung epithelial cells and fibroblasts; implications for COPD
17-02-2015 Petra Nathan
University of Borstel Effects of maternal smoking on the offspring’s phenotype, genetic and epigenetic investigations
24-02-2015 Carian Boorsma
Pharmacokinetics, Toxicology and Targeting
The RANKL-OPG balance in pulmonary fibrosis
03-03-2015 Kim de Jong
Epidemiology Air pollution exposure and lung function levels in LifeLines
17-03-2015 Alen Faiz
Expire, Pathology & Medical Biology, Pulmonology
Effect of long term corticosteroid treatment on microRNA and gene expression profiles in COPD
24-03-2015 Francesca Tang
Woolcock Institute, University of Sydney
Neutrophils in viral induced asthma exacerbations
31-03-2015 Grissel Faura Tellez
Pediatric Pulmonology & Medical Biology, Experimental Pulmonology and Inflammation Research
PCDH1 and smoking: work in progress
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Date Speaker Title 07-04-2015 Hataitip Tasena
Pathology, Experimental Pulmonology and Inflammation Research
MicroRNA regulation of chronic mucus hypersecretion (CMH) in COPD: a fibroblastic niche for goblet cell differentiation?
14-04-2015 Navessa Padma Tania
Molecular Pharmacology
Endothelial follistatin-like 1 is crucial for normal maturation of the pulmonary vasculature in mice
28-04-2015 Karin Klooster
Pulmonolgy The STELVIO trial
12-05-2015 All ATS posters and oral presentations 26-05-2015 Juan Song
Pathology Epigenetics and airway epithelial cell differentiation
02-06-2015 Eline van Dijk
Molecular Pharmacology
WNT-5B: role in inflammation, repair and interaction with oxidative stress in pulmonary fibroblasts
09-06-2015
Corneel Vermeulen Pulmonology
New project: A better understanding of asthma remission: an integrative genomic approach for biomarker development
16-06-2015 Diana van der Plaat
Epidemiology Identification of novel genes related to airway obstruction in never-smokers
23-06-2015 Jennie Ong
Pathology The functional relevance of miRNAs in COPD
30-06-2015 Esther Metting
General Practice Development of a digital individualized self-management tool for asthma patients: presentation of the ‘scaffolding’ process
01-09-2015 Xiang Zeng
Epidemiology Blood lead and cadmium levels and lung function in children from an electronic waste recycling area
08-09-2015 Reinoud Gosens
Molecular Pharmacology GRIAC-chair Alen Faiz Expire, Pathology & Medical Biology, Pulmonology
Introduction to GRIAC Oral presentation ERS: MiR-320D: a novel anti-inflammatory miRNA upregulated by corticosteroids
15-09-2015 All ERS posters and oral presentations 22-09-2015 All ERS posters and oral presentations
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Date Speaker Title 06-10-2015 Margot Klijnsma
Pulmonology Transmural care for COPD patients; reducing hospitalization days
13-10-2015 Tim Koopmans
Molecular Pharmacology
Therapeutic implications of beta-catenin inhibition in airway smooth muscle, using the small-molecule compound ICG-001
20-10-2015 Cheng Xu
Pulmonology Epigenome wide association study of asthma
27-10-2015 All ATS abstracts 03-11-2015 Laura Hesse
Medical Biology, Experimental Pulmonology and Inflammation Research
Peptide SCIT in a mouse model of allergic asthma
10-11-2015 Maaike de Vries
Pathology Accelerated lung ageing in COPD: a lung tissue gene expression signature
17-11-2015 Dirkje Postma
Pulmonology ACOS and the Dutch Hypothesis
24-11-2015 Alen Faiz
Expire, Pathology & Medical Biology, Pulmonology
Investigating the genetics of corticosteroid resistance in COPD
01-12-2015 Juan Song
Pathology SND1 in mouse lung: mRNA and DNA methylation related to smoke
08-12-2015 Nicole Dijk
Pediatric Pulmonology (Epi)genetic regulation of expression of IL1RL1 mRNA and IL1RL1-a protein levels in asthma
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Brainstorm sessions 2015 Date Initiator Subject
24-03-2015 Prof. dr. A. de Bruin University of Utrecht
Laboratory animal pathology
28-04-2015 Dr. P.J. Wijkstra &
Prof. dr. D.S. Postma Respiratory insufficiency & Pulmonology UMCG
NRS roadmap
22-09-2015 B. Kirenga, MD
General Practice UMCG & Makerere University, Kampala,Uganda
What is the burden and characteristics of severe asthma in Eastern Africa?
27-10-2015 W. Poppinga
Molecular Pharmacology RUG/UMCG
AKAP1: from epigenetics of asthma to gene function?
24-11-2015 Dr. M. de Vries
Pathology UMCG
Reverse the aging: new therapeutic targets for the treatment of COPD
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Research projects 2015 Aeris Medical, USA. A randomized Controlled Multi-center Trial of the AeriSeal® System in Patients with Advanced Emphysema: ASPIRE-trial, FDA-IDE RCT, Aeris USA. 2012-2018, Dr. D.J. Slebos. Aimmune Therapeutics Inc., USA. The Palisade Study: Peanut Allergy Oral Immunotherapy Study of AR101 for Desensitization in Children and Adults. 2015–2016. Prof.dr.A.E.J.Dubois, Dr. J.N.G. Oude Elberink. MD/PhD-student: M.E. Pettersson Almirall educational grant: Self-reported side effects of inhaled corticosteroids in patients with COPD, an educational project focusing on feasibility and benefits. 2012-2015. Dr. C. de Jong, Prof.dr. T. van der Molen. AstraZeneca; Health status guided-COPD care; the MARCH study. 2008-2016. Prof.dr. T. van der Molen, Prof.dr. H.A.M. Kerstjens. Res. Fellows: Dr. J.W.H. Kocks, Dr. C. de Jong. AstraZeneca; CARAT; identifying cutoff values. 2014-2016. Prof.dr. T. van der Molen, Dr. BMJ Flokstra – de Blok, Dr. C. de Jong. AstraZeneca: risk to develop pneumonia in COPD: Comparing the effects of fluticasone propionate and budesonide on epithelial defense. 2015-2016. Prof. dr. I. Heijink, Prof. D.S. Postma, Dr. M. van den Berge. Techinician: M.R. Jonker. Boehringer Ingelheim International GmbH:, Evaluation of the anti-inflammatory and anti-
remodeling effects of the novel ultralong-acting 2-agonist olodaterol, alone and in concerted action with tiotropium, in an animal model of COPD. 2015-2016. Prof.dr. H. Meurs, Prof.dr. R. Gosens, Dr. H .Maarsingh. Boehringer Ingelheim International GmbH: The protective effects of tiotropium: role of the muscarinic M3 receptor. 2013-2016. Prof.dr. R. Gosens. Research Fellow: Dr. L.E.M. Kistemaker Boehringer Ingelheim International GmbH. A phase II/III randomised, double blind, placebo-controlled, parallel group trial to evaluate safety and efficacy of tiotropium inhalation solution (2.5 mcg and 5 mcg) administered once daily in the afternoon via respimat inhaler for 12 weeks in patients 1 to 5 years old with persistent asthma. 2012-2015. Dr. E.J.L.E. Vrijlandt, Dr. B.W.M. Willemse, M. van Smaalen Brazil Science Without Borders: Targeting the histone acetyltransferases and histondeacetylase balance in the inflammatory lung diseases asthma and COPD. 2012-2015. Prof.dr. M. Schmidt. Sandwich PhD student: E. Kennedy Feitosa, post-doc: vacancy Brazil Science Without Borders: Genes and environments underlying COPD: genetic susceptibiity to air pollution. 2015-2016. Prof.dr. H.M. Boezen, Prof.dr. T. Mauad (Sao Paolo, Brasil). Postdoc: Dr. A.J. de Faria Coimbra Lichtenfelds. CAPES/NUFFIC (Edital 68/2013): Activation of nuclear factor (erythroid=derived 2)-like 2 (Nrf2) & antioxidant response element (ARE) as therapeutic target for tissue repair in chronic degenerative lung disease. 2013-2017. Prof.dr. S. dos Santos; Prof.dr. L.C. de Moraes Sobrino Porto; Prof.dr. M. Schmidt
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Chiesi: the role of small airways in asthma. Development of the SADT questionnaire. 2011-2016. Prof.dr. T. van der Molen, Prof.dr. D.S. Postma, Dr. M. van den Berge. CSA Medical: A Prospective Study of RejuvenAir™ System Radial Spray Cryotherapy to Determine Safety and Histological Effect in the Lung. 2014-2015. Dr. D.J. Slebos, K. Klooster. CSA-Medical USA “RejuvenAir trial": “A Prospective Study of RejuvenAir™ System Radial Spray Cryotherapy to Determine Safety and Histological Effect in the Lung. 2015-2108. Dr. D.J. Slebos, Dr. J.E. Hartman, K. Klooster. European Community (KP7, Innovative Medicines Initiative). PROactive. Physical Activity as a Crucial Patient Reported Outcome in COPD. 2009-2015. Prof.dr. M. Decramer, Prof.dr. T. Troosters, Prof.dr. W. MacNee, Prof.dr. C. Roussos, Prof.dr. M Polkey, Dr. P. de Boer, Prof.dr. T. van der Molen, Dr. S. Schokker, Dr. C. de Jong. European Community (FP7); European Union MeDALL-mechanisms of the Development of Allergy. 2010-2015. Prof.dr. D.S. Postma, Prof.dr. G.H. Koppelman, Prof.dr. C. Wijmenga. Postdocs: Dr. M. Kerkhof, Dr. C. Xu, technician: S.A. Jankipersadsing, B. van Rijkom. European Community (FP7); European Union MeDALL-mechanisms of the Development of Allergy. 2010-2015. Dr. M.C. Nawijn, Prof.dr. G.H. Koppelman, Prof.dr. A van Oosterhout. Technician:U. Brouwer. ERS, longterm-fellow ship. Impact of High-Intensity-NPPV on cardiac and pulmonary function in stable hypercapnic COPD. 2015. Dr. M.L. Duiverman. European Union/COST action (European Cooperation in the field of Scientific and Technical Research): Developmental Origins of Chronic Lung Disease. 2012-2016. Dr. M.N. Hylkema, Prof.dr. R. Gosens, Prof.dr. D.S. Postma European Union (Horizon 2020): FRESH AIR: prevalence and burden of COPD in Uganda, Kyrgyz Republic, Vietnam and Greece. 2015-2018. Prof.dr. T. van der Molen, prof.dr. N.H. Chavannes, dr. J.F.M. van Boven, PhD student: F. van Gemert. Faculty of Mathematics and Natural Sciences. Macrophages in the pathogenesis of pulmonary lung fibrosis and their potential as drug targets. 2011-2015. Prof.dr. B.N. Melgert, Prof.dr. W. Timens, Prof.dr. K. Poelstra. PhD student: C.E. Boorsma. Genentech: Molecular Phenotying of COPD Patients by Inhaled Corticosteroids (ICS) Response. 2015-2017. Dr. C.A. Brandsma, Prof.dr. W.Timens, Prof.dr. D.S. Postma, Dr. M. van den Berge. GlaxoSmithKline: A better understanding of asthma remission: An integrative genomic approach for biomarker development. 2014-2017. Dr. M. van den Berge, Dr. N.H.T. ten Hacken, Prof.dr. W. Timens, Prof.dr. I.H. Heijink, Dr. C. Xu, Prof.dr. G.H. Koppelman, Dr. J.M. Vonk, Prof.dr. D.S. Postma. Post-doc: Dr. C. Vermeulen. GlaxoSmithKline: Single cell sequencing of CD4+ lymphocytes to better understand the molecular mechanisms leading to asthma and its remission. 2015-2017. Dr. M.C. Nawijn, Prof.dr. D.S. Postma, Prof.dr. G.H. Koppelman, Dr. J.M. Vonk, Prof.dr. W. Timens, Prof.dr. I.H. Heijink, Dr. M. van den Berge.
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Goedebuure / Air Liquide: Cost-effectiveness of obstRuctivE Sleep apnea Therapy (REST study): Comparison of MRA therapy versus CPAP therapy in moderate OSAS. 2011-2016. Dr. P.J. Wijkstra , Prof.dr. H.A.M. Kerstjens. PhD-student: G de Vries Groningen Graduate School of Science (Ubbo Emmius PhD-position); Key role of A-kinase anchoring proteins in the pathophysiology of asthma. 2011-2015. Prof.dr. M. Schmidt, Dr. H. Maarsingh. PhD-student: B. Han. Groningen Research Institute for Pharmacy (MPDI fellowship): Role of MIF in pulmonary fibrosis. 2015-2019. Prof.dr. B.N. Melgert, Prof.dr. G.J. Poelarends, PhD student: L. Florez-Sampedro GSK/Unlock. Health economics of COPD. 2011-2015. Prof.dr. M.J. Postma, Prof.dr. T van der Molen, Dr. M. Roman (Mallorca). PhD student: J. van Boven GSMS: An old dilemma: Asthma with irreversible airway obstruction or COPD? 2009-2016. Dr. N.H.T. ten Hacken, Dr. M.N. Hylkema, Prof.dr. W. Timens and Prof.dr. D.S. Postma. PhD student: F. Fattahi. GSMS/Joint project University of Southampton: Unravelling the protective role of Pim kinases in airways diseases. 2011-2015. Dr. M.C. Nawijn Prof.dr. D.E. Davies. PhD student: M. de Vries GSMS/Joint project University of Southampton: Functional characterisation of PCDH1, a novel gene for asthma and bronchial hyperresponsiveness. 2011-2015. Prof.dr. G.H. Koppelman, Prof.dr. J. Holloway, Dr. M.C. Nawijn, Dr. B.M. Willemse. PhD student: G. Faura Tellez GSMS/ Shantou University Medical College, China (Abel Tasman bursaal). Effect of toxic exposures during pregnancy on fetal immune and lung development. 2012-2016. Dr. M.N. Hylkema, Prof.dr. X. Huo. PhD student: J.J. Cao GSMS/Shantou University Medical College. Genes, environment and respiratory health 2011-2015. Prof.dr. H. M. Boezen. PhD Student: X. Zeng GSMS/TianJin Medical University. Maternal smoking during pregnancy: Aberrant epigenetic regulation of genes involved in lung development, ageing and repair. 2013-2016. Dr. M.N. Hylkema, Prof.dr. M. Rots. PhD student: J. Song GSMS-UBC: Dysfunctional crosstalk between epithelial cells and fibroblasts contributes to abnormal tissue repair and remodeling processes in COPD. 2013-2017. Dr. C.A. Brandsma, Dr. I.H. Heijink, Prof.dr. W. Timens, Prof.dr. D.S. Postma, Dr. T.L. Hackett, Dr. S. Wadsworth. PhD student: E. Osei GSMS: MicroRNA regulation of chronic mucus hypersecretion in COPD. 2015-2019. Prof.dr. W. Timens, Prof.dr. I.H. Heijink, Dr. C.A. Brandsma. PhD-student: H. Tasena. Holaira, USA: A Sequential Two Phase Multicenter, Randomized Study to Optimize Dose Selection and Evaluate Safety After Treatment with the Holaira™ Lung Denervation System in Patients with Moderate to Severe COPD, 2014-2018 The AIRFLOW-1 trial. Dr DJ Slebos, Dr J Hartman, K. Klooster. International Primary Care Respiratory Group. UNLOCK: Uncovering and Noting Long-term Outcomes in COPD to enhance Knowledge. 2010-2016. Dr. N. Chavannes, Dr. I. Tsiligianni, Prof.dr. D. Price, Prof.dr. T. van der Molen.
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IPCRG: The I-HARP SERVICE: international, cross-sectional evaluation of inhaler technique and associated predictors of asthma control in patients receiving fixed dose combination inhaled corticosteroid / long-acting beta2-agonist therapy in general practice. 2011-2017. Prof.dr. D. Price, Prof.dr. T. van der Molen, E.C.M. van Heijst. IPCRG: Fresh Air: prevalence and burden of COPD in a rural area of sub-Saharan Africa. 2010-2016. Prof.dr. T. van der Molen, Dr. N.H. Chavannes, Dr. C. de Jong. PhD student: F.A. van Gemert IPCRG: Fresh Air: Biomass fuel induced COPD, prevalence and pathophysiology. 2010-2018. Prof.dr. T. van der Molen, Dr. C. de Jong. PhD student: B.J. Kirenga IPCRG: Does the use of inhaled corticosteroids reduce diabetic control in patients with concomitant COPD and Diabetes: an international primary care cohort study. 2014-2016. Dr. J.W.H. Kocks, Prof.dr. T van der Molen, Prof.dr. D. Price. Longfonds/ZonMW/Boston Scientific: Unraveling Targets of Therapy in Bronchial Thermoplasty in Severe Asthma: TASMA Study, Multicenter trial (AMC/London/Heidelberg/UMCG). 2014-2016. UMCG: Dr. D.J. Slebos, Dr. N.H.T. Ten Hacken Lung Alliance Netherlands. National clinical managed care pathway for patients hospitalized for a COPD exacerbation. 2015-2017. Prof.dr. H.A.M. Kerstjens. PhD Student: M. Klijnsma MD/PhD/ALK: Epinephrine auto-injector prescription, compliance and quality of life. 2011 – 2016. Prof.dr. A.E.J. Dubois, Dr. B.M.J. Flokstra-de Blok. MD/PhD student: J. Saleh-Langenberg MD/PhD: COPD in primary care and pulmonary rehabilitation: discovering the dynamics of the Minimal Clinically Important Difference (MCID) 2014-2018. Prof.dr. T van der Molen, Dr. C. de Jong. PhD student: H.J. Alma MD/PhD: Insensitivity to glucocorticosteroid treatment in obstructive pulmonary diseases. 2009-2015. Dr. N.H.T. ten Hacken, Prof.dr. A.J.M. van Oosterhout, Dr. I.H. Heijink. MD/PhD student: J. Zijlstra MD/PhD: Translating asthma associated genetic variation in IL33 and IL1RL1 into pathophysiology and clinical expression of asthma. 2013 – 2017. Prof.dr. G.H. Koppelman and Dr. M.C. Nawijn. MD/PhD student: M. Ketelaar MD/PhD. Genetics of food allergy. 2013-2018. Prof.dr. A.E.J. Dubois, Prof.dr. G.H. Koppelman. MD/PhD student: C.D. van Ginkel MD/PhD: Diagnosis, treatment and risk factors for therapy failure of Hymenoptera venom allergy. 2012-2016. Prof.dr. A.E.J. Dubois, Dr. J.N.G. Oude Elberink. PhD-student: B.J.P.R Vos MD/PhD: Severity of Anaphylaxis. 2015-2017. Prof.dr. A.E.J.Dubois, Prof.dr.G.H.Koppelman. MD/PhD student: M.E. Pettersson. MRC: The roles of Pellino-1 in the control of airway viral infection. 2015. Prof. Dr. Ian Sabroe, Prof. I. H.Heijink. Technician: M.R. Jonker.
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NAF 3.2.10.042. Wnt/Frizzled signalling in small airway remodelling in COPD. 2010-2015. Prof.dr. R. Gosens, Prof.dr. H.I. Heijink, Dr. W.M. Blankesteijn. PhD student: A.I.R. Spanjer. NAF 3.4.06.044: The effect of chronic non–invasive ventilation at home after treatment of acute respiratory failure in hypercapnic COPD patients. 2007-2015. Dr. P.J. Wijkstra, Prof.dr.H.A.M. Kerstjens. PhD student: F.M. Struik; research nurse: G. Bladder NAF, special grant for translational research in Pediatric Pulmonology: Asthma phenotypes. 2009-2015. Prof.dr. G.H. Koppelman, Prof.dr. J.C. de Jongste. PhD students: N.S. Grotenboer, F.N. Dijk NAF 3.2.09.055: Protocadherin-1 expression in airway epithelium: Investigations into a novel cause of bronchial hyperresponsiveness and asthma. 2009-2016. Prof.dr. G.H. Koppelman, Dr. M.C. Nawijn, Prof.dr. D.S. Postma. NAF 3.2.09.036: Th17 responses in asthma: Protection against atopy versus development of non-allergic asthma. 2010-2015. Dr. M.N.Hylkema, Dr. I. Wouters. PhD student: P. Robbe. NAF 3.2.09.031. The role of alternatively activated macrophages in the pathogenesis of asthma. 2011-2015. Prof.dr. B.N. Melgert, Dr. M.N. Hylkema, Prof.dr. K. Poelstra. PhD student: C. Draijer. NAF 3.2.11.015: A-kinase anchoring proteins as novel drug targets in the development and progression of airway obstruction in COPD. 2011-2015. Prof.dr. M. Schmidt, Dr. H. Maarsingh, Prof.dr. H.I. Heijink. PhD-student: W. Poppinga. NAF 3.2.10.060: Vitamin D3 as adjuvant in a therapeutic vaccine for allergic asthma. 2011-2015. Prof.dr. A.J.M. van Oosterhout, Dr. J.H.N. Oude Elberink, Dr. M.C. Nawijn. PhD-student: L. Hesse. NAF 3.2.11.025: Epithelial cells alarming the immune system in COPD – at the root of COPD susceptibility? 2011-2015. Dr. M.C. Nawijn, Dr. N.H.T. ten Hacken, Prof.dr. A.J. van Oosterhout, Dr. I.H. Heijink. PhD-student: S.D. Pouwels. NAF 3.2.12.044: The functional relevance of microRNAs in COPD; elucidating their role in regulating pulmonary fibroblast function in COPD development. 2012-2016. Dr. C.A. Brandsma, Prof.dr. W. Timens, Prof.dr. DS Postma, Prof.dr. A. van de Berg, Dr. J. Kluiver. PhD-student: J. Ong NAF 3.2.12.083: Follistatin-like 1, a crucial factor in lung development, as a novel regulator in COPD. 2012-2017. Dr. H. Maarsingh, Dr. M. van den Hoff, Prof.dr. M. Schmidt. PhD student: N.P. Tania NAF 3.2.12.079: Laminin α4 and α5 as regulators of airway inflammation and remodelling in allergic asthma. 2013-2016. Dr. B.G.J. Dekkers, Prof.dr. L.M. Sorokin, Prof.dr. H. Meurs. Post-doc: Dr. D.B. Wright NAF 3.2.11.013: Prenatal programming by maternal smoking during pregnancy: susceptibility for development of COPD. 2012-2016. Dr. M.N. Hylkema, Prof.dr. W. Timens, Prof.dr. L. Kobzik. PhD student: K. Meyer Netherlands Lung Foundation 4.1.13.007. Genes and exposures underlying COPD onset. 2013 – 2016. Nederlands Longfonds consortium project in collaboration with Erasmus Medical Center. Prof.dr. H.M. Boezen, Prof.dr. C.M. van Duijn, Dr. C.C. van Diemen, Prof.dr. D.S. Postma. Postdoc: Dr. K. de Jong. PhD students: D. van der Plaat, I. Nedeljković
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Netherlands Lung Foundation 1.14.001. Prevention of epigenetic programming of asthma. 2014 – 2018. Nederlands Longfonds consortium project in collaboration with University of Utrecht and RIVM. Prof. dr. G.H. Koppelman, Dr. U. Gehring, Prof. dr. H. A. Smit, Dr. A. Wijga. Netherlands Lung Foundation 5.1.14.020 Identifying causal mechanisms of the inception of asthma through a novel experimental model for the interaction on the PCDH1 gene and environment. 2014 – 2017. Nederlands Longfonds consortium project in collaboration with University of Utrecht and University of Ghent. Dr. M. Nawijn, Prof. dr. G.H. Koppelman, Prof. dr. L. Bont , Prof. dr. B. Lambrecht Netherlands Lung Foundation 6.1.14.009: Tissue repair in COPD: WNT you get it right? 2014-2018. Prof.dr. R. Gosens, Dr. J. Stolk, Dr. M. Königshoff. Postdoc: Dr. J-P Ng-Blichfeldt, 1 post-doc vacancy. Netherlands Lung Foundation 4.1.15.002: Does high baseline oxidative stress attenuate macrophage function during exacerbations of COPD and asthma? 2015-2020. Prof.dr. B.N. Melgert, Dr. R. Lutter, Dr. F.O. Martinez, Prof.dr. H.A.M. Kerstjens; 2 PhD vacancies, 2 technician vacancies. Northern CARA Foundation: Characterization of macrophage subsets in airways of patients with COPD and their controls. 2014-2015. Prof.dr. B.N. Melgert, C.E. Boorsma Northern CARA Foundation: Characterization of macrophage subsets in airway biopsies of healthy controls. 2014-2015. Prof.dr. B.N. Melgert, C. Draijer Novartis: Effects of a combination of the beta-adrenoceptor agonist indacaterol and the muscarinic receptor antagonist glycopyrrolate on intrapulmonary airway constriction. 2015-2017. Prof.dr. M. Schmidt. Post-doc: Dr. B. Han Pender Foundation for Pulmonary Fibrosis: Exchange of fresh human lung tissue of patients transplanted for pulmonary fibrosis between RUG/UMCG (Groningen) and Erasmus MC (Rotterdam). 2014-2018. Dr. B.N. Melgert, Dr. B. van den Blink Phadia; In vitro Diagnostiek en Eerstelijns Allergie Leidraad (IDEAL) 2009-2016. Prof.dr. A.E.J. Dubois, Prof.dr. T. van der Molen, Dr. B.M.J. Flokstra-de Blok. PneumRx/BTG, Inc. USA: Lung Volume Reduction Coil for Treatment in Patients with Emphysema (RENEW) Study, FDA-IDE RCT, PneumRx, Inc. USA. 2012-2018. Dr. D.J. Slebos, K. Klooster, Dr. J.E. Hartman, Dr. N.H.T. Ten Hacken PneumRx/BTG: Lung Volume Reduction Coil for Treatment in Patients with Emphysema (RENEW-Crossover) Study, 2013-2018. Dr. D.J. Slebos, K. Klooster, Dr. J.E. Hartman, Dr. N.H.T. Ten Hacken PneumRx/BTG, Icc: The safety and feasibility of re-treating patients with severe emphysema with the RePneu LVRC system: a pilot study (RECOIL study). 2014-2015. Dr. D.J. Slebos, K. Klooster PneumRx/BTG:Identifying REsponders and exploring mechanisms of ACTION of the endobronchial coil treatment for emphysema (“REACTION”-TRIAL), UMCG & Royal Brompton. 2014-2017. Dr. D.J. Slebos, Dr. J.E. Hartman, PhD student: W. van Geffen, MD.
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PulmonX Inc: A Multi-center, Prospective, Randomized, Controlled, one-way Crossover Investigation of Endobronchial Valve Therapy vs Standard of Care in Homogeneous Emphysema: IMPACT trial. 2014 – 2015. Dr D.J. Slebos, Dr N.H.T. Ten Hacken, Dr J.E. Hartman, K. Klooster. PulmonX Inc: Study of proactive treatment of collateral ventilation in CV-positive emphysema patients before EBV treatment: “MIND THE GAP”. 2014-2016. Dr D.J. Slebos, Dr J.E. Hartman, K. Klooster. PulmonX Inc. Lung Function Improvement after Bronchoscopic Lung Volume Reduction with Pulmonx Endobronchial Valves used in Treatment of Emphysema: “LIBERATE STUDY”, 2015-2109. Dr. D.J. Slebos, Dr. J.E. Hartman, Dr. N.H.T. Ten Hacken, K. Klooster. Roche: Periostin: a key contributor to airway inflammation and remodelling in asthma. 2015. Prof. dr. I.H. Heijink, Dr. M. van den Berge, Prof. Dr. D.S. Postma. Technician: M.R. Jonker. SMF; Remission and progression of asthma: genetic and epigenetic regulation. 2012-2015. Prof.dr. D.S. Postma, Prof.dr. G.H. Koppelman, Dr. J.M. Vonk. PhD student: M.A.E. Nieuwenhuis. STW Improvement of Diagnostic mEthods for ALlergy assessment. Cashew allergy in children as a showcase (IDEAL/ORCA study). 2012-2016. Prof.dr. A.E.J. Dubois, Dr. B.M.J. Flokstra-de Blok. MD/PhD-student: C.D. van Ginkel. technician: A. Oomkes-Pilon STW Open Technology Programme: Design, synthesis and validation of potent and isozyme selective arginase inhibitors for therapeutic use in asthma. 2015-2020. Prof. dr. A.S.S. Dömling, Prof. dr. H. Meurs, Prof. dr. P.H. Elsinga, 2 PhD students, 1 postdoc: vacancies Top Instituut Pharma 1-108; Groningen, Utrecht; Acute and chronic inflammatory responses induced by smoking in individuals susceptible and non-susceptible for development of COPD: from complex disease phenotype toward novel tailor-made therapy. 2008-2015. Prof.dr. D.S. Postma, Prof.dr. L. Koenderman, Prof.dr. J.W.J. Lammers, Dr. N.H.T. ten Hacken, Dr. P. Zanen, Dr. R. Schweizer, Prof.dr. R.P.H. Bischoff. Technicians; J. van der Leij, M. Lodewijk, T. Bijma, S. Brouwer. PhD students: S.J.M. Hoonhorst, L. Franciosi. Research nurse. R.G.A. Hiltermann-Tilanus. Ubbo Emmius Sandwich Scholarship. Studies on the potential role of Epac between interactions of A. fumigatus and host. 2014-2018. Joint project University of Bejing, China. Prof.dr. M. Schmidt, Prof.dr. L. Han. PhD student: X. Han. Ubbo Emmius Sandwich Scholarship. Airway epithelial-to-mesenchymal transition. Compartmentalized cyclic AMP signaling? 2014-2018. Joint project University of Gottingen, Germany. Prof.dr. M. Schmidt, Prof.dr. N. Viacheslaev. PhD student: H. Zuo. University of Groningen. Application of eHealth to improve care for asthma and COPD patients in primary care: from focus groups to data mining. 2012-2016. Prof.dr. T. van der Molen, Prof.dr. R. Sanderman. PhD student: E.I. Metting University Medical Center Groningen (Innovative research): “A structured life style intervention on enhancement of daily physical activity and physical fitness in COPD patients in the first, second, and third line. 2006-2015. Dr. N.H.T. ten Hacken, Dr. M.H. de Greef, Dr. J.B. Wempe. PhD-student: W. Altenburg.
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University Medical Center Groningen (doelmatigheidsonderzoek): Feasibility of an allergy service in primary care. 2013-2015. Dr. B.M. Flokstra-de Blok. Prof.dr. A.E.J. Dubois, Prof.dr. T. van der Molen, Dr. J.N.G. Oude Elberink, Dr. M.L.A. Schuttelaar, Prof.dr. P.J. Coenraads. University Medical Center Groningen / GSK NL: Phenotyping airways disease by cluster analysis in primary care. 2013-2015. Dr. J.W.H. Kocks, Prof.dr. T. van der Molen, Prof.dr. R. Beasley, Prof.dr. M. Weatherall University Medical Center Groningen (Doelmatigheidsonderzoek). Improving Quality of Life and reducing length of stay for COPD exacerbations by protocolised care. 2014-2016. Prof.dr. H.A.M. Kerstjens, Dr N.H.T. ten Hacken. PhD Student: M. Klijnsma. Research nurse: J. Remmelink, A. Niemeijer. University Medical Center Groningen (Doelmatigheidsonderzoek) & Stichting Vrienden van het Beatrixkinderziekenhuis (Grantnumber 671437): GERAS-project NeoLifes (prof dr AF Bos)/Neolifes-lungs. Dr. E.J.L.E. Vrijlandt, W.Stalman, M. van Smaalen ZonMW 016.126.307: On the origins of airway smooth muscle thickening in asthma. Vidi-award. 2012-2017. Prof.dr. R. Gosens. PhD students: T. Koopmans, E. van Dijk. Technician: M. Menzen ZonMW 837002501. Initiation of HOme MEchanical ventilation at home in patients with chronic hypercapnic Respiratory failUre in the Netherlands (HOMERUN). 2014-2018. Dr. P.J. Wijkstra, Prof.dr. H.A.M. Kerstjens. PhD-student: R. van den Biggelaar Zorggroep Zwolle: Development of patient satisfaction with care questionnaire and validation of HowRu & HowRwe questionnaires. 2012-2015. Dr. J.W.H. Kocks, Prof.dr. H.J.G. Bilo, Dr. M.H. Blanker. Student researcher: J. Rutgers. Also a substantial contribution for several projects has been obtained from the Stichting Astma Bestrijding (SAB). Research projects of the GRIAC spin-off company Aquilo: Aquilo: Evaluation of two novel compounds in a guinea pig model of acute asthma. 2015-2016. Prof.dr. R. Gosens, Dr. L.E.M. Kistemaker. Aquilo: Evaluation of two novel compounds on airway remodeling in guinea pig lung slices. 2015-2016. Prof.dr. R. Gosens, Dr. L.E.M. Kistemaker. Aquilo: Evaluation of two novel compounds in an animal model of chronic asthma. 2015-2016. Prof.dr. R. Gosens, Dr. L.E.M. Kistemaker.
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Publications 2015
Dissertations
E. van der Wiel The clinical expression of large and small airway dysfunction in asthma 11-02-2015 Promotor: Prof. Dr. D.S. Postma Co-promotores: Dr. N.H.T. ten Hacken, Dr. M. van den Berge K. Kumawat WNT signaling in airway remodeling in asthma. Novel roles for WNT-5A in airway smooth muscle 20-02-2015 Promotores: Prof. Dr. R. Gosens, Prof. Dr. M. Schmidt L.E.M. Kistemaker Acetylcholine beyond bronchoconstriction: A regulator of inflammation and remodeling 06-03-2015 Promotores: Prof. Dr. R. Gosens, Prof. Dr. H. Meurs, Prof. Dr. H.A.M. Kerstjens F. Verdonk-Struik Chronic non-invasive ventilation in COPD. Where do we stand 08-04-2015 Promotor: Prof. Dr. H.A.M. Kerstjens Copromotor: Dr. P.J. Wijkstra F.F. Berkhof Measurement and improvements of health status in patients with COPD 29-04-2015 Promotor: Prof. Dr. H.A.M. Kerstjens Copromotor: Dr. J.W.K. van den Berg W. Altenburg Physical activity and fitness in patients with COPD. Making a change 15-06-2015 Promotor: Prof. Dr. H.A.M. Kerstjens Copromotores: Dr. J.B. Wempe, Dr. N.H.T. ten Hacken, Dr. M.H.G. de Greef P. Robbe Farming exposure and phenotypes of asthma 22-06-2015 Promotor: Prof. Dr. W. Timens Co-promotor: Dr. M.N. Hylkema M. de Vries Pim1 kinase: a double-edged sword. The divergent roles of a survival kinase in environmet-airway interaction. 01-07-2015 Promotor: Prof. Dr. A.J.M. van Oosterhout Co-promotor: Dr. M. Nawijn, Dr. I.H. Heijink
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J.F.M. van Boven Enhancing adherence in patients with COPD: Targets, interventions and cost-effectiveness 25-09-2015 Promotores: Prof. Dr. M.J. Postma, Prof. Dr. T. van der Molen O. Akkerman Tuberculosis and its sequelae. Diagnostic, epidemiological and therapeutic studies 11-11-2015 Promotores: Prof. Dr. T.S. van der Werf, Prof. Dr. H.A.M. Kerstjens, Prof. Dr. H.W. Frijlink Copromotor: Dr. A.G.M. van der Zanden L. Franciosi Development and application of proteomics as aid for unraveling smoke induced COPD 27-11-2015 Promotores: Prof. Dr. R. Bisschoff, Prof. Dr. D.S. Postma Co-promotor: Dr. N.H.T. ten Hacken
Publications SCI journals
Aalderen van WM, Grigg J, Guilbert TW, Roche N, Israel E, Martin RJ, Colice G, Postma DS, Hillyer EV, Burden A, Thomas V, von Ziegenweidt J, Price D. Small-particle Inhaled Corticosteroid as First-line or Step-up Controller Therapy in Childhood Asthma. J Allergy Clin Immunol Pract. 2015;3(5):721-731.e16.
Aarnoutse RE, Sturkenboom MG, Robijns K, Harteveld AR, Greijdanus B, Uges DR, Touw DJ, Alffenaar JW. An interlaboratory quality control programme for the measurement of tuberculosis drugs. Eur Respir J. 2015;46:268-271.
Adhyatmika A, Putri KS, Beljaars L, Melgert BN. The Elusive Antifibrotic Macrophage. Front Med (Lausanne). 2015;2:81.
Adrichem van EJ, Siebelink MJ, Rottier BL, Dilling JM, Kuiken G, van der Schans CP, Verschuuren EA. Tolerance of Organ Transplant Recipients to Physical Activity during a High-Altitude Expedition: Climbing Mount Kilimanjaro. PLoS One. 2015;10(11):e0142641.
Altenburg WA, ten Hacken NH, Bossenbroek L, Kerstjens HA, de Greef MH, Wempe JB. Short- and long-term effects of a physical activity counselling programme in COPD: a randomized controlled trial. Respir Med. 2015;109(1):112-121.
Altenburg WA, Duiverman ML, Ten Hacken NH, Kerstjens HA, de Greef MH, Wijkstra PJ, Wempe JB. Changes in the endurance shuttle walk test in COPD patients with chronic respiratory failure after pulmonary rehabilitation: the minimal important difference obtained with anchor- and distribution-based method. Respir Res. 2015;16:27.
Andiappan AK, Narayanan S, Myers RA, Lee B, Nieuwenhuis MA, Nardin A, Park S, Shin HD, Kim JH, Westra HJ, Franke L, Esko T, Metspalu A, Teo YY, Saw SM, Khor CC, Liu J, Koppelman GH, Postma DS, Poidinger M, Connolly JE, Wang de Y, Rotzschke O, Curotto de Lafaille MA, Chew FT. Genetic variants of inducible costimulator are associated with allergic asthma susceptibility. J Allergy Clin Immunol. 2015;135(2):556-558.
Antolin-Amerigo D, Cerecedo Carballo I, Muriel A, Fernández-Rivas M, Diéguez Pastor M, Flokstra-de Blok B, Dubois A, De la Hoz Caballer B. Validation of the Spanish Version of the Food Allergy Quality of Life Questionnaire-Adult Form (S-FAQLQ-AF). Investig Allergol Clin Immunol. 2015;25(4):270-275.
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Anzueto A, Jenkins CR, Make BJ, Lindberg M, Calverley PM, Fagerås M, Postma DS, Rennard SI, Tashkin DP. Efficacy of an inhaled corticosteroid/long-acting β2-agonist combination in symptomatic COPD patients in GOLD groups B and D. Eur Respir J. 2015;46(1):255-258.
Bekkers MB, Wijga AH, Gehring U, Koppelman GH, de Jongste JC, Smit HA, Brunekreef B. BMI, waist circumference at 8 and 12 years of age and FVC and FEV1 at 12 years of age; the PIAMA birth cohort study. BMC Pulm Med. 2015;15:39.
Berentzen NE, van Stokkom VL, Gehring U, Koppelman GH, Schaap LA, Smit HA, Wijga AH. Associations of sugar-containing beverages with asthma prevalence in 11-year-old children: the PIAMA birth cohort. Eur J Clin Nutr. 2015;69(3):303-308.
Berkhof FF, van den Berg JW, Uil SM, Kerstjens HA. Telemedicine, the effect of nurse-initiated telephone follow up, on health status and health-care utilization in COPD patients: a randomized trial. Respirology. 2015;20(2):279-285.
Bidan CM, Veldsink AC, Meurs H, Gosens R. Airway and Extracellular Matrix Mechanics in COPD. Front Physiol. 2015;6:346.
Boland MR, van Boven JF, Kocks JW, van der Molen T, Goossens LM, Chavannes NH, Rutten-van Molken MP. Mapping the clinical chronic obstructive pulmonary disease questionnaire onto generic preference-based EQ-5D values. Value Health 2015;18:299-307.
Bonadonna P, Pagani M, Aberer W, Bilò MB, Brockow K, Oude Elberink H, Garvey L, Mosbech H, Romano A, Zanotti R, Torres MJ. Drug hypersensitivity in clonal mast cell disorders: ENDA/EAACI position paper. Allergy. 2015;70(7):755-763.
Boudewijn IM, Postma DS, Telenga ED, Ten Hacken NH, Timens W, Oudkerk M, Ross BD, Galbán CJ, van den Berge M. Effects of ageing and smoking on pulmonary computed tomography scans using parametric response mapping. Eur Respir J. 2015;46(4):1193-1196.
Boudewijn IM, Savenije OE, Koppelman GH, Wijga AH, Smit HA, de Jongste JC, Gehring U, Postma DS, Kerkhof M. Nocturnal dry cough in the first 7 years of life is associated with asthma at school age. Pediatr Pulmonol.;50(9):848-855.
Bousquet J, Anto JM, Wickman M, Keil T, Valenta R, Haahtela T, Lodrup Carlsen K, van Hage M, Akdis C, Bachert C, Akdis M, Auffray C, Annesi-Maesano I, Bindslev-Jensen C, Cambon-Thomsen A, Carlsen KH, Chatzi L, Forastiere F, Garcia-Aymerich J, Gehrig U, Guerra S, Heinrich J, Koppelman GH, Kowalski ML, Lambrecht B, Lupinek C, Maier D, Melén E, Momas I, Palkonen S, Pinart M, Postma D, Siroux V, Smit HA, Sunyer J, Wright J, Zuberbier T, Arshad SH, Nadif R, Thijs C, Andersson N, Asarnoj A, Ballardini N, Ballereau S, Bedbrook A, Benet M, Bergstrom A, Brunekreef B, Burte E, Calderon M, De Carlo G, Demoly P, Eller E, Fantini MP, Hammad H, Hohman C, Just J, Kerkhof M, Kogevinas M, Kull I, Lau S, Lemonnier N, Mommers M, Nawijn M, Neubauer A, Oddie S, Pellet J, Pin I, Porta D, Saes Y, Skrindo I, Tischer CG, Torrent M, von Hertzen L. Are allergic multimorbidities and IgE polysensitization associated with the persistence or re-occurrence of foetal type 2 signalling? The MeDALL hypothesis. Allergy. 2015;70(9):1062-1078.
Bousquet J, Schunemann HJ, Fonseca J, Samolinski B, Bachert C, Canonica GW, Casale T, Cruz AA, Demoly P, Hellings P, Valiulis A, Wickman M, Zuberbier T, Bosnic-Anticevitch S, Bedbrook A, Bergmann KC, Caimmi D, Dahl R, Fokkens WJ, Grisle I, Lodrup Carlsen K, Mullol J, Muraro A, Palkonen S, Papadopoulos N, Passalacqua G, Ryan D, Valovirta E, Yorgancioglu A, Aberer W, Agache I, Adachi M, Akdis CA, Akdis M, Annesi-Maesano I, Ansotegui IJ, Anto JM, Arnavielhe S, Arshad H, Baiardini I, Baigenzhin AK, Barbara C, Bateman ED, Beghé B, Bel EH, Ben heder A, Bennoor KS, Benson M, Bewick M, Bieber T, Bindslev-Jensen C, Bjermer L, Blain H, Boner AL, Boulet LP, Bonini M, Bonini S, Bosse I,
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Bourret R, Bousquet PJ, Braido F, Briggs AH, Brightling CE, Brozek J, Buhl R, Burney PG, Bush A, Caballero-Fonseca F, Calderon MA, Camargos PA, Camuzat T, Carlsen KH, Carr W, Cepeda Sarabia AM, Chavannes NH, Chatzi L, Chen YZ, Chiron R, Chkhartishvili E, Chuchalin AG, Ciprandi G, Cirule I, Correia de Sousa J, Cox L, Crooks G, Costa DJ, Custovic A, Dahlen SE, Darsow U, De Carlo G, De Blay F, Dedeu T, Deleanu D, Denburg JA, Devillier P, Didier A, Dinh-Xuan AT, Dokic D, Douagui H, Dray G, Dubakiene R, Durham SR, Dykewicz MS, El-Gamal Y, Emuzyte R, Fink Wagner A, Fletcher M, Fiocchi A, Forastiere F, Gamkrelidze A, Gemicioğlu B, Gereda JE, González Diaz S, Gotua M, Grouse L, Guzmán MA, Haahtela T, Hellquist-Dahl B, Heinrich J, Horak F, Hourihane JO, Howarth P, Humbert M, Hyland ME, Ivancevich JC, Jares EJ, Johnston SL, Joos G, Jonquet O, Jung KS, Just J, Kaidashev I, Kalayci O, Kalyoncu AF, Keil T, Keith PK, Khaltaev N, Klimek L, Koffi N'Goran B, Kolek V, Koppelman GH, Kowalski ML, Kull I, Kuna P, Kvedariene V, Lambrecht B, Lau S, Larenas-Linnemann D, Laune D, Le LT, Lieberman P, Lipworth B, Li J, Louis R, Magard Y, Magnan A, Mahboub B, Majer I, Makela MJ, Manning P, De Manuel eenoy E, Marshall GD, Masjedi MR, Maurer M, Mavale-Manuel S, Melén E, Melo-Gomes E, Meltzer EO, Merk H, Miculinic N, Mihaltan F, Milenkovic B, Mohammad Y, Molimard M, Momas I, Montilla-Santana A, Morais-Almeida M, Mösges R, Namazova-Baranova L, Naclerio R, Neou A, Neffen H, Nekam K, Niggemann B, Nyembue TD, O'Hehir RE, Ohta K, Okamoto Y, Okubo K, Ouedraogo S, Paggiaro P, Pali-Schöll I, Palmer S, Panzner P, Papi A, Park HS, Pavord I, Pawankar R, Pfaar O, Picard R, Pigearias B, Pin I, Plavec D, Pohl W, Popov TA, Portejoie F, Postma D, Potter P, Price D, Rabe KF, Raciborski F, Radier Pontal F, Repka-Ramirez S, Robalo-Cordeiro C, Rolland C, Rosado-Pinto J, Reitamo S, Rodenas F, Roman Rodriguez M, Romano A, Rosario N, Rosenwasser L, Rottem M, Sanchez-Borges M, Scadding GK, Serrano E, Schmid-Grendelmeier P, Sheikh A, Simons FE, Sisul JC, Skrindo I, Smit HA, Solé D, Sooronbaev T, Spranger O, Stelmach R, Strandberg T, Sunyer J, Thijs C, Todo-Bom A, Triggiani M, Valenta R, Valero AL, van Hage M, Vandenplas O, Vezzani G, Vichyanond P, Viegi G, Wagenmann M, Walker S, Wang DY, Wahn U, Williams DM, Wright J, Yawn BP, Yiallouros PK, Yusuf OM, Zar HJ, Zernotti ME, Zhang L, Zhong N, Zidarn M, Mercier J. MACVIA-ARIA Sentinel NetworK for allergic rhinitis (MASK-rhinitis): the new generation guideline implementation. Allergy. 2015;70(11):1372-1392.
Bousquet J, Anto JM, Berkouk K, Gergen P, Antunes JP, Augé P, Camuzat T, Bringer J, Mercier J, Best N, Bourret R, Akdis M, Arshad SH, Bedbrook A, Berr C, Bush A, Cavalli G, Charles MA, Clavel-Chapelon F, Gillman M, Gold DR, Goldberg M, Holloway JW, Iozzo P, Jacquemin S, Jeandel C, Kauffmann F, Keil T, Koppelman GH, Krauss-Etschmann S, Kuh D, Lehmann S, Carlsen KC, Maier D, Méchali M, Melén E, Moatti JP, Momas I, Nérin P, Postma DS, Ritchie K, Robine JM, Samolinski B, Siroux V, Slagboom PE, Smit HA, Sunyer J, Valenta R, Van de Perre P, Verdier JM, Vrijheid M, Wickman M, Yiallouros P, Zins M. Developmental determinants in non-communicable chronic diseases and ageing. Thorax. 2015;70(6):595-597.
Bousquet J, Malva J, Nogues M, Mañas LR, Vellas B, Farrell J; MACVIA Research Group. Operational Definition of Active and Healthy Aging (AHA): The European Innovation Partnership (EIP) on AHA Reference Site Questionnaire: Montpellier October 20-21, 2014, Lisbon July 2, 2015. J Am Med Dir Assoc. 2015;16(12):1020-1026.
Bousquet J, Kuh D, Bewick M, Standberg T, Farrell J, Pengelly R, Joel ME, Rodriguez Mañas L, Mercier J, Bringer J, Camuzat T, Bourret R, Bedbrook A, Kowalski ML, Samolinski B, Bonini S, Brayne C, Michel JP, Venne J, Viriot-Durandal P, Alonso J, Avignon A, Ben-Shlomo Y, Bousquet PJ, Combe B, Cooper R, Hardy R, Iaccarino G, Keil T, Kesse-Guyot E, Momas I, Ritchie K, Robine JM, Thijs C, Tischer C, Vellas B, Zaidi A, Alonso F, Andersen Ranberg K, Andreeva V, Ankri J, Arnavielhe S, Arshad H, Augé P, Berr C, Bertone P, Blain H, Blasimme A, Buijs GJ, Caimmi D, Carriazo A, Cesario A, Coletta J, Cosco T, Criton M, Cuisinier F, Demoly P, Fernandez-Nocelo S, Fougère B, Garcia-Aymerich J, Goldberg M, Guldemond N, Gutter Z, Harman D, Hendry A, Heve D, Illario M, Jeandel C, Krauss-Etschmann S, Krys O, Kula D, Laune D, Lehmann S, Maier D, Malva J, Matignon P, Melen
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E, Mercier G, Moda G, Nizinkska A, Nogues M, O'Neill M, Pelissier JY, Poethig D, Porta D, Postma D, Puisieux F, Richards M, Robalo-Cordeiro C, Romano V, Roubille F, Schulz H, Scott A, Senesse P, Slagter S, Smit HA, Somekh D, Stafford M, Suanzes J, Todo-Bom A, Touchon J, Traver-Salcedo V, Van Beurden M, Varraso R, Vergara I, Villalba-Mora E, Wilson N, Wouters E, Zins M. Operational Definition of Active and Healthy Ageing (AHA): A Conceptual Framework. J Nutr Health Aging. 2015;19(9):955-960.
Boven van JF, Roman-Rodriguez M, Kocks JW, Soriano JB, Postma MJ, van der Molen T. Predictors of cost-effectiveness of selected COPD treatments in primary care: UNLOCK study protocol. NPJ Prim Care Respir Med 2015;25:15051.
Boven van JF, Trappenburg JC, van der Molen T, Chavannes NH. Towards tailored and targeted adherence assessment to optimise asthma management. NPJ Prim Care Respir Med 2015;25:15046.
Brandsma CA, van den Berge M, Postma DS, Jonker MR, Brouwer S, Paré PD, Sin DD, Bossé Y, Laviolette M, Karjalainen J, Fehrmann RS, Nickle DC, Hao K, Spanjer AI, Timens W, Franke L. A large lung gene expression study identifying fibulin-5 as a novel player in tissue repair in COPD. Thorax. 2015;70(1):21-32.
Brusse-Keizer M, Zuur-Telgen M, van der Palen J, VanderValk P, Kerstjens H, Boersma W, Blasi F, Kostikas K, Milenkovic B, Tamm M, Stolz D. Adrenomedullin optimises mortality prediction in COPD patients. Respir Med. 2015;109(6):734-742.
Chen W, Brehm JM, Manichaikul A, Cho MH, Boutaoui N, Yan Q, Burkart KM, Enright PL, Rotter JI, Petersen H, Leng S, Obeidat M, Bosse Y, Brandsma CA, Hao K, Rich SS, Powell R, Avila L, Soto-Quiros M, Silverman EK, Tesfaigzi Y, Barr RG, Celedon JC. A genome-wide association study of chronic obstructive pulmonary disease in Hispanics. Ann Am Thorac Soc 2015;12:340-348.
Chen Y, Zhou J, Cheng Z, Yang S, Chu H, Fan Y, Li C, Wong BH, Zheng S, Zhu Y, Yu F, Wang Y, Liu X, Gao H, Yu L, Tang L, Cui D, Hao K, Bosse Y, Obeidat M, Brandsma CA, Song YQ, To KK, Sham PC, Yuen KY, Li L. Functional variants regulating LGALS1 (Galectin 1) expression affect human susceptibility to influenza A(H7N9). Sci Rep 2015;5:8517.
Cheng Z, Zhou J, To KK, Chu H, Li C, Wang D, Yang D, Zheng S, Hao K, Bosse Y, Obeidat M, Brandsma CA, Song YQ, Chen Y, Zheng BJ, Li L, Yuen KY. Identification of TMPRSS2 as a Susceptibility Gene for Severe 2009 Pandemic A(H1N1) Influenza and A(H7N9) Influenza. J Infect Dis 2015;212:1214-1221.
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Jenkins CR, Postma DS, Anzueto AR, Make BJ, Peterson S, Eriksson G, Calverley PM. Reliever salbutamol use as a measure of exacerbation risk in chronic obstructive pulmonary disease. BMC Pulm Med. 2015;15:97.
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Klaassen EM, Penders J, Jöbsis Q, van de Kant KD, Thijs C, Mommers M, van Schayck CP, van Eys G, Koppelman GH, Dompeling E. An ADAM33 polymorphism associates with progression of preschool wheeze into childhood asthma: a prospective case-control study with replication in a birth cohort study. PLoS One. 2015;10(3):e0119349.
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Koegelenberg CF, Theron J, Dheda K, Bruwer W, Allwood B, Vorster M, Von Groote-Bidlingmaier F, Slebos DJ, Shah P, Herth F. Recommendations for the use of endoscopic lung volume reduction in South Africa: Role in the treatment of emphysema. S Afr Med J. 2015;105:810-815.
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Kunz LI, Van't Wout EF, van Schadewijk A, Postma DS, Kerstjens HA, Sterk PJ, Hiemstra PS. Regulation of YKL-40 expression by corticosteroids: effect on pro-inflammatory macrophages in vitro and its modulation in COPD in vivo. Respir Res. 2015;16:154.
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Metting EI, Riemersma RA, Kocks JH, Piersma-Wichers MG, Sanderman R, van der Molen T. Feasibility and effectiveness of an asthma/COPD service for primary care: a cross-sectional baseline description and longitudinal results. NPJ Prim Care Respir Med. 2015;25:14101.
Moeller A, Carlsen KH, Sly PD, Baraldi E, Piacentini G, Pavord I, Lex C, Saglani S; ERS Task Force Monitoring Asthma in Children. Monitoring asthma in childhood: lung function, bronchial responsiveness and inflammation. Eur Respir Rev. 2015;24(136):204-215.
Molen van der T, Kirenga BJ. COPD: early diagnosis and treatment to slow disease progression. Int J Clin Pract. 2015;69(5):513-514.
Mölter A, Simpson A, Berdel D, Brunekreef B, Custovic A, Cyrys J, de Jongste J, de Vocht F, Fuertes E, Gehring U, Gruzieva O, Heinrich J, Hoek G, Hoffmann B, Klümper C, Korek M, Kuhlbusch TA, Lindley S, Postma D, Tischer C, Wijga A, Pershagen G, Agius R. A multicentre study of air pollution exposure and childhood asthma prevalence: the ESCAPE project. Eur Respir J. 2015;45(3):610-624.
Ngkelo A, Hoffmann RF, Durham AL, Marwick JA, Brandenburg SM, de Bruin HG, Jonker MR, Rossios C, Tsitsiou E, Caramori G, Contoli M, Casolari P, Monaco F, Andò F, Speciale G, Kilty I, Chung KF, Papi A, Lindsay MA, Ten Hacken NH, van den Berge M, Timens W, Barnes PJ, van Oosterhout AJ, Adcock IM, Kirkham PA, Heijink IH. Glycogen synthase kinase-3β modulation of glucocorticoid responsiveness in COPD. Am J Physiol Lung Cell Mol Physiol. 2015;309(10):L1112-1123.
Obeidat M, Hao K, Bossé Y, Nickle DC, Nie Y, Postma DS, Laviolette M, Sandford AJ, Daley DD, Hogg JC, Elliott WM, Fishbane N, Timens W, Hysi PG, Kaprio J, Wilson JF, Hui J, Rawal R, Schulz H, Stubbe B, Hayward C, Polasek O, Järvelin MR, Zhao JH, Jarvis D, Kähönen M, Franceschini N, North KE, Loth DW, Brusselle GG, Smith AV, Gudnason V, Bartz TM, Wilk JB, O'Connor GT, Cassano PA, Tang W, Wain LV, Soler Artigas M, Gharib SA, Strachan DP, Sin DD, Tobin MD, London SJ, Hall IP, Paré PD. Molecular mechanisms underlying variations in lung function: a systems genetics analysis. Lancet Respir Med. 2015;3(10):782-795.
Osei ET, Florez-Sampedro L, Timens W, Postma DS, Heijink IH, Brandsma CA. Unravelling the complexity of COPD by microRNAs: it's a small world after all. Eur Respir J. 2015;46(3):807-818.
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Ostrem A, Williams S, Pinnock H, International Primary Care Respiratory Group. We must join forces in the battle against COPD. Eur Respir J 2015;46:1526-1528.
Paternoster L, Standl M, Waage J, Baurecht H, Hotze M, Strachan DP, Curtin JA, Bønnelykke K, Tian C, Takahashi A, Esparza-Gordillo J, Alves AC, Thyssen JP, den Dekker HT, Ferreira MA, Altmaier E, Sleiman PM, Xiao FL, Gonzalez JR, Marenholz I, Kalb B, Pino-Yanes M, Xu CJ, Carstensen L, Groen-Blokhuis MM, Venturini C, Pennell CE, Barton SJ, Levin AM, Curjuric I, Bustamante M, Kreiner-Møller E, Lockett GA, Bacelis J, Bunyavanich S, Myers RA, Matanovic A, Kumar A, Tung JY, Hirota T, Kubo M, McArdle WL, Henderson AJ, Kemp JP, Zheng J, Smith GD, Rüschendorf F, Bauerfeind A, Lee-Kirsch MA, Arnold A, Homuth G, Schmidt CO, Mangold E, Cichon S, Keil T, Rodríguez E, Peters A, Franke A, Lieb W, Novak N, Fölster-Holst R, Horikoshi M, Pekkanen J, Sebert S, Husemoen LL, Grarup N, de Jongste JC, Rivadeneira F, Hofman A, Jaddoe VW, Pasmans SG, Elbert NJ, Uitterlinden AG, Marks GB, Thompson PJ, Matheson MC, Robertson CF; Australian Asthma Genetics Consortium (AAGC), Ried JS, Li J, Zuo XB, Zheng XD, Yin XY, Sun LD, McAleer MA, O'Regan GM, Fahy CM, Campbell L, Macek M, Kurek M, Hu D, Eng C, Postma DS, Feenstra B, Geller F, Hottenga JJ, Middeldorp CM, Hysi P, Bataille V, Spector T, Tiesler CM, Thiering E, Pahukasahasram B, Yang JJ, Imboden M, Huntsman S, Vilor-Tejedor N, Relton CL, Myhre R, Nystad W, Custovic A, Weiss ST, Meyers DA, Söderhäll C, Melén E, Ober C, Raby BA, Simpson A, Jacobsson B, Holloway JW, Bisgaard H, Sunyer J, Probst-Hensch NM, Williams LK, Godfrey KM, Wang CA, Boomsma DI, Melbye M, Koppelman GH, Jarvis D, McLean WH, Irvine AD, Zhang XJ, Hakonarson H, Gieger C, Burchard EG, Martin NG, Duijts L, Linneberg A, Jarvelin MR, Nöthen MM, Lau S, Hübner N, Lee YA, Tamari M, Hinds DA, Glass D, Brown SJ, Heinrich J, Evans DM, Weidinger S; EArly Genetics and Lifecourse Epidemiology (EAGLE) Eczema Consortium. Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nat Genet. 2015;47(12):1449-1456.
Pijnenburg MW, Baraldi E, Brand PL, Carlsen KH, Eber E, Frischer T, Hedlin G, Kulkarni N, Lex C, Mäkelä MJ, Mantzouranis E, Moeller A, Pavord I, Piacentini G, Price D, Rottier BL, Saglani S, Sly PD, Szefler SJ, Tonia T, Turner S, Wooler E, Lødrup Carlsen KC. Monitoring asthma in children. Eur Respir J. 2015;45(4):906-925.
Pizzichini MM, Kerstjens HA, Pizzichini E. Current role of anticholinergic drugs in the treatment of asthma - key messages for clinical practice. Pol Arch Med Wewn. 2015;125(11):859-866.
Poirier JG, Brennan P, McKay JD, Spitz MR, Bickeböller H, Risch A, Liu G, Le Marchand L, Tworoger S, McLaughlin J, Rosenberger A, Heinrich J, Brüske I, Muley T, Henderson BE, Wilkens LR, Zong X, Li Y, Hao K, Timens W, Bossé Y, Sin DD, Obeidat M, Amos CI, Hung RJ. Informed genome-wide association analysis with family history as a secondary phenotype identifies novel loci of lung cancer. Genet Epidemiol. 2015;39(3):197-206.
Poppinga WJ, Heijink IH, Holtzer LJ, Skroblin P, Klussmann E, Halayko AJ, Timens W, Maarsingh H, Schmidt M. A-kinase-anchoring proteins coordinate inflammatory responses to cigarette smoke in airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2015;308(8):L766-775.
Post S, Rozeveld D, Jonker MR, Bischoff R, van Oosterhout AJ, Heijink IH. ADAM10 mediates the house dust mite-induced release of chemokine ligand CCL20 by airway epithelium. Allergy. 2015;70(12):1545-1552.
Postma DS, Weiss ST, van den Berge M, Kerstjens HA, Koppelman GH. Revisiting the Dutch hypothesis. J Allergy Clin Immunol. 2015;136(3):521-529.
Postma DS, van den Berge M. The different faces of the asthma-COPD overlap syndrome. Eur Respir J. 2015;46(3):587-590.
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Postma DS, Rabe KF. The Asthma-COPD Overlap Syndrome. N Engl J Med. 2015;373(13):1241-1249.
Postma DS, Bush A, van den Berge M. Risk factors and early origins of chronic obstructive pulmonary disease. Lancet. 2015;385(9971):899-909.
Postma DS, Brightling C, Fabbri L, van der Molen T, Nicolini G, Papi A, Rabe KF, Siddiqui S, Singh D, van den Berge M, Kraft M. Unmet needs for the assessment of small airways dysfunction in asthma: introduction to the ATLANTIS study. Eur Respir J. 2015;45(6):1534-1538.
Pouwels SD, Nawijn MC, Bathoorn E, Riezebos-Brilman A, van Oosterhout AJ, Kerstjens HA, Heijink IH. Increased serum levels of LL37, HMGB1 and S100A9 during exacerbation in COPD patients. Eur Respir J. 2015;45(5):1482-1485.
Pouwels SD, Heijink IH, Brouwer U, Gras R, den Boef LE, Boezen HM, Korstanje R, van Oosterhout AJ, Nawijn MC. Genetic variation associates with susceptibility for cigarette smoke-induced neutrophilia in mice. Am J Physiol Lung Cell Mol Physiol. 2015;308(7):L693-709.
Robbe P, Draijer C, Borg TR, Luinge M, Timens W, Wouters IM, Melgert BN, Hylkema MN. Distinct macrophage phenotypes in allergic and nonallergic lung inflammation. Am J Physiol Lung Cell Mol Physiol. 2015;308(4):L358-367.
Roche N, Postma DS, Colice G, Burden A, Guilbert TW, Israel E, Martin RJ, van Aalderen WM, Grigg J, Hillyer EV, von Ziegenweidt J, Price DB. Differential effects of inhaled corticosteroids in smokers/ex-smokers and nonsmokers with asthma. Am J Respir Crit Care Med. 2015;191(8):960-964.
Rochester CL, Vogiatzis I, Holland AE, Lareau SC, Marciniuk DD, Puhan MA, Spruit MA, Masefield S, Casaburi R, Clini EM, Crouch R, Garcia-Aymerich J, Garvey C, Goldstein RS, Hill K, Morgan M, Nici L, Pitta F, Ries AL, Singh SJ, Troosters T, Wijkstra PJ, Yawn BP, ZuWallack RL. An Official American Thoracic Society/European Respiratory Society Policy Statement: Enhancing Implementation, Use, and Delivery of Pulmonary Rehabilitation.; ATS/ERS Task Force on Policy in Pulmonary Rehabilitation. Am J Respir Crit Care Med. 2015;192(11):1373-1386.
Rossi A, van der Molen T, Del Olmo R, Wehbe L. Salmeterol/fluticasone combination instead of indacaterol or vice-versa? Eur Respir J 2015;45:1188-1189.
Rottier BL, Eber E, Hedlin G, Turner S, Wooler E, Mantzourani E, Kulkarni N; ERS Task Force Monitoring Asthma in Children. Monitoring asthma in childhood: management-related issues. Eur Respir Rev. 2015;24(136):194-203.
Saferali A, Obeidat M, Bérubé JC, Lamontagne M, Bossé Y, Laviolette M, Hao K, Nickle DC, Timens W, Sin DD, Postma DS, Strug LJ, Gallins PJ, Paré PD, Bingle D, Sandford AJ. Polymorphisms associated with expression of BPIFA1/BPIFB1 and lung disease severity in cystic fibrosis. Am J Respir Cell Mol Biol. 2015;53(5):607-614.
Saleh-Langenberg J, Goossens NJ, Flokstra-de Blok BM, Kollen BJ, van der Meulen GN, Le TM, Knulst AC, Jedrzejczak-Czechowicz M, Kowalski ML, Rokicka E, Starosta P, de la Hoz Caballer B, Vazquez-Cortés S, Cerecedo I, Barreales L, Asero R, Clausen M, DunnGalvin A, Hourihane JO, Purohit A, Papadopoulos NG, Fernandéz-Rivas M, Frewer L, Burney P, Duiverman EJ, Dubois AE. Predictors of health-related quality of life of European food-allergic patients. Allergy. 2015;70(6):616-624.
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Saleh-Langenberg J, Dubois AE, Groenhof F, Kocks JW, van der Molen T, Flokstra-de Blok BM. Epinephrine auto-injector prescriptions to food-allergic patients in primary care in The Netherlands. Allergy Asthma Clin Immunol. 2015;11:28.
Saluja R, Ketelaar ME, Hawro T, Church MK, Maurer M, Nawijn MC. The role of the IL-33/IL-1RL1 axis in mast cell and basophil activation in allergic disorders. Mol Immunol. 2015;63(1):80-85.
Sansone VA, Gagnon C; participants of the 207th ENMC Workshop 207th ENMC Workshop on chronic respiratory insufficiency in myotonic dystrophies: management and implications for research, 27-29 June 2014, Naarden, The Netherlands. Neuromuscul Disord. 2015;25(5):432-442.
Sivapalan P, Diamant Z, Ulrik CS. Obesity and asthma: current knowledge and future needs. Curr Opin Pulm Med 2015;21:80-85.
Slebos DJ, van Rikxoort EM, van der Bij W. "Air Trapping in Emphysema". Am J Respir Crit Care Med 2015;192:e45.
Slebos DJ, Hartman JE, Klooster K, Blaas S, Deslee G, Gesierich W, Hetzel J, Hetzel M, McNulty W, Kemp SV, Kessler R, Leroy S, Stanzel F, Witt C, Zoumot Z, Herth FJ, Shah PL. Bronchoscopic Coil Treatment for Patients with Severe Emphysema: A Meta-Analysis. Respiration. 2015;90(2):136-145.
Slebos DJ, Klooster K, Koegelenberg CF, Theron J, Styen D, Valipour A, Mayse M, Bolliger CT. Targeted lung denervation for moderate to severe COPD: a pilot study. Thorax. 2015;70:411-419.
Snoeck-Stroband JB, Lapperre TS, Sterk PJ, Hiemstra PS, Thiadens HA, Boezen HM, Ten Hacken NH, Kerstjens HA, Postma DS, Timens W, Sont JK; GLUCOLD Study Group. Prediction of Long-Term Benefits of Inhaled Steroids by Phenotypic Markers in Moderate-to-Severe COPD: A Randomized Controlled Trial. PLoS One. 2015;10(12):e0143793.
Soler Artigas M, Wain LV, Miller S, Kheirallah AK, Huffman JE, Ntalla I, Shrine N, Obeidat M, Trochet H, McArdle WL, Alves AC, Hui J, Zhao JH, Joshi PK, Teumer A, Albrecht E, Imboden M, Rawal R, Lopez LM, Marten J, Enroth S, Surakka I, Polasek O, Lyytikainen LP, Granell R, Hysi PG, Flexeder C, Mahajan A, Beilby J, Bosse Y, Brandsma CA, Campbell H, Gieger C, Glaser S, Gonzalez JR, Grallert H, Hammond CJ, Harris SE, Hartikainen AL, Heliovaara M, Henderson J, Hocking L, Horikoshi M, Hutri-Kahonen N, Ingelsson E, Johansson A, Kemp JP, Kolcic I, Kumar A, Lind L, Melen E, Musk AW, Navarro P, Nickle DC, Padmanabhan S, Raitakari OT, Ried JS, Ripatti S, Schulz H, Scott RA, Sin DD, Starr JM, UK BiLEVE, Vinuela A, Volzke H, Wild SH, Wright AF, Zemunik T, Jarvis DL, Spector TD, Evans DM, Lehtimaki T, Vitart V, Kahonen M, Gyllensten U, Rudan I, Deary IJ, Karrasch S, Probst-Hensch NM, Heinrich J, Stubbe B, Wilson JF, Wareham NJ, James AL, Morris AP, Jarvelin MR, Hayward C, Sayers I, Strachan DP, Hall IP, Tobin MD. Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation. Nat Commun 2015;6:8658.
Spierenburg EA, Smit LAM, Heederik D, Robbe P, Hylkema MN, Wouters IM. Healthy worker survivor analysis in an occupational cohort study of Dutch agricultural workers. Int Arch Occup Environ Health. 2015;88(8):1165-1173.
Taghizadeh N, Vonk JM, Hospers JJ, Postma DS, de Vries EG, Schouten JP, Boezen HM. Objective allergy markers and risk of cancer mortality and hospitalization in a large population-based cohort. Cancer Causes Control. 2015;26(1):99-109.
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Tang FSM, Foxley GJ, Gibson PG, Burgess JK, Baines KJ, Oliver BG. Altered Innate Immune Responses in Neutrophils from Patients with Well- and Suboptimally Controlled Asthma. Med Inflam. 2015:219374.
Taylor SL, Houben GF, Baumert JL, Crevel RR, Allen KJ, Dubois AE, Knulst AC, Remington BC, Kruizinga AG, Blom WM, Brooke-Taylor S. Understanding food allergen thresholds requires careful analysis of the available clinical data. J Allergy Clin Immunol. 2015;135(2):583-584.
Tsiligianni I, Goodridge D, Marciniuk D, Hull S, Bourbeau J. Four patients with a history of acute exacerbations of COPD: implementing the CHEST/Canadian Thoracic Society guidelines for preventing exacerbations. NPJ Prim Care Respir Med 2015;25:15023.
Tsiligianni IG, Papadokostakis P, Prokopiadou D, Stefanaki I, Tsakountakis N, Lionis C. Impact of the financial crisis on adherence to treatment of a rural population in Crete, Greece. Qual Prim Care 2014;22:238-244.
Velzen van AJ, Uges JW, Le Brun PP, Shahbabai P, Touw DJ, Heijerman HG. The influence of breathing mode on tobramycin serum levels using the I-neb AAD system in adults with cystic fibrosis. J Cyst Fibros. 2015;14:748-754.
Vijverberg SJ, Koster ES, Tavendale R, Leusink M, Koenderman L, Raaijmakers JA, Postma DS, Koppelman GH, Turner SW, Mukhopadhyay S, Tse SM, Tantisira KG, Hawcutt DB, Francis B, Pirmohamed M, Pino-Yanes M, Eng C, Burchard EG, Palmer CN, Maitland-van der Zee AH. ST13 polymorphisms and their effect on exacerbations in steroid-treated asthmatic children and young adults. Clin Exp Allergy. 2015;45(6):1051-1059.
Vos BJ, van der Veer E, van Voorst Vader PC, Mulder AB, van der Heide S, Arends S, Kluin-Nelemans JC, de Monchy JG, van Doormaal JJ, Oude Elberink JN. Diminished reliability of tryptase as risk indicator of mastocytosis in older overweight subjects. J Allergy Clin Immunol. 2015;135(3):792-798.
Vries de GE, van der Wal HH, Kerstjens HA, van Deursen VM, Stegenga B, van Veldhuisen DJ, van der Hoeven JH, van der Meer P, Wijkstra PJ. Validity and Predictive Value of a Portable Two-Channel Sleep-Screening Tool in the Identification of Sleep Apnea in Patients With Heart Failure. J Card Fail. 2015;21(10):848-855.
Vries de GE, Hoekema A, Doff MH, Kerstjens HA, Meijer PM, van der Hoeven JH, Wijkstra PJ. Usage of positional therapy in adults with obstructive sleep apnea. J Clin Sleep Med. 2015;11(2):131-137.
Vries de M, Smithers NP, Howarth PH, Nawijn MC, Davies DE. Inhibition of Pim1 kinase reduces viral replication in primary bronchial epithelial cells. Eur Respir J. 2015;45(6):1745-1748.
Vries de M, Hesse L, Jonker MR, van den Berge M, van Oosterhout AJ, Heijink IH, Nawijn MC. Pim1 kinase activity preserves airway epithelial integrity upon house dust mite exposure. Am J Physiol Lung Cell Mol Physiol. 2015;309(11):L1344-1353.
Vrijsen B, Chatwin M, Contal O, Derom E, Janssens JP, Kampelmacher MJ, Muir JF, Pinto S, Rabec C, Ramsay M, Randerath WJ, Storre JH, Wijkstra PJ, Windisch W, Testelmans.D. Hot Topics in Noninvasive Ventilation: Report of a Working Group at the International Symposium on Sleep-Disordered Breathing in Leuven, Belgium. Respir Care. 2015; 60(9):1337-1362.
Wagenaar GT, Hiemstra PS, Gosens R. Therapeutic potential of soluble guanylate cyclase modulators in neonatal chronic lung disease. Am J Physiol Lung Cell Mol Physiol. 2015;309(10):L1037-1040.
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Wain LV, Shrine N, Miller S, Jackson VE, Ntalla I, Soler Artigas M, Billington CK, Kheirallah AK, Allen R, Cook JP, Probert K, Obeidat M, Bossé Y, Hao K, Postma DS, Paré PD, Ramasamy A; UK Brain Expression Consortium (UKBEC), Mägi R, Mihailov E, Reinmaa E, Melén E, O'Connell J, Frangou E, Delaneau O; OxGSK Consortium, Freeman C, Petkova D, McCarthy M, Sayers I, Deloukas P, Hubbard R, Pavord I, Hansell AL, Thomson NC, Zeggini E, Morris AP, Marchini J, Strachan DP, Tobin MD, Hall IP. Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): a genetic association study in UK Biobank. Lancet Respir Med. 2015;3(10):769-781.
Wang M, Gehring U, Hoek G, Keuken M, Jonkers S, Beelen R, Eeftens M, Postma DS, Brunekreef B. Air Pollution and Lung Function in Dutch Children: A Comparison of Exposure Estimates and Associations Based on Land Use Regression and Dispersion Exposure Modeling Approaches. Environ Health Perspect. 2015;123(8):847-851.
Welling JB, Hartman JE, Ten Hacken NH, Klooster K, Slebos DJ. The minimal important difference for the St George's Respiratory Questionnaire in patients with severe COPD. Eur Respir J. 2015;46(6):1598-1604.
Xu X, Zeng X, Boezen HM, Huo X. E-waste environmental contamination and harm to public health in China. Front Med. 2015 Jun;9(2):220-228.
Zuiker RG, Kamerling IM, Morelli N, Calderon C, Boot JD, de Kam M, Diamant Z, Burggraaf J, Cohen AF. Reproducibility of biomarkers in induced sputum and in serum from chronic smokers. Pulm Pharmacol Ther 2015;33:81-86.
Publications in Dutch
Alma HJ. Praktische Epidemiologie: Klinisch relevant en statistisch significant. Huisarts en Wetenschap 2015;58:577.
Boven van JF, van der Molen T, Postma MJ. Ingrijpen bij therapieontrouwe COPD-patiënt al snel lonend. Pharmaceutisch Weeklblad 2015;150:18-19.
Flokstra-de Blok BMJ, van der Molen T. Meten van astmacontrole in de praktijk: zijn er voordelen verbonden aan de Control of Allergic Rhinitis and Asthma Test (CARAT)? Spreekuur Longziekten 2015;6:1.
Flokstra-de Blok BMJ, van der Molen T. Patiëntgerapporteerde uitkomstmaten voor astma en allergische rhinitis in de huisartsenpraktijk. Modern Medicine 2015;39:29.
Gemert van FA, Speksnijder C. Longziekten rukt op in stilte. Volkskrant 2015:17.
Kistemaker LEM. Anticholinergica overtreffen de verwachting bij COPD en astma. Wens: anticholinergicum dat nog selectiever is voor M3-receptoren Pharm Weekblad 2015; 150 (19): 14-15.
Klooster K, ten Hacken NH, Hartman JE, Kerstjens HA, Slebos DJ. [Bronchoscopic interventions in severe COPD: improvement of pulmonary function, exercise capacity and quality of life]. Ned Tijdschr Geneeskd. 2015;159:A8497. (In Dutch).
Postma DS. ATLANTIS studie: Kleine luchtwegen bij astma grootschalig bekeken. Modern Medicine 2015;1:25-26
Postma DS, Kerstjens HAM: Combinatie visuele en moleculaire technieken opent nieuwe wegen in longzorg. Salute 3, 2015:20-22
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Books/Book chapters
Ginkel van CD, Dubois AEJ, Koppelman GH. Genetics of Allergic Disorders. In: Manual of Allergy and Clinical Immunology for Otolaryngologists. Rosenstreich DL, Fried MP, De Vos GS, Jackman AH (eds.). San Diego, CA: Plural Publishing, Inc., 2015, p. 89-104.
Groothuis GMM, Casini A, Meurs H, Olinga P. Translational research in pharmacology and toxicology using precision-cut tissue slices. In: Human-based Systems for Translational Research, ed. R. Coleman, Cambridge, RSC publishing, 2015, pp. 38-65.
Contributions to other research institutes
Dissertations
J.Jaffar The extracellular matrix protein fibulin-1 in idiopathic pulmonary fibrosis 27-02-2015 Promotor: Dr. J.K. Burgess Co-Promotores: Dr. B. Oliver, Prof. Dr. J. Black P.A. Muñoz Llancao Role of EPAC in axon determination 23-11-2015 Promotores: Prof. Dr. H.W.G.M. Boddeke, Prof. Dr. M. Schmidt, Prof. Dr. C. Gonzalez-Billault
Publications SCI journals
Alffenaar JW, Bolhuis M, van Hateren K, Sturkenboom M, Akkerman O, de Lange W, Greijdanus B, van der Werf T, Touw D. Determination of bedaquiline in human serum using liquid chromatography-tandem mass spectrometry. Antimicrob Agents Chemother. 2015;59:5675-5680.
Bilenko N, Brunekreef B, Beelen R, Eeftens M, de Hoogh K, Hoek G, Koppelman GH, Wang M, van Rossem L, Gehring U. Associations between particulate matter composition and childhood blood pressure--The PIAMA study. Environ Int. 2015;84:1-6.
Boer H, Proost JH, Nuver J, Bunskoek S, Gietema JQ, Geubels BM, Altena R, Zwart N, Oosting SF, Vonk JM, Lefrandt JD, Uges DR, Meijer C, de Vries EG, Gietema JA. Long-term exposure to circulating platinum is associated with late effects of treatment in testicular cancer survivors. Ann Oncol. 2015;26(11):2305-2310.
Braithwaite I, Hunt A, Riley J, Fingleton J, Kocks J, Corin A, Helm C, Sheahan D, Tofield C, Montgomery B, Holliday M, Weatherall M, Beasley R. Randomised controlled trial of topical kanuka honey for the treatment of rosacea. BMJ Open 2015;5:e007651-2015-007651.
Cernecka H, Kersten K, Maarsingh H, Elzinga CRS, de Jong IJ, Korstanje C, Michel MC, Schmidt M. β3-Adrenoceptor-mediated relaxation of rat and human urinary bladder: roles of BKCa channels and Rho kinase. Naunyn-Schmiedebergs Arch Pharmacol 2015; 388: 749-759.
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Dijkmans AC, Wilms EB, Kamerling IM, Birkhoff W, Ortiz-Zacarías NV, van Nieuwkoop C, Verbrugh HA, Touw DJ. Colistin: Revival of an Old Polymyxin Antibiotic. Ther Drug Monit. 2015;37:419-427.
Dijkstra JA, Alsaad NS, Hateren Kv, Greijdanus B, Touw DJ, Alffenaar JW. Quantification of co-trimoxazole in serum and plasma using MS/MS. Bioanalysis. 2015;7:2741-2749.
Ge Q, Chen L, Jaffar J, Argraves WS, Twal WO, Hansbro P, Black JL, Burgess JK, Oliver B. Fibulin1C peptide induces cell attachment and extracellular matrix deposition in lung fibroblasts. Scientific reports 2015;5:9496.
Harkness LM, Ashton AW, Burgess JK. Asthma is not only an airway disease, but also a vascular disease. Pharmacol Therapeut 2015; 148: 17-33.
Jansen H, Wijga AH, Scholtens S, Koppelman GH, Postma DS, Brunekreef B, de Jongste JC, Smit HA, Stolk RP. Change in HbA1c levels between the age of 8 years and the age of 12 years in Dutch children without diabetes: the PIAMA birth cohort study. PLoS One. 2015;10(4):e0119615.
Jansen SR, Holman R, Hedemann I, Frankes E, Elzinga CRS, Timens W, Gosens R, de Bont ES, Schmidt M. Prostaglandin E2 promotes MYCN non-amplified neuroblastoma cell survival via β-catenin stabilization. J Cell Mol Med 2015; 19: 210-226.
Jong de C, Kikkert HK, Seggers J, Boehm G, Decsi T, Hadders-Algra M. Neonatal fatty acid status and neurodevelopmental outcome at 9 years. Early Hum Dev 2015;91:587-591.
Klemenc-Ketis Z, Kurpas D, Tsiligianni I, Petrazzuoli F, Jacquet JP, Buono N, Lopez-Abuin J, Lionis C. Is a practice-based rural research network feasible in Europe? Eur J Gen Pract 2015;21:203-209.
Koster RA, Alffenaar JW, Botma R, Greijdanus B, Touw DJ, Uges DR, Kosterink JG. What is the right blood hematocrit preparation procedure for standards and quality control samples for dried blood spot analysis? Bioanalysis. 2015;7:345-351.
Koster RA, Alffenaar JW, Botma R, Greijdanus B, Uges DR, Kosterink JG, Touw DJ. The relation of the number of hydrogen-bond acceptors with recoveries of immunosuppressants in DBS analysis. Bioanalysis. 2015;7:1717-1722.
Koster RA, Botma R, Greijdanus B, Uges DR, Kosterink JG, Touw DJ, Alffenaar JW. The performance of five different dried blood spot cards for the analysis of six immunosuppressants. Bioanalysis. 2015;7:1225-1235.
Koster RA, Greijdanus B, Alffenaar JW, Touw DJ. Dried blood spot analysis of creatinine with LC-MS/MS in addition to immunosuppressants analysis. Anal Bioanal Chem. 2015;407:1585-1594.
Koster RA, Vereecke HE, Greijdanus B, Touw DJ, Struys MM, Alffenaar JW. Analysis of remifentanil with liquid chromatography-tandem mass spectrometry and an extensive stability investigation in EDTA whole blood and acidified EDTA plasma. Anesth Analg. 2015;120:1235-1241.
Laan van der ME, Schat TE, Olthuis AJ, Boezen HM, Bos AF, Kooi EM. The Association between Multisite Near-Infrared Spectroscopy and Routine emodynamic Measurements in Relation to Short-Term Outcome in Preterms with Clinical Sepsis. Neonatology. 2015;108(4):297-304.
Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, Powell C, Vedantam S, Buchkovich ML, Yang J, Croteau-Chonka DC, Esko T, Fall T, Ferreira T, Gustafsson S,
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Meijering RAM, Wiersma M, van Marion DMS, Zhang D, Hoogstra-Berends F, Dijkhuis A-J, Schmidt M., Wieland T, Kampinga HH, Henning RH, Brundel BJM. RhoA Activation Sensitizes Cells to Proteotoxic Stimuli by Abrogating the HSF1-Dependent Heat Shock Response. PLoS ONE 2015; 10: e0133553.
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Rossem van L, Wijga AH, Gehring U, Koppelman GH, Smit HA. Maternal Gestational and Postdelivery Weight Gain and Child Weight. Pediatrics. 2015;136(5):e1294-1301.
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Strijbos E, Coenradie S, Touw DJ, Aerden L. High-dose methylprednisolone for multiple sclerosis during lactation: Concentrations in breast milk. Mult Scler. 2015;21:797-798.
Taghizadeh N, Boezen HM, Schouten JP, Schröder CP, Elisabeth de Vries EG, Vonk JM. BMI and lifetime changes in BMI and cancer mortality risk. PLoS One. 2015;10(4):e0125261.
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Books/Book chapters
Burgess JK, Tjin G. Extracellular matrix specification of regenerative cells in the adult lung. In: Stem Cells in the Lung – Development, Repair and Regeneration, ed. Ivan Bertoncello. Springer Series “Stem Cell Biology and Regenerative Medicine: Series Editor Kursad Turksen, 2015.
Touw, D.J. Irrigations and Dialysis Solutions. In Practical Pharmaceutics. An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer 2015, p 301-307.
Touw, D.J. Stability. In Practical Pharmaceutics. An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer 2015, p 435-461.