Publications
Below you can find a list of our published research.
Below you can find a list of our published research.
440 results
Cited 16 times since 2022 (6.8 per year) source: EuropePMC
Thorax, Volume 77, Issue 4, 11 2 2022, Pages 408-416 Lung epithelial cells interact with immune cells and bacteria to shape the microenvironment in tuberculosis. de Waal AM, Hiemstra PS, Ottenhoff TH, Joosten SA, van der Does AM
The lung epithelium has long been overlooked as a key player in tuberculosis disease. In addition to acting as a direct barrier to Mycobacterium tuberculosis (Mtb), epithelial cells (EC) of the airways and alveoli act as first responders during Mtb infections; they directly sense and respond to Mtb by producing mediators such as cytokines, chemokines and antimicrobials. Interactions of EC with innate and adaptive immune cells further shape the immune response against Mtb. These three essential c... Abstract
Cited 4 times since 2022 (1.7 per year) source: EuropePMC
PloS one, Volume 17, Issue 1, 6 1 2022, Pages e0262082 The lower airways microbiome and antimicrobial peptides in idiopathic pulmonary fibrosis differ from chronic obstructive pulmonary disease. Knudsen KS, Lehmann S, Nielsen R, Tangedal S, Haaland I, Hiemstra PS, Eagan TM
Background: The lower airways microbiome and host immune response in chronic pulmonary diseases are incompletely understood. We aimed to investigate possible microbiome characteristics and key antimicrobial peptides and proteins in idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Methods: 12 IPF patients, 12 COPD patients and 12 healthy controls were sampled with oral wash (OW), protected bronchoalveolar lavage (PBAL) and right lung protected sterile brushing... Abstract
Cited 51 times since 2021 (21.2 per year) source: EuropePMC
Nature immunology, Volume 23, Issue 1, 22 4 2021, Pages 23-32 Prolonged activation of nasal immune cell populations and development of tissue-resident SARS-CoV-2-specific CD8<sup>+</sup> T cell responses following COVID-19. Roukens AHE, Pothast CR, König M, Huisman W, Dalebout T, Tak T, Azimi S, Kruize Y, Hagedoorn RS, Zlei M, Staal FJT, de Bie FJ, van Dongen JJM, Arbous SM, Zhang JLH, Verheij M, Prins C, van der Does AM, Hiemstra PS, de Vries JJC, Janse JJ, Roestenberg M, Myeni SK, Kikkert M, Yazdanbakhsh M, Heemskerk MHM, Smits HH, Jochems SP, in collaboration with BEAT-COVID group, in collaboration with COVID-19 LUMC group
Systemic immune cell dynamics during coronavirus disease 2019 (COVID-19) are extensively documented, but these are less well studied in the (upper) respiratory tract, where severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates1-6. Here, we characterized nasal and systemic immune cells in individuals with COVID-19 who were hospitalized or convalescent and compared the immune cells to those seen in healthy donors. We observed increased nasal granulocytes, monocytes, CD11c+ natura... Abstract
Cited 13 times since 2021 (5.1 per year) source: EuropePMC
Allergy, Volume 77, Issue 2, 3 1 2021, Pages 690-694 Determinants of expression of SARS-CoV-2 entry-related genes in upper and lower airways. Aliee H, Massip F, Qi C, Stella de Biase M, van Nijnatten J, Kersten ETG, Kermani NZ, Khuder B, Vonk JM, Vermeulen RCH, U-BIOPRED study group, Cambridge Lung Cancer Early Detection Programme, INER-Ciencias Mexican Lung Program, Neighbors M, Tew GW, Grimbaldeston MA, Ten Hacken NHT, Hu S, Guo Y, Zhang X, Sun K, Hiemstra PS, Ponder BA, Mäkelä MJ, Malmström K, Rintoul RC, Reyfman PA, Theis FJ, Brandsma CA, Adcock IM, Timens W, Xu CJ, van den Berge M, Schwarz RF, Koppelman GH, Nawijn MC, Faiz A
Cited 2 times since 2021 (0.8 per year) source: EuropePMC
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Volume 35, Issue 10, 1 1 2021, Pages e21838 Kallikrein-related peptidase 5 contributes to the remodeling and repair of bronchial epithelium. Lenga Ma Bonda W, Lavergne M, Vasseur V, Brisson L, Roger S, Legras A, Guillon A, Guyétant S, Hiemstra PS, Si-Tahar M, Iochmann S, Reverdiau P
Inflammation, oxidative stress, and protease/protease inhibitor imbalance with excessive production of proteases are factors associated with pathogenesis of the chronic obstructive pulmonary disease (COPD). In this study, we report that kallikrein-related peptidase 5 (KLK5) is a crucial protease involved in extracellular matrix (ECM) remodeling and bronchial epithelial repair after injury. First, we showed that KLK5 degrades the basal layer formed by culture of primary bronchial epithelial cells... Abstract
Cited 13 times since 2021 (4.7 per year) source: EuropePMC
American journal of physiology. Lung cellular and molecular physiology, Volume 321, Issue 4, 11 2 2021, Pages L775-L786 Disease modeling following organoid-based expansion of airway epithelial cells. Eenjes E, van Riet S, Kroon AA, Slats AM, Khedoe PPSJ, Boerema-de Munck A, Buscop-van Kempen M, Ninaber DK, Reiss IKM, Clevers H, Rottier RJ, Hiemstra PS
Air-liquid interface (ALI) cultures are frequently used in lung research but require substantial cell numbers that cannot readily be obtained from patients. We explored whether organoid expansion [three-dimensional (3D)] can be used to establish ALI cultures from clinical samples with low epithelial cell numbers. Airway epithelial cells were obtained from tracheal aspirates (TA) from preterm newborns and from bronchoalveolar lavage (BAL) or bronchial tissue (BT) from adults. TA and BAL cells wer... Abstract
Cited 1 times since 2021 (0.4 per year) source: EuropePMC
International journal of molecular sciences, Volume 22, Issue 15, 27 4 2021, Pages 8031 The Course of AαVal541 as a Proteinase 3 Specific Neo-Epitope after Alpha-1-Antitrypsin Augmentation in Severe Deficient Patients. Schouten IGM, Mumford RA, Moes DJAR, Hiemstra PS, Stolk J
In alpha-1-antitrypsin deficiency (AATD), neutrophil serine proteases such as elastase and proteinase 3 (PR3) are insufficiently inhibited. A previous study in AATD patients showed a higher plasma level of the specific PR3-generated fibrinogen-derived peptide AαVal541, compared with healthy controls. Here, we analyzed the course of AαVal541 plasma levels during 4 weeks after a single iv dose of 240 mg/kg AAT in ten patients with genotype Z/Rare or Rare/Rare. To this end, we developed an immunoas... Abstract
Cited 6 times since 2021 (2.1 per year) source: EuropePMC
Current opinion in pharmacology, Volume 59, 22 4 2021, Pages 85-94 Repairing damaged lungs using regenerative therapy. Khedoe PPPSJ, Wu X, Gosens R, Hiemstra PS
There is an urgent need for better treatment of lung diseases that are a major cause of morbidity and mortality worldwide. This urgency is illustrated by the current COVID-19 health crisis. Moderate-to-extensive lung injury characterizes several lung diseases, and not only therapies that reduce such lung injury are needed but also those that regenerate lung tissue and repair existing lung injury. At present, such therapies are not available, but as a result of a rapid increase in our understandi... Abstract
Cited 7 times since 2021 (2.4 per year) source: EuropePMC
Scientific reports, Volume 11, Issue 1, 18 3 2021, Pages 12848 Gender specific airway gene expression in COPD sub-phenotypes supports a role of mitochondria and of different types of leukocytes. Esteve-Codina A, Hofer TP, Burggraf D, Heiss-Neumann MS, Gesierich W, Boland A, Olaso R, Bihoreau MT, Deleuze JF, Moeller W, Schmid O, Soler Artigas M, Renner K, Hohlfeld JM, Welte T, Fuehner T, Jerrentrup L, Koczulla AR, Greulich T, Prasse A, Müller-Quernheim J, Gupta S, Brightling C, Subramanian DR, Parr DG, Kolsum U, Gupta V, Barta I, Döme B, Strausz J, Stendardo M, Piattella M, Boschetto P, Korzybski D, Gorecka D, Nowinski A, Dabad M, Fernández-Callejo M, Endesfelder D, Zu Castell W, Hiemstra PS, Venge P, Noessner E, Griebel T, Heath S, Singh D, Gut I, Ziegler-Heitbrock L
Chronic obstructive pulmonary disease (COPD) is a destructive inflammatory disease and the genes expressed within the lung are crucial to its pathophysiology. We have determined the RNAseq transcriptome of bronchial brush cells from 312 stringently defined ex-smoker patients. Compared to healthy controls there were for males 40 differentially expressed genes (DEGs) and 73 DEGs for females with only 26 genes shared. The gene ontology (GO) term "response to bacterium" was shared, with se... Abstract
Cited 5 times since 2021 (1.7 per year) source: EuropePMC
Thorax, Volume 77, Issue 1, 10 2 2021, Pages 31-39 Bronchial gene expression signature associated with rate of subsequent FEV<sub>1</sub> decline in individuals with and at risk of COPD. Becker EJ, Faiz A, van den Berge M, Timens W, Hiemstra PS, Clark K, Liu G, Xiao X, Alekseyev YO, O'Connor G, Lam S, Spira A, Lenburg ME, Steiling K
Background: COPD is characterised by progressive lung function decline. Leveraging prior work demonstrating bronchial airway COPD-associated gene expression alterations, we sought to determine if there are alterations associated with differences in the rate of FEV1 decline. Methods: We examined gene expression among ever smokers with and without COPD who at baseline had bronchial brushings profiled by Affymetrix microarrays and had longitudinal lung function measurements (n=134; mean follow-up=6... Abstract
Frontiers in allergy, Volume 2, 8 2 2021, Pages 628400 Personalized Pollen Monitoring and Symptom Scores: A Feasibility Study in Grass Pollen Allergic Patients. de Weger LA, van Hal PTW, Bos B, Molster F, Mostert M, Hiemstra PS
Background: Pollen is a major trigger for allergic symptoms in sensitized individuals. Airborne pollen is usually monitored by Hirst type pollen samplers located at rooftop level, providing a general overview of the pollen distribution in the larger surroundings. In this feasibility study, grass pollen-sensitized subjects monitored the pollen in their direct environment using a portable pollen sampler (Pollensniffer) and scored their symptoms, to study the relation between symptom severity and p... Abstract
Cited 1 times since 2021 (0.3 per year) source: EuropePMC
ERJ open research, Volume 7, Issue 2, 1 1 2021, Pages 104-2021 Comparison of genome-wide gene expression profiling by RNA Sequencing <i>versus</i> microarray in bronchial biopsies of COPD patients before and after inhaled corticosteroid treatment: does it provide new insights? Ditz B, Boekhoudt JG, Aliee H, Theis FJ, Nawijn M, Brandsma CA, Hiemstra PS, Timens W, Tew GW, Grimbaldeston MA, Neighbors M, Guryev V, van den Berge M, Faiz A
More DEGs are detected by RNA-Seq than microarrays in COPD lung biopsies and are associated with immunological pathways. Performing bulk tissue cell-type deconvolution in microarray lung samples, using the SVR method, reflects RNA-Seq results. https://bit.ly/2N8sY3s. Abstract
Cited 8 times since 2021 (2.5 per year) source: EuropePMC
Membranes, Volume 11, Issue 3, 11 2 2021, Pages 197 Development of an In Vitro Airway Epithelial-Endothelial Cell Culture Model on a Flexible Porous Poly(Trimethylene Carbonate) Membrane Based on Calu-3 Airway Epithelial Cells and Lung Microvascular Endothelial Cells. Pasman T, Baptista D, van Riet S, Truckenmüller RK, Hiemstra PS, Rottier RJ, Hamelmann NM, Paulusse JMJ, Stamatialis D, Poot AA
Due to the continuing high impact of lung diseases on society and the emergence of new respiratory viruses, such as SARS-CoV-2, there is a great need for in vitro lung models that more accurately recapitulate the in vivo situation than current models based on lung epithelial cell cultures on stiff membranes. Therefore, we developed an in vitro airway epithelial-endothelial cell culture model based on Calu-3 human lung epithelial cells and human lung microvascular endothelial cells (LMVECs), cult... Abstract
Cited 7 times since 2020 (2 per year) source: EuropePMC
Membranes, Volume 10, Issue 11, 5 1 2020, Pages E330 Development of Porous and Flexible PTMC Membranes for In Vitro Organ Models Fabricated by Evaporation-Induced Phase Separation. Pasman T, Baptista D, van Riet S, Truckenmüller RK, Hiemstra PS, Rottier RJ, Stamatialis D, Poot AA
Polymeric membranes are widely applied in biomedical applications, including in vitro organ models. In such models, they are mostly used as supports on which cells are cultured to create functional tissue units of the desired organ. To this end, the membrane properties, e.g., morphology and porosity, should match the tissue properties. Organ models of dynamic (barrier) tissues, e.g., lung, require flexible, elastic and porous membranes. Thus, membranes based on poly (dimethyl siloxane) (PDMS) ar... Abstract
Cited 9 times since 2020 (2.5 per year) source: EuropePMC
Allergy, Volume 76, Issue 4, 15 3 2020, Pages 1123-1135 RAGE and TLR4 differentially regulate airway hyperresponsiveness: Implications for COPD. Allam VSRR, Faiz A, Lam M, Rathnayake SNH, Ditz B, Pouwels SD, Brandsma CA, Timens W, Hiemstra PS, Tew GW, Neighbors M, Grimbaldeston M, van den Berge M, Donnelly S, Phipps S, Bourke JE, Sukkar MB
Background: The receptor for advanced glycation end products (RAGE) and Toll-like receptor 4 (TLR4) is implicated in COPD. Although these receptors share common ligands and signalling pathways, it is not known whether they act in concert to drive pathological processes in COPD. We examined the impact of RAGE and/or TLR4 gene deficiency in a mouse model of COPD and also determined whether expression of these receptors correlates with airway neutrophilia and airway hyperresponsiveness (AHR) in COP... Abstract
Cited 18 times since 2020 (5 per year) source: EuropePMC
Biomaterials, Volume 266, 10 2 2020, Pages 120436 3D alveolar in vitro model based on epithelialized biomimetically curved culture membranes. Baptista D, Teixeira LM, Birgani ZT, van Riet S, Pasman T, Poot A, Stamatialis D, Rottier RJ, Hiemstra PS, Habibović P, van Blitterswijk C, Giselbrecht S, Truckenmüller R
There is increasing evidence that surface curvature at a near-cell-scale influences cell behaviour. Epithelial or endothelial cells lining small acinar or tubular body lumens, as those of the alveoli or blood vessels, experience such highly curved surfaces. In contrast, the most commonly used culture substrates for in vitro modelling of these human tissue barriers, ion track-etched membranes, offer only flat surfaces. Here, we propose a more realistic culture environment for alveolar cells based... Abstract
Cited 11 times since 2020 (2.9 per year) source: EuropePMC
The European respiratory journal, Volume 56, Issue 2, 20 3 2020, Pages 1902320 Host-microbe cross-talk in the lung microenvironment: implications for understanding and treating chronic lung disease. Gosens R, Hiemstra PS, Adcock IM, Bracke KR, Dickson RP, Hansbro PM, Krauss-Etschmann S, Smits HH, Stassen FRM, Bartel S
Chronic respiratory diseases are highly prevalent worldwide and will continue to rise in the foreseeable future. Despite intensive efforts over recent decades, the development of novel and effective therapeutic approaches has been slow. However, there is new and increasing evidence that communities of micro-organisms in our body, the human microbiome, are crucially involved in the development and progression of chronic respiratory diseases. Understanding the detailed mechanisms underlying this c... Abstract
Cited 43 times since 2020 (11.4 per year) source: EuropePMC
The Science of the total environment, Volume 749, 13 2 2020, Pages 141676 An emerging class of air pollutants: Potential effects of microplastics to respiratory human health? Amato-Lourenço LF, Dos Santos Galvão L, de Weger LA, Hiemstra PS, Vijver MG, Mauad T
It is increasingly recognized that the ubiquity of convenient single-use plastic has resulted in a global plastic pollution challenge, with substantial environmental and health consequences. Physical, chemical, and biological processes result in plastic weathering, with eventual formation of debris in the micro to nano size range. There is an increasing awareness that plastic fragments are dispersed in the air and can be inhaled by humans, which may cause adverse effects on the respiratory syste... Abstract
Cited 7 times since 2020 (1.8 per year) source: EuropePMC
American journal of respiratory and critical care medicine, Volume 202, Issue 3, 1 1 2020, Pages 312-313 Vitamin D Deficiency in Asthma and Chronic Obstructive Pulmonary Disease. A Chicken-or-Egg Story. Hiemstra PS, de Jongh RT
Cited 60 times since 2020 (15.7 per year) source: EuropePMC
Antimicrobial agents and chemotherapy, Volume 64, Issue 8, 22 4 2020, Pages e00900-20 Suramin Inhibits SARS-CoV-2 Infection in Cell Culture by Interfering with Early Steps of the Replication Cycle. Salgado-Benvindo C, Thaler M, Tas A, Ogando NS, Bredenbeek PJ, Ninaber DK, Wang Y, Hiemstra PS, Snijder EJ, van Hemert MJ
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic that originated in Wuhan, China, in December 2019 has impacted public health, society, the global economy, and the daily lives of billions of people in an unprecedented manner. There are currently no specific registered antiviral drugs to treat or prevent SARS-CoV-2 infections. Therefore, drug repurposing would be the fastest route to provide at least a temporary solution while better, more specific drugs are being develop... Abstract