Publications
Below you can find a list of our published research.
Below you can find a list of our published research.
440 results
Cited 3 times since 2022 (2.1 per year) source: EuropePMC
Journal of inflammation (London, England), Volume 19, Issue 1, 14 2 2022, Pages 26 Combination of IL-17A/F and TNF-α uniquely alters the bronchial epithelial cell proteome to enhance proteins that augment neutrophil migration. Altieri A, Piyadasa H, Hemshekhar M, Osawa N, Recksiedler B, Spicer V, Hiemstra PS, Halayko AJ, Mookherjee N
Background: The heterodimer interleukin (IL)-17A/F is elevated in the lungs in chronic respiratory disease such as severe asthma, along with the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). Although IL-17A/F and TNF-α are known to functionally cooperate to exacerbate airway inflammation, proteins altered by their interaction in the lungs are not fully elucidated. Results: We used Slow Off-rate Modified Aptamer-based proteomic array to identify proteins that are uniquely and/or syne... Abstract
Cited 5 times since 2022 (3.5 per year) source: EuropePMC
Thorax, Volume 78, Issue 4, 7 1 2022, Pages 335-343 Th2 high and mast cell gene signatures are associated with corticosteroid sensitivity in COPD. Faiz A, Pavlidis S, Kuo CH, Rowe A, Hiemstra PS, Timens W, Berg M, Wisman M, Guo YK, Djukanović R, Sterk P, Meyer KB, Nawijn MC, Adcock I, Chung KF, van den Berge M
Rationale: Severe asthma and chronic obstructive pulmonary disease (COPD) share common pathophysiological traits such as relative corticosteroid insensitivity. We recently published three transcriptome-associated clusters (TACs) using hierarchical analysis of the sputum transcriptome in asthmatics from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort comprising one Th2-high inflammatory signature (TAC1) and two Th2-low signatures (TAC2 and TAC3). Obje... Abstract
Cited 3 times since 2022 (2 per year) source: EuropePMC
Respirology (Carlton, Vic.), Volume 28, Issue 2, 22 4 2022, Pages 132-142 Smoking induces shifts in cellular composition and transcriptome within the bronchial mucus barrier. Rathnayake SNH, Ditz B, van Nijnatten J, Sadaf T, Hansbro PM, Brandsma CA, Timens W, van Schadewijk A, Hiemstra PS, Ten Hacken NHT, Oliver B, Kerstjens HAM, van den Berge M, Faiz A
Background and objective: Smoking disturbs the bronchial-mucus-barrier. This study assesses the cellular composition and gene expression shifts of the bronchial-mucus-barrier with smoking to understand the mechanism of mucosal damage by cigarette smoke exposure. We explore whether single-cell-RNA-sequencing (scRNA-seq) based cellular deconvolution (CD) can predict cell-type composition in RNA-seq data. Methods: RNA-seq data of bronchial biopsies from three cohorts were analysed using CD. The coh... Abstract
Cited 12 times since 2022 (8.1 per year) source: EuropePMC
eLife, Volume 11, 21 3 2022, Pages e82050 SARS-CoV-2-specific CD4<sup>+</sup> and CD8<sup>+</sup> T cell responses can originate from cross-reactive CMV-specific T cells. Pothast CR, Dijkland RC, Thaler M, Hagedoorn RS, Kester MGD, Wouters AK, Hiemstra PS, van Hemert MJ, Gras S, Falkenburg JHF, Heemskerk MHM
Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific CD4+ and CD8+ T cells in SARS-CoV-2-unexposed donors has been explained by the presence of T cells primed by other coronaviruses. However, based on the relatively high frequency and prevalence of cross-reactive T cells, we hypothesized cytomegalovirus (CMV) may induce these cross-reactive T cells. Stimulation of pre-pandemic cryo-preserved peripheral blood mononuclear cells (PBMCs) with SARS-CoV-2 peptides reveale... Abstract
Cited 3 times since 2022 (1.9 per year) source: EuropePMC
Microbiome, Volume 10, Issue 1, 19 3 2022, Pages 175 The lower airways microbiota and antimicrobial peptides indicate dysbiosis in sarcoidosis. Knudsen KS, Lehmann S, Nielsen R, Tangedal S, Paytuvi-Gallart A, Sanseverino W, Martinsen EMH, Hiemstra PS, Eagan TM
Background: The role of the pulmonary microbiome in sarcoidosis is unknown. The objectives of this study were the following: (1) examine whether the pulmonary fungal and bacterial microbiota differed in patients with sarcoidosis compared with controls; (2) examine whether there was an association between the microbiota and levels of the antimicrobial peptides (AMPs) in protected bronchoalveolar lavage (PBAL). Methods: Thirty-five sarcoidosis patients and 35 healthy controls underwent bronchoscop... Abstract
Cited 1 times since 2022 (0.6 per year) source: EuropePMC
Antioxidants (Basel, Switzerland), Volume 11, Issue 10, 12 2 2022, Pages 2018 Cigarette Smoke Impairs Airway Epithelial Wound Repair: Role of Modulation of Epithelial-Mesenchymal Transition Processes and Notch-1 Signaling. Di Vincenzo S, Ninaber DK, Cipollina C, Ferraro M, Hiemstra PS, Pace E
Cigarette smoke (CS) induces oxidative stress and chronic inflammation in airway epithelium. It is a major risk factor for respiratory diseases, characterized by epithelial injury. The impact of CS on airway epithelial repair, which involves epithelial-mesenchymal transition (EMT) and the Notch-1 pathway, is incompletely understood. In this study, we used primary bronchial epithelial cells (PBECs) to evaluate the effect of CS on epithelial repair and these mechanisms. The effect of CS and/or TGF... Abstract
Cited 3 times since 2022 (1.8 per year) source: EuropePMC
Respiratory research, Volume 23, Issue 1, 2 1 2022, Pages 227 Early transcriptional responses of bronchial epithelial cells to whole cigarette smoke mirror those of in-vivo exposed human bronchial mucosa. van der Does AM, Mahbub RM, Ninaber DK, Rathnayake SNH, Timens W, van den Berge M, Aliee H, Theis FJ, Nawijn MC, Hiemstra PS, Faiz A
Background: Despite the well-known detrimental effects of cigarette smoke (CS), little is known about the complex gene expression dynamics in the early stages after exposure. This study aims to investigate early transcriptomic responses following CS exposure of airway epithelial cells in culture and compare these to those found in human CS exposure studies. Methods: Primary bronchial epithelial cells (PBEC) were differentiated at the air-liquid interface (ALI) and exposed to whole CS. Bulk RNA-s... Abstract
Cellular and molecular life sciences : CMLS, Volume 79, Issue 9, 1 1 2022, Pages 503 Keratin 8 is a scaffolding and regulatory protein of ERAD complexes. Pranke IM, Chevalier B, Premchandar A, Baatallah N, Tomaszewski KF, Bitam S, Tondelier D, Golec A, Stolk J, Lukacs GL, Hiemstra PS, Dadlez M, Lomas DA, Irving JA, Delaunay-Moisan A, van Anken E, Hinzpeter A, Sermet-Gaudelus I, Edelman A
Early recognition and enhanced degradation of misfolded proteins by the endoplasmic reticulum (ER) quality control and ER-associated degradation (ERAD) cause defective protein secretion and membrane targeting, as exemplified for Z-alpha-1-antitrypsin (Z-A1AT), responsible for alpha-1-antitrypsin deficiency (A1ATD) and F508del-CFTR (cystic fibrosis transmembrane conductance regulator) responsible for cystic fibrosis (CF). Prompted by our previous observation that decreasing Keratin 8 (K8) express... Abstract
Clinical and translational allergy, Volume 12, Issue 8, 1 1 2022, Pages e12173 Association of bronchial steroid inducible methylation quantitative trait loci with asthma and chronic obstructive pulmonary disease treatment response. Slob EMA, Faiz A, van Nijnatten J, Vijverberg SJH, Longo C, Kutlu M, Chew FT, Sio YY, Herrera-Luis E, Espuela-Ortiz A, Perez-Garcia J, Pino-Yanes M, Burchard EG, Potočnik U, Gorenjak M, Palmer C, Maroteau C, Turner S, Verhamme K, Karimi L, Mukhopadhyay S, Timens W, Hiemstra PS, Pijnenburg MW, Neighbors M, Grimbaldeston MA, Tew GW, Brandsma CA, Berce V, Aliee H, Theis F, Sin DD, Li X, van den Berge M, Maitland-van der Zee AH, Koppelman GH
Cited 9 times since 2022 (5 per year) source: EuropePMC
The American journal of clinical nutrition, Volume 116, Issue 2, 1 1 2022, Pages 491-499 Vitamin D supplementation in chronic obstructive pulmonary disease patients with low serum vitamin D: a randomized controlled trial. Rafiq R, Aleva FE, Schrumpf JA, Daniels JM, Bet PM, Boersma WG, Bresser P, Spanbroek M, Lips P, van den Broek TJ, Keijser BJF, van der Ven AJAM, Hiemstra PS, den Heijer M, de Jongh RT, PRECOVID-study group
Background: Vitamin D deficiency is frequently found in patients with chronic obstructive pulmonary disease (COPD). Vitamin D has antimicrobial, anti-inflammatory, and immunomodulatory effects. Therefore, supplementation may prevent COPD exacerbations, particularly in deficient patients. Objectives: We aimed to assess the effect of vitamin D supplementation on exacerbation rate in vitamin D-deficient patients with COPD. Methods: We performed a multicenter, double-blind, randomized controlled tri... Abstract
Cited 1 times since 2022 (0.5 per year) source: EuropePMC
International journal of molecular sciences, Volume 23, Issue 14, 13 2 2022, Pages 7749 miR449 Protects Airway Regeneration by Controlling AURKA/HDAC6-Mediated Ciliary Disassembly. Wildung M, Herr C, Riedel D, Wiedwald C, Moiseenko A, Ramírez F, Tasena H, Heimerl M, Alevra M, Movsisyan N, Schuldt M, Volceanov-Hahn L, Provoost S, Nöthe-Menchen T, Urrego D, Freytag B, Wallmeier J, Beisswenger C, Bals R, van den Berge M, Timens W, Hiemstra PS, Brandsma CA, Maes T, Andreas S, Heijink IH, Pardo LA, Lizé M
Airway mucociliary regeneration and function are key players for airway defense and are impaired in chronic obstructive pulmonary disease (COPD). Using transcriptome analysis in COPD-derived bronchial biopsies, we observed a positive correlation between cilia-related genes and microRNA-449 (miR449). In vitro, miR449 was strongly increased during airway epithelial mucociliary differentiation. In vivo, miR449 was upregulated during recovery from chemical or infective insults. miR0449-/- mice (both... Abstract
Cited 11 times since 2022 (5.4 per year) source: EuropePMC
The EMBO journal, Volume 41, Issue 12, 4 1 2022, Pages e108306 Host succinate inhibits influenza virus infection through succinylation and nuclear retention of the viral nucleoprotein. Guillon A, Brea-Diakite D, Cezard A, Wacquiez A, Baranek T, Bourgeais J, Picou F, Vasseur V, Meyer L, Chevalier C, Auvet A, Carballido JM, Nadal Desbarats L, Dingli F, Turtoi A, Le Gouellec A, Fauvelle F, Donchet A, Crépin T, Hiemstra PS, Paget C, Loew D, Herault O, Naffakh N, Le Goffic R, Si-Tahar M
Influenza virus infection causes considerable morbidity and mortality, but current therapies have limited efficacy. We hypothesized that investigating the metabolic signaling during infection may help to design innovative antiviral approaches. Using bronchoalveolar lavages of infected mice, we here demonstrate that influenza virus induces a major reprogramming of lung metabolism. We focused on mitochondria-derived succinate that accumulated both in the respiratory fluids of virus-challenged mice... Abstract
Cited 16 times since 2022 (7.8 per year) source: EuropePMC
ACS biomaterials science & engineering, Volume 8, Issue 6, 3 1 2022, Pages 2684-2699 3D Lung-on-Chip Model Based on Biomimetically Microcurved Culture Membranes. Baptista D, Moreira Teixeira L, Barata D, Tahmasebi Birgani Z, King J, van Riet S, Pasman T, Poot AA, Stamatialis D, Rottier RJ, Hiemstra PS, Carlier A, van Blitterswijk C, Habibović P, Giselbrecht S, Truckenmüller R
A comparatively straightforward approach to accomplish more physiological realism in organ-on-a-chip (OoC) models is through substrate geometry. There is increasing evidence that the strongly, microscale curved surfaces that epithelial or endothelial cells experience when lining small body lumens, such as the alveoli or blood vessels, impact their behavior. However, the most commonly used cell culture substrates for modeling of these human tissue barriers in OoCs, ion track-etched porous membran... Abstract
Cited 1 times since 2022 (0.5 per year) source: EuropePMC
Scientific reports, Volume 12, Issue 1, 4 1 2022, Pages 5610 High miR203a-3p and miR-375 expression in the airways of smokers with and without COPD. van Nijnatten J, Brandsma CA, Steiling K, Hiemstra PS, Timens W, van den Berge M, Faiz A
Smoking is a leading cause of chronic obstructive pulmonary disease (COPD). It is known to have a significant impact on gene expression and (inflammatory) cell populations in the airways involved in COPD pathogenesis. In this study, we investigated the impact of smoking on the expression of miRNAs in healthy and COPD individuals. We aimed to elucidate the overall smoking-induced miRNA changes and those specific to COPD. In addition, we investigated the downstream effects on regulatory gene expre... Abstract
Cited 6 times since 2022 (2.8 per year) source: EuropePMC
Disease models & mechanisms, Volume 15, Issue 3, 28 4 2022, Pages dmm049247 Dysregulated mitochondrial metabolism upon cigarette smoke exposure in various human bronchial epithelial cell models. Tulen CBM, Wang Y, Beentjes D, Jessen PJJ, Ninaber DK, Reynaert NL, van Schooten FJ, Opperhuizen A, Hiemstra PS, Remels AHV
Exposure to cigarette smoke (CS) is the primary risk factor for developing chronic obstructive pulmonary disease. The impact of CS exposure on the molecular mechanisms involved in mitochondrial quality control in airway epithelial cells is incompletely understood. Undifferentiated or differentiated primary bronchial epithelial cells were acutely/chronically exposed to whole CS (WCS) or CS extract (CSE) in submerged or air-liquid interface conditions. Abundance of key regulators controlling mitoc... Abstract
Cited 28 times since 2022 (13 per year) source: EuropePMC
European respiratory review : an official journal of the European Respiratory Society, Volume 31, Issue 163, 23 4 2022, Pages 210112 Role of air pollutants in airway epithelial barrier dysfunction in asthma and COPD. Aghapour M, Ubags ND, Bruder D, Hiemstra PS, Sidhaye V, Rezaee F, Heijink IH
Chronic exposure to environmental pollutants is a major contributor to the development and progression of obstructive airway diseases, including asthma and COPD. Understanding the mechanisms underlying the development of obstructive lung diseases upon exposure to inhaled pollutants will lead to novel insights into the pathogenesis, prevention and treatment of these diseases. The respiratory epithelial lining forms a robust physicochemical barrier protecting the body from inhaled toxic particles... Abstract
Cited 2 times since 2022 (0.9 per year) source: EuropePMC
Pathogens (Basel, Switzerland), Volume 11, Issue 3, 11 2 2022, Pages 340 Performance of Five Metagenomic Classifiers for Virus Pathogen Detection Using Respiratory Samples from a Clinical Cohort. Carbo EC, Sidorov IA, van Rijn-Klink AL, Pappas N, van Boheemen S, Mei H, Hiemstra PS, Eagan TM, Claas ECJ, Kroes ACM, de Vries JJC
Viral metagenomics is increasingly applied in clinical diagnostic settings for detection of pathogenic viruses. While several benchmarking studies have been published on the use of metagenomic classifiers for abundance and diversity profiling of bacterial populations, studies on the comparative performance of the classifiers for virus pathogen detection are scarce. In this study, metagenomic data sets (n = 88) from a clinical cohort of patients with respiratory complaints were used for compariso... Abstract
Cited 15 times since 2022 (6.6 per year) source: EuropePMC
American journal of physiology. Lung cellular and molecular physiology, Volume 322, Issue 4, 9 2 2022, Pages L526-L538 Organoid-based expansion of patient-derived primary alveolar type 2 cells for establishment of alveolus epithelial Lung-Chip cultures. van Riet S, van Schadewijk A, Khedoe PPSJ, Limpens RWAL, Bárcena M, Stolk J, Hiemstra PS, van der Does AM
Development of effective treatment strategies for lung tissue destruction as seen in emphysema would greatly benefit from representative human in vitro models of the alveolar compartment. Studying how cellular cross talk and/or (altered) biomechanical cues affect alveolar epithelial function could provide new insight for tissue repair strategies. Preclinical models of the alveolus ideally combine human primary patient-derived lung cells with advanced cell culture applications such as breathing-r... Abstract
COPD, Volume 19, Issue 1, 4 1 2022, Pages 81-87 The Microbiome in Bronchial Biopsies from Smokers and Ex-Smokers with Stable COPD - A Metatranscriptomic Approach. Ditz B, Boekhoudt J, Couto N, Brandsma CA, Hiemstra PS, Tew GW, Neighbors M, Grimbaldeston MA, Timens W, Kerstjens HAM, Rossen JWA, Guryev V, van den Berge M, Faiz A
Current knowledge about the respiratory microbiome is mainly based on 16S ribosomal RNA gene sequencing. Newer sequencing approaches, such as metatranscriptomics, offer the technical ability to measure the viable microbiome response to environmental conditions such as smoking as well as to explore its functional role by investigating host-microbiome interactions. However, knowledge about its feasibility in respiratory microbiome research, especially in lung biopsies, is still very limited. RNA s... Abstract
Cited 7 times since 2022 (3 per year) source: EuropePMC
The European respiratory journal, Volume 59, Issue 1, 27 4 2022, Pages 2100267 Novel insights into surfactant protein C trafficking revealed through the study of a pathogenic mutant. Dickens JA, Rutherford EN, Abreu S, Chambers JE, Ellis MO, van Schadewijk A, Hiemstra PS, Marciniak SJ
Background: Alveolar epithelial cell dysfunction plays an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), but remains incompletely understood. Some monogenic forms of pulmonary fibrosis are associated with expression of mutant surfactant protein C (SFTPC). The commonest pathogenic mutant, I73T, mislocalises to the alveolar epithelial cell plasma membrane and displays a toxic gain of function. Because the mechanisms explaining the link between this mutant and IPF are in... Abstract