Research

Publications

Below you can find a list of our published research.

431 results

The European respiratory journal, Volume 62, Issue 3, 28 4 2023, Pages 2301301 Oxidation alters IL-33 function: new insights in the biology of different forms of IL-33 and their relevance for COPD. Hiemstra PS, Heijink IH

Abstract

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 26 4 2023 Visceral adipose tissue: A relevant inflammatory compartment in obesity-related asthma? Türk Y, Witte JA, van Huisstede A, Melgert BN, van Schadewijk A, Taube C, Hiemstra PS, Kappen JH, Braunstahl GJ

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Nature genetics, 25 4 2023 Author Correction: Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk. Shrine N, Izquierdo AG, Chen J, Packer R, Hall RJ, Guyatt AL, Batini C, Thompson RJ, Pavuluri C, Malik V, Hobbs BD, Moll M, Kim W, Tal-Singer R, Bakke P, Fawcett KA, John C, Coley K, Piga NN, Pozarickij A, Lin K, Millwood IY, Chen Z, Li L, China Kadoorie Biobank Collaborative Group, Wijnant SRA, Lahousse L, Brusselle G, Uitterlinden AG, Manichaikul A, Oelsner EC, Rich SS, Barr RG, Kerr SM, Vitart V, Brown MR, Wielscher M, Imboden M, Jeong A, Bartz TM, Gharib SA, Flexeder C, Karrasch S, Gieger C, Peters A, Stubbe B, Hu X, Ortega VE, Meyers DA, Bleecker ER, Gabriel SB, Gupta N, Smith AV, Luan J, Zhao JH, Hansen AF, Langhammer A, Willer C, Bhatta L, Porteous D, Smith BH, Campbell A, Sofer T, Lee J, Daviglus ML, Yu B, Lim E, Xu H, O'Connor GT, Thareja G, Albagha OME, Qatar Genome Program Research (QGPR) Consortium, Suhre K, Granell R, Faquih TO, Hiemstra PS, Slats AM, Mullin BH, Hui J, James A, Beilby J, Patasova K, Hysi P, Koskela JT, Wyss AB, Jin J, Sikdar S, Lee M, May-Wilson S, Pirastu N, Kentistou KA, Joshi

Abstract

American journal of respiratory and critical care medicine, 14 2 2023 IL-33 Expression Is Lower in Current Smokers at Both Transcriptomic and Protein Level. Faiz A, Mahbub RM, Boedijono FS, Tomassen MI, Kooistra W, Timens W, Nawijn M, Hansbro PM, Johansen MD, Pouwels SD, Heijink IH, Massip F, de Biase MS, Schwarz RF, Adcock IM, Chung KF, van der Does A, Hiemstra PS, Goulaouic H, Xing H, Abdulai R, de Rinaldis E, Cunoosamy D, Harel S, Lederer D, Nivens MC, Wark PA, Kerstjens HAM, Hylkema MN, Brandsma CA, van den Berge M, Cambridge Lung Cancer Early Detection Programme

Introduction: IL-33 is a pro-inflammatory cytokine thought to play a role in the pathogenesis of asthma and COPD. A recent clinical trial using the anti-IL33 antibody showed a reduction in exacerbation and improved lung function in ex-smokers but not current smokers with COPD. In this study, we aimed to understand the effects of smoking status on IL-33. Methods: We investigated the association of smoking status with the level of gene expression of IL33 in the airways in eight independent transcr... Abstract

Respiratory research, Volume 24, Issue 1, 23 4 2023, Pages 207 Acute cigarette smoke exposure leads to higher viral infection in human bronchial epithelial cultures by altering interferon, glycolysis and GDF15-related pathways. Wang Y, Ninaber DK, Faiz A, van der Linden AC, van Schadewijk A, Lutter R, Hiemstra PS, van der Does AM, Ravi A

Background: Acute exacerbations of chronic inflammatory lung diseases, such as chronic obstructive pulmonary disease (COPD), are frequently associated with rhinovirus (RV) infections. Despite these associations, the pathogenesis of virus-induced exacerbations is incompletely understood. We aimed to investigate effects of cigarette smoke (CS), a primary risk factor for COPD, on RV infection in airway epithelium and identify novel mechanisms related to these effects. Methods: Primary bronchial epi... Abstract

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, Volume 34, Issue 8, 1 1 2023, Pages e14008 Farm dust reduces mucin production in rhinovirus-infected primary bronchial epithelial cells. Schrumpf JA, Ninaber DK, Müller C, Rankl B, von Mutius E, Smits HH, Hiemstra PS

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Materials today. Bio, Volume 21, 27 4 2023, Pages 100713 Breathing on chip: Dynamic flow and stretch accelerate mucociliary maturation of airway epithelium in vitro. Nawroth JC, Roth D, van Schadewijk A, Ravi A, Maulana TI, Senger CN, van Riet S, Ninaber DK, de Waal AM, Kraft D, Hiemstra PS, Ryan AL, van der Does AM

Human lung function is intricately linked to blood flow and breathing cycles, but it remains unknown how these dynamic cues shape human airway epithelial biology. Here we report a state-of-the-art protocol for studying the effects of dynamic medium and airflow as well as stretch on human primary airway epithelial cell differentiation and maturation, including mucociliary clearance, using an organ-on-chip device. Perfused epithelial cell cultures displayed accelerated maturation and polarization... Abstract

Cited 1 times since 2023 (2.8 per year) source: EuropePMC

Journal of visualized experiments : JoVE, Issue 195, 26 4 2023 Isolating Bronchial Epithelial Cells from Resected Lung Tissue for Biobanking and Establishing Well-Differentiated Air-Liquid Interface Cultures. Ninaber DK, van der Does AM, Hiemstra PS

The airway epithelial cell layer forms the first barrier between lung tissue and the outside environment and is thereby constantly exposed to inhaled substances, including infectious agents and air pollutants. The airway epithelial layer plays a central role in a large variety of acute and chronic lung diseases, and various treatments targeting this epithelium are administered by inhalation. Understanding the role of epithelium in pathogenesis and how it can be targeted for therapy requires robu... Abstract

Cited 1 times since 2023 (2.5 per year) source: EuropePMC

Respiratory research, Volume 24, Issue 1, 11 2 2023, Pages 130 Smoking increases expression of the SARS-CoV-2 spike protein-binding long ACE2 isoform in bronchial epithelium. Pouwels SD, van den Berge M, Vasse GF, Timens W, Brandsma CA, Aliee H, Hiemstra PS, Guryev V, Faiz A

After more than two years the COVID-19 pandemic, that is caused by infection with the respiratory SARS-CoV-2 virus, is still ongoing. The risk to develop severe COVID-19 upon SARS-CoV-2 infection is increased in individuals with a high age, high body mass index, and who are smoking. The SARS-CoV-2 virus infects cells of the upper respiratory tract by entering these cells upon binding to the Angiotensin-converting enzyme 2 (ACE2) receptor. ACE2 is expressed in various cell types in the lung but t... Abstract

Cited 1 times since 2023 (1.9 per year) source: EuropePMC

Journal of innate immunity, 25 4 2023 Impact of changes in human airway epithelial cellular composition and differentiation on SARS-CoV-2 infection biology. Thaler M, Wang Y, van der Does AM, Faiz A, Ninaber DK, Ogando NS, Beckert H, Taube C, Salgado-Benvindo C, Snijder EJ, Bredenbeek PJ, Hiemstra PS, van Hemert MJ

The consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can range from asymptomatic to fatal disease. Variations in epithelial susceptibility to SARS-CoV-2 infection depend on the anatomical location from the proximal to distal respiratory tract. However, the cellular biology underlying these variations is not completely understood. Thus, air-liquid interface (ALI) cultures of well-differentiated primary human tracheal and bronchial epithelial cells were e... Abstract

Cited 5 times since 2023 (8.9 per year) source: EuropePMC

Nature genetics, Volume 55, Issue 3, 13 2 2023, Pages 410-422 Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk. Shrine N, Izquierdo AG, Chen J, Packer R, Hall RJ, Guyatt AL, Batini C, Thompson RJ, Pavuluri C, Malik V, Hobbs BD, Moll M, Kim W, Tal-Singer R, Bakke P, Fawcett KA, John C, Coley K, Piga NN, Pozarickij A, Lin K, Millwood IY, Chen Z, Li L, China Kadoorie Biobank Collaborative Group, Wijnant SRA, Lahousse L, Brusselle G, Uitterlinden AG, Manichaikul A, Oelsner EC, Rich SS, Barr RG, Kerr SM, Vitart V, Brown MR, Wielscher M, Imboden M, Jeong A, Bartz TM, Gharib SA, Flexeder C, Karrasch S, Gieger C, Peters A, Stubbe B, Hu X, Ortega VE, Meyers DA, Bleecker ER, Gabriel SB, Gupta N, Smith AV, Luan J, Zhao JH, Hansen AF, Langhammer A, Willer C, Bhatta L, Porteous D, Smith BH, Campbell A, Sofer T, Lee J, Daviglus ML, Yu B, Lim E, Xu H, O'Connor GT, Thareja G, Albagha OME, Qatar Genome Program Research (QGPR) Consortium, Suhre K, Granell R, Faquih TO, Hiemstra PS, Slats AM, Mullin BH, Hui J, James A, Beilby J, Patasova K, Hysi P, Koskela JT, Wyss AB, Jin J, Sikdar S, Lee M, May-Wilson S, Pirastu N, Kentistou KA, Joshi

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking... Abstract

Cited 1 times since 2022 (1.2 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

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 2 times since 2022 (2.3 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 3 times since 2022 (3.5 per year) source: EuropePMC

eLife, Volume 11, 21 3 2022, Pages e82050 SARS-CoV-2-specific CD4+ and CD8+ 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 1 times since 2022 (1 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

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 1 times since 2022 (0.9 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

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