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3. Clinical effects of the three CFTR potentiator treatments curcumin, genistein and ivacaftor in patients with the CFTR-S1251N gating mutation

Author

Berkers, Gitte, van der Meer, Renske, van Mourik, Peter, Vonk, Annelotte M, Kruisselbrink, Evelien, Suen, Sylvia WF, Heijerman, Harry GM, Majoor, Christof J, Koppelman, Gerard H, Roukema, Jolt, Janssens, Hettie M, de Rijke, Yolanda B, Kemper, E. Marleen, Beekman, Jeffrey M, van der Ent, Cornelis K, and de Jonge, Hugo R

Published
2020
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9. Real‐life efficacy and safety of elexacaftor/tezacaftor/ivacaftor on severe cystic fibrosis lung disease patients.

Author

Kos, Renate, Neerincx, Anne H., Fenn, Dominic W., Brinkman, Paul, Lub, Rianne, Vonk, Steffie E. M., Roukema, Jolt, Reijers, Monique H., Terheggen‐Lagro, Suzanne W. J., Altenburg, Josje, Majoor, Christof J., Bos, Lieuwe D., Haarman, Eric G., and Maitland‐van der Zee, Anke H.

Subjects
PULMONARY fibrosis, CYSTIC fibrosis, LUNGS, LUNG diseases, WILCOXON signed-rank test
Abstract

Elexacaftor/tezacaftor/ivacaftor (ETI) is a cystic fibrosis (CF) transmembrane conductance regulator modulator, which has shown efficacy in CF patients (≥6 years) with ≥1 Phe508del mutation and a minimal function mutation. In October 2019, ETI became available on compassionate use basis for Dutch CF patients with severe lung disease. Our objective was to investigate safety and efficacy of ETI in this patient group in a real‐life setting. A multicenter longitudinal observational study was conducted to examine changes in FEV1, BMI, and adverse events at initiation and 1, 3, 6, and 12 months after starting ETI. The number of exacerbations was recorded in the 12 months before and the 12 months after ETI treatment. Patients eligible for compassionate use had a FEV1 <40% predicted. Wilcoxon signed‐rank test analyzed changes over time. Twenty subjects were included and followed up for up to 12 months after starting ETI. Treatment was well tolerated with mild side effects reported, namely, rash (15%) and stomach ache (20%) with 80% resolving within 1 month. Mean absolute increase of FEV1 was 11.8/13.7% (p ≤.001) and BMI was 0.49/1.87 kg/m2 (p <.001–0.02) after 1/12 months, respectively. In comparison to the number of exacerbations pretrial, there was a marked reduction in exacerbations after initiation. Our findings show long‐term effects of treatment with ETI in patients with severe CF lung disease in a real‐life setting. Treatment with ETI is associated with increased lung function and BMI, less exacerbations, and only mild side effects. [ABSTRACT FROM AUTHOR]

Published
2022
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10. Lumacaftor/ivacaftor changes the lung microbiome and metabolome in cystic fibrosis patients

Author

Neerincx, Anne H., Whiteson, Katrine, Phan, Joann L., Brinkman, Paul, Abdel-Aziz, Mahmoud I., Weersink, Els J.M., Altenburg, Josje, Majoor, Christof J., Maitland-van der Zee, Anke H., Bos, Lieuwe D.J., Haarman, E., Rutjes, N. W., Terheggen-Lagro, S. W.J., Seljogi, D., Kemper, E. M., Lutter, R., Vijverberg, S. J., Vonk, S. E.M., Adriaens, N., Lub, R., van Brederode, M., van der Schaaf, L., Verkleij, M., van Gilst, N. A., Hofsteenge, G. H., Brackel, C. L.H., Lakeman, P., Bon, I. C.M., Tanner, S. P.M., Sterk, P. J., Longo, C., Sinha, A., Fenn, D., Lammers, A., Richards, L. B., van Bragt, J. M., Kos, R., Dagelet, J. W.F., Lone-Latif, S. J.A., Schultz, M. J., Smit, M. R., Hagens, L. A., Pulmonary medicine, Pediatrics, Amsterdam Reproduction & Development (AR&D), Psychiatry, CCA - Cancer biology and immunology, Pulmonology, AII - Inflammatory diseases, Graduate School, APH - Personalized Medicine, Paediatric Pulmonology, Intensive Care Medicine, and ACS - Heart failure & arrhythmias

Subjects
Pulmonary and Respiratory Medicine, Lung microbiome, medicine.medical_specialty, Cystic Fibrosis, medicine.disease_cause, Cystic fibrosis, Gastroenterology, Ivacaftor, 03 medical and health sciences, chemistry.chemical_compound, Internal medicine, Medicine, Microbiome, 030304 developmental biology, 0303 health sciences, 030306 microbiology, business.industry, Pseudomonas aeruginosa, Lumacaftor, Original Articles, medicine.disease, Epithelial fluid transport, chemistry, Sputum, medicine.symptom, business, medicine.drug
Abstract

Rationale Targeted cystic fibrosis (CF) therapy with lumacaftor/ivacaftor partly restores chloride channel function and improves epithelial fluid transport in the airways. Consequently, changes may occur in the microbiome, which is adapted to CF lungs. Objectives To investigate the effects of lumacaftor/ivacaftor on respiratory microbial composition and microbial metabolic activity by repeatedly sampling the lower respiratory tract. Methods This was a single-centre longitudinal observational cohort study in adult CF patients with a homozygous Phe508del mutation. Lung function measurements and microbial cultures of sputum were performed as part of routine care. An oral and nasal wash, and a breath sample, were collected before and every 3 months after starting therapy, for up to 12 months. Results Twenty patients were included in this study. Amplicon 16S RNA and metagenomics sequencing revealed that Pseudomonas aeruginosa was most abundant in sputum and seemed to decrease after 6 months of treatment, although this did not reach statistical significance after correction for multiple testing. Two types of untargeted metabolomics analyses in sputum showed a change in metabolic composition between 3 and 9 months that almost returned to baseline levels after 12 months of treatment. The volatile metabolic composition of breath was significantly different after 3 months and remained different from baseline until 12 months follow-up. Conclusions After starting CF transmembrane conductance regulator (CFTR) modulating treatment in CF patients with a homozygous Phe508del mutation, a temporary and moderate change in the lung microbiome is observed, which is mainly characterised by a reduction in the relative abundance of Pseudomonas aeruginosa., Lumacaftor/ivacaftor in adult cystic fibrosis patients with homozygous Phe508del results in temporal and moderate changes in lung microbiome and metabolome, that are mainly characterised by a reduction in the relative abundance of Pseudomonas aeruginosa https://bit.ly/3pcPUfX

Published
2021

11. Pulmonary embolism, myocardial infarction, and ischemic stroke in lung cancer patients: results from a longitudinal study

Author

van Herk-Sukel, Myrthe P.P., Shantakumar, Sumitra, Penning-van Beest, Fernie J.A., Kamphuisen, Pieter W., Majoor, Christof J., Overbeek, Lucy I.H., and Herings, Ron M.C.

Subjects
Stroke (Disease) -- Risk factors -- Research, Heart attack -- Risk factors -- Research, Pulmonary embolism -- Research, Lung cancer -- Complications and side effects -- Diagnosis -- Research -- Patient outcomes -- Control, Health
Abstract

Purpose In this cohort study, the rates of pulmonary embolism (PE), myocardial infarction (MI), and ischemic stroke (IS) before and after lung cancer (LC) diagnosis were compared to cancer-free controls. Methods Patients with LC during 2000-2007 were selected from PALGA, the Dutch Pathology Registry, and linked to the PHARMO medical record linkage system, including drug use and hospitalizations of 3 million inhabitants in the Netherlands. Included LC patients were matched 1:10 by age and gender to cancer-free controls. Hospitalizations for PE, MI, and IS were assessed in the 12 months before and after LC diagnosis. Results LC patients (N = 3,717) were six times more likely than cancer-free controls to have had a PE in the 12 months before diagnosis. After LC diagnosis, patients experienced an extremely increased risk of PE in the first 6 months (hazard ratio [HR] 16.8; 95 % confidence interval [CI] 7.6-36.8) compared with controls), which decreased to a five times increased risk (HR 5.1; 95 % CI 2.7-9.4) thereafter. However, there were less than two events per 100 person years during both time periods. LC patients receiving chemotherapy were eight times more likely to develop PE, whereas surgery increased the risk on PE three times. For MI and IS, no significant difference was observed compared with cancer-free controls before or after LC diagnosis. Conclusions LC patients have a higher risk of developing PE compared with cancer-free controls, although the frequency of PE hospitalizations was low. Surgery and chemotherapy were associated with an increased risk of PE. Keywords Ischemic stroke * Myocardial infarction * Non-small cell lung cancer * Pulmonary embolism * Risk * Small cell lung cancer, Introduction The association between cancer and thrombosis, especially venous thrombosis, is well established in the published literature [1-3]. Cancer patients are at increased risk of thromboembolic complications due to the [...]

Published
2013
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12. Quantitative Method for the Analysis of Ivacaftor, Hydroxymethyl Ivacaftor, Ivacaftor Carboxylate, Lumacaftor, and Tezacaftor in Plasma and Sputum Using Liquid Chromatography With Tandem Mass Spectrometry and Its Clinical Applicability

Author

Vonk, Steffie E. M., primary, van der Meer-Vos, Marloes, additional, Bos, Lieuwe D. J., additional, Neerincx, Anne H., additional, Majoor, Christof J., additional, Maitland-van der Zee, Anke-Hilse, additional, Mathôt, Ron A. A., additional, and Kemper, E. Marleen, additional

Published
2021
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13. Individual and group response of treatment with ivacaftor on airway and gut microbiota in people with cf and a s1251n mutation

Author

Kristensen, Maartje I., de Winter-De Groot, Karin M., Berkers, Gitte, Chu, Mei Ling J.N., Arp, Kayleigh, Ghijsen, Sophie, Heijerman, Harry G.M., Arets, Hubertus G.M., Majoor, Christof J., Janssens, Hettie M., van der Meer, Renske, Bogaert, Debby, van der Ent, Cornelis K., Kristensen, Maartje I., de Winter-De Groot, Karin M., Berkers, Gitte, Chu, Mei Ling J.N., Arp, Kayleigh, Ghijsen, Sophie, Heijerman, Harry G.M., Arets, Hubertus G.M., Majoor, Christof J., Janssens, Hettie M., van der Meer, Renske, Bogaert, Debby, and van der Ent, Cornelis K.

Abstract

Ivacaftor has been shown to restore the functionality of the S1251N (also known as c.3752G>A) mutated CFTR, which may cause alterations in both airway and gut physiology and micro-environment, resulting in a change of microbiota in these organs. The aim of the present study was to analyze the effects of ivacaftor on the microbial community composition of both airway and gut in subjects with CF carrying one S1251N mutation, using a 16S rRNA gene-based sequencing approach. In 16 subjects with CF, repetitive samples from airways and gut were collected just before, and 2 months after, and, for 8 patients, also 9 and 12 months after, start of ivacaftor. 16S rRNA based sequencing identified 344 operational taxonomical units (OTUs) in a total of 139 samples (35 nasopharyngeal, 39 oropharyngeal, 29 sputum, and 36 fecal samples). Ivacaftor significantly enhanced bacterial diversity and overall microbiota composition in the gut (p < 0.01). There were no significant changes in the overall microbial composition and alpha diversity in upper and lower airways of these patients after ivacaftor treatment. Treatment with ivacaftor induces changes in gut microbiota whereas airway microbiota do not change significantly over time.

Published
2021

14. Individual and Group Response of Treatment with Ivacaftor on Airway and Gut Microbiota in People with CF and a S1251N Mutation

Author

Child Health, Longziekten onderzoek 1, Klinische zorg, Longziekten patientenzorg, Longziekten, Infection & Immunity, Cluster B, Speerpunt Child Health, Kristensen, Maartje I, de Winter-de Groot, Karin M, Berkers, Gitte, Chu, Mei Ling J N, Arp, Kayleigh, Ghijsen, Sophie, Heijerman, Harry G M, Arets, Hubertus G M, Majoor, Christof J, Janssens, Hettie M, van der Meer, Renske, Bogaert, Debby, van der Ent, Cornelis K, Child Health, Longziekten onderzoek 1, Klinische zorg, Longziekten patientenzorg, Longziekten, Infection & Immunity, Cluster B, Speerpunt Child Health, Kristensen, Maartje I, de Winter-de Groot, Karin M, Berkers, Gitte, Chu, Mei Ling J N, Arp, Kayleigh, Ghijsen, Sophie, Heijerman, Harry G M, Arets, Hubertus G M, Majoor, Christof J, Janssens, Hettie M, van der Meer, Renske, Bogaert, Debby, and van der Ent, Cornelis K

Published
2021

15. Epidemiology of Mycobacterium bovis disease in humans, the Netherlands, 1993-2007

Author

Majoor, Christof J., Magis-Escurra, Cecile, van Ingen, Jakko, Boeree, Martin J., and van Soolingen, Dick

Subjects
DNA, Rheumatoid factor, Diseases -- Netherlands -- Development and progression -- Risk factors -- Care and treatment, Cross infection -- Development and progression -- Risk factors -- Care and treatment, Bacterial infections -- Development and progression -- Risk factors -- Care and treatment, Tuberculosis -- Development and progression -- Risk factors -- Care and treatment, Anti-infective agents, Food contamination, Ethambutol, Drug therapy, Combination, Nosocomial infections -- Development and progression -- Risk factors -- Care and treatment, Epidemiology, Rheumatoid arthritis -- Development and progression -- Risk factors -- Care and treatment, Health
Abstract

Mycobacterium bovis disease was common in the Western world in the era before pasteurization of milk products. In 1938, the percentage of M. bovis disease among all patients with tuberculosis [...]

Published
2011
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16. Individual and Group Response of Treatment with Ivacaftor on Airway and Gut Microbiota in People with CF and a S1251N Mutation

Author

Kristensen, Maartje I., primary, de Winter-de Groot, Karin M., additional, Berkers, Gitte, additional, Chu, Mei Ling J. N., additional, Arp, Kayleigh, additional, Ghijsen, Sophie, additional, Heijerman, Harry G. M., additional, Arets, Hubertus G. M., additional, Majoor, Christof J., additional, Janssens, Hettie M., additional, van der Meer, Renske, additional, Bogaert, Debby, additional, and van der Ent, Cornelis K., additional

Published
2021
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17. Systemic tryptophan and kynurenine catabolite levels relate to severity of rhinovirus-induced asthma exacerbation: a prospective study with a parallel-group design

Author

van der Sluijs, Koenraad F, van de Pol, Marianne A, Kulik, Wim, Dijkhuis, Annemiek, Smids, Barbara S, van Eijk, Hetty W, Karlas, Jos A, Molenkamp, Richard, Wolthers, Katja C, Johnston, Sebastian L, van der Zee, Jaring S, Sterk, Peter J, Lutter, René, Berger, Marieke, Fens, Niki, Yick, David, Wagener, Ariane H, Amelink, Marijke, Reesink, Herre J, Bresser, Paul, Kunst, Peter W A, Venekamp, Lisette N, Majoor, Christof J, van Steenwijk, Reindert P, and Jonkers, René E

Published
2013
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18. Clinical effects of the three CFTR potentiator treatments curcumin, genistein and ivacaftor in patients with the CFTR-S1251N gating mutation

Author

Longziekten onderzoek 1, Child Health, Beleid & Communicatie, CTI, Longziekten, Infection & Immunity, Longziekten onderzoek 2, Onderzoek, Regenerative Medicine and Stem Cells, Longziekten patientenzorg, Speerpunt Child Health, Berkers, Gitte, van der Meer, Renske, van Mourik, Peter, Vonk, Annelotte M, Kruisselbrink, Evelien, Suen, Sylvia Wf, Heijerman, Harry Gm, Majoor, Christof J, Koppelman, Gerard H, Roukema, Jolt, Janssens, Hettie M, de Rijke, Yolanda B, Kemper, E Marleen, Beekman, Jeffrey M, van der Ent, Cornelis K, de Jonge, Hugo R, Longziekten onderzoek 1, Child Health, Beleid & Communicatie, CTI, Longziekten, Infection & Immunity, Longziekten onderzoek 2, Onderzoek, Regenerative Medicine and Stem Cells, Longziekten patientenzorg, Speerpunt Child Health, Berkers, Gitte, van der Meer, Renske, van Mourik, Peter, Vonk, Annelotte M, Kruisselbrink, Evelien, Suen, Sylvia Wf, Heijerman, Harry Gm, Majoor, Christof J, Koppelman, Gerard H, Roukema, Jolt, Janssens, Hettie M, de Rijke, Yolanda B, Kemper, E Marleen, Beekman, Jeffrey M, van der Ent, Cornelis K, and de Jonge, Hugo R

Published
2020

22. Targeted exhaled breath analysis for detection of Pseudomonas aeruginosa in cystic fibrosis patients

Author

Kos, Renate, primary, Brinkman, Paul, additional, Neerincx, Anne H, additional, Paff, Tamara, additional, Gerritsen, Marije G, additional, Lammers, Ariane, additional, Kraneveld, Aletta D, additional, Heijerman, Harry G M, additional, Davies, Jane C, additional, Janssens, Hettie M, additional, Majoor, Christof J, additional, Weersink, Els J, additional, Sterk, Peter J, additional, Haarman, Eric G, additional, Bos, Lieuwe, additional, and Maitland-Van Der Zee, Anke H, additional

Published
2020
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25. Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis

Author

Berkers, Gitte, van Mourik, Peter, Vonk, Annelotte M, Kruisselbrink, Evelien, Dekkers, Johanna F, de Winter-de Groot, Karin M, Arets, Hubertus G M, Marck-van der Wilt, Rozemarijn E P, Dijkema, Jasper S, Vanderschuren, Maaike M, Houwen, Roderick H J, Heijerman, Harry G M, van de Graaf, Eduard A, Elias, Sjoerd G, Majoor, Christof J, Koppelman, Gerard H, Roukema, Jolt, Bakker, Marleen, Janssens, Hettie M, van der Meer, Renske, Vries, Robert G J, Clevers, Hans C, de Jonge, Hugo R, Beekman, Jeffrey M, van der Ent, Cornelis K, Berkers, Gitte, van Mourik, Peter, Vonk, Annelotte M, Kruisselbrink, Evelien, Dekkers, Johanna F, de Winter-de Groot, Karin M, Arets, Hubertus G M, Marck-van der Wilt, Rozemarijn E P, Dijkema, Jasper S, Vanderschuren, Maaike M, Houwen, Roderick H J, Heijerman, Harry G M, van de Graaf, Eduard A, Elias, Sjoerd G, Majoor, Christof J, Koppelman, Gerard H, Roukema, Jolt, Bakker, Marleen, Janssens, Hettie M, van der Meer, Renske, Vries, Robert G J, Clevers, Hans C, de Jonge, Hugo R, Beekman, Jeffrey M, and van der Ent, Cornelis K

Published
2019

26. Home videos of cystic fibrosis patients using tobramycin inhalation powder : Relation of flow and cough

Author

Meerburg, Jennifer J, Albasri, Mehdi, van der Wiel, Els C, Andrinopoulou, Eleni-Rosalina, van der Eerden, Menno M, Majoor, Christof J, Arets, Hubertus G M, Heijerman, Harry G M, Tiddens, Harm A W M, Meerburg, Jennifer J, Albasri, Mehdi, van der Wiel, Els C, Andrinopoulou, Eleni-Rosalina, van der Eerden, Menno M, Majoor, Christof J, Arets, Hubertus G M, Heijerman, Harry G M, and Tiddens, Harm A W M

Published
2019

27. Eosinophils capture viruses, a capacity that is defective in asthma

Author

Sabogal Piñeros, Yanaika S, Bal, Suzanne M, Dijkhuis, Annemiek, Majoor, Christof J, Dierdorp, Barbara S, Dekker, Tamara, Hoefsmit, Esmée P, Bonta, Peter I, Picavet, Daisy, van der Wel, Nicole N, Koenderman, Leo, Sterk, Peter J, Ravanetti, Lara, Lutter, René, Sabogal Piñeros, Yanaika S, Bal, Suzanne M, Dijkhuis, Annemiek, Majoor, Christof J, Dierdorp, Barbara S, Dekker, Tamara, Hoefsmit, Esmée P, Bonta, Peter I, Picavet, Daisy, van der Wel, Nicole N, Koenderman, Leo, Sterk, Peter J, Ravanetti, Lara, and Lutter, René

Published
2019

28. Home videos of cystic fibrosis patients using tobramycin inhalation powder: Relation of flow and cough

Author

Longziekten patientenzorg, Child Health, Longziekten, Infection & Immunity, Meerburg, Jennifer J, Albasri, Mehdi, van der Wiel, Els C, Andrinopoulou, Eleni-Rosalina, van der Eerden, Menno M, Majoor, Christof J, Arets, Hubertus G M, Heijerman, Harry G M, Tiddens, Harm A W M, Longziekten patientenzorg, Child Health, Longziekten, Infection & Immunity, Meerburg, Jennifer J, Albasri, Mehdi, van der Wiel, Els C, Andrinopoulou, Eleni-Rosalina, van der Eerden, Menno M, Majoor, Christof J, Arets, Hubertus G M, Heijerman, Harry G M, and Tiddens, Harm A W M

Published
2019

29. Eosinophils capture viruses, a capacity that is defective in asthma

Author

Experimentele Afdeling Longziekten, Cancer, Infection & Immunity, Sabogal Piñeros, Yanaika S, Bal, Suzanne M, Dijkhuis, Annemiek, Majoor, Christof J, Dierdorp, Barbara S, Dekker, Tamara, Hoefsmit, Esmée P, Bonta, Peter I, Picavet, Daisy, van der Wel, Nicole N, Koenderman, Leo, Sterk, Peter J, Ravanetti, Lara, Lutter, René, Experimentele Afdeling Longziekten, Cancer, Infection & Immunity, Sabogal Piñeros, Yanaika S, Bal, Suzanne M, Dijkhuis, Annemiek, Majoor, Christof J, Dierdorp, Barbara S, Dekker, Tamara, Hoefsmit, Esmée P, Bonta, Peter I, Picavet, Daisy, van der Wel, Nicole N, Koenderman, Leo, Sterk, Peter J, Ravanetti, Lara, and Lutter, René

Published
2019

30. Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis

Author

Longziekten onderzoek 1, Child Health, CTI, Longziekten patientenzorg, MDL, Longziekten, Infection & Immunity, Epi Kanker Team A, Cancer, JC onderzoeksprogramma Kanker, Hubrecht Institute with UMC, CMM Sectie Molecular Cancer Research, Regenerative Medicine and Stem Cells, Longziekten onderzoek 2, Onderzoek, Berkers, Gitte, van Mourik, Peter, Vonk, Annelotte M, Kruisselbrink, Evelien, Dekkers, Johanna F, de Winter-de Groot, Karin M, Arets, Hubertus G M, Marck-van der Wilt, Rozemarijn E P, Dijkema, Jasper S, Vanderschuren, Maaike M, Houwen, Roderick H J, Heijerman, Harry G M, van de Graaf, Eduard A, Elias, Sjoerd G, Majoor, Christof J, Koppelman, Gerard H, Roukema, Jolt, Bakker, Marleen, Janssens, Hettie M, van der Meer, Renske, Vries, Robert G J, Clevers, Hans C, de Jonge, Hugo R, Beekman, Jeffrey M, van der Ent, Cornelis K, Longziekten onderzoek 1, Child Health, CTI, Longziekten patientenzorg, MDL, Longziekten, Infection & Immunity, Epi Kanker Team A, Cancer, JC onderzoeksprogramma Kanker, Hubrecht Institute with UMC, CMM Sectie Molecular Cancer Research, Regenerative Medicine and Stem Cells, Longziekten onderzoek 2, Onderzoek, Berkers, Gitte, van Mourik, Peter, Vonk, Annelotte M, Kruisselbrink, Evelien, Dekkers, Johanna F, de Winter-de Groot, Karin M, Arets, Hubertus G M, Marck-van der Wilt, Rozemarijn E P, Dijkema, Jasper S, Vanderschuren, Maaike M, Houwen, Roderick H J, Heijerman, Harry G M, van de Graaf, Eduard A, Elias, Sjoerd G, Majoor, Christof J, Koppelman, Gerard H, Roukema, Jolt, Bakker, Marleen, Janssens, Hettie M, van der Meer, Renske, Vries, Robert G J, Clevers, Hans C, de Jonge, Hugo R, Beekman, Jeffrey M, and van der Ent, Cornelis K

Published
2019

31. Effect of C1‐inhibitor in adults with mild asthma: A randomized controlled trial

Author

Yang, Jack, primary, Engelen, Tjitske S. R., additional, Haak, Bastiaan W., additional, Bonta, Peter I., additional, Majoor, Christof J., additional, Veer, Cornelis, additional, Vos, Alex F., additional, Kemper, E. Marleen, additional, Lutter, René, additional, Mierlo, Gerard, additional, Zeerleder, Sacha S., additional, Bel, Elisabeth H., additional, and Poll, Tom, additional

Published
2019
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33. Eosinophils capture viruses, a capacity that is defective in asthma

Author

Sabogal Piñeros, Yanaika S., primary, Bal, Suzanne M., additional, Dijkhuis, Annemiek, additional, Majoor, Christof J., additional, Dierdorp, Barbara S., additional, Dekker, Tamara, additional, Hoefsmit, Esmée P., additional, Bonta, Peter I., additional, Picavet, Daisy, additional, van der Wel, Nicole N., additional, Koenderman, Leo, additional, Sterk, Peter J., additional, Ravanetti, Lara, additional, and Lutter, René, additional

Published
2019
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34. Anti–IL-5 in Mild Asthma Alters Rhinovirus-induced Macrophage, B-Cell, and Neutrophil Responses (MATERIAL). A Placebo-controlled, Double-Blind Study

Author

Sabogal Piñeros, Yanaika S., primary, Bal, Suzanne M., additional, van de Pol, Marianne A., additional, Dierdorp, Barbara S., additional, Dekker, Tamara, additional, Dijkhuis, Annemiek, additional, Brinkman, Paul, additional, van der Sluijs, Koen F., additional, Zwinderman, Aeilko H., additional, Majoor, Christof J., additional, Bonta, Peter I., additional, Ravanetti, Lara, additional, Sterk, Peter J., additional, and Lutter, René, additional

Published
2019
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35. Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis

Author

Berkers, Gitte, primary, van Mourik, Peter, additional, Vonk, Annelotte M., additional, Kruisselbrink, Evelien, additional, Dekkers, Johanna F., additional, de Winter-de Groot, Karin M., additional, Arets, Hubertus G.M., additional, Marck-van der Wilt, Rozemarijn E.P., additional, Dijkema, Jasper S., additional, Vanderschuren, Maaike M., additional, Houwen, Roderick H.J., additional, Heijerman, Harry G.M., additional, van de Graaf, Eduard A., additional, Elias, Sjoerd G., additional, Majoor, Christof J., additional, Koppelman, Gerard H., additional, Roukema, Jolt, additional, Bakker, Marleen, additional, Janssens, Hettie M., additional, van der Meer, Renske, additional, Vries, Robert G.J., additional, Clevers, Hans C., additional, de Jonge, Hugo R., additional, Beekman, Jeffrey M., additional, and van der Ent, Cornelis K., additional

Published
2019
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36. Intestinal Organoid Swelling And Relation With Disease Severity And Response To Therapy

Author

Berkers, Gitte, de Winter-de Groot, Karin M., Dekkers, Johanna F., Vonk, Annelotte M., Kruisselbrink, Evelien, Hagemeijer, Marne C., Heida-Michel, Sabine, Geerdink, Margot, Arets, Hubertus G., van der Wilt, Roos E., Houwen, Roderick H., van de Graaf, Ed, Majoor, Christof J., Koppelman, Gerard H., Roukema, Jolt, Heijerman, H., van der Meer, Renske, Vries, Robert, Clevers, Hans C., de Jonge, Hugo, Escher, J. C., Tiddens, Harm, Janssens, Hettie, Beekman, Jeffrey, and van der Ent, Cornelis K.

Published
2016

39. β2-Adrenergic receptor agonists activate CFTR in intestinal organoids and subjects with cystic fibrosis

Author

Vijftigschild, Lodewijk A W, Berkers, Gitte, Dekkers, Johanna F, Zomer-van Ommen, Domenique D, Matthes, Elizabeth, Kruisselbrink, Evelien, Vonk, Annelotte, Hensen, Chantal E, Heida-Michel, Sabine, Geerdink, Margot, Janssens, Hettie M, van de Graaf, Eduard A, Bronsveld, Inez, de Winter-de Groot, Karin M, Majoor, Christof J, Heijerman, Harry G M, de Jonge, Hugo R, Hanrahan, John W, van der Ent, Cornelis K, Beekman, Jeffrey M, Vijftigschild, Lodewijk A W, Berkers, Gitte, Dekkers, Johanna F, Zomer-van Ommen, Domenique D, Matthes, Elizabeth, Kruisselbrink, Evelien, Vonk, Annelotte, Hensen, Chantal E, Heida-Michel, Sabine, Geerdink, Margot, Janssens, Hettie M, van de Graaf, Eduard A, Bronsveld, Inez, de Winter-de Groot, Karin M, Majoor, Christof J, Heijerman, Harry G M, de Jonge, Hugo R, Hanrahan, John W, van der Ent, Cornelis K, and Beekman, Jeffrey M

Published
2016

40. Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis

Author

Dekkers, Johanna F., Berkers, Gitte, Kruisselbrink, Evelien, Vonk, Annelotte, De Jonge, Hugo R., Janssens, Hettie M., Bronsveld, Inez, van de Graaf, Eduard A, Nieuwenhuis, Edward E S, Houwen, Roderick H J, Vleggaar, Frank P., Escher, Johanna C., De Rijke, Yolanda B., Majoor, Christof J., Heijerman, Harry G M, De Winter-De Groot, Karin M., Clevers, Hans, Van Der Ent, Cornelis K., Beekman, Jeffrey M, Dekkers, Johanna F., Berkers, Gitte, Kruisselbrink, Evelien, Vonk, Annelotte, De Jonge, Hugo R., Janssens, Hettie M., Bronsveld, Inez, van de Graaf, Eduard A, Nieuwenhuis, Edward E S, Houwen, Roderick H J, Vleggaar, Frank P., Escher, Johanna C., De Rijke, Yolanda B., Majoor, Christof J., Heijerman, Harry G M, De Winter-De Groot, Karin M., Clevers, Hans, Van Der Ent, Cornelis K., and Beekman, Jeffrey M

Published
2016

41. Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis

Author

Dekkers, Johanna F, Berkers, Gitte, Kruisselbrink, Evelien, Vonk, Annelotte, de Jonge, Hugo R, Janssens, Hettie M, Bronsveld, Inez, van de Graaf, Eduard A, Nieuwenhuis, Edward E S, Houwen, Roderick H J, Vleggaar, Frank P, Escher, Johanna C, de Rijke, Yolanda B, Majoor, Christof J, Heijerman, Harry G M, de Winter-de Groot, Karin M, Clevers, Hans, van der Ent, Cornelis K, Beekman, Jeffrey M, Dekkers, Johanna F, Berkers, Gitte, Kruisselbrink, Evelien, Vonk, Annelotte, de Jonge, Hugo R, Janssens, Hettie M, Bronsveld, Inez, van de Graaf, Eduard A, Nieuwenhuis, Edward E S, Houwen, Roderick H J, Vleggaar, Frank P, Escher, Johanna C, de Rijke, Yolanda B, Majoor, Christof J, Heijerman, Harry G M, de Winter-de Groot, Karin M, Clevers, Hans, van der Ent, Cornelis K, and Beekman, Jeffrey M

Abstract

Identifying subjects with cystic fibrosis (CF) who may benefit from cystic fibrosis transmembrane conductance regulator (CFTR)-modulating drugs is time-consuming, costly, and especially challenging for individuals with rare uncharacterized CFTR mutations. We studied CFTR function and responses to two drugs-the prototypical CFTR potentiator VX-770 (ivacaftor/KALYDECO) and the CFTR corrector VX-809 (lumacaftor)-in organoid cultures derived from the rectal epithelia of subjects with CF, who expressed a broad range of CFTR mutations. We observed that CFTR residual function and responses to drug therapy depended on both the CFTR mutation and the genetic background of the subjects. In vitro drug responses in rectal organoids positively correlated with published outcome data from clinical trials with VX-809 and VX-770, allowing us to predict from preclinical data the potential for CF patients carrying rare CFTR mutations to respond to drug therapy. We demonstrated proof of principle by selecting two subjects expressing an uncharacterized rare CFTR genotype (G1249R/F508del) who showed clinical responses to treatment with ivacaftor and one subject (F508del/R347P) who showed a limited response to drug therapy both in vitro and in vivo. These data suggest that in vitro measurements of CFTR function in patient-derived rectal organoids may be useful for identifying subjects who would benefit from CFTR-correcting treatment, independent of their CFTR mutation.

Published
2016

42. Intestinal Organoid Swelling And Relation With Disease Severity And Response To Therapy

Author

Longziekten onderzoek 1, Other research (not in main researchprogram), Child Health, Longziekten patientenzorg, CTI, Longziekten onderzoek 2, MDL patientenzorg, Cluster C, Longziekten, Infection & Immunity, CMM Sectie Molecular Cancer Research, Hubrecht Institute with UMC, Cancer, Regenerative Medicine and Stem Cells, Beekman, Berkers, Gitte, de Winter-de Groot, Karin M., Dekkers, Johanna F., Vonk, Annelotte M., Kruisselbrink, Evelien, Hagemeijer, Marne C., Heida-Michel, Sabine, Geerdink, Margot, Arets, Hubertus G., van der Wilt, Roos E., Houwen, Roderick H., van de Graaf, Ed, Majoor, Christof J., Koppelman, Gerard H., Roukema, Jolt, Heijerman, H., van der Meer, Renske, Vries, Robert, Clevers, Hans C., de Jonge, Hugo, Escher, J. C., Tiddens, Harm, Janssens, Hettie, Beekman, Jeffrey, van der Ent, Cornelis K., Longziekten onderzoek 1, Other research (not in main researchprogram), Child Health, Longziekten patientenzorg, CTI, Longziekten onderzoek 2, MDL patientenzorg, Cluster C, Longziekten, Infection & Immunity, CMM Sectie Molecular Cancer Research, Hubrecht Institute with UMC, Cancer, Regenerative Medicine and Stem Cells, Beekman, Berkers, Gitte, de Winter-de Groot, Karin M., Dekkers, Johanna F., Vonk, Annelotte M., Kruisselbrink, Evelien, Hagemeijer, Marne C., Heida-Michel, Sabine, Geerdink, Margot, Arets, Hubertus G., van der Wilt, Roos E., Houwen, Roderick H., van de Graaf, Ed, Majoor, Christof J., Koppelman, Gerard H., Roukema, Jolt, Heijerman, H., van der Meer, Renske, Vries, Robert, Clevers, Hans C., de Jonge, Hugo, Escher, J. C., Tiddens, Harm, Janssens, Hettie, Beekman, Jeffrey, and van der Ent, Cornelis K.

Published
2016

43. Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis

Author

Longziekten onderzoek 1, Other research (not in main researchprogram), CTI, Longziekten, Infection & Immunity, Zorg en O&O, Child Health, Regenerative Medicine and Stem Cells, MDL patientenzorg, Cluster C, MS MDL Oncologie, Cancer, MS MDL 1, Longziekten patientenzorg, CMM Sectie Molecular Cancer Research, Hubrecht Institute with UMC, Beekman, Dekkers, Johanna F., Berkers, Gitte, Kruisselbrink, Evelien, Vonk, Annelotte, De Jonge, Hugo R., Janssens, Hettie M., Bronsveld, Inez, van de Graaf, Eduard A, Nieuwenhuis, Edward E S, Houwen, Roderick H J, Vleggaar, Frank P., Escher, Johanna C., De Rijke, Yolanda B., Majoor, Christof J., Heijerman, Harry G M, De Winter-De Groot, Karin M., Clevers, Hans, Van Der Ent, Cornelis K., Beekman, Jeffrey M, Longziekten onderzoek 1, Other research (not in main researchprogram), CTI, Longziekten, Infection & Immunity, Zorg en O&O, Child Health, Regenerative Medicine and Stem Cells, MDL patientenzorg, Cluster C, MS MDL Oncologie, Cancer, MS MDL 1, Longziekten patientenzorg, CMM Sectie Molecular Cancer Research, Hubrecht Institute with UMC, Beekman, Dekkers, Johanna F., Berkers, Gitte, Kruisselbrink, Evelien, Vonk, Annelotte, De Jonge, Hugo R., Janssens, Hettie M., Bronsveld, Inez, van de Graaf, Eduard A, Nieuwenhuis, Edward E S, Houwen, Roderick H J, Vleggaar, Frank P., Escher, Johanna C., De Rijke, Yolanda B., Majoor, Christof J., Heijerman, Harry G M, De Winter-De Groot, Karin M., Clevers, Hans, Van Der Ent, Cornelis K., and Beekman, Jeffrey M

Published
2016

45. β2-Adrenergic receptor agonists activate CFTR in intestinal organoids and subjects with cystic fibrosis

Author

Vijftigschild, Lodewijk A.W., primary, Berkers, Gitte, additional, Dekkers, Johanna F., additional, Zomer-van Ommen, Domenique D., additional, Matthes, Elizabeth, additional, Kruisselbrink, Evelien, additional, Vonk, Annelotte, additional, Hensen, Chantal E., additional, Heida-Michel, Sabine, additional, Geerdink, Margot, additional, Janssens, Hettie M., additional, van de Graaf, Eduard A., additional, Bronsveld, Inez, additional, de Winter-de Groot, Karin M., additional, Majoor, Christof J., additional, Heijerman, Harry G.M., additional, de Jonge, Hugo R., additional, Hanrahan, John W., additional, van der Ent, Cornelis K., additional, and Beekman, Jeffrey M., additional

Published
2016
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46. Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis

Author

Dekkers, Johanna F., primary, Berkers, Gitte, additional, Kruisselbrink, Evelien, additional, Vonk, Annelotte, additional, de Jonge, Hugo R., additional, Janssens, Hettie M., additional, Bronsveld, Inez, additional, van de Graaf, Eduard A., additional, Nieuwenhuis, Edward E. S., additional, Houwen, Roderick H. J., additional, Vleggaar, Frank P., additional, Escher, Johanna C., additional, de Rijke, Yolanda B., additional, Majoor, Christof J., additional, Heijerman, Harry G. M., additional, de Winter–de Groot, Karin M., additional, Clevers, Hans, additional, van der Ent, Cornelis K., additional, and Beekman, Jeffrey M., additional

Published
2016
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48. Effect of C1‐inhibitor in adults with mild asthma: A randomized controlled trial.

Author

Yang, Jack, Engelen, Tjitske S. R., Haak, Bastiaan W., Bonta, Peter I., Majoor, Christof J., Veer, Cornelis, Vos, Alex F., Kemper, E. Marleen, Lutter, René, Mierlo, Gerard, Zeerleder, Sacha S., Bel, Elisabeth H., and Poll, Tom

Subjects
RANDOMIZED controlled trials, ASTHMA, MACROPHAGE inflammatory proteins, ADULTS, FLUTICASONE propionate, METHACHOLINE chloride
Abstract

Effect of C1-inhibitor in adults with mild asthma: A randomized controlled trial To the Editor, Several newly approved monoclonal antibodies targeting type 2 inflammation have shown remarkable beneficial effects in patients with severe asthma. GLO:1X5/01apr20:all14053-fig-0002.jpg PHOTO (COLOR): Intravenous C1-inhibitor infusion reduces vascular leak following HDM/LPS challenge in the airways of asthma patients. [Extracted from the article]

Published
2020
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50. Occurrence of myocardial infarction, Ischemic stroke and pulmonary embolism in lung cancer patients

Author

Van Herk-Sukel, Myrthe P.P., Shantakumar, Sumitra, Kamphuisen, Pieter W., Majoor, Christof J., Overbeek, Lucy I.H., Penning-Van Beest, Fernie J.A., Herings, Ron M.C., Cardiovascular Centre (CVC), and Vascular Ageing Programme (VAP)

Subjects
cancer patient, pharmacoepidemiology, diagnosis, heart infarction, prevalence, chemotherapy, risk management, surgery, hazard ratio, cytopathology, male, gender, artery thrombosis, human, antilipemic agent, risk, drug use, Netherlands, register, brain ischemia, lung cancer, risk factor, vein thrombosis, cardiovascular agent, antihypertensive agent, patient, lung embolism, neoplasm, hospitalization
Abstract

Background: Patients with lung cancer (LC) are at increased risk of venous and arterial thrombosis due to cancer itself and its treatment. Although some studies have assessed the incidence of venous thrombosis among LC patients, data on the occurrence of specific venous and arterial thrombotic events is scarce. Objectives: To study the rate of myocardial infarction (MI), ischemic stroke (IS) and pulmonary embolism (PE) before and after LC diagnosis compared with cancer-free controls. Methods: Patients with LC during 2000-2007 were selected from PALGA, the Dutch nationwide registry of histo-and cytopathology, and linked to the PHARMO RLS, including drug use and hospitalizations of approximately three million inhabitants in the Netherlands. Included LC patients were matched 1:10 by age and gender to cancer-free controls. The occurrence of MI, IS and PE were assessed in the 12 months before and after LC diagnosis. Results: This study included 3,717 LC patients, with a mean (±SD) age of 59 (±14) years and 69% males. LC patients were six times as likely as their cancer-free controls to have had a hospitalization for PE in the 12 months before diagnosis, though prevalence was

Published
2011

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