Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2018-A03017-48 | Other Identifier | ID-RCB Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Institut National de la Santé Et de la Recherche Médicale, France | OTHER_GOV |
| URC-CIC Paris Descartes Necker Cochin | OTHER |
Not provided
Not provided
Not provided
The purpose of this prospective study is to analyze function and phenotype of blood neutrophils in cystic fibrosis patients and the impact of Pseudomonas aeruginosa chronic infection, treatment with CFTR modulators and acute exacerbation on blood neutrophils phenotype and function.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Stable state | Experimental | 45 adult cystic fibrosis patients followed in the respiratory medicine department of Cochin hospital, paris, France:
|
|
| Starting Ivacaftor-Tezacaftor-Elexacaftor | Experimental | 40 adult cystic fibrosis patients followed in the respiratory medicine department of Cochin hospital, paris, France:
|
|
| Exacerbation | Experimental | 15 adult cystic fibrosis patients followed in the respiratory medicine department of Cochin hospital, paris, France and hospitalized for respiratory exacerbation |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 1 blood sample | Other | 4 tubes of 7 ml per sample (a single sample) |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Quantification of blood low density neutrophils in cystic fibrosis (CF) | Quantitative flow cytometric evaluation of neutrophil membrane markers that differ according to whether they are :
| Through study completion, an average of 1 year |
| Transcriptomic analysis of blood neutrophils in cystic fibrosis (CF) | Transcriptomic analysis of blood neutrophil proinflammatory or immunomodulatory potential. Comparison of transcriptomic blood neutrophil profile in CF patients versus control blood-donors. | Through study completion, an average of 1 year |
| Effector function analysis of blood neutrophils in CF. | Comparison of effector function analysis of blood neutrophils of CF patients versus control blood-donors. | Through study completion, an average of 1 year |
| Phagocytosis potential of blood neutrophils in CF. | Comparison of phagocytosis potential of blood neutrophils of CF patients versus control blood-donors. | Through study completion, an average of 1 year |
| Survival/apoptosis balance analysis in CF | Survival / apoptosis balance analysis : (PCNA localization) in CF patients blood neutrophils versus control blood-donors. | Through study completion, an average of 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Quantification of blood low density neutrophils in CF vs other chronic inflammatory disorders. | Quantitative flow cytometric evaluation of neutrophil membrane markers that differ according to whether they are:
|
Not provided
Inclusion Criteria:
Patient over the age of 18 who is not under legal protection
Patients with CF according to the diagnostic criteria of the Cystic Fibrosis Foundation including:
No change in baseline treatment for 15 days (including antibiotic treatment).
Patient affiliated to a social security system
Free, informed and written consent, dated and signed by the patient and the investigator, at the latest on the day of inclusion and before any action required by the study.
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Pierre-Régis BURGEL, MD PHD | APHP | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cochin hospital, AP-HP | Paris | 75014 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18026571 | Background | Adib-Conquy M, Pedron T, Petit-Bertron AF, Tabary O, Corvol H, Jacquot J, Clement A, Cavaillon JM. Neutrophils in cystic fibrosis display a distinct gene expression pattern. Mol Med. 2008 Jan-Feb;14(1-2):36-44. doi: 10.2119/2007-00081.Adib-Conquy. | |
| 20870018 | Background | Bonvillain RW, Painter RG, Adams DE, Viswanathan A, Lanson NA Jr, Wang G. RNA interference against CFTR affects HL60-derived neutrophil microbicidal function. Free Radic Biol Med. 2010 Dec 15;49(12):1872-80. doi: 10.1016/j.freeradbiomed.2010.09.012. Epub 2010 Sep 24. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| D011552 | Pseudomonas Infections |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| 2 blood samples |
| Other |
4 tubes of 7 ml per sample / 2 samples : before / after antibiotic treatment |
|
| Through study completion, an average of 1 year |
| Quantification of blood low density neutrophils in CF according to different clinical situations. | Quantitative flow cytometric evaluation of neutrophil membrane markers.
| Through study completion, an average of 1 year |
| Transcriptomic analysis of blood neutrophils in CF according to different clinical situations. | Transcriptomic analysis of blood neutrophil proinflammatory or immunomodulatory potential.
| Through study completion, an average of 1 year |
| Effector function analysis of blood neutrophils in CF according to different clinical situations. | Effector function analysis of blood neutrophils:
| Through study completion, an average of 1 year |
| Phagocytosis potential of blood neutrophils in CF according to different clinical situations. | Phagocytosis potential analysis of blood neutrophils in CF:
| Through study completion, an average of 1 year |
| Survival/apoptosis balance analysis in CF according to different clinical situations. | Survival / apoptosis balance analysis (PCNA localization):
| Through study completion, an average of 1 year |
| 22846997 | Background | Bouayad D, Pederzoli-Ribeil M, Mocek J, Candalh C, Arlet JB, Hermine O, Reuter N, Davezac N, Witko-Sarsat V. Nuclear-to-cytoplasmic relocalization of the proliferating cell nuclear antigen (PCNA) during differentiation involves a chromosome region maintenance 1 (CRM1)-dependent export and is a prerequisite for PCNA antiapoptotic activity in mature neutrophils. J Biol Chem. 2012 Sep 28;287(40):33812-25. doi: 10.1074/jbc.M112.367839. Epub 2012 Jul 30. |
| 25977288 | Background | Bruijnzeel PL, Uddin M, Koenderman L. Targeting neutrophilic inflammation in severe neutrophilic asthma: can we target the disease-relevant neutrophil phenotype? J Leukoc Biol. 2015 Oct;98(4):549-56. doi: 10.1189/jlb.3VMR1214-600RR. Epub 2015 May 14. |
| 28891346 | Background | Bulloch MN, Hanna C, Giovane R. Lumacaftor/ivacaftor, a novel agent for the treatment of cystic fibrosis patients who are homozygous for the F580del CFTR mutation. Expert Rev Clin Pharmacol. 2017 Oct;10(10):1055-1072. doi: 10.1080/17512433.2017.1378094. Epub 2017 Sep 22. |
| 23181059 | Background | Chiara AD, Pederzoli-Ribeil M, Burgel PR, Danel C, Witko-Sarsat V. Targeting cytosolic proliferating cell nuclear antigen in neutrophil-dominated inflammation. Front Immunol. 2012 Oct 9;3:311. doi: 10.3389/fimmu.2012.00311. eCollection 2012. |
| 7697269 | Background | Cantin A. Cystic fibrosis lung inflammation: early, sustained, and severe. Am J Respir Crit Care Med. 1995 Apr;151(4):939-41. doi: 10.1164/ajrccm.151.4.7697269. No abstract available. |
| 10557320 | Background | Dibbert B, Weber M, Nikolaizik WH, Vogt P, Schoni MH, Blaser K, Simon HU. Cytokine-mediated Bax deficiency and consequent delayed neutrophil apoptosis: a general mechanism to accumulate effector cells in inflammation. Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13330-5. doi: 10.1073/pnas.96.23.13330. |
| 19103874 | Background | Downey DG, Bell SC, Elborn JS. Neutrophils in cystic fibrosis. Thorax. 2009 Jan;64(1):81-8. doi: 10.1136/thx.2007.082388. |
| 11581295 | Background | Fadok VA, Bratton DL, Henson PM. Phagocyte receptors for apoptotic cells: recognition, uptake, and consequences. J Clin Invest. 2001 Oct;108(7):957-62. doi: 10.1172/JCI14122. No abstract available. |
| 27558332 | Background | Futosi K, Mocsai A. Tyrosine kinase signaling pathways in neutrophils. Immunol Rev. 2016 Sep;273(1):121-39. doi: 10.1111/imr.12455. |
| 15136788 | Background | Gilroy DW, Lawrence T, Perretti M, Rossi AG. Inflammatory resolution: new opportunities for drug discovery. Nat Rev Drug Discov. 2004 May;3(5):401-16. doi: 10.1038/nrd1383. No abstract available. |
| 21311988 | Background | Hayes E, Pohl K, McElvaney NG, Reeves EP. The cystic fibrosis neutrophil: a specialized yet potentially defective cell. Arch Immunol Ther Exp (Warsz). 2011 Apr;59(2):97-112. doi: 10.1007/s00005-011-0113-6. Epub 2011 Feb 11. |
| 7697234 | Background | Khan TZ, Wagener JS, Bost T, Martinez J, Accurso FJ, Riches DW. Early pulmonary inflammation in infants with cystic fibrosis. Am J Respir Crit Care Med. 1995 Apr;151(4):1075-82. doi: 10.1164/ajrccm/151.4.1075. |
| 24934274 | Background | Koenderman L, Chilvers ER. Future treatment in patients with chronic obstructive pulmonary disease: to reverse or not to reverse steroid resistance-that is the question. J Allergy Clin Immunol. 2014 Aug;134(2):323-4. doi: 10.1016/j.jaci.2014.04.030. Epub 2014 Jun 13. No abstract available. |
| 23690474 | Background | Laval J, Touhami J, Herzenberg LA, Conrad C, Taylor N, Battini JL, Sitbon M, Tirouvanziam R. Metabolic adaptation of neutrophils in cystic fibrosis airways involves distinct shifts in nutrient transporter expression. J Immunol. 2013 Jun 15;190(12):6043-50. doi: 10.4049/jimmunol.1201755. Epub 2013 May 20. |
| 26441976 | Background | Leliefeld PH, Koenderman L, Pillay J. How Neutrophils Shape Adaptive Immune Responses. Front Immunol. 2015 Sep 14;6:471. doi: 10.3389/fimmu.2015.00471. eCollection 2015. |
| 21785456 | Background | Mantovani A, Cassatella MA, Costantini C, Jaillon S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol. 2011 Jul 25;11(8):519-31. doi: 10.1038/nri3024. |
| 26517580 | Background | Martin C, Ohayon D, Alkan M, Mocek J, Pederzoli-Ribeil M, Candalh C, Thevenot G, Millet A, Tamassia N, Cassatella MA, Thieblemont N, Burgel PR, Witko-Sarsat V. Neutrophil-Expressed p21/waf1 Favors Inflammation Resolution in Pseudomonas aeruginosa Infection. Am J Respir Cell Mol Biol. 2016 May;54(5):740-50. doi: 10.1165/rcmb.2015-0047OC. |
| 18587042 | Background | McKeon DJ, Condliffe AM, Cowburn AS, Cadwallader KC, Farahi N, Bilton D, Chilvers ER. Prolonged survival of neutrophils from patients with Delta F508 CFTR mutations. Thorax. 2008 Jul;63(7):660-1. doi: 10.1136/thx.2008.096834. No abstract available. |
| 26987072 | Background | Meijer L, Nelson DJ, Riazanski V, Gabdoulkhakova AG, Hery-Arnaud G, Le Berre R, Loaec N, Oumata N, Galons H, Nowak E, Gueganton L, Dorothee G, Prochazkova M, Hall B, Kulkarni AB, Gray RD, Rossi AG, Witko-Sarsat V, Norez C, Becq F, Ravel D, Mottier D, Rault G. Modulating Innate and Adaptive Immunity by (R)-Roscovitine: Potential Therapeutic Opportunity in Cystic Fibrosis. J Innate Immun. 2016;8(4):330-49. doi: 10.1159/000444256. Epub 2016 Mar 18. |
| 19454722 | Background | Moriceau S, Kantari C, Mocek J, Davezac N, Gabillet J, Guerrera IC, Brouillard F, Tondelier D, Sermet-Gaudelus I, Danel C, Lenoir G, Daniel S, Edelman A, Witko-Sarsat V. Coronin-1 is associated with neutrophil survival and is cleaved during apoptosis: potential implication in neutrophils from cystic fibrosis patients. J Immunol. 2009 Jun 1;182(11):7254-63. doi: 10.4049/jimmunol.0803312. |
| 20375556 | Background | Moriceau S, Lenoir G, Witko-Sarsat V. In cystic fibrosis homozygotes and heterozygotes, neutrophil apoptosis is delayed and modulated by diamide or roscovitine: evidence for an innate neutrophil disturbance. J Innate Immun. 2010;2(3):260-6. doi: 10.1159/000295791. Epub 2010 Mar 10. |
| 27759041 | Background | Ohayon D, De Chiara A, Chapuis N, Candalh C, Mocek J, Ribeil JA, Haddaoui L, Ifrah N, Hermine O, Bouillaud F, Frachet P, Bouscary D, Witko-Sarsat V. Cytoplasmic proliferating cell nuclear antigen connects glycolysis and cell survival in acute myeloid leukemia. Sci Rep. 2016 Oct 19;6:35561. doi: 10.1038/srep35561. |
| 20171075 | Background | Peranzoni E, Zilio S, Marigo I, Dolcetti L, Zanovello P, Mandruzzato S, Bronte V. Myeloid-derived suppressor cell heterogeneity and subset definition. Curr Opin Immunol. 2010 Apr;22(2):238-44. doi: 10.1016/j.coi.2010.01.021. Epub 2010 Feb 17. |
| 22156198 | Background | Pillay J, Kamp VM, van Hoffen E, Visser T, Tak T, Lammers JW, Ulfman LH, Leenen LP, Pickkers P, Koenderman L. A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1. J Clin Invest. 2012 Jan;122(1):327-36. doi: 10.1172/JCI57990. Epub 2011 Dec 12. |
| 20400675 | Background | Pillay J, Ramakers BP, Kamp VM, Loi AL, Lam SW, Hietbrink F, Leenen LP, Tool AT, Pickkers P, Koenderman L. Functional heterogeneity and differential priming of circulating neutrophils in human experimental endotoxemia. J Leukoc Biol. 2010 Jul;88(1):211-20. doi: 10.1189/jlb.1209793. Epub 2010 Apr 16. |
| 23423530 | Background | Pillay J, Tak T, Kamp VM, Koenderman L. Immune suppression by neutrophils and granulocytic myeloid-derived suppressor cells: similarities and differences. Cell Mol Life Sci. 2013 Oct;70(20):3813-27. doi: 10.1007/s00018-013-1286-4. Epub 2013 Feb 20. |
| 16951685 | Background | Rossi AG, Sawatzky DA, Walker A, Ward C, Sheldrake TA, Riley NA, Caldicott A, Martinez-Losa M, Walker TR, Duffin R, Gray M, Crescenzi E, Martin MC, Brady HJ, Savill JS, Dransfield I, Haslett C. Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis. Nat Med. 2006 Sep;12(9):1056-64. doi: 10.1038/nm1468. Epub 2006 Sep 3. |
| 27558327 | Background | Scapini P, Marini O, Tecchio C, Cassatella MA. Human neutrophils in the saga of cellular heterogeneity: insights and open questions. Immunol Rev. 2016 Sep;273(1):48-60. doi: 10.1111/imr.12448. |
| 28146645 | Background | Uhel F, Azzaoui I, Gregoire M, Pangault C, Dulong J, Tadie JM, Gacouin A, Camus C, Cynober L, Fest T, Le Tulzo Y, Roussel M, Tarte K. Early Expansion of Circulating Granulocytic Myeloid-derived Suppressor Cells Predicts Development of Nosocomial Infections in Patients with Sepsis. Am J Respir Crit Care Med. 2017 Aug 1;196(3):315-327. doi: 10.1164/rccm.201606-1143OC. |
| 16407840 | Background | Warbrick E. A functional analysis of PCNA-binding peptides derived from protein sequence, interaction screening and rational design. Oncogene. 2006 May 11;25(20):2850-9. doi: 10.1038/sj.onc.1209320. |
| 23548924 | Background | Witko-Sarsat V. Neutrophils in the innate immunity conundrum of cystic fibrosis: a CFTR-related matter? J Innate Immun. 2013;5(3):195-6. doi: 10.1159/000350215. Epub 2013 Mar 23. No abstract available. |
| 8805680 | Background | Witko-Sarsat V, Allen RC, Paulais M, Nguyen AT, Bessou G, Lenoir G, Descamps-Latscha B. Disturbed myeloperoxidase-dependent activity of neutrophils in cystic fibrosis homozygotes and heterozygotes, and its correction by amiloride. J Immunol. 1996 Sep 15;157(6):2728-35. |
| 10498622 | Background | Witko-Sarsat V, Cramer EM, Hieblot C, Guichard J, Nusbaum P, Lopez S, Lesavre P, Halbwachs-Mecarelli L. Presence of proteinase 3 in secretory vesicles: evidence of a novel, highly mobilizable intracellular pool distinct from azurophil granules. Blood. 1999 Oct 1;94(7):2487-96. |
| 9841834 | Background | Witko-Sarsat V, Halbwachs-Mecarelli L, Sermet-Gaudelus I, Bessou G, Lenoir G, Allen RC, Descamps-Latscha B. Priming of blood neutrophils in children with cystic fibrosis: correlation between functional and phenotypic expression of opsonin receptors before and after platelet-activating factor priming. J Infect Dis. 1999 Jan;179(1):151-62. doi: 10.1086/314532. |
| 20975039 | Background | Witko-Sarsat V, Mocek J, Bouayad D, Tamassia N, Ribeil JA, Candalh C, Davezac N, Reuter N, Mouthon L, Hermine O, Pederzoli-Ribeil M, Cassatella MA. Proliferating cell nuclear antigen acts as a cytoplasmic platform controlling human neutrophil survival. J Exp Med. 2010 Nov 22;207(12):2631-45. doi: 10.1084/jem.20092241. Epub 2010 Oct 25. |
| 27558345 | Background | Witko-Sarsat V, Ohayon D. Proliferating cell nuclear antigen in neutrophil fate. Immunol Rev. 2016 Sep;273(1):344-56. doi: 10.1111/imr.12449. |
| 21317039 | Background | Witko-Sarsat V, Pederzoli-Ribeil M, Hirsch E, Sozzani S, Cassatella MA. Regulating neutrophil apoptosis: new players enter the game. Trends Immunol. 2011 Mar;32(3):117-24. doi: 10.1016/j.it.2011.01.001. Epub 2011 Feb 12. |
| 10830774 | Background | Witko-Sarsat V, Rieu P, Descamps-Latscha B, Lesavre P, Halbwachs-Mecarelli L. Neutrophils: molecules, functions and pathophysiological aspects. Lab Invest. 2000 May;80(5):617-53. doi: 10.1038/labinvest.3780067. No abstract available. |
| 10704083 | Background | Witko-Sarsat V, Sermet-Gaudelus I, Lenoir G, Descamps-Latscha B. Inflammation and CFTR: might neutrophils be the key in cystic fibrosis? Mediators Inflamm. 1999;8(1):7-11. doi: 10.1080/09629359990658. |
| 11827991 | Background | Worlitzsch D, Tarran R, Ulrich M, Schwab U, Cekici A, Meyer KC, Birrer P, Bellon G, Berger J, Weiss T, Botzenhart K, Yankaskas JR, Randell S, Boucher RC, Doring G. Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients. J Clin Invest. 2002 Feb;109(3):317-25. doi: 10.1172/JCI13870. |
| 27601627 | Background | Wright HL, Makki FA, Moots RJ, Edwards SW. Low-density granulocytes: functionally distinct, immature neutrophils in rheumatoid arthritis with altered properties and defective TNF signalling. J Leukoc Biol. 2017 Feb;101(2):599-611. doi: 10.1189/jlb.5A0116-022R. Epub 2016 Sep 6. |
| 31679946 | Background | Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis E, Mall MA, Welter JJ, Ramsey BW, McKee CM, Marigowda G, Moskowitz SM, Waltz D, Sosnay PR, Simard C, Ahluwalia N, Xuan F, Zhang Y, Taylor-Cousar JL, McCoy KS; VX17-445-103 Trial Group. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1940-1948. doi: 10.1016/S0140-6736(19)32597-8. Epub 2019 Oct 31. |
| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |