- Article
- Source : Campus Sanofi
- 13 mai 2024
L'impact des exacerbations dans la BPCO
Le risque d’exacerbation augmente après chaque exacerbation1
Basé sur les données d'une vaste cohorte de 73 106 patients canadiens hospitalisés (âge moyen 75 ans) pour la première fois en raison d'une exacerbation sévère de la BPCO (1990-2005, suivis jusqu'au décès ou jusqu'au 31 mars 2007).
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*Les exacerbations sévères ont été définies comme celles ayant entraîné une hospitalisation suite à un diagnostic primaire de BPCO.
b Ajusté en fonction de l’age, du sexe et du score de la maladie.2
De nombreux patients peuvent être encore symptomatiques voire continuer de souffrir d’exacerbations, malgré un traitement optimisé.
Écoutez le professeur Nicola Hanania : « La prévention des exacerbations est l'objectif clé »
2:07 minutes
Nicola Hanania est professeur de médecine, chef de section des soins intensifs pulmonaires et de médecine du sommeil à l'hôpital Ben Taub de Houston, au Texas, et directeur du centre de recherche clinique sur les voies respiratoires, ACRC, au Bear College of Medicine.
Écoutez l'intégralité de l'épisode du podcast sur le site d'EMJ.
Sponsorisé par Sanofi et Regeneron, en partenariat avec EMJ.
"COPD unfortunately is a chronic disease as the name implies. So, it’s a progressive disease. While we cannot cure it, we can manage it, we can treat it. Unfortunately, there are several events in the course of the disease that makes it worse, not only for the patient but for the healthcare system: it increases risk of hospitalization, mortality… And one of them is exacerbations. I call it “lung attacks”. Pretty much what happens with exacerbations is these patients who have daily symptoms become having more symptoms, they may have more cough, increasing sputum production, sometimes these exacerbations are driven by infections – most of the time actually – and they end up needing more and more treatments including antibiotics, steroids. And sometimes unfortunately may end up pushing the patient to go to emergency department or getting hospitalized. Unfortunately, exacerbations is not just the fact that they occur and we can treat them, it’s every time the patient gets an exacerbation it puts his or her lung function down. In fact, there has been good data now to show that repeated exacerbations can contribute to increase risk of worsening exacerbations subsequently, but worsening lung function over long time, and they don’t recuperate lung function, so, meaning every time they get an exacerbation it puts them down both the lung function and the quality of life. There is definitely good data to show that repeated exacerbations have been linked to increased mortality and so on. So that’s why one of the major goals in managing this disease is try to prevent these lung attacks from occurring. Prevention of exacerbations is the key goal in managing this disease. Naturally exacerbations tend to be more frequent in those patients with more severe disease. But they can occur even in moderate COPD as well, in some situations." - Nicola Hanania
Les exacerbations de BPCO peuvent entraîner un déclin accéléré de la fonction pulmonaire3,e
- La perte annuelle de fonction pulmonaire a presque doublé3
- Un déclin irréversible de la fonction pulmonaire peut survenir après une seule exacerbation de BPCO3
c- Ou bithérapie inhalée si les CSI sont contre-indiqués.15
d- Essai de phase 3, randomisé, en double aveugle, de 52 semaines, évaluant l'efficacité et l'innocuité de la trithérapie furoate de fluticasone/uméclidinium/vilanterol par rapport au furoate de fluticasone/vilanterol ou à l'uméclidinium/vilanterol chez des patients âgés de ≥ 40 ans atteints de BPCO symptomatique et d'un antécédents d'exacerbations.2
e- VEMS diminue après une seule exacerbation modérée à sévère. Basé sur une analyse rétrospective des données de 586 patients atteints de BPCO modérée à sévère.5
HRA, rapport de risque ajusté ; BPCO, Bronchopneumopathie chronique obstructive ; VEMS, volume expiratoire forcé en 1 seconde ; QdV, qualité de vie
Références
1. Halpin DMG, Dransfield MT, Han MK, et al. The effect of exacerbation history on outcomes in the IMPACT trial. Eur Respir J. 2020;55:1901921. doi:10.1183/13993003.01921-2019
2. Suissa S, Dell’Anniello S, Ernst P. Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality. Thorax. 2012;67(11):957-963.
3. Halpin DMG, Decramer M, Celli BR, Mueller A, Metzdorf N, Tashkin DP. Effect of a single exacerbation on decline in lung function in COPD. Respir Med. 2017;128:85-91.
4. Cosio Piqueras MG, Cosio MG. Disease of the airways in chronic obstructive pulmonary disease. Eur Respir J. 2001;18(suppl 34):41s-49s.
5. Tajti G, Gesztelyi R, Pak K, et al. Positive correlation of airway resistance and serum asymmetric dimethylarginine level in COPD patients with systemic markers of low-grade inflammation. Int J Chron Obstruct Pulmon Dis. 2017;12:873-884.
6. Higham A, Quinn AM, Cançado JED, Singh D. The pathology of small airways disease in COPD: historical aspects and future directions. Respir Res. 2019;20(1):49. doi:10.1186/s12931-019-1017-y
7. O’Donnell DE, Parker CM. COPD exacerbations. 3: Pathophysiology. Thorax. 200661(4):354-361.
8. Calverley PMA. Respiratory failure in chronic obstructive pulmonary disease. Eur Respir J. 2003;22:26s-30s.
9. Roussos C, Koutsoukou A. Respiratory failure. Eur Respir J. 2003;22(suppl 47):3s-14s.
10. Aghapour M, Raee P, Moghaddam SJ, Hiemstra PS, Heijink IH. Airway epithelial barrier dysfunction in chronic obstructive pulmonary disease: role of cigarette smoke exposure. Am J Respir Cell Mol Biol. 2018;58(2):157-169.
11. Brightling CE, Saha S, Hollins F. Interleukin-13: prospects for new treatment. Clin Exp Allergy. 2010;40(1):42-49.
12. Barberà JA, Peinado VI, Santos S. Pulmonary hypertension in chronic obstructive pulmonary disease. Eur Respir J. 2003;21(5):892-905.
13. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2024 report). Accessed [February 9, 2024]. https://goldcopd.org/2024-gold-report-2/
14. Jones PW. St George’s Respiratory Questionnaire: MCID. COPD. 2005 Mar;2(1):75-79.
15. Jones P. St George’s Respiratory Questionnaire Manual. [Version 2.4, March 2022]. Accessed [February 9, 2024]. https://www.sgul.ac.uk/research/research-operations/research-administration/st-georges-respiratory-questionnaire/docs/SGRQ-Manual-March-2022.pdf
16. Evidera website. EXACT and E-RS:COPD content. Accessed [February 9, 2024]. https://www.evidera.com/what-we-do/patient-centered-research/coa-instrument-management-services/exact-program/ exact-content/
17. Leidy NK, Bushnell DM, Thach C, Hache C, Gutzwiller FS. Interpreting Evaluating Respiratory Symptoms in COPD diary scores in clinical trials: terminology, methods, and recommendations. Chronic Obstr Pulm Dis. 2022;9(4):576-590.
18. Oshagbemi OA, Franssen FME, van Kraaij S, et al. Blood eosinophil counts, withdrawal of inhaled corticosteroids and risk of COPD exacerbations and mortality in the clinical practice research datalink (CPRD). COPD. 2019;16(2):152-159.
19. Casanova C, Celli BR, de-Torres JP, et al. Prevalence of persistent blood eosinophilia: relation to outcomes in patients with COPD. Eur Respir J. 2017;50:1701162. doi:10.1183/13993003.01162-2017
20. Singh D, Kolsum U, Brightling CE, Locantore N, Agusti A, Tal-Singer R; ECLIPSE investigators. Eosinophilic inflammation in COPD: prevalence and clinical characteristics. Eur Respir J. 2014;44(6):1697-1700.
21. Bafadhel M, McKenna S, Terry S, et al. Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. Am J Respir Crit Care Med. 2011;184(6):662-671.
22. Oshagbemi OA, Burden AM, Braeken DCW, et al. Stability of blood eosinophils in patients with chronic obstructive pulmonary disease and in control subjects, and the impact of sex, age, smoking, and baseline counts. Am J Respir Crit Care Med. 2017;195(10):1402-1404.
23. Yun JH, Lamb A, Chase R, et al; COPDGene and ECLIPSE Investigators. Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2018;141(6):2037-2047.e10. doi:10.1016/j.jaci.2018.04.010
24. Bélanger M, Couillard S, Courteau J, et al. Eosinophil counts in first COPD hospitalizations: a comparison of health service utilization. Int J Chron Obstruct Pulmon Dis. 2018;13:3045-3054.
25. Fritzsching B, Zhou-Suckow Z, Trojanek JB, et al. Hypoxic epithelial necrosis triggers neutrophilic inflammation via IL-1 receptor signaling in cystic fibrosis lung disease. Am J Respir Crit Care Med. 2015;191(8):902-913.
26. Vedel-Krogh S, Nielsen SF, Lange P, Vestbo J, Nordestgaard BG. Blood eosinophils and exacerbations in chronic obstructive pulmonary disease. The Copenhagen General Population Study. Am J Respir Crit Care Med. 2016;193(9):965-974.
27. George L, Taylor AR, Esteve- Codina A, et al; U-BIOPRED and the EvA study teams. Blood eosinophil count and airway epithelial transcriptome relationships in COPD versus asthma. Allergy. 2020;75(2):370-380.
28. Yousuf A, Ibrahim W, Greening NJ, Brightling CE. T2 biologics for chronic obstructive pulmonary disease. J Allergy Clin Immunol Pract. 2019;7(5):1406-1416.
29. Barnes PJ. Inflammatory endotypes in COPD. Allergy. 2019;74(7):1249-1256.
30. Oishi K, Matsunaga K, Shirai T, Hirai K, Gon Y. Role of type 2 inflammatory biomarkers in chronic obstructive pulmonary disease. J Clin Med. 2020;9(8):2670. doi:10.3390/jcm9082670
31. Gabryelska A, Kuna P, Antczak A, Białasiewicz P, Panek M. IL-33 mediated inflammation in chronic respiratory diseases—understanding the role of the member of IL-1 superfamily. Front Immunol. 2019;10:692. doi:10.3389/fimmu.2019.00692
32. Allinne J, Scott G, Lim WK, et al. IL-33 blockade affects mediators of persistence and exacerbation in a model of chronic airway inflammation. J Allergy Clin Immunol. 2019;144(6):1624-1637.e10.
33. Calderon AA, Dimond C, Choy DF, et al. Targeting interleukin-33 and thymic stromal lymphopoietin pathways for novel pulmonary therapeutics in asthma and COPD. Eur Respir Rev. 2023;32(167):220144. doi:10.1183/16000617.0144-2022
34. Gandhi NA, Bennett BL, Graham NMH, Pirozzi G, Stahl N, Yancopoulos D. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35-50.
35. Rosenberg HF, Phipps S, Foster PS. Eosinophil trafficking in allergy and asthma. J Allergy Clin Immunol. 2007;119(6):1303-1310.
36. Doyle AD, Mukherjee M, LeSuer WE, et al. Eosinophil-derived IL-13 promotes emphysema. Eur Respir J. 2019;53(5):1801291. doi:10.1183/13993003.01291-2018
37. Barnes PJ. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2016;138(1):16-27.
38. Defrance T, Carayon P, Billian G, et al. Interleukin 13 is a B cell stimulating factor. J Exp Med. 1994;179(1):135-143.
39. Yanagihara Y, Ikizawa K, Kajiwara K, Koshio T, Basaki Y, Akiyama K. Functional significance of IL-4 receptor on B cells in IL-4– induced human IgE production. J Allergy Clin Immunol. 1995;96(6 pt 2):1145-1151.
40. Gandhi NA, Pirozzi G, Graham NMH. Commonality of the IL-4/IL-13 pathway in atopic diseases. Expert Rev Clin Immunol. 2017;13(5):425-437.
41. Kaur D, Hollins F, Woodman L, et al. Mast cells express IL-13Rα1: IL-13 promotes human lung mast cell proliferation and FcεRI expression. Allergy. 2006;61(9):1047-1053.
42. Saatian B, Rezaee F, Desando S, et al. Interleukin-4 and interleukin-13 cause barrier dysfunction in human epithelial cells. Tissue Barriers. 2013;1(2):e24333. doi:10.4161/tisb.24333
43. Zheng T, Zhu Z, Wang Z, et al. Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase– and cathepsin-dependent emphysema. J Clin Invest. 2000;106(9):1081-1093.
44. Garudadri S, Woodruff PG. Targeting chronic obstructive pulmonary disease phenotypes, endotypes, and biomarkers. Ann Am Thorac Soc. 2018;15(suppl 4):S234-S238.
45. Alevy YG, Patel AC, Romero AG, et al. IL-13–induced airway mucus production is attenuated by MAPK13 inhibition. J Clin Invest. 2012;122(12):4555-4568.
46. Singanayagam A, Footitt J, Marczynski M, et al. Airway mucins promote immunopathology in virus-exacerbated chronic obstructive pulmonary disease. J Clin Invest. 2022;132(8):e12901. doi:10.1172/JCI120901
47. Zhu Z, Homer RJ, Wang Z, et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest. 1999;103(6):779-788.
48. Cooper PR, Poll CT, Barnes PJ, Sturton RG. Involvement of IL-13 in tobacco smoke-induced changes in the structure and function of rat intrapulmonary airways. Am J Respir Cell Mol Biol. 2010;43(2):220-226.
49. Arora S, Dev K, Agarwal B, Das P, Syed MA. Macrophages: their role, activation, and polarization in pulmonary diseases. Immunobiology. 2018;223(4-5):383-396.
50. He S, Xie L, Lu J, Sun S. Characteristics and potential role of M2 macrophages in COPD. Int J Chron Obstruct Pulmon Dis. 2017;12:3029-3039.
51. Wang X, Xu C, Ji J, et al. IL-4/IL-13 upregulates Sonic hedgehog expression to induce allergic airway epithelial remodeling. Am J Physiol Lung Cell Mol Physiol. 2020;318(5):L888-L899.
52. Linden D, Guo-Parke H, Coyle PV, et al. Respiratory viral infection: a potential “missing link” in the pathogenesis of COPD. Eur Respir Rev. 2019;28(151):180063. doi:10.1183/16000617.0063-2018
53. Wang Z, Bafadhel M, Haldar K, et al. Lung microbiome dynamics in COPD exacerbations. Eur Respir J. 2016;47(4):1082-1092.
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