Preview

Meditsinskiy sovet = Medical Council

Advanced search

Targeted therapy as a new perspective in the treatment of COPD

https://doi.org/10.21518/ms2024-519

Abstract

Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition characterized by persistent airflow limitation caused by chronic airway inflammation in response to harmful particles and gases. The diversity of clinical manifestations and pathophysiological mechanisms necessitates an individualized approach to treatment. The disease is driven by inflammatory processes, including the activation of macrophages, neutrophils, and T-cells, as well as the release of various inflammatory mediators that contribute to chronic airway damage. In recent years, attention has turned to eosinophilic inflammation, traditionally associated with asthma, which is also found in a significant portion of COPD patients. Eosinophilia is observed in a considerable number of COPD patients and is associated with more severe disease and an increased risk of exacerbations. However, data on the role of eosinophils in COPD are mixed: some studies find no difference in disease severity between high- and low-eosinophil groups, while others confirm an elevated risk of exacerbations in patients with high eosinophil levels. A promising therapeutic agent in this area is dupilumab — a monoclonal antibody that blocks interleukin-4 and -13 receptors, demonstrating the ability to reduce exacerbation frequency and improve lung function in COPD patients by targeting eosinophilic inflammation. Clinical trial results indicate that dupilumab provides significant clinical improvement and may become an important tool in treating eosinophilic COPD, offering a new approach based on the molecular understanding of the disease. This publication presents the latest data on the use of dupilumab in COPD treatment.

About the Authors

N. V. Trushenko
Sechenov First Moscow State Medical University (Sechenov University); Research Institute for Pulmonology of the Federal Medical Biological Agency
Russian Federation

Natalia V. Trushenko - Cand. Sci. (Med.), Associate Professor, Department of Pulmonology, Sechenov First Moscow State Medical University (Sech- enov University); Researcher, Research Institute for Pulmonology of the Federal Medical Biological Agency.

8, Bldg. 2, Trubetskaya St., Moscow, 119991; 8, Orekhovy Boulevard, Moscow, 115682



B. B. Lavginova
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Baina B. Lavginova - Clinical Resident of the Pulmonology Department, Sechenov First Moscow State Medical University (Sechenov University).

8, Bldg. 2, Trubetskaya St., Moscow, 119991



O. S. Belkina
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Olesia S. Belkina - Student of the Clinical Institute of Child Health named after. N.F. Filatov, Sechenov First Moscow State Medical University (Sechenov University).

8, Bldg. 2, Trubetskaya St., Moscow, 119991



S. N. Avdeev
Sechenov First Moscow State Medical University (Sechenov University); Research Institute for Pulmonology of the Federal Medical Biological Agency
Russian Federation

Sergey N. Avdeev - Dr. Sci. (Med.), Professor, Acad. RAS, Head of the Pulmonology Department, Sechenov First Moscow State Medical University (Sechenov University); Head of the Clinical Department, Research Institute for Pulmonology of the Federal Medical Biological Agency.

8, Bldg. 2, Trubetskaya St., Moscow, 119991; 8, Orekhovy Boulevard, Moscow, 115682



References

1. Fragoso E, Andre S, Boleo-Tome JP, Areias V, Munha J, Cardoso J. Understanding COPD: A vision on phenotypes, comorbidities and treatment approach. GI COPD - Interest Group on Chronic Obstructive Pulmonary Disease. Rev Port Pneumol (2006). 2016;22(2):101-111. https://doi.org/10.1016/j.rppnen.2015.12.001.

2. Pavord ID. Biologics and chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2018;141(6):1983-1991. https://doi.org/10.1016/j.jaci.2018.04.020.

3. Brightling CE. Chronic obstructive pulmonary disease phenotypes, biomarkers, and prognostic indicators. Allergy Asthma Proc. 2016;37(6):432-438. https://doi.org/10.2500/aap.2016.37.3996.

4. Barnes PJ. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2016;138(1):16-27. https://doi.org/10.1016/j.jaci.2016.05.011.

5. Brightling C, Greening N. Airway inflammation in COPD: progress to precision medicine. Eur Respir J. 2019;54(2):1900651. https://doi.org/10.1183/13993003.00651-2019.

6. Landis S, Suruki R, Maskell J, Bonar K, Hilton E, Compton C. Demographic and Clinical Characteristics of COPD Patients at Different Blood Eosinophil Levels in the UK Clinical Practice Research Datalink. COPD. 2018;15(2):177-184. https://doi.org/10.1080/15412555.2018.1441275.

7. Pascoe S, Locantore N, Dransfield MT, Barnes NC, Pavord ID. Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: a secondary analysis of data from two parallel randomised controlled trials. Lancet Respir Med. 2015;3(6):435-442. https://doi.org/10.1016/S2213-2600(15)00106-X.

8. Singh D, Kolsum U, Brightling CE, Locantore N, Agusti A, Tal-Singer R. Eosinophilic inflammation in COPD: prevalence and clinical characteristics. Eur Respir J. 2014;44(6):1697-1700. https://doi.org/10.1183/09031936.00162414.

9. George L, Brightling CE. Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease. Ther Adv Chronic Dis. 2016;7(1):34-51. https://doi.org/10.1177/2040622315609251.

10. Avdeev SN, Trushenko NV, Merzhoeva ZM, Ivanova MS, Kusraeva EV. Eosinophilic inflammation in chronic obstructive pulmonary disease. Terapevticheskii Arkhiv. 2019;91(10):144-152. (In Russ.) https://doi.org/10.26442/00403660.2019.10.000426.

11. Brusselle G, Pavord ID, Landis S, Pascoe S, Lettis S, Morjaria N et al. Blood eosinophil levels as a biomarker in COPD. Respir Med. 2018;138:21-31. https://doi.org/10.1016/j.rmed.2018.03.016.

12. Eltboli O, Bafadhel M, Hollins F, Wright A, Hargadon B, Kulkarni N, Brightling C. COPD exacerbation severity and frequency is associated with impaired macrophage efferocytosis of eosinophils. BMC Pulm Med. 2014;14:112. https://doi.org/10.1186/1471-2466-14-112.

13. Kolsum U, Damera G, Pham TH, Southworth T, Mason S, Karur P et al. Pulmonary inflammation in patients with chronic obstructive pulmonary disease with higher blood eosinophil counts. J Allergy Clin Immunol. 2017;140(4):1181-1184.e7. https://doi.org/10.1016/j.jaci.2017.04.027.

14. Bhatt SP, Rabe KF, Hanania NA, Vogelmeier CF, Bafadhel M, Christenson SA et al. Dupilumab for COPD with Blood Eosinophil Evidence of Type 2 Inflammation. N Engl J Med. 2024;390(24):2274-2283. https://doi.org/10.1056/NEJMoa2401304.

15. Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 2004;350(26):2645-2653. https://doi.org/10.1056/NEJMoa032158.

16. Turato G, Semenzato U, Bazzan E, Biondini D, Tine M, Torrecilla N et al. Blood Eosinophilia Neither Reflects Tissue Eosinophils nor Worsens Clinical Outcomes in Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2018;197(9):1216-1219. https://doi.org/10.1164/rccm.201708-1684LE.

17. Hastie AT, Martinez FJ, Curtis JL, Doerschuk CM, Hansel NN, Christenson S et al. Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: an analysis of the SPIROMICS cohort. Lancet Respir Med. 2017;5(12):956-967. https://doi.org/10.1016/S2213-2600(17)30432-0.

18. Cheng SL, Lin CH. Effectiveness using higher inhaled corticosteroid dosage in patients with COPD by different blood eosinophilic counts. Int J Chron Obstruct Pulmon Dis. 2016;11:2341-2348. https://doi.org/10.2147/COPD.S115132.

19. Kerkhof M, Freeman D, Jones R, Chisholm A, Price DB. Predicting frequent COPD exacerbations using primary care data. Int J Chron Obstruct Pulmon Dis. 2015;10:2439-2450. https://doi.org/10.2147/COPD.S94259.

20. Siva R, Green RH, Brightling CE, Shelley M, Hargadon B, McKenna S et al. Eosinophilic airway inflammation and exacerbations of COPD: a randomised controlled trial. Eur Respir J. 2007;29(5):906-913. https://doi.org/10.1183/09031936.00146306.

21. Couillard S, Larivee P, Courteau J, Vanasse A. Eosinophils in COPD Exacerbations Are Associated With Increased Readmissions. Chest. 2017;151(2):366-373. https://doi.org/10.1016/j.chest.2016.10.003.

22. Mullerova H, Meeraus WH, Galkin DV, Albers FC, Landis SH. Clinical burden of illness among patients with severe eosinophilic COPD. Int J Chron Obstruct Pulmon Dis. 2019;14:741-755. https://doi.org/10.2147/COPD.S194511.

23. Criner GJ, Celli BR, Brightling CE, Agusti A, Papi A, Singh D et al. Benralizumab for the Prevention of COPD Exacerbations. N Engl J Med. 2019;381(11):1023-1034. https://doi.org/10.1056/NEJMoa1905248.

24. Lommatzsch M, Mohme SN, Stoll P, Virchow JC. Response to Various Biologics in Patients with Both Asthma and Chronic Obstructive Pulmonary Disease. Respiration. 2023;102(12):986-990. https://doi.org/10.1159/000534922.

25. Bhatt SP, Rabe KF, Hanania NA, Vogelmeier CF, Cole J, Bafadhel M et al. Dupilumab for COPD with Type 2 Inflammation Indicated by Eosinophil Counts. N Engl J Med. 2023;389(3):205-214. https://doi.org/10.1056/NEJMoa2303951.

26. Castro M, Corren J, Pavord ID, Maspero J, Wenzel S, Rabe KF et al. N Engl J Med. 2018;378(26):2486-2496. https://doi.org/10.1056/NEJMoa1804092.


Review

For citations:


Trushenko NV, Lavginova BB, Belkina OS, Avdeev SN. Targeted therapy as a new perspective in the treatment of COPD. Meditsinskiy sovet = Medical Council. 2024;(20):10-16. (In Russ.) https://doi.org/10.21518/ms2024-519

Views: 453


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2079-701X (Print)
ISSN 2658-5790 (Online)