Email this article Effect of the inhalation inhibitor PDE-4 CHF6001 on some pathogenetic links in chronic obstructive pulmonary disease development
- Authors: Salukhov V.V.1, Kharitonov M.A.1, Pivovich A.V.1, Voloshin N.I.1
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Affiliations:
- Military Medical Academy named after S.M. Kirov of the Ministry of Defense of the Russian Federation
- Issue: Vol 23, No 4 (2021)
- Pages: 235-246
- Section: Reviews
- URL: https://journals.eco-vector.com/1682-7392/article/view/63652
- DOI: https://doi.org/10.17816/brmma63652
- ID: 63652
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Abstract
CHF6001 is a new inhaled phosphodiesterase-4 inhibitor that is safe and well tolerated by both healthy people and patients with bronchial asthma. The effect of CHF6001, in addition to standard triple therapy for chronic obstructive pulmonary disease, was evaluated on some inflammatory markers in induced sputum and blood in 61 patients (54 completed the study) with chronic obstructive pulmonary disease and chronic bronchitis. From October 2016 to November 2017, a multicenter, three-period (every 32 days), tripartite, placebo-controlled, double-blind, complete block cross-sectional study was conducted in Great Britain and Germany. Patients were treated by CHF6001 at doses of 800 or 1600 µg, or the corresponding placebo using the dry powder inhaler NEXThaler. The induced sputum was collected on day 1 before the treatment and days 20, 26, and 32 after the treatment. Blood was also collected on day 1 before the treatment and day 32 before and after the treatment. Result analyses took into account the inflammatory biomarkers in induced sputum and blood, respiratory function, and symptoms and side effects. CHF6001, which supplements triple therapy in patients with moderate to severe chronic obstructive pulmonary disease and chronic bronchitis, was well tolerated and significantly reduces the number of key biomarkers of airway inflammation in sputum and blood after 32 days of treatment. CHF6001, administered by inhalation, creates a high therapeutic concentration in the lungs compared with other systemic phosphodiesterase-4 inhibitors and improves the therapeutic index due to anti-inflammatory effects while minimizing the possible side effects typical of the latter.
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About the authors
Vladimir V. Salukhov
Military Medical Academy named after S.M. Kirov of the Ministry of Defense of the Russian Federation
Email: vlasaluk@yandex.ru
ORCID iD: 0000-0003-1851-0941
SPIN-code: 4531-6011
doctor of medical sciences
Russian Federation, Saint PetersburgMikhail A. Kharitonov
Military Medical Academy named after S.M. Kirov of the Ministry of Defense of the Russian Federation
Email: micjul11@yandex.ru
ORCID iD: 0000-0002-6521-7986
SPIN-code: 7678-2278
Doctor of medical sciences
Russian Federation, Saint-PetersburgAndrey V. Pivovich
Military Medical Academy named after S.M. Kirov of the Ministry of Defense of the Russian Federation
Author for correspondence.
Email: pivovich.andrey@gmail.com
Russian Federation, Saint Petersburg
Nikita I. Voloshin
Military Medical Academy named after S.M. Kirov of the Ministry of Defense of the Russian Federation
Email: Nikitavoloshin1990@gmail.com
ORCID iD: 0000-0002-3880-9548
SPIN-code: 6061-4342
adjunct
Russian Federation, Saint PetersburgReferences
- Practical Pulmonology: guide for doctors. Salukhov VV, Kharitonov MA, editors. Мoscow: GEOTAR-Media; 2017. 416 p. (In Russ.).
- Moroz EV, Karateev AE, Kryukov EV. Gastrointestinal bleeding with the use of new oral anticoagulants: epidemiology, risk factors, treatment, and prevention. Rheumatology Science and Practice. 2017;55(6): 827–836. (In Russ.). doi: 10.14412/1995-4484-2017-675-684
- Savushkina OI, Chernyak AV, Kameneva MY, et al. Possibilities of pulse oscillometry in the diagnosis of mild airway obstruction. Pulmonology. 2018;28(4):391–398. (In Russ.). doi: 10.18093/0869-0189-2018-28-4-391-398
- Savushkina OI, Chernyak AV, Kryukov EV, et al. Impulse оscillometry in the diagnosis of moderate airway obstruction. Journal of Clinical Practice. 2018;9(4):33–39 (In Russ.). doi: 10.17816/clinpract9433-39
- Zaitsev AA, Okovity SV, Kryukov EV. Cough: а practical guide for doctors. Мoscow: The Main Military Clinical Hospital named after NN. Burdenko; 2015. 59 p.
- Fabbri LM, Calverley PM, Izquierdo-Alonso JL, et al. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials. The Lancet. 2009;374(9691):695–703. doi: 10.1016/S0140-6736(09)61252-6
- Moretto N, Caruso P, Bosco R, et al. CHF6001 I: A Novel Highly Potent and Selective Phosphodiesterase 4 Inhibitor with Robust Anti-Inflammatory Activity and Suitable for Topical Pulmonary Administration. J Pharmacol Exp Ther. 2015;352(3):559–567. doi: 10.1124/jpet.114.220541
- Rabe K, Watz H, Baraldo S, et al. Anti-inflammatory effects of roflumilast in chronic obstructive pulmonary disease (ROBERT): a 16-week, randomised, placebo-controlled trial. The Lancet Respiratory Medicine. 2018;6(11):827–836. doi: 10.1016/S2213-2600(18)30331-X
- Villetti G, Carnini C, Battipaglia L, et al. CHF6001 II: A novel phosphodiesterase 4 inhibitor, suitable for topical pulmonary administration – in vivo preclinical pharmacology profile defines a potent anti-inflammatory compound with a wide therapeutic window. J Pharmacol Exp Ther. 2015;352(3):568–578. doi: 10.1124/jpet.114.220558
- Singh D, Roche N, Halpin D, et al. Current Controversies in the Pharmacological Treatment of Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2016;194(5):541–549.
- Shmelev EI, Shmeleva NV. Sovremennye vozmozhnosti protivovospalitel’noj terapii v pul’monologii. Vrach. 2012;(2):19–23.
- Watz H, Mistry SJ, Lazaar AL. Safety and tolerability of the inhaled phosphodiesterase 4 inhibitor GSK256066 in moderate COPD. Pulmonary Pharmacology Therapeutics. 2013;26(5): 588–595.
- Calverley PM, Rabe FK, Goehring U., et al. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. The Lancet. 2009;374(9691):685–694. doi: 10.1016/S0140-6736(09)61255-1
- Vestbo J Tan L, Atkinson G, et al. Controlled trial of 6-weeks’ treatment with a novel inhaled phosphodiesterase type-4 inhibitor in COPD. European Respiratory Journal. 2009;33(5):1039–1044.
- Hodge S, Hodge G, Scicchitano R, et al. Alveolar macrophages from subjects with chronic obstructive pulmonary disease are deficient in their ability to phagocytose apoptotic airway epithelial cells. Immunol Cell Biol. 2003;81(4):289–296.
- Higham A, Booth G, Lea S, et al. The effects of corticosteroids on COPD lung macrophages: a pooled analysis. Respir Res. 2015;16:98.
- Singh D, Beeh KM, Colgan B, et al. Effect of the inhaled PDE4 inhibitor CHF6001 on biomarkers of inflammation in COPD. Respiratory Research. 2019;20(1):180.
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