Потенциальные предикторы тяжелого течения и исхода внебольничной пневмонии
https://doi.org/10.18093/0869-0189-2023-33-2-225-232
Аннотация
Тяжелая пневмония (ТП) — состояние, при котором отмечается высокий риск летального исхода, а госпитализация в отделение интенсивной терапии является обязательной. Заболеваемость ТП резко возросла в период пандемии новой коронавирусной инфекции. Своевременная диагностика и раннее начало адекватного лечения ТП имеют решающее значение для повышения выживаемости тяжелобольных пациентов.
Целью обзора явился анализ научных публикаций, посвященных изучению молекулярных маркеров, позволяющих уже при поступлении в стационар объективно оценить степень тяжести пневмонии и определить тактику лечения, основываясь на прогнозе возможного исхода заболевания. Систематический поиск проведен в электронных базах данных PubMed, Medline, Web of Science за 2019—2022 гг.
Заключение. В обзоре внимание уделено прогностической роли ряда маркеров иммунного ответа организма, сосудистой трансформации, а также ангиотензина II и ангиотензинпревращающего фермента-2. Дальнейшие проспективные исследования потенциальных предикторов течения ТП позволят включить определение молекул-маркеров в комплексную клинико-лабораторную диагностику с целью раннего прогнозирования состояния госпитализируемого пациента и предполагаемого исхода.
Ключевые слова
Об авторах
Е. В. ВолчковаРоссия
Волчкова Елизавета Владимировна — аспирант кафедры анестезиологии и реаниматологии.
194100, Санкт-Петербург, ул. Литовская, 2; тел.: (812) 591-79-11
Конфликт интересов:
Конфликт интересов авторами не заявлен
О. Н. Титова
Россия
Титова Ольга Николаевна — доктор медицинских наук, профессор, директор Научно-исследовательского института пульмонологии.
197022, Санкт-Петербург, ул. Льва Толстого, 6-8; тел.: (812) 338-68-40
Конфликт интересов:
Конфликт интересов авторами не заявлен
Н. А. Кузубова
Россия
Кузубова Наталия Анатольевна — доктор медицинских наук, заместитель директора по научной работе Научно-исследовательского института пульмонологии.
197022, Санкт-Петербург, ул. Льва Толстого, 6-8; тел.: (812) 338-66-06
Конфликт интересов:
Конфликт интересов авторами не заявлен
Е. С. Лебедева
Россия
Лебедева Елена Сергеевна — кандидат биологических наук, ведущий научный сотрудник Научно-исследовательского института пульмонологии.
197022, Санкт-Петербург, ул. Льва Толстого, 6-8; тел.: (812) 338-78-20
Конфликт интересов:
Конфликт интересов авторами не заявлен
Список литературы
1. Авдеев С.Н., Белобородов В.Б., Белоцерковский Б.З. и др. Тяжелая внебольничная пневмония у взрослых. Клинические рекомендации Федерации анестезиологов и реаниматологов России. Анестезиология и реаниматология. 2022; (1): 6—35. DOI: 10.17116/anaesthesiology20220116. /
2. Chen C.H., Lin S.W., Shen C.F. et al. Biomarkers during COVID-19: Mechanisms of change and implications for patient outcomes. Diagnostics (Basel). 2022; 12 (2): 509. DOI: 10.3390/diagnostics12020509.
3. Espinoza R., Silva J.R.L.E., Bergmann A. et al. Factors associated with mortality in severe community-acquired pneumonia: a multicenter cohort study. J. Crit. Care. 2019; 50: 82-86. DOI: 10.1016/j.jcrc.2018.11.024.
4. Cilldniz C., Torres A., Niederman M.S. Management of pneumonia in critically ill patients. BMJ. 2021; 375: e065871. DOI: 10.1136/bmj-2021-065871.
5. Robb M.A., McInnes P.M., Califf R.M. Biomarkers and surrogate endpoints: developing common terminology and definitions. JAMA. 2016; 315 (11): 1107-1108. DOI: 10.1001/jama.2016.2240.
6. Samprathi M., Jayashree M. Biomarkers in COVID-19: an up-to-date review. Front. Pediatr. 2021; 8: 607647. DOI: 10.3389/fped.2020.607647.
7. Frisoni P., Neri M., D’Errico S. et al. Cytokin storm and histopa-thological findings in 60 cases of COVID-19-related death: from viral load research to immunohistochemical quantification of major players IL-1|3, IL-6, IL-15 and TNF-a. Forensic Sci. Med. Pathol. 2022; 18 (1): 4-19. DOI: 10.1007/s12024-021-00414-9.
8. Du P., Geng J., Wang F. et al. Role of IL-6 inhibitor in treatment of COVID-19-related cytokine release syndrome. Int. J. Med. Sci. 2021; 18 (6): 1356-1362. DOI: 10.7150/ijms.53564.
9. Mojtabavi H., Saghazadeh A., Rezaei N. Interleukin-6 and severe COVID-19: a systematic review and meta-analysis. Eur. Cytokine Netw. 2020; 31 (2): 44-49. DOI: 10.1684/ecn.2020.0448.
10. Giannakodimos I., Gkountana G.V., Lykouras D. et al. The role of interleukin-6 in the pathogenesis, prognosis and treatment of severe COVID-19. Curr. Med. Chem. 2021; 28 (26): 5328-5338. DOI: 10.2174/0929867328666201209100259.
11. Liu T., Zhang J., Yang Y. et al. The role of interleukin-6 in monitoring severe case of coronavirus disease 2019. EMBO Mol. Med. 2020; 12 (7): e12421. DOI: 10.15252/emmm.202012421.
12. Avila-Nava A., Cortes-Telles A., Torres-Erazo D. et al. Serum IL-6: a potential biomarker of mortality among SARS-CoV-2 infected pations in Mexico. Cytokine. 2021; 143: 155543. DOI: 10.1016/j.cyto.2021.155543.
13. Sayah W., Berkane I., Guermache I. et al. Interleukin-6, procalcitonin and neutrophil-to-lymphocite ratio: Potential immune-inflammatory parameters to identify severe and fatal forms of COVID-19. Cytokine. 2021; 141: 155428. DOI: 10.1016/j.cyto.2021.155428.
14. Chen R., Sang L., Jiang M. et al. Longitudinal hematologic and immunologic variations associated with the progression of COVID-19 patients in China. J. Allergy Clin. Immunol. 2020; 146 (1): 89-100. DOI: 10.1016/j.jaci.2020.05.003.
15. Patra T., Meyer K., Geerling L. et al. SARS-Cov-2 spike protein promotes IL-6 trabs-signaling by activation of angiotensin II receptor signaling in epithelial cells. PLoS Pathog. 2020; 16 (12): e1009128. DOI: 10.1371/journal.ppat.1009128.
16. Kumar M., Al Khodor S. Pathophysiology and treatment strategies for COVID-19. J. Transl. Med. 2020; 18 (1): 353. DOI: 10.1186/s12967-020-02520-8.
17. Galvdn-Romdn J.M., Rodriguez-Garcia S.C., Roy-Vallejo E. et al. IL-6 serum levels predict severity and response to tocilizumab in COVID-19: an observational study. J. Allergy Clin. Immunol. 2020; 147 (1): 72-80.e.8. DOI: 10.1016/j.jaci.2020.09.018.
18. Coomes E.A., Haghbayan H. Interleukin-6 in COVID-19: a systematic review and meta-analysis. Rev. Med. Virol. 2020; 30 (6): 1-9. DOI: 10.1002/rmv.2141.
19. Smieszek S.P., Przychodzen B.P., Polymeropoulos V.M. et al. Assessing the potential correlation of polymorphisms in the IL6R with relative IL6 elevation in severely ill COVID-19 patients. Cytokine. 2021; 148: 155662. DOI: 10.1016/j.cyto.2021.155662.
20. Vakil M.K., Mansoori Y., Al-Awsi G.R.L. et al. Individual genetic variability mainly of proinflammatory cytokines, cytokine receptors, anf toll-like receptors dictates pathophysiology of COVID-19 disease. J. Med. Virol. 2022; 94 (9): 4088-4096. DOI: 10.1002/jmv.27849.
21. Udomsinprasert W., Jittikoon J., Sangroongruangsri S., Chaikled-kaew U. Circulating levels of interleukin-6 and interleukin-10, but not tumor necrosis factor-alpha, as potential biomarkers of severity and mortality for COVID-19: systematic review with meta-analysis. J. Clin. Immunol. 2021; 41 (1): 11-22. DOI: 10.1007/s10875-020-00899-z.
22. Jimdnez-Gastdlum G.R., Espinoza-Ortega A.M., Ramos-Paydn R. et al. More evidence of the link of interleukin-6 and interleukin-10 with critical COVID-19: a report in mexican parients. Iran J. Immunol. 2021; 18 (4): 331-337. DOI: 10.22034/IJI.2021.89905.1978.
23. Han H., Ma Q., Li C. et al. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg. Microbes Infect. 2020; 9 (1): 1123-1130. DOI: 10.1080/22221751.2020.1770129.
24. Hong W., Zhou X., Jin S. et al. A comparison of XGBoost, random forest, and nomograph for the prediction of disease severity in patients with COVID-19 pneumonia: implications of cytokine and immune cell profile. Front. Cell. Infect. Microbiol. 2022; 12: 819267. DOI: 10.3389/fcimb.2022.819267.
25. Ling L., Chen Z., Lui G. et al. Longitudinal cytokine profile in patients with mild to critical COVID-19. Front. Immunol. 2021; 12: 763292. DOI: 10.3389/fimmu.2021.763292.
26. Ackermann M., Verleden S.E., Kuehnel M. et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19. N. Engl. J. Med. 2020; 383 (2): 120-128. DOI: 10.1056/NEJMoa2015432.
27. Сизякина Л.П., Скрипкина Н.А., Антонова Е.А. и др. Динамика показателей иммунного статуса у пациентов с COVID-19, получающих терапию с включением антагониста рецептора ИЛ-6. Иммунология. 2022; 43 (2): 188-196. DOI: 10.33029/0206-4952-2022-43-2-188-196. /
28. Tharmarajah E., Buazon A., Patel V. et al. IL-6 inhibition in the treatment of COVID-19: a meta-analysis and meta-regression. J. Infect. 2021; 82 (5): 178-185. https://doi.org/10.1016/j.jinf.2021.03.008
29. Xu X., Han M., Li T. et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc. Natl. Acad. Sci. USA. 2020; 117 (20): 10970-10975. DOI: 10.1073/pnas.2005615117.
30. Azmy V., Kaman K., Tang D. et al. Cytokine profiles before and after immune modulation in hospitalized patients with COVID-19. J. Clin. Immunol. 2021; 41 (4): 738-747. DOI: 10.1007/s10875-020-00949-6.
31. Бобкова С.С., Тюрин И.Н., Трощанский Д.В. и др. Применение блокаторов рецепторов к IL-6 у пациентов с COVID-19 тяжелого течения. Пульмонология. 2021; 31 (3): 263-271. DOI: 10.18093/0869-0189-2021-31-3-263-271. /
32. Ahmed S., Mansoor M., Shaikh M.S., Siddiqui I. Presepsin as a predictive biomarker of severity in COVID-19: a systematic review. Indian J. Crit. Care Med. 2021; 25 (9): 1051-1054. DOI: 10.5005/jp-journals-10071-23967.
33. Fukada A., Kitagawa Y., Matsuoka M. et al. Presepsin as a predictive biomarker of severity in COVID-19: a case series. J. Med. Virol. 2021; 93 (1): 99-101. DOI: 10.1002/jmv.26164.
34. Lippi G., Sanchis-Gomar F., Henry B.M. Presepsin value predicts the risk of developing severe/critical COVID-19 illness: results of a pooled analysis. Clin. Chem. Lab. Med. 2021; 60 (1): e1—3. DOI: 10.1515/cclm-2021-0848.
35. Mabrey F.L., Morrell E.D., Bhatraju P.K. et al. Plasma soluble CD14 subtype levels are associated with clinical outcomes in critically ill subjects with coronavirus disease 2019. Crit. CareExplor. 2021; 3 (12): e0591. DOI: 10.1097/CCE.0000000000000591.
36. Arakawa N., Matsuyama S., Matsuoka M. et al. Serum stratifin and presepsin as candidate biomarkers for early detection of COVID-19 disease progression. J. Pharmacol. Sci. 2022; 150 (1): 21-30. DOI: 10.1016/j.jphs.2022.06.002.
37. Assal H.H., Abdelrahman S.M., Abdelbasset M.A. et al. Presepsin as a novel biomarker in predicting in-hospital mortality in patients with COVID-19 pneumonia. Int. J. Infec. Dis. 2022; 118: 155-163. DOI: 10.1016/j.ijid.2022.02.054.
38. Kim S.W., Lee H., Lee S.H. et al. Usefulness of monocyte distribution width and presepsin for early assessment of disease severity in COVID-19 patients. Medicine (Baltimore). 2022; 101 (27): e29592. DOI: 10.1097/MD.0000000000029592.
39. Зайцев А.А., Кондратьева Т.В. Биомаркеры воспаления при заболеваниях органов дыхания: клиническая практика и перспективы. Consilium Medicum. 2020; 22 (3): 34-39.
40. Ozkan S., Kahveci U., Hur I., Halici A. Prognostic importance of serum presepsin level in pneumonia focal sepsis and its relationship with other biomarkers and clinical severity scores. Saudi Med. J. 2021; 42 (9): 994-1001. DOI: 10.15537/smj.2021.42.9.20210163.
41. Ugajin M., Matsuura Y., Matsuura K., Matsuura H. Impact of initial presepsin level for clinical outcome in hospitalized patients with pneumonia. J. Thorac. Dis. 2019; 11 (4): 1387-1396. DOI: 10.21037/jtd.2019.03.74.
42. Domi H., Matsuura H., Kuroda M. et al. Simple prognostic factors and change of inflammatory markers in patients with severe corona-virus disease 2019: a single-center observation study. Acute Med. Surg. 2021; 8 (1): e683. DOI: 10.1002/ams2.683.
43. Park M., Hur M., Kim H. et al. Prognostic utility of procalcitonin, presepsin, and the VACO index for predicting 30-day mortality in hospitalized COVID-19 patients. Ann. Lab. Med. 2022; 42 (4): 406-414. DOI: 10.3343/alm.2022.42.4.406.
44. Zaninotto M., Mion M.M., Cosma C. et al. Presepsin in risk stratification of SARS-CoV-2 patients. Clin. Chim. Acta. 2020; 507: 161-163. DOI: 10.1016/j.cca.2020.04.020.
45. Halici A., Hur 1., Abatay K. et al. The role of presepsin in the diagnosis of chronic obstructive pulmonary disease acute exacerbation with pneumonia. Biomark. Med. 2020; 14 (1): 31-41. DOI: 10.2217/bmm-2019-0183.
46. Титова Е.А., Эйрих А.Р., Титова З.А. Роль пресепсина в диагностике и оценке тяжести течения сепсиса и тяжелой пневмонии. Терапевтический архив. 2018; 90 (11): 44-47.
47. Ham J.Y., Song K.E. A prospective study of presepsin as an indicator of the severity of community-acquired pneumonia in emergency departments: Comparison with pneumonia severity index and CURB-65 scores. Lab. Med. 2019; 50 (4): 364-369. https://doi.org/10.1093/labmed/lmz005
48. George P.M., Wells A.U., Jenkins R.G. Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy. Lancet Respir. Med. 2020; 8 (8): 807-815. DOI: 10.1016/S2213-2600(20)30225-3.
49. Fernandez-Patron C., Hardy E. Matrix metalloproteinases in health and disease in the times of COVID-19. Biomolecules. 2022; 12 (5): 692. DOI: 10.3390/biom12050692.
50. Hazra S., Chaudhuri A.G., Tiwary B.K., Chakrabarti N. Matrix metallopeptidase 9 as a host protein target of chloroquine and melatonin for immunoregulation in COVID-19: a network-based meta-analysis. Life Sci. 2020; 257: 118096. DOI: 10.1016/j.lfs.2020.118096.
51. Karakurt H.U., Plr P. Integration of transcriptomic profile of SARS-CoV-2 infected normal human bronchial epithelial cells with metabolic and protein-protein interaction networks. Turk. J. Biol. 2020; 44 (3): 168-177. DOI: 10.3906/biy-2005-115.
52. Meng W., Cao X., Sun W. et al. A functional polymorphism at the miR-491-5p binding site in the 3-untranslated region of the MMP-9 gene increase the risk of developing ventilator-associated pneumonia. Int. J. Mol. Med. 2021; 48 (6): 217. DOI: 10.3892/ijmm.2021.5050.
53. Qin L., Liu L., Wu Y. et al. Mycoplasms pneumonia downregulates RECK to promote matrix metalloproteinase-9 secretion by bronchial epithelial cells. Virulence. 2022; 13 (1): 1270-1284. DOI: 10.1080/21505594.2022.2101746.
54. D Avila-Mesquita C., Couto A.E.S., Campos L.C.B. et al. MMP-2 and MMP-9 levels in plasma are altered and associated with mortality in COVID-19 patients. Biomed. Pharmacother. 2021; 142: 112067. DOI: 10.1016/j.biopha.2021.112067.
55. Gelzo M., Cacciapuoti S., Pinchera B. et al. Matrix metalloproteinases (MMP) 3 and 9 as biomarkers of severity in COVID-19 patients. Sci. Rep. 2022; 12 (1): 1212. DOI: 10.1038/s41598-021-04677-8.
56. Kassianidis G., Siampanos A., Poulakou G. et al. Calprotectin and imbalances between acute-phase mediators are associated with critical illness in COVID-19. Int. J. Mol. Sci. 2022; 23 (9): 4894. DOI: 10.3390/ijms23094894.
57. Abers M.S., Delmonte O.M., Ricotta E.E. et al. An immune-based biomarker signature is associated with mortality in COVID-19 patients. JCIInsight. 2021; 6 (1): e144455. DOI: 10.1172/jci.in-sight.144455.
58. Duda I., Krzych L., Jqdrzejowska-Szypulka H., Lewin-Kowa-lik J. Plasma matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 as prognostic biomarkers in critically ill patients. Open Med. (Wars.). 2020; 15: 50-56. DOI: 10.1515/med-2020-0008.
59. Lerum T.V., Maltzahn N.N., Aukrust P. et al. Persistent pulmonary pathology after COVID-19 is associated with high viral load, weak antibody response, and high levels of matrix metalloproteinase-9. Sci. Rep. 2021; 11 (1): 23205. DOI: 10.1038/s41598-021-02547-x.
60. Ueland T., Hotter J., Holten A. et al. Distinct and early increase in circulating MMP-9 in COVID-19 patients with respiratory failure. J. Infect. 2020; 81 (3): e41-43. DOI: 10.1016/j.jinf.2020.06.061.
61. Chiang T.Y., Yu Y.L., Lin C.W. et al. The circulating level of MMP-9 and its ratio to TIMP-1 as a predictor of severity in patients with community-acquired pneumonia. Clin. Chim. Acta. 2013; 424: 261-266. DOI: 10.1016/j.cca.2013.06.013.
62. Birnhuber A., FlieBer E., Gorkiewicz G. et al. Between inflammatiom and thrombosis: endothelial cells in COVID-19. Eur. Respir. J. 2021; 58 (3): 2100377. DOI: 10.1183/13993003.00377-2021.
63. Karakas Celik S., Cakmak Genc G., Dursun A. A bioinformatic approach to investigating cytokine genes and their receptor variants in relation to COVID-19 progression. Int. J. Immunogenet. 2021; 48 (2): 211-218. DOI: 10.1111/iji.12522.
64. Biberoglu S., Ipekci A., Ikizceli 1. et al. Role of plasma angiotensin II and angiotensin-converting enzyme 2 levels on prognosis and mortality in hypertensive patients with COVID-19. Biomark. Med. 2021; 15 (17): 1581-1588. DOI: 10.2217/bmm-2021-0121.
65. Wu Z., Hu R., Zhang C. et al. Elevation of plasma angiotensin II level is a potential pathogenesis for the critically ill COVID-19 patients. Crit. Care. 2020; 24 (1): 290. DOI: 10.1186/s13054-020-03015-0.
66. Wang K., Gheblawi M., Nikhanj A. et al. Dysregulation of ACE (Angiotensin-Converting Enzyme)-2 and renin-angiotensin peptides in SARS-CoV-2 mediated mortality and end-organ injuries. Hypertension. 2022; 79 (2): 365-378. DOI: 10.1161/HYPERTEN-SIONAHA.121.18295.
67. Amezcua-Guerra L.M., Del Valle L., Gonzdlez-Pacheco H. et al. The prognostic importance of the angiotensin II/angiotensin-(1-7) ratio in patients with SARS-CoV-2 infection. Ther. Adv. Respir. Dis. 2022; 16: 17534666221122544. DOI: 10.1177/17534666221122544.
68. Lundstrom A., Ziegler L., Havervall S. et al. Soluble angiotensin-converting enzyme 2 is transiently elevated in COVID-19 and correlates with specific inflammatory and endothelial markers. J. Med. Virol. 2021; 93 (10): 5908-5916. DOI: 10.1002/jmv.27144.
69. Diaz-Troyano N., Gabriel-Medina P., Weber S. et al. Soluble an-giotensin-cinvertting enzyme 2 as a prognostic biomarker for disease progression in patients infected with SARS-CoV-2. Diagnostics (Basel). 2022; 12 (4): 886. DOI: 10.3390/diagnostics12040886.
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Для цитирования:
Волчкова Е.В., Титова О.Н., Кузубова Н.А., Лебедева Е.С. Потенциальные предикторы тяжелого течения и исхода внебольничной пневмонии. Пульмонология. 2023;33(2):225-232. https://doi.org/10.18093/0869-0189-2023-33-2-225-232
For citation:
Volchkova E.V., Titova O.N., Kuzubova N.A., Lebedeva E.S. Potential predictors of severe course and outcome of community-acquired pneumonia. PULMONOLOGIYA. 2023;33(2):225-232. (In Russ.) https://doi.org/10.18093/0869-0189-2023-33-2-225-232