Clinical experience with the use of oxygen-helium mixture in rehabilitation and outpatient treatment of patients with acute community-acquired pneumonia with ischemic heart disease

Background. Community-acquired pneumonia in elderly patients with concomitant coronary artery disease is characterized by high risk of cardiovascular complications and mortality due to systemic inflammatory response, endothelial dysfunction, and hypoxemia. Standard therapeutic protocols demonstrate insufficient efficacy, necessitating the search for innovative rehabilitation strategies.
Objective. To evaluate the clinical efficacy and safety of heated helium-oxygen mixture (thermoheliox) inhalations in the complex therapy and rehabilitation of patients with moderate-to-severe community-acquired pneumonia with underlying coronary artery disease.
Materials and methods. An open-label randomized clinical trial included 320 patients (aged 40-80 years) with CT-verified community-acquired pneumonia and concomitant CAD, discharged from hospital within 5 days. Patients were divided into two groups: the main group (n=160) received standard therapy supplemented with a 10- day course of thermoheliox inhalations (70% helium, 30% oxygen, temperature 50-80°C) in cyclic regimen; the control group (n=160) received standard treatment only. Clinical, laboratory (CRP, leukocytes, ESR), instrumental (spirometry, echocardiography, chest CT, capnometry, pulse oximetry), and psychometric parameters (TOBOL test, 6-minute walk test) were assessed.
Results. The thermoheliox therapy group demonstrated significant acceleration of clinical symptom resolution, with CRP normalization on day 10 in 90% vs 75% in controls (p<0.05). The incidence of pulmonary complications (bronchiolitis, atelectasis, emphysematous bullae) at 3 months was 12% vs 37% in the control group. Gas exchange parameters improved faster: PaCO₂ normalization was achieved in 85% vs 69%, SpO₂ ≥95% on day 5 in 100% vs 93-94% in controls. Exercise tolerance by 6-minute walk test increased by 8.1% vs 1.2%. Central hemodynamic parameters showed reduction in total peripheral resistance from 1480±150 to 980±56 dyn/sec/cm⁻⁵ and increase in cardiac output from 3.5±0.6 to 5.3±1.0 L/min. Psychological testing revealed an increase in patients with harmonious attitude toward disease from 52% to 82% vs 54% to 64% in controls.
Conclusions. The use of heated heliumoxygen mixture in rehabilitation of patients with community-acquired pneumonia with underlying CAD demonstrates pronounced clinical effect, reduces pulmonary complications by 66%, improves central hemodynamic parameters by 42%, and shows high safety profile. The method is recommended for inclusion in comprehensive treatment programs for this patient category.

1. Chyong T.T., Shogenova L.V. Ispol'zovanie geliy-kislorodnoy smesi pri respiratornykh zabolevaniyakh. Prakticheskaya pul'monologiya. 2021;1. (In Russ.)

2. Austin A, Winskog C, van den Heuvel C, Byard RW. Recent trends in suicides utilizing helium. Journal of Forensic Science. 2011 May;56(3):649-51.

3. Corrales-Medina VF, Alvarez KN, Weissfeld LA, Angus DC, Chirinos JA, Chang CC, Newman A, Loehr L, Folsom AR, Elkind MS, Lyles MF, Kronmal RA, Yende S. Association between hospitalization for pneumonia and subsequent risk of cardiovascular disease. JAMA. 2015 Jan 20;313(3):264-74. doi: 10.1001/jama.2014.18229. PMID: 25602997; PMCID: PMC4687729.

4. Musher DM, Rueda AM, Kaka AS, Mapara SM. The association between pneumococcal pneumonia and acute cardiac events. Clin Infect Dis. 2007 Jul 15;45(2):158-65. Epub 2007 Jun 6. PMID: 17578773. https://doi.org/10.1086/518849

5. Pokhaznikova M.A. Commgnity-acqgired pneumonia in adults: outpatient treatment. Russian Family Doctor. 2016;20(1):4-16. (In Russ.) https://doi.org/10.17816/RFD201614-16

6. Mezhirova N.M., Danilova V.V., Ovcharenko S.S. Pathophysiological and diagnostic aspects of systemic inflammatory response syndrome. Emergency Medicine. 2011;1-2(32-33):34-40. (In Russ.)

7. Bone R.C., Balk R.A., Cerra F.B., Dellinger R.P., Fein A.M., Knaus W.A., Schein R.M., Sibbald W.J. Defi nitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101:1644–55. https://doi.org/10.1378/chest.101.6.1644

8. Melnikova Yu.S., Makarova T.P. Endothelial dysfunction as a central link in the pathogenesis of chronic diseases. Kazan Medical Journal. 2015;96(4):659-665. (In Russ.)

9. Cillóniz C, Ewig S, Polverino E, Marcos MA, Esquinas C, Gabarrús A, Mensa J, Torres A. Microbial aetiology of community-acquired pneumonia and its relation to severity. Thorax. 2011 Apr;66(4):340-6. https://doi.org/10.1136/thx.2010.143982. Epub 2011 Jan 21. PMID: 21257985.

10. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007 Mar 1;44 Suppl 2(Suppl 2):S27-72. https://doi.org/10.1086/511159. PMID: 17278083; PMCID: PMC7107997.

11. Gainnier M, Arnal JM, Gerbeaux P, Donati S, Papazian L, Sainty JM. Helium-oxygen reduces work of breathing in mechanically ventilated patients with chronic obstructive pulmonary disease. Intensive Care Med. 2003 Oct;29(10):1666-70. https://doi.org/10.1007/s00134-003-1911-z. Epub 2003 Jul 25. PMID: 12897990.

12. Metodicheskie rekomendatsii primenenie termicheskogo gelioksa (t he/o2) v lechenii bol'nykh s dn (sindromom dykhatel'nykh rasstroystv). Rassmotren i utverzhden Rossiyskim Respiratornym obshchestvom 15 oktyabrya 2018g. Protokol predstavlen na XXVIII Natsional'nom Kongresse po boleznyam organov dykhaniya 19 oktyabrya 2018 goda, g. Moskva. (In Russ.)

13. Potapnev M.P. Cytokine storm: causes and consequences. Immunologiya. 2021;42(2):175–188. (In Russ.) https://doi.org/10.33029/0206-4952-2021-42-2-175-188

14. Chatenoud L., Ferran C., Reuter A., Legendre C., Gevaert Y., Kreis H., Frachimont P., Bach J.-F. Systemic reaction to the anti-Tcell monoclonal antibody OKT3 in relation to serum levels of tumor necrosis factor and interferon-α. N. Engl. J. Med. 1989;320(21):1420–1. https://doi.org/10.1056/nejm198905253202117

15. Blackwell T.S., Christman J.W. Sepsis and cytokines: current status. Br. J. Anaesth, 1996;77:110–7. https://doi.org/10.1093/ bja/77.1.110

16. Tisoncik J.R., Korth M.J., Simmons C.P., Farrar J., Martin T.R., Katze M.G. Into the eye of the cytokine storm. Microbiol. Mol. Biol. Rev. 2012;76(1):16–32. https://doi.org/10.1128/ MMBR.05015-11

17. Simbirtsev A.S. Сytokines in the pathogenesis of infectious and noninfectious human diseases. Meditsinskiy akademicheskiy zhurnal. 2013;3: 18–41. https://doi.org/10.17816/MAJ13318-41

18. Dinarello C.A. Proinfl ammatory cytokines. Chest. 2000;118(2):503–8. https://doi.org/10.1378/chest.118.2.503

19. Winkler U., Jensen M., Manzke O., Schulz H., Diehl V., Engert A. Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood. 1999;94(7): 2217–24. PMID: 10498591.

20. Porter D.L., Levine B.L., Kalos M., Bagg A., June C.H. Chimeric antigen receptor-modifi ed T cells in chronic lymphoid leukemia. N. Engl. J. Med. 2011;365 (8):725–33. https://doi.org/10.1056/ nejmoa1103849

21. Panelli M.C., White R., Foster M., Martin B., Wang E., Smith K., Marincola F.M. Forecasting the cytokine storm following systemic interleukin (IL)-2 administration. J. Transl. Med. 2004; 2: 17. https://doi.org/10.1186/1479-5876-2-17

22. Cherniak A.V., Savushkina O.I. Spirometry in clinical practice. Bulletin Physiology and Pathology of Respiration. 2020;(77):125-133. (In Russ.) https://doi.org/10.36604/1998-5029-2020-77-125-133

23. Urazalina S.Zh., Nurgalieva G.K., Aymakhanova G.T. Vozmozhnosti ekhokardiografii v diagnostike neotlozhnykh sostoyaniy. Vestnik Kazakhskogo Natsional'nogo meditsinskogo universiteta. 2019;4:61-69. (In Russ.)

24. Bubnova M.G., Persiyanova-Dubrova A.L. Six-minute walk test in cardiac rehabilitation. Cardiovascular Therapy and Prevention. 2020;19(4):2561. (In Russ.) https://doi.org/10.15829/1728-8800-2020-2561

25. Fuzhenko E., Pogoreltsev V., Dzhanelidze T., Krajnyukov P. MSCT imaging of pulmonary tissue lesions in acute respiratory distress syndrome. Glavnyy vrach Yuga Rossii. 2017;2(54):59-65. (In Russ.)

26. Dedov II. Personalized Medicine. Annals of the Russian Academy of Medical Sciences. 2019;74(1):61–70. https://doi.org/10.15690/vramn1108

27. Singh SJ, Puhan MA, Andrianopoulos V, et al. An official systematic review of the European Respiratory Society/American Thoracic Society: measurement properties of field walking tests in chronic respiratory disease. Eur Respir J. 2014;44(6):1447-78. https://doi.org/10.1183/09031936.00150414

28. Krasnovsky A.L. , Grogoriev S.P., Alekhin A.I., Potapov V.N. Application of heated oxygen-helium mixture for combined treatment of communityacquired pneumonia. Clinical Medicine. 2013;91(5):38-41. (In Russ.)

29. Pleshko A.A. Vnebol'nichnaya pnevmoniya: serdechnososudistye sobytiya v ostrom periode. Aktual'nye problemy sovremen-noy meditsiny i farmatsii 2020 : sb. materialov LXXIII Mezhdunar. nauch.-prakt. konf. studentov i molodykh uchenykh, 15-17 apr. Minsk, 2020 g. / pod red. A. V. Sikorskogo, V. Ya. Khryshchanovicha. Minsk, 2020:692–696. (In Russ.)