Abstract
Background. Bronchobstructive diseases are accompanied by changes in autonomic and hemodynamic regulation. Nonlinear characteristics of circulatory rhythms may serve as integrative functional features of individual rehabilitation response, but they are not direct molecular biomarkers.
Objective. To identify individual profiles of changes in nonlinear parameters of neural and hemodynamic regulation in patients with bronchobstructive diseases after rehabilitation and to assess their associations with baseline clinical and functional characteristics.
Material and methods. Twenty patients with bronchobstructive syndrome were examined before and after inpatient rehabilitation. Sample entropy, Poincaré plot parameters, and pseudo-attractor measures were calculated for RR, SSTI, and DDTI intervals. Paired changes were assessed with the Wilcoxon signed-rank test; Bonferroni correction was applied to four key comparisons. Individual trajectories were clustered by k-means; clinical associations were explored by Spearman correlation.
Results. Nominal increases were observed in RR SampEn and RR SD1, whereas SSTI SD2 and SSTI S decreased. After Bonferroni correction, only the increase in RR SD1 remained statistically significant (p = 0.01). No material change was found for DDTI. Nominal associations of RR SampEn change with baseline FEV1, RR SD1 change with BMI, and SSTI SD2 change with baseline dyspnea were considered exploratory. Three preliminary response profiles were identified: homeodynamic (45%), borderline (30%), and dissociative (25%).
Conclusion. The observed interindividual heterogeneity supports functional phenotyping for personalized rehabilitation monitoring. Clinical use of these profiles requires independent validation and comparison with clinical outcomes and molecular and cellular markers.
Keywords
Authors and affiliations
https://elibrary.ru/ghonpd
A.V. Rubinskiy, G.I. Lobov
I.P. Pavlov Institute of Physiology of the Russian Academy of Sciences, Makarova Emb., 6, Saint-Petersburg, 199034, Russian Federation
References
1. Alqahtani J.S., Aldhahir A.M., Alghamdi S.M., Al Ghamdi S.S., AlDraiwiesh I.A., Alsulayyim A.S., Alqahtani A.S. et al. A systematic review and meta-analysis of heart rate variability in COPD. Front Cardiovasc Med. 2023; 10: 1070327. DOI: 10.3389/fcvm.2023.1070327
2. Поликлиническая терапия: учебник. Под ред. И.Л. Давыдкина, Ю.В. Щукина. 2-е изд., перераб. и доп. Москва: ГЭОТАР-Медиа, 2020; 840. ISBN: 978-5-9704-5545-6 [Outpatient Therapy: a textbook. Edited by I.L. Davydkin, Yu.V. Shchukin. 2nd ed., revised and expanded. Moscow: GEOTAR-Media, 2020; 840. ISBN: 978-5-9704-5545-6 (in Russian)].
3. Magri D., Fiori E., Agostoni P., Correale M., Piepoli M., Nodari S., Beltrami M., Paolillo S., Filardi P.P., Palazzuoli A.; Working Group on Heart Failure of the Italian Society of Cardiology. Heart failure and chronic obstructive pulmonary disease. A combination not to be underestimated. Heart failure reviews. 2025; 30 (6): 1525–38. DOI: 10.1007/s10741-025-10566-3
4. Huang Y.C., Lin T.Y., Wu H.T., Chang P.J., Lo C.Y., Wang T.Y., Kuo C.S., Lin S.M., Chung F.T., Lin H.C., Hsieh M.H., Lo Y.L. Cardiorespiratory coupling is associated with exercise capacity in patients with chronic obstructive pulmonary disease. BMC Pulm Med. 2021; 21 (1): 22. DOI: 10.1186/s12890-021-01400-1.
5. Oliveira R., Brito J.P., Ceylan H.İ., Soares M.B., Martins A.D., Vasconcelos T., Moutão J., Alves S. Characteristics of Physical Exercise Programs and Their Effects on Quality of Life and Functional Capacity in Individuals with Chronic Obstructive Pulmonary Disease: A Scoping Review. Medicina (Kaunas). 2025; 61 (6): 970. DOI: 10.3390/medicina61060970.
6. Gronwald T., Rogers B., Hoos O. Fractal Correlation Properties of Heart Rate Variability: A New Biomarker for Intensity Distribution in Endurance Exercise and Training Prescription? Front Physiol. 2020; 11: 550572. DOI: 10.3389/fphys.2020.550572.
7. Zimatore G., Falcioni L., Gallotta M.C., Bonavolontà V., Campanella M., De Spirito M., Guidetti L., Baldari C. Recurrence quantification analysis of heart rate variability to detect both ventilatory thresholds. PLoS One. 2021; 16 (10): e0249504. DOI: 10.1371/journal.pone.0249504.
8. Santos A.A., Ricci-Vitor A.L., Bragatto V.S., Santos A.P., Ramos E.M., Vanderlei L.C. Can geometric indices of heart rate variability predict improvement in autonomic modulation after resistance training in chronic obstructive pulmonary disease? Clin. Physiol Funct Imaging. 2017; 37 (2): 124–30. DOI: 10.1111/cpf.12275.
9. Al Chikhanie Y., Bailly S., Amroussa I., Veale D., Hérengt F., Verges S. Clustering of COPD patients and their response to pulmonary rehabilitation. Respir Med. 2022; 198: 106861. DOI: 10.1016/j.rmed.2022.106861.
10. Penáz J., Voigt A., Teichmann W. Beitrag zur fortlaufenden indirekten Blutdruckmessung [Contribution to the continuous indirect blood pressure measurement]. Z Gesamte Inn Med. 1976; 31 (24): 1030–3.
11. Henriques T., Ribeiro M., Teixeira A., Castro L., Antunes L., Costa-Santos C. Nonlinear Methods Most Applied to Heart-Rate Time Series: A Review. Entropy (Basel, Switzerland). 2020; 22 (3): 309. DOI: 10.3390/e22030309.
12. Zivanovic I., Zupanic E., Avbelj V., Zibert J., Lainscak M., Kalisnik J.M. Nonlinear Heart Rate Variability in Patients with Chronic Obstructive Pulmonary Disease and Changes after 4-week Comprehensive Inpatient Pulmonary Rehabilitation. Nonlinear Dynamics, Psychology & Life Sciences. 2022; 26 (2): 149–62.
13. Sharma R.K., Bhatt A., Dwivedi S.K. Effect of obesity on autonomic functions of Heart among healthy volunteers at a teaching Institute. J. of Family Medicine and Primary Care. 2022; 11 (7): 3636–41. DOI: 10.4103/jfmpc.jfmpc_2413_21.
14. van Gestel A.J., Clarenbach C.F., Stöwhas A.C., Rossi V.A., Sievi N.A., Camen G., Kohler M. The speed of blood pressure fluctuations in patients with chronic obstructive pulmonary disease. Heart, Lung and Circulation. 2014; 23 (3): 280–6. DOI: 10.1016/j.hlc.2013.08.010.
15. Ambrosino P., Nolano M., Candia C., Grassi G., Maniscalco M. Addressing Oxidative Stress and Endothelial Dysfunction in Chronic Respiratory Diseases: The Role of Exercise and Multidisciplinary Rehabilitation. Antioxidants (Basel). 2024; 13 (12): 1543. DOI: 10.3390/antiox13121543.
16. Marcuccio G., Candia C., Maniscalco M., Ambrosino P. Endothelial dysfunction in chronic obstructive pulmonary disease: an update on mechanisms, assessment tools and treatment strategies. Front Med (Lausanne). 2025; 12: 1550716. DOI: 10.3389/fmed.2025.1550716.
17. Maniscalco M., Paris D., Cuomo P., Fuschillo S., Ambrosino P., Tramice A., Palomba L., Motta A. Metabolomics of COPD Pulmonary Rehabilitation Outcomes via Exhaled Breath Condensate. Cells. 2022; 11 (3): 344. DOI: 10.3390/cells11030344.
18. Ali H., Brooks C., Tzeng Y.-C., Crane J., Beasley R., Gibson P. et al. Heart rate variability as a marker of autonomic nervous system activity in young people with eosinophilic and non-eosinophilic asthma. J. Asthma. 2023; 60 (3): 534–42. DOI: 10.1080/02770903.2022.2070763.