Dynamic Inflammatory–Immune Biomarker Profiles Associated with Clinical Recovery in Elderly Patients with Severe Pneumonia: A Prospective Study

Inflammatory–Immune Biomarkers in Severe Pneumonia Recovery

  • Keling Peng The First Department of Respiratory and Critical Care Medical Center, The First People's Hospital of Baiyin City
  • Leilei Qu The First Department of Respiratory and Critical Care Medical Center, The First People's Hospital of Baiyin City
  • Zirong Zhang The Second Department of Respiratory and Critical Care Medicine, The First People's Hospital of Baiyin City
DOI: https://doi.org/10.5937/jomb0-66413
Keywords: Severe pneumonia, Inflammatory biomarkers, Immune function, Interleukin-6, Neutrophil-to-lymphocyte ratio, CD4-positive T-lymphocytes

Abstract


Background: Severe pneumonia in elderly patients is characterized by dysregulated inflammatory responses and impaired immune recovery. However, the dynamic interplay between inflammatory–immune biomarkers and clinical recovery remains insufficiently elucidated from a biochemical perspective.

Methods: This prospective study included 276 elderly patients with severe pneumonia. Serial measurements of inflammatory biomarkers [C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and neutrophil-to-lymphocyte ratio (NLR)] and immune indicators (CD4+ T cells and natural killer cells) were performed at baseline, day 3, and end-of-treatment. Clinical recovery was evaluated using time to clinical stability, oxygenation index (PaO₂/FiO₂), and length of hospital stay. Associations between biomarker dynamics and recovery outcomes were analyzed.

Results: All inflammatory biomarkers exhibited significant declines over time, accompanied by partial restoration of immune function. Greater reductions in CRP, PCT, and IL-6 at early time points were associated with faster clinical stabilization and improved oxygenation (all P < 0.01). NLR showed a pronounced early decrease, reflecting attenuation of systemic inflammatory stress. Notably, recovery of CD4+ T cells was significantly associated with improved clinical outcomes (P = 0.001), suggesting coordinated immune reconstitution. Patients with more favorable biomarker trajectories demonstrated shorter hospitalization and earlier transition to clinical stability. These findings indicate that integrated inflammatory–immune biomarker dynamics closely reflect the biological recovery process in severe pneumonia.

Conclusions: Dynamic monitoring of inflammatory and immune biomarkers provides valuable biochemical insights into recovery trajectories in elderly patients with severe pneumonia. Combined biomarker profiling may serve as a practical tool for evaluating disease progression and guiding individualized management strategies.

References

1. Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Resp Crit Care 2019; 200(7): e45-67.
2. Jones BE, Ramirez JA, Oren E, Soni NJ, Sullivan LR, Restrepo MI, et al. Diagnosis and Management of Community-acquired Pneumonia: An Official American Thoracic Society Clinical Practice Guideline. Am J Resp Crit Care 2026; 212(1): 24-44.
3. Martin-Loeches I, Torres A, Nagavci B, Aliberti S, Antonelli M, Bassetti M, et al. ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia. The European Respiratory Journal 2023; 61(4): 2200735.
4. Reyes LF, Conway Morris A, Serrano-Mayorga C, Derde LPG, Dickson RP, Martin-Loeches I. Community-acquired pneumonia. Lancet (London, England) 2025; 406(10517): 2371-88.
5. Mancinetti F, Marinelli A, Boccardi V, Mecocci P. Challenges of infectious diseases in older adults: From immunosenescence and inflammaging through antibiotic resistance to management strategies. Mech Ageing Dev 2024; 222: 111998.
6. Bulut O, Kilic G, Domínguez-Andrés J, Netea MG. Overcoming immune dysfunction in the elderly: trained immunity as a novel approach. Int Immunol 2020; 32(12): 741-53.
7. Cunha LL, Perazzio SF, Azzi J, Cravedi P, Riella LV. Remodeling of the Immune Response With Aging: Immunosenescence and Its Potential Impact on COVID-19 Immune Response. Front Immunol 2020; 11: 1748.
8. Ciabattini A, Nardini C, Santoro F, Garagnani P, Franceschi C, Medaglini D. Vaccination in the elderly: The challenge of immune changes with aging. Semin Immunol 2018; 40(83-94.
9. Halm EA, Fine MJ, Marrie TJ, Coley CM, Kapoor WN, Obrosky DS, et al. Time to clinical stability in patients hospitalized with community-acquired pneumonia: implications for practice guidelines. Jama-J Am Med Assoc 1998; 279(18): 1452-7.
10. Hedlund J, Hansson LO. Procalcitonin and C-reactive protein levels in community-acquired pneumonia: correlation with etiology and prognosis. Infection 2000; 28(2): 68-73.
11. Hirakata Y, Yanagihara K, Kurihara S, Izumikawa K, Seki M, Miyazaki Y, et al. Comparison of usefulness of plasma procalcitonin and C-reactive protein measurements for estimation of severity in adults with community-acquired pneumonia. Diagn Micr Infec Dis 2008; 61(2): 170-4.
12. Andrijevic I, Matijasevic J, Andrijevic L, Kovacevic T, Zaric B. Interleukin-6 and procalcitonin as biomarkers in mortality prediction of hospitalized patients with community acquired pneumonia. Ann Thorac Med 2014; 9(3): 162-7.
13. Cataudella E, Giraffa CM, Di Marca S, Pulvirenti A, Alaimo S, Pisano M, et al. Neutrophil-To-Lymphocyte Ratio: An Emerging Marker Predicting Prognosis in Elderly Adults with Community-Acquired Pneumonia. J Am Geriatr Soc 2017; 65(8): 1796-801.
14. Huang L, Weng B, Wang M, Weng J, Du X, Ju Y, et al. The improved prediction value of neutrophil to lymphocyte ratio to pneumonia severity scores for mortality in the older people with community-acquired pneumonia. Bmc Geriatr 2025; 25(1): 485.
15. Tamura G, Ichinose M, Fukuchi Y, Miyamoto T. Transdermal tulobuterol patch, a long-actingβ(2)-agonist. Allergology International: Official Journal of the Japanese Society of Allergology 2012; 61(2): 219-29.
16. Uematsu T, Nakano M, Kosuge K, Kanamaru M, Nakashima M. The pharmacokinetics of the beta 2-adrenoceptor agonist, tulobuterol, given transdermally and by inhalation. Eur J Clin Pharmacol 1993; 44(4): 361-4.
17. Fukuchi Y, Nagai A, Seyama K, Nishimura M, Hirata K, Kubo K, et al. Clinical efficacy and safety of transdermal tulobuterol in the treatment of stable COPD: an open-label comparison with inhaled salmeterol. Treatments in Respiratory Medicine 2005; 4(6): 447-55.
18. Sugawara T, Nanjo Y, Yamazaki M, Higashihara K, Tsuda Y, Mochizuki H, et al. Comparison of adherence and efficacy between inhaled salmeterol and transdermal tulobuterol patch in elderly patients with chronic obstructive pulmonary disorder. J Am Geriatr Soc 2009; 57(5): 919-20.
19. Wang J, Pei L, Zhao T, Liu X, Wang Q, Zhang S, et al. CD4(+) T cells related to disease severity in elderly and frailty community-acquired pneumonia patients: A retrospective cohort study. Immun Inflamm Dis 2023; 11(9): e1009.
20. Méndez R, Menéndez R, Amara-Elori I, Feced L, Piró A, Ramírez P, et al. Lymphopenic community-acquired pneumonia is associated with a dysregulated immune response and increased severity and mortality. The Journal of Infection 2019; 78(6): 423-31.
Published
2026/05/16
Issue
Ahead of print
Section
Original paper

Copyright (c) 2026 Keling Peng, Leilei Qu, Zirong Zhang

Creative Commons License

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

The published articles will be distributed under the Creative Commons Attribution 4.0 International License (CC BY). It is allowed to copy and redistribute the material in any medium or format, and remix, transform, and build upon it for any purpose, even commercially, as long as appropriate credit is given to the original author(s), a link to the license is provided and it is indicated if changes were made. Users are required to provide full bibliographic description of the original publication (authors, article title, journal title, volume, issue, pages), as well as its DOI code. In electronic publishing, users are also required to link the content with both the original article published in Journal of Medical Biochemistry and the licence used.

Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.