Role of P-selectin and the receptor for advanced glycation end products (RAGE) in the development of obesity-associated bronchial asthma in adults

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Abstract

BACKGROUND: Obesity-associated bronchial asthma is a common and difficult-to-treat phenotype of adult asthma. Currently, asthma is classified into two major endotypes: Th2 and non-Th2. The non-Th2 endotype reflects a non-allergic inflammatory mechanism but lacks clearly defined laboratory criteria, unlike the Th2 endotype. In this context, P-selectin and the receptor for advanced glycation end products (RAGE) are of particular interest as potential markers of non-allergic inflammation. However, their role remains insufficiently studied.

AIM: This study aimed to evaluate the role of P-selectin and the receptor for advanced glycation end products (RAGE) in the development of bronchial asthma in adults with obesity.

METHODS: A cross-sectional consecutive study was conducted. Clinical characteristics, spirometric parameters, and immunological markers were assessed in patients with and without obesity, depending on the presence of bronchial asthma. Immunological markers were evaluated using enzyme-linked immunosorbent assay, including P-selectin, receptor for advanced glycation end products (RAGE), interleukin-4, interleukin-8, tumor necrosis factor alpha, and interferon gamma.

RESULTS: 96 participants were divided into four groups: group I, patients with bronchial asthma without obesity (n = 29); group II, patients with bronchial asthma and obesity (n = 27); group III (control), normal-weight individuals (n = 22); group IV (control), individuals with obesity (n = 8). Comparative analysis between the two asthma groups revealed no substantial differences in the analyzed markers; however, both groups differed remarkably from the control group III. Median P-selectin levels in groups I and II were 57.49 (46.82–129.29) pg/mL and 114.4 (58.5–161.5) pg/mL, respectively, which were significantly higher than in the control group III: 44.99 (34.00–60.07) pg/mL (p < 0.05). Elevated levels of RAGE and TNF-α were also observed, indicating the presence of a systemic inflammatory response associated with obesity in patients with bronchial asthma.

CONCLUSION: The study demonstrated substantial similarity of immunological responses in bronchial asthma and obesity. In the presence of both conditions, P-selectin demonstrated the most specific response, confirming the neutrophilic nature of inflammation.

About the authors

Vitalii I. Kupaev

North-West State Medical University named after I.I. Mechnikov

Author for correspondence.
Email: vk1964sam@rambler.ru
ORCID iD: 0000-0003-2639-0003
SPIN-code: 1458-5872

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Saint Petersburg

Dmitry V. Senyushkin

Samara State Medical University

Email: dimasen389@gmail.com
ORCID iD: 0009-0004-5138-382X
SPIN-code: 9255-0970

MD

Russian Federation, Samara

Kseniya M. Tkachenko

Samara Regional Clinical Hospital named after V.D. Seredavin

Email: Ksenya2009@list.ru
ORCID iD: 0009-0006-7433-6609

MD

Russian Federation, Samara

References

  1. Khudiakova AD, Ragino YuU. Influence of adipocytokines on the bronchopulmonary system in abdominal obesity. Pulmonologiya. 2024;34(1):74–79. doi: 10.18093/0869-0189-2024-34-1-74-79 EDN: RZWVSC
  2. Beuther DA, Sutherland ER. Overweight, obesity, and incident asthma: a metaanalysis of prospective epidemiologic studies. Am J Respir Crit Care Med. 2007;175(7):661–666. doi: 10.1164/rccm.200611-1717OC
  3. Akinbami LJ, Fryar CD. Current asthma prevalence by weight status among adults:United States, 2001-2014. NCHS data brief. 2016;(239):1–8.
  4. Holguin F, Bleecker ER, Busse WW, et al. Obesity and asthma: an association modified by age of asthma onset. J Allergy Clin Immunol. 2011;127(6):1486–1493.e2. doi: 10.1016/j.jaci.2011.03.036
  5. Vortmann M, Eisner MD. BMI and health status among adults with asthma. Obesity (Silver Spring). 2008;16(1):146–152. doi: 10.1038/oby.2007.7
  6. Boulet LP, Franssen E. Influence of obesity on response to fluticasone with or without salmeterol in moderate asthma. Respir Med. 2007;101(11):2240–2247. doi: 10.1016/j.rmed.2007.06.031
  7. Ovsyannikov ES, Avdeev SN, Budnevsky AV. Systemic inflammation in patients with chronic obstructive pulmonary disease and obesity. Terapevticheskii Arkhiv. 2020;92(3):13–18. doi: 10.26442/00403660.2020.03.000265 EDN: EXZWYY
  8. Scott HA, Gibson PG, Garg ML, Wood LG. Airway inflammation is augmented by obesity and fatty acids in asthma. Eur Respir J. 2011;38(3):594–602. doi: 10.1183/09031936.00139810
  9. Schumacher A, Liebers U, John M, et al. P-selectin glycoprotein ligand-1 (PSGL-1) is up-regulated on leucocytes from patients with chronic obstructive pulmonary disease. Clin Exp Immunol. 2005;142(2):370–376. doi: 10.1111/j.1365-2249.2005.02920.x
  10. Wang S, Song R, Wang Z, et al. S100A8/A9 in Inflammation. Front Immunol. 2018;9:1298. doi: 10.3389/fimmu.2018.01298 EDN: FQAKWW
  11. Qu L, Chen C, Chen Y, et al. High-Mobility Group Box 1 (HMGB1) and autophagy in Acute Lung Injury (ALI): a review. Med Sci Monit. 2019;25:1828–1837. doi: 10.12659/MSM.912867
  12. Buckley ST, Ehrhardt C. The receptor for advanced glycation end products (RAGE) and the lung. J Biomed Biotechnol. 2010;2010:917108. doi: 10.1155/2010/917108
  13. Hamada Y, Gibson PG, Clark VL, et al. Dysfunctional breathing and depression are core extrapulmonary and behavior/risk factor traits in type 2-high severe asthma. J Allergy Clin Immunol Pract. 2025;13(7):1743–1754.e12. doi: 10.1016/j.jaip.2025.03.017
  14. Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med. 2012;18(5):716–725. doi: 10.1038/nm.2678
  15. Olejnik AE, Kuznar-Kaminska B. Association of obesity and severe asthma in adults. J Clin Med. 2024;13(12):3474. doi: 10.3390/jcm13123474 EDN: QMRQMF
  16. Al-Ahmad M, Ali A. Obesity in severe asthma: unveiling challenges and exploring new therapeutic options. World Allergy Organ J. 2025;18(4):101042. doi: 10.1016/j.waojou.2025.101042
  17. Patel MS, Miranda-Nieves D, Chen J, et al. Targeting PSGL-1/P-selectin interactions as a novel therapy for metabolic syndrome. Transl Res. 2017;183:1–13. doi: 10.1016/j.trsl.2016.11.007 EDN: YWFQHF
  18. Kong P, Cui ZY, Huang XF, et al. Inflammation and atherosclerosis: signaling pathways and therapeutic intervention. Signal Transduct Target Ther. 2022;7(1):131. doi: 10.1038/s41392-022-00955-7
  19. Sorokina LN, Mineev VN, Pavlova AS, Trofimov VI. The role of the receptor for advanced glycation endproducts (RAGE) in the pathogenesis of asthma. Pulmonologiya. 2025;35(1):95–101. doi: 10.18093/0869-0189-2025-35-1-95-10 EDN: NEYNKR

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