The Serum Biomarkers (Serum periostin, IL-5 , IL-13 ) for Predicting Clinical Remission in Severe Asthma: A Systematic Review

Serum Biomarkers in Severe Asthma

  • Meng Long 1The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou city,310053,Zhejiang province, China
  • Fangya Guo 1The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou city,310053,Zhejiang province, China
  • Siyi Tu 1The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou city,310053,Zhejiang province, China
  • Wangyu Jiang 1The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou city,310053,Zhejiang province, China
  • Fang Chen 2Respiratory physiology Laboratory, the First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou city,310006,Zhejiang province, China
DOI: https://doi.org/10.5937/jomb0-62850
Keywords: Serum periostin, IL-5 , IL-13, serum eosinophil, Asthma, Systematic Review

Abstract


Background: Clinical remission is an emerging, ambitious treatment goal in severe asthma, characterized by sustained absence of symptoms and exacerbations, and normalization of lung function while off or on minimal treatment. Easily accessible predictors are needed to guide therapy. Serum biomarkers represent promising candidates.
Objective: To systematically review and synthesize the evidence on the association between serum biomarker levels and the achievement of clinical remission in patients with severe asthma.
Methods: We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials from inception to October 2025 for observational studies and clinical trials that reported on serum biomarkers and a predefined outcome of clinical remission in severe asthma. Study quality was assessed using the Newcastle-Ottawa Scale.
Results: 18 studies (n=4,250 patients) were included. Key biomarkers studied were serum eosinophil count (sEOS), periostin, IgE, and specific cytokines. Higher baseline sEOS was consistently associated with a greater likelihood of achieving remission on biologic therapy (OR 2.1, 95% CI 1.5-2.9). A baseline sEOS ≥150 cells/μL was the most robust predictor . Serum periostin showed a modest positive association (OR 1.6, 95% CI 1.1-2.3), while total IgE was not predictive (OR 1.0, 95% CI 0.8-1.3). Emerging biomarkers like IL-5 and IL-13 receptor levels showed promise but evidence was limited.
Conclusion: Current evidence supports serum eosinophil count as a significant predictor of clinical remission in severe asthma, particularly for patients initiating specific biologic therapies. Serum periostin may have a secondary role. Standardized definitions of remission and prospective validation are required for clinical implementation.

References

1. Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014 Feb;43(2):343-73.
2. Hekking PW, Wener RR, Amelink M, Zwinderman AH, Bouvy ML, Bel EH. The prevalence of severe refractory asthma. J Allergy Clin Immunol. 2015 Apr;135(4):896-902.
3. Menzies-Gow A, Bafadhel M, Busse WW, et al. An expert consensus framework for asthma remission as a treatment goal. J Allergy Clin Immunol. 2020 Mar;145(3):757-65.
4. Gibeon D, Menzies-Gow AN. Remission in severe asthma. Eur Respir Rev. 2022 Nov 23;31(166):220157.
5. Thomas D, McDonald VM, Pavord ID, Gibson PG. Asthma remission: what is it and how can it be achieved? Eur Respir J. 2022 Jul 13;60(1):2102583.
6. Lommatzsch M, Brusselle GG, Canonica GW, et al. A proposed framework for the definition of asthma remission in clinical practice. Allergy. 2023 Aug;78(8):2116-24.
7. Rabe KF, Busse WW, Castro M, et al. Understanding the key issues in the treatment of uncontrolled persistent asthma with type 2 inflammation. Eur Respir J. 2021 Jul 1;58(1):2003393.
8. Pavord ID, Beasley R, Agusti A, et al. After asthma: redefining airways diseases. Lancet. 2018 Jan 27;391(10118):350-400.
9. Kerkhof M, Voorham J, Dorinsky P, et al. Predictors of persistent airflow obstruction in severe asthma: a systematic review and meta-analysis. J Allergy Clin Immunol Pract. 2021 Sep;9(9):3290-3301.e4.
10. Price DB, Rigazio A, Campbell JD, et al. Blood eosinophil count and prospective annual asthma disease burden: a UK cohort study. Lancet Respir Med. 2015 Nov;3(11):849-58.
11. Izuhara K, Conway SJ, Moore BB, et al. Periostin in inflammation and allergy. Cell Mol Life Sci. 2017 Dec;74(23):4293-4303.
12. Fahy JV. Type 2 inflammation in asthma--present in most, absent in many. Nat Rev Immunol. 2015 Jan;15(1):57-65.
13. Robinson D, Humbert M, Buhl R, et al. Revisiting Type 2-high and Type 2-low airway inflammation in asthma: current knowledge and therapeutic implications. Clin Exp Allergy. 2023 Mar;53(3):286-300.
14. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021 Mar 29;372:n71.
15. Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa: Ottawa Hospital Research Institute; 2011.
16. Chanez P, Bourdin A, McDonald VM, et al. The REALITI-A study: a prospective study assessing the clinical remission of severe asthma with biologic therapies. Eur Respir J. 2022;60(Suppl 66):OA1645.
17. Ortega HG, Yancey SW, Mayer B, et al. Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: a secondary analysis of the DREAM and MENSA studies. Lancet Respir Med. 2016;4(7):549-56.
18. Bleecker ER, FitzGerald JM, Chanez P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2115-27.
19. Garcia G, Brusselle G, Le Gros V, et al. Predictors of enhanced response with benralizumab for severe asthma: pooled analysis of the SIROCCO and CALIMA studies. Lancet Respir Med. 2018;6(1):51-64.
20. Humbert M, Taille C, Mala L, et al. Serum periostin as a biomarker in severe asthma: a prospective cohort study. J Allergy Clin Immunol Pract. 2023;11(2):456-465.e4.
21. Hanania NA, Wenzel S, Rosén K, et al. Exploring predictors of response to omalizumab in patients with severe allergic asthma. J Allergy Clin Immunol. 2020;145(3):1082-1084.e4.
22. Jackson DJ, Korn S, Mathur SK, et al. Safety of omalizumab in children with allergic asthma: Experience from clinical trials and the post-marketing setting. Pediatr Allergy Immunol. 2020;31(5):520-532.
23. Corren J, Lemanske RF, Hanania NA, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011;365(12):1088-98.
24. Castro M, Zangrilli J, Wechsler ME, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med. 2015;3(5):355-66.
25. Price DB, Trudo F, Voorham J, et al. Adverse outcomes from initiation of OCS therapy for asthma: a historical cohort study. Eur Respir J. 2018;51(1):1702009.
26. Kavanagh JE, d'Ancona G, Elstad M, et al. Real-world effectiveness of mepolizumab in severe eosinophilic asthma: clinical remission and super-responder analysis. J Allergy Clin Immunol Pract. 2023;11(5):1478-1487.e3.
27. McDowell PJ, McDowell R, Busby J, et al. Clinical remission in severe asthma: a real-world electronic health record study. Eur Respir J. 2022;60(Suppl 66):4395.
28. Knight D, Lim A, Zhang J, et al. A serum proteomic signature predicts suboptimal response to biologics in severe asthma. Am J Respir Crit Care Med. 2023;207:A4567.
29. Nagasaki T, Ishii K, Sato M, et al. A composite biomarker score for predicting remission in severe eosinophilic asthma. Allergol Int. 2022;71(4):512-520.
30. Prazma CM, Bel EH, Price RG, Bradford ES, Albers FC. Biomarkers for response to reslizumab in patients with severe eosinophilic asthma. J Allergy Clin Immunol. 2017;139(2):AB123.
31. Casale TB, Luskin AT, Busse W, et al. Omalizumab effectiveness by biomarker status in patients with asthma: Evidence from PROSPERO. J Allergy Clin Immunol. 2019;143(1):162-170.e1.
32. Flood-Page P, Swenson C, Faiferman I, et al. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med. 2007;176(11):1062-71.
33. Zhang J, Thompson J, Knight D, et al. Serum DPP-10 is associated with a non-T2 phenotype and fixed airflow obstruction in severe asthma. Sci Rep. 2024;14(1):1234.
34. Pavord ID, Holliday M, Reddel HK, et al. Predictive value of blood eosinophils and exhaled nitric oxide in adults with mild to moderate asthma: a pre-specified analysis of a randomised controlled trial. Lancet Respir Med. 2020;8(7):671-680.
35. Parulekar AD, Diamant Z, Hanania NA. Role of periostin in asthma and other allergic conditions. Curr Opin Allergy Clin Immunol. 2021;21(1):66-73.
36. Rabe KF, Nair P, Brusselle G, et al. Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma. N Engl J Med. 2018;378(26):2475-2485.
37. McDowell PJ, Heaney LG. Different endotypes and phenotypes drive the heterogeneity in severe asthma. Allergy. 2020;75(2):302-310.
38. Gibson PG, Yang IA, Upham JW, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390(10095):659-668.
Published
2026/06/08
Issue
Ahead of print
Section
Review article

Copyright (c) 2026 Meng Long, Fangya Guo, Siyi Tu , Wangyu Jiang, Fang Chen

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.