1-Minute SUMMARY: Biomarkers for Severe Asthma: Lessons From Longitudinal Cohort Studies

Expert Name
Dr Youngsoo Lee, Dr Quang Luu Quoc, Dr Hae-Sim Park

Severe asthma (SA) is a heterogenous disease and the prevalence has increased recently [2]. SA is characterised by uncontrolled symptoms, frequent exacerbations and decline of lung functioning. The disease’s heterogeneity is not only related to airway inflammation and responsiveness to treatment, but also to distinct disease symptoms and comorbidities.

Promising type 2 inflammatory biomarkers are immunoglobulin E (IgE), interleukins (IL)-4, IL-5 and IL-13. Additionally, total eosinophils count (TEC), sputum eosinophil count and the fraction of exhaled nitric oxide (FeNO) levels are current available type 2 biomarkers [3][4][5]. These biomarkers are suggested to diagnose SA, indicate the severity of eosinophilic airway inflammation and predict treatment responsiveness to biologics (Table).

Further, serum periostin was suggested to be a biomarker for SA, especially for predicting treatment response to inhaled corticosteroids (ICSs) [6][7]. However, further research is needed to determine its ability to identify phenotypes and endotypes of SA. Additionally, periostin may induce serum TGF-ß1 release, which is thought to contribute to airway remodelling and lung function decline in asthma [8].

Recently, serum eosinophil-derived neurotoxin (EDN) was suggested to be a useful SA biomarker as it appeared to predict phenotypes of asthma [9]. Nonetheless, more research is needed to validate EDN’s ability to predict long-term outcome.

Biologics as treatment for SA block inflammatory molecules and thereby reduce type 2 inflammation in asthma. Examples of potential biologics are omalizumab, reslizumab, benralizumab and mepolizumab. Most biologics improve lung functioning, reduce inflammation, and thereby reduce corticosteroid usage. However, further research is needed to study their effect on airway remodelling [10] (Table).

In conclusion, clinical research suggested various type 2 biomarkers for SA, including IgE, interleukins, blood/sputum eosinophils, FeNO, serum periostin, TGF-ß1 and serum EDN. The therapeutic approach of using biomarkers aims to use biologics to improve SA outcomes. Unfortunately, most biomarkers were insufficient to assess asthma severity. Therefore, to identify and validate new and current SA biomarkers, further real-world, multi-dimensional and cross-sectional and longitudinal analyses are needed.

References

  1. Lee, Y., Quoc, Q. L., & Park, H. S. (2021). Biomarkers for Severe Asthma: Lessons From Longitudinal Cohort Studies. Allergy, Asthma & Immunology Research, 13(3), 375. https://doi.org/10.4168/aair.2021.13.3.375
  2. Lee, E., Kim, A., Ye, Y. M., Choi, S. E., & Park, H. S. (2020). Increasing Prevalence and Mortality of Asthma With Age in Korea, 2002–2015: A Nationwide, Population-Based Study. Allergy, Asthma & Immunology Research, 12(3), 467. https://doi.org/10.4168/aair.2020.12.3.467
  3. Szefler, S. J., Wenzel, S., Brown, R., Erzurum, S. C., Fahy, J. V., Hamilton, R. G., Hunt, J. F., Kita, H., Liu, A. H., Panettieri, R. A., Schleimer, R. P., & Minnicozzi, M. (2012). Asthma outcomes: Biomarkers. Journal of Allergy and Clinical Immunology, 129(3), S9–S23. https://doi.org/10.1016/j.jaci.2011.12.979
  4. Horn, B. R., Robin, E. D., Theodore, J., & Van Kessel, A. (1975). Total Eosinophil Counts in the Management of Bronchial Asthma. New England Journal of Medicine, 292(22), 1152–1155. https://doi.org/10.1056/nejm197505292922204
  5. Pavord, I. D., Afzalnia, S., Menzies-Gow, A., & Heaney, L. G. (2017). The current and future role of biomarkers in type 2 cytokine-mediated asthma management. Clinical & Experimental Allergy, 47(2), 148–160. https://doi.org/10.1111/cea.12881
  6. Matsumoto, H. (2014). Serum Periostin: A Novel Biomarker for Asthma Management. Allergology International, 63(2), 153–160. https://doi.org/10.2332/allergolint.13-rai-0678
  7. Kim, S. H., Uuganbayar, U., Trinh, H. K. T., Le Pham, D., Kim, N., Kim, M., Sohn, H., & Park, H. S. (2019). Evaluation of Neutrophil Activation Status According to the Phenotypes of Adult Asthma. Allergy, Asthma & Immunology Research, 11(3), 381. https://doi.org/10.4168/aair.2019.11.3.381
  8. Al-Alawi, M., Hassan, T., & Chotirmall, S. H. (2014). Transforming growth factor β and severe asthma: A perfect storm. Respiratory Medicine, 108(10), 1409–1423. https://doi.org/10.1016/j.rmed.2014.08.008
  9. Kim, C. K., Callaway, Z., Fletcher, R., & Koh, Y. Y. (2010). Eosinophil-Derived Neurotoxin in Childhood Asthma: Correlation With Disease Severity. Journal of Asthma, 47(5), 568–573. https://doi.org/10.3109/02770901003792833
  10. Kardas, G., Kuna, P., & Panek, M. (2020). Biological Therapies of Severe Asthma and Their Possible Effects on Airway Remodeling. Frontiers in Immunology, 11, 0. https://doi.org/10.3389/fimmu.2020.01134