Asthma: Why Pharmacogenomics Cannot Deliver a Decisive Prognosis
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Abstract
In its “multifactorialness, asthma, as a condition, has continued to see a marked increase in prevalence. Even though this may be tied to the population explosion that is witnessed in the world, the multifactorial nature of the condition makes it an ever-present issue in the world today. The condition’s prognosis is not tied to how very developed a certain country is; as such, it is necessary to approach it as a global phenomenon affecting all and sundry. This, therefore, requires an increase in the research into its existential prevalence. Health research foray into pharmacogenomics has shown great promise in tackling many genetically induced medical conditions. Thus, even though the process is financially demanding, its promise should not be downplayed. The simple question that this inquiry seeks to underscore is, why is pharmacogenomics stunted in dealing decisively with the asthmatic condition in individuals, ergo ensuring that we still have this as an issue? We might say that it is because it is multi-factorial, a combination of genetic and environmental factors. However, this clause is not as simple as it presents itself. Therefore, the inquiry still stands. This research seeks to bring to the fore the most recent advancement in that which pertains to the asthmatic condition, including the pharmacological breakthroughs that have been witnessed. However, the above-stated inquiry as to pharmacogenomics and its failure in dealing decisively with the asthmatic condition remains.
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Golden J, Hashmi MF, Cataletto ME. Asthma. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 May 3 [cited 2025 Dec 12]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430901/
Lee J, McDonald C. Immunotherapy improves some symptoms and reduces long-term medication use in mild to moderate asthma. Ann Intern Med. 2018;169(4):JC17. Available from: https://doi.org/10.7326/ACPJC-2018-169-4-017
Kuruvilla ME, Lee FE, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol. 2019;56(2):219-233. Available from: https://doi.org/10.1007/s12016-018-8712-1
Sakagami T, Hasegawa T, Koya T, Furukawa T, Kawakami H, Kimura Y, et al. Cluster analysis identifies characteristic phenotypes of asthma with accelerated lung function decline. J Asthma. 2014;51:113-118. Available from: https://doi.org/10.3109/02770903.2013.852201
Alves AM, Marques de Mello L, Lima Matos AS, Cruz ÁA. Severe asthma: comparison of different classifications of severity and control. Respir Med. 2019;156:1-7.
Barnes PJ. Pathophysiology of asthma. Br J Clin Pharmacol. 1996;42(1):3-10. Available from: https://doi.org/10.1016/j.rmed.2019.07.015
Diamant Z, Diderik Boot JD, Virchow JC. Summing up 100 years of asthma. Respir Med. 2007;101(3):378-388. Available from: https://doi.org/10.1016/j.rmed.2006.12.004
Townsend J, Hails S, McKean M. Diagnosis of asthma in children. BMJ. 2007;335(7612):198-202.
Foppiano F, Schaub B. Childhood asthma phenotypes and endotypes: a glance into the mosaic. Mol Cell Pediatr. 2023;10(1):9. Available from: https://link.springer.com/article/10.1186/s40348-023-00159-1
Kathuria PC, Manisha R. Phenotypes and endotypes in asthma: practical approach.2024; 38(1): 3-12. Available from: https://journals.lww.com/ijaa/fulltext/2024/38010/phenotypes_and_endotypes_in_asthma_practical.2.aspx
Pignatti P, Visca D, Cherubino F, Zampogna E, Saderi L, Zappa M, Sotgiu G, Spanevello A. Mixed granulocyte phenotype in asthmatic patients. Eur Respir J. 2019;54(Suppl 63):PA2587. Available from: https://doi.org/10.1183/13993003.congress-2019.PA2587
Thomsen SF. Genetics of asthma: an introduction for the clinician. Eur Clin Respir J. 2015;2. Available from: https://doi.org/10.3402/ecrj.v2.24643
Moffatt MF, Gut IG, Demenais F, Strachan DP, Bouzigon E, Heath S, et al. A large-scale, consortium-based genomewide association study of asthma. N Engl J Med. 2010;363:1211-1221. Available from: https://doi.org/10.1056/nejmoa0906312
Ranjbar M, Whetstone CE, Omer H, Power L, Cusack RP, Gauvreau GM. The genetic factors of the airway epithelium associated with the pathology of asthma. Genes. 2022;13(10):1870. Available from: https://doi.org/10.3390/genes13101870
Lima DS, Rechenmacher C, Michalowski MB, Goldani MZ. Epigenetics, hypersensibility and asthma: what do we know so far? Clinics. 2023;78. Available from: https://doi.org/10.1016/j.clinsp.2023.100296
Steiropoulos P, Ito K. Genes and severe asthma. Pneumon. 2011;24(3):321-329. Available from: https://www.pneumon.org/pdf-136976-67231?filename=Genes%20and%20severe%20asthma.pdf
Han X, Liu L, Huang S, Xiao W, Gao Y, Zhou W, et al. RNA m6A methylation modulates airway inflammation in allergic asthma via PTX3-dependent macrophage homeostasis. Nat Commun. 2023;14:7328. Available from: https://www.nature.com/articles/s41467-023-43219-w
Cardenas A, Sordillo JE, Rifas-Shiman SL, Chung W, Liang L, Coull BA, et al. The nasal methylome as a biomarker of asthma and airway inflammation in children. Nat Commun. 2019;10:3095. Available from: https://doi.org/10.1038/s41467-019-11058-3
Nicodemus-Johnson J, Myers RA, Sakabe NJ, Sobreira DR, Hogarth DK, Naureckas ET, et al. DNA methylation in lung cells is associated with asthma endotypes and genetic risk. JCI Insight. 2016;1(20):e90151. Available from: https://insight.jci.org/articles/view/90151
von Mutius E, Smits HH. Primary prevention of asthma: from risk and protective factors to targeted strategies for prevention. Lancet. 2020;396(10254):854-866. Available from: https://doi.org/10.1016/S0140-6736(20)31861-4
Fakhar M, Gul M, Li W. Structural and functional studies on key epigenetic regulators in asthma. Biomolecules. 2025;15(9):1255. Available from: https://doi.org/10.3390/biom15091255
Qian W, Yang L, Li T, Li W, Zhou J, Xie S. RNA modifications in pulmonary diseases. MedComm. 2024;5:e546. Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/mco2.546
Ito K, Caramori G, Lim S, Oates T, Chung KF, Barnes PJ, et al. Expression and activity of histone deacetylases in human asthmatic airways. Am J Respir Crit Care Med. 2002;166:392-396. Available from: https://doi.org/10.1164/rccm.2110060
Stefanowicz D, Lee JY, Lee K, Shaheen F, Koo HK, Booth S, et al. Elevated H3K18 acetylation in airway epithelial cells of asthmatic subjects. Respir Res. 2015;16:95. Available from: https://link.springer.com/article/10.1186/s12931-015-0254-y
Stefanowicz D, Ullah J, Lee K, Shaheen F, Olumese E, Fishbane N, et al. Epigenetic modifying enzyme expression in asthmatic airway epithelial cells and fibroblasts. BMC Pulm Med. 2017;17:24. Available from: https://link.springer.com/article/10.1186/s12890-017-0371-0
Wawrzyniak P, Wanke K, Akdis M, Sanak M, Akdis CA, et al. Regulation of bronchial epithelial barrier integrity by type 2 cytokines and histone deacetylases in asthmatic patients. J Allergy Clin Immunol. 2017;139:93-103. Available from: https://www.jacionline.org/article/S0091-6749(16)30277-9/fulltext
Bhavsar P, Ahmad T, Adcock IM. The role of histone deacetylases in asthma and allergic diseases. J Allergy Clin Immunol. 2008;121:580–584. Available from: https://doi.org/10.1016/j.jaci.2007.12.1156
Leus NGJ, Zwinderman MRH, Dekker FJ. Histone deacetylase 3 (HDAC 3) as emerging drug target in NF-κB-mediated inflammation. Curr Opin Chem Biol. 2016;33:160–168. Available from: https://doi.org/10.1016/j.cbpa.2016.06.019
Liu Y, Shi G. Roles of sirtuins in asthma. Respir Res. 2022;23:251. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9482752/
Kim YY, Hur G, Lee SW, Lee SJ, Lee S, Kim SH, Rho MC. AGK2 ameliorates mast cell-mediated allergic airway inflammation and fibrosis by inhibiting FcRI/TGF-β signaling pathway. Pharmacol Res. 2020;159:105027. Available from: https://doi.org/10.1016/j.phrs.2020.105027
Song J, Wang J. SIRT3 regulates bronchial epithelium apoptosis and aggravates airway inflammation in asthma. Mol Med Rep. 2022;25:144. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC8915391/
Jang HY, Gu S, Lee SM, Park BH. Overexpression of sirtuin 6 suppresses allergic airway inflammation through deacetylation of GATA3. J Allergy Clin Immunol. 2016;138:1452–1455. Available from: https://www.jacionline.org/article/S0091-6749(16)30438-9/fulltext
Fang P, Xue Y, Zhang Y, Fan N, Ou L, Leng L, et al. SIRT7 regulates the TGF-β1-induced proliferation and migration of mouse airway smooth muscle cells by modulating the expression of TGF-β receptor I. Biomed Pharmacother. 2018;104:781–787. Available from: https://doi.org/10.1016/j.biopha.2018.05.060
Verma M, Chattopadhyay BD, Kumar S, Kumar K, Verma D. DNA methyltransferase 1 (DNMT1) induced the expression of suppressors of cytokine signaling3 (Socs3) in a mouse model of asthma. Mol Biol Rep. 2014;41:4413–4424. Available from: https://doi.org/10.1007/s11033-014-3312-5
Yu Q, Zhou B, Zhang Y, Nguyen ET, Kaplan MH. DNA methyltransferase 3a limits the expression of interleukin-13 in T helper 2 cells and allergic airway inflammation. Proc Natl Acad Sci U S A. 2012;109:541–546. Available from: https://doi.org/10.1073/pnas.1103803109
Chen Z, Yuan Y, He Y, Wasti B, Duan W, Jia J, et al. MBD2 as a potential novel biomarker for identifying severe asthma with different endotypes. Front Med. 2021;8:693605. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC8527858/
Somineni HK. Ten-eleven translocation 1 (TET1) methylation is associated with childhood asthma and traffic-related air pollution. J Allergy Clin Immunol. 2016;137:797–805.
Dai B, Sun F, Cai X, Li C, Liu H, Shang Y. Significance of RNA N6-methyladenosine regulators in the diagnosis and subtype classification of childhood asthma using the Gene Expression Omnibus database. Front Genet. 2021;12:634162. Available from: https://doi.org/10.3389/fgene.2021.634162
Chen X, Dai L. WTAP promotes the excessive proliferation of airway smooth muscle cells in asthma by enhancing AXIN1 levels through the recognition of YTHDF2. Biochem Genet. 2024;1–18. Available from: https://doi.org/10.1007/s10528-024-10947-7
Chen Z, Shang Y, Zhang X, Duan W, Li J, Zhu L, et al. METTL3 mediates SOX5 M6A methylation in bronchial epithelial cells to attenuate Th2 cell differentiation in T2 asthma. Heliyon. 2024;10:e28884. Available from: https://doi.org/10.1016/j.heliyon.2024.e28884
Wang J, Zhou Y, Zhang M, Wu Y, Wu Q, Su W, et al. YTHDF1-CLOCK axis contributes to pathogenesis of allergic airway inflammation through LLPS. Cell Rep. 2024;43:113947. Available from: https://doi.org/10.1016/j.celrep.2024.113947
Gao G, Hao YQ, Gao C. Role and regulators of N6-methyladenosine (M6A) RNA methylation in inflammatory subtypes of asthma: a comprehensive review. Front Pharmacol. 2024;15:1360607. Available from: https://doi.org/10.3389/fphar.2024.1360607
Wang X, Ji Y, Feng P, Liu R, Li G, Zheng J, et al. The M6A reader IGF2BP2 regulates macrophage phenotypic activation and inflammatory diseases by stabilizing TSC1 and PPARγ. Adv Sci. 2021;8:2100209. Available from: https://doi.org/10.1002/advs.202100209
Xiong A, He X, Liu S, Ran Q, Zhang L, Wang J, et al. Oxidative stress-mediated activation of FTO exacerbates impairment of the epithelial barrier by up-regulating IKBKB via N6-methyladenosine-dependent mRNA stability in asthmatic mice exposed to PM2.5. Ecotoxicol Environ Saf. 2024;272:116067. Available from: https://doi.org/10.1002/advs.202100209
DeVries A, Vercelli D. The neonatal methylome as a gatekeeper in the trajectory to childhood asthma. Epigenomics. 2017;9:585–593. Available from: https://experts.azregents.edu/en/publications/the-neonatal-methylome-as-a-gatekeeper-in-the-trajectory-to-child/
DeVries A, Wlasiuk G, Miller SJ, Bosco A, Stern DA, Lohman IC, et al. Epigenome-wide analysis links SMAD3 methylation at birth to asthma in children of asthmatic mothers. J Allergy Clin Immunol. 2017;140:534–542. Available from: https://doi.org/10.1016/j.jaci.2016.10.041
Forno E, Wang T, Yan Q, Brehm J, Acosta-Perez E, Colon-Semidey A, et al. A multiomics approach to identify genes associated with childhood asthma risk and morbidity. Am J Respir Cell Mol Biol. 2017;57:439–447. Available from: https://doi.org/10.1165/rcmb.2017-0002oc
Qi C, Xu CJ, Koppelman GH. The role of epigenetics in the development of childhood asthma. Expert Rev Clin Immunol. 2019;15:1287–1302. Available from: https://doi.org/10.1080/1744666x.2020.1686977
Ortega VE, Meyers DA, Bleecker ER. Asthma pharmacogenetics and the development of genetic profiles for personalized medicine. Pharmgenomics Pers Med. 2015;8:9–22. Available from: https://doi.org/10.2147/pgpm.s52846
Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013;368:2455–2466. Available from: https://doi.org/10.1056/nejmoa1304048
Slager RE, Otulana BA, Hawkins GA, Yen YP, Peters SP, Wenzel SE, et al. IL-4 receptor polymorphisms predict reduction in asthma exacerbations during response to an anti–IL-4 receptor alpha antagonist. J Allergy Clin Immunol. 2012;130:516–522.e14. Available from: https://doi.org/10.1016/j.jaci.2012.03.030
Landgraf-Rauf K, Anselm B, Schaub B. The puzzle of immune phenotypes of childhood asthma. Mol Cell Pediatr. 2016;3:27. Available from: https://doi.org/10.1186/s40348-016-0057-3