COMPARATIVE ASSESSMENT OF THE TREATMENT EFFECTIVENESS OF ASTHMA PATIENTS WITH OBESITY DEPENDING ON THE AGE OF DEBUT
DOI:
https://doi.org/10.11603/1811-2471.2024.v.i1.14531Keywords:
asthma, obesity, debut, transforming growth factor-β, control, lung function, atorvastatin, vitamin DAbstract
SUMMARY. The aim – comparative evaluation of the clinical and laboratory effectiveness of atorvastatin and vitamin D in addition to basic treatment of asthma patients with obesity depending on the age of onset.
Material and Methods. 195 asthma patients with obesity and 95 practically healthy individuals were examined. Patients were divided into two groups depending on the age of asthma onset: the 1st group included 100 patients with an early onset, and the 2nd group – 95 with a late onset. Patients with complete control at baseline visit and those who achieved control after adjustment of baseline treatment were excluded from further study. Patients of I (n=65) and II groups (n=68) were divided into subgroups A, B and C: IA (n=23) and IIA (n=22) subgroups received basic treatment in combination with vitamin D; IB (n=20) and IIB (n=25) – with atorvastatin; IC (n=22) and IIC (n=21) – only basic therapy. TGF-β1 level was determined using IBL International GMBH (Hamburg, Germany) enzyme immunoassay kits. The content of 25(OH)D was determined by an immunochemical method with chemiluminescence detection (Abbott Diagnostics, USA). Asthma control was assessed using the ACQ-5 questionnaire. The study was approved by the Bioethics Commission of the Educational and Scientific Medical Institute of Sumy State University. Statistical analysis of the obtained results was carried out using the SPSS-17 program.
Results. The level of TGF-β1 in patients with early asthma with obesity did not change against the background of basic treatment, however was lower, in groups with a combination of atorvastatin and vitamin D (p=0.001) and was lower compared to that in patients with IB and IC subgroups. In patients with late-onset asthma, the level of TGF-β1 was lower in IIA (p=0.001) and IIB (p=0.001) subgroups. A decreasing in TGF-β1 was accompanied by an increase in the level of vitamin D only in patients with IA (p=0.001) and IIA (p=0.001) subgroups. A medium-strength negative correlation was found in patients of the I (r= - 0.523; p=0.001) and II (r=- 0.379; p=0.001) groups between the level of vitamin D and TGF-β1. There was an increase in the level of asthma control in patients of IA and IB subgroups, but it was higher in IA compared to patients of B (p=0.001) and C (p=0.001) subgroups. Control of late asthma increased in patients of all subgroups, but its level was higher in patients with IIB compared to IIA (p=0.001) and IIC (p=0.017) subgroups. Lung Function significantly increased in patients with early asthma in the group who received basic treatment with vitamin D, and in patients with late asthma with the add-on of atorvastatin.
Conclusions. The content of TGF-β1 significantly decreased in patients of IA, IIa and IIB subgroups. Vitamin D content increased in patients of IA and IIA subgroups. A medium strength correlation was revealed in patients of I (r=-0.523; p=0.001) and II (r=-0.379; p=0.001) groups between the content of vitamin D and TGF-β1. Higher control and better improvement of lung function were in patients with early asthma and obesity who had the combination of basic therapy with vitamin D, and in patients with late asthma with the add-on of atorvastatin.
References
Woo, J., Koziol-White, C., Panettieri, R., Jr, & Jude, J. (2021). TGF-β: The missing link in obesity-associated airway diseases? Current research in pharmacology and drug discovery, 2, 100016. DOI: 10.1016/j.crphar.2021.100016.
Park, Y.H., Oh, E.Y., Han, H., Yang, M., Park, H.J., Park, K.H., Lee, J.H., & Park, J.W. (2019). Insulin resistance mediates high-fat diet-induced pulmonary fibrosis and airway hyperresponsiveness through the TGF-β1 pathway. Experimental & molecular medicine, 51(5), 1-12. DOI: 10. 1038/s12276-019-0258-7.
E-Lacerda, R.R., Anhê, G.F., Page, C.P., & Riffo-Vasquez, Y. (2020). Sex differences in the influence of obesity on a murine model of allergic lung inflammation. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 50(2), 256-266. DOI: 10.1111/cea.13541.
Wnuk, D., Paw, M., Ryczek, K., Bochenek, G., Sładek, K., Madeja, Z., & Michalik, M. (2020). Enhanced asthma-related fibroblast to myofibroblast transition is the result of profibrotic TGF-β/Smad2/3 pathway intensification and antifibrotic TGF-β/Smad1/5/(8)9 pathway impairment. Scientific reports, 10(1), 16492. DOI: 10.1038/s41598-020-73473-7.
Chielle, E., Ogliari, V. C., de Carvalho, D., & Remor, A. (2018). Influence of obesity and overweight on transforming growth factor beta 1 levels and other oxidative and cardiometabolic parameters Journal of Clinical and Biomedical Research, 38(3), 273-280.
Han, H., Chung, S.I., Park, H.J., Oh, E.Y., Kim, S.R., Park, K.H., Lee, J.H., & Park, J.W. (2021). Obesity-induced Vitamin D Deficiency Contributes to Lung Fibrosis and Airway Hyperresponsiveness. American journal of respiratory cell and molecular biology, 64(3), 357-367. DOI: 10.1165/rcmb.2020-0086OC.
Aguiar, M., Andronis, L., Pallan, M., Högler, W., & Frew, E. (2020). The economic case for prevention of population vitamin D deficiency: a modelling study using data from England and Wales. European journal of clinical nutrition, 74(5), 825-833. DOI: 10.1038/s41430-019-0486-x.
Roizen, J.D., Long, C., Casella, A., Lear, L., Caplan, I., Lai, M., ... & Levine, M.A. (2019). Obesity Decreases Hepatic 25-Hydroxylase Activity Causing Low Serum 25-Hydroxyvitamin D. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 34(6), 1068-1073. DOI: 10.1002/jbmr.3686.
Migliaccio, S., Di Nisio, A., Mele, C., Scappaticcio, L., Savastano, S., Colao, A., & Obesity Programs of nutrition, Education, Research and Assessment (OPERA) Group (2019). Obesity and hypovitaminosis D: causality or casualty?. International journal of obesity supplements, 9(1), 20-31. DOI: 10.1038/s41367-019-0010-8.
Shi, Y., Liu, T., Yao, L., Xing, Y., Zhao, X., Fu, J., & Xue, X. (2017). Chronic vitamin D deficiency induces lung fibrosis through activation of the renin-angiotensin system. Scientific reports, 7(1), 3312. DOI: 10.1038/s41598-017-03474-6.
Li, S.R., Tan, Z.X., Chen, Y.H., Hu, B., Zhang, C., Wang, H., Zhao, H., & Xu, D.X. (2019). Vitamin D deficiency exacerbates bleomycin-induced pulmonary fibrosis partially through aggravating TGF-β/Smad2/3-mediated epithelial-mesenchymal transition. Respiratory research, 20(1), 266. DOI: 10.1186/s12931-019-1232-6.
O’Sullivan, B.P., James, L., Majure, J.M., Bickel, S., Phan, L.T., Serrano Gonzalez, M., Staples, H., Tam-Williams, J., Lang, J., Snowden, J., & IDeA States Pediatric Clinical Trials Network (2021). Obesity-related asthma in children: A role for vitamin D. Pediatric pulmonology, 56(2), 354-361. DOI: 10.1002/ppul.25053.
Park, J.W. (2022). Asthma Phenotype with Metabolic Dysfunction. Yonsei medical journal, 63(1), 1-7. DOI: 10.3349/ymj.2022.63.1.1
Farzan, S., Coyle, T., Coscia, G., Rebaza, A., & Santiago, M. (2022). Clinical Characteristics and Management Strategies for Adult Obese Asthma Patients. Journal of asthma and allergy, 15, 673-689. DOI: 10.2147/JAA.S285738.
Holguin, F., Bleecker, E., & Busse, W. (2011). Obesity and asthma: An association modified by age of asthma onset. The journal of allergy and clinical immunology, 127, 1486-1493. DOI: 10.1016/j.jaci.2011.03.036.
Ferreira, M.A.R., Mathur, R., Vonk, J.M., Szwajda, A., Brumpton, B., Granell, R., Brew, B.K., ... & Almqvist, C. (2019). Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct. American journal of human genetics, 104(4), 665-684. DOI: 10.1016/j.ajhg.2019.02.022.
Thompson, C.A., Eslick, S.R., Berthon, B.S., & Wood, L.G. (2021). Asthma medication use in obese and healthy weight asthma: systematic review/meta-analysis. The European respiratory journal, 57(3), 2000612. DOI: 10.1183/13993003.00612-2020.
Hsieh, A., Assadinia, N., & Hackett, T.L. (2023). Airway remodeling heterogeneity in asthma and its relationship to disease outcomes. Frontiers in physiology, 14, 1113100. DOI: 10.3389/fphys.2023.1113100.
Kim, M.L., Sung, K.R., Kwon, J., & Shin, J.A. (2020). Statins Suppress TGF-β2-Mediated MMP-2 and MMP-9 Expression and Activation Through RhoA/ROCK Inhibition in Astrocytes of the Human Optic Nerve Head. Investigative ophthalmology & visual science, 61(5), 29. DOI: 10.1167/iovs.61.5.29.
Mehrabi, S., Torkan, J., & Hosseinzadeh, M. (2021). Effect of atorvastatin on serum periostin and blood eosinophils in asthma – a placebo-controlled randomized clinical trial. The Journal of international medical research, 49(12). DOI: 10.1177/03000605211063721.
Saadat, S., Mohamadian Roshan, N., Aslani, M.R., & Boskabady, M.H. (2020). Rosuvastatin suppresses cytokine production and lung inflammation in asthmatic, hyperlipidemic and asthmatic-hyperlipidemic rat models. Cytokine, 128, 154993. DOI: 10.1016/j.cyto.2020.154993.
Nageeb, E.S., Abumossalam A.M., Arram E.O., Aboshehata M.E. (2019). Evaluation of the effect of statin therapy on airway inflammation and clinical outcome of moderate and severe bronchial asthma. The Egyptian Journal of Chest Diseases and Tuberculosis, 68, 328-337.
Hu, G., Dong, T., Wang, S., Jing, H., & Chen, J. (2019). Vitamin D3-vitamin D receptor axis suppresses pulmonary emphysema by maintaining alveolar macrophage homeostasis and function. EBioMedicine, 45, 563-577. DOI: 10.1016/j.ebiom.2019.06.039.
Ojiaku, C.A., Cao, G., Zhu, W., Yoo, E.J., Shumyatcher, M., Himes, B.E., An, S.S., & Panettieri, R.A., Jr. (2018). TGF-β1 Evokes Human Airway Smooth Muscle Cell Shortening and Hyperresponsiveness via Smad3. American journal of respiratory cell and molecular biology, 58(5), 575-584. DOI: 10.1165/rcmb.2017-0247OC.
Ojiaku, C.A., Chung, E., Parikh, V., Williams, J.K., Schwab, A., Fuentes, A.L., ... & Panettieri, R.A., Jr. (2019). Transforming Growth Factor-β1 Decreases β2-Agonist-induced Relaxation in Human Airway Smooth Muscle. American journal of respiratory cell and molecular biology, 61(2), 209-218. DOI: 10.1165/rcmb.2018-0301OC.
McBrien, C. N., & Menzies-Gow, A. (2017). The Biology of Eosinophils and Their Role in Asthma. Frontiers in medicine, 4, 93. DOI: 10.3389/fmed.2017.00093.
Januskevicius, A., Vaitkiene, S., Gosens, R., Janulaityte, I., Hoppenot, D., Sakalauskas, R., & Malakauskas, K. (2016). Eosinophils enhance WNT-5a and TGF-β1 genes expression in airway smooth muscle cells and promote their proliferation by increased extracellular matrix proteins production in asthma. BMC pulmonary medicine, 16(1), 94. DOI: 10.1186/s12890-016-0254-9.
Han, Y.Y., Forno, E., & Celedón, J.C. (2017). Vitamin D Insufficiency and Asthma in a US Nationwide Study. The journal of allergy and clinical immunology. In practice, 5(3), 790-796.e1. DOI: 10.1016/j.jaip.2016.10.013.
Zhu, Y., Jing, D., Liang, H., Li, D., Chang, Q., Shen, M., Pan, P., Liu, H., & Zhang, Y. (2022). Vitamin D status and asthma, lung function, and hospitalization among British adults. Frontiers in nutrition, 9, 954768. DOI: 10.3389/fnut. 2022.954768.
Han, W., Li, J., Tang, H., & Sun, L. (2017). Treatment of obese asthma in a mouse model by simvastatin is associated with improving dyslipidemia and decreasing leptin level. Biochemical and biophysical research communications, 484(2), 396-402. DOI: 10.1016/j.bbrc.2017.01.135.
Wang, Z., Zhang, H., Sun, X., & Ren, L. (2016). The protective role of vitamin D3 in a murine model of asthma via the suppression of TGF-β/Smad signaling and activation of the Nrf2/HO-1 pathway. Molecular medicine reports, 14(3), 2389-2396. DOI: 10.3892/mmr. 2016.5563.
Mohammadzadeh, I., Darvish, S., Qujeq, D., Hajiahmadi, M., & Vaghari-Tabari, M. (2020). Association of serum 25-OH vitamin D₃ with serum IgE and the Pediatric Asthma Severity Score in patients with pediatric asthma. Allergy and asthma proceedings, 41(2), 126-133. DOI: 10.2500/aap.2020.41.190025.
Sobczak, M., & Pawliczak, R. (2022). Does Vitamin D Work Synergistically with Anti-Asthmatic Drugs in Airway Remodeling? International journal of molecular sciences, 23(21), 12798. DOI: 10.3390/ijms232112798.
Park, J.E., Pichiah, P.B. T., & Cha, Y.S. (2018). Vitamin D and Metabolic Diseases: Growing Roles of Vitamin D. Journal of obesity & metabolic syndrome, 27(4), 223-232. DOI: 10.7570/jomes.2018.27.4.223.
Alabed, M., Elemam, N.M., Ramakrishnan, R.K., Sharif-Askari, N.S., Kashour, T., Hamid, Q., & Halwani, R. (2022). Therapeutic effect of statins on airway remodeling during asthma. Expert review of respiratory medicine, 16(1), 17-24. DOI: 10.1080/17476348.2021.1987890.
Ramadan, A., Sallam, S., Yousef, R., Elsheikh, M., Ali, A., Elhusseny, Y., & Ishak, S. (2022). Evaluation of IGF-1, TNF-α, and TGF-β Gene Expression after Oral Vitamin D Supplementation in School-Aged Children with Chronic Bronchial Asthma. Open Access Macedonian Journal of Medical Sciences, 10, 1358-1364.
Sun, S., Han, W., & Hao, W. (2017). Clinical studies of simvastatin in treatment of adult-onset obesity with asthma. Biomedical Research, 28(14), 6514-6517.
