The Role of Th17/Treg Imbalance, FeNO, Eosinophils, IgE and their Correlation with Lung Function Parameters with Asthma-Chronic Obstructive Pulmonary Disease
-
Chenli Xie
,
Weixia Xu
,
Shuke Rao
,
Yanshen Xie
,
Qingting Liang
,
Lichong Chen
,
Weiliang Yuan
,
Ying Xie
,
Huafeng Li
,
Guihua Xu
Abstract
This study explored the link between clinical features, immune markers, and asthma-chronic obstructive pulmonary disease overlap (ACO), aiming to enhance diagnostic precision and tailor treatment.
The study included 60 patients per group: COPD patients, ACO patients, and healthy controls. Biological indicators such as fractional exhaled nitric oxide (FeNO), eosinophils, immunoglobulin E (IgE), T helper (Th) 17 cell counts, regulatory T-cell (Treg) counts, and cytokine levels of interleukin-17 (IL-17) and interleukin-10 (IL-10) were measured using standard enzyme-linked immunosorbent assay and flow cytometry techniques.
Elevated Th17 cells, IL-17, and Th17/Treg ratio, alongside reduced IL-10 and Treg levels, were observed in COPD and ACO patients. ACO patients showed worse lung function, with a negative correlation between FeNO, Th17 cells, Th17/Treg ratio, IL-17, and lung function indices, and a positive correlation with residual volume/total lung capacity (RV/TLC) ratio.
The study suggests that Th17/Treg imbalance, FeNO, eosinophils, and IgE could be key in ACO pathogenesis, potentially aiding early diagnosis and targeted treatment. Future research may utilize these findings to develop preventative and therapeutic strategies for ACO.
1. Christenson SA, Steiling K, van den Berge M. Asthma-COPD overlap. Clinical relevance of genomic signatures of type 2 inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2015;191(7):758-66.
2. Christenson SA, Steiling K, van den Berge M. Asthma-COPD overlap. Clinical relevance of genomic signatures of type 2 inflammation in chronic obstructive pulmonary disease. Am J Resp Crit Care. 2015;191(7):758-66
3. Fuhlbrigge AL. Epidemiology of Asthma-Chronic Obstructive Pulmonary Disease Overlap. Immunol Allergy Clin. 2022;42(3):533-47.
4. Wurst KE, Kelly-Reif K, Bushnell GA, Pascoe S, Barnes N. Understanding asthma-chronic obstructive pulmonary disease overlap syndrome. Resp Med. 2016;110(1-11).
5. Christenson SA, Smith BM, Bafadhel M, Putcha N. Chronic obstructive pulmonary disease. Lancet. 2022;399(10342):2227-42.
6. Zheng J, Shi Y, Xiong L. The Expression of IL-6, TNF-alpha, and MCP-1 in Respiratory Viral Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease. J Immunol Res. 2017;2017(8539294).
7. Cho MH, Hobbs BD, Silverman EK. Genetics of chronic obstructive pulmonary disease: understanding the pathobiology and heterogeneity of a complex disorder. Lancet Resp Med. 2022;10(5):485-96.
8. Ramirez-Jimenez F, Pavon-Romero GF, Velasquez-Rodriguez JM, et al. Biologic Therapies for Asthma and Allergic Disease: Past, Present, and Future. Pharmaceuticals-Base. 2023;16(2):270.
9. Kraft M, Richardson M, Hallmark B, Billheimer D, Van den Berge M, Fabbri LM, et al. The role of small airway dysfunction in asthma control and exacerbations: a longitudinal, observational analysis using data from the ATLANTIS study. Lancet Resp Med. 2022;10(7):661-8.
10. Ornago AM, Pinardi E, Okoye C, Mazzola P, Ferrara MC, Finazzi A, et al. Analysis of Blood Biomarkers in Patients with Chronic Obstructive Pulmonary Disease (COPD) and with Asthma-COPD Overlap (ACO). Eur Geriatr Med. 2020;17(3):306-10.
11. Bui DS, Burgess JA, Lowe AJ. Childhood Lung Function Predicts Adult Chronic Obstructive Pulmonary Disease and Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome. Am J Resp Crit Care. 2017;196(1):39-46.
12. Dasgupta S, Ghosh N, Bhattacharyya P, Roy CS, Chaudhury K. Metabolomics of asthma, COPD, and asthma-COPD overlap: an overview. Crit Rev Cl Lab Sci. 2023;60(2):153-70.
13. Yamauchi Y, Yasunaga H, Matsui H, et al; Comparison of in-hospital mortality in patients with COPD, asthma and asthma-COPD overlap exacerbations. Respirology. 2015;20(6):940-6.
14. Lange P, Colak Y, Ingebrigtsen TS, Vestbo J, Marott JL. Long-term prognosis of asthma, chronic obstructive pulmonary disease, and asthma-chronic obstructive pulmonary disease overlap in the Copenhagen City Heart study: a prospective population-based analysis. Lancet Resp Med. 2016;4(6):454-62.
15. Laucho-Contreras M, de Oca MM, Owen CA. Asthma COPD Overlap Syndrome: An Approach to A Real -World Endotype in Obstructive Lung Disease? Curr Pharm Des. 2016;22(41):6273-82.
16. Albertson TE, Chenoweth JA, Pearson SJ, Murin S. The pharmacological management of asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS). Expert Opin Pharmacother. 2020;21(2):213-31.
17. Xie M, Wang W, Dou S, Cui L, Xiao W. Quantitative computed tomography measurements of emphysema for diagnosing asthma-chronic obstructive pulmonary disease overlap syndrome. Int J Chronic Obstr. 2016;11:953-61.
18. Wei Y, Liu B, Sun J, et al; Regulation of Th17/Treg function contributes to the attenuation of chronic airway inflammation by icariin in ovalbumin-induced murine asthma model. Immunobiology. 2015;220(6):789-97.
19. Hikichi M, Hashimoto S, Gon Y. Asthma and COPD overlap pathophysiology of ACO. Allergol Int. 2018;67(2):179-86.
20. Sorino C, Scichilone N, D'Amato M, Patella V, DI Marco F. Asthma-COPD overlap syndrome: recent advances in diagnostic criteria and prognostic significance. Minerva Med. 2017;108(3 Suppl 1):1-5.
21. Backdahl L, Aoun M, Norin U, Holmdahl R. Identification of Clec4b as a novel regulator of bystander activation of auto-reactive T cells and autoimmune disease. Plos Genet. 2020;16(6):e1008788.
22. van der Veeken J, Campbell C, Pritykin Y, Schizas M, Verter J, Hu W, et al. Genetic tracing reveals transcription factor Foxp3-dependent and Foxp3-independent functionality of peripherally induced Tregs. Immunity. 2022;55(7):1173-84.
23. Tan DB, Fernandez S, Price P, French MA, Thompson PJ, Moodley YP. Impaired function of regulatory T-cells in patients with chronic obstructive pulmonary disease (COPD). Immunobiology. 2014;219(12):975-9.
24. Zheng X, Zhang L, Chen J, Gu Y, Xu J, Ouyang Y. Dendritic cells and Th17/Treg ratio play critical roles in pathogenic process of chronic obstructive pulmonary disease. Biomed Pharmacother. 2018;108:1141-51.
25. Lourenco JD, Ito JT, Martins MA, Tiberio I, Lopes F. Th17/Treg Imbalance in Chronic Obstructive Pulmonary Disease: Clinical and Experimental Evidence. Front Immunol. 2021;12:804919.
26. Ji T, Li H. T-helper cells and their cytokines in pathogenesis and treatment of asthma. Front Immunol. 2023;14:1149203.
27. Akhter S, Tasnim FM, Islam MN. Role of Th17 and IL-17 Cytokines on Inflammatory and Auto-immune Diseases. Curr Pharm Design. 2023;29(26):2078-90.
28. Dey S, Eapen MS, Chia C, Gaikwad AV, Wark P, Sohal SS. Pathogenesis, clinical features of asthma COPD overlap, and therapeutic modalities. Am J Physiol-Lung C. 2022;322(1):L64-L83.
29. Barnes PJ. Therapeutic approaches to asthma-chronic obstructive pulmonary disease overlap syndromes. J Allergy Clin Immun. 2015;136(3):531-45.
30. Hudler AC, Sharma S. Understanding the Genetics of Asthma-COPD Overlap. Chest. 2022;161(5):1125-26.
31. Song Q, Chen P, Liu XM. The role of cigarette smoke-induced pulmonary vascular endothelial cell apoptosis in COPD. Resp Res. 2021;22(1):39.
32. Lin JL, Pei J, Feng XK, Zhang DM, Sun HY. The Impact of Non-Invasive Ventilation Combined with Montelukast on Clinical Efficiency and Pulmonary Function in Patients with Bronchial Asthma Complicated by Obstructive Sleep Apnea Hypopnea Syndrome. Altern Ther Health Med. 2022;28(2):124-8.
33. Uruma Y, Manabe T, Fujikura Y, Iikura M, Hojo M, Kudo K. Effect of asthma, COPD, and ACO on COVID-19: A systematic review and meta-analysis. Plos One. 2022;17(11):e0276774.
34. Ramesh R, Georgiou A, Harries T. Role of FeNO in predicting the responsiveness of inhaled corticosteroids in COPD: a systematic review. Br J Gen Pract. 2024;74(suppl 1):bjgp24X737745.
35. Choi JY, Kim SK, Lee JH, Jung KS, Yoo KH, Hwang KE, et al. Differences in clinical significance of bronchodilator responses measured by forced expiratory volume in 1 second and forced vital capacity. PLoS One. 2023;18(2):e0282256.
36. Tamada T, Sugiura H, Takahashi T, Matsunaga K, Kimura K, Katsumata U, et al. Biomarker-based detection of asthma-COPD overlap syndrome in COPD populations. Int J Chron Obstruct Pulmon Dis. 2015;10:2169-2176.
37. Alsayed AR, Abu-Samak MS, Alkhatib M. Asthma-COPD Overlap in Clinical Practice (ACO_CP 2023): Toward Precision Medicine. J Pers Med. 2023;13(4):677.
38. Postma DS, Rabe KF. The Asthma-COPD Overlap Syndrome. New Engl J Med. 2015;373(13):1241-9.
39. Horak F, Doberer D, Eber E, Horak E, Pohl W, Riedler J, et al. Diagnosis and management of asthma - Statement on the 2015 GINA Guidelines. Wien Klin Wochenschr. 2016;128(15-16):541-54.
40. Wang W, Ma D, Li T, Ying Y, Xiao W. People with older age and lower FEV1%pred tend to have a smaller FVC than VC in pre-bronchodilator spirometry. Resp Physiol Neurobi. 2014;194:1-5.
41. Mekov E, Nuñez A, Sin DD, Ichinose M, Rhee CK, Maselli DJ, Coté A, Suppli Ulrik C, Maltais F, Anzueto A, Miravitlles M. Update on Asthma-COPD Overlap (ACO): A Narrative Review. Int J Chron Obstruct Pulmon Dis. 2021 Jun 17;16:1783-99.
42. Doyen V, Casset A, Divaret-Chauveau A, Khayath N, Peiffer G, Bonniaud P, et al. [Diagnosis of allergy in asthma]. Rev Mal Respir. 2020;37(3):243-56.
43. Al Ghobain MO, Alsubaie AS, Aljumah WA, Alrumayh FM, Aldawsari KF, Alqahtani AM, et al. The Correlation Between Fractional Exhaled Nitric Oxide (FeNO), Blood Eosinophil Count, Immunoglobulin E Levels, and Spirometric Values in Patients with Asthma. Cureus J Med Science. 2023;15(2):e35289.
44. Thomas R, Qiao S, Yang X. Th17/Treg Imbalance: Implications in Lung Inflammatory Diseases. Int J Mol Sci. 2023;24(5):4865.
45. Kubysheva N, Boldina M, Eliseeva T, Soodaeva S, Klimanov I, Khaletskaya A, et al. Relationship of Serum Levels of IL-17, IL-18, TNF-alpha, and Lung Function Parameters in Patients with COPD, Asthma-COPD Overlap, and Bronchial Asthma. Mediat Inflamm. 2020;2020:4652898.
46. Sun L, Cornell TT, LeVine A, Berlin AA, Hinkovska-Galcheva V, Fleszar AJ, et al. Dual role of interleukin-10 in the regulation of respiratory syncitial virus (RSV)-induced lung inflammation. Clin Exp Immunol. 2013;172(2):263-79.
47. Qianmei Y, Zehong S, Guang W, Hui L, Lian G. Recent advances in the role of Th17/Tregs in tumor immunity and tumor therapy. Immunol Res. 2021;69(5):398-414.
48. Paradowska-Gorycka A, Wajda A, Romanowska-Prochnicka K. Th17/Treg-Related Transcriptional Factor Expression and Cytokine Profile in Patients with Rheumatoid Arthritis. Front Immunol. 2020;11(6):572858.
49. Ding B, Enstone A. Asthma and chronic obstructive pulmonary disease overlap syndrome (ACOS): structured literature review and physician insights. Expert Rev Resp Med. 2016;10(3):363-71.
2. Christenson SA, Steiling K, van den Berge M. Asthma-COPD overlap. Clinical relevance of genomic signatures of type 2 inflammation in chronic obstructive pulmonary disease. Am J Resp Crit Care. 2015;191(7):758-66
3. Fuhlbrigge AL. Epidemiology of Asthma-Chronic Obstructive Pulmonary Disease Overlap. Immunol Allergy Clin. 2022;42(3):533-47.
4. Wurst KE, Kelly-Reif K, Bushnell GA, Pascoe S, Barnes N. Understanding asthma-chronic obstructive pulmonary disease overlap syndrome. Resp Med. 2016;110(1-11).
5. Christenson SA, Smith BM, Bafadhel M, Putcha N. Chronic obstructive pulmonary disease. Lancet. 2022;399(10342):2227-42.
6. Zheng J, Shi Y, Xiong L. The Expression of IL-6, TNF-alpha, and MCP-1 in Respiratory Viral Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease. J Immunol Res. 2017;2017(8539294).
7. Cho MH, Hobbs BD, Silverman EK. Genetics of chronic obstructive pulmonary disease: understanding the pathobiology and heterogeneity of a complex disorder. Lancet Resp Med. 2022;10(5):485-96.
8. Ramirez-Jimenez F, Pavon-Romero GF, Velasquez-Rodriguez JM, et al. Biologic Therapies for Asthma and Allergic Disease: Past, Present, and Future. Pharmaceuticals-Base. 2023;16(2):270.
9. Kraft M, Richardson M, Hallmark B, Billheimer D, Van den Berge M, Fabbri LM, et al. The role of small airway dysfunction in asthma control and exacerbations: a longitudinal, observational analysis using data from the ATLANTIS study. Lancet Resp Med. 2022;10(7):661-8.
10. Ornago AM, Pinardi E, Okoye C, Mazzola P, Ferrara MC, Finazzi A, et al. Analysis of Blood Biomarkers in Patients with Chronic Obstructive Pulmonary Disease (COPD) and with Asthma-COPD Overlap (ACO). Eur Geriatr Med. 2020;17(3):306-10.
11. Bui DS, Burgess JA, Lowe AJ. Childhood Lung Function Predicts Adult Chronic Obstructive Pulmonary Disease and Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome. Am J Resp Crit Care. 2017;196(1):39-46.
12. Dasgupta S, Ghosh N, Bhattacharyya P, Roy CS, Chaudhury K. Metabolomics of asthma, COPD, and asthma-COPD overlap: an overview. Crit Rev Cl Lab Sci. 2023;60(2):153-70.
13. Yamauchi Y, Yasunaga H, Matsui H, et al; Comparison of in-hospital mortality in patients with COPD, asthma and asthma-COPD overlap exacerbations. Respirology. 2015;20(6):940-6.
14. Lange P, Colak Y, Ingebrigtsen TS, Vestbo J, Marott JL. Long-term prognosis of asthma, chronic obstructive pulmonary disease, and asthma-chronic obstructive pulmonary disease overlap in the Copenhagen City Heart study: a prospective population-based analysis. Lancet Resp Med. 2016;4(6):454-62.
15. Laucho-Contreras M, de Oca MM, Owen CA. Asthma COPD Overlap Syndrome: An Approach to A Real -World Endotype in Obstructive Lung Disease? Curr Pharm Des. 2016;22(41):6273-82.
16. Albertson TE, Chenoweth JA, Pearson SJ, Murin S. The pharmacological management of asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS). Expert Opin Pharmacother. 2020;21(2):213-31.
17. Xie M, Wang W, Dou S, Cui L, Xiao W. Quantitative computed tomography measurements of emphysema for diagnosing asthma-chronic obstructive pulmonary disease overlap syndrome. Int J Chronic Obstr. 2016;11:953-61.
18. Wei Y, Liu B, Sun J, et al; Regulation of Th17/Treg function contributes to the attenuation of chronic airway inflammation by icariin in ovalbumin-induced murine asthma model. Immunobiology. 2015;220(6):789-97.
19. Hikichi M, Hashimoto S, Gon Y. Asthma and COPD overlap pathophysiology of ACO. Allergol Int. 2018;67(2):179-86.
20. Sorino C, Scichilone N, D'Amato M, Patella V, DI Marco F. Asthma-COPD overlap syndrome: recent advances in diagnostic criteria and prognostic significance. Minerva Med. 2017;108(3 Suppl 1):1-5.
21. Backdahl L, Aoun M, Norin U, Holmdahl R. Identification of Clec4b as a novel regulator of bystander activation of auto-reactive T cells and autoimmune disease. Plos Genet. 2020;16(6):e1008788.
22. van der Veeken J, Campbell C, Pritykin Y, Schizas M, Verter J, Hu W, et al. Genetic tracing reveals transcription factor Foxp3-dependent and Foxp3-independent functionality of peripherally induced Tregs. Immunity. 2022;55(7):1173-84.
23. Tan DB, Fernandez S, Price P, French MA, Thompson PJ, Moodley YP. Impaired function of regulatory T-cells in patients with chronic obstructive pulmonary disease (COPD). Immunobiology. 2014;219(12):975-9.
24. Zheng X, Zhang L, Chen J, Gu Y, Xu J, Ouyang Y. Dendritic cells and Th17/Treg ratio play critical roles in pathogenic process of chronic obstructive pulmonary disease. Biomed Pharmacother. 2018;108:1141-51.
25. Lourenco JD, Ito JT, Martins MA, Tiberio I, Lopes F. Th17/Treg Imbalance in Chronic Obstructive Pulmonary Disease: Clinical and Experimental Evidence. Front Immunol. 2021;12:804919.
26. Ji T, Li H. T-helper cells and their cytokines in pathogenesis and treatment of asthma. Front Immunol. 2023;14:1149203.
27. Akhter S, Tasnim FM, Islam MN. Role of Th17 and IL-17 Cytokines on Inflammatory and Auto-immune Diseases. Curr Pharm Design. 2023;29(26):2078-90.
28. Dey S, Eapen MS, Chia C, Gaikwad AV, Wark P, Sohal SS. Pathogenesis, clinical features of asthma COPD overlap, and therapeutic modalities. Am J Physiol-Lung C. 2022;322(1):L64-L83.
29. Barnes PJ. Therapeutic approaches to asthma-chronic obstructive pulmonary disease overlap syndromes. J Allergy Clin Immun. 2015;136(3):531-45.
30. Hudler AC, Sharma S. Understanding the Genetics of Asthma-COPD Overlap. Chest. 2022;161(5):1125-26.
31. Song Q, Chen P, Liu XM. The role of cigarette smoke-induced pulmonary vascular endothelial cell apoptosis in COPD. Resp Res. 2021;22(1):39.
32. Lin JL, Pei J, Feng XK, Zhang DM, Sun HY. The Impact of Non-Invasive Ventilation Combined with Montelukast on Clinical Efficiency and Pulmonary Function in Patients with Bronchial Asthma Complicated by Obstructive Sleep Apnea Hypopnea Syndrome. Altern Ther Health Med. 2022;28(2):124-8.
33. Uruma Y, Manabe T, Fujikura Y, Iikura M, Hojo M, Kudo K. Effect of asthma, COPD, and ACO on COVID-19: A systematic review and meta-analysis. Plos One. 2022;17(11):e0276774.
34. Ramesh R, Georgiou A, Harries T. Role of FeNO in predicting the responsiveness of inhaled corticosteroids in COPD: a systematic review. Br J Gen Pract. 2024;74(suppl 1):bjgp24X737745.
35. Choi JY, Kim SK, Lee JH, Jung KS, Yoo KH, Hwang KE, et al. Differences in clinical significance of bronchodilator responses measured by forced expiratory volume in 1 second and forced vital capacity. PLoS One. 2023;18(2):e0282256.
36. Tamada T, Sugiura H, Takahashi T, Matsunaga K, Kimura K, Katsumata U, et al. Biomarker-based detection of asthma-COPD overlap syndrome in COPD populations. Int J Chron Obstruct Pulmon Dis. 2015;10:2169-2176.
37. Alsayed AR, Abu-Samak MS, Alkhatib M. Asthma-COPD Overlap in Clinical Practice (ACO_CP 2023): Toward Precision Medicine. J Pers Med. 2023;13(4):677.
38. Postma DS, Rabe KF. The Asthma-COPD Overlap Syndrome. New Engl J Med. 2015;373(13):1241-9.
39. Horak F, Doberer D, Eber E, Horak E, Pohl W, Riedler J, et al. Diagnosis and management of asthma - Statement on the 2015 GINA Guidelines. Wien Klin Wochenschr. 2016;128(15-16):541-54.
40. Wang W, Ma D, Li T, Ying Y, Xiao W. People with older age and lower FEV1%pred tend to have a smaller FVC than VC in pre-bronchodilator spirometry. Resp Physiol Neurobi. 2014;194:1-5.
41. Mekov E, Nuñez A, Sin DD, Ichinose M, Rhee CK, Maselli DJ, Coté A, Suppli Ulrik C, Maltais F, Anzueto A, Miravitlles M. Update on Asthma-COPD Overlap (ACO): A Narrative Review. Int J Chron Obstruct Pulmon Dis. 2021 Jun 17;16:1783-99.
42. Doyen V, Casset A, Divaret-Chauveau A, Khayath N, Peiffer G, Bonniaud P, et al. [Diagnosis of allergy in asthma]. Rev Mal Respir. 2020;37(3):243-56.
43. Al Ghobain MO, Alsubaie AS, Aljumah WA, Alrumayh FM, Aldawsari KF, Alqahtani AM, et al. The Correlation Between Fractional Exhaled Nitric Oxide (FeNO), Blood Eosinophil Count, Immunoglobulin E Levels, and Spirometric Values in Patients with Asthma. Cureus J Med Science. 2023;15(2):e35289.
44. Thomas R, Qiao S, Yang X. Th17/Treg Imbalance: Implications in Lung Inflammatory Diseases. Int J Mol Sci. 2023;24(5):4865.
45. Kubysheva N, Boldina M, Eliseeva T, Soodaeva S, Klimanov I, Khaletskaya A, et al. Relationship of Serum Levels of IL-17, IL-18, TNF-alpha, and Lung Function Parameters in Patients with COPD, Asthma-COPD Overlap, and Bronchial Asthma. Mediat Inflamm. 2020;2020:4652898.
46. Sun L, Cornell TT, LeVine A, Berlin AA, Hinkovska-Galcheva V, Fleszar AJ, et al. Dual role of interleukin-10 in the regulation of respiratory syncitial virus (RSV)-induced lung inflammation. Clin Exp Immunol. 2013;172(2):263-79.
47. Qianmei Y, Zehong S, Guang W, Hui L, Lian G. Recent advances in the role of Th17/Tregs in tumor immunity and tumor therapy. Immunol Res. 2021;69(5):398-414.
48. Paradowska-Gorycka A, Wajda A, Romanowska-Prochnicka K. Th17/Treg-Related Transcriptional Factor Expression and Cytokine Profile in Patients with Rheumatoid Arthritis. Front Immunol. 2020;11(6):572858.
49. Ding B, Enstone A. Asthma and chronic obstructive pulmonary disease overlap syndrome (ACOS): structured literature review and physician insights. Expert Rev Resp Med. 2016;10(3):363-71.
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| Keywords | ||
| Asthma-COPD overlap syndrome Cytokines Lung function Regulatory T cells Systemic inflammation Th17 cells | ||
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How to Cite
1.
Xie C, Xu W, Rao S, Xie Y, Liang Q, Chen L, Yuan W, Xie Y, Li H, Xu G. The Role of Th17/Treg Imbalance, FeNO, Eosinophils, IgE and their Correlation with Lung Function Parameters with Asthma-Chronic Obstructive Pulmonary Disease. Iran J Allergy Asthma Immunol. 2024;:1-16.
