Araştırma Makalesi
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Hafif-Orta Persistan Astımlı Çocuklarda İnhale Kortikosteroid (Budesonide)'in Serum α -1-Antitiripsin, Sistatin C, ACE, IL-8 ve Klinik Üzerine Etkisinin Araştırılması

Yıl 2024, , 120 - 128, 30.08.2024
https://doi.org/10.29058/mjwbs.1428191

Öz

Amaç: Bu çalışma astımlı çocukların tedavisinde önemli yeri olan inhale kortikosteroidlerin çocukluk çağı astımında klinik ve laboratuvar parametreleri üzerine etkilerinin incelenmesi amacıyla yapılmıştır.
Gereç ve Yöntemler: Zonguldak Bülent Ecevit Üniversitesi Tıp Fakültesi Çocuk Alerji polikliniğinde Mayıs-Ekim 2004 tarihlerinde yapılan prospektif bir çalışmadır. Hafif-orta persistan astım tanısı olan 27 çocuk hasta grubu, 25 sağlıklı çocuk kontrol grubu olarak alındı. Çalışmanın başlangıcında hasta grubuna gündüz ve gece belirtilerini puanlamaları için takip kartları verildi. Hasta grubu 0-4. haftalarda 4x100 µgr salbutamol, 5-8. haftalarda 1x400 µgr inhale kortikosteroid verilerek toplam 8 hafta izlendi. Beşinci haftanın başında ve 8. hafta sonunda hastaların fizik incelemeleri yapılarak laboratuvar değerleri (serum total IgE, eozinofil, eozinofilik katyonik protein, serum alfa -1-antitripsin, sistatin c, anjiyotensin dönüştürücü enzim, IL-8 ) ve solunum fonksiyonları değerlendirildi.
Bulgular: Çalışmanın başlangıcında hasta grubu ve kontrol grubu arasında cinsiyet, ağırlık ve boy açısından anlamlı bir farklılık yok iken, hasta grubunda serum total IgE (p=0.001), eozinofil (p=0.001), eozinofilik katyonik protein (p=0.001) ve ACE (p=0.004) değerleri anlamlı düzeyde yüksek bulundu. Hasta grubunda dördüncü ve sekizinci haftaların sonundaki laboratuvar değerleri ve solunum fonksiyon testleri karşılaştırıldı. FEVı (p=0.001), PEF (p=0.003) ve FEF %25-75 (p=0.002) de artış, total Ig E (p=0.017), serum eozinofil (p=0.014), eozinofilik katyonik protein (p=0.015) ve sistatin C (p=0.002) düzeylerinde anlamlı azalma gözlendi. Hasta grubunun gündüz ve gece belirtileri ardışık olarak karşılaştırıldığında haftalar arasında farklılık gözlenmedi.
Sonuç: Çalışmamızdaki laboratuvar değerlerinden serum total IgE, eozinofil, eozinofilik katyonik protein ve sistatin C, astım tedavisine yanıtın izlenmesinde yol gösterebilir.

Etik Beyan

Zonguldak Bülent Ecevit Üniversitesi Tıp Fakültesi Hastanesi Etik Kurulu tarafından 27.05.2004 tarihinde 2004/05 toplantı numarası ile onaylanmıştır.

Destekleyen Kurum

Yoktur

Teşekkür

Yoktur

Kaynakça

  • 1. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention, 2023. Sayfa 22. (https://ginasthma. org/wp-content/uploads/2023/07/GINA-2023-Full-report- 23_07_06-WMS.pdf, Erişim tarihi: 06.08.2024
  • 2. Türk Toraks Derneği Astım Tanı ve Tedavi Rehberi, 2016. Sayfa 2. https://toraks.org.tr/site/sf/books/pre_migration/2109b- 422ca4358f59497baaf8a744af15ea33bdca7993a5e948d- 4b64e8b75091.pdf ErişimTarihi : 06.08.2024
  • 3. Levy ML, Fletcher M, Price DB, Hausen T, Halbert RJ, Yawn BP. International Primary Care Respiratory Group (IPCRG) Guidelines: diagnosis of respiratory diseases in primary care. Primary Care Respiratory Journal 2006; 15: 20-34.
  • 4. Liu AH, Zeiger R, Sorkness C, Mahr T, Ostrom N, Burgess S, Rozenweig JC, Manjunath R. Development and cross-sectional validation of the Childhood Asthma Control Test. J Allergy Clin Immunol 2007; 119: 817-825.
  • 5. Juniper EF, Gruffydd-Jones K, Ward S, Svensson K. Asthma Control Questionnaire in children: validation, measurement properties, interpretation. Eur Respir J 2010; 36: 1410-1416.
  • 6. Shah SN, Grunwell JR, Mohammad AF, Stephenson ST, Lee GB, Vickery BP, Fizpatric AM. Performance of Eosinophil Cationic Protein as a Biomarker in Asthmatic Children. J Allergy Clin Immunol Pract. 2021; 9(7): 2761–2769.
  • 7. Koller DY, Herouy Y, Götz M, Hagel E, Urbanek R, Eichler I. Clinical value of monitoring eosinophil activity in asthma. Arch Dis Child 1995; 73: 413-417.
  • 8. Aderele WI, Ojo C, Osanyintuyi VO, Oduwole O. Serum alpha 1-antitrypsin levels in asthmatic children. Afr J Med Med Sci 1985; 14(3-4): 161-7.
  • 9. Mousavi S A, Mohammadzadeh V, Loni E. Determination of Alpha-1 Antitrypsin Level in Patients with Severe Asthma. Tanaffos 2013; 12(4): 19-22
  • 10. Shigemura M, Konno S, Nasuhara Y, Shimizu C, Matsuno K, Nishimura M. Impact of asthmatic control status on serum cystatin C concentrations. Clin Chem Lab Med 2012; 50(8): 1367- 71.
  • 11. Cimerman N, Brguljan P M, Krasovec M, Suskovic S, Kos J. Serum cystatin C, a potent inhibitor of cysteine proteinases, is elevated in asthmatic patients. Clin Chim Acta 2000; 300(1-2): 83-95.
  • 12. Hui Q, Hao Y, Ye F, Pang B, Niu W, Zhang Q. Genetically high angiotensin-converting enzyme concentrations causally increase asthma risk: A meta-analysis using Mendelian randomization. Front Med (Lausanne) 2022; 9: 941944.
  • 13. Ayada C, Toru Ü, Genç O, Şahin S, Bulut İ, Arık Ö, Acat M. Evaluation of Serum Levels of Renin Angiotensin System Components in Asthmatic Patients. Erciyes Med J 2015; 37(3): 87- 90.
  • 14. Charrad R, Kaabachi W, Rafrafi A, Berraies A, Hamzaoui K, Hamzaoui A. IL-8 Gene Variants and Expression in Childhood Asthma. Lung. 2017; 195(6): 749-757.
  • 15. Brown KR, Krouse RZ, Calatroni A, Visness CM, Sivaprasad U, Kercsmar CM, Matsui EC, West JB, Makhija MM, Gill MA, Kim H, Kattan M, Pillai D, Gern JE, Busse WW, Togias A ,Liu AH, KhuranaHershey GK. Endotypes of difficult-to-control asthma in inner-city African American children. PLoS One. 2017;12(7): e0180778.
  • 16. Busse WW, Pedersen S, Pauwels RA, Tan WC, Chen Y, Lamm CJ, O’Byrne PM; START Investigators Group. The Inhaled Steroid Treatment As Regular Therapy in Early Asthma (START) study 5-year follow-up: effectiveness of early intervention with budesonide in mild persistent asthma. J Allergy Clin Immunol 2008; 121: 1167-1174.
  • 17. Selroos O, Pietinalho A, Lofroos AB, Riska H. Effect of early vs late intervention with inhaled corticosteroids in asthma. Chest 1995; 108: 1228-1234.
  • 18. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention, 2004. Sayfa 74-76. https:// ginasthma.org/wp-content/uploads/2023/04/GINA-Main-Report- 2004-WMSA.pdf ErişimTarihi: 06.08.2024
  • 19. Türktas İ, Demirsoy S, Koç, Gökçora N, Elbeg S. Effects of inhaled steroid treatment on serum eosinophilic cationic protein (ECP) and low affinity receptor for IgE (Fc E RII/sCD23) in childhood bronchial asthma. Archives of Disease in Childhood 1996; 75: 314-318.
  • 20. Lommatzsch M, Klein M, Stoll P, Virchow JC. Impact of an increase in the inhaled corticosteroid dose on blood eosinophils in asthma. Thorax 2019; 74(4): 417-418.
  • 21. Ohrui T, Funayama T, Sekizawa K, Yamaya M, Sasaki H. Effects of inhaled beclomethasone dipropionate on serum IgE levels and clinical symptoms in atopic asthma. Clin Exp Allergy 1999; 29(3): 357-361.
  • 22. Guo C, Sun X, Wang X, Guo Q. Serum Eosinophil Cationic Protein Is a Useful Marker for Assessing the Efficacy of Inhaled Corticosteroid Therapy in Children with Bronchial Asthma. Thoku J. Exp. Med. 2017; 242 (4): 263-271
  • 23. Devulapalli C.S, Haaland G, Pettersen M, Carlsen KH, Carlsen KCL. Effect of inhaled steroids on lung function in young children: a cohort study. European Respiratory Journal 2004; 23(6): 869-875.
  • 24. Bime C, Gerald JK, Wei CY, Holbrook JT, Teague WG, Wise RA, Gerald LB. Measurement characteristics of the childhood Asthma-Control Test and a shortened, child-only version. NPJ Prim Care Respir Med. 2016; 26: 16075.
  • 25. Lara, M, Duan N, Sherbourne C, Lewis MA, Landon C, Halfon N, Brook RH. Differences between child and parent reports of symptoms among Latino children with asthma. Pediatrics. 1998; 102(6): E68.
  • 26. Le Coq EM, Boeke AJ, Bezemer PD, Colland VT, van Eijk JT. Which source should we use to measure quality of life in children with asthma: the children themselves or their parents? Qual. Life Res. 2000; 9(6): 625–636.
  • 27. Hedman L, Lindgren B, Perzanowski M, Rönmark E. Agreement between parental and self-completed questionnaires about asthma in teenagers. Pediatr. Allergy Immunol 2005; 16(2): 176–181.
  • 28. Mohamed SF, Abd-Elwahab FM, Shokry DM, Mohammed- Samy W. Relation between Interleukin 8 and Bronchial Asthma in Children: Review Article. The Egyptian Journal of Hospital Medicine 2021;85(2): 3621-3623
  • 29. Zhang J, Bai C. Elevated Serum Interleukin-8 Level as a Preferable Biomarker for Identifying Uncontrolled Asthma and Glucocorticosteroid Responsiveness. Tanaffos 2017; 16(4): 260–269.
  • 30. Wei Q, Liao J, Jiang M, Liu J, Liang X, Nong G. Relationship between Th17‑mediated immunity and airway inflammation in childhood neutrophilic asthma. Allergy Asthma Clin Immunol 2021; 17(1): 4
  • 31. Ramphul M, Welsh K G, May R D, Ghebre MA, Rapley L, Cohen ES, Herath A, Monteiro W, Rousseau K, Thornton DJ, Brightling CE, Gaillard EA. Sputum biomarkers during acute severe asthma attacks in children-a case-control study. Acta Paediatr . 2022; 111(3):620-627.
  • 32. El-Esawy NM, Morad MA, Abdin AA. Urinary Creatinine and Serum Cystatin C in Asthmatic Children Treated with Inhaled Corticosteroid and Beta 2 Agonist. Alexandria Journal of Pediatrics 2005; 19(2): 231-239.
  • 33. Schwartz RH, Van Ess JD, Johnstone DE, Dreyfuss EM, Abrishami MA, Chai H. Alpha-1 antitrypsin in childhood asthma. J Allergy Clin Immunol. 1977; 59(1): 31-34.
  • 34. Mue S, Takahashi M, Ohmi T, Shibahara S, Yamauchi K, Fujimoto S, Okayama H, Takishima T. Serum angiotensin converting enzyme level in bronchial asthma. Ann Allergy . 1978; 40(1): 51-57.
  • 35. Frank-Piskorska A, Lypka A, Konieczna M. Serum angiotensin converting enzyme (SACE) in patients with atopic bronchial asthma. Pneumonol Alergol Pol. 1991; 59(7-8):13-16.
  • 36. Millar EA, Angus RM, Hulks G, Morton JJ, Connell JM, Thomson NC. Activity of the renin-angiotensin system in acute severe asthma and the effect of angiotensin II on lung function. Thorax 1994; 49(5): 492-495.

Evaluation of Effects of Inhaled Corticosteroid (Budesonide) on Cycstatin C, Angiotensin Converting Enzyme, α -1-Antityripsin, Interleukin–8 and Clinical Status in Mild to Moderate Persistant Asthmatic Children

Yıl 2024, , 120 - 128, 30.08.2024
https://doi.org/10.29058/mjwbs.1428191

Öz

Aim: Inhaled corticosteroids have a major role in treating childhood asthma. This study evaluated the effects of budesonide on the clinical and laboratory parameters in asthmatic children.
Material and Methods: This prospective study was conducted at the Zonguldak Bülent Ecevit School of Medicine Hospital Pediatric Allergy outpatient clinic between May and October 2004 with 27 mild to moderate persistent asthmatic children and 25 healthy children as the control group. For the first four weeks, the patient group was given symptom score charts, inhaled salbutamol 4x100 µgr daily, and between the fifth and eighth weeks inhaled corticosteroid 1x400 µgr daily. At the beginning of the fifth week and the end of the eighth week, the patient group’s physical examinations were performed, lung functions were assessed, and serum parameters (serum total IgE, eosinophil, ECP, cystatin C, angiotensin-converting enzyme, α-1-antitrypsin, and IL-8) were collected.
Results: Although the two groups were similar in terms of sex, weight, and height at the beginning of the study, serum total IgE (p=0.001), eosinophil (p=0.001), eosinophil cationic protein (p=0.001), and ACE values (p=0.004) were significantly higher in the patient group. The comparison of the fourth and eighth weeks' lung function parameters revealed significant improvement in FEV1 (p=0.001), PEF (p=0.003), and FEF %25-75 (p=0.002) in the patient group. A significant decrease was detected in total Ig E (p=0.017), serum eosinophil (p=0.014), eosinophil cationic protein (p=0.015), and, cystatin C (p=0.002) values as well. When the daytime and nighttime symptoms of the patient group were compared consecutively, no differences were observed between the weeks.
Conclusion: We conclude that total IgE, eosinophil, ECP, and cystatin C levels may be useful for the follow-up of the treatment of asthma in children.

Kaynakça

  • 1. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention, 2023. Sayfa 22. (https://ginasthma. org/wp-content/uploads/2023/07/GINA-2023-Full-report- 23_07_06-WMS.pdf, Erişim tarihi: 06.08.2024
  • 2. Türk Toraks Derneği Astım Tanı ve Tedavi Rehberi, 2016. Sayfa 2. https://toraks.org.tr/site/sf/books/pre_migration/2109b- 422ca4358f59497baaf8a744af15ea33bdca7993a5e948d- 4b64e8b75091.pdf ErişimTarihi : 06.08.2024
  • 3. Levy ML, Fletcher M, Price DB, Hausen T, Halbert RJ, Yawn BP. International Primary Care Respiratory Group (IPCRG) Guidelines: diagnosis of respiratory diseases in primary care. Primary Care Respiratory Journal 2006; 15: 20-34.
  • 4. Liu AH, Zeiger R, Sorkness C, Mahr T, Ostrom N, Burgess S, Rozenweig JC, Manjunath R. Development and cross-sectional validation of the Childhood Asthma Control Test. J Allergy Clin Immunol 2007; 119: 817-825.
  • 5. Juniper EF, Gruffydd-Jones K, Ward S, Svensson K. Asthma Control Questionnaire in children: validation, measurement properties, interpretation. Eur Respir J 2010; 36: 1410-1416.
  • 6. Shah SN, Grunwell JR, Mohammad AF, Stephenson ST, Lee GB, Vickery BP, Fizpatric AM. Performance of Eosinophil Cationic Protein as a Biomarker in Asthmatic Children. J Allergy Clin Immunol Pract. 2021; 9(7): 2761–2769.
  • 7. Koller DY, Herouy Y, Götz M, Hagel E, Urbanek R, Eichler I. Clinical value of monitoring eosinophil activity in asthma. Arch Dis Child 1995; 73: 413-417.
  • 8. Aderele WI, Ojo C, Osanyintuyi VO, Oduwole O. Serum alpha 1-antitrypsin levels in asthmatic children. Afr J Med Med Sci 1985; 14(3-4): 161-7.
  • 9. Mousavi S A, Mohammadzadeh V, Loni E. Determination of Alpha-1 Antitrypsin Level in Patients with Severe Asthma. Tanaffos 2013; 12(4): 19-22
  • 10. Shigemura M, Konno S, Nasuhara Y, Shimizu C, Matsuno K, Nishimura M. Impact of asthmatic control status on serum cystatin C concentrations. Clin Chem Lab Med 2012; 50(8): 1367- 71.
  • 11. Cimerman N, Brguljan P M, Krasovec M, Suskovic S, Kos J. Serum cystatin C, a potent inhibitor of cysteine proteinases, is elevated in asthmatic patients. Clin Chim Acta 2000; 300(1-2): 83-95.
  • 12. Hui Q, Hao Y, Ye F, Pang B, Niu W, Zhang Q. Genetically high angiotensin-converting enzyme concentrations causally increase asthma risk: A meta-analysis using Mendelian randomization. Front Med (Lausanne) 2022; 9: 941944.
  • 13. Ayada C, Toru Ü, Genç O, Şahin S, Bulut İ, Arık Ö, Acat M. Evaluation of Serum Levels of Renin Angiotensin System Components in Asthmatic Patients. Erciyes Med J 2015; 37(3): 87- 90.
  • 14. Charrad R, Kaabachi W, Rafrafi A, Berraies A, Hamzaoui K, Hamzaoui A. IL-8 Gene Variants and Expression in Childhood Asthma. Lung. 2017; 195(6): 749-757.
  • 15. Brown KR, Krouse RZ, Calatroni A, Visness CM, Sivaprasad U, Kercsmar CM, Matsui EC, West JB, Makhija MM, Gill MA, Kim H, Kattan M, Pillai D, Gern JE, Busse WW, Togias A ,Liu AH, KhuranaHershey GK. Endotypes of difficult-to-control asthma in inner-city African American children. PLoS One. 2017;12(7): e0180778.
  • 16. Busse WW, Pedersen S, Pauwels RA, Tan WC, Chen Y, Lamm CJ, O’Byrne PM; START Investigators Group. The Inhaled Steroid Treatment As Regular Therapy in Early Asthma (START) study 5-year follow-up: effectiveness of early intervention with budesonide in mild persistent asthma. J Allergy Clin Immunol 2008; 121: 1167-1174.
  • 17. Selroos O, Pietinalho A, Lofroos AB, Riska H. Effect of early vs late intervention with inhaled corticosteroids in asthma. Chest 1995; 108: 1228-1234.
  • 18. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention, 2004. Sayfa 74-76. https:// ginasthma.org/wp-content/uploads/2023/04/GINA-Main-Report- 2004-WMSA.pdf ErişimTarihi: 06.08.2024
  • 19. Türktas İ, Demirsoy S, Koç, Gökçora N, Elbeg S. Effects of inhaled steroid treatment on serum eosinophilic cationic protein (ECP) and low affinity receptor for IgE (Fc E RII/sCD23) in childhood bronchial asthma. Archives of Disease in Childhood 1996; 75: 314-318.
  • 20. Lommatzsch M, Klein M, Stoll P, Virchow JC. Impact of an increase in the inhaled corticosteroid dose on blood eosinophils in asthma. Thorax 2019; 74(4): 417-418.
  • 21. Ohrui T, Funayama T, Sekizawa K, Yamaya M, Sasaki H. Effects of inhaled beclomethasone dipropionate on serum IgE levels and clinical symptoms in atopic asthma. Clin Exp Allergy 1999; 29(3): 357-361.
  • 22. Guo C, Sun X, Wang X, Guo Q. Serum Eosinophil Cationic Protein Is a Useful Marker for Assessing the Efficacy of Inhaled Corticosteroid Therapy in Children with Bronchial Asthma. Thoku J. Exp. Med. 2017; 242 (4): 263-271
  • 23. Devulapalli C.S, Haaland G, Pettersen M, Carlsen KH, Carlsen KCL. Effect of inhaled steroids on lung function in young children: a cohort study. European Respiratory Journal 2004; 23(6): 869-875.
  • 24. Bime C, Gerald JK, Wei CY, Holbrook JT, Teague WG, Wise RA, Gerald LB. Measurement characteristics of the childhood Asthma-Control Test and a shortened, child-only version. NPJ Prim Care Respir Med. 2016; 26: 16075.
  • 25. Lara, M, Duan N, Sherbourne C, Lewis MA, Landon C, Halfon N, Brook RH. Differences between child and parent reports of symptoms among Latino children with asthma. Pediatrics. 1998; 102(6): E68.
  • 26. Le Coq EM, Boeke AJ, Bezemer PD, Colland VT, van Eijk JT. Which source should we use to measure quality of life in children with asthma: the children themselves or their parents? Qual. Life Res. 2000; 9(6): 625–636.
  • 27. Hedman L, Lindgren B, Perzanowski M, Rönmark E. Agreement between parental and self-completed questionnaires about asthma in teenagers. Pediatr. Allergy Immunol 2005; 16(2): 176–181.
  • 28. Mohamed SF, Abd-Elwahab FM, Shokry DM, Mohammed- Samy W. Relation between Interleukin 8 and Bronchial Asthma in Children: Review Article. The Egyptian Journal of Hospital Medicine 2021;85(2): 3621-3623
  • 29. Zhang J, Bai C. Elevated Serum Interleukin-8 Level as a Preferable Biomarker for Identifying Uncontrolled Asthma and Glucocorticosteroid Responsiveness. Tanaffos 2017; 16(4): 260–269.
  • 30. Wei Q, Liao J, Jiang M, Liu J, Liang X, Nong G. Relationship between Th17‑mediated immunity and airway inflammation in childhood neutrophilic asthma. Allergy Asthma Clin Immunol 2021; 17(1): 4
  • 31. Ramphul M, Welsh K G, May R D, Ghebre MA, Rapley L, Cohen ES, Herath A, Monteiro W, Rousseau K, Thornton DJ, Brightling CE, Gaillard EA. Sputum biomarkers during acute severe asthma attacks in children-a case-control study. Acta Paediatr . 2022; 111(3):620-627.
  • 32. El-Esawy NM, Morad MA, Abdin AA. Urinary Creatinine and Serum Cystatin C in Asthmatic Children Treated with Inhaled Corticosteroid and Beta 2 Agonist. Alexandria Journal of Pediatrics 2005; 19(2): 231-239.
  • 33. Schwartz RH, Van Ess JD, Johnstone DE, Dreyfuss EM, Abrishami MA, Chai H. Alpha-1 antitrypsin in childhood asthma. J Allergy Clin Immunol. 1977; 59(1): 31-34.
  • 34. Mue S, Takahashi M, Ohmi T, Shibahara S, Yamauchi K, Fujimoto S, Okayama H, Takishima T. Serum angiotensin converting enzyme level in bronchial asthma. Ann Allergy . 1978; 40(1): 51-57.
  • 35. Frank-Piskorska A, Lypka A, Konieczna M. Serum angiotensin converting enzyme (SACE) in patients with atopic bronchial asthma. Pneumonol Alergol Pol. 1991; 59(7-8):13-16.
  • 36. Millar EA, Angus RM, Hulks G, Morton JJ, Connell JM, Thomson NC. Activity of the renin-angiotensin system in acute severe asthma and the effect of angiotensin II on lung function. Thorax 1994; 49(5): 492-495.
Toplam 36 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Klinik Tıp Bilimleri (Diğer)
Bölüm Araştırma Makalesi
Yazarlar

Tunç Tunçer 0000-0003-2558-8851

Nazan Tomaç 0009-0006-6090-0838

Yayımlanma Tarihi 30 Ağustos 2024
Gönderilme Tarihi 30 Ocak 2024
Kabul Tarihi 25 Temmuz 2024
Yayımlandığı Sayı Yıl 2024

Kaynak Göster

Vancouver Tunçer T, Tomaç N. Hafif-Orta Persistan Astımlı Çocuklarda İnhale Kortikosteroid (Budesonide)’in Serum α -1-Antitiripsin, Sistatin C, ACE, IL-8 ve Klinik Üzerine Etkisinin Araştırılması. Med J West Black Sea. 2024;8(2):120-8.

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