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Astımlı hastalarda rosuvastatin tedavisinin havayolu inflamatuvar belirteçleri ve yaşam kalitesi göstergeleri üzerine etkisi

Yıl 2017, Cilt: 30 Sayı: 2, 73 - 81, 14.05.2017
https://doi.org/10.5472/marumj.344816

Öz

Amaç: Statinler kan lipid düzeylerinde azalma sağlamakla beraber

aynı zamanda pleiotropik ve anti-inflamatuvar etkileri olan ilaçlardır.

Statinlerin bir çok inflamatuvar hastalıkta yararlı etkileri gösterilmiş

olmasına karşın sonuçlar halen tartışmalıdır. Bu çalışmanın amacı

astım hastalarında rosuvastatin tedavisinin klinik ve anti-inflamatuvar

etkilerini incelemektir.

Hastalar ve Yöntem: Astım hastalarında vaka-control çalışması

planlanmıştır. Toplam 136 astım hastası incelenmiş ve 74 hasta

çalışmaya uygun bulunarak dahil edilmiştir. Elli bir hasta çalışmayı

tamamlayabilmiştir. Hastalar başlangıçta yapılan kan tahlilinde serum

düşük dansiteli lipoprotein (LDL) seviyesine göre iki gruba ayrılmıştır,

LDL düzeyi 130mg/dL üzerinde olan 25 hasta mevcut tedavilerine ek

olarak 8 hafta boyunca 40mg rosuvastatin tedavisi alırken, 26 hasta

kontrol grubu olarak almakta oldukları tedaviye devam etmişlerdir.

Her iki gruptaki hastalar, başlangıçta ve 8. haftanın sonunda solunum

fonksiyon testi (SFT), bronş provokasyon testi (PD20), indükte

balgamda serum inflamatuvar belirteçleri, astım kontrol testi (AKT) ve

yaşam kalitesi skorları (QoL) ile değerlendirilmişlerdir.

Bulgular: Statin kullanan grupta 8. hafta sonunda SFT’de FEV1/

FVC (pp) (%85,8±11,1 vs .%90,2±8,8 P<0,043), FEF % 25-75 (%

63,6±7,8 vs %74,6±8,4, P<0.0001) ve FEF25-75(L/sc) (3,51±0,4 vs

4,1±0,4 P<0,05) düzelme saptanırken statin kullanmayan grupta anlamlı

fark saptanmamıştır (P>0,05). Rosuvastatin tedavisi ile indükte balgam

eosinofilisinde (P<0,05); IL-6 ve TNF-alfa seviyelerinde azalma

(P<0,05) saptanırken, AKT ve QoL skorları ve bronş provakasyon

testinde anlamlı değişiklik saptanmamıştır.

Sonuç: Bu çalışmada, astım hastalarında rosuvastatin 40mg ile

8 haftalık tedavi sonrasında periferik eosinofili, total IgE seviyesi,

indükte balgamda inflamatuvar belirteçlerde anlamlı düzeyde azalma

saptanmıştır. Yine SFT parametrelerinde düzelme izlenmiştir ancak

buna karşın AKT ve QoL skorlarında değişim saptanmamıştır.Bu

sonuçlara göre rosuvastatin tedavisinin astım hastaları üzerinde bir

takım potensiyel anti-inflamatuar etkileri bulunmaktadır. Rosuvastatinin

klinik etkilerinin saptanması için daha fazla sayıda randomize çalışmaya

ihtiyaç vardır.

Kaynakça

  • Corsini A, Maggi FM, Catapano AL. Pharmacology of competitive inhibitors of HMG-CoA reductase. Pharmacol Res 1995;31:9-27. doi: 1043-6618(95)80042-5
  • Hothersall EJ, Chaudhuri R, McSharry C, et al. Effects of atorvastatin added to inhaled corticosteroids on lung function and sputum cell counts in atopic asthma. Thorax 2008;63:1070-5. doi: 10.1136/thx.2008.100198
  • Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator. Nature Medicine 2000;6:1399-402. doi: 10.1038/82219
  • Zeki AA, Oldham J, Wilson M, et al. Statin use and asthma control in patients with severe asthma. BMJ Open 2013;3:e003314. doi: 10.1136/bmjopen-2013-003314
  • Braganza G, Chaudhuri R, McSharry C, et al. Effects of shortterm treatment with atorvastatin in smokers with asthma. A randomized controlled trial. BMC Pulm Med 2011;11:16. doi: 10.1186/1471-2466-11-6.
  • Christiansen SC, Eddleston J, Wagelie-Steffen A, Yang AJ, Chen W, Zuraw BL. Influence of HMC-CoA reductase inhibitors on asthma severity. J Allergy Clin Immunol 2009;123:No 2 S84 Abst 313
  • Ostroukhova M, Kouides RW, Friedman E. The effect of statin therapy on allergic patients with asthma. Ann Allergy Asthma Immunol 2009;103:463-8. doi: 10.1016/S1081- 1206(10)60261-X
  • Report G. Global Initiative for Asthma:GINA Report, Global Strategy for Asthma Management and Prevention- updated 2012. 2012. Available at : (http://www.ginasthma.org). 2012 (Accessed:
  • Standardization of Spirometry, 1994 Update. American Thoracic Society. American Journal of Respiratory and Critical Care Medicine 1995;152:1107-36. doi: 10.1164/ ajrccm.152.3.7663792 1 Chai H, Farr RS, Froehlich LA, et al. Standardization of bronchial inhalation challenge procedures. J Allergy Clin Immunol 1975;56:323-7.
  • Schatz M, Sorkness CA, Li JT, et al. Asthma Control Test: reliability, validity, and responsiveness in patients notpreviously followed by asthma specialists. J Allergy Clinical Immunol 2006;117:549-56. doi: 10.1016/j.jaci.2006.01.011
  • Pinnock H, Sheikh A, Juniper EF. Evaluation of an intervention to improve successful completion of the Mini- AQLQ: comparison of postal and supervised completion. Primary Care Respiratory Journal : Journal of the General Practice Airways Group 2004;13:36-41. doi: 10.1016/j. pcrj.2003.11.004
  • Efthimiadis A, Jayaram L, Weston S, Carruthers S, Hargreave FE. Induced sputum: time from expectoration to processing. Europ Respir J 2002;19:706-8.
  • Foumani S, Nejatifar F, Forghan Parast K, Heidarinejad S, Mortazhejri G. Effects of atorvastatin in asthmatic patients under treatment with high dose oral or inhaled steroid. (Abstract) European Respirotary Society Annual Congress, Barcelona, Spain, September 18-22, 2010. (372).
  • Menzies D, Nair A, Meldrum KT, Fleming D, Barnes M, Lipworth BJ. Simvastatin does not exhibit therapeutic antiinflammatory effects in asthma. J Allergy Clinic Immunol 2007;119:328-35 doi: 10.1016/j.jaci.2006.10.014
  • Fahimi F, Jamaati H, Taheri ZM, Fakharian A, Salamzadeh J. Does atorvastatin have effect on lung function and morbiditiy as add on therapy in asthmatic patients? Europ Respir J 2007:490s:2960.
  • Moini A, Azimi G, Farivar A. Evaluation of atorvastatin for the treatment of patients with asthma: a double-blind randomized clinical trial. Allergy, Asthma Immunol Res 2012;4:290-4. doi: 10.4168/aair.2012.4.5.290
  • Cowan DC, Cowan JO, Palmay R, Williamson A, Taylor DR. Simvastatin in the treatment of asthma: lack of steroid-sparing effect. Thorax 2010;65:891-6. doi: 10.1136/thx.2010.138990
  • Feschenko Y, Lashyna L, Kramarskaya N, Polianska M, Matvienko J. Clinical and functional effectiveness of atorvastatin in complex therapy of severe bronchial asthma. (Abstract) European Respiratory Society Annual Congress, Berlin, Germany, October 4-8 2009. [E4554].
  • Liu PY, Liu YW, Lin LJ, Chen JH, Liao JK. Evidence for statin pleiotropy in humans: differential effects of statins and ezetimibe on rho-associated coiled-coil containing protein kinase activity, endothelial function, and inflammation. Circulation 2009;119:131-8. doi: 10.1161/ CIRCULATIONAHA.108.813311
  • Malek Mohammad M, Fahimi F, Fakharian A, et al. Methacoline Challenge test as an evaluator of response to statins in bronchial hyperresponsiveness. Iranian J Pharmaceutical Res 2012;11:969-77.
  • Deanin GG, Cutts JL, Pfeiffer JR, Oliver JM. Role of isoprenoid metabolism in IgE receptor-mediated signal transduction. J Immunol 1991;146:3528-35.
  • Roche CM, Trimble ER, Ennis M. Effect of in vivo and invitro lovastatin treatment on mast cell activation. Int Arch Allergy Immunol 1995;108:240-6.
  • Krauth MT, Majlesi Y, Sonneck K, et al. Effects of various statins on cytokine-dependent growth and IgEdependent release of histamine in human mast cells. Allergy 2006;61:281-8. doi: 10.1111/j.1398-9995.2006.00997.x
  • Kim DY, Ryu SY, Lim JE, Lee YS, Ro JY. Anti-inflammatory mechanism of simvastatin in mouse allergic asthma model. Eur J Pharmacol 2007;557:76-86. doi: 10.1016/j. ejphar.2006.11.027
  • Yilmaz F, Gunduz H, Arinc H, et al. Does the prevalence of nasal polyps increase in patients using statins? Adv Ther 2007;24:1330-9.
  • Kim YM, Kim YS, Jeon SG, Kim YK. Immunopathogenesis of allergic asthma: more than the th2 hypothesis. Allergy Asthma Immunol Res 2013;5:189-96. doi: 10.4168/ aair.2013.5.4.189
  • Kips JC. Cytokines in asthma. Eur Respir J Suppl 2001;34:24s-33s
  • Pennings HJ, Kramer K, Bast A, Buurman WA, Wouters EF. Tumour necrosis factor-alpha induces hyperreactivity in tracheal smooth muscle of the guinea-pig in vitro. Eur Respir J 1998;12:45-9.
  • Howarth PH, Babu KS, Arshad HS, et al. Tumour necrosis factor (TNFalpha) as a novel therapeutic target in symptomatic corticosteroid dependent asthma. Thorax 2005;60:1012-8. doi: 10.1136/thx.2005.045260
  • Berry MA, Hargadon B, Shelley M, et al. Evidence of a role of tumor necrosis factor alpha in refractory asthma. N Engl J Med 2006;354:697-708. doi:10.1056/NEJMoa050580
  • Camara J, Jarai G. Epithelial-mesenchymal transition in primary human bronchial epithelial cells is Smad-dependent and enhanced by fibronectin and TNF-alpha. Fibrogen Tiss Rep 2010;3:2. doi: 10.1186/1755-1536-3-2
  • Shyu KG, Chua SK, Wang BW, Kuan P. Mechanism of inhibitory effect of atorvastatin on resistin expression induced by tumor necrosis factor-alpha in macrophages. J Biomed Sci 2009;16:50. doi: 10.1186/1423-0127-16-50
  • Awad AS, El Sharif A. Immunomodulatory effects of rosuvastatin on hepatic ischemia/reperfusion induced injury. Immunopharmacol Immunotoxicol 2010;32:555-61. doi: 10.3109/08923970903575716
  • Rubin BK. Statins for the treatment of asthma: a discovery well, dry hole or just snake oil. Thorax 2009;64:4-5. doi: 10.1136/thx.2008.106757
  • Fessler MB, Jaramillo R, Crockett PW, Zeldin DC. Relationship of serum cholesterol levels to atopy in the US population. Allergy 2010;

Influence of rosuvastatin treatment on airway inflammatory markers and health related quality of life domains in asthmatic patients

Yıl 2017, Cilt: 30 Sayı: 2, 73 - 81, 14.05.2017
https://doi.org/10.5472/marumj.344816

Öz

Objectives: Statins are lipid lowering agents which have pleiotropic and

anti-inflammatory effects. Beneficial effects of statins have been shown

in many inflammatory and asthmatic diseases. However, the results are

still not consistent. The aim of this study is to determine the clinical and

anti-inflammatory effects of rosuvastatin in asthmatic patients.

Patients and Metods: A case control study among asthmatic

patients was conducted. One hundred and thirty-six participants were

screened. Seventy-four patients were eligible. Fifty-one patients

have completed the trial. Twenty-five patients with blood levels of

low-density-lipoprotein (LDL) above 130mg/dL, were treated with

rosuvastatin 40mg for 8 weeks in addition to their standard treatment

for asthma; 26 asthmatic patients were followed as control group. In

both groups baseline and 8th week evaluation were recorded including

pulmonary function test (PFT), bronchial provocation test (PD20),

induced sputum and serum inflammatory markers, asthma control test

(ACT) and quality of life scores (QoL).

Results: Statin group showed improvement in FEV1/FVC (pp)

(85.8±11.1% vs 90.2±8.8% P<0.043), FEF 25-75 % (63.6±7.8 %

vs 74.6±8.4 %, P<0.0001) and FEF25-75(L/sc) (3.51±0.4 vs 4.1±0.4

P<0.05) and no change was seen in non-statin group (P>0.05) at the

end of the 8-week treatment. Treatment with rosuvastatin resulted in

decreased sputum eosinophilia percentage (P<0.05); IL-6 and TNFalpha

levels (P<0.05) however, bronchial challenge test, ACT and QoL

domains did not change in both groups (P>0.05).

Conclusion: An 8-week treatment with 40mg rosuvastatin in asthma

decreased the peripheral eosinophilia, total IgE levels and inflammatory

markers in the induced sputum samples. Beneficial effects in PFT have

also been observed. However, ACT and QoL domains were not affected.

The implication of this study is that rosuvastatin could potentially have

anti-inflammatory effects on asthmatic airways. Prospective randomised

trials to evalute the clinical effects of rosuvastatin are warranted.

Kaynakça

  • Corsini A, Maggi FM, Catapano AL. Pharmacology of competitive inhibitors of HMG-CoA reductase. Pharmacol Res 1995;31:9-27. doi: 1043-6618(95)80042-5
  • Hothersall EJ, Chaudhuri R, McSharry C, et al. Effects of atorvastatin added to inhaled corticosteroids on lung function and sputum cell counts in atopic asthma. Thorax 2008;63:1070-5. doi: 10.1136/thx.2008.100198
  • Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator. Nature Medicine 2000;6:1399-402. doi: 10.1038/82219
  • Zeki AA, Oldham J, Wilson M, et al. Statin use and asthma control in patients with severe asthma. BMJ Open 2013;3:e003314. doi: 10.1136/bmjopen-2013-003314
  • Braganza G, Chaudhuri R, McSharry C, et al. Effects of shortterm treatment with atorvastatin in smokers with asthma. A randomized controlled trial. BMC Pulm Med 2011;11:16. doi: 10.1186/1471-2466-11-6.
  • Christiansen SC, Eddleston J, Wagelie-Steffen A, Yang AJ, Chen W, Zuraw BL. Influence of HMC-CoA reductase inhibitors on asthma severity. J Allergy Clin Immunol 2009;123:No 2 S84 Abst 313
  • Ostroukhova M, Kouides RW, Friedman E. The effect of statin therapy on allergic patients with asthma. Ann Allergy Asthma Immunol 2009;103:463-8. doi: 10.1016/S1081- 1206(10)60261-X
  • Report G. Global Initiative for Asthma:GINA Report, Global Strategy for Asthma Management and Prevention- updated 2012. 2012. Available at : (http://www.ginasthma.org). 2012 (Accessed:
  • Standardization of Spirometry, 1994 Update. American Thoracic Society. American Journal of Respiratory and Critical Care Medicine 1995;152:1107-36. doi: 10.1164/ ajrccm.152.3.7663792 1 Chai H, Farr RS, Froehlich LA, et al. Standardization of bronchial inhalation challenge procedures. J Allergy Clin Immunol 1975;56:323-7.
  • Schatz M, Sorkness CA, Li JT, et al. Asthma Control Test: reliability, validity, and responsiveness in patients notpreviously followed by asthma specialists. J Allergy Clinical Immunol 2006;117:549-56. doi: 10.1016/j.jaci.2006.01.011
  • Pinnock H, Sheikh A, Juniper EF. Evaluation of an intervention to improve successful completion of the Mini- AQLQ: comparison of postal and supervised completion. Primary Care Respiratory Journal : Journal of the General Practice Airways Group 2004;13:36-41. doi: 10.1016/j. pcrj.2003.11.004
  • Efthimiadis A, Jayaram L, Weston S, Carruthers S, Hargreave FE. Induced sputum: time from expectoration to processing. Europ Respir J 2002;19:706-8.
  • Foumani S, Nejatifar F, Forghan Parast K, Heidarinejad S, Mortazhejri G. Effects of atorvastatin in asthmatic patients under treatment with high dose oral or inhaled steroid. (Abstract) European Respirotary Society Annual Congress, Barcelona, Spain, September 18-22, 2010. (372).
  • Menzies D, Nair A, Meldrum KT, Fleming D, Barnes M, Lipworth BJ. Simvastatin does not exhibit therapeutic antiinflammatory effects in asthma. J Allergy Clinic Immunol 2007;119:328-35 doi: 10.1016/j.jaci.2006.10.014
  • Fahimi F, Jamaati H, Taheri ZM, Fakharian A, Salamzadeh J. Does atorvastatin have effect on lung function and morbiditiy as add on therapy in asthmatic patients? Europ Respir J 2007:490s:2960.
  • Moini A, Azimi G, Farivar A. Evaluation of atorvastatin for the treatment of patients with asthma: a double-blind randomized clinical trial. Allergy, Asthma Immunol Res 2012;4:290-4. doi: 10.4168/aair.2012.4.5.290
  • Cowan DC, Cowan JO, Palmay R, Williamson A, Taylor DR. Simvastatin in the treatment of asthma: lack of steroid-sparing effect. Thorax 2010;65:891-6. doi: 10.1136/thx.2010.138990
  • Feschenko Y, Lashyna L, Kramarskaya N, Polianska M, Matvienko J. Clinical and functional effectiveness of atorvastatin in complex therapy of severe bronchial asthma. (Abstract) European Respiratory Society Annual Congress, Berlin, Germany, October 4-8 2009. [E4554].
  • Liu PY, Liu YW, Lin LJ, Chen JH, Liao JK. Evidence for statin pleiotropy in humans: differential effects of statins and ezetimibe on rho-associated coiled-coil containing protein kinase activity, endothelial function, and inflammation. Circulation 2009;119:131-8. doi: 10.1161/ CIRCULATIONAHA.108.813311
  • Malek Mohammad M, Fahimi F, Fakharian A, et al. Methacoline Challenge test as an evaluator of response to statins in bronchial hyperresponsiveness. Iranian J Pharmaceutical Res 2012;11:969-77.
  • Deanin GG, Cutts JL, Pfeiffer JR, Oliver JM. Role of isoprenoid metabolism in IgE receptor-mediated signal transduction. J Immunol 1991;146:3528-35.
  • Roche CM, Trimble ER, Ennis M. Effect of in vivo and invitro lovastatin treatment on mast cell activation. Int Arch Allergy Immunol 1995;108:240-6.
  • Krauth MT, Majlesi Y, Sonneck K, et al. Effects of various statins on cytokine-dependent growth and IgEdependent release of histamine in human mast cells. Allergy 2006;61:281-8. doi: 10.1111/j.1398-9995.2006.00997.x
  • Kim DY, Ryu SY, Lim JE, Lee YS, Ro JY. Anti-inflammatory mechanism of simvastatin in mouse allergic asthma model. Eur J Pharmacol 2007;557:76-86. doi: 10.1016/j. ejphar.2006.11.027
  • Yilmaz F, Gunduz H, Arinc H, et al. Does the prevalence of nasal polyps increase in patients using statins? Adv Ther 2007;24:1330-9.
  • Kim YM, Kim YS, Jeon SG, Kim YK. Immunopathogenesis of allergic asthma: more than the th2 hypothesis. Allergy Asthma Immunol Res 2013;5:189-96. doi: 10.4168/ aair.2013.5.4.189
  • Kips JC. Cytokines in asthma. Eur Respir J Suppl 2001;34:24s-33s
  • Pennings HJ, Kramer K, Bast A, Buurman WA, Wouters EF. Tumour necrosis factor-alpha induces hyperreactivity in tracheal smooth muscle of the guinea-pig in vitro. Eur Respir J 1998;12:45-9.
  • Howarth PH, Babu KS, Arshad HS, et al. Tumour necrosis factor (TNFalpha) as a novel therapeutic target in symptomatic corticosteroid dependent asthma. Thorax 2005;60:1012-8. doi: 10.1136/thx.2005.045260
  • Berry MA, Hargadon B, Shelley M, et al. Evidence of a role of tumor necrosis factor alpha in refractory asthma. N Engl J Med 2006;354:697-708. doi:10.1056/NEJMoa050580
  • Camara J, Jarai G. Epithelial-mesenchymal transition in primary human bronchial epithelial cells is Smad-dependent and enhanced by fibronectin and TNF-alpha. Fibrogen Tiss Rep 2010;3:2. doi: 10.1186/1755-1536-3-2
  • Shyu KG, Chua SK, Wang BW, Kuan P. Mechanism of inhibitory effect of atorvastatin on resistin expression induced by tumor necrosis factor-alpha in macrophages. J Biomed Sci 2009;16:50. doi: 10.1186/1423-0127-16-50
  • Awad AS, El Sharif A. Immunomodulatory effects of rosuvastatin on hepatic ischemia/reperfusion induced injury. Immunopharmacol Immunotoxicol 2010;32:555-61. doi: 10.3109/08923970903575716
  • Rubin BK. Statins for the treatment of asthma: a discovery well, dry hole or just snake oil. Thorax 2009;64:4-5. doi: 10.1136/thx.2008.106757
  • Fessler MB, Jaramillo R, Crockett PW, Zeldin DC. Relationship of serum cholesterol levels to atopy in the US population. Allergy 2010;
Toplam 35 adet kaynakça vardır.

Ayrıntılar

Konular Klinik Tıp Bilimleri
Bölüm Makaleler
Yazarlar

Sehnaz Olgun Yıldızelı

Derya Kocakaya Bu kişi benim

Baran Balcan Bu kişi benim

Aygun Ikıncı Bu kişi benim

Rengin Ahıskalı Bu kişi benim

Berrin Ceyhan Bu kişi benim

Yayımlanma Tarihi 14 Mayıs 2017
Yayımlandığı Sayı Yıl 2017 Cilt: 30 Sayı: 2

Kaynak Göster

APA Olgun Yıldızelı, S., Kocakaya, D., Balcan, B., Ikıncı, A., vd. (2017). Influence of rosuvastatin treatment on airway inflammatory markers and health related quality of life domains in asthmatic patients. Marmara Medical Journal, 30(2), 73-81. https://doi.org/10.5472/marumj.344816
AMA Olgun Yıldızelı S, Kocakaya D, Balcan B, Ikıncı A, Ahıskalı R, Ceyhan B. Influence of rosuvastatin treatment on airway inflammatory markers and health related quality of life domains in asthmatic patients. Marmara Med J. Mayıs 2017;30(2):73-81. doi:10.5472/marumj.344816
Chicago Olgun Yıldızelı, Sehnaz, Derya Kocakaya, Baran Balcan, Aygun Ikıncı, Rengin Ahıskalı, ve Berrin Ceyhan. “Influence of Rosuvastatin Treatment on Airway Inflammatory Markers and Health Related Quality of Life Domains in Asthmatic Patients”. Marmara Medical Journal 30, sy. 2 (Mayıs 2017): 73-81. https://doi.org/10.5472/marumj.344816.
EndNote Olgun Yıldızelı S, Kocakaya D, Balcan B, Ikıncı A, Ahıskalı R, Ceyhan B (01 Mayıs 2017) Influence of rosuvastatin treatment on airway inflammatory markers and health related quality of life domains in asthmatic patients. Marmara Medical Journal 30 2 73–81.
IEEE S. Olgun Yıldızelı, D. Kocakaya, B. Balcan, A. Ikıncı, R. Ahıskalı, ve B. Ceyhan, “Influence of rosuvastatin treatment on airway inflammatory markers and health related quality of life domains in asthmatic patients”, Marmara Med J, c. 30, sy. 2, ss. 73–81, 2017, doi: 10.5472/marumj.344816.
ISNAD Olgun Yıldızelı, Sehnaz vd. “Influence of Rosuvastatin Treatment on Airway Inflammatory Markers and Health Related Quality of Life Domains in Asthmatic Patients”. Marmara Medical Journal 30/2 (Mayıs 2017), 73-81. https://doi.org/10.5472/marumj.344816.
JAMA Olgun Yıldızelı S, Kocakaya D, Balcan B, Ikıncı A, Ahıskalı R, Ceyhan B. Influence of rosuvastatin treatment on airway inflammatory markers and health related quality of life domains in asthmatic patients. Marmara Med J. 2017;30:73–81.
MLA Olgun Yıldızelı, Sehnaz vd. “Influence of Rosuvastatin Treatment on Airway Inflammatory Markers and Health Related Quality of Life Domains in Asthmatic Patients”. Marmara Medical Journal, c. 30, sy. 2, 2017, ss. 73-81, doi:10.5472/marumj.344816.
Vancouver Olgun Yıldızelı S, Kocakaya D, Balcan B, Ikıncı A, Ahıskalı R, Ceyhan B. Influence of rosuvastatin treatment on airway inflammatory markers and health related quality of life domains in asthmatic patients. Marmara Med J. 2017;30(2):73-81.