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Relationship between chronic obstructive pulmonary disease and levels of vitamin D

Year 2015, Volume: 42 Issue: 2, 158 - 165, 08.07.2015
https://doi.org/10.5798/diclemedj.0921.2015.02.0551

Abstract

Objective: Vitamin D deficiency may be associated with pulmonary function deterioration. The aim of this study is to assess the relationship of serum vitamin D levels with pulmonary functions, disease severity and exacerbation frequency in Chronic Obstructive Pulmonary Disease (COPD) patients.

Methods: Seventy consecutive patients with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II-IV) who presented to our outpatient clinic and thirdty controls entered to the study. Diagnosis of COPD was confirmed according to clinical findings and pulmonary function test. Serum 25-hydroxyvitamin D (25(OH)D levels were measured by immunofluorescence method. Levels <20 ng/mL defined deficiency. Associations between Vitamin D levels and sex, age, body mass index (BMI), smoking habit, comorbidities, exacerbation frequency were examined.

Results: The mean age of patients was 60.7 years. The proportion of patients in stages 2 of GOLD was 40 %, in stages 3 was 30 % and stages 4was 30 %. There was no significant difference in serum levels of 25(OH)D between COPD patients and controls. Vitamin D level was 9.3 ±6.0 ng/mL in control group and 9.7± 8.5 ng/mL in GOLD stage 2, 9.6 ± 6.2 ng/mL in stage 3 and 5.1 ±2.4 ng/mL in stage 4. In stage 4, vitamin D levels was significantly lower statistically (p=0.03). Among the COPD patients, lower FEV1 was associated with lower levels of 25(OH)D (p= 0.03). The most frequent comorbidities were hypertension (61.4%) and heart failure (27.1%). Among the COPD patients smoking associated with significantly lower levels of serum 25(OH) D (p=0.04). We find an association with exacerbation frequency in the previous 12 months and levels of 25(OH) D (p=0.02).

Conclusion: COPD severity according to GOLD stage is also associated with low levels of 25(OH)D. Serum vitamin D levels are lower in COPD patients who are current smokers. Severe vitamin D deficiency is related to more frequent disease exacerbations. These findings indicated a relationship between serum 25(OH)D concentrations and COPD which suggests optimization of serum vitamin D levels in COPD.

Key words: Pulmonary functions, Vitamin D, COPD

References

  • Holick MF.Vitamin D deficiency. N Engl J Med 2007;
  • :266-281.
  • Cosio BG, Agusti A. Update in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2009; 181:655-660.
  • Penna G, Adorini L. 1 Alpha, 25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol 2000; 164: 2405-2411.
  • Lemire JM, Adams JS, Kermani-Arab V, et al. 1,25-Dihy droxyvitamin D3 suppresses human T helper/inducer lymphocyte activity in vitro. J Immunol 1985; 134:3032-3035.
  • Adams JS, Hewison M. Unexpected actions of vitamin D:
  • new perspectives on the regulation of innate and adaptive
  • immunity. Nat Clin Pract Endocrinol Metab 2008; 4:80-90.
  • Hansdottir S, Monick MM, Hinde SL, et al. Respiratory
  • epithelial cells convert inactive vitamin D to its active
  • form: potential effects on host defense. J Immunol 2008;
  • :7090-7099.
  • Donaldson GC, Seemungal TA, Bhowmik A, Wedzicha JA.
  • Relationship between exacerbation frequency and lung
  • function decline in chronic obstructive pulmonary disease.
  • Thorax 2008; 57:847-852.
  • Schlaich C, Minne HW, Bruckner T, et al. Reduced pulmonary function in patients with spinal osteoporotic fractures. Osteoporos Int 1998; 8:261-267.
  • Dursun A. D vitamininin kemik metabolizması dışındaki
  • etkileri. Beslenmede Yenilikler I-II, Katkı Pediatri Dergisi
  • ; 28:225-234.
  • Timms PM, Mannan N, Hitman GA, et al. Circulating
  • MMP9, vitamin D and variation in the TIMP-1 response
  • with VDR genotype: mechanisms for inflammatory damage in chronic disorders? QJM 2002; 95:787-796.
  • Banerjee A, Panettieri RJr. Vitamin D modulates airway
  • smooth muscle function in COPD. Curr opin Pharmacol 2012.
  • Wright RJ. Make no nounes about it: epidemiologic evidence links vitamin D to pulmonary function and COPD. Chest 2005;128: 3871-3873.
  • Sundar IK, Rahman I. Vitamin D and susceptibility of
  • chronic lung disease: role of epigenetics. Front Pharmacol
  • ; 2:50.
  • Erkkola M, Kaila M, Nwaru BI, et al. Maternal vitamin D
  • intake during pregnancy is inversely associated with asthma
  • and allergic rhinitis. Clin Exp Allergy 2009; 39:875-882.
  • Janssens W, Bouillon R, Claes B, et al. Vitamin D deficien
  • cy is highly prevalent in COPD and correlates with variants
  • in the vitamin D-binding gene. Thorax 2010; 65:215-220.
  • Janssens W, Mathieu C, Boonen S, Decramer M. Vitamin
  • D deficiency and chronic obstructive pulmonary disease: a
  • vicious circle. Vitam Horm 2011; 86:379-99.
  • Heulens N, Decramer M, Janssens W. Severe vitamin D
  • deficiency: a biomarker of exacerbation risk? Am J Respir
  • Crit Care Med. 2013; 187:214-215.
  • Holick MF.Vitamin D deficiency. N Engl J Med 2007;
  • :266-281.
  • Murray CJ, Lopez AD. Alternative projections of mortalityand disability by cause 1990-2020: Global Burden of Disease Study.Lancet 1997; 349:1498-1504.
  • Strassels SA, Smith DH, Sullivan SD, Mahajan PS.The
  • costs of treating COPD in the United States. Chest
  • ;119:344-352.
  • Global Initiative for Chronic Obstructive Lung Disease.
  • Global strategy for the diagnosis, management and prevention of COPD, 2015 (update) www.goldcopd.com.
  • Norman AW, Bouillon R, Whiting SJ, et al. 13th Workshop
  • consensus for vitamin D nutritional guidelines. J Steroid
  • Biochem Mol Biol 2007; 103:204-205.
  • Dawson-Hughes B, Heaney RP, Holick MF, et al. Estimates
  • of optimal vitamin D status. Osteoporos Int 2005; 16:713-716.
  • Alagöl F, Shihadeh Y, Boztepe H, et al. Sunlight exposure
  • and vitamin D deficiency in Turkish Women. J Endocrinol
  • Invest 2000; 23:173-177.
  • Pehlivan İ, Hatun Ş, Aydoğan M, et al. Maternal serum vitamin D levels in the third trimester of pregnancy. Turk J Med
  • Sci 2002; 32:237-241.
  • Malabanan A, Veronikis IE, Holick MF.Redefining vitamin
  • D insufficiency.Lancet 1998; 351:805-806.
  • Vitamin D: extraskeletal health.Holick MF. Rheum Dis Clin
  • North Am. 2012 Feb; 38:141-160.
  • Kunisaki KM, Niewoehner DE, Singh RJ, Connett JE. Vitamin D status and longitudinal lung function decline in the Lung Health Study. Eur Respir J 2011; 37:238-243.
  • Black PN, Scragg R. Relationship between serum 25-hydroxyvitamin D and pulmonary function in the third national health and nutrition examination survey.Chest 2005;
  • :3792-3798.
  • Ringbaek T, Martinez G, Durakovic A, et al. Vitamin D status in patients with chronic obstructive pulmonary disease who participate in pulmonary rehabilitation. J Cardiopulmonary Rehab Prevention 2011; 31:261-267.
  • Franco CB, PazFillho G, Gomes PE, et al. Chronic obstructive pulmonary disease is associated with osteoporosis and low levels of vitamin D. Osteoporos Int 2009;20:1881-1887.
  • Persson LJP, Aanerud M, Hiemstra PS, et al. COPD is associated with low levels of vitamin D. PLoS One 2012;7:6.
  • Celli BR, MacNee W. ATS/ERS Task Force. Standards for
  • the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 2004;23:932-946.
  • Semba RD, Chang SS, Sun K, et al.Serum 25-Hydroxyvitamin D and Pulmonary Function in Older Disabled Community-Dwelling Women. J Gerontol A Biol Sci Med Sci
  • ; 67:683-689.
  • Shaheen SO, Jameson KA, Robinson SM, et al.Relationship
  • of vitamin D status to adult lung function and COPD. Thorax 2011; 66:692-698.
  • Ampikaipakan SN, Hughes DA, Hughes JC, et al. Vitamin
  • D and COPD: seasonal variation is important. Thorax 2011;
  • :541-542.
  • Jenkins CR, Celli B, Anderson JA, et al. Seasonality and
  • determinants of moderate and severe COPD exacerbations
  • in the TORCH study.Eur Respir J. 2012; 39:38-45.
  • Lange NE, Sparrow D, Vokonas P, Litonjua AA.Vitamin
  • D deficiency, Smoking, and Lung Function in the Normative Aging Study. Am J Respir Crit Care Med. 2012 Oct 1;186:616-621.
  • Hughes DA, Norton R. Vitamin D and respiratory health.
  • Clin Exp Immunol 2009; 158:20-25.
  • Lee JH, O’Keefe JH, Bell D. Vitamin D deficiency an important, common, and easily treatable cardiovascular risk
  • factor? J Am Coll Cardiol 2008; 52:1949-1956.
  • Forman JP, Williams JS, Fisher ND.Plasma 25-hydroxyvitamin D and regulation of the renin angiotensin system in humans. Hypertension 2010; 55:1283-1288.
  • Wortsman J, Matsuoka LY, Chen TC, et al. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 2000;
  • :690-693.
  • Mathieu C, Gysemans C, Giulietti A, Bouillon R. Vitamin D
  • and Diabetes. Diabetologia 2005; 48:1247-1257.
  • McGill AT, Stewart JM, Lithander FE, et al. Relationships
  • of low serum vitamin D3 with anthropometry and markers
  • of the metabolic syndrome and diabetes in overweight and
  • obesity. Nutr J 2008; 28:4-7.
  • Agusti A, Soriano JB.COPD as a systemic disease. COPD
  • ; 5:133-138.
  • Marquis K, Debigare R, Lacasse Y, et al. Midthigh muscle
  • crosssectional area is a better predictor of mortality than
  • body mass index in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002; 166:809-813.
  • Cannell JJ, Vieth R, Umhau JC, et al. Epidemic influenza
  • and vitamin D. Epidemiol Infect 2006;134: 1129-1140.
  • Wang TT, Nestel FP, Bourdeau V, et al. Cutting edge:
  • ,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 2004; 173:2909-2912.
  • Lehouck A, Mathieu C, Carremans C, et al. High doses of
  • vitamin D to reduce exacerbations in chronic obstructive
  • pulmonary disease: a randomized trial. Ann Intern Med
  • ; 156:105-114.

Kronik obstruktif akciğer hastalığı ile vitamin D düzeyi arasındaki ilişki

Year 2015, Volume: 42 Issue: 2, 158 - 165, 08.07.2015
https://doi.org/10.5798/diclemedj.0921.2015.02.0551

Abstract

Amaç: Vitamin D eksikliği, solunum fonksiyonlarında bozulma ile ilişkili olabilir. Çalışmamızda Kronik Obstruktif Akciğer Hastalığı (KOAH) hastalarında solunum fonksiyonları, hastalığın şiddeti ve alevlenme sıklığı ile serum Vitamin D düzeyi arasındaki ilişkiyi belirlemeyi amaçladık. Yöntemler: Polikliniğimize başvuran 70 KOAH hastası (GOLD Sınıflaması Evre II-IV) çalışmaya alındı. 30 sağlıklı gönüllü kontrol grubunu oluşturdu. Klinik bulgular ve solunum fonksiyon testine göre KOAH tanısı kondu. Serum 25-hidroksi vitamin D (25(OH)D) seviyesi immünofloresan yöntemi ile ölçüldü. 20 ng/mL altındaki değerler eksiklik olarak kabul edildi. Vitamin D düzeyi ile cinsiyet, yaş, Vücut Kitle İndeksi (VKİ), sigara içme durumu, komorbiditeler, alevlenme sıklığı arasındaki ilişki araştırıldı.Bulgular: Hasta grubunun yaş ortalaması 60,7 yıldı. Hastaları GOLD sınıflamasına göre ayırdığımızda %40’ı Evre II, %30’u Evre III, %30’u Evre IV KOAH’tı. Hasta ve kontrol grupları arasında serum 25(OH)D düzeyi bakımından anlamlı farklılık görülmedi. Vitamin D düzeyi kontrol grubunda 9,3 ±6,0 ng/mL, Evre II KOAH’da 9,7± 8,5 ng/mL, Evre III’te 9,6 ± 6,2 ng/mL ve Evre IV’te 5,1 ±2,4 ng/mL olarak belirlendi. Evre IV te Vitamin D düzeyi düşüklüğü istatistiksel olarak anlamlıydı (p=0.03).Hasta grubunda düşük FEV1, düşük 25(OH)D ile ilişkili bulundu (p=0.03). En sık görülen komorbidite hipertansiyon (%61,4) ve kalp yetmezliği idi (%27,1). Sigara içenlerde 25(OH)D düzeyi daha düşüktü (p=0,004). Son 12 aydaki alevlenme sıklığı ile serum 25(OH)D düzeyi düşüklüğü arasında ilişki saptandı (p=0.02).Sonuç: GOLD evrelemesine göre KOAH şiddeti ile 25(OH)D düzeyi düşüklüğü arasında ilişki vardır. Sigara içen KOAH hastalarında 25(OH)D düzeyi daha düşüktür. Ciddi Vitamin D eksikliği alevlenme sıklığında artış ile ilişkilidir. 25(OH)D düzeyi ile KOAH arasındaki ilişki, KOAH hastalarında Vitamin D düzeyini iyileştirmek gerektiğini düşündürmektedir

References

  • Holick MF.Vitamin D deficiency. N Engl J Med 2007;
  • :266-281.
  • Cosio BG, Agusti A. Update in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2009; 181:655-660.
  • Penna G, Adorini L. 1 Alpha, 25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol 2000; 164: 2405-2411.
  • Lemire JM, Adams JS, Kermani-Arab V, et al. 1,25-Dihy droxyvitamin D3 suppresses human T helper/inducer lymphocyte activity in vitro. J Immunol 1985; 134:3032-3035.
  • Adams JS, Hewison M. Unexpected actions of vitamin D:
  • new perspectives on the regulation of innate and adaptive
  • immunity. Nat Clin Pract Endocrinol Metab 2008; 4:80-90.
  • Hansdottir S, Monick MM, Hinde SL, et al. Respiratory
  • epithelial cells convert inactive vitamin D to its active
  • form: potential effects on host defense. J Immunol 2008;
  • :7090-7099.
  • Donaldson GC, Seemungal TA, Bhowmik A, Wedzicha JA.
  • Relationship between exacerbation frequency and lung
  • function decline in chronic obstructive pulmonary disease.
  • Thorax 2008; 57:847-852.
  • Schlaich C, Minne HW, Bruckner T, et al. Reduced pulmonary function in patients with spinal osteoporotic fractures. Osteoporos Int 1998; 8:261-267.
  • Dursun A. D vitamininin kemik metabolizması dışındaki
  • etkileri. Beslenmede Yenilikler I-II, Katkı Pediatri Dergisi
  • ; 28:225-234.
  • Timms PM, Mannan N, Hitman GA, et al. Circulating
  • MMP9, vitamin D and variation in the TIMP-1 response
  • with VDR genotype: mechanisms for inflammatory damage in chronic disorders? QJM 2002; 95:787-796.
  • Banerjee A, Panettieri RJr. Vitamin D modulates airway
  • smooth muscle function in COPD. Curr opin Pharmacol 2012.
  • Wright RJ. Make no nounes about it: epidemiologic evidence links vitamin D to pulmonary function and COPD. Chest 2005;128: 3871-3873.
  • Sundar IK, Rahman I. Vitamin D and susceptibility of
  • chronic lung disease: role of epigenetics. Front Pharmacol
  • ; 2:50.
  • Erkkola M, Kaila M, Nwaru BI, et al. Maternal vitamin D
  • intake during pregnancy is inversely associated with asthma
  • and allergic rhinitis. Clin Exp Allergy 2009; 39:875-882.
  • Janssens W, Bouillon R, Claes B, et al. Vitamin D deficien
  • cy is highly prevalent in COPD and correlates with variants
  • in the vitamin D-binding gene. Thorax 2010; 65:215-220.
  • Janssens W, Mathieu C, Boonen S, Decramer M. Vitamin
  • D deficiency and chronic obstructive pulmonary disease: a
  • vicious circle. Vitam Horm 2011; 86:379-99.
  • Heulens N, Decramer M, Janssens W. Severe vitamin D
  • deficiency: a biomarker of exacerbation risk? Am J Respir
  • Crit Care Med. 2013; 187:214-215.
  • Holick MF.Vitamin D deficiency. N Engl J Med 2007;
  • :266-281.
  • Murray CJ, Lopez AD. Alternative projections of mortalityand disability by cause 1990-2020: Global Burden of Disease Study.Lancet 1997; 349:1498-1504.
  • Strassels SA, Smith DH, Sullivan SD, Mahajan PS.The
  • costs of treating COPD in the United States. Chest
  • ;119:344-352.
  • Global Initiative for Chronic Obstructive Lung Disease.
  • Global strategy for the diagnosis, management and prevention of COPD, 2015 (update) www.goldcopd.com.
  • Norman AW, Bouillon R, Whiting SJ, et al. 13th Workshop
  • consensus for vitamin D nutritional guidelines. J Steroid
  • Biochem Mol Biol 2007; 103:204-205.
  • Dawson-Hughes B, Heaney RP, Holick MF, et al. Estimates
  • of optimal vitamin D status. Osteoporos Int 2005; 16:713-716.
  • Alagöl F, Shihadeh Y, Boztepe H, et al. Sunlight exposure
  • and vitamin D deficiency in Turkish Women. J Endocrinol
  • Invest 2000; 23:173-177.
  • Pehlivan İ, Hatun Ş, Aydoğan M, et al. Maternal serum vitamin D levels in the third trimester of pregnancy. Turk J Med
  • Sci 2002; 32:237-241.
  • Malabanan A, Veronikis IE, Holick MF.Redefining vitamin
  • D insufficiency.Lancet 1998; 351:805-806.
  • Vitamin D: extraskeletal health.Holick MF. Rheum Dis Clin
  • North Am. 2012 Feb; 38:141-160.
  • Kunisaki KM, Niewoehner DE, Singh RJ, Connett JE. Vitamin D status and longitudinal lung function decline in the Lung Health Study. Eur Respir J 2011; 37:238-243.
  • Black PN, Scragg R. Relationship between serum 25-hydroxyvitamin D and pulmonary function in the third national health and nutrition examination survey.Chest 2005;
  • :3792-3798.
  • Ringbaek T, Martinez G, Durakovic A, et al. Vitamin D status in patients with chronic obstructive pulmonary disease who participate in pulmonary rehabilitation. J Cardiopulmonary Rehab Prevention 2011; 31:261-267.
  • Franco CB, PazFillho G, Gomes PE, et al. Chronic obstructive pulmonary disease is associated with osteoporosis and low levels of vitamin D. Osteoporos Int 2009;20:1881-1887.
  • Persson LJP, Aanerud M, Hiemstra PS, et al. COPD is associated with low levels of vitamin D. PLoS One 2012;7:6.
  • Celli BR, MacNee W. ATS/ERS Task Force. Standards for
  • the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 2004;23:932-946.
  • Semba RD, Chang SS, Sun K, et al.Serum 25-Hydroxyvitamin D and Pulmonary Function in Older Disabled Community-Dwelling Women. J Gerontol A Biol Sci Med Sci
  • ; 67:683-689.
  • Shaheen SO, Jameson KA, Robinson SM, et al.Relationship
  • of vitamin D status to adult lung function and COPD. Thorax 2011; 66:692-698.
  • Ampikaipakan SN, Hughes DA, Hughes JC, et al. Vitamin
  • D and COPD: seasonal variation is important. Thorax 2011;
  • :541-542.
  • Jenkins CR, Celli B, Anderson JA, et al. Seasonality and
  • determinants of moderate and severe COPD exacerbations
  • in the TORCH study.Eur Respir J. 2012; 39:38-45.
  • Lange NE, Sparrow D, Vokonas P, Litonjua AA.Vitamin
  • D deficiency, Smoking, and Lung Function in the Normative Aging Study. Am J Respir Crit Care Med. 2012 Oct 1;186:616-621.
  • Hughes DA, Norton R. Vitamin D and respiratory health.
  • Clin Exp Immunol 2009; 158:20-25.
  • Lee JH, O’Keefe JH, Bell D. Vitamin D deficiency an important, common, and easily treatable cardiovascular risk
  • factor? J Am Coll Cardiol 2008; 52:1949-1956.
  • Forman JP, Williams JS, Fisher ND.Plasma 25-hydroxyvitamin D and regulation of the renin angiotensin system in humans. Hypertension 2010; 55:1283-1288.
  • Wortsman J, Matsuoka LY, Chen TC, et al. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 2000;
  • :690-693.
  • Mathieu C, Gysemans C, Giulietti A, Bouillon R. Vitamin D
  • and Diabetes. Diabetologia 2005; 48:1247-1257.
  • McGill AT, Stewart JM, Lithander FE, et al. Relationships
  • of low serum vitamin D3 with anthropometry and markers
  • of the metabolic syndrome and diabetes in overweight and
  • obesity. Nutr J 2008; 28:4-7.
  • Agusti A, Soriano JB.COPD as a systemic disease. COPD
  • ; 5:133-138.
  • Marquis K, Debigare R, Lacasse Y, et al. Midthigh muscle
  • crosssectional area is a better predictor of mortality than
  • body mass index in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002; 166:809-813.
  • Cannell JJ, Vieth R, Umhau JC, et al. Epidemic influenza
  • and vitamin D. Epidemiol Infect 2006;134: 1129-1140.
  • Wang TT, Nestel FP, Bourdeau V, et al. Cutting edge:
  • ,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 2004; 173:2909-2912.
  • Lehouck A, Mathieu C, Carremans C, et al. High doses of
  • vitamin D to reduce exacerbations in chronic obstructive
  • pulmonary disease: a randomized trial. Ann Intern Med
  • ; 156:105-114.
There are 109 citations in total.

Details

Primary Language English
Journal Section Research Articles
Authors

Buket Çilingir

Hülya Günbatar This is me

Publication Date July 8, 2015
Submission Date July 8, 2015
Published in Issue Year 2015 Volume: 42 Issue: 2

Cite

APA Çilingir, B., & Günbatar, H. (2015). Relationship between chronic obstructive pulmonary disease and levels of vitamin D. Dicle Tıp Dergisi, 42(2), 158-165. https://doi.org/10.5798/diclemedj.0921.2015.02.0551
AMA Çilingir B, Günbatar H. Relationship between chronic obstructive pulmonary disease and levels of vitamin D. diclemedj. July 2015;42(2):158-165. doi:10.5798/diclemedj.0921.2015.02.0551
Chicago Çilingir, Buket, and Hülya Günbatar. “Relationship Between Chronic Obstructive Pulmonary Disease and Levels of Vitamin D”. Dicle Tıp Dergisi 42, no. 2 (July 2015): 158-65. https://doi.org/10.5798/diclemedj.0921.2015.02.0551.
EndNote Çilingir B, Günbatar H (July 1, 2015) Relationship between chronic obstructive pulmonary disease and levels of vitamin D. Dicle Tıp Dergisi 42 2 158–165.
IEEE B. Çilingir and H. Günbatar, “Relationship between chronic obstructive pulmonary disease and levels of vitamin D”, diclemedj, vol. 42, no. 2, pp. 158–165, 2015, doi: 10.5798/diclemedj.0921.2015.02.0551.
ISNAD Çilingir, Buket - Günbatar, Hülya. “Relationship Between Chronic Obstructive Pulmonary Disease and Levels of Vitamin D”. Dicle Tıp Dergisi 42/2 (July 2015), 158-165. https://doi.org/10.5798/diclemedj.0921.2015.02.0551.
JAMA Çilingir B, Günbatar H. Relationship between chronic obstructive pulmonary disease and levels of vitamin D. diclemedj. 2015;42:158–165.
MLA Çilingir, Buket and Hülya Günbatar. “Relationship Between Chronic Obstructive Pulmonary Disease and Levels of Vitamin D”. Dicle Tıp Dergisi, vol. 42, no. 2, 2015, pp. 158-65, doi:10.5798/diclemedj.0921.2015.02.0551.
Vancouver Çilingir B, Günbatar H. Relationship between chronic obstructive pulmonary disease and levels of vitamin D. diclemedj. 2015;42(2):158-65.