Association of plasma netrin-1 level with inflammatory balance and comorbidities in patients with acute exacerbation of COPD

Association of plasma netrin-1 level with inflammatory balance and comorbidities in patients with acute exacerbation of COPD Introduction: Chronic obstructive pulmonary disease (COPD) is a common lung disease characterized by airflow restriction and systemic inflammation. Netrin-1 is a protein mainly produced in the central nervous system and has proven anti-inflammatory activity. The aim of this study was to determine netrin-1 level and its relationship with comorbidities in patients with acute exacerbation of COPD. Materials and Methods: The study included 232 patients aged over 40 years who were divided into 3 groups: Group 1: ex-smokers (≥ 20 pack-years) with COPD hospitalized for COPD exacerbation (n= 142), Group 2: current-smokers (≥ 20 pack-years) without COPD (n= 30), Group 3: a control group comprising healthy non-smokers (n= 60). Plasma netrin-1 levels were measured using commercial enzyme-linked immunosorbent assay (ELISA) kit. Results: There were significant differences in forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, C-reactive protein (CRP), and plasma netrin-1 levels between patients with acute exacerbation of COPD and current smokers without COPD, healthy controls (p= 0.001 for all). Netrin-1 levels at discharge were lower in COPD patients with diabetes mellitus (DM) compared to nondiabetic COPD patients (p= 0.01). Weak correlation was observed between netrin-1 level at admission and FEV1, FVC, partial pressure of oxygen, and CRP levels (r= 0.394, p= 0.01; r= -0.366, p= 0.01; r= -0.19, p= 0.05; r= 0.306, p= 0.01). Netrin-1 level at admission was also moderately correlated with smoking history (pack-years) (r= 0.579, p= 0.01). Conclusion: Netrin-1 was elevated in acute exacerbation of COPD and may be an important element in inflammatory balance. Patients with both COPD and DM were found to have lower netrin-1 levels at discharge after resolution of the acute exacerbation.

KOAH akut alevlenme hastalarında plasma netrin-1 düzeyinin inflamatuar denge ve komorbiditeler üzerine etkisi

Giriş: Kronik obstrüktif akciğer hastalığı (KOAH) hava akım kısıtlaması ve sistemik inflamasyon ile karakterize yaygın bir akciğer hastalığıdır. Netrin-1 ön planda santral sinir sisteminden sentezlenen anti-inflamatuar etkinliği tespit edilmiş bir proteindir. Çalışmamızda netrin-1 düzeyinin KOAH akut alevlenme ve komorbiditelerle ilişkisini tespit etmeyi amaçladık. Materyal ve Metod: Çalışmamıza 40 yaş üzeri 3 grupta 232 hasta dahil edildi. Grup 1: 20 paket/yıl üzeri sigara içmiş, ex-smoker ve KOAH akut alevlenme nedeniyle hastanede yatan hastalar (n= 142), grup 2: aktif sigara içen ve KOAH olmayan hastalar, grup 3 (n= 30) non-smoker sağlıklı grup (n= 60). Hasta ve sağlıklı gruplardan 5 cc periferik venöz kan alındı. Plazma netrin-1 seviyesi enzime bağlı immünosorbent (ELİSA) yöntemiyle ölçüldü. Bulgular: Çalışmamızda FEV1, FVC, FEV1/FVC, CRP ve plasma netrin-1 düzeyinde KOAH akut alevlenme ile gelen hastalarla, kontrol grubu ve aktif sigara içen grup arasında istatistiksel olarak anlamli düzeyde farkli idi (tüm parametreler için p= 0,001). KOAH akut alevlenme ile gelen ve diyabetes mellitusu (DM) olan hastalarda taburculuk sırasında yalnızca KOAH gözlenen hastalara nazaran daha düşük netrin-1 düzeyi tespit edildi (p= 0,01). Netrin-1’in başvuru anındaki düzeyinin FEV1, FVC, PaO2 ve CRP düzeyi ile yapılan korelasyon analizinde düşük düzeyde korelasyon gözlendi (sırasıyla r= -0,394, p= 0,01, r= -0,366, p= 0,01, r= -0,19, p= 0,05, r= 0,306, p= 0,01). Netrin-1’in başvuru anındaki düzeyi ile sigara içme süresi (paket/yıl) ile yapılan korelasyon analizinde ise pozitif yönlü orta düzeyde korelasyon gözlendi (r= 0,579, p= 0,01). Sonuç: KOAH akut alevlenmede artış gösteren netrin-1 inflamatuar dengenin sağlanmasında önemli olabilir. KOAH ile birlikte DM gözlenen hastalarda ise akut alevlenme tablosu geriledikten sonra taburculuk esnasında daha düşük plasma netrin-1 düzeyi tespit edildi.

___

1. Singh D, Agusti A, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease: the GOLD science committee report 2019. Eur Res J 2019; 53(5): 1900164.

2. Kerget B, Afşin DE, Kerget F, Aşkın S, Akgün M. Is metrnl an adipokine involved in the anti-inflammatory response to acute exacerbations of COPD? Lung 2020; 198(2): 307-14.

3. Aherne CM, Collins CB, Eltzschig HK. Netrin-1 guides inflammatory cell migration to control mucosal immune responses during intestinal inflammation. Tissue barriers 2013; 1(2): 695-705.

4. Kennedy TE, Serafini T, de la Torre J, Tessier-Lavigne M. Netrins are diffusible chemotropic factors for commissural axons in the embryonic spinal cord. Cell 1994; 78(3): 425-35.

5. Ko FW, Chan KP, Hui DS, Goddard JR, Shaw JG, Reid DW, et al. Acute exacerbation of COPD. Respirology 2016; 21(7): 1152-65.

6. Roca-Ferrer J, Pujols L, Agusti C, Xaubet A, Mullol J, Gimferrer JM, et al. Cyclooxigenase-2 levels are increased in the lung tissue and bronchial tumors of patients with chronic obstructive pulmonary disease. Arch Bronc 2011; 47(12): 584-9.

7. O’Byrne KJ, Dalgleish AG. Chronic immune activation and inflammation as the cause of malignancy. Bri J Cancer 2001; 85(4): 473-83.

8. Brown JR, DuBois RN. Cyclooxygenase-2 in lung carcinogenesis and chemoprevention: Roger S. Mitchell lecture. Chest 2004; 125(5): 134-40.

9. Mohamed R, Jayakumar C, Ranganathan PV, Ganapathy V, Ramesh G. Kidney proximal tubular epithelial-specific overexpression of netrin-1 suppresses inflammation and albuminuria through suppression of COX-2-mediated PGE2 production in streptozotocin-induced diabetic mice. Am J Pathol 2012; 181(6): 1991-2002.

10. Ranganathan PV, Jayakumar C, Ramesh G. Netrin-1- treated macrophages protect the kidney against ischemiareperfusion injury and suppress inflammation by inducing M2 polarization. Am J Physicol 2013; 304(7): 948-57.

11. Han Y, Shao Y, Lin Z, Qu Y-L, Wang H, Zhou Y, et al. Netrin-1 simultaneously suppresses corneal inflammation and neovascularization. Invest Ophthalmol Vis Sci 2012; 53(3): 1285-95.

12. Liu J, Du J, Cheng X, Zhang X, Li Y, Fu X, et al. Effect of netrin-1 anti-inflammatory factor on acute lung injury in sepsis rats. Med Sci Monit 2019; 25: 7928-35.

13. Ranganathan PV, Jayakumar C, Mohamed R, Dong Z, Ramesh G. Netrin-1 regulates the inflammatory response of neutrophils and macrophages, and suppresses ischemic acute kidney injury by inhibiting COX-2-mediated PGE2 production. Kidney Int 2013; 83(6): 1087-98.

14. Liu T, Han C, Sun L, Ding Z, Shi F, Wang R, et al. Association between new circulating proinflammatory and anti-inflammatory adipocytokines with coronary artery disease. Coronary Art Dis 2019; 30(7): 528-35.

15. Yim J, Kim G, Lee B-W, Kang ES, Cha B-S, Kim J-H, et al. Relationship between circulating netrin-1 concentration, impaired fasting glucose, and newly diagnosed type 2 diabetes. Front Endoc 2018; 9: 691.

16. Liu C, Ke X, Wang Y, Feng X, Li Q, Zhang Y, et al. The level of netrin-1 is decreased in newly diagnosed type 2 diabetes mellitus patients. BMC Endoc Disord 2016; 16(1): 1-5.

17. De Breuck S, Lardon J, Rooman I, Bouwens L. Netrin-1 expression in fetal and regenerating rat pancreas and its effect on the migration of human pancreatic duct and porcine islet precursor cells. Diabetologia 2003; 46(7): 926-33.

18. Huang A-X, Lu L-W, Liu W-J, Huang M. Plasma inflammatory cytokine IL-4, IL-8, IL-10, and TNF-α levels correlate with pulmonary function in patients with asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome. Med Sci Monit 2016; 22: 2800-8.
Tüberküloz ve Toraks-Cover
  • ISSN: 0494-1373
  • Yayın Aralığı: 4
  • Başlangıç: 1951
  • Yayıncı: Tuba Yıldırım
Sayıdaki Diğer Makaleler

Göğüs hastalıkları yoğun bakım ünitesinde mikroorganizmaların dağılımı ve antibiyotik direnç profili: Tek merkezli çalışma

Hasan HASANZADE, Aslıhan GÜRÜN KAYA, Aydın ÇİLEDAĞ, Serhat EROL, Fatma ÇİFTÇİ, Haluk GÜRİZ, Akın KAYA

CovId-19 hastalığının bir komplikasyonu olarak pnömomediastinum: Bir olgu sunumu

Bünyamin SERTOĞULLARINDAN, Ceyda MAHLEÇ ANAR, Betül İkbal DOĞAN, Muzaffer Onur TURAN

Birt Hogg Dube syndrome: Rare family lung disease

Şaban Melih ŞİMŞEK, Recep SAVAŞ, Peyker TEMİZ, Pınar ÇELİK

Comparison of spirometry and impulse oscillometry in methacholine challenge test for the detection of airway hyperresponsiveness in adults

Masoud NAZEMIYAH, Khalil ANSARIN, Masoud NOURIVASKEH, Tohid SADEGI, Akbar SHARIFI

ABPA’lı hastalarda biyolojik tedaviler

Ömür AYDIN, Sevim BAVBEK, Merve ERKOÇ

Cerrahi doku yapıştırıcılar akciğer kanseri rezeksiyonu sonrası takip pozitron emisyon tomografisinde yanlış pozitifliğe neden olur mu?

Murat TUNCEL, Burcu ANCIN, Ulaş KUMBASAR, Rıza DOĞAN, Serkan UYSAL, Deniz KÖKSAL

Ağır COVID-19 enfeksiyonunda tosilizumab'ın etkinliği: Güncel çalışmaların derlemesi

Asiye KANBAY, Ahmet Cemal PAZARLI, Handan İNÖNÜ KÖSEOĞLU, Halil İbrahim YAKAR

Do meteorological changes and air pollution increase the risk of pneumonia?

Engin ŞAHİN, Berna AKINCI ÖZYÜREK, Barış DULKADİR

Understanding university students’ smoking behaviors towards tobacco-free campus policy

Mehmet KARADAĞ, Özge AYDIN GÜÇLÜ, Aslı GÖREK DİLEKTAŞLI, Funda COSKUN, Esra UZASLAN

Birt Hogg Dube sendromu: Nadir görülen ailesel akciğer hastalığı

Recep SAVAŞ, Peyker TEMİZ, Pınar ÇELİK, Şaban Melih ŞİMŞEK