Deneysel Künt Toraks Travması Modelinde Serum Clara Hücresi Salgı Proteini Düzeyinin Tanısal Değeri
Year 2024,
, 660 - 665, 31.10.2024
Hasan Kara
,
Aysegül Bayır
,
Ahmet Ak
,
Yeşim Şerife Bayraktar
,
Atilla Can
,
Bahadir Ozturk
,
Nejat Ünlükal
,
Fatih Akbuğa
,
Abdullah Akkuş
,
Muhammed Eseroğlu
Abstract
Amaç: Künt toraks travması akciğerlerde ölümcül olabilen hasara yol açan önemli bir klinik problemdir. Deneysel künt toraks travması hayvan modelleriyle iyi bir şekilde ortaya konmuştur. Bu çalışmada deneysel olarak oluşturulan künt toraks travması modelinde Clara hücresi salgı proteininin (CC16) biyobelirteç olarak kullanımının araştırılması amaçlandı.
Gereç ve Yöntemler: Çalışmamızda toplam 30 adet tavşan kullanıldı. Farklı düzeylerde pulmoner kontüzyon oluşturmak için modifiye edilmiş iki taraflı künt toraks travma modeli kullanıldı. Künt toraks travmasının uygulandığı enerji düzeyine göre tavşanları dört gruba ayırdık. Kontrol ve travma gruplarından 0, 12 ve 24. saatlerde CC16 düzeylerini değerlendirmek için kan örnekleri alındı.
Bulgular: Deneyin başlangıcında ölçülen CC16 seviyeleri kontrol ve düşük enerji gruplarında orta ve yüksek enerji gruplarına göre anlamlı derecede düşüktü (p =.002). 12. saatte ölçülen CC16 düzeyleri arasında anlamlı fark bulunurken (p=0,004), 24. saatte gruplar arasında anlamlı fark bulunamadı. Grupların CC16 düzeylerinin zaman içindeki değişimini incelediğimizde CC16 düzeylerinin 0-12. saatlerde azaldığını, 12. saatten sonra ise arttığını gözlemledik. Histopatolojik olarak farklı gruplarda travmanın ciddiyeti ile orantılı olarak kontüzyon seviyesinin arttığını gözlemledik.
Sonuç: Tasarlanan platformla tavşanlarda künt toraks travmasından kaynaklanan pulmoner kontüzyonun tekrarlanabilir deneysel bir modelini oluşturduk. Pulmoner kontüzyonu takiben artan CC16 seviyeleri, klinik karar vermenin temelini oluşturabilir. Bu nedenle CC16, akut travmatik akciğer hasarı için hızlı ve basit bir biyokimyasal gösterge olarak kullanılma potansiyeline sahiptir.
Supporting Institution
Selçuk Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü
References
- Dogrul BN, Kiliccalan I, Asci ES, Peker SC. Blunt trauma related chest wall and pulmonary injuries: An overview. Chin J Traumatol 2020; 23(3): 125-138. doi: 10.1016/j.cjtee.2020.04.003. PMID: 32417043.
- Yadollahi M, Arabi AH, Mahmoudi A, Zamani M, Farahmand M. Blunt Thoracic Injury Mortality and Clinical Presentation. Trauma Mon 2018; 23(4): e13079. doi: 10.5812/traumamon.13079.
- Miller PR, Croce MA, Bee TK, Qaisi WG, Smith CP, Collins GL, et al. ARDS after pulmonary contusion: accurate measurement of contusion volume identifies high-risk patients. J Trauma 2001; 51(2): 223-230. doi: 10.1097/00005373-200108000-00003. PMID: 11493778.
- Yamamoto L, Schroeder C, Morley D, Beliveau C. Thoracic trauma: the deadly dozen. Crit Care Nurs Q. 2005; 28(1): 22-40. doi: 10.1097/00002727-200501000-00004. PMID: 15732422.
- Fremont RD, Koyama T, Calfee CS, Wu W, Dossett LA, Bossert FR, et al. Acute lung injury in patients with traumatic injuries: utility of a panel of biomarkers for diagnosis and pathogenesis. J Trauma 2010; 68(5): 1121-1127. doi: 10.1097/TA.0b013e3181c40728. PMID: 20038857.
- Johnson ER, Matthay MA. Acute lung injury: epidemiology, pathogenesis, and treatment. J Aerosol Med Pulm Drug Deliv 2010; 23(4): 243-252. doi: 10.1089/jamp.2009.0775. PMID: 20073554.
- Hudson LD, Steinberg KP. Epidemiology of acute lung injury and ARDS. Chest. 1999;116(1 Suppl): 74S-82S. doi: 10.1378/chest.116.suppl_1.74s-a. PMID: 10424602.
- Cohn SM, Zieg PM. Experimental pulmonary contusion: review of the literature and description of a new porcine model. J Trauma 1996; 41(3): 565-571. doi: 10.1097/00005373-199609000-00036. PMID: 8810987.
- Cohn SM. Pulmonary contusion: review of the clinical entity. J Trauma 1997; 42(5): 973-979. doi: 10.1097/00005373-199705000-00033. PMID: 9191684.
- Broeckaert F, Bernard A. Clara cell secretory protein (CC16): characteristics and perspectives as lung peripheral biomarker. Clin Exp Allergy. 2000; 30(4): 469-475. doi: 10.1046/j.1365-2222.2000.00760.x. PMID: 10718843.
- Plopper CG, Hyde DM, Buckpitt AR. Clara cells. In: Crystal RG, West JB, Barnes PJ, Weibel ER, eds. The lung. Philadelphia: Lippincott-Raven Publishers, 1997: 517-533.
- Kropski JA, Fremont RD, Calfee CS, Ware LB. Clara cell protein (CC16), a marker of lung epithelial injury, is decreased in plasma and pulmonary edema fluid from patients with acute lung injury. Chest 2009; 135(6): 1440-1447. doi: 10.1378/chest.08-2465. PMID: 19188556.
- Doyle IR, Hermans C, Bernard A, Nicholas TE, Bersten AD. Clearance of Clara cell secretory protein 16 (CC16) and surfactant proteins A and B from blood in acute respiratory failure. Am J Respir Crit Care Med 1998; 158: 1528-1535. doi: 10.1164/ajrccm.158.5.9712097. PMID: 9817704.
- R Core Team (2013) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. http://www.R-project.org/. Accessed 15 December 2023.
- Recknagel S, Bindl R, Kurz J, Wehner T, Ehrnthaller C, Knöferl MW, et al. Experimental blunt chest trauma impairs fracture healing in rats. J Orthop Res 2011; 29(5): 734-739. doi: 10.1002/jor.21299. PMID: 21437953.
- Battle CE, Hutchings H, Evans PA. Risk factors that predict mortality in patients with blunt chest wall trauma: a systematic review and meta-analysis. Injury 2012; 43(1): 8-17. doi: 10.1016/j.injury.2011.01.004. PMID: 21256488.
- Störmann P, Lustenberger T, Relja B, Marzi I, Wutzler S. Role of biomarkers in acute traumatic lung injury. Injury 2017; 48(11): 2400-2406. doi: 10.1016/j.injury.2017.08.041. PMID: 28888717.
- Arsalane K, Broeckaert F, Knoops B, Wiedig M, Toubeau G, Bernard A. Clara cell specific protein (CC16) expression after acute lung inflammation induced by intratracheal lipopolysaccharide administration. Am J Respir Crit Care Med 2000; 161(5): 1624-1630. doi: 10.1164/ajrccm.161.5.9812157. PMID: 10806166.
- McAuley DF, Matthay MA. Clara cell protein CC16. A new lung epithelial biomarker for acute lung injury. Chest 2009; 135(6): 1408-1410. doi: 10.1378/chest.09-0304. PMID: 19497890.
- Wen MN, Zhao G, Zhang JY, Zhao YH. Clinical study on the changes of lung-specific proteins: CC16 after lung contusion. Exp Ther Med 2017; 14(3): 2733-2736. doi: 10.3892/etm.2017.4842. PMID: 28962220.
- Van Wijck SFM, Smith EF, Werner NL, Madden K, Moore EE, Wijffels MME, et al. Evolution of Pulmonary Contusions in Patients With Severe Rib Fractures: Cause for Concern? Am Surg 2024; 90(2): 261-269. doi: 10.1177/00031348231198111. PMID: 37646136.
- Broeckaert F, Clippe A, Knoops B, Hermans C, Bernard A. Clara cell secretory protein (CC16): features as a peripheral lung biomarker. Ann N Y Acad Sci 2000; 923: 68-77. doi: 10.1111/j.1749-6632.2000.tb05520.x. PMID: 11193780.
- Michel O, Murdoch R, Bernard A. Inhaled LPS induces blood release of Clara cell specific protein (CC16) in human beings. J Allergy Clin Immunol. 2005; 115(6): 1143-1147. doi: 10.1016/j.jaci.2005.01.067. PMID: 15940126.
- Helleday R, Segerstedt B, Forsberg B, Nordberg G, Svensson M, Bernard A, et al. Diurnal variation in serum levels of Clara cell protein (CC16) in humans. (Abstract). Eur Resp J 2003; 22(Suppl. 45): 75s
Diagnostic Value of Serum Clara Cell Secretory Protein Level in an Experimental Blunt Chest Trauma Model
Year 2024,
, 660 - 665, 31.10.2024
Hasan Kara
,
Aysegül Bayır
,
Ahmet Ak
,
Yeşim Şerife Bayraktar
,
Atilla Can
,
Bahadir Ozturk
,
Nejat Ünlükal
,
Fatih Akbuğa
,
Abdullah Akkuş
,
Muhammed Eseroğlu
Abstract
Objective: Blunt chest trauma is a significant clinical problem leading to injury of the lungs that may be fatal. Experimental blunt chest trauma is well established in animal models. This study aimed to investigate whether Clara cell secretory protein (CC16) can be a biomarker in an experimentally created blunt chest trauma model.
Material and Methods: A total of 30 rabbits were used in our study. A modified bilateral blunt thoracic trauma model was used to produce different levels of lung contusion. We divided the rabbits into four groups according to the energy level at which blunt thoracic trauma was applied. Blood samples were taken from the control and trauma groups to evaluate CC16 levels at 0, 12, and 24 hours.
Results: The CC16 levels measured at the start of the experiment were significantly lower in the control and low-energy groups compared to the medium- and high-energy groups (p =.002). While there was a significant difference in CC16 levels measured at the 12th hour (p =.004), no significant difference was found among the groups at the 24th hour. Upon analyzing the change in CC16 levels over time within the groups, we observed that CC16 levels decreased from 0–12 hours and subsequently increased after the 12th hour. Histopathologically, we observed that the level of contusion increased in proportion to the severity of trauma across the different groups.
Conclusion: With the designed platform, we created a reproducible experimental model of pulmonary contusion from blunt thoracic trauma in rabbits. Increased levels of CC16 following a lung contusion could serve as a foundation for clinical decision-making. Thus, CC16 has the potential to serve as a rapid and simple biochemical indicator for acute traumatic lung injury.
References
- Dogrul BN, Kiliccalan I, Asci ES, Peker SC. Blunt trauma related chest wall and pulmonary injuries: An overview. Chin J Traumatol 2020; 23(3): 125-138. doi: 10.1016/j.cjtee.2020.04.003. PMID: 32417043.
- Yadollahi M, Arabi AH, Mahmoudi A, Zamani M, Farahmand M. Blunt Thoracic Injury Mortality and Clinical Presentation. Trauma Mon 2018; 23(4): e13079. doi: 10.5812/traumamon.13079.
- Miller PR, Croce MA, Bee TK, Qaisi WG, Smith CP, Collins GL, et al. ARDS after pulmonary contusion: accurate measurement of contusion volume identifies high-risk patients. J Trauma 2001; 51(2): 223-230. doi: 10.1097/00005373-200108000-00003. PMID: 11493778.
- Yamamoto L, Schroeder C, Morley D, Beliveau C. Thoracic trauma: the deadly dozen. Crit Care Nurs Q. 2005; 28(1): 22-40. doi: 10.1097/00002727-200501000-00004. PMID: 15732422.
- Fremont RD, Koyama T, Calfee CS, Wu W, Dossett LA, Bossert FR, et al. Acute lung injury in patients with traumatic injuries: utility of a panel of biomarkers for diagnosis and pathogenesis. J Trauma 2010; 68(5): 1121-1127. doi: 10.1097/TA.0b013e3181c40728. PMID: 20038857.
- Johnson ER, Matthay MA. Acute lung injury: epidemiology, pathogenesis, and treatment. J Aerosol Med Pulm Drug Deliv 2010; 23(4): 243-252. doi: 10.1089/jamp.2009.0775. PMID: 20073554.
- Hudson LD, Steinberg KP. Epidemiology of acute lung injury and ARDS. Chest. 1999;116(1 Suppl): 74S-82S. doi: 10.1378/chest.116.suppl_1.74s-a. PMID: 10424602.
- Cohn SM, Zieg PM. Experimental pulmonary contusion: review of the literature and description of a new porcine model. J Trauma 1996; 41(3): 565-571. doi: 10.1097/00005373-199609000-00036. PMID: 8810987.
- Cohn SM. Pulmonary contusion: review of the clinical entity. J Trauma 1997; 42(5): 973-979. doi: 10.1097/00005373-199705000-00033. PMID: 9191684.
- Broeckaert F, Bernard A. Clara cell secretory protein (CC16): characteristics and perspectives as lung peripheral biomarker. Clin Exp Allergy. 2000; 30(4): 469-475. doi: 10.1046/j.1365-2222.2000.00760.x. PMID: 10718843.
- Plopper CG, Hyde DM, Buckpitt AR. Clara cells. In: Crystal RG, West JB, Barnes PJ, Weibel ER, eds. The lung. Philadelphia: Lippincott-Raven Publishers, 1997: 517-533.
- Kropski JA, Fremont RD, Calfee CS, Ware LB. Clara cell protein (CC16), a marker of lung epithelial injury, is decreased in plasma and pulmonary edema fluid from patients with acute lung injury. Chest 2009; 135(6): 1440-1447. doi: 10.1378/chest.08-2465. PMID: 19188556.
- Doyle IR, Hermans C, Bernard A, Nicholas TE, Bersten AD. Clearance of Clara cell secretory protein 16 (CC16) and surfactant proteins A and B from blood in acute respiratory failure. Am J Respir Crit Care Med 1998; 158: 1528-1535. doi: 10.1164/ajrccm.158.5.9712097. PMID: 9817704.
- R Core Team (2013) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. http://www.R-project.org/. Accessed 15 December 2023.
- Recknagel S, Bindl R, Kurz J, Wehner T, Ehrnthaller C, Knöferl MW, et al. Experimental blunt chest trauma impairs fracture healing in rats. J Orthop Res 2011; 29(5): 734-739. doi: 10.1002/jor.21299. PMID: 21437953.
- Battle CE, Hutchings H, Evans PA. Risk factors that predict mortality in patients with blunt chest wall trauma: a systematic review and meta-analysis. Injury 2012; 43(1): 8-17. doi: 10.1016/j.injury.2011.01.004. PMID: 21256488.
- Störmann P, Lustenberger T, Relja B, Marzi I, Wutzler S. Role of biomarkers in acute traumatic lung injury. Injury 2017; 48(11): 2400-2406. doi: 10.1016/j.injury.2017.08.041. PMID: 28888717.
- Arsalane K, Broeckaert F, Knoops B, Wiedig M, Toubeau G, Bernard A. Clara cell specific protein (CC16) expression after acute lung inflammation induced by intratracheal lipopolysaccharide administration. Am J Respir Crit Care Med 2000; 161(5): 1624-1630. doi: 10.1164/ajrccm.161.5.9812157. PMID: 10806166.
- McAuley DF, Matthay MA. Clara cell protein CC16. A new lung epithelial biomarker for acute lung injury. Chest 2009; 135(6): 1408-1410. doi: 10.1378/chest.09-0304. PMID: 19497890.
- Wen MN, Zhao G, Zhang JY, Zhao YH. Clinical study on the changes of lung-specific proteins: CC16 after lung contusion. Exp Ther Med 2017; 14(3): 2733-2736. doi: 10.3892/etm.2017.4842. PMID: 28962220.
- Van Wijck SFM, Smith EF, Werner NL, Madden K, Moore EE, Wijffels MME, et al. Evolution of Pulmonary Contusions in Patients With Severe Rib Fractures: Cause for Concern? Am Surg 2024; 90(2): 261-269. doi: 10.1177/00031348231198111. PMID: 37646136.
- Broeckaert F, Clippe A, Knoops B, Hermans C, Bernard A. Clara cell secretory protein (CC16): features as a peripheral lung biomarker. Ann N Y Acad Sci 2000; 923: 68-77. doi: 10.1111/j.1749-6632.2000.tb05520.x. PMID: 11193780.
- Michel O, Murdoch R, Bernard A. Inhaled LPS induces blood release of Clara cell specific protein (CC16) in human beings. J Allergy Clin Immunol. 2005; 115(6): 1143-1147. doi: 10.1016/j.jaci.2005.01.067. PMID: 15940126.
- Helleday R, Segerstedt B, Forsberg B, Nordberg G, Svensson M, Bernard A, et al. Diurnal variation in serum levels of Clara cell protein (CC16) in humans. (Abstract). Eur Resp J 2003; 22(Suppl. 45): 75s