The role of biomarkers in the diagnosis and treatment follow-up of idiopathic pulmonary fibrosis
Main Article Content
Keywords
Idiopathic pulmonary fibrosis, biomarkers, diagnosis, follow-up
Abstract
Background and aim: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease of unknown cause with a poor prognosis. The aim of our study is to determine the role of Krebs von den Lungen-6(KL-6),Matrix metalloproteinase (MMP)-7, Surfactant protein A (SP-A), Surfactant protein D(SP-D), vascular endothelial growth factor (VEGF) and periostin in the diagnosis of IPF and in the response monitoring of patients treated. Method: 47 IPF patients, 27 non-IPF interstitial lung disease (ILD) patients and 21 healthy individuals were included in the study. Demographic data, pulmonary function test- Diffusing capacity of the lung for carbon monoxide (PFT-DLCO) measurements, High-resolution computed tomography (HRCT) findings of the patients were recorded, and serum samples were taken. Results:While periostin and SP-A levels were not significantly different between IPF and non-IPF ILD, they were significantly higher in both IPF and non-IPF ILD compared to healthy control group (p=0.002,p=0.006 for periostin and p=0.002,p<0.001 for SP-A, respectively).By receiver operating characteristic (ROC) analysis, the cut-off point for periostin to distinguish IPF is >594.5 pg/ml (sensitivity 72%, specificity 76%), while the cut-off point for SP-A is found >6.62 ng/ml (sensitivity 87.2%,specificity 57.1%). In the combined ROC analysis based on SP-A=6.62 ng/ml and periostin >634.6 pg/ml values, sensitivity was found to be 85% and specificity was 57%.Considering the correlation of forced expiratory volume in the first second (FEV1)(%), forced vital capacity (FVC)(%), restriction and diffusion severities with biomarker levels in the 6th month of IPF patients treated, a correlation was detected between MMP-7 levels and restriction severities (p=0.020), between KL-6 levels and restriction and diffusion severities (p=0.002), and between SP-A levels and FVC(%)(p=0.006).Conclusion:It is thought that biomarkers SP-A and periostin may contribute significantly to the diagnosis of patients with IPF, and SP-A, MMP-7 and KL-6 levels may contribute significantly to treatment follow-up.
References
2. Hutchinson J, Fogarty A, Hubbard R, et al. Global incidence and mortality of idiopathic pulmonary fibrosis: a systematic review. Eur Respir J 2015;46:795-806.
3. Sauleda J, Núñez B, Sala E, et al. Idiopathic Pulmonary Fibrosis: Epidemiology, Natural History, Phenotypes. Med Sci (Basel) 2018;6:pii:E110.
4. Musellim B, Okumus G, Uzaslan E, et al. Turkish Interstitial Lung Diseases Group. Epidemiology and distribution of interstitial lung diseases in Turkey. Clin Respir J 2013;8:55-62.
5. Özlü T, Metintaş M, Karadağ M, Kaya A. Solunum Sistemi ve Hastalıkları Temel Başvuru Kitabı. In: Özlü T, Metintaş M (eds). Bölüm V ve XVII, İstanbul: İstanbul Medikal Yayıncılık; 2011.
6. Thomeer M, Demedts M, Vandeurzen K, et al. Registration of interstitial lung diseases by 20 centres of respiratory medicine in flanders. Acta Clin Belg 2001;56:163-72.
7. Baumgartner KB, Samet JM, Stidley CA, et al. Cigarette smoking: a risk factor for idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1997;155:242-8.
8. Hubbard R, Cooper M, Antoniak M, et al. Risk of cryptogenic fibrosing alveolitis in metal workers. Lancet 2000;355:466-7.
9. Paolocci G, Folletti I, Toren K, et al. Occupational risk factors for idiopathic pulmonary fibrosis in Southern Europe: A case-control study. BMC Pulm Med 2018;18:75.
10. Jingxian W, Peiyan Z, Zhifeng H, et al. Serum SP-A and KL-6 levels can predict the improvement and deterioration of patients with interstitial pneumonia with autoimmune features. BMC Pulm Med. 2020;20(1):315
11. Iwasawa T, Ogura T, Sakai F, et al. CT analysis of the effect of pirfenidone in patients with idiopathic pulmonary fibrosis. Eur J Radiol. 2014;83(1):32–38.
12. Hamai K, Iwamoto H, Ishikawa N, et al. Comparative study of circulating MMP-7, CCL18, KL-6, SP-A, and SP-D as disease markers of idiopathic pulmonary fibrosis. Dis Markers. 2016;2016:4759040.
13. Okamoto M, Hoshino T, Kitasato Y, et al. Periostin, a matrix protein, is a novel biomarker for idiopathic interstitial pneumonias. Eur Respir J 2011;37:1119-27.
14. Masaru A, Eishi M, Takeo Ito, et al. Significance of serum vascular endothelial growth factor level in patients with idiopathic pulmonary fibrosis. Lung. 2010;188(3):247-52.
15. Barlo NP, van Moorsel CH, Ruven HJ, Zanen P, van den Bosch JM, Grutters JC. Surfactant protein-D predicts survival in patients with idiopathic pulmonary fibrosis. Sarcoidosis Vasc Difuse Lung Dis 2009; 26(2): 155-61.
16. Demirdöğen E, Görek Dilektaşlı A, Acet Öztürk NA, et al.Sarcoidosis Vasc Diffuse Lung Dis. 2022 Dec 19;39(4):e2022035.
17. Argyris T, Jose D, Martin S, et al. Validation of the prognostic value of MMP-7 in Idiopathic Pulmonary Fibrosis. Respirology. 2017;22(3):486–493.
18. Ikeda K, Chiba H, Nishikiori H, et al. Serum surfactant protein D as a predictive biomarker for the efficacy of pirfenidone in patients with idiopathic pulmonary fibrosis: a post-hoc analysis of the phase 3 trial in Japan. Respir Res. 2020 Nov 30;21(1):316.
19. Takumi Y, Mitsuo O, Hirofumi C, et al. Surfactant protein A as a biomarker of outcomes of anti-fibrotic drug therapy in patients with idiopathic pulmonary fibrosis. BMC Pulmonary Medicine 2020;20:27.
20. Xue M, Guo Z, Cai C, Sun B, Wang H. Evaluation of the DiagnosticEfficacies of Serological Markers KL-6, SP-A, SP-D, CCL2, and CXCL13 in IdiopathicInterstitial Pneumonia.Respiration. 2019;98(6):534-545.
21. Simler NR, Brenchley PE, Horrocks AW, et al. Angiogenic cytokines in patients with idiopathic interstitial pneumonia. Thorax 2004;59:581–585.
22. Tajiri M, Okamoto M, Fujimoto K, et al. Serum level of periostin can predict long-term outcome of idiopathic pulmonary fibrosis. Respir Investig. 2015;53(2):73-81.