Use of the routine complete blood count to predict steroid resistance in patients with chronic obstructive pulmonary disease
https://doi.org/10.18093/0869-0189-2018-28-6-681-692
Abstract
The aim of the present study was to investigate the significance of complete blood count, lymphocyte subpopulations, and cytokines in the peripheral blood in order to evaluate steroid resistance in patients with chronic obstructive pulmonary disease (COPD).
Methods. Forty five patients with acute exacerbation of COPD (AECOPD) who underwent bronchoscopy the next day after hospital admission were included in the study. The patients were considered as steroid-sensitive or steroid-resistant according to the ability of dexamethasone to inhibit 50% of interleukin-8 production by alveolar macrophages. Complete blood count, lymphocyte subpopulations, cytokines, immunoglobulin E, and hormone level were measured in the peripheral blood of all patients with COPD.
Results. Macrophage migration inhibitory factor (MIF) level, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were higher, and absolute and relative eosinophil numbers were lower in steroid-resistant patients with COPD compared to steroid-sensitive COPD patients. Absolute eosinophil number below the cut-off value of 0.126 × 109/L was predictive for steroid resistance with the sensitivity of 83.3%, the specificity of 55.6% and the area under ROC curve (AUC) of 0.677. Relative eosinophil number below 1.2% predicted steroid resistance with sensitivity, specificity and AUC of 83.3%, 63.0%, and 0.751, respectively. NLR, PLR, and MIF higher than 2.75, 116, and 2.24 ng/mL, respectively, predicted steroid resistance with the sensitivities of 66.7%, 61.1%, and 72.2%, respectively; the specificities of 74.1%, 77.8%, and 70.4%, respectively; and the AUCs of 0.731, 0.678, and 0.740, respectively. The combination of relative eosinophil number, NLR and PLR increased the sensitivity to 83.3%, specificity to 77.8%, and AUC to 0.805. The combination of relative eosinophil number, PLR and MIF increased the sensitivity to 83.3%, specificity to 88.9%, and AUC to 0.889.
Conclusion. Steroid-resistant and steroid-sensitive COPD patients differ in absolute and relative eosinophil numbers, LNR, PLR, and MIF level. These parameters could be used to predict steroid resistance in COPD.
About the Authors
A. G. KadushkinBelarus
Aleksey G. Kadushkin - Candidate of Medicine, Associate Professor, Department of Biological Chemistry.
Pr. Dzerzhinskogo 83, Minsk, 220116, tel.: (37517) 207-93-92
Competing Interests: No conflict of interest
A. D. Taganovich
Belarus
Anatoliy D. Taganovich - Doctor of Medicine, Head of Department of Biological Chemistry.
Pr. Dzerzhinskogo 83, Minsk, 220116, tel.: (37517) 277-17-64
Competing Interests: No conflict of interest
L. V. Movchan
Belarus
Lyudmila V. Movchan - Candidate of Biology, Laboratory Physician, Clinical Diagnostic Laboratory.
Ul. Frunzenskaya 43, Borovlyany village, Minsk region, 223053,tel.: (37517) 265-40-89
Competing Interests: No conflict of interest
T. V. Shman
Belarus
Tat’yana V. Shman - Candidate of Biology, Head of Laboratory of Immunological Investigations.
Ul. Frunzenskaya 43, Borovlyany village, Minsk region, 223053, tel.: (37517) 265-40-89
Competing Interests: No conflict of interest
V. K. Panasyuk
Belarus
Vasiliy K. Panasyuk - Head of Endoscopy Department.
Dolginovskiy tract 157, Minsk, 220053, tel.: (37517) 289-83-53
Competing Interests: No conflict of interest
G. K. Novskaya
Belarus
Galina K. Novskaya - Head of Pulmonology Department
Dolginovskiy tract 157, Minsk, 220053,tel.: (37517) 289-03-54
Competing Interests: No conflict of interest
References
1. Vestbo J., Edwards L.D., Scanlon P.D. et al. Changes in forced expiratory volume in 1 second over time in COPD. N. Engl. J. Med. 2011; 365 (13): 1184–1192. DOI: 10.1056/NEJMoa1105482.
2. Calverley P., Pauwels R., Vestbo J. et al. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Lancet. 2003; 361 (9356): 449–456. DOI: 10.1016/S0140-6736(03)12459-2.
3. Nannini L.J., Poole P., Milan S.J., Kesterton A. Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus inhaled corticosteroids alone for chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. 2013; (8): CD006826. DOI: 10.1002/14651858.CD006826.pub2.
4. Kew K.M., Seniukovich A. Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease. Cochrane Database Syst. Rev 2014; (3): CD010115. DOI: 10.1002/14651858.CD010115.pub2.
5. Saha S., Brightling C.E. Eosinophilic airway inflammation in COPD. Int. J. Chron. Obstruct. Pulmon. Dis. 2006; 1 (1): 39–47. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2706606/
6. Tashkin D.P., Wechsler M.E. Role of eosinophils in airway inflammation of chronic obstructive pulmonary disease Int. J. Chron. Obstruct. Pulmon. Dis. 2018; 13: 335–349. DOI: 10.2147/COPD.S152291.
7. Barnes N.C., Sharma R., Lettis S., Calverley P.M. Blood eosinophils as a marker of response to inhaled corticosteroids in COPD. Eur. Respir. J. 2016; 47 (5): 1374–1382. DOI: 10.1183/13993003.01370-2015.
8. Siddiqui S.H., Guasconi A., Vestbo J. et al. Blood eosinophils: a biomarker of response to extrafine beclomethasone/formoterol in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care. Med. 2015; 192 (4): 523–525. DOI: 10.1164/rccm.201502-0235LE.
9. Selders G.S., Fetz A.E., Radic M.Z., Bowlin G.L. An overview of the role of neutrophils in innate immunity, inflammation and host-biomaterial integration. Regen. Biomater. 2017; 4 (1): 55–68. DOI: 10.1093/rb/rbw041.
10. Calandra T., Roger T. Macrophage migration inhibitory factor: a regulator of innate immunity. Nat. Rev. Immunol. 2003; 3 (10): 791–800. DOI: 10.1038/nri1200.
11. Kadushkin A.G., Taganovich A.D. Molecular mechanisms of corticosteroid resistance in patients with chronic obstructive pulmonary disease. Pul'monologiya. 2016; 26 (6): 736–747. DOI: 10.18093/0869-0189-2016-26-6-736-747 (in Russian).
12. Arman M., Payne H., Ponomaryov T., Brill A. Role of platelets in inflammation. In: Kerrigan S.W., Moran N., eds. The Non-Thrombotic Role of Platelets in Health and Disease. Intech Publishers; 2015: 37–53. DOI: 10.5772/60536.
13. Paliogiannis P., Fois A.G., Sotgia S. et al. Neutrophil to lymphocyte ratio and clinical outcomes in COPD: recent evidence and future perspectives. Eur. Respir. Rev. 2018; 27 (147): pii: 170113. DOI: 10.1183/16000617.0113-2017.
14. Kumar P., Law S., Sriram K.B. Evaluation of platelet lymphocyte ratio and 90-day mortality in patients with acute exacerbation of chronic obstructive pulmonary disease. J. Thorac. Dis. 2017; 9 (6): 1509–1516. DOI: 10.21037/jtd.2017.05.77.
15. Jones P.W., Harding G., Berry P. et al. Development and first validation of the COPD Assessment Test. Eur. Respir. J. 2009; 34 (3): 648–654. DOI: 10.1183/09031936.00102509.
16. Kadushkin A.G., Taganovich A.D., Arabey A.A. et al. Sensitivity to glucocorticoids and heterogeneity of in vitro cell response in patients with chronic obstructive pulmonary disease. Pul'monologiya. 2018; 28 (5): 558–566. DOI: 10.18093/0869-0189-2018-28-5-558-566 (in Russian).
17. Lang T. Documenting research in scientific articles: Guidelines for authors: 3. Reporting multivariate analyses. Chest. 2007; 131 (2): 628–632. DOI: 10.1378/chest.06-2088.
18. Youngstrom E.A. A primer on receiver operating characteristic analysis and diagnostic efficiency statistics for pediatric psychology: we are ready to ROC. J. Pediatr. Psychol. 2014; 39 (2): 204–221. DOI: 10.1093/jpepsy/jst062.
19. Higham A., Booth G., Lea S. et al. The effects of corticosteroids on COPD lung macrophages: a pooled analysis. Respir. Res. 2015; 16 (1): 98. DOI: 10.1186/s12931-015-0260-0.
20. Hinds D.R., DiSantostefano R.L., Le H.V., Pascoe S. Identification of responders to inhaled corticosteroids in a chronic obstructive pulmonary disease population using cluster analysis. BMJ Open. 2016; 6 (6): e010099. DOI: 10.1136/bmjopen-2015-010099.
21. Calverley P.M.А., Tetzlaff K., Vogelmeier C. et al. Eosinophilia, frequent exacerbations, and steroid response in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2017; 196 (9): 1219–1221. DOI: 10.1164/rccm.201612-2525LE.
22. Sørensen A.K., Holmgaard D.B., Mygind L.H. et al. Neutrophil-to-lymphocyte ratio, calprotectin and YKL-40 in patients with chronic obstructive pulmonary disease: correlations and 5-year mortality – a cohort study. J. Inflamm. (Lond). 2015; 12: 20. DOI: 10.1186/s12950-015-0064-5.
23. Lee H., Um S.J., Kim Y.S. et al. Association of the neutrophil-to-lymphocyte ratio with lung function and exacerbations in patients with chronic obstructive pulmonary disease. PLoS One. 2016; 11 (6): e0156511. DOI: 10.1371/journal.pone.0156511.
24. Karadeniz G., Aktoğu S., Erer O.F. et al. Predictive value of platelet-to-lymphocyte ratio in exacerbation of chronic obstructive pulmonary disease. Biomark. Med. 2016; 10 (7): 701–710. DOI: 10.2217/bmm-2016-0046.
25. Kurtipek E., Bekci T.T., Kesli R. et al. The role of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in exacerbation of chronic obstructive pulmonary disease. J. Pak. Med. Assoc. 2015; 65 (12): 1283–1287.
26. Richard V., Kindt N., Saussez S. Macrophage migration inhibitory factor involvement in breast cancer (Review). Int. J. Oncol. 2015; 47 (5): 1627–1633. DOI: 10.3892/ijo.2015.3185.
27. Daun J.M., Cannon J.G. Macrophage migration inhibitory factor antagonizes hydrocortisone-induced increases in cytosolic IκBα. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2000; 279 (3): R1043–R1049. DOI: 10.1152/ajpregu.2000.279.3.R1043.
28. Roger T., Chanson A.L., Knaup-Reymond M., Calandra T. Macrophage migration inhibitory factor promotes innate immune responses by suppressing glucocorticoid-induced expression of mitogen-activated protein kinase phosphatase-1. Eur. J. Immunol. 2005; 35 (12): 3405–3413. DOI: 10.1002/eji.200535413.
29. Wang F.F., Zhu L.A., Zou Y.Q. et al. New insights into the role and mechanism of macrophage migration inhibitory factor in steroid-resistant patients with systemic lupus erythematosus. Arthritis Res. Ther. 2012; 14 (3): R103. DOI: 10.1186/ar3828.
30. Yao C., Liu X., Tang Z. Prognostic role of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio for hospital mortality in patients with AECOPD. Int. J. Chron. Obstruct. Pulmon. Dis. 2017; 12: 2285–2290. DOI: 10.2147/COPD.S141760.
31. Stolz D., Meyer A., Rakic J. et al. Mortality risk prediction in COPD by a prognostic biomarker panel. Eur. Respir. J. 2014; 44 (6): 1557–1570. DOI: 10.1183/09031936.00043814.
Review
For citations:
Kadushkin A.G., Taganovich A.D., Movchan L.V., Shman T.V., Panasyuk V.K., Novskaya G.K. Use of the routine complete blood count to predict steroid resistance in patients with chronic obstructive pulmonary disease. PULMONOLOGIYA. 2018;28(6):681-692. (In Russ.) https://doi.org/10.18093/0869-0189-2018-28-6-681-692