SYSTEMIC INFLAMMATORY PROFILE IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

  • Angjela Debreshlioska University Clinic of Pulmonology and Allergology, Skopje, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Irina Angelovska University Clinic of Pulmonology and Allergology, Skopje, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Sava Pejkovska University Clinik of Pulmonology and Allergology, Faculty of Medicine, Ss Cyril and Methodius University in Skopje, North Macedonia
  • Meri Kirijas Institute of Immunobiology and Human Genetics, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Aleksandar Petlichovski Institute of Immunobiology and Human Genetics, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia

Abstract

Chronic obstructive pulmonary disease (COPD) is heterogeneous condition with various phenotypes that have their own pathogenetic mechanisms and certain inflammatory mediators, as C-reactive protein, interleukins, circulating leukocytes. Uncovering the inflammatory profile may identify disease biomarkers. We aimed to compare the values ​​of systemic inflammatory parameters ​​in patients with different clinical phenotypes and determine their correlation with clinical parameters. In 30 COPD patients we analyzed demographic and clinical data, history of allergies, cigarette smoking and history of exacerbations.  We phenotyped them into non-exacerbator, exacerbator and COPD with asthma phenotype. COPD assessment test, modified dyspnea scale and the BODE (Body mass index, Obstruction, Dyspnea, Exercise capacity) index were calculated. Spirometry and lung X-ray were performed. Peripheral blood was taken for analysis of inflammatory parameters.


There were 16 patients (53.33%) with phenotype of non-exacerbator, and 7 (23.33%) with exacerbator and COPD with asthma phenotype each. COPD assessment test had significantly lowest value in non-exacerbator and modified dyspnea scale significantly highest value in exacerbator phenotype. There were no mild grade patients in exacerbator, and no very severe grade in nonexacerbator phenotype. C-reactive protein  and interleukin 8 had significantly lowest value in non-exacerbator; leucocytes significantly highest value in exacerbator; eosinophyls and interleukin 4 significantly highest value in COPD with asthma phenotype. There was no significant difference among the three phenotypes in neutrophyls and interleukin 18. The three clinical phenotypes: non-exacerbator, exacerbator and COPD with asthma have their own specific clinical and inflammatory features that have clinical, prognostic and therapeutic implications.


Keywords: COPD, inflammatory parameters, phenotypes.

References

1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for Prevention, Diagnosis and Management of COPD: 2021 Report.
2. Agustí A, Hogg JC. Update on the pathogenesis of chronic obstructive pulmonary disease. New England Journal of Medicine 2019;381(13):1248-56.
3. Barnes, P.J. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease. Journal of Allergy and Clinical Immunology 2016;138(1):16-27.
4. Bradford E, Jacobson S, Varasteh J, Comellas AP, Woodruff P, O’Neal W et al. The value of blood cytokines and chemokines in assessing COPD. Respiratory research 2017;18(1):180.
5. Ardestani ME, Zaerin O. Role of serum interleukin 6, albumin and C-reactive protein in COPD patients. Tanaffos 2015;14(2):134.
6. Fermont JM, Masconi KL, Jensen MT, Ferrari R, Di Lorenzo VA, Marott JM et al. Biomarkers and clinical outcomes in COPD: a systematic review and meta-analysis. Thorax 2019;74(5):439-46.
7. Vitenberga Z, Pilmane M, Babjoniševa A. An Insight into COPD Morphopathogenesis: Chronic Inflammation, Remodeling, and Antimicrobial Defense. Medicina. 2019; 55(8):496.
8. Rincon M, Irvin CG. Role of IL-6 in asthma and other inflammatory pulmonary diseases. International journal of biological sciences 2012;8(9):1281.
9. Zhang J, Bai C. The Significance of Serum Interleukin-8 in Acute Exacerbations of Chronic Obstructive Pulmonary Disease. Tanaffos. 2018 Jan;17(1):13-21.
10. Dima E, Koltsida O, Katsaounou P, Vakali S, Koutsoukou A, Koulouris NG, Rovina N. Implication of Interleukin (IL)-18 in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cytokine. 2015 Aug;74(2):313-7.
11. Lange P, Halpin DM, O’Donnell DE, MacNee W. Diagnosis, assessment, and phenotyping of COPD: beyond FEV1. International journal of chronic obstructive pulmonary disease 2016;11(Spec Iss):3.
12. Mirza S, Benzo R. Chronic Obstructive Pulmonary Disease Phenotypes: Implications for Care. Mayo Clinic Proceedings 2017;92(7):1104-1112.
13. Centers for Disease Control and Prevention (CDC) Cigarette smoking among adults – United States, 1992, and changes in the definition of current cigarette smoking. MMWR Morb Mortal Wkly Rep. 1994;43(19):342–346.
14. Burgel PR. Chronic cough and sputum production: a clinical COPD phenotype? Eur Respir J. 2012;40(1):4–6.
15. García-Sidro P, Naval E, Rivera CM, Bonnin-Vilaplana M, Garcia-Rivero JL, Herrejón A et аl. The CAT (COPD Assessment Test) questionnaire as a predictor of the evolution of severe COPD exacerbations. Respiratory medicine 2015;109(12):1546-52.
16. Munari AB, Gulart AA, Dos Santos K, Venâncio RS, Karloh M, Mayer AF. Modified Medical Research Council dyspnea scale in GOLD classification better reflects physical activities of daily living. Respiratory care 2018;63(1):77-85.
17. Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med 2004;350(10):1005-12.
18. Graham BL, Steenbruggen I, Miller MR, Barjaktarevic IZ, Cooper BG, Hall GL, Hallstrand TS, Kaminsky DA, McCarthy K, McCormack MC, Oropez CE. Standardization of spirometry 2019 update. An official American thoracic society and European respiratory society technical statement. American journal of respiratory and critical care medicine. 2019 Oct 15;200(8):e70-88.
19. Washko GR. Diagnostic imaging in COPD. In Seminars in respiratory and critical care medicine 2010;31(3):276-285.
20. Miravitlles M, Soler-Cataluña JJ, Calle M, et al. Spanish guidelines for management of chronic obstructive pulmonary disease (GesEPOC) 2017. Pharmacological treatment of stable phase. Arch Bronconeumol. 2017;53(6):324–335.
21. Soler-Cataluña JJ, Martínez García MA, Catalán P. The frequent exacerbator. A new phenotype in COPD? Hot Topics Respir Med. 2011;19:7–12.
22. Miravitlles M, Alvarez-Gutierrez FJ, Calle M, et al. Algorithm for identification of asthma-COPD overlap: consensus between the Spanish COPD and asthma guidelines. Eur Respir J. 2017;49(5):1700068.
23. Khalifian S, Raimondi G, Brandacher G. The use of luminex assays to measure cytokines. The Journal of investigative dermatology. 2015 Apr 1;135(4):e31.
24. Vestbo J. COPD: definition and phenotypes. Clinics in chest medicine. 2014 Mar 1;35(1):1-6.
25. Weatherall M, Travers J, Shirtcliffe PM, Marsh SE, Williams MV, Nowitz MR, Aldington S, Beasley R. Distinct clinical phenotypes of airways disease defined by cluster analysis. European Respiratory Journal. 2009 Oct 1;34(4):812-8.
26. Papi A, Magnoni MS, Muzzio CC, Benso G, Rizzi A. Phenomenology of COPD: interpreting phenotypes with the ECLIPSE study. Monaldi Archives for Chest Disease. 2016 Oct 14;83(1-2).
27. Miravitlles M, Barrecheguren M, Román-Rodríguez M. Frequency and characteristics of different clinical phenotypes of chronic obstructive pulmonary disease. Int J Tuberc Lung Dis. 2015 Aug;19(8):992-8. doi: 10.5588/ijtld.15.0021. PMID: 26162367.
28. Gupta N, Pinto LM, Morogan A, Bourbeau J. The COPD assessment test: a systematic review. European Respiratory Journal. 2014 Oct 1;44(4):873-84.
29. Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA. Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax 1999; 54(7): 581-6.
30. Cosio BG, Soriano JB, López-Campos JL, et al.CHAIN study Distribution and outcomes of a phenotype-based approach to guide COPD management: results from the chain cohort. PLoS One. 2016;11(9):e0160770.
31. Corlateanu A, Botnaru V, Rusu D, Scutaru E, Covantev S. Assessment of health-related quality of life in different phenotypes of COPD. Current Respiratory Medicine Reviews. 2017 Jun 1;13(2):105-9.
32. Chai CS, Liam CK, Pang YK, Ng DL, Tan SB, Wong TS, Sia JE. Clinical phenotypes of COPD and health-related quality of life: a cross-sectional study. International journal of chronic obstructive pulmonary disease. 2019;14:565.
33. Golpe R, Suárez-Valor M, Martín-Robles I, Sanjuán-López P, Cano-Jiménez E, Castro-Añón O, de Llano LA. Mortality in COPD patients according to clinical phenotypes. International Journal of Chronic Obstructive Pulmonary Disease. 2018;13:1433.
34. Young KA, Regan EA, Han MK, Lutz SM, Ragland M, Castaldi PJ, Washko GR, Cho MH, Strand M, Curran-Everett D, Beaty TH. Subtypes of COPD have unique distributions and differential risk of mortality. Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation. 2019;6(5):400.
35. Aksu F, Capan N, Aksu K, OfluoÄŸlu R, Canbakan S, Yavuz B, Akin KO. C-reactive protein levels are raised in stable Chronic obstructive pulmonary disease patients independent of smoking behavior and biomass exposure. J Thorac Dis. 2013 Aug;5(4):414-21. doi: 10.3978/j.issn.2072-1439.2013.06.27. PMID: 23991296; PMCID: PMC3755654.
36. DeTorres JP, Cordoba-Lanus E, López-Aguilar C, et al.C-reactive protein levels and clinically important predictive outcomes in stable COPD patients. Eur Respir J 2006;27:902-7.
37. Nuñez A, Marras V, Harlander M, Mekov E, Esquinas C, Turel M, et al. Association Between Routine Blood Biomarkers and Clinical Phenotypes and Exacerbations in Chronic Obstructive Pulmonary Disease. Int J Chron Obstruct Pulmon Dis. 2020 Mar 31;15:681-690.
38. Vestbo J, Edwards LD, Scanlon PD, Yates JC, Agusti A, Bakke P, et al. Changes in forced expiratory volume in 1 second over time in COPD. N Engl J Med. 2011;365:1184–1192.
39. Celli BR, Locantore N, Yates J, Tal-Singer R, Miller BE, Bakke P, et al. Inflammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;185:1065–1072.
40. Papaporfyriou A, Bakakos P, Hillas G, Papaioannou AI, Loukides S. Blood eosinophils in COPD: friend or foe? Expert Rev Respir Med. 2022 Jan;16(1):35-41.
41. Agusti A, Sin DD. Biomarkers in COPD. Clin Chest Med 2014;35(1):131–41.
42. Imaoka H, Hoshino T, Takei S, Kinoshita T, Okamoto M, Kawayama T, Kato S, Iwasaki H, Watanabe K, Aizawa H. Interleukin-18 production and pulmonary function in COPD. Eur Respir J. 2008 Feb;31(2):287-97.
43. Kang MJ, Choi JM, Kim BH, Lee CM, Cho WK, Choe G, Kim DH, Lee CG, Elias JA. IL-18 induces emphysema and airway and vascular remodeling via IFN-γ, IL-17A, and IL-13. Am J Respir Crit Care Med. 2012 Jun 1;185(11):1205-17.
Published
2024-05-01
How to Cite
DEBRESHLIOSKA, Angjela et al. SYSTEMIC INFLAMMATORY PROFILE IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE. Journal of Morphological Sciences, [S.l.], v. 7, n. 1, p. 142-153, may 2024. ISSN 2545-4706. Available at: <https://jms.mk/jms/article/view/vol7no1-18>. Date accessed: 20 june 2024.
Section
Articles