Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2018, vol. 27, nr 12, December, p. 1677–1682

doi: 10.17219/acem/75904

Publication type: original article

Language: English

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The peripheral neutrophils in subjects with COPD-OSA overlap syndrome and severe comorbidities: A feasible inflammatory biomarker?

Madalina Macrea1,2,A,B,C,D,E,F, Sabrina Campbell1,3,B, Thomas Martin1,2,E,F, Kris Ann Oursler1,3,A,C,E,F

1 Salem Veterans Affairs Medical Center, USA

2 Department of Medicine, University of Virginia School of Medicine, Charlottesville, USA

3 Virginia Tech Carilion School of Medicine, Roanoke, USA

Abstract

Background. Overlap syndrome (OS) describes the association of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) in a single individual. Subjects with OS have increased cardiovascular mortality which is presumed to be inflammation-mediated. As a clinical biomarker, an increased neutrophil count correlates with the severity of coronary artery stenosis.
Objectives. As little is known about the role of neutrophils in the underlying inflammatory mechanisms in OS, we aimed to assess the percentage of peripheral neutrophils (PPN) in OS vs in COPD alone.
Material and Methods. A cross-sectional study of patients with COPD and severe comorbidities, as defined by a Care Assessment Need score over 95, were seen in the Pulmonary Tele-Health Clinic at the Salem Veteran Affairs Medical Center, USA, over a 1-year period. Demographic and polysomnographic data, FEV1 and the Charlson Comorbidity Index (CCI) were extracted from the Electronic Medical Records. Obstructive sleep apnea was defined according to the American Academy of Sleep Medicine (AASM) guidelines. Serum inflammatory markers (PPN, CRP, fibrinogen and procalcitonin) were obtained after the Tele-Health appointment.
Results. Out of the 38 subjects with COPD, 17 (44%) had OS. Compliance with continuous positive airway pressure therapy (CPAP) was excellent in 7 OS subjects (41%). There was a significant difference in the PPN of subjects with OS vs COPD alone, regardless of whether they were compliant (p = 0.03) with the CPAP therapy or not (p = 0.005). No differences in the severity of COPD, baseline comorbidity, smoking, or inflammatory markers were found between the OS and COPD-only subjects. Body mass index (BMI), COPD severity, smoking, and home oxygen therapy (HOT) use were not associated with PPN (p > 0.2).
Conclusion. Overlap syndrome subjects have higher PPN than those with COPD alone, regardless of their CPAP compliance. Our results could be used to motivate OS subjects to improve their lifestyles and to comply with drug therapies aimed at reducing cardiovascular disease (CVD).

Key words

obstructive sleep apnea, chronic obstructive pulmonary disease, cardiovascular, systemic inflammation, neutrophils

References (33)

  1. Marin J, Soriano J, Carrizo SJ, Boldova A, Celli BR. Outcomes in patients with COPD and OSA. Am J Respir Crit Care Med. 2010;182(3):325–331.
  2. Lopez‐Acevedo M, Torres‐Palacios A, Elena Ocasio‐Tascón M, Campos‐Santiago Z, Rodríguez‐Cintrón W. Overlap syndrome: An indication for sleep studies? Sleep Breath. 2009;13(4):409–413.
  3. McNicholas WT. Chronic obstructive pulmonary disease and obstructive sleep apnoea: The overlap syndrome. J Thorac Dis. 2016;8(2):236–242.
  4. Madjid M, Awan I, Willerson JT, Casscells SW. Leukocyte count and coronary heart disease: Implications for risk assessment. J Am Coll Cardiol. 2004;44(10):1945–1956.
  5. Harlan JM, Killen PD, Harker LA, Striker GE, Wright DG. Neutrophil‐mediated endothelial injury in vitro mechanisms of cell detachment. J Clin Invest. 1981;68(6):1394–1403.
  6. Mehta J, Dinerman J, Mehta P, et al. Neutrophil function in ischemic heart disease. Circulation. 1989;79(3):549–556.
  7. Chen J, Chen MH, Li S, et al. Usefulness of the neutrophil‐to‐lymphocyte ratio in predicting the severity of coronary artery disease: A Gensini score assessment. J Atheroscler Thromb. 2014;21(12):1271–1282.
  8. Green SM, Vowels J, Waterman B, Rothrock SG, Kuniyoshi G. Leukocytosis: A new look at an old marker for acute myocardial infarction. Acad Emerg Med. 1996;3(11):1034–1041.
  9. Office of Informatics and Analytics Veterans Health Administration. Care Assessment Need (CAN) Score and the Patient Care Assessment System (PCAS): Tools for Care Management. http://www.hsrd.research.va.gov/for_researchers/cyber_seminars/archives/713‐notes.pdf. Accessed June 8, 2018.
  10. Hall WH, Ramachandran R, Narayan S, Jani AB, Vijayakumar S. An electronic application for rapidly calculating Charlson comorbidity score. BMC Cancer. 2004;94. doi: 10.1186/1471-2407-4-94
  11. National Heart Lung and Blood Institute. Assessing Cardiovascular Risk: Systematic Evidence Review from the Risk Assessment Work Group. http://cvdrisk.nhlbi.nih.gov/calculator.asp. Accessed June 18, 2018.
  12. Stenton C. The MRC breathlessness scale. Occup Med (Lond). 2008;58(3):226–227.
  13. Kales A, Rechtschaffen A, eds. 13A Manual of Standardized Terminology and Techniques and Scoring System for Sleep Stages of Human Subjects. Bethesda, MD: National Institute of Neurological Diseases and Blindness, Neurological Information Network; 1968.
  14. Department of Health and Human Services, Centers for Medicare and Medicaid Services. Continuous and Bi‐level Positive Airway Pressure(CPAP/BPAP) Devices: Complying with Documentation and Coverage Requirements. https://www.cms.gov/Outreach-and-Education/Medicare-Learning-Network-MLN/MLNProducts/downloads/PAP_DocCvg_FactSheet_ICN905064.pdf. Accessed June 18, 2018.
  15. Nadeem R, Molnar J, Madbouly EM, et al. Serum inflammatory markers in obstructive sleep apnea: A meta‐analysis. J Clin Sleep Med. 2013;9(10):1003–1012.
  16. Agustí A, Edwards LD, Rennard SI, et al.; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Persistent systemic inflammation is associated with poor clinical outcomes in COPD: A novel phenotype. PLoS One. 2012;7(5):e37483. doi: 10.1371/journal.pone.0037483
  17. Guven SF, Turkkani MH, Ciftci B, Ciftci TU, Erdogan Y. The relationship between high‐sensitivity C‐reactive protein levels and the severity of obstructive sleep apnea. Sleep Breath. 2012;16(1):217–221.
  18. Nural S, Günay E, Halici B, Celik S, Ünlü M. Inflammatory processes and effects of continuous positive airway pressure (CPAP) in overlap syndrome. Inflammation. 2013;36(1):66–74.
  19. Mansour H, Fathy A, Aref H. Effect of nasal continuous positive airway pressure on inflammatory mediators inpatients with overlap syndrome. Egyptian Journal of Ear, Nose, Throat and Allied Sciences. 2011;12:99–104.
  20. Quan SF, Gersh BJ. Cardiovascular consequences of sleep‐disordered breathing: Past, present and future report of a workshop from the National Center on Sleep Disorders Research and the National Heart, Lung, and Blood Institute. Circulation. 2004;109(8):951–957.
  21. Dixon JB, O’Brien PE. Obesity and the white blood cell count: Changes with sustained weight loss. Obes Surg. 2006;16(3):251–257.
  22. Xu X, Su S, Wang X, et al. Obesity is associated with more activated neutrophils in African American male youth. Int J Obes (Lond). 2015;39(1):26–32.
  23. Ilavská S, Horváthová M, Szabová M, et al. Association between the human immune response and body mass index. Hum Immunol. 2012;73(5):480–485.
  24. Zhang J, He J, Xia J, Chen Z, Chen X. Delayed apoptosis by neutrophils from COPD patients is associated with altered bak, bcl‐xl, and mcl‐1 mRNA expression. Diagn Pathol. 2012;7:65. doi: 10.1186/1746-1596-7-65
  25. Dyugovskaya L, Polyakov A, Lavie P, Lavie L. Delayed neutrophil apoptosis in patients with sleep apnea. Am J Respir Crit Care Med. 2008;177(5):544–554.
  26. Dyugovskaya L, Polyakov A, Ginsberg D, Lavie P, Lavie L. Molecular pathways of spontaneous and TNF‐α-mediated neutrophil apoptosis under intermittent hypoxia. Am J Respir Cell Mol Biol. 2011;45(1):154–162.
  27. Dyugovskaya L, Polyakov A, Cohen‐Kaplan V, Lavie P, Lavie L. Bax/Mcl‐1 balance affects neutrophil survival in intermittent hypoxia and obstructive sleep apnea: Effects of p38MAPK and ERK1/2 signalling. J Transl Med. 2012;10:211. doi: 10.1186/1479-5876-10-211
  28. Schulz R, Mahmoudi S, Hattar K, et al. Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea. Impact of continuous positive airway pressure therapy. Am J Respir Crit Care Med. 2000;162(2 Pt 1):566–570.
  29. Stockley JA, Walton GM, Lord JM, Sapey E. Aberrant neutrophil functions in stable chronic obstructive pulmonary disease: The neutrophil as an immunotherapeutic target. Int Immunopharmacol. 2013;17(4):1211–1217.
  30. Pilkauskaite G, Miliauskas S, Sakalauskas R. Reactive oxygen species production in peripheral blood neutrophils of obstructive sleep apnea patients. ScientificWorldJournal. 2013;12:421763. doi: 10.1155/2013/421763
  31. Xie X, Pan L, Ren D, et al. Effects of continuous positive airway pressure therapy on systemic inflammation in obstructive sleep apnea: A meta‐analysis. Sleep Med. 2013;14(11):1139–1150.
  32. Drager LF, Bortolotto LA, Figueiredo AC, et al. Effects of continuous positive airway pressure on early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med. 2007;176(7):706–712.
  33. Kohler M, Ayers L, Pepperell J, et al. Effects of continuous positive airway pressure on systemic inflammation in patients with moderate to severe obstructive sleep apnoea: A randomized controlled trial. Thorax. 2009;64(1):67–73.
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