Eosinophilic Inflammation in COPD: Mechanisms, Diagnostic Markers, Clinical Features and Therapy Guidance

Aigerim Aitkazina 1, Natalya Latypova 2, Meirzhan Abishev 1, Aleksey Pak 3, Nurmakhan Zholshybek 4 * , Samat Suleimenov 4, Madi Malik 4
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1 Department of Pulmonology, City Multidisciplinary Hospital No. 2, Astana, Kazakhstan
2 Department of Family Medicine No. 2, Astana Medical University, Astana, Kazakhstan
3 Institute of Internal Medicine, National Scientific Medical Center, Astana, Kazakhstan
4 Department of Medicine, School of Medicine, Nazarbayev University, Astana, Kazakhstan
* Corresponding Author
J CLIN MED KAZ, Volume 21, Issue 3, pp. 4-10. https://doi.org/10.23950/jcmk/14640
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Author Contributions:
Conceptualization, A.A. and M.A.; methodology, N.L. and A.P.; investigation, A.A. and M.A.; resources, A.A.; data curation, S.S. and M.M.; writing – original draft preparation, A.A., S.S. and M.M.; writing – review and editing, N.Z.; visualization, S.S. and M.M.; supervision, N.L. and N.Z. All authors have read and agreed to the published version of the manuscript.

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is one of the main causes of morbidity and mortality worldwide. Eosinophilia, which may have a significant role in the inflammation process and obstruction of airways, is present in about one third patients suffering from COPD. The significance of eosinophil counts in COPD is currently debated, but they can potentially serve as biomarkers for treatment selection. Blood eosinophil counts can assist in determining the patients who can benefit from inhaled corticosteroid therapy to prevent or eliminate exacerbations.
The aim of this review is to demonstrate the significance of eosinophilic inflammation COPD and the use of eosinophilic inflammation biomarkers to guide therapy decisions.
To reach this goal, a search of relevant literature on the subject was conducted. Articles were searched in electronic sources: PubMed and Google Scholar. The keywords "COPD and eosinophilia", "COPD exacerbations and eosinophilia", "inhaled corticosteroids, COPD and eosinophilia" were used. One hundred and twenty sources were found, of which 66 were selected.
Results of the review showed high frequency of eosinophilic phenotype detection in COPD. Blood eosinophilia becomes a potential universal marker of eosinophilic COPD. Blood eosinophils level can predict response to inhaled corticosteroids treatment patients with COPD, but increases the likelihood of pneumonia. Overall, the role of eosinophilia in COPD has not been obtained to date, which suggests it needs further study.

CITATION

Aitkazina A, Latypova N, Abishev M, Pak A, Zholshybek N, Suleimenov S, et al. Eosinophilic Inflammation in COPD: Mechanisms, Diagnostic Markers, Clinical Features and Therapy Guidance. J CLIN MED KAZ. 2024;21(3):4-10. https://doi.org/10.23950/jcmk/14640

REFERENCES

  • Halpin DM, Criner GJ, Papi A, Singh D, Anzueto A, Martinez FJ, et al. Global initiative for the diagnosis, management, and prevention of chronic obstructive lung disease. The 2020 GOLD science committee report on COVID-19 and chronic obstructive pulmonary disease. American journal of respiratory and critical care medicine. 2021 Jan 1;203(1):24-36. https://doi.org/10.1164/rccm.202009-3533SO
  • Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study. The lancet. 1997 May 24;349(9064):1498-504. https://doi.org/10.1016/S0140-6736(96)07492-2
  • Carson-Chahhoud K, Noori M, Nejadghaderi SA, Sullman M, Ahmadian Heris J, Ansarin K, et al. The burden of chronic obstructive pulmonary disease and its attributable risk factors in 204 countries and territories, 1990-2019: Results from the Global Burden of Disease Study 2019.
  • Nugmanova D, Feshchenko Y, Iashyna L, Gyrina O, Malynovska K, Mammadbayov E, et al. The prevalence, burden and risk factors associated with chronic obstructive pulmonary disease in Commonwealth of Independent States (Ukraine, Kazakhstan and Azerbaijan): results of the CORE study. BMC pulmonary medicine. 2018 Dec;18(1):1-4. https://doi.org/10.1186/s12890-018-0589-5
  • Public health Republic of Kazakhstan and activities organizations health care in 2020 year. [Internet]. [cited 2023 Dec 28]. Available from: https://www.gov.kz/memleket/entities/dsm/documents/details/246287?lang=en
  • Viegi G, Maio S, Fasola S, Baldacci S. Global burden of chronic respiratory diseases. Journal of aerosol medicine and pulmonary drug delivery. 2020 Aug 1;33(4):171-7. https://doi.org/10.1089/jamp.2019.1576
  • McDaniel JT. Prevalence of chronic obstructive pulmonary disease: county-level risk factors based on the Social Ecological Model. Perspectives in Public Health. 2018 Jul;138(4):200-8. https://doi.org/10.1177/1757913918772598
  • Venkatesan P. GOLD report: 2022 update. The Lancet Respiratory Medicine. 2022 Feb 1;10(2):e20. https://doi.org/10.1016/S2213-2600(21)00561-0
  • Torén K, Olin AC, Lindberg A, Vikgren J, Schiöler L, Brandberg J, et al. Vital capacity and COPD: the Swedish cardiopulmonary bioImage study (SCAPIS). International journal of chronic obstructive pulmonary disease. 2016 May 2:927-33. https://doi.org/10.2147/COPD.S104644
  • Olloquequi J, Jaime S, Parra V, Cornejo-Córdova E, Valdivia G, Agustí À, Silva O R. Comparative analysis of COPD associated with tobacco smoking, biomass smoke exposure or both. Respiratory research. 2018 Dec;19(1):1-8. https://doi.org/10.1186/s12931-018-0718-y
  • Golpe R, Martín-Robles I, Sanjuán-López P, Pérez-de-Llano L, González-Juanatey C, López-Campos JL, et al. Differences in systemic inflammation between cigarette and biomass smoke-induced COPD. International journal of chronic obstructive pulmonary disease. 2017 Sep 1:2639-46. https://doi.org/10.2147/COPD.S141068
  • Lange P, Celli B, Agustí A, Boje Jensen G, Divo M, Faner R, et al. Lung-function trajectories leading to chronic obstructive pulmonary disease. New England Journal of Medicine. 2015 Jul 9;373(2):111-22. https://doi.org/10.1056/NEJMoa1411532
  • Górska K, Paplińska-Goryca M, Nejman-Gryz P, Goryca K, Krenke R. Eosinophilic and neutrophilic airway inflammation in the phenotyping of mild-to-moderate asthma and chronic obstructive pulmonary disease. COPD: Journal of Chronic Obstructive Pulmonary Disease. 2017 Mar 30;14(2):181-9. https://doi.org/10.1080/15412555.2016.1260539
  • Saha S, Brightling CE. Eosinophilic airway inflammation in COPD. International journal of chronic obstructive pulmonary disease. 2006 Jan 1;1(1):39-47. https://doi.org/10.2147/copd.2006.1.1.39
  • Singh D, Kolsum U, Brightling CE, Locantore N, Agusti A, Tal-Singer R. Eosinophilic inflammation in COPD: prevalence and clinical characteristics. European Respiratory Journal. 2014 Dec 1;44(6):1697-700. https://doi.org/10.1183/09031936.00162414
  • Bedolla-Barajas M, Morales-Romero J, Bedolla-Pulido TI, Flores-Razo MM, Morales MA, Rosales G, et al. Prevalence of blood eosinophilia in adults with COPD according to the cut-off point. Revista Alergia de Mexico. 2021 Jul 1;68(3). https://doi.org/10.29262/ram.v67i3.893
  • Yang M, Yang T, Li X, Li D, Liao Z, Shen Y, et al. Clinical predictors of high blood eosinophils in chronic obstructive pulmonary disease. International Journal of Chronic Obstructive Pulmonary Disease. 2021 Aug 28:2467-74. https://doi.org/10.2147/COPD.S324511
  • Li A, Chan HP, Gan PX, Liew MF, Wong WF, Lim HF. Eosinophilic endotype of chronic obstructive pulmonary disease: similarities and differences from asthma. The Korean Journal of Internal Medicine. 2021 Nov;36(6):1305. https://doi.org/10.3904/kjim.2021.180
  • Vedel-Krogh S, Nielsen SF, Lange P, Vestbo J, Nordestgaard BG. Blood eosinophils and exacerbations in chronic obstructive pulmonary disease. The Copenhagen General Population Study. American journal of respiratory and critical care medicine. 2016 May 1;193(9):965-74. https://doi.org/10.1164/rccm.201509-1869OC
  • Bafadhel M, McKenna S, Terry S, Mistry V, Reid C, Haldar P, et al. Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. American journal of respiratory and critical care medicine. 2011 Sep 15;184(6):662-71. https://doi.org/10.1164/rccm.201104-0597OC
  • Bafadhel M, Saha S, Siva R, McCormick M, Monteiro W, Rugman P, et al. Sputum IL-5 concentration is associated with a sputum eosinophilia and attenuated by corticosteroid therapy in COPD. Respiration. 2009 Sep 1;78(3):256-62. https://doi.org/10.1159/000221902
  • Varricchi G, Bagnasco D, Borriello F, Heffler E, Canonica GW. Interleukin-5 pathway inhibition in the treatment of eosinophilic respiratory disorders: evidence and unmet needs. Current opinion in allergy and clinical immunology. 2016 Apr;16(2):186. https://doi.org/10.1097/ACI.0000000000000251
  • Molfino NA, Gossage D, Kolbeck R, Parker JM, Geba GP. Molecular and clinical rationale for therapeutic targeting of interleukin‐5 and its receptor. Clinical & Experimental Allergy. 2012 May;42(5):712-37. https://doi.org/10.1111/j.1365-2222.2011.03854.x
  • Brusselle G, Pavord ID, Landis S, Pascoe S, Lettis S, Morjaria N, et al. Blood eosinophil levels as a biomarker in COPD. Respiratory medicine. 2018 May 1;138:21-31. https://doi.org/10.1016/j.rmed.2018.03.016
  • George L, Brightling CE. Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease. Therapeutic advances in chronic disease. 2016 Jan;7(1):34-51. https://doi.org/10.1177/2040622315609251
  • Davoine F, Lacy P. Eosinophil cytokines, chemokines, and growth factors: emerging roles in immunity. Frontiers in immunology. 2014 Nov 10;5:570. https://doi.org/10.3389/fimmu.2014.00570
  • McDonald VM, Higgins I, Wood LG, Gibson PG. Multidimensional assessment and tailored interventions for COPD: respiratory utopia or common sense?. Thorax. 2013 Mar 1:thoraxjnl-2012. https://doi.org/10.1136/thoraxjnl-2012-202646
  • Leigh R, Pizzichini MM, Morris MM, Maltais F, Hargreave FE, Pizzichini E. Stable COPD: predicting benefit from high-dose inhaled corticosteroid treatment. European Respiratory Journal. 2006 May 1;27(5):964-71. https://doi.org/10.1183/09031936.06.00072105
  • Hastie AT, Martinez FJ, Curtis JL, Doerschuk CM, Hansel NN, Christenson S, et al. Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: an analysis of the SPIROMICS cohort. The Lancet Respiratory Medicine. 2017 Dec 1;5(12):956-67. https://doi.org/10.1016/S2213-2600(17)30432-0
  • Kolsum U, Ravi A, Hitchen P, Maddi S, Southworth T, Singh D. Clinical characteristics of eosinophilic COPD versus COPD patients with a history of asthma. Respiratory research. 2017 Dec;18(1):1-7. https://doi.org/10.1186/s12931-017-0559-0
  • Negewo NA, McDonald VM, Baines KJ, Wark PA, Simpson JL, Jones PW, Gibson PG. Peripheral blood eosinophils: a surrogate marker for airway eosinophilia in stable COPD. International journal of chronic obstructive pulmonary disease. 2016 Jul 1:1495-504. https://doi.org/10.2147/COPD.S100338
  • Singh D, Watz H, Beeh KM, Kornmann O, Leaker B, Colgan B, et al. COPD sputum eosinophils: relationship to blood eosinophils and the effect of inhaled PDE4 inhibition. European Respiratory Journal. 2020 Aug 1;56(2). https://doi.org/10.1183/13993003.00237-2020
  • Shin SH, Park HY, Kang D, Cho J, Kwon SO, Park JH, et al. Serial blood eosinophils and clinical outcome in patients with chronic obstructive pulmonary disease. Respiratory research. 2018 Dec;19:1-9. https://doi.org/10.1186/s12931-018-0840-x
  • Yilmaz I, Turk M. What should be the cutoff value of blood eosinophilia as a predictor of inhaled corticosteroid responsiveness in patients with chronic obstructive pulmonary disease?. American Journal of Respiratory and Critical Care Medicine. 2017 Nov 1;196(9):1229-30. https://doi.org/10.1164/rccm.201705-0892LE
  • Oshagbemi OA, Burden AM, Braeken DC, Henskens Y, Wouters EF, Driessen JH, et al. Stability of blood eosinophils in patients with chronic obstructive pulmonary disease and in control subjects, and the impact of sex, age, smoking, and baseline counts. American journal of respiratory and critical care medicine. 2017 May 15;195(10):1402-4. https://doi.org/10.1164/rccm.201701-0009LE
  • Casanova C, Celli BR, de-Torres JP, Martínez-Gonzalez C, Cosio BG, Pinto-Plata V, et al. Prevalence of persistent blood eosinophilia: relation to outcomes in patients with COPD. European Respiratory Journal. 2017 Nov 1;50(5). https://doi.org/10.1183/13993003.01162-2017
  • Soter S, Barta I, Antus B. Predicting sputum eosinophilia in exacerbations of COPD using exhaled nitric oxide. Inflammation. 2013 Oct;36:1178-85. https://doi.org/10.1007/s10753-013-9653-8
  • Gao J, Zhang M, Zhou L, Yang X, Wu H, Zhang J, Wu F. Correlation between fractional exhaled nitric oxide and sputum eosinophilia in exacerbations of COPD. International Journal of Chronic Obstructive Pulmonary Disease. 2017 Apr 27:1287-93. https://doi.org/10.2147%2FCOPD.S134998
  • Tang B, Huang D, Wang J, Luo LL, Li QG. Relationship of blood eosinophils with fractional exhaled nitric oxide and pulmonary function parameters in chronic obstructive pulmonary disease (COPD) exacerbation. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research. 2020;26:e921182-1. https://doi.org/10.12659%2FMSM.921182
  • Wu CW, Lan CC, Hsieh PC, Tzeng IS, Wu YK. Role of peripheral eosinophilia in acute exacerbation of chronic obstructive pulmonary disease. World Journal of Clinical Cases. 2020 Jul 7;8(13):2727. https://doi.org/10.12998/wjcc.v8.i13.2727
  • Xue J, Cui YN, Chen P, Cai S, Chen L, Dai ZS, Chen Y. Blood eosinophils: a biomarker of response to glucocorticoids and increased readmissions in severe hospitalized exacerbations of COPD. Zhonghua jie he he hu xi za zhi= Zhonghua jiehe he huxi zazhi= Chinese journal of tuberculosis and respiratory diseases. 2019 Jun 1;42(6):426-31. https://doi.org/10.3760/cma.j.issn.1001-0939.2019.06.005
  • Turato G, Semenzato U, Bazzan E, Biondini D, Tinè M, Torrecilla N, et al. Blood eosinophilia neither reflects tissue eosinophils nor worsens clinical outcomes in chronic obstructive pulmonary disease. American journal of respiratory and critical care medicine. 2018 May 1;197(9):1216-9. https://doi.org/10.1164/rccm.201708-1684LE
  • Chou KT, Su KC, Hsiao YH, Huang SF, Ko HK, Tseng CM, et al. Post-bronchodilator reversibility of FEV1 and eosinophilic airway inflammation in COPD. Archivos de Bronconeumología (English Edition). 2017 Oct 1;53(10):547-53. https://doi.org/10.1016/j.arbr.2017.01.027
  • Papaioannou AI, Kostikas K, Papaporfyriou A, Angelakis L, Papathanasiou E, Hillas G, et al. Emphysematous phenotype is characterized by low blood eosinophils: a cross-sectional study. COPD: Journal of Chronic Obstructive Pulmonary Disease. 2017 Nov 2;14(6):635-40. https://doi.org/10.1080/15412555.2017.1386644
  • Oh YM, Lee KS, Hong Y, Hwang SC, Kim JY, Kim DK, et al. Blood eosinophil count as a prognostic biomarker in COPD. International journal of chronic obstructive pulmonary disease. 2018 Oct 31:3589-96. https://doi.org/10.2147/COPD.S179734
  • Müllerová H, Hahn B, Simard EP, Mu G, Hatipoğlu U. Exacerbations and health care resource use among patients with COPD in relation to blood eosinophil counts. International Journal of Chronic Obstructive Pulmonary Disease. 2019 Mar 22:683-92. https://doi.org/10.2147/COPD.S194367
  • Kerkhof M, Sonnappa S, Postma DS, Brusselle G, Agustí A, Anzueto A, et al. Blood eosinophil count and exacerbation risk in patients with COPD. European Respiratory Journal. 2017 Jul 1;50(1). https://doi.org/10.1183/13993003.00761-2017
  • Hegewald MJ, Horne BD, Trudo F, Kreindler JL, Chung Y, Rea S, Blagev DP. Blood eosinophil count and hospital readmission in patients with acute exacerbation of chronic obstructive pulmonary disease. International Journal of Chronic Obstructive Pulmonary Disease. 2020 Oct 23:2629-41. https://doi.org/10.2147/COPD.S251115
  • Cheng SL, Lin CH. Effectiveness using higher inhaled corticosteroid dosage in patients with COPD by different blood eosinophilic counts. International Journal of Chronic Obstructive Pulmonary Disease. 2016 Sep 21:2341-8. https://doi.org/10.2147/COPD.S115132
  • Vogelmeier CF, Kostikas K, Fang J, Tian H, Jones B, Morgan CL, et al. Evaluation of exacerbations and blood eosinophils in UK and US COPD populations. Respiratory research. 2019 Dec;20:1-0. https://doi.org/10.1186/s12931-019-1130-y
  • Yun JH, Lamb A, Chase R, Singh D, Parker MM, Saferali A, et al. Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease. Journal of allergy and clinical immunology. 2018 Jun 1;141(6):2037-47. https://doi.org/10.1016/j.jaci.2018.04.010
  • Hamitov RF, Zinnatullina AR, Mihoparova OJu. Eozinofilija krovi i obostrenija HOBL: vse li odnoznachno (Blood eosinophilia and exacerbations of COPD: whether everything is clear). [in Russian]. Vestnik sovremennoj klinicheskoj mediciny. 2022;15(4):60-4.
  • Acet‐Öztürk NA, Dilektasli AG, Aydın‐Güçlü Ö, Demirdöğen E, Coşkun F, Ursavaş A, et al. Long‐term oxygen treatment need is less frequent in eosinophilic COPD patients. The Clinical Respiratory Journal. 2022 Jan;16(1):49-56. https://doi.org/10.1111/crj.13451
  • Bafadhel M, Greening NJ, Harvey-Dunstan TC, Williams JE, Morgan MD, Brightling CE, et al. Blood eosinophils and outcomes in severe hospitalized exacerbations of COPD. Chest. 2016 Aug 1;150(2):320-8. https://doi.org/10.1016/j.chest.2016.01.026
  • Zysman M, Deslée G, Caillaud D, Chanez P, Escamilla R, Court-Fortune I, et al. Relationship between blood eosinophils, clinical characteristics, and mortality in patients with COPD. International journal of chronic obstructive pulmonary disease. 2017 Jun 20:1819-24. https://doi.org/10.2147/COPD.S129787
  • Saad AB, Khemakhem R, Mhamed SC, Fahem N, Migaou A, Joobeur S, Rouatbi N. Etude de l’intérêt de l’éosinophilie sanguine au cours des exacerbations aigues sévères de bronchopneumopathie chronique obstructive (BPCO) dans un centre tunisien. Pan African Medical Journal. 2019 Nov 8;34(1). https://doi.org/10.11604/pamj.2019.34.138.17392
  • Pavord ID, Lettis S, Locantore N, Pascoe S, Jones PW, Wedzicha JA, Barnes NC. Blood eosinophils and inhaled corticosteroid/long-acting β-2 agonist efficacy in COPD. Thorax. 2015 Nov 19:thoraxjnl-2015. https://doi.org/10.1136%2Fthoraxjnl-2015-207021
  • Liu T, Xiang ZJ, Hou XM, Chai JJ, Yang YL, Zhang XT. Blood eosinophil count-guided corticosteroid therapy and as a prognostic biomarker of exacerbations of chronic obstructive pulmonary disease: a systematic review and meta-analysis. Therapeutic Advances in Chronic Disease. 2021 Jul;12:20406223211028768. https://doi.org/10.1177/204062232110287
  • Ramakrishnan S, Jeffers H, Langford-Wiley B, Davies J, Thulborn SJ, Mahdi M, et al. Blood eosinophil-guided oral prednisolone for COPD exacerbations in primary care in the UK (STARR2): a non-inferiority, multicentre, double-blind, placebo-controlled, randomised controlled trial. The Lancet Respiratory Medicine. 2024 Jan 1;12(1):67-77. https://doi.org/10.1016/S2213-2600(23)00298-9
  • Bafadhel M, Davies L, Calverley PM, Aaron SD, Brightling CE, Pavord ID. Blood eosinophil guided prednisolone therapy for exacerbations of COPD: a further analysis. European Respiratory Journal. 2014 Sep 1;44(3):789-91. https://doi.org/10.1183/09031936.00062614
  • Pascoe S, Locantore N, Dransfield MT, Barnes NC, Pavord ID. Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: a secondary analysis of data from two parallel randomised controlled trials. The Lancet Respiratory medicine. 2015 Jun 1;3(6):435-42. https://doi.org/10.1016/S2213-2600(15)00106-X
  • Roche N, Chapman KR, Vogelmeier CF, Herth FJ, Thach C, Fogel R, et al. Blood eosinophils and response to maintenance chronic obstructive pulmonary disease treatment. Data from the FLAME trial. American journal of respiratory and critical care medicine. 2017 May 1;195(9):1189-97. https://doi.org/10.1164/rccm.201701-0193OC
  • Pavord ID, Lettis S, Anzueto A, Barnes N. Blood eosinophil count and pneumonia risk in patients with chronic obstructive pulmonary disease: a patient-level meta-analysis. The Lancet Respiratory medicine. 2016 Sep 1;4(9):731-41. https://doi.org/10.1016/S2213-2600(16)30148-5
  • Barnes NC, Sharma R, Lettis S, Calverley PM. Blood eosinophils as a marker of response to inhaled corticosteroids in COPD. European Respiratory Journal. 2016 May 1;47(5):1374-82. https://doi.org/10.1183/13993003.01370-2015
  • Tashkin DP, Miravitlles M, Celli BR, Metzdorf N, Mueller A, Halpin DM, Anzueto A. Concomitant inhaled corticosteroid use and the risk of pneumonia in COPD: a matched-subgroup post hoc analysis of the UPLIFT® trial. Respiratory research. 2018 Dec;19:1-1. https://doi.org/10.1186/s12931-018-0874-0
  • Cheng SL. Blood eosinophils and inhaled corticosteroids in patients with COPD: systematic review and meta-analysis. International journal of chronic obstructive pulmonary disease. 2018 Sep 6:2775-84. https://doi.org/10.2147/COPD.S175017