References
- Saetta M, Turato G, Facchini FM, et al. Inflammatory cells in the bronchial glands of smokers with chronic bronchitis. Am J Respir Crit Care Med. 1997;156(5):1633–1639. DOI:https://doi.org/10.1164/ajrccm.156.5.9701081
- O’Shaughnessy TC, Ansari TW, Barnes NC, et al. Inflammation in bronchial biopsies of subjects with chronic bronchitis: inverse relationship of CD8+ T lymphocytes with FEV1. Am J Respir Crit Care Med. 1997;155(3):852–857. DOI:https://doi.org/10.1164/ajrccm.155.3.9117016
- Kostikas K, Bakakos P, Papiris S, et al. Systemic biomarkers in the evaluation and management of COPD patients: are we getting closer to clinical application? Curr Drug Targets. 2013;14(2):177–191. DOI:https://doi.org/10.2174/1389450111314020005
- Martin RJ, Bel EH, Pavord ID, et al. Defining severe obstructive lung disease in the biologic era: an endotype-based approach. Eur Respir J. 2019;54(5):1900108. DOI:https://doi.org/10.1183/13993003.00108-2019
- Leigh R, Pizzichini MM, Morris MM, et al. Stable COPD: predicting benefit from high-dose inhaled corticosteroid treatment. Eur Respir J. 2006;27(5):964–971. DOI:https://doi.org/10.1183/09031936.06.00072105
- Proboszcz M, Mycroft K, Paplinska-Goryca M, et al. Relationship between blood and induced sputum eosinophils, bronchial hyperresponsiveness and reversibility of airway obstruction in mild-to-Moderate chronic obstructive pulmonary disease. COPD. 2019;16(5–6):354–361. DOI:https://doi.org/10.1080/15412555.2019.1675150
- Kim VL, Coombs NA, Staples KJ, et al. Impact and associations of eosinophilic inflammation in COPD: analysis of the AERIS cohort. Eur Respir J. 2017;50(4):1700853. DOI:https://doi.org/10.1183/13993003.00853-2017
- Website [Internet]. [cited 2020 May 1]. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease 2020 report. https://goldcopd.org/wp-content/uploads/2019/11/GOLD-2020-REPORT-ver1.1wms.pdf.
- Barnes PJ. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2016;138(1):16–27. DOI:https://doi.org/10.1016/j.jaci.2016.05.011
- George L, Brightling CE. Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease. Ther Adv Chronic Dis. 2016;7(1):34–51. DOI:https://doi.org/10.1177/2040622315609251
- Woodruff PG, Modrek B, Choy DF, et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med. 2009;180(5):388–395. DOI:https://doi.org/10.1164/rccm.200903-0392OC
- Robinson D, Humbert M, Buhl R, et al. Revisiting type 2-high and type 2-low airway inflammation in asthma: current knowledge and therapeutic implications. Clin Exp Allergy. 2017;47(2):161–175. DOI:https://doi.org/10.1111/cea.12880
- Fahy JV. Type 2 inflammation in asthma-present in most, absent in many. Nat Rev Immunol. 2015;15(1):57–65. DOI:https://doi.org/10.1038/nri3786
- Kostikas K, Brindicci C, Patalano F. Blood eosinophils as biomarkers to drive treatment choices in asthma and COPD. Curr Drug Targets. 2018;19(16):1882–1896. DOI:https://doi.org/10.2174/1389450119666180212120012
- Tashkin DP, Wechsler ME. Role of eosinophils in airway inflammation of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2018;13:335–349. DOI:https://doi.org/10.2147/COPD.S152291
- Ying S, O’Connor B, Ratoff J, et al. Expression and cellular provenance of thymic stromal lymphopoietin and chemokines in patients with severe asthma and chronic obstructive pulmonary disease. J Immunol. 2008;181(4):2790–2798. DOI:https://doi.org/10.4049/jimmunol.181.4.2790
- Brusselle GG, Maes T, Bracke KR. Eosinophils in the spotlight: Eosinophilic airway inflammation in nonallergic asthma. Nat Med. 2013;19(8):977–979. DOI:https://doi.org/10.1038/nm.3300
- Rosenberg HF, Dyer KD, Foster PS. Eosinophils: changing perspectives in health and disease. Nat Rev Immunol. 2013;13(1):9–22. DOI:https://doi.org/10.1038/nri3341
- Lopez AF, Sanderson CJ, Gamble JR, et al. Recombinant human interleukin 5 is a selective activator of human eosinophil function. J Exp Med. 1988;167(1):219–224. DOI:https://doi.org/10.1084/jem.167.1.219
- Siva R, Green RH, Brightling CE, et al. Eosinophilic airway inflammation and exacerbations of COPD: a randomised controlled trial. Eur Respir J. 2007;29(5):906–913. DOI:https://doi.org/10.1183/09031936.00146306
- Bafadhel M, McKenna S, Terry S, et al. Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. Am J Respir Crit Care Med. 2011;184(6):662–671. DOI:https://doi.org/10.1164/rccm.201104-0597OC
- Bafadhel M, McKenna S, Terry S, et al. Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: a randomized placebo-controlled trial. Am J Respir Crit Care Med. 2012;186(1):48–55. DOI:https://doi.org/10.1164/rccm.201108-1553OC
- Sivapalan P, Lapperre TS, Janner J, et al. Eosinophil-guided corticosteroid therapy in patients admitted to hospital with COPD exacerbation (CORTICO-COP): a multicentre, randomised, controlled, open-label, non-inferiority trial. Lancet Respir Med. 2019;7(8):699–709. DOI:https://doi.org/10.1016/S2213-2600(19)30176-6
- Lapperre TS, Janner J, Laub RR, et al. Eosinophil-Guided Corticosteroid-Sparing Therapy in Hospitalized Patients with Exacerbated COPD(CORTICOsteroid Reduction in COPD (CORTICO-COP)): A Randomized Prospective Multicenter Investigator-Initiated Trial. B14. LATE BREAKING CLINICAL TRIALS. p. A7352–A7352.
- Bafadhel M, Davies L, Calverley PM, et al. Blood eosinophil guided prednisolone therapy for exacerbations of COPD: a further analysis. Eur Respir J. 2014;44(3):789–791. DOI:https://doi.org/10.1183/09031936.00062614
- Steer J, Gibson J, Bourke SC. The DECAF score: predicting hospital mortality in exacerbations of chronic obstructive pulmonary disease. Thorax. 2012;67(11):970–976. DOI:https://doi.org/10.1136/thoraxjnl-2012-202103
- Couillard S, Larivee P, Courteau J, et al. Eosinophils in COPD exacerbations are associated with increased readmissions. Chest. 2017;151(2):366–373. DOI:https://doi.org/10.1016/j.chest.2016.10.003
- Bafadhel M, Greening NJ, Harvey-Dunstan TC, et al. Blood eosinophils and outcomes in severe hospitalized exacerbations of COPD. Chest. 2016;150(2):320–328. DOI:https://doi.org/10.1016/j.chest.2016.01.026
- MacDonald MI, Osadnik CR, Bulfin L, et al. Low and high blood eosinophil counts as biomarkers in hospitalized acute exacerbations of COPD. Chest. 2019;156(1):92–100. DOI:https://doi.org/10.1016/j.chest.2019.02.406
- Kostikas K, Papathanasiou E, Papaioannou AI, et al. Blood eosinophils as predictor of outcomes in patients hospitalized for COPD exacerbations: a prospective observational study. Biomarkers. 2021;26(4):354–362. DOI:https://doi.org/10.1080/1354750X.2021.1903998
- Vedel-Krogh S, Nielsen SF, Lange P, et al. Blood eosinophils and exacerbations in chronic obstructive pulmonary disease. The Copenhagen general population study. Am J Respir Crit Care Med. 2016;193(9):965–974. DOI:https://doi.org/10.1164/rccm.201509-1869OC
- Yun JH, COPDGene and ECLIPSE Investigators, Lamb A, Chase R, et al. Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2018;141(6):2037–2047.e10.
- Casanova C, Celli BR, de-Torres JP, et al. Prevalence of persistent blood eosinophilia: relation to outcomes in patients with COPD. Eur Respir J. 2017;50(5):1701162. DOI:https://doi.org/10.1183/13993003.01162-2017
- Hastie AT, Martinez FJ, Curtis JL, et al. Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: an analysis of the SPIROMICS cohort. Lancet Respir Med. 2017;5(12):956–967. DOI:https://doi.org/10.1016/S2213-2600(17)30432-0
- Zysman M, Deslee G, Caillaud D, et al. Relationship between blood eosinophils, clinical characteristics, and mortality in patients with COPD. COPD. 2017;12:1819–1824. DOI:https://doi.org/10.2147/COPD.S129787
- Singh D, Wedzicha JA, Siddiqui S, et al. Blood eosinophils as a biomarker of future COPD exacerbation risk: pooled data from 11 clinical trials. Respir Res. 2020;21(1):240. DOI:https://doi.org/10.1186/s12931-020-01482-1
- Kerkhof M, Sonnappa S, Postma DS, et al. Blood eosinophil count and exacerbation risk in patients with COPD. Eur Respir J. 2017;50(1):1700761. DOI:https://doi.org/10.1183/13993003.00761-2017
- Pascoe S, Locantore N, Dransfield MT, et al. 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. Lancet Respir Med. 2015;3(6):435–442. DOI:https://doi.org/10.1016/S2213-2600(15)00106-X
- Siddiqui SH, 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:https://doi.org/10.1164/rccm.201502-0235LE
- Bafadhel M, Peterson S, De Blas MA, et al. Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomised trials. Lancet Respir Med. 2018;6(2):117–126. DOI:https://doi.org/10.1016/S2213-2600(18)30006-7
- Roche N, Chapman KR, Vogelmeier CF, et al. Blood eosinophils and response to maintenance chronic obstructive pulmonary disease treatment. Data from the FLAME trial. Am J Respir Crit Care Med. 2017;195(9):1189–1197. DOI:https://doi.org/10.1164/rccm.201701-0193OC
- Wedzicha JA, Banerji D, Chapman KR, et al. Indacaterol-glycopyrronium versus salmeterol-fluticasone for COPD. N Engl J Med. 2016;374(23):2222–2234. DOI:https://doi.org/10.1056/NEJMoa1516385
- Papi A, Kostikas K, Wedzicha JA, et al. Dual bronchodilation response by exacerbation history and eosinophilia in the FLAME study. Am J Respir Crit Care Med. 2018;197(9):1223–1226. DOI:https://doi.org/10.1164/rccm.201709-1822LE
- GOLD Reports. 2021. [Internet]. 2020 [cited 2021 May 5]. Available from: https://goldcopd.org/2021-gold-reports/.
- Papi A, Vestbo J, Fabbri L, et al. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial. Lancet. 2018;391(10125):1076–1084. DOI:https://doi.org/10.1016/S0140-6736(18)30206-X
- Lipson DA, Barnhart F, Brealey N, et al. Once-Daily Single-Inhaler triple versus dual therapy in patients with COPD. N Engl J Med. 2018;378(18):1671–1680. DOI:https://doi.org/10.1056/NEJMoa1713901
- Rabe KF, Martinez FJ, Ferguson GT, et al. Triple inhaled therapy at two glucocorticoid doses in moderate-to-Very-Severe COPD. N Engl J Med. 2020;383(1):35–48. DOI:https://doi.org/10.1056/NEJMoa1916046
- Pascoe S, Barnes N, Brusselle G, et al. Blood eosinophils and treatment response with triple and dual combination therapy in chronic obstructive pulmonary disease: analysis of the IMPACT trial. Lancet Respir Med. 2019;7(9):745–756. DOI:https://doi.org/10.1016/S2213-2600(19)30190-0
- Halpin DMG, Vogelmeier CF, Mezzi K, et al. Efficacy of indacaterol/glycopyrronium versus salmeterol/fluticasone in current and ex-smokers: a pooled analysis of IGNITE trials. ERJ Open Res. 2021;7(1):00816–2020. DOI:https://doi.org/10.1183/23120541.00816-2020
- Suissa S, Dell’Aniello S, Ernst P. Comparative effects of LAMA-LABA-ICS vs LAMA-LABA for COPD: Cohort study in Real-World clinical practice. Chest. 2020;157(4):846–855. DOI:https://doi.org/10.1016/j.chest.2019.11.007
- Voorham J, Corradi M, Papi A, et al. Comparative effectiveness of triple therapy versus dual bronchodilation in COPD. ERJ Open Res. 2019;5(3):00106–2019. DOI:https://doi.org/10.1183/23120541.00106-2019
- Nici L, Mammen MJ, Charbek E, et al. Pharmacologic management of chronic obstructive pulmonary disease. An official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020;201(9):e56–e69. DOI:https://doi.org/10.1164/rccm.202003-0625ST
- Overview | Chronic obstructive pulmonary disease in over 16s: diagnosis and management | Guidance | NICE. NICE; 2021. [cited 2021 May 8]; Available from: https://www.nice.org.uk/guidance/ng115.
- Suissa S, Patenaude V, Lapi F, et al. Inhaled corticosteroids in COPD and the risk of serious pneumonia. Thorax. 2013;68(11):1029–1036. DOI:https://doi.org/10.1136/thoraxjnl-2012-202872
- Contoli M, Pauletti A, Rossi MR, et al. Long-term effects of inhaled corticosteroids on sputum bacterial and viral loads in COPD. Eur Respir J. 2017;50(4):1700451. DOI:https://doi.org/10.1183/13993003.00451-2017
- Brode SK, Campitelli MA, Kwong JC, et al. The risk of mycobacterial infections associated with inhaled corticosteroid use. Eur Respir J. 2017;50(3):1700037. DOI:https://doi.org/10.1183/13993003.00037-2017
- Price DB, Voorham J, Brusselle G, et al. Inhaled corticosteroids in COPD and onset of type 2 diabetes and osteoporosis: matched cohort study. NPJ Prim Care Respir Med. 2019;29(1):38.
- Gonzalez AV, Coulombe J, Ernst P, et al. Long-term use of inhaled corticosteroids in COPD and the risk of fracture. Chest. 2018;153(2):321–328. DOI:https://doi.org/10.1016/j.chest.2017.07.002
- Chalmers JD, Laska IF, Franssen FME, et al. Withdrawal of inhaled corticosteroids in COPD: a european respiratory society guideline. Eur Respir J. 2020;55(6):2000351. DOI:https://doi.org/10.1183/13993003.00351-2020
- Watz H, Tetzlaff K, Wouters EF, et al. Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal of inhaled corticosteroids: a post-hoc analysis of the WISDOM trial. Lancet Respir Med. 2016;4(5):390–398. DOI:https://doi.org/10.1016/S2213-2600(16)00100-4
- Chapman KR, Hurst JR, Frent SM, et al. Long-term triple therapy de-escalation to indacaterol/glycopyrronium in patients with chronic obstructive pulmonary disease (SUNSET): a randomized, Double-Blind, Triple-Dummy clinical trial. Am J Respir Crit Care Med. 2018;198(3):329–339. DOI:https://doi.org/10.1164/rccm.201803-0405OC
- Magnussen H, Disse B, Rodriguez-Roisin R, et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med. 2014;371(14):1285–1294. DOI:https://doi.org/10.1056/NEJMoa1407154
- Wedzicha JA, Banerji D, Kostikas K. Single-Inhaler triple versus dual therapy in patients with COPD. N Engl J Med. 2018;379(6):591. DOI:https://doi.org/10.1056/NEJMc1807380
- Brusselle GG, Bracke K, Lahousse L. Targeted therapy with inhaled corticosteroids in COPD according to blood eosinophil counts. Lancet Respir Med. 2015;3(6):416–417. DOI:https://doi.org/10.1016/S2213-2600(15)00145-9
- Agusti A, Fabbri LM, Singh D, et al. Inhaled corticosteroids in COPD: friend or foe? Eur Respir J. 2018;52(6):1801219. DOI:https://doi.org/10.1183/13993003.01219-2018
- Stolz D, Miravitlles M. The right treatment for the right patient with COPD: lessons from the IMPACT trial. Eur Respir J. 2020;55(5):2000881. DOI:https://doi.org/10.1183/13993003.00881-2020
- Vogelmeier CF, Chapman KR, Miravitlles M, et al. Exacerbation heterogeneity in COPD: subgroup analyses from the FLAME study. Int J Chron Obstruct Pulmon Dis. 2018;13:1125–1134. DOI:https://doi.org/10.2147/COPD.S160011
- van Bragt J, Vijverberg SJH, Weersink EJM, et al. Blood biomarkers in chronic airways diseases and their role in diagnosis and management. Expert Rev Respir Med. 2018;12(5):361–374. DOI:https://doi.org/10.1080/17476348.2018.1457440
- Schleich F, Corhay JL, Louis R. Blood eosinophil count to predict bronchial eosinophilic inflammation in COPD. Eur Respir J. 2016;47(5):1562–1564. DOI:https://doi.org/10.1183/13993003.01659-2015
- Turato G, Semenzato U, Bazzan E, et al. Blood eosinophilia neither reflects tissue eosinophils nor worsens clinical outcomes in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2018;197(9):1216–1219. DOI:https://doi.org/10.1164/rccm.201708-1684LE
- Vogelmeier CF, Kostikas K, Fang J, et al. Evaluation of exacerbations and blood eosinophils in UK and US COPD populations. Respir Res. 2019;720(1):178. DOI:https://doi.org/10.1186/s12931-019-1130-y
- Oshagbemi OA, Burden AM, Braeken DCW, 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. Am J Respir Crit Care Med. 2017;195(10):1402–1404. DOI:https://doi.org/10.1164/rccm.201701-0009LE
- Schumann DM, Tamm M, Kostikas K, et al. Stability of the blood eosinophilic phenotype in stable and exacerbated COPD. Chest. 2019;156(3):456–465. DOI:https://doi.org/10.1016/j.chest.2019.04.012
- Hamad GA, Cheung W, Crooks MG, et al. Eosinophils in COPD: how many swallows make a summer? Eur Respir J. 2018;51(1):1702177. DOI:https://doi.org/10.1183/13993003.02177-2017
- Martinez FJ, Rabe KF, Calverley PMA, et al. Determinants of response to roflumilast in severe chronic obstructive pulmonary disease. Pooled analysis of two randomized trials. Am J Respir Crit Care Med. 2018;198(10):1268–1278. DOI:https://doi.org/10.1164/rccm.201712-2493OC
- Pavord ID, Chanez P, Criner GJ, et al. Mepolizumab for eosinophilic chronic obstructive pulmonary disease. N Engl J Med. 2017;377(17):1613–1629. DOI:https://doi.org/10.1056/NEJMoa1708208
- Brightling CE, Bleecker ER, Panettieri RA, Jr, et al. Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study. Lancet Respir Med. 2014;2(11):891–901. DOI:https://doi.org/10.1016/S2213-2600(14)70187-0
- Criner GJ, Celli BR, Brightling CE, et al. Benralizumab for the prevention of COPD exacerbations. N Engl J Med. 2019;381(11):1023–1034. DOI:https://doi.org/10.1056/NEJMoa1905248
- Criner GJ, Celli BR, Singh D, et al. Predicting response to benralizumab in chronic obstructive pulmonary disease: analyses of GALATHEA and TERRANOVA studies. Lancet Respir Med. 2020;8(2):158–170. DOI:https://doi.org/10.1016/S2213-2600(19)30338-8
- Efficacy and Safety of Benralizumab in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With a History of Frequent Exacerbations - Full Text View - ClinicalTrials.Gov [Internet]. [cited 2021 May 8]. Available from: https://clinicaltrials.gov/ct2/show/NCT04053634.
- Case medical research. Mepolizumab as add-on treatment in participants with COPD characterized by frequent exacerbations and eosinophil level (MATINEE). Case Med Res [Internet] Case J. 2019. [cited 2021 May 8]; Available from: https://clinicaltrials.gov/ct2/show/NCT04133909.
- Pivotal Study to Assess the Efficacy, Safety and Tolerability of Dupilumab in Patients With Moderate to Severe COPD With Type 2 Inflammation - Full Text View - ClinicalTrials.Gov [Internet]. [cited 2021 May 8]. Available from: https://clinicaltrials.gov/ct2/show/NCT04456673.