嗜酸性粒细胞在慢性阻塞性肺疾病中的临床研究进展
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摘要
嗜酸性粒细胞在慢性阻塞性肺疾病(简称慢阻肺)患者中的作用近年来备受关注。研究发现在部分慢阻肺稳定期和急性加重期患者的循环血、气道、肺组织中均可发现嗜酸性粒细胞增高。近期的研究显示嗜酸性粒细胞与慢阻肺患者急性加重风险升高、病死率升高、肺功能下降有关,并可预测慢阻肺患者对糖皮质激素的治疗反应。该文主要综述嗜酸性粒细胞在慢阻肺患者中作为生物标志物的研究进展。
The role of eosinophils in patients with chronic obstructive pulmonary disease(COPD) has attracted much attention in recent years.Researchers have found that eosinophils are elevated in blood,airway and lung tissues in both stable and acute exacerbated COPD patients.Recent studies have showed that eosinophils are associated with the risk of acute exacerbation,mortality and lung function decline,and that eosinophils can predict the therapeutic response to glucocorticoids in patients with COPD.This review focuses on the research progress of eosinophils as a biomarker in COPD.
The role of eosinophils in patients with chronic obstructive pulmonary disease(COPD) has attracted much attention in recent years.Researchers have found that eosinophils are elevated in blood,airway and lung tissues in both stable and acute exacerbated COPD patients.Recent studies have showed that eosinophils are associated with the risk of acute exacerbation,mortality and lung function decline,and that eosinophils can predict the therapeutic response to glucocorticoids in patients with COPD.This review focuses on the research progress of eosinophils as a biomarker in COPD.
引文
1 Beeh KM,Beier J,Kornmann O,et al.Long-term repeatability of induced sputum cells and inflammatory markers in stable,moderately severe COPD[J].Chest,2003,123(3):778-783.
2 Brightling CE,Monterio W,Green RH,et al.Induced sputum and other outcome measures in chronic obstructive pulmonary disease:safety and repeatability[J].Respir Med,2001,95(12):999-1002.
3 Singh D,Kolsum U,Brightling CE,et al.Eosinophilic inflammation in COPD:prevalence and clinical characteristics[J].Eur Respir J,2014,44(6):1697-1700.
4 Bafadhel M,Mc Kenna S,Terry S,et al.Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease:a randomized placebo-controlled trial[J].Am J Respir Crit Care Med,2012,186(1):48-55.
5 Bafadhel M,Mc Kenna S,Terry S,et al.Acute exacerbations of chronic obstructive pulmonary disease:identification of biologic clusters and their biomarkers[J].Am J Respir Crit Care Med,2011,184(6):662-671.
6 Britton J,Pavord I,Richards K,et al.Factors influencing the occurrence of airway hyperreactivity in the general population:the importance of atopy and airway calibre[J].Eur Respir J,1994,7(5):881-887.
7 Anand A,Ahmed O,Pavord ID,et al.Blood eosinophil counts in normal controls with no history of allergic disease[J].Thorax,2015,70:A111.
8 Hospers JJ,Rijcken P,Schouten JP,et al.Eosinophilia and positive skin tests predict cardiovascular mortality in a general population sample followed for 30 years[J].Am J Epidemiol,1999,150(5):482-491.
9 Hospers JJ,Schouten JP,Weiss ST,et al.Eosinophilia is associated with increased all-cause mortality after a follow-up of 30 years in a general population sample[J].Epidemiology,2000,11(3):261-268.
10 Hospers JJ,Schouten JP,Weiss ST,et al.Asthma attacks with eosinophilia predict mortality from chronic obstructive pulmonary disease in a general population sample[J].Am J Respir Crit Care Med,1999,160(6):1869-1874.
11 Vedel-Krogh S,Nielsen SF,Lange P,et al.Blood Eosinophils and Exacerbations in Chronic Obstructive Pulmonary Disease.The Copenhagen General Population Study[J].Am J Respir Crit Care Med,2016,193(9):965-974.
12 Barnes NC,Sharma R,Lettis S,et al.Blood eosinophils as a marker of response to inhaled corticosteroids in COPD[J].Eur Respir J,2016,47(5):1374-1382.
13 Rogliani P,Puxeddu E,Ciaprini C,et al.The Time Course of Pulmonary Function Tests in COPD Patients with Different Levels of Blood Eosinophils[J].Biomed Res Int,2016,2016:4547953.
14 Shim C,Stover DE,Williams MH Jr.Response to corticosteroids in chronic bronchitis[J].J Allergy Clin Immunol,1978,62(6):363-367.
15 Leigh R,Pizzichini MM,Morris MM,et al.Stable COPD:predicting benefit from high-dose inhaled corticosteroid treatment[J].Eur Respir J,2006,27(5):964-971.
16 Pizzichini E,Pizzichini MM,Gibson P,et al.Sputum eosinophilia predicts benefit from prednisone in smokers with chronic obstructive bronchitis[J].Am J Respir Crit Care Med,1998,158(5 Pt 1):1511-1517.
17 Brightling CE,Mc Kenna S,Hargadon B,et al.Sputum eosinophilia and the short term response to inhaled mometasone in chronic obstructive pulmonary disease[J].Thorax,2005,60(3):193-198.
18 Siva R,Green RH,Brightling CE,et al.Eosinophilic airway inflammation and exacerbations of COPD:a randomised controlled trial[J].Eur Respir J,2007,29(5):906-913.
19 Singh D,Papi A,Corradi M,et al.Single inhaler triple therapy versus inhaled corticosteroid plus long-actingβ2-agonist therapy for chronic obstructive pulmonary disease(TRILOGY):a double-blind,parallel group,randomised controlled trial[J].Lancet,2016,388(10048):963-973.
20 Calverley PM,Boonsawat W,Cseke Z,et al.Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease[J].Eur Respir J,2003,22(6):912-919.
21 Calverley P,Pauwels R,Vestbo J,et al.Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease:a randomised controlled trial[J].Lancet,2003,361(9356):449-456.
22 Dransfield MT,Bourbeau J,Jones PW,et al.Once-daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD:two replicate double-blind,parallelgroup,randomised controlled trials[J].Lancet Respir Med,2013,1(3):210-223.
23 Wedzicha JA,Singh D,Vestbo J,et al.Extrafine beclomethasone/formoterol in severe COPD patients with history of exacerbations[J].Respir Med,2014,108(8):1153-1162.
24 Burge PS,Calverley PM,Jones PW,et al.Randomised,double blind,placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease:the ISOLDE trial[J].BMJ,2000,320(7245):1297-1303.
25 Wedzicha JA,Calverley PMA,Seemungal TA,et al.The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide[J].Am J Respir Crit Care Med,2008,177(1):19-26.
26 Calverley PM,Anderson JA,Celli B,et al.Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease[J].N Engl J Med,2007,356(8):775-789.
27 Vestbo J,Anderson JA,Brook RD,et al.Fluticasone furoate and vilanterol and survival in chronic obstructive pulmonary disease with heightened cardiovascular risk(SUMMIT):a double-blind randomised controlled trial[J].Lancet,2016,387(10030):1817-1826.
28 Suissa S.Number needed to treat in COPD:exacerbations versus pneumonias[J].Thorax,2013,68(6):540-543.
29 Janson C,Larsson K,Lisspers KH,et al.Pneumonia and pneumonia related mortality in patients with COPD treated with fixed combinations of inhaled corticosteroid and long actingβ2 agonist:observational matched cohort study(PATHOS)[J].BMJ,2013,346:f3306.
30 Suissa S,Patenaude V,Lapi F,et al.Inhaled corticosteroids in COPD and the risk of serious pneumonia[J].Thorax,2013,68(11):1029-1036.
31 Magnussen H,Disse B,Rodriguez-Roisin R,et al.Withdrawal of inhaled glucocorticoids and exacerbations of COPD[J].N Engl JMed,2014,371(14):1285-1294.
32 Zhong N,Wang C,Zhou X,et al.LANTERN:a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD[J].Int J Chron Obstruct Pulmon Dis,2015,10:1015-1026.
33 Vogelmeier CF,Bateman ED,Pallante J,et al.Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol-fluticasone in patients with chronic obstructive pulmonary disease(ILLU-MINATE):a randomised,double-blind,parallel group study[J].Lancet Respir Med,2013,1(1):51-60.
34 Wedzicha JA,Banerji D,Chapman KR,et al.Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD[J].N Engl JMed,2016,374(23):2222-2234.
35 Vogelmeier CF,Criner GJ,Martinez FJ,et al.Global Strategy for the Diagnosis,Management,and Prevention of Chronic Obstructive Lung Disease 2017 Report.GOLD Executive Summary[J].Am JRespir Crit Care Med,2017,195(5):557-582.
36 Saetta M,Di Stefano A,Maestrelli P,et al.Airway eosinophilia in chronic bronchitis during exacerbations[J].Am J Respir Crit Care Med,1994,150(6 Pt 1):1646-1652.
37 Bathoorn E,Liesker JJW,Postma DS,et al.Change in inflammation in out-patient COPD patients from stable phase to a subsequent exacerbation[J].Int J Chron Obstruct Pulmon Dis,2009,4:101-109.
38 Bafadhel M,Davies L,Calverley PM,et al.Blood eosinophil guided prednisolone therapy for exacerbations of COPD:a further analysis[J].Eur Respir J,2014,44(3):789-791.
39 Couillard S,Larivée P,Courteau J,et al.Eosinophils in COPD Exacerbations Are Associated With Increased Readmissions[J].Chest,2017,151(2):366-373.
40 Bafadhel M,Greening NJ,Harvey-Dunstan TC,et al.Blood Eosinophils and Outcomes in Severe Hospitalized Exacerbations of COPD[J].Chest,2016,150(2):320-328.
2 Brightling CE,Monterio W,Green RH,et al.Induced sputum and other outcome measures in chronic obstructive pulmonary disease:safety and repeatability[J].Respir Med,2001,95(12):999-1002.
3 Singh D,Kolsum U,Brightling CE,et al.Eosinophilic inflammation in COPD:prevalence and clinical characteristics[J].Eur Respir J,2014,44(6):1697-1700.
4 Bafadhel M,Mc Kenna S,Terry S,et al.Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease:a randomized placebo-controlled trial[J].Am J Respir Crit Care Med,2012,186(1):48-55.
5 Bafadhel M,Mc Kenna S,Terry S,et al.Acute exacerbations of chronic obstructive pulmonary disease:identification of biologic clusters and their biomarkers[J].Am J Respir Crit Care Med,2011,184(6):662-671.
6 Britton J,Pavord I,Richards K,et al.Factors influencing the occurrence of airway hyperreactivity in the general population:the importance of atopy and airway calibre[J].Eur Respir J,1994,7(5):881-887.
7 Anand A,Ahmed O,Pavord ID,et al.Blood eosinophil counts in normal controls with no history of allergic disease[J].Thorax,2015,70:A111.
8 Hospers JJ,Rijcken P,Schouten JP,et al.Eosinophilia and positive skin tests predict cardiovascular mortality in a general population sample followed for 30 years[J].Am J Epidemiol,1999,150(5):482-491.
9 Hospers JJ,Schouten JP,Weiss ST,et al.Eosinophilia is associated with increased all-cause mortality after a follow-up of 30 years in a general population sample[J].Epidemiology,2000,11(3):261-268.
10 Hospers JJ,Schouten JP,Weiss ST,et al.Asthma attacks with eosinophilia predict mortality from chronic obstructive pulmonary disease in a general population sample[J].Am J Respir Crit Care Med,1999,160(6):1869-1874.
11 Vedel-Krogh S,Nielsen SF,Lange P,et al.Blood Eosinophils and Exacerbations in Chronic Obstructive Pulmonary Disease.The Copenhagen General Population Study[J].Am J Respir Crit Care Med,2016,193(9):965-974.
12 Barnes NC,Sharma R,Lettis S,et al.Blood eosinophils as a marker of response to inhaled corticosteroids in COPD[J].Eur Respir J,2016,47(5):1374-1382.
13 Rogliani P,Puxeddu E,Ciaprini C,et al.The Time Course of Pulmonary Function Tests in COPD Patients with Different Levels of Blood Eosinophils[J].Biomed Res Int,2016,2016:4547953.
14 Shim C,Stover DE,Williams MH Jr.Response to corticosteroids in chronic bronchitis[J].J Allergy Clin Immunol,1978,62(6):363-367.
15 Leigh R,Pizzichini MM,Morris MM,et al.Stable COPD:predicting benefit from high-dose inhaled corticosteroid treatment[J].Eur Respir J,2006,27(5):964-971.
16 Pizzichini E,Pizzichini MM,Gibson P,et al.Sputum eosinophilia predicts benefit from prednisone in smokers with chronic obstructive bronchitis[J].Am J Respir Crit Care Med,1998,158(5 Pt 1):1511-1517.
17 Brightling CE,Mc Kenna S,Hargadon B,et al.Sputum eosinophilia and the short term response to inhaled mometasone in chronic obstructive pulmonary disease[J].Thorax,2005,60(3):193-198.
18 Siva R,Green RH,Brightling CE,et al.Eosinophilic airway inflammation and exacerbations of COPD:a randomised controlled trial[J].Eur Respir J,2007,29(5):906-913.
19 Singh D,Papi A,Corradi M,et al.Single inhaler triple therapy versus inhaled corticosteroid plus long-actingβ2-agonist therapy for chronic obstructive pulmonary disease(TRILOGY):a double-blind,parallel group,randomised controlled trial[J].Lancet,2016,388(10048):963-973.
20 Calverley PM,Boonsawat W,Cseke Z,et al.Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease[J].Eur Respir J,2003,22(6):912-919.
21 Calverley P,Pauwels R,Vestbo J,et al.Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease:a randomised controlled trial[J].Lancet,2003,361(9356):449-456.
22 Dransfield MT,Bourbeau J,Jones PW,et al.Once-daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD:two replicate double-blind,parallelgroup,randomised controlled trials[J].Lancet Respir Med,2013,1(3):210-223.
23 Wedzicha JA,Singh D,Vestbo J,et al.Extrafine beclomethasone/formoterol in severe COPD patients with history of exacerbations[J].Respir Med,2014,108(8):1153-1162.
24 Burge PS,Calverley PM,Jones PW,et al.Randomised,double blind,placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease:the ISOLDE trial[J].BMJ,2000,320(7245):1297-1303.
25 Wedzicha JA,Calverley PMA,Seemungal TA,et al.The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide[J].Am J Respir Crit Care Med,2008,177(1):19-26.
26 Calverley PM,Anderson JA,Celli B,et al.Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease[J].N Engl J Med,2007,356(8):775-789.
27 Vestbo J,Anderson JA,Brook RD,et al.Fluticasone furoate and vilanterol and survival in chronic obstructive pulmonary disease with heightened cardiovascular risk(SUMMIT):a double-blind randomised controlled trial[J].Lancet,2016,387(10030):1817-1826.
28 Suissa S.Number needed to treat in COPD:exacerbations versus pneumonias[J].Thorax,2013,68(6):540-543.
29 Janson C,Larsson K,Lisspers KH,et al.Pneumonia and pneumonia related mortality in patients with COPD treated with fixed combinations of inhaled corticosteroid and long actingβ2 agonist:observational matched cohort study(PATHOS)[J].BMJ,2013,346:f3306.
30 Suissa S,Patenaude V,Lapi F,et al.Inhaled corticosteroids in COPD and the risk of serious pneumonia[J].Thorax,2013,68(11):1029-1036.
31 Magnussen H,Disse B,Rodriguez-Roisin R,et al.Withdrawal of inhaled glucocorticoids and exacerbations of COPD[J].N Engl JMed,2014,371(14):1285-1294.
32 Zhong N,Wang C,Zhou X,et al.LANTERN:a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD[J].Int J Chron Obstruct Pulmon Dis,2015,10:1015-1026.
33 Vogelmeier CF,Bateman ED,Pallante J,et al.Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol-fluticasone in patients with chronic obstructive pulmonary disease(ILLU-MINATE):a randomised,double-blind,parallel group study[J].Lancet Respir Med,2013,1(1):51-60.
34 Wedzicha JA,Banerji D,Chapman KR,et al.Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD[J].N Engl JMed,2016,374(23):2222-2234.
35 Vogelmeier CF,Criner GJ,Martinez FJ,et al.Global Strategy for the Diagnosis,Management,and Prevention of Chronic Obstructive Lung Disease 2017 Report.GOLD Executive Summary[J].Am JRespir Crit Care Med,2017,195(5):557-582.
36 Saetta M,Di Stefano A,Maestrelli P,et al.Airway eosinophilia in chronic bronchitis during exacerbations[J].Am J Respir Crit Care Med,1994,150(6 Pt 1):1646-1652.
37 Bathoorn E,Liesker JJW,Postma DS,et al.Change in inflammation in out-patient COPD patients from stable phase to a subsequent exacerbation[J].Int J Chron Obstruct Pulmon Dis,2009,4:101-109.
38 Bafadhel M,Davies L,Calverley PM,et al.Blood eosinophil guided prednisolone therapy for exacerbations of COPD:a further analysis[J].Eur Respir J,2014,44(3):789-791.
39 Couillard S,Larivée P,Courteau J,et al.Eosinophils in COPD Exacerbations Are Associated With Increased Readmissions[J].Chest,2017,151(2):366-373.
40 Bafadhel M,Greening NJ,Harvey-Dunstan TC,et al.Blood Eosinophils and Outcomes in Severe Hospitalized Exacerbations of COPD[J].Chest,2016,150(2):320-328.