Cytologic Profile of Induced Sputum and Its Relationship with Treatment Response in Patients with Chronic Obstructive Pulmonary Disease_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

LiuWei ^# ,  ChenRongchang

State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, Department of Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China;

Corresponding author：

ChenRongchang, Email: rongchangchencn@126.com

Keywords：

Chronic obstructive pulmonary disease; Induced sputum; Eosinophil; Treatment response

DOI：

10.7507/1671-6205.2016124

Video：

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Objective To explore the cytologic profile of induced sputum and its relationship with the treatment response in patients with chronic obstructive pulmonary disease (COPD). Methods Sixty-five treatment-naive patients with COPD and 26 normal subjects were recruited for the study. Sputums induced by the inhalation of hypertonic saline were collected, and the associations of differential cell counting were analyzed with pulmonary function, modified Medical Research Council dyspnea scale, St. George's Respiratory Questionnaire score (SGRQ) before and after the treatment with inhaled corticosteroid and long-acting β₂-agonist. Results The cell percentages of neutrophil (Neu), macrophage, eosinophil (Eos) and lymphocyte in induced sputum of the COPD patients were (86.24±15.04)%, (5.75±6.96)%, (4.71±4.79)%, and (1.30±1.09)%, respectively. The eosinophil percentage (Eos%) was≥3% in 31 patients (60.78%). The neutrophil percentage (Neu%) was inversely correlated with forced expiratory volume in 1 second (FEV₁), percent of predicted value of FEV₁ (FEV₁% pred), forced vital capacity (FVC), and percent of predicted value of FVC (FVC% pred) (P < 0.01, respectively), and positively correlated with the SGRQ symptom score (r=0.304, P=0.034). The Eos% was inversely correlated with FEV₁/FVC ratio (r=-0.399, P=0.004). The patients with Eos%≥3% improved significantly in FEV₁ and symptom score (P < 0.05, respectively) than the patients with Eos% < 3%. Conclusions An eosinophilic airway inflammation is present in a subgroup of COPD. The Eos% is inversely correlated with pulmonary function and may be a predictive indicator of response to treatment with inhaled corticosteroids and long-acting β₂-agonists.

Citation： LiuWei, ChenRongchang. Cytologic Profile of Induced Sputum and Its Relationship with Treatment Response in Patients with Chronic Obstructive Pulmonary Disease. Chinese Journal of Respiratory and Critical Care Medicine, 2016, 15(6): 537-541. doi: 10.7507/1671-6205.2016124 Copy

1.	Negewo NA, McDonald VM, Baines KJ, et al. Peripheral blood eosinophils:a surrogate marker for airway eosinophilia in stable COPD. Int J Chron Obstruct Pulmon Dis, 2016, 11:1495-1504.
2.	Zanini A, Cherubino F, Zampogna E, et al. Bronchial hyperresponsiveness, airway inflammation, and reversibility in patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis, 2015, 10:1155-1161.
3.	Brightling CE, Monteiro W, Ward R, et al. Sputum eosinophilia and short-term response to prednisolone in chronic obstructive pulmonary disease:a randomised controlled trial. Lancet, 2000, 356:1480-1485.
4.	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, 2:891-901.
5.	Barnes NC, Sharma R, Lettis S, et al. Blood eosinophils as a marker of response to inhaled corticosteroids in COPD. Eur Respir J, 2016, 47:1374-1382.
6.	Kang HS, Rhee CK, Kim SK, et al. Comparison of the clinical characteristics and treatment outcomes of patients requiring hospital admission to treat eosinophilic and neutrophilic exacerbations of COPD. Int J Chron Obstruct Pulmon Dis, 2016, 11:2467-2473.
7.	Bafadhel M, Greening NJ, Harvey-Dunstan TC, et al. Blood eosinophils and outcomes in severe hospitalized exacerbations of COPD. Chest, 2016, 150:320-328.
8.	Eltboli O, Bafadhel M, Hollins F, et al. COPD exacerbation severity and frequency is associated with impaired macrophage efferocytosis of eosinophils. BMC Pulmon Med, 2014, 14:112-121.
9.	Duman D, Aksoy E, Agca MC, et al. The utility of inflammatory markers to predict readmissions and mortality in COPD cases with or without eosinophilia. Int J Chron Obstruct Pulmon Dis, 2015, 10:2469-2478.
10.	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. Epidemiology, 2000, 11:261-268.
11.	Siva R, Green RH, Brightling CE, et al. Eosinophilic airway inflammation and exacerbations of COPD:a randomized controlled trial. Eur Respir J, 2007, 29:906-913.
12.	Soter S, Barta I, Antus B. Predicting sputum eosinophilia in exacerbations of COPD using exhaled nitric oxide. Inflammation, 2013, 36:1178-1185.
13.	中华医学会呼吸病学分会慢性阻塞性肺疾病学组.慢性阻塞性肺疾病诊治指南(2013年修订版).中华结核和呼吸杂志, 2013, 36:255-264.
14.	张伟兵, 王欣燕, 田晓彦, 等.ADAM33基因多态性影响慢性阻塞性肺疾病气道炎症.中国呼吸与危重监护杂志, 2012, 11:15-18.
15.	郑劲平.关于制定我国用力肺功能检测质量控制指引的建议.中华结核和呼吸杂志, 2004, 27:716-717.
16.	Celli BR, MacNee W, ATS/ERS Task Force. Standards for the diagnosis and treatment of patients with COPD:a summary of the ATS/ERS position paper. Eur Respir J, 2004, 23:932-946.
17.	Djukanovi Ac'G R, Sterk PJ, Fahy JV, et al. Standardised methodology of sputum inductionf and processing. Eur Respir J Suppl, 2002, 37:1s-2s.
18.	Perng DW, Huang HY, Chen HM, et al. Characteristics of airway inflammation and bronchodilator reversibility in COPD:a potential guide to treatment. Chest, 2004, 126:375-381.
19.	罗炜, 赖克方, 钟南山.诱导痰检测的方法学及其在气道炎症评价中的应用.国外医学呼吸系统分册, 2004, 24:395-397.
20.	Davidson WJ, Verity WS, Traves SL, et al. Effect of incremental exercise on airway and systemic inflammation in patients with COPD. J Appl Physiol, 2012, 112:2049-2056.
21.	Liesker JJ, Bathoorn E, Postma DS, et al. Sputum inflammation predicts exacerbations after cessation of inhaled corticosteroids in COPD. Respir Med, 2011, 105:1853-1860.
22.	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, 186:48-55.
23.	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, 184:662-671.
24.	Brightling CE, McKenna S, Hargadon B, et al. Sputum eosinophilia and the short term response to inhaled mometasone in chronic obstructive pulmonary disease. Thorax, 2005, 60:193-198.
25.	Ernst P, Saad N, Suissa S. Inhaled corticosteroids in COPD:the clinical evidence. Eur Respir J, 2015, 45:525-37.
26.	Vestbo J, Pauwels R, Anderson JA, et al. Early onset of effect of salmeterol and fluticasone propionate in chronic obstructive pulmonary disease. Thorax, 2005, 60:301-314.

1. Negewo NA, McDonald VM, Baines KJ, et al. Peripheral blood eosinophils:a surrogate marker for airway eosinophilia in stable COPD. Int J Chron Obstruct Pulmon Dis, 2016, 11:1495-1504.
2. Zanini A, Cherubino F, Zampogna E, et al. Bronchial hyperresponsiveness, airway inflammation, and reversibility in patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis, 2015, 10:1155-1161.
3. Brightling CE, Monteiro W, Ward R, et al. Sputum eosinophilia and short-term response to prednisolone in chronic obstructive pulmonary disease:a randomised controlled trial. Lancet, 2000, 356:1480-1485.
4. 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, 2:891-901.
5. Barnes NC, Sharma R, Lettis S, et al. Blood eosinophils as a marker of response to inhaled corticosteroids in COPD. Eur Respir J, 2016, 47:1374-1382.
6. Kang HS, Rhee CK, Kim SK, et al. Comparison of the clinical characteristics and treatment outcomes of patients requiring hospital admission to treat eosinophilic and neutrophilic exacerbations of COPD. Int J Chron Obstruct Pulmon Dis, 2016, 11:2467-2473.
7. Bafadhel M, Greening NJ, Harvey-Dunstan TC, et al. Blood eosinophils and outcomes in severe hospitalized exacerbations of COPD. Chest, 2016, 150:320-328.
8. Eltboli O, Bafadhel M, Hollins F, et al. COPD exacerbation severity and frequency is associated with impaired macrophage efferocytosis of eosinophils. BMC Pulmon Med, 2014, 14:112-121.
9. Duman D, Aksoy E, Agca MC, et al. The utility of inflammatory markers to predict readmissions and mortality in COPD cases with or without eosinophilia. Int J Chron Obstruct Pulmon Dis, 2015, 10:2469-2478.
10. 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. Epidemiology, 2000, 11:261-268.
11. Siva R, Green RH, Brightling CE, et al. Eosinophilic airway inflammation and exacerbations of COPD:a randomized controlled trial. Eur Respir J, 2007, 29:906-913.
12. Soter S, Barta I, Antus B. Predicting sputum eosinophilia in exacerbations of COPD using exhaled nitric oxide. Inflammation, 2013, 36:1178-1185.
13. 中华医学会呼吸病学分会慢性阻塞性肺疾病学组.慢性阻塞性肺疾病诊治指南(2013年修订版).中华结核和呼吸杂志, 2013, 36:255-264.
14. 张伟兵, 王欣燕, 田晓彦, 等.ADAM33基因多态性影响慢性阻塞性肺疾病气道炎症.中国呼吸与危重监护杂志, 2012, 11:15-18.
15. 郑劲平.关于制定我国用力肺功能检测质量控制指引的建议.中华结核和呼吸杂志, 2004, 27:716-717.
16. Celli BR, MacNee W, ATS/ERS Task Force. Standards for the diagnosis and treatment of patients with COPD:a summary of the ATS/ERS position paper. Eur Respir J, 2004, 23:932-946.
17. Djukanovi Ac'G R, Sterk PJ, Fahy JV, et al. Standardised methodology of sputum inductionf and processing. Eur Respir J Suppl, 2002, 37:1s-2s.
18. Perng DW, Huang HY, Chen HM, et al. Characteristics of airway inflammation and bronchodilator reversibility in COPD:a potential guide to treatment. Chest, 2004, 126:375-381.
19. 罗炜, 赖克方, 钟南山.诱导痰检测的方法学及其在气道炎症评价中的应用.国外医学呼吸系统分册, 2004, 24:395-397.
20. Davidson WJ, Verity WS, Traves SL, et al. Effect of incremental exercise on airway and systemic inflammation in patients with COPD. J Appl Physiol, 2012, 112:2049-2056.
21. Liesker JJ, Bathoorn E, Postma DS, et al. Sputum inflammation predicts exacerbations after cessation of inhaled corticosteroids in COPD. Respir Med, 2011, 105:1853-1860.
22. 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, 186:48-55.
23. 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, 184:662-671.
24. Brightling CE, McKenna S, Hargadon B, et al. Sputum eosinophilia and the short term response to inhaled mometasone in chronic obstructive pulmonary disease. Thorax, 2005, 60:193-198.
25. Ernst P, Saad N, Suissa S. Inhaled corticosteroids in COPD:the clinical evidence. Eur Respir J, 2015, 45:525-37.
26. Vestbo J, Pauwels R, Anderson JA, et al. Early onset of effect of salmeterol and fluticasone propionate in chronic obstructive pulmonary disease. Thorax, 2005, 60:301-314.

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Cytologic Profile of Induced Sputum and Its Relationship with Treatment Response in Patients with Chronic Obstructive Pulmonary Disease

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