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.	中華醫學會呼吸病學分會慢性阻塞性肺疾病學組.慢性阻塞性肺疾病診治指南(2013年修訂版).中華結核和呼吸雜志, 2013, 36:255-264.
14.	張偉兵, 王欣燕, 田曉彥, 等.ADAM33基因多態性影響慢性阻塞性肺疾病氣道炎癥.中國呼吸與危重監護雜志, 2012, 11:15-18.
15.	鄭勁平.關于制定我國用力肺功能檢測質量控制指引的建議.中華結核和呼吸雜志, 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.	羅煒, 賴克方, 鐘南山.誘導痰檢測的方法學及其在氣道炎癥評價中的應用.國外醫學呼吸系統分冊, 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. 中華醫學會呼吸病學分會慢性阻塞性肺疾病學組.慢性阻塞性肺疾病診治指南(2013年修訂版).中華結核和呼吸雜志, 2013, 36:255-264.
14. 張偉兵, 王欣燕, 田曉彥, 等.ADAM33基因多態性影響慢性阻塞性肺疾病氣道炎癥.中國呼吸與危重監護雜志, 2012, 11:15-18.
15. 鄭勁平.關于制定我國用力肺功能檢測質量控制指引的建議.中華結核和呼吸雜志, 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. 羅煒, 賴克方, 鐘南山.誘導痰檢測的方法學及其在氣道炎癥評價中的應用.國外醫學呼吸系統分冊, 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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