Prospective research on persistent systemic inflammation of COPD patients_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

JIANG Xuelian ¹ ^# , HU Xu ² ^# , ZHONG Ping ¹ , HUANG Chengliang ¹ ,  FAN Xianming ¹

1. Department of Respiratory and Critical Care Medicine, Inflammation & Allergic Diseases Research Unit, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P. R. China;
2. First Department of Respiratory Medicine, The First Ziyang People’s Hospital, Ziyang, Sichuan 641300, P. R. China;

Corresponding?author：

FAN Xianming, Email: fxm129@163.com

Keywords：

Chronic obstructive pulmonary disease; Persistent systemic inflammation; Acute exacerbation; Body mass index

DOI：

10.7507/1671-6205.201905036

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Objective To investigate the existence of persistent systemic inflammation (PSI) among patients with chronic obstructive pulmonary disease (COPD) in local areas, and identify the risk factors of PSI.Methods A total of 150 patients with stable COPD and 70 non-smoking healthy individuals were enrolled in our study. The levels of interleukin-6 (IL-6), IL-18 and activin A in serum were detected. Pulmonary function was tested, and basic information of the candidates was acquired at the same time. All of the patients were followed-up at 6 months, 12 months and 24 months for two years. The value at the 95^th percentile of the concentration of inflammation markers of non-smoking healthy samples was defined as the threshold value, also known as normal ceiling limit value. Existence of PSI was defined as the condition that two or more kinds of inflammation markers exceed the threshold at each follow-up visit. The COPD patients were categorized into three classes, in which there were respectively none, one and two or more kinds of inflammation markers with over-threshold values. Based on a 2-year followup, patients with two or more kinds of inflammation markers exceeding threshold values were classified as PSI subgroup, and patients without inflammation markers exceeding threshold values as never inflamed subgroup.Results There were 22 patients (14.7%) had persistent systemic inflammation, whereas 60 patients (40.0%) did not show evidence of systemic inflammation. Single factor analysis of two subgroups showed that the patients in PSI subgroup had higher body mass index (BMI), higher smoking index, higher prior frequency of time to exacerbation, higher proportion of patients at high risk for recurrent acute exacerbation during 2-year followup, higher SGRQ total score, lower FEV₁%pred and lower FEV₁/FVC ratio significantly (all P<0.05). Higher BMI and higher risk of recurrent acute exacerbation were independent risk factors leading to PSI, of which the higher risk of recurrent acute exacerbation had a more important effect on PSI.Conclusions Some COPD patients have PSI in this region, which may constitute a novel COPD phenotype (called systemic inflammatory phenotype). Higher BMI and higher risk of recurrent acute exacerbation are independent risk factors leading to PSI. Individualized treatment to prevent acute exacerbation and appropriate weight control may be a better intervention for these patients.

Citation： JIANG Xuelian, HU Xu, ZHONG Ping, HUANG Chengliang, FAN Xianming. Prospective research on persistent systemic inflammation of COPD patients. Chinese Journal of Respiratory and Critical Care Medicine, 2020, 19(6): 536-542. doi: 10.7507/1671-6205.201905036 Copy

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2.	Wang M, Zhang Y, Xu M, et al. Roles of TRPA1 and TRPV1 in cigarette smoke-induced airway epithelial cell injury model. Free Radic Biol Med, 2019, 134: 229-238.
3.	Global Initiative for Chronic Obstructive Lung Disease (GOLD): Global Strategy for the Diagnosis, Management and prevention Of Chronic Obstructive Pulmonary Disease. (2017 REPORT). http://www.goldcopd.org.
4.	Nishimura M, Makita H, Nagai K, et al. Annual change in pulmonary function and clinical phenotype in chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2012, 185(1): 44-52.
5.	謝曉然, 鮑文華, 楊澤. 腫瘤壞死因子-α 基因多態性與黑龍江省東部地區慢性阻塞性肺疾病人群易感性的研究. 中國呼吸與危重監護雜志, 2019, 18(3): 217-223.
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9.	Vasan RS. Biomarkers of cardiovascular disease: molecular basis and practical considerations. Circulation, 2006, 113(19): 2335-2362.
10.	Han MK, Agusti A, Calverley PM, et al. Chronic obstructive pulmonary disease phenotypes: the future of COPD. Am J Respir Crit Care Med, 2010, 182(5): 598-604.
11.	趙春柳, 黃靚雯, 張利, 等. 慢性阻塞性肺疾病急性加重住院患者呼吸道病毒感染與炎癥細胞因子的相關性. 中華結核和呼吸雜志, 2018, 41(12): 942-948.
12.	Calvano SE, Xiao W, Richards DR, et al. A network-based analysis of systemic inflammation in humans. Nature, 2005, 437(7061): 1032-1037.
13.	Barabási AL, Gulbahce N, Loscalzo J. Network medicine: a network-based approach to human disease. Nat Rev Genet, 2011, 12(1): 56-68.
14.	Sin DD, Man SFP, Marciniuk DD, et al. The effects of fluticasone with or without salmeterol on systemic biomarkers of inflammation in chronic obstructive pulmonary disease. Respir Crit Care Med, 2008, 177(11): 1207-1214.
15.	Di Stefano A, Coccini T, Roda E, et al. Blood MCP-1 levels are increased in chronic obstructive pulmonary disease patients with prevalent emphysema. Int J Chron Obstruct Pulmon Dis, 2018, 13: 1691-1700.
16.	Vitenberga Z, Pilmane M, Babjoni?eva A. The evaluation of inflammatory, anti-inflammatory and regulatory factors contributing to the pathogenesis of COPD in airways. Pathol Res Pract, 2019, 215(1): 97-105.
17.	Ryrs? CK, Thaning P, Siebenmann C, et al. Effect of endurance versus resistance training on local muscle and systemic inflammation and oxidative stress in COPD. Scand J Med Sci Sports, 2018, 28(11): 2339-2348.
18.	Verhamme FM, Bracke KR, Amatngalim GD, et al. Role of activin-A in cigarette smoke-induced inflammation and COPD. Eur Respir J, 2014, 43(4): 1028-1041.
19.	Tania NP, Schmidt M, Gosens R. Activin-A: active in inflammation in COPD. Eur Respir J, 2014, 43(4): 954-955.
20.	Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature, 2006, 444(7121): 875-880.
21.	Fuller-Thomson E, Howden KEN, Fuller-Thomson LR, et al. A strong graded relationship between level of obesity and COPD: findings from a national population-based study of lifelong nonsmokers, J Obes. 2018, 2018: 6149263.
22.	Janssen DJ, Müllerova H, Agusti A, et al. Persistent systemic inflammation and symptoms of depression among patients with COPD in the ECLIPSE cohort. Respir Med, 2014, 108(11): 1647-1654.

1. Yin P, Wang HD, Vos T, et al. A subnational analysis of mortality and prevalence of COPD in China from 1990 to 2013: findings from the global burden of disease study 2013. Chest, 2016, 150(6): 1269-1280.
2. Wang M, Zhang Y, Xu M, et al. Roles of TRPA1 and TRPV1 in cigarette smoke-induced airway epithelial cell injury model. Free Radic Biol Med, 2019, 134: 229-238.
3. Global Initiative for Chronic Obstructive Lung Disease (GOLD): Global Strategy for the Diagnosis, Management and prevention Of Chronic Obstructive Pulmonary Disease. (2017 REPORT). http://www.goldcopd.org.
4. Nishimura M, Makita H, Nagai K, et al. Annual change in pulmonary function and clinical phenotype in chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2012, 185(1): 44-52.
5. 謝曉然, 鮑文華, 楊澤. 腫瘤壞死因子-α 基因多態性與黑龍江省東部地區慢性阻塞性肺疾病人群易感性的研究. 中國呼吸與危重監護雜志, 2019, 18(3): 217-223.
6. 何子凡, 高巖, 王曉玲, 等. NLRP3 炎性小體在慢性阻塞性肺疾病患者機體炎癥反應中作用的研究. 中國呼吸與危重監護雜志, 2018, 17(2): 119-123.
7. Agusti A, Edwards LD, Rennard SI, et al. Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype. PLoS One, 2012, 7(5): e37483.
8. 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(4): 255-264.
9. Vasan RS. Biomarkers of cardiovascular disease: molecular basis and practical considerations. Circulation, 2006, 113(19): 2335-2362.
10. Han MK, Agusti A, Calverley PM, et al. Chronic obstructive pulmonary disease phenotypes: the future of COPD. Am J Respir Crit Care Med, 2010, 182(5): 598-604.
11. 趙春柳, 黃靚雯, 張利, 等. 慢性阻塞性肺疾病急性加重住院患者呼吸道病毒感染與炎癥細胞因子的相關性. 中華結核和呼吸雜志, 2018, 41(12): 942-948.
12. Calvano SE, Xiao W, Richards DR, et al. A network-based analysis of systemic inflammation in humans. Nature, 2005, 437(7061): 1032-1037.
13. Barabási AL, Gulbahce N, Loscalzo J. Network medicine: a network-based approach to human disease. Nat Rev Genet, 2011, 12(1): 56-68.
14. Sin DD, Man SFP, Marciniuk DD, et al. The effects of fluticasone with or without salmeterol on systemic biomarkers of inflammation in chronic obstructive pulmonary disease. Respir Crit Care Med, 2008, 177(11): 1207-1214.
15. Di Stefano A, Coccini T, Roda E, et al. Blood MCP-1 levels are increased in chronic obstructive pulmonary disease patients with prevalent emphysema. Int J Chron Obstruct Pulmon Dis, 2018, 13: 1691-1700.
16. Vitenberga Z, Pilmane M, Babjoni?eva A. The evaluation of inflammatory, anti-inflammatory and regulatory factors contributing to the pathogenesis of COPD in airways. Pathol Res Pract, 2019, 215(1): 97-105.
17. Ryrs? CK, Thaning P, Siebenmann C, et al. Effect of endurance versus resistance training on local muscle and systemic inflammation and oxidative stress in COPD. Scand J Med Sci Sports, 2018, 28(11): 2339-2348.
18. Verhamme FM, Bracke KR, Amatngalim GD, et al. Role of activin-A in cigarette smoke-induced inflammation and COPD. Eur Respir J, 2014, 43(4): 1028-1041.
19. Tania NP, Schmidt M, Gosens R. Activin-A: active in inflammation in COPD. Eur Respir J, 2014, 43(4): 954-955.
20. Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature, 2006, 444(7121): 875-880.
21. Fuller-Thomson E, Howden KEN, Fuller-Thomson LR, et al. A strong graded relationship between level of obesity and COPD: findings from a national population-based study of lifelong nonsmokers, J Obes. 2018, 2018: 6149263.
22. Janssen DJ, Müllerova H, Agusti A, et al. Persistent systemic inflammation and symptoms of depression among patients with COPD in the ECLIPSE cohort. Respir Med, 2014, 108(11): 1647-1654.

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