Association between inhaled corticosteroids and the risk of lung cancer in patients with chronic obstructive pulmonary disease: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

QIAO Yanyan , WANG Zaiqiang , WANG Ying , FENG Yanzhen , LI Chan ,  FU Enqing

Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Air Force Military Medical University, Xi’an 710038, P. R. China;

Corresponding author：

FU Enqing, Email: fuenqing@sina.com

Keywords：

Inhaled glucocorticoids; Chronic obstructive pulmonary disease; Lung cancer; Cohort study; Meta-analysis; Systematic review

DOI：

10.7507/1672-2531.202210059

Video：

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Objective To systematically review the association between inhaled corticosteroids (ICS) and the risk of lung cancer in patients with chronic obstructive pulmonary disease (COPD). Methods PubMed, EMbase, Web of Science, Cochrane Library, CNKI, WanFang Data and VIP databases were electronically searched to collect cohort studies on the risk of lung cancer in COPD patients using ICS from inception to August 15, 2022. Two reviewers independently screened the literature, extracted data, and evaluated the risk of bias of the included studies. Meta-analysis was then performed by using RevMan 5.4 software. Results A total of 8 cohort studies involving 1 184 238 patients were included. The results of meta-analysis showed that ICS use decreased risk of lung cancer in COPD patients (HR=0.68, 95%CI 0.62 to 0.75, P<0.01). The dose of ICS was an influencing factor for the risk of lung cancer in COPD patients and a large dose of ICS could significantly reduce the risk. Conclusion Current evidence shows that the use of ICS can reduce the risk of lung cancer in patients with COPD, especially in high-dose patients. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.

Citation： QIAO Yanyan, WANG Zaiqiang, WANG Ying, FENG Yanzhen, LI Chan, FU Enqing. Association between inhaled corticosteroids and the risk of lung cancer in patients with chronic obstructive pulmonary disease: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2023, 23(3): 298-302. doi: 10.7507/1672-2531.202210059 Copy

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19.	Jian ZH, Huang JY, Lin FC, et al. The use of corticosteroids in patients with COPD or asthma does not decrease lung squamous cell carcinoma. BMC Pulm Med, 2015, 15: 154.
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21.	Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
22.	艾飞玲, 胡葵茹, 石钰霖, 等. 基于纽卡斯尔-渥太华量表对中国吸烟队列研究文献的质量评价. 中华疾病控制杂志, 2021, 25(6): 722-729.
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25.	Parimon T, Chien JW, Bryson CL, et al. Inhaled corticosteroids and risk of lung cancer among patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2007, 175(7): 712-719.
26.	Raymakers AJN, Sadatsafavi M, Sin DD, et al. Inhaled corticosteroids and the risk of lung cancer in COPD: a population-based cohort study. Eur Respir J, 2019, 53(6): 1801257.
27.	Wu MF, Jian ZH, Huang JY, et al. Post-inhaled corticosteroid pulmonary tuberculosis and pneumonia increases lung cancer in patients with COPD. BMC Cancer, 2016, 16(1): 778.
28.	Young RP, Hopkins RJ, Christmas T, et al. COPD prevalence is increased in lung cancer, independent of age, sex and smoking history. Eur Respir J, 2009, 34(2): 380-386.
29.	中华医学会呼吸病学分会慢性阻塞性肺疾病学组, 中国医师协会呼吸医师分会慢性阻塞性肺疾病工作委员会. 慢性阻塞性肺疾病诊治指南(2021年修订版). 中华结核和呼吸杂志, 2021, 44(3): 170-205.
30.	Wasswa-Kintu S, Gan WQ, Man SF, et al. Relationship between reduced forced expiratory volume in one second and the risk of lung cancer: a systematic review and meta-analysis. Thorax, 2005, 60(7): 570-575.
31.	Fry JS, Hamling JS, Lee PN. Systematic review with meta-analysis of the epidemiological evidence relating FEV1 decline to lung cancer risk. BMC Cancer, 2012, 12: 498.
32.	Estensen RD, Jordan MM, Wiedmann TS, et al. Effect of chemopreventive agents on separate stages of progression of benzo[alpha]pyrene induced lung tumors in A/J mice. Carcinogenesis, 2004, 25(2): 197-201.
33.	Miller YE, Keith RL. Inhaled corticosteroids and lung cancer chemoprevention. Am J Respir Crit Care Med, 2007, 175(7): 636-637.
34.	Soltani A, Mahmood MQ, Reid DW, et al. Cancer-protective effects of inhaled corticosteroids in COPD are likely related to modification of epithelial activation. Eur Respir J, 2019, 54(3): 1901088.
35.	Mahmood MQ, Sohal SS, Shukla SD, et al. Epithelial mesenchymal transition in smokers: large versus small airways and relation to airflow obstruction. Int J Chron Obstruct Pulmon Dis, 2015, 10: 1515-1524.
36.	Lu W, Sharma P, Eapen MS, et al. Inhaled corticosteroids attenuate epithelial mesenchymal transition: implications for COPD and lung cancer prophylaxis. Eur Respir J, 2019, 54(1): 1900778.
37.	Pitre T, Kiflen M, Ho T, et al. Inhaled corticosteroids, COPD, and the incidence of lung cancer: a systematic review and dose response meta-analysis. BMC Pulm Med, 2022, 22(1): 275.
38.	Lin P, Fu S, Li W, et al. Inhaled corticosteroids and risk of lung cancer: a systematic review and meta-analysis. Eur J Clin Invest, 2021, 51(2): e13434.

1. GBD 2016 Causes of Death Collaborators. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet, 2017, 390(10100): 1151-1210.
2. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med, 2006, 3(11): e442.
3. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
4. Yang L, Lu X, Deng J, et al. Risk factors shared by COPD and lung cancer and mediation effect of COPD: two center case-control studies. Cancer Causes Control, 2015, 26(1): 11-24.
5. Wang C, Xu J, Yang L, et al. Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health study): a national cross-sectional study. Lancet, 2018, 391(10131): 1706-1717.
6. Repine JE, Bast A, Lankhorst I. Oxidative stress in chronic obstructive pulmonary disease. Oxidative Stress Study Group. Am J Respir Crit Care Med, 1997, 156(2 Pt 1): 341-357.
7. Durham AL, Adcock IM. The relationship between COPD and lung cancer. Lung Cancer, 2015, 90(2): 121-127.
8. Malkinson AM. Role of inflammation in mouse lung tumorigenesis: a review. Exp Lung Res, 2005, 31(1): 57-82.
9. Parris BA, O'Farrell HE, Fong KM, et al. Chronic obstructive pulmonary disease (COPD) and lung cancer: common pathways for pathogenesis. J Thorac Dis, 2019, 11(Suppl 17): S2155-S2172.
10. Caramori G, Ruggeri P, Mumby S, et al. Molecular links between COPD and lung cancer: new targets for drug discovery. Expert Opin Ther Targets, 2019, 23(6): 539-553.
11. Agustí 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.
12. Larj MJ, Bleecker ER. Therapeutic responses in asthma and COPD. Corticosteroids. Chest, 2004, 126(2 Suppl): 138S-149S, 159S-161S.
13. Sohal SS, Soltani A, Reid D, et al. A randomized controlled trial of inhaled corticosteroids (ICS) on markers of epithelial-mesenchymal transition (EMT) in large airway samples in COPD: an exploratory proof of concept study. Int J Chron Obstruct Pulmon Dis, 2014, 9: 533-542.
14. Lee G, Walser TC, Dubinett SM. Chronic inflammation, chronic obstructive pulmonary disease, and lung cancer. Curr Opin Pulm Med, 2009, 15(4): 303-307.
15. Lee CH, Hyun MK, Jang EJ, et al. Inhaled corticosteroid use and risks of lung cancer and laryngeal cancer. Respir Med, 2013, 107(8): 1222-1233.
16. Liu SF, Kuo HC, Lin MC, et al. Inhaled corticosteroids have a protective effect against lung cancer in female patients with chronic obstructive pulmonary disease: a nationwide population-based cohort study. Oncotarget, 2017, 8(18): 29711-29721.
17. Husebø GR, Nielsen R, Hardie J, et al. Risk factors for lung cancer in COPD - results from the Bergen COPD cohort study. Respir Med, 2019, 152: 81-88.
18. Szabo E, Mao JT, Lam S, et al. Chemoprevention of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest, 2013, 143(5 Suppl): e40S-e60S.
19. Jian ZH, Huang JY, Lin FC, et al. The use of corticosteroids in patients with COPD or asthma does not decrease lung squamous cell carcinoma. BMC Pulm Med, 2015, 15: 154.
20. Sørli K, Thorvaldsen SM, Hatlen P. Use of inhaled corticosteroids and the risk of lung cancer, the HUNT Study. Lung, 2018, 196(2): 179-184.
21. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
22. 艾飞玲, 胡葵茹, 石钰霖, 等. 基于纽卡斯尔-渥太华量表对中国吸烟队列研究文献的质量评价. 中华疾病控制杂志, 2021, 25(6): 722-729.
23. Sandelin M, Mindus S, Thuresson M, et al. Factors associated with lung cancer in COPD patients. Int J Chron Obstruct Pulmon Dis, 2018, 13: 1833-1839.
24. Kiri VA, Fabbri LM, Davis KJ, et al. Inhaled corticosteroids and risk of lung cancer among COPD patients who quit smoking. Respir Med, 2009, 103(1): 85-90.
25. Parimon T, Chien JW, Bryson CL, et al. Inhaled corticosteroids and risk of lung cancer among patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2007, 175(7): 712-719.
26. Raymakers AJN, Sadatsafavi M, Sin DD, et al. Inhaled corticosteroids and the risk of lung cancer in COPD: a population-based cohort study. Eur Respir J, 2019, 53(6): 1801257.
27. Wu MF, Jian ZH, Huang JY, et al. Post-inhaled corticosteroid pulmonary tuberculosis and pneumonia increases lung cancer in patients with COPD. BMC Cancer, 2016, 16(1): 778.
28. Young RP, Hopkins RJ, Christmas T, et al. COPD prevalence is increased in lung cancer, independent of age, sex and smoking history. Eur Respir J, 2009, 34(2): 380-386.
29. 中华医学会呼吸病学分会慢性阻塞性肺疾病学组, 中国医师协会呼吸医师分会慢性阻塞性肺疾病工作委员会. 慢性阻塞性肺疾病诊治指南(2021年修订版). 中华结核和呼吸杂志, 2021, 44(3): 170-205.
30. Wasswa-Kintu S, Gan WQ, Man SF, et al. Relationship between reduced forced expiratory volume in one second and the risk of lung cancer: a systematic review and meta-analysis. Thorax, 2005, 60(7): 570-575.
31. Fry JS, Hamling JS, Lee PN. Systematic review with meta-analysis of the epidemiological evidence relating FEV1 decline to lung cancer risk. BMC Cancer, 2012, 12: 498.
32. Estensen RD, Jordan MM, Wiedmann TS, et al. Effect of chemopreventive agents on separate stages of progression of benzo[alpha]pyrene induced lung tumors in A/J mice. Carcinogenesis, 2004, 25(2): 197-201.
33. Miller YE, Keith RL. Inhaled corticosteroids and lung cancer chemoprevention. Am J Respir Crit Care Med, 2007, 175(7): 636-637.
34. Soltani A, Mahmood MQ, Reid DW, et al. Cancer-protective effects of inhaled corticosteroids in COPD are likely related to modification of epithelial activation. Eur Respir J, 2019, 54(3): 1901088.
35. Mahmood MQ, Sohal SS, Shukla SD, et al. Epithelial mesenchymal transition in smokers: large versus small airways and relation to airflow obstruction. Int J Chron Obstruct Pulmon Dis, 2015, 10: 1515-1524.
36. Lu W, Sharma P, Eapen MS, et al. Inhaled corticosteroids attenuate epithelial mesenchymal transition: implications for COPD and lung cancer prophylaxis. Eur Respir J, 2019, 54(1): 1900778.
37. Pitre T, Kiflen M, Ho T, et al. Inhaled corticosteroids, COPD, and the incidence of lung cancer: a systematic review and dose response meta-analysis. BMC Pulm Med, 2022, 22(1): 275.
38. Lin P, Fu S, Li W, et al. Inhaled corticosteroids and risk of lung cancer: a systematic review and meta-analysis. Eur J Clin Invest, 2021, 51(2): e13434.

Chinese Journal of Evidence-Based Medicine

Association between inhaled corticosteroids and the risk of lung cancer in patients with chronic obstructive pulmonary disease: a meta-analysis

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