Inhaled Corticosteroids and Risk of Lung Cancer Among Chronic Obstructive Pulmonary Disease Patients

A Comprehensive Analysis of Nine Prospective Cohorts

Fan Ge; Yi Feng; Zhenyu Huo; Caichen Li; Runchen Wang; Yaokai Wen; Sirui Gao; Haoxin Peng; Xiangrong Wu; Hengrui Liang; Bo Cheng; Ran Zhong; Jianxing He; Wenhua Liang


Transl Lung Cancer Res. 2021;10(3):1266-1276. 

In This Article

Abstract and Introduction


Background: It remains uncertain whether there is a protective effect of inhaled corticosteroids (ICs) against lung cancer in chronic obstructive pulmonary disease (COPD) patients.

Methods: Databases including PubMed, Web of Science, EMBASE, and Medline were comprehensively searched. Random-effects model meta-analysis was conducted to calculate the hazard ratios (HRs) for lung cancer incidence among ICs users versus non-ICs users in patients with COPD. Stratified analysis was performed based on region and age of each study. This review was registered on PROSPERO (registration number CRD42020159082).

Results: Based on data from 181,859 COPD patients with a total follow-up duration of 1,109,339.9 person-years, we identified that the use of ICs in COPD patients was associated with a decreased risk of lung cancer [HR: 0.73, 95% confidence interval (CI): 0.62–0.86; P<0.001]. The region-specific HRs for lung cancer incidence were 0.62 (95% CI: 0.62–0.86; P=0.004), 0.77 (95% CI: 0.60–0.97; P=0.028) and 0.81 (95% CI: 0.61–1.08; P=0.155) among European, Asian and North American COPD patients, respectively. Additionally, we found the consistent outcome among age groups (≥70 years old: HR: 0.73, 95% CI: 0.65–0.99, P=0.043; <70 years old: HR: 0.74, 95% CI: 0.56–0.99, P=0.040).

Conclusions: This study demonstrates that ICs have a protective effect against lung cancer in COPD patients. It could provide guidance for clinicians in the prevention of lung cancer among patients with COPD.


With a prevalence of 10.2% among people more than 40 years old around the world, chronic obstructive pulmonary disease (COPD) seems to be a rather prevalent respiratory disease.[1] COPD is a disease with insidious onsets and a poor prognosis. More than 70% COPD patients are at stage 1 or 2 of Global Initiative for Chronic Obstructive Lung Disease (GOLD), with very mild respiratory symptoms such as Shortness of Breath on Exertion (SOBOE). As a result, few of them would seek medical consultations before acute exacerbation.[2,3]

COPD is an inflammatory disease of the respiratory system and is considered as a risky element of lung cancer.[4] A comprehensive review of studies reported some possible pathogenic mechanisms to explain the potential association between COPD and lung cancer.[5] Other literature suggested that the severity of COPD was positively correlated with the development of lung cancer.[6,7] Inflammation is also associated with lung cancer. Some studies found that chronic inflammation was involved at the onset of lung cancer through some mechanisms, which were partially independent of smoking.[8,9] Therefore, it is reasonable to carry out some research on early anti-inflammatory therapy in COPD patients to prevent malignant transformation.

Some cohort studies showed that inhaled corticosteroids (ICs) may delay or prevent the incidence of lung cancer to some extent.[10–12] Nevertheless, some cohort studies showed that compared with general population, COPD patients using ICs demonstrated an increased risk of lung cancer.[13,14] Therefore, the protective effect of ICs for lung cancer in COPD patients was not clear. We performed a systematic review including a meta-analysis to determine the exact effect of ICs of lung cancer in COPD patients. We present the following article in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting checklist (available at: