A Critical Systematic Review for Inhaled Corticosteroids on Lung Cancer Incidence: Not Yet Concluded Story

BACKGROUND: To systematically review studies on inhaled corticosteroids (ICS) and lung cancer incidence in chronic airway disease patients. METHODS: We conducted electronic bibliographic searches on OVID-MEDLINE, EM-BASE, and the Cochrane Database before May 2020 to identify relevant studies. Detailed data on the study population, exposure, and outcome domains were reviewed. RESULTS: Of 4,058 screened publications, 13 eligible studies in adults with chronic obstructive pulmonary disease (COPD) or asthma evaluated lung cancer incidence after ICS exposure. Pooled hazard ratio and odds ratio for developing lung cancer in ICS exposure were 0.81 (95% confidence interval, 0.64 to 1.02; I(2)=95.7%) from 10 studies and 1.02 (95% confidence interval 0.50 to 2.07; I(2)=94.7%) from three studies. Meta-regression failed to explain the substantial heterogeneity of pooled estimates. COPD and asthma were variously defined without spirometry in 11 studies. Regarding exposure assessment, three and 10 studies regarded ICS exposure as a time-dependent and fixed variable, respectively. Some studies assessed ICS use for the entire study period, whereas others assessed ICS use for 6 months to 2 years within or before study entry. Smoking was adjusted in four studies, and only four studies introduced 1 to 2 latency years in their main or subgroup analysis. CONCLUSION: Studies published to date on ICS and lung cancer incidence had heterogeneous study populations, exposures, and outcome assessments, limiting the generation of a pooled conclusion. The beneficial effect of ICS on lung cancer incidence has not yet been established, and understanding the heterogeneities will help future researchers to establish robust evidence on ICS and lung cancer incidence.