Background: We aimed to assess the association between inhaled corticosteroids (ICSs) and the risk of upper respiratory tract infection (URTI) in patients with chronic obstructive pulmonary disease (COPD).
Methods: PubMed, Embase, Cochrane Library and Clinical Trials.gov were searched from inception to October 2019. Randomized controlled trials (RCTs) of any ICSs vs control for COPD with reporting of URTI as an adverse event were included. The study was registered with PROSPERO prospectively (#CRD42020153134).
Results: Seventeen RCTs (20,478 patients) were included. ICSs significantly increased the risk of URTI in COPD patients (RR, 1.13; 95% CI 1.03-1.24; P = 0.01; heterogeneity: I2 = 7%). Futher subgroup analyses suggested that short-term use of ICSs increased the risk of URTI (RR, 1.29; 95% CI 1.06-1.56; P = 0.01; heterogeneity: I2 = 14%) but not for long-term use (RR, 1.08; 95% CI 0.97-1.2; P = 0.14; heterogeneity: I2 = 0%). Short-term use of high-dose fluticasone increased the risk of URTI (RR, 1.33; 95% CI 1.03-1.71; P = 0.03; heterogeneity: I2 = 0%) but not for long-term use (RR, 1.12; 95% CI 0.97-1.29; P = 0.13; heterogeneity: I2 = 50%). Medium-dose (RR, 0.97; 95% CI 0.71-1.32; P = 0.84; heterogeneity: I2 = 0%) and low-dose (RR, 1.39; 95% CI 0.92-2.1; P = 0.12; heterogeneity: I2 = 30%) fluticasone did not increase the risk of URTI regardless of duration. Neither mometasone (RR, 1.05; 95% CI 0.87-1.26; P = 0.61; heterogeneity: I2 = 0%) nor budesonide (RR, 1.08; 95% CI 0.77-1.5; P = 0.67; heterogeneity: I2 = 46%) increased the risk of URTI, regardless of dosage or duration.
Conclusions: Long-term use of ICSs does not increase the risk of URTI in patients with COPD. Short-term use of high-dose fluticasone increases the risk of URTI in patients with COPD, but not mometasone or budesonide.
Keywords: Chronic obstructive pulmonary disease (COPD); Inhaled corticosteroids (ICS); Meta-analysis; Risk; Upper respiratory tract infection (URTI).