Inhaled Corticosteroids and the Pneumonia Risk in Patients With Chronic Obstructive Pulmonary Disease: A Meta-analysis of Randomized Controlled Trials

Background: Whether all types of inhaled corticosteroids (ICSs) would increase the pneumonia risk in patients with chronic obstructive pulmonary disease (COPD) remains controversial. We aimed to assess the association between ICSs treatment and pneumonia risk in COPD patients, and the impact of medication details and baseline characteristics of patients on the association. Methods: Four databases (PubMed, Embase, Cochrane Library, and Clinical Trials.gov) were searched to identify eligible randomized controlled trials (RCTs) comparing ICSs treatment with non-ICSs treatment on the pneumonia risk in COPD patients. Pooled results were calculated using Peto odds ratios (Peto ORs) with corresponding 95% confidence intervals (CIs). Results: A total of 59 RCTs enrolling 103,477 patients were analyzed. All types of ICSs significantly increased the pneumonia risk (Peto OR, 1.43; 95% CI, 1.34-1.53). Subgroup analysis showed that there was a dose-response relationship between ICSs treatment and pneumonia risk (low-dose: Peto OR, 1.33; 95% CI, 1.22-1.45; medium-dose: Peto OR, 1.50; 95% CI, 1.28-1.76; and high-dose: Peto OR, 1.64; 95% CI, 1.45-1.85). Subgroup analyses based on treatment durations and baseline characteristics (severity, age, and body mass index) of patients were consistant with the above results. Subgroup analysis based on severity of pneumonia showed that fluticasone (Peto OR, 1.75; 95% CI, 1.44-2.14) increased the risk of serious pneumonia, while budesonide and beclomethasone did not. Conclusions: ICSs treatment significantly increased the risk of pneumonia in COPD patients. There was a dose-response relationship between ICSs treatment and pneumonia risk. The pneumonia risk was related with COPD severity.