Abstract
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.
Highlights
Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death in the world, and acute exacerbations contribute substantially to this (GBD 2015 Chronic Respiratory Disease Collaborators, 2017; Viniol and Vogelmeier, 2018; López-Campos et al, 2019)
Subgroup analysis based on types of inhaled corticosteroids (ICSs) showed that all types of ICSs increased the pneumonia risk ([fluticasone: Peto odds ratio (Peto OR), 1.47; 95% confidence interval (CI), 1.36–1.59]; [budesonide: Peto OR, 1.24; 95% CI, 1.05–1.47]; [mometasone: Peto OR, 1.62; 95% CI, 1.05–2.49]; [beclomethasone: Peto OR, 1.43; 95% CI, 1.03–1.97])
ICSs treatment significantly increased the pneumonia risk in all severity subgroups of COPD patients: ([Moderate COPD: Peto OR, 1.26; 95% CI, 1.11–1.43]; [Severe COPD: Peto OR, 1.54; 95% CI, 1.42–1.68]; [Very severe COPD: Peto OR, 2.52; 95% CI, 1.88–3.38]) (Table 2 and Figure 7)
Summary
Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death in the world, and acute exacerbations contribute substantially to this (GBD 2015 Chronic Respiratory Disease Collaborators, 2017; Viniol and Vogelmeier, 2018; López-Campos et al, 2019). The reliability and generalizability of these studies might be weakened by their small sample size, since a large number of important randomized controlled trials (RCTs) after 2017 were not included in these meta-analyses (Bhatt et al, 2017; Papi et al, 2017; Siler et al, 2017; Vestbo et al, 2017; Betsuyaku et al, 2018; Chapman et al, 2018; Ferguson et al, 2018a, Ferguson et al, 2018b; Frith et al, 2018; Lipson et al, 2018; Papi et al, 2018; Ichinose et al, 2019; Kerwin et al, 2019; Rabe et al, 2020) None of these studies assessed the difference in the pneumonia risk in COPD patients with different demographic characteristics (including severity of airflow limitation, age, body mass index [BMI], etc.). 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
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