High versus Medium Dose of Inhaled Corticosteroid in Chronic Obstructive Lung Disease: A Systematic Review and Meta-Analysis

Int J Chron Obstruct Pulmon Dis. 2023 Apr 6:18:469-482. doi: 10.2147/COPD.S401736. eCollection 2023.


Background: Inhaled corticosteroids (ICSs) combined with bronchodilators have been identified to improve outcomes in COPD but also to be associated with certain adverse effects.

Objective: We performed a systematic review and meta-analysis to compile and summarize data on the efficacy and safety of dosing levels (high versus medium/low) of ICS alongside ancillary bronchodilators following PRISMA guidelines.

Data sources: Medline and Embase were systematically searched until December 2021. Randomized, clinical trials (RCTs) that met predefined inclusion criteria were included.

Data extraction: Risk ratios (RRs) with 95% confidence intervals (CI) were extracted. Any acute exacerbation of COPD (AECOPD) risk was chosen as the primary efficacy outcome, mortality rate as the primary safety outcome, moderate/severe AECOPD risk as the secondary efficacy outcome and pneumonia risk as the secondary safety outcome. Subgroup analyses of individual ICS agents, of patients with baseline moderate/severe/very severe COPD and of patients with recent COPD exacerbation history were also performed. A random-effects model was used.

Results: We included 13 RCTs in our study. No data on low doses were included in the analysis. High dose ICS was not associated with a statistically significant difference in any AECOPD risk (RR: 0.98, 95% CI: 0.91-1.05, I2: 41.3%), mortality rate (RR: 0.99, 95% CI: 0.75-1.32, I2: 0.0%), moderate/severe AECOPD risk (RR: 1.01, 95% CI: 0.96-1.06, I2: 0.0%) or pneumonia risk (RR: 1.07, 95% CI: 0.86 -1.33, I2: 9.3%) compared to medium dose ICS. The same trend was identified with the several subgroup analyses.

Conclusion: Our study collected RCTs investigating the optimal dosing level of ICS prescribed alongside ancillary bronchodilators to patients with COPD. We identified that the high ICS dose neither reduces AECOPD risk and mortality rates nor increases pneumonia risk relative to the medium dose.

Keywords: acute COPD exacerbation; chronic obstructive lung disease; inhaled corticosteroids; mortality; pneumonia.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones
  • Bronchodilator Agents
  • Humans
  • Pneumonia* / chemically induced
  • Pneumonia* / diagnosis
  • Pneumonia* / drug therapy
  • Pulmonary Disease, Chronic Obstructive* / diagnosis
  • Pulmonary Disease, Chronic Obstructive* / drug therapy


  • Bronchodilator Agents
  • Adrenal Cortex Hormones

Grants and funding

There is no funding to report.