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

Abstract

Paraschos Archontakis Barakakis,1 Thuonghien Tran,2 Jee Young You,3 Gabriel J Hernandez Romero,4 Vipul Gidwani,1 Fernando J Martinez,5 Spyridon Fortis2,6 1Northeast Internal Medicine Associates, LaGrange, IN, USA; 2Division of Pulmonary, Critical Care, and Occupational Medicine, Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA; 3Department of Pulmonary and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH, USA; 4Department of Medicine, Albert Einstein College of Medicine/Jacobi Medical Center, Bronx, NY, USA; 5Departments of Medicine and Genetic Medicine, Weill Cornell Medicine, New York, NY, USA; 6Veterans Rural Health Resource Center, VA Office of Rural Health, and Center for Access and Delivery Research and Evaluation (CADRE) at the Iowa City VA Healthcare System, Iowa City, IA, USACorrespondence: Paraschos Archontakis Barakakis, Northeast Internal Medicine Associates, 4344 Love Grass Lane, Fort Wayne, LaGrange, IN, 46845, USA, Tel [phone], Email [email protected]: 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: chronic obstructive lung disease, acute COPD exacerbation, mortality, pneumonia, inhaled corticosteroids

Keywords

• • chronic obstructive lung disease • acute copd exacerbation • mortality • pneumonia • inhaled corticosteroids