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

Abstract

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:

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

IRB Review

This study is a review and meta‐analysis, which does not require IRB review.

Data Sharing Statement

Our data is derived from public domain resources. All data source material that supports the findings of this study are available on Medline and Embase.

Author Contributions

PAB was involved in the study execution, data analysis and data interpretation and was involved in the manuscript drafting and writing.

TT was involved in the study design, study execution and acquisition of data and was involved in substantially revising the article.

JYY, GJHR and VG were involved in the study execution, acquisition of data and were involved in substantially revising the article.

FJM was involved in the study conception, data (result) interpretation and was involved in substantially revising and critically reviewing the article.

SF was involved in the study conception, study design, study execution and was involved in article writing, substantially revising and critically reviewing the article.

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

FJM reports grants from NHLBI, National Institutes of Health, personal fees from Continuing Education, personal fees from Forest Laboratories, Janssen, GlaxoSmithKline, Nycomed/Takeda, AstraZeneca, Boehringer Ingelheim, Bellerophon (formerly Ikaria), Genentech, Novartis, Pearl, Roche, Sunovion, Theravance, CME Incite, Annenberg Center for Health Sciences at Eisenhower, Integritas, InThought, National Association for Continuing Education, Paradigm Medical Communications, LLC, PeerVoice, UpToDate, Haymarket Communications, Western Society of Allergy and Immunology, Proterixbio (formerly Bioscale), Unity Biotechnology, ConCert Pharmaceuticals, Lucid, Methodist Hospital, Columbia University, Prime Healthcare Ltd, WebMD, PeerView Network, California Society of Allergy and Immunology, Chiesi, Puerto Rico Thoracic Society, outside the submitted work. He is also a part of the event adjudication committee for Medtronic. SF has received grants from American Thoracic Society and Fisher & Paykel; personal fees from Hospital Medicine (SHM) and has consulted Genentech. The authors report no other conflicts of interest in this work.

Additional information

Funding

There is no funding to report.