Dose–Response Relationship of Inhaled Corticosteroids on Pulmonary Function and Exacerbation Risk in Copd

Abstract

OBJECTIVE: To compare the dose–response of inhaled corticosteroid (ICS) on pulmonary function trajectories, exacerbation rates and adverse event profiles in patients with moderate-to-very severe Chronic Obstructive Pulmonary Disease (COPD).

MATERIAL AND METHODS: A multicenter, prospective, dose stratified observational cohort study was performed. Patients were divided into three groups in all of which a background regimen of Long-Acting Beta-Agonist/Long-Acting Muscarinic Antagonist was used (N=4,850). The primary outcomes were the annualized rate of decline of post-bronchodilator FEV1 and rate of moderate-to-severe COPD exacerbations over 24 months.

RESULTS: There was a statistically significant reduction in the rate of moderate to severe exacerbations (Rate Ratio 0.78, 95% CI 0.71-0.86, p<0.001) in the high dose ICS groups compared to medium and low dose groups. There was a strong association between high-dose ICS and the risk of treated pneumonia (Hazard Ratio 1.65, 95% CI 1.42-1.91, p<0.001).

CONCLUSION: There is a clear ceiling effect for the response of ICS on pulmonary function in COPD and for the reduction of exacerbations, and an increase in the risk of pneumonia with increasing dose of ICS. A medium dose of ICS seems to be the sweet-spot between efficacy and safety.

KEYWORDS: Chronic Obstructive Pulmonary Disease, Inhaled Corticosteroids, Dose-Response Relationship, Pulmonary Function, Exacerbation, Pneumonia.