Inhaled corticosteroids for chronic obstructive pulmonary disease: what is their role in therapy?

Abstract

Inhaled corticosteroids (ICSs) are a mainstay of COPD treatment for patients with a history of exacerbations. Initial studies evaluating their use as monotherapy failed to show an effect on rate of pulmonary function decline in COPD, despite improvements in symptoms and reductions in exacerbations. Subsequently, ICS use in combination with long-acting β₂-agonists (LABAs) was shown to provide improved reductions in exacerbations, lung function, and health status. ICS-LABA combination therapy is currently recommended for patients with a history of exacerbations despite treatment with long-acting bronchodilators alone. The presence of eosinophilic bronchial inflammation, detected by high blood eosinophil levels or a history of asthma or asthma-COPD overlap, may define a population of patients in whom ICSs may be of particular benefit. Prospective clinical studies to determine an appropriate threshold of eosinophil levels for predicting the beneficial effects of ICSs are needed. Further study is also required in COPD patients who continue to smoke to assess the impact of cell- and tissue-specific changes on ICS responsiveness. The safety profile of ICSs in COPD patients is confounded by comorbidities, age, and prior use of systemic corticosteroids. The risk of pneumonia in patients with COPD is increased, particularly with more advanced age and worse disease severity. ICS-containing therapy also has been shown to increase pneumonia risk; however, differences in study design and the definition of pneumonia events have led to substantial variability in risk estimates, and some data indicate that pneumonia risk may differ by the specific ICS used. In summary, treatment with ICSs has a role in dual and triple therapy for COPD to reduce exacerbations and improve symptoms. Careful assessment of COPD phenotypes related to risk factors, triggers, and comorbidities may assist in individualizing treatment while maximizing the benefit-to-risk ratio of ICS-containing COPD treatment.

Keywords: COPD; bronchodilators; dual/triple therapy; inhaled corticosteroids; pneumonia; safety.

Figure 1

Effectiveness of ICS-LABA inhalers. Notes: Pooled effect estimates of combined ICS-LABA inhalers vs (A) placebo and (B) LABA on moderate-severe exacerbations. Copyright ©2014. Dove Medical Press. Reproduced with permission from Oba Y and Lone NA. Comparative efficacy of inhaled corticosteroid and long-acting beta agonist combinations in preventing COPD exacerbations: a Bayesian network meta-analysis. Int J Chron Obstruct Pulmon Dis. 2014;9:469–479. Abbreviations: BDP, beclomethasone dipropionate; BUD, budesonide; CrI, credibility interval; FF, fluticasone furoate; FM, formoterol; FP, fluticasone propionate; ICS, inhaled corticosteroid; LABA, long-acting β₂-agonist; MF, mometasone furoate; SAL, salmeterol; VI, vilanterol.

Figure 2

The role of ICS in patients with COPD. Notes: Eosinophil thresholds for beneficial ICS effect are discussed in the text. Data regarding the effect of ICS on comorbidity presence or course are limited. Abbreviations: ACO, asthma–COPD overlap; ICS, inhaled corticosteroid; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; WBCs, white blood cells.

Figure 3

COPD exacerbations in the TRILOGY study. Notes: Unadjusted annual rate of COPD exacerbations of differing severity in the intent-to-treat population for the TRILOGY study. Reprinted from The Lancet, 388(10048), Singh D, Papi A, Corradi M, et al. Single inhaler triple therapy versus inhaled corticosteroid plus long-acting β2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY): a double-blind, parallel group, randomised controlled trial, Pages 963–973, Copyright 2016, with permission from Elsevier. Abbreviations: BDP, beclomethasone dipropionate; FF, fluticasone furoate; GB, glycopyrronium bromide.