Use of inhaled corticosteroids in COPD: improving efficacy

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is a chronic, inflammatory lung disease characterized by airflow limitation that is not fully reversible. The pathological changes in COPD lead to alveolar destruction (emphysema) and chronic airway inflammation, resulting in airflow obstruction and recurrent exacerbations. Inhaled corticosteroids (ICS) are anti-inflammatory agents that are widely used, especially in combination with long-acting beta-agonists, in patients with COPD. Here, we will summarize the benefits and risks of ICS use for COPD, and discuss approaches to more personalized medicine when selecting COPD patients to commence (or withdraw) ICS use. The conclusion arising is that further validation of clinical and biological markers should be undertaken in COPD, in order to individualize ICS therapy to maximize efficacy for patients.

KEYWORDS:

• Corticosteroids
• inhaled
• chronic obstructive pulmonary disease
• treatment
• adverse effects
• biomarkers

Acknowledgements

The authors sincerely thank the patients and staff who have been involved in their research programs.

Financial & competing interests disclosure

The authors were supported by an NHMRC project grant (DR APP1084130), NHMRC Career Development Fellowship (IY APP1026215) and The Prince Charles Hospital Foundation grant (IY, JS MS2014-24). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• The pathology of COPD involves chronic inflammation of the airways with pro-inflammatory cytokine production from inflammatory and structural cells, airway remodeling, and lung parenchymal destruction.

• ICS act via genomic and non-genomic mechanisms of action to reduce airway inflammation.

• ICS (especially ICS/LABA in combination) reduce the rate of exacerbations and slow the rate of decline of quality of life in patients with COPD, compared to placebo.

• However, there is an increased risk of pneumonia with ICS use in patients with COPD, as well as local and systemic adverse effects of ICS.

• Withdrawal of ICS may be contemplated in some patients, although the selection of patients for this strategy is still uncertain at present.

• More rational selection of COPD patients who would experience the greatest efficacy with ICS use is needed, based on clinical and biological phenotypes (e.g. exacerbations, peripheral eosinophilia, lung microbiome).

• Improved monitoring of clinical and molecular markers would optimize decision-making about whether to continue ICS, once commenced in individual patients.

• Future prospective studies should incorporate integration of clinical and biological markers to predict responders to ICS, and monitor this response (both for benefits and adverse effects).