Inhaled corticosteroids in COPD: when are they needed, when not needed and when harmful?

Twenty years ago, there was little interest in varying treatment of airways diseases from the recommended treatments for asthma. In the 1990s, new guidelines for diagnosis and treatment of COPD were developed, based on new research involving both old and new drugs as well as pulmonary rehabilitation. These guidelines included the evolving Australian and New Zealand guidelines for the management of COPD (the COPD-X plan) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop Report initiated in 2001.^2,3,5,6 

Why, or why not, consider inhaled corticosteroids?

ICS have cemented their position as the single most important drug treatment for asthma, and correct use of ICS in that setting has contributed greatly to reducing hospitalisations and deaths from asthma over the past 30 years.^7,8 ICS are most effective in patients with eosinophil-based inflammation (the predominant pattern in asthma). 

On the other hand, in COPD neutrophils drive the predominant inflammatory pathways, and eosinophilic inflammation is uncommon, making the routine use of ICS unnecessary. However, when ICS are used with inhaled long-acting beta-2 agonists (LABAs), extensive reports have shown better lung function and quality of life and fewer exacerbations in people who have had previous exacerbations and more severe airflow limitation, summarised in the COPD-X plan.^6,9 

In the past 10 years, it has also become clear that use of ICS in patients with COPD contributes to increased risk of pneumonia, tuberculosis and non-tuberculous mycobacterial infections.^9,10 Other potential important adverse consequences include oropharyngeal side effects, diabetes mellitus, low bone mineral density and cataracts.^11-14 Limiting the use of ICS to specific settings is therefore now advisable. 

Curiously, ICS use has not been associated with pneumonia in patients with asthma, although this may be explained by different patterns of inflammation and an altered microbiome in COPD. Moreover, information from large trials in patients with COPD has begun to show that low eosinophil levels predict a higher likelihood of pneumonia, sepsis and worse outcomes from exacerbations in patients who are receiving ICS.^15,16 

In Australia, the COPD-X guidelines recommend use of ICS (as part of combination inhalers) for COPD only for patients with severe symptomatic COPD and FEV₁ less than 50% predicted who also have frequent exacerbations.² ICS are subsidised by the PBS only for this patient group, now as a ‘streamlined authority’ for ICS-LABA or ICS-LABA-LAMA (inhaled long-acting muscarinic antagonist) combinations.

Although definitions of ‘frequent exacerbations’ vary, GOLD suggests that they be defined as:

• one or more severe exacerbations in a year requiring hospitalisation, or 
• two or more moderate exacerbations requiring oral corticosteroid and/or antibiotic therapy in the past year.³

What evidence supports  ICS for patients with frequent exacerbations? 

Exacerbations are events that are associated with an escalation of respiratory symptoms requiring added therapies (or even hospitalisation) to control.³ They are experienced by many patients with COPD and have major consequences, with prolonged diminution of quality of life through heightened breathing difficulties, cough and other symptoms.^17,18 In addition, 12-month mortality rates after a severe exacerbation of COPD (requiring hospitalisation) are higher than after myocardial infarction.³

Given the impact of exacerbations, one of the two central goals of COPD treatment is to reduce the risk of exacerbations by identifying characteristics of patients that predict that risk. The leading predictor is a previous history of exacerbations.^3,19 There are recent suggestions that the risk may be even better predicted by a combination of historical exacerbations and blood eosinophil counts, although convincing evidence of this is not available. 

Randomised controlled trials of ICS in COPD have been conducted over the past 20 years.^20,21 They have resulted in many editorials, systematic reviews and meta-analyses. These reports have been enhanced by two recent large trials and a systematic review, which showed that the risk of exacerbations reduces with ICS use compared with both placebo and LABA use.^22-24 A recent study also shows that adding an ICS to therapy for patients hospitalised for an exacerbation may reduce subsequent exacerbations.²⁵