The link between the use of inhaled corticosteroids (ICS) and pneumonia in people with COPD remains unclear, with conflicting data and no clear biological mechanisms, a respiratory insights forum held in Melbourne has been told.

Speaking during a session called ‘ICS and pneumonia risk’ Professor Ian Yang, Director of Thoracic Medicine at The Prince Charles Hospital and The University of Queensland in Brisbane, said that while there was definitely a higher risk of pneumonia with ICS use in COPD, this did not seem to translate into poorer outcomes reported in clinical trials.

He queried whether pneumonia reported as an adverse event was a robust endpoint in clinical trials, since definitions (including those based on radiological imaging) were not clearly defined at the start of most of the trials.

“I believe we need to strike a balance…If we continue ICS, there are benefits, but with an increased risk of pneumonia,” he told delegates.

“If we discontinue ICS, we could reduce pneumonia risk but increase other risks, especially if the patient has coexisting asthma.”

Stopping ICS was possible as long as clinicians remained alert to exacerbations, he said.

“Use ICS selectively in the right COPD patient group to avoid over-treatment,” he advised.

“Dose and duration of treatment could be important, although more studies on these topics are needed,” he added.

Theories on ICS and pneumonia link

Professor Yang said it was not understood why ICS led to an increased rate of pneumonia in COPD patients.

One theory was that the use of ICS may reduce the impact of an exacerbation, so patients are not prescribed antibiotics and their risk of pneumonia increases.

Other theories are that ICS affects macrophage function, or that it may lead to changes to the microbiome, resulting in an imbalance in bacterial communities in the lungs.

There was also evidence of immune suppression and changes in inflammatory cytokines in COPD patients treated with ICS.

Professor Yang noted that many studies on the association between ICS and pneumonia risk had methodological issues including heterogeneity in populations and interventions and a lack of radiological confirmation.

However, a Cochrane review ¹ published in 2012 concluded that ICS did indeed reduce exacerbations but increase the risk of pneumonia in COPD patients. It recommended that clinicians should balance the potential benefits against the risks.

Lung Foundation Australia guidelines recommend a stepwise approach to the management of COPD, in which ICS and LABA could be considered for COPD patients with FEV₁ less than 50% predicted AND a history of frequent exacerbations (2 or more in the past 12 months).

These guidelines may need to be modified in future based on new information about personalised medicine using phenotypes and endotypes of COPD, Professor Yang said.

“If a COPD patient doesn’t have asthma, has FEV₁ >50% predicted and has infrequent exacerbations, they probably don’t need to be on ICS. However, it’s still not certain if we should stop ICS if they become clear of exacerbations.”

The WIDSOM trial² showed it was valid to contemplate withdrawal from ICS in patients not meeting the criteria for ICS use, if dual bronchodilators were continued, he noted.

However, pneumonia risk did not seem to change, and there was a modest chance of adverse effects from ICS withdrawal in some patients, warranting close monitoring.

“I think dose and duration is very important and potentially the actual agent…in the future, testing for COPD phenotypes and endotypes will likely be useful for clinical care of patients,” he told delegates.

References:

1 Yang et al. Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews. 2012 July 11; (7).

2 Magnussen H et al. Withdrawal of Inhaled Glucocorticoids and Exacerbations of COPD. N Engl J Med. 2014; 371:1285-1294