COPD

Eosinophils worth checking in COPD exacerbations

Thursday, 9 Nov 2017


Phenotyping via eosinophils may help identify which patients with COPD exacerbations are most likely to have a favourable risk/benefit ratio for inhaled corticosteroids and those who will not.

However a sizeable grey area remains in between, the Respiratory Insights Forum in Melbourne was told.
Dr James Chalmers, from the University of Dundee in Scotland, said changes to GOLD1 mean LABA/LAMAs are the first choice for patients with frequent exacerbations.

“We’ve gone from about 70% of patients previously on inhaled corticosteroids to ICS being prescribed in a select group of COPD patients,” he said.

While COPD was predominately a neutrophilic disease that was steroid resistant, he said an important minority of patients had eosinophilic inflammation that was steroid sensitive.

A peripheral blood eosinophil count was the best biomarker for sputum eosinophils – ahead of exhaled nitric oxide and serum periostin2.

Dr Chalmers said a post-hoc analysis of two randomised controlled trials has shown the potential of eosinophils to predict patient response to inhaled corticosteroids3.

A 2016 study also showed an elevated blood eosinophil count identified a group of patients with a slower decline in FEV1 when treated with ICS4.

“Eosinophils clearly have significant supporting data for their role in directing ICS therapy.”

Additionally, he said there was evidence from a study he co-authored that inhaled corticosteroids change the way neutrophils fight infection in the lung5.

By inhibiting the normal process of neutrophils phagocytosing bacteria, corticosteroids encourage an alternative method of defence.

Neutrophil extracellular trap (NET) formation was associated with disease severity and microbial dysbiosis dominated by Haemophilus influenzae in patients with COPD.

Limitations of evidence

Dr Chalmers told the limbic his advice was to treat patients with frequent exacerbations and eosinophils consistently above 300 cells/μL with inhaled corticosteroids.

“In patients with very low eosinophils – less than 150 cells/μL – I would be looking to avoid steroids and think about long-term antibiotics.”

The risks of inhaled corticosteroids outweighed the benefits in this group of patients.

“The ones in the middle, I think you can’t make anything of their eosinophil count so you need to go back to your clinical judgment.”

“Is this a patient I am having to treat with oral steroids three, four or five times a year? – in which case it’s entirely reasonable to try an inhaled steroid even though the evidence is not perfect.”

“It’s important to look at evidence but also important to recognise the limitations of the evidence.”

Withdrawal of ICS

Dr Chalmers told the forum that common concerns about ICS withdrawal included adrenal insufficiency and the risk of increased exacerbations.

However, the WISDOM trial6 showed a stepwise withdrawal of glucocorticoids was non-inferior to triple therapy with tiotropium, salmeterol and fluticasone in terms of exacerbations.

There was a transient, but not significant increase in exacerbations soon after complete withdrawal of glucocorticoids.

Triple therapy concerns

The advent of triple therapy was a legitimate concern, Dr Chalmers said.

“At the moment a lot of patients are on triple therapy through different inhalers and the temptation will be, instead of trying to phenotype them, to put them on one inhaler that contains all three drugs.”

“And we run the risk then of over-treating people and using too many inhaled steroids with all of the additional risks. It will be very much a case of pick the right patient rather than put everybody onto triple therapy.”

References

1. The Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2017 report). Available from: http://goldcopd.org.

2. Wagener AH, de Nijs SB, et al. External validation of blood eosinophils, FE(NO) and serum periostin as surrogates for sputum eosinophils in asthma. Thorax. 2015; 70(2):115-20.

3. Pascoe S, Locantore N, et al. Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with COPD: a secondary analysis of data from two parallel randomised controlled trials. Lancet. 2015;3(6):435-42.

4. Barnes NC, Sharma R, Lettis S & Calverley PM. Blood eosinophils as a marker of response to inhaled corticosteroids in COPD. Eur Resp J. 2016;47(5):1374-82.

5. Dicker AJ, Crichton ML, et al. Neutrophil extracellular traps are associated with disease severity and microbiota diversity in patients with COPD. J Allergy Clin Immunol. 2017; May 13. doi: 10.1016/j.jaci.2017.04.022.

6. Magnussen H, Disse B et al. Withdrawal of Inhaled Glucocorticoids and Exacerbations of COPD. NEJM. 2014;371:1285- 94.

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