30 October 2019

Keep low-eo COPD patients off inhaled steroids

Clinical Respiratory

Inhaled corticosteroids are bad news for COPD patients without high eosinophils, with evidence showing they do no good and do harm, the ERS Congress in Madrid has heard.

Professor David Price, who holds positions in Sydney, Singapore and Aberdeen and is the editorial board chair of  Allergy & Respiratory Republic, spoke at a session on optimising treatment for COPD patients.

He said the terminology in the title of his presentation – “The right treatment for the predominant treatable trait: What are the practical realities?” – had been about for a few years and referred to “losing our obsession with disease labels and thinking about exactly what we’re treating when managing patients in front of us”.

In COPD, these treatable traits were chiefly airflow limitation and airway inflammation. Addressing the former would improve symptoms, lung function and exercise capacity, while fixing the latter was likely to reduce exacerbations.

For patients, breathlessness was a bigger concern than exacerbations.

While a lot of attention was on eosinophils, Professor Price asked the audience to think of the low-eosinophil patient, “as I think you may be surprised by some of the emerging data in this space”.

Combination long-acting beta agonists and long-acting muscarinic antagonists (LAMA/LABA) bronchodilators were the predominant treatment, as patients received more benefit from both than monotherapy.

While some benefit had been shown in trials when inhaled corticosteroids were added to LAMA/LABA therapy, the effect was small and heavily moderated by the eosinophil count. Patients with low eosinophils – about half of the COPD population – got no benefit from the triple therapy.

Withdrawing ICS made little difference in exacerbation risk except in those with high eosinophils, especially the minority with more than 400 cells/µL.

Real-life [non-RCT] studies had shown a strong dose-response relationship: the lower the eosinophil count, the less benefit from triple therapy. Additionally, the higher the patient’s exacerbation rate, the more benefit.

The huge DIAPLO study found the same patients – very high eosinophils and high exacerbation rates – had less lung function decline on ICS.

Patients with high FeNO did better on inhaled steroids, those with low FeNO did not respond at all. FeNO and eosinophils were independent predictors of response.

Putting the wrong patients on steroids came with a heavy price in side-effects, he said, especially diabetes and osteoporosis. Interestingly, the patients who least justified ICS were the most likely to develop diabetes.

And patients on steroids with the lowest eosinophils were also the most likely to end up in hospital with bacterial infections.

As for alternatives, roflumilast and azithromycin reduced exacerbations in low-eosinophil patients.

In an earlier presentation, Professor Sebastian Johnston from the National Heart and Lung Institute at Imperial College London, discussed the interactions of viral and bacterial infections in COPD and the increased risk of pneumonia in COPD patients treated with inhaled corticosteroids.

Rhinovirus infections were the most common cause of acute exacerbations of COPD, and many of those were accompanied by secondary bacterial infections, he said. Sputum glucose was higher in COPD, which might encourage bacterial growth.

He said while the association between ICS and pneumonia had been shown in many studies, the mechanism had only recently been studied.

A series of animal and human studies had found innate and acquired immune responses to viruses and bacteria were suppressed by steroids, via the LL37 peptide.

These effects could be reversed with interferon-beta, making it a potential therapy to reduce the risk of pneumonia in COPD patients, who tended to be deficient in interferons anyway.

Other options to consider for treatment and prevention were specific antivirals, antimicrobial peptides, elastase inhibitors and cathepsin D inhibitors.