Altering the trajectory of COPD

The Irish Thoracic Society Annual Scientific Meeting heard an engaging and evidence-based talk on altering the trajectory of chronic obstructive pulmonary disease (COPD) from incoming Chair of the European Respiratory Society’s airways pharmacology and treatment group, Dr Alexander Mathioudakis. Dr Mathioudakis is National Institute for Health and Care Research (NIHR) Clinical Lecturer in Respiratory Medicine at the University of Manchester and Manchester University NHS Foundation Trust, UK. His research focuses on personalised medicine and airways disease phenotypes, much of which he shared during the presentation.

COPD patients experience “an unacceptable disease burden despite optimal treatment”, Dr Mathioudakis told the conference. He noted that the heterogenous nature of the disease is a major challenge for clinicians. “Patients do not respond to the same treatment,” he said, adding that grouping this cohort into phenotypes has not provided a solution since patients often overlap across these groups. Dr Mathioudakis told delegates that carefully identifying, characterising, and targeting treatable traits which contribute to, or cause, COPD exacerbations, such as bacterial or viral infections, airway eosinophilic inflammation, poor adherence to treatment, air pollution, mucus plugging, and others, can achieve more personalised interventions.

Attendees heard that effective management of these treatable traits can help to improve patient outcomes and reduce the unnecessary use of medications – “primarily antibiotics and steroids that can have severe adverse effects”. Dr Mathioudakis also said that identifying traits which contribute to long-term deterioration will lead to treatments that can “prevent lung function decline and salvage lung tissue after exacerbations”.

Treatment of exacerbations

Dr Mathioudakis proceeded to discuss the characterisation of COPD exacerbations – namely those caused by the presence of bacteria, viruses, and eosinophilic inflammation, or those that lack a notable eosinophilic response – and acknowledged the “significant overlap” among these categories. “It is estimated that up to 50 per cent of exacerbations are associated with bacterial infection, however, and unfortunately, we treat a significantly higher proportion with antibiotics,” he said. Dr Mathioudakis described this situation as “problematic” in view of risks like antimicrobial resistance and microbial dysbiosis.

Moving on to explore the benefits and limitations of common biomarkers which guide antimicrobial prescribing, Dr Mathioudakis said that using sputum purulence as an indicator results in around 60 per cent of COPD exacerbations being treated with antibiotics. “Purulence is not a sensitive biomarker,” he concluded, before presenting the empirical data from the CATCH study, PACE trial, and others that examined C-reactive protein (CRP) to guide antimicrobial prescribing in COPD exacerbations. “CRP seems to be a good biomarker,” he outlined, “but we have a few limitations”, such as the lack of a universally accepted threshold and non-specificity of the test. He also detailed data indicating that procalcitonin is a more specific biomarker than CRP, which can also reduce the use of antibiotics, but noted that evidence to support its implementation is lacking, that the test is expensive, and not widely accessible.

COPD patients experience ‘an unacceptable disease burden despite optimal treatment’

Delegates then received a comprehensive overview of the existing knowledge to guide steroid prescribing in COPD exacerbations. “There is emergent evidence that eosinophil levels can predict response to steroids,” Dr Mathioudakis said, and described findings to suggest that it is “safe not to give steroids for patients with low blood eosinophils”. He did note that further data is needed to reach definitive conclusions regarding systemic corticosteroid administration, before discussing viral exacerbations of COPD and the substantial burdens associated with comorbidities like pulmonary embolism and heart failure. Dr Mathioudakis said “it’s really important to be more vigilant” about assessing for comorbid conditions.

Prevention of exacerbations

Dr Mathioudakis acknowledged that many of the treatable traits associated with COPD exacerbations, such as infections, chronic inflammation, comorbidities, reflux, ongoing smoking, and poor treatment adherence, are already addressed in clinical practice. He then noted that 20-to-40 per cent of patients have an eosinophilic phenotype, meaning they have ongoing inflammation, and discussed the conflicts and evidence-base underpinning inhaled corticosteroid (ICS) prescribing in COPD. “Data shows that ICS increases the risk of pneumonia,” stated Dr Mathioudakis, who described the complexity surrounding ICS administration and associated risks.

Delegates heard that although serum eosinophil levels can predict which patients will respond to ICS administration, clinicians “need to assess several variants over time”, as these biomarkers are reduced in 40 per cent of patients who benefit from ICS therapy, remain stable in another 40 per cent of patients who experience neither benefit nor harm from ICS therapy, and increase in 20 per cent of patients who are harmed by ICS and face a “significantly higher risk of exacerbation and accelerated lung function decline”.

“Instead of looking at patients with high eosinophils, it might be smarter to look for patients that have recurrent chest infections and try discontinuation of ICS,” Dr Mathioudakis suggested.

“Measure blood eosinophils, stop ICS, and measure eosinophils two weeks later. If eosinophils were suppressed on ICS, it’s likely that these are the people who are benefitting from therapy and we probably need to restart ICS. But if the blood eosinophils are not suppressed by ICS, it is probably a good decision to stop the treatment.”

Dr Mathioudakis went on to present research showing that current smokers are not gaining as much benefit from ICS as ex-smokers, before exploring the role of biologics in COPD. He described findings from the BOREAS and NOTUS trials that showed a decreased risk of exacerbations and improved lung function in COPD patients that resulted in the recent US Food and Drug Administration and European Medicines Agency approval of dupilumab for the disease. Data was also discussed from trials evaluating the effects of benralizumab and mepolizumab in COPD and Dr Mathioudakis concluded his talk with “exciting findings”, potential new treatment options with biologics and a bright outlook in the area of eosinophilic subtypes for managing the disease in future.