Are all COPD the same?

2025: ERS satellite online

Andningsvägar

DELA MED SIG

COPD is a disease with multiple risk factors that differ throughout life.

There are various etiotypes acknowledged¹ including COPD of genetic cause (eg. alpha 1 antitrypsin deficiency), COPD caused by early-life events such as low birthweight, COPD related to infections such as HIV or infections during childhood, COPD related to chronic asthma, in particular childhood asthma, and finally and still most common, environmental COPD caused by tobacco smoke-exposure, biomass fume and air pollution.

Fast drop in early stages

When monitoring lung function over time, an accelerated decline is not present in all patients, and often it is accelerated predominantly during early stages of COPD. Airway tapering, ie. luminal narrowing affecting the resistance of the airways², and emphysema, proven to precede airflow limitations³, are both signs for early disease. However, the extent of emphysema will increase with severity stage.

Sputum neutrophilia in COPD

In addition, differences in the inflammatory phenotype underline the diversity of COPD: increased sputum neutrophil counts in COPD have been described almost 30 years ago, although partly also naturally occurring with increasing age. Neutrophilia and interleukin-8 increase the susceptibility to exacerbations⁴. The increased sputum neutrophilia in COPD is related to bacterial colonisation of the lungs, also implying that an antibiotic treatment can be of help.⁵ From his clinical experience, Professor Louis estimates that 50% of persons living with COPD show sputum neutrophilia.

Previous exacerbations, not eosinophilic counts, predict exacerbations

Other patients present with airway eosinophilia and increased mast cell-activation bringing them close to what is normally associated with asthma; however, there appear to be mechanistic differences in drivers of this eosinophilia and mast cell-activation: while immunoglobulin E-driven mast cell activation and interleukin-4 play an important role in asthma, in COPD these features are more related to interleukin-5 and -13. Research has shown that eosinophilia is not associated with disease severity, and eosinophil counts do not predict exacerbations⁶– in fact, the best predictor for exacerbations are previous exacerbations!^4,6

Eosinophils predict treatment response

A certain protection towards the progression of emphysema can be observed in eosinophilic COPD. High eosinophil counts are a risk factor for lung function decline in early COPD, and of course, blood eosinophils as biomarker predict the treatment response towards inhaled corticosteroids with the potential to reduce exacerbations and mortality⁷, and towards biologics such as dupilumab, the later in a minority of COPD patients which can be classified as “T2-high”, ie. with high expression of mediators associated with Type 2 inflammation⁸. The eosinophilic phenotype appears to be stable over time, at least for the investigated period of one year, although variations in the inflammatory phenotype can occur during a bacterial infection^5,9.

Thus, all COPD are definitively not the same, and the need to proper phenotype the disease and to individualise its treatment is obvious.

Barbara Fuchs
Medical Manager, Chiesi Nordic

References